ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis

PubMed Central

Caster, Dawn J.; Korte, Erik A.; Nanda, Sambit K.; McLeish, Kenneth R.; Oliver, Rebecca K.; G'Sell, Rachel T.; Sheehan, Ryan M.; Freeman, Darrell W.; Coventry, Susan C.; Kelly, Jennifer A.; Guthridge, Joel M.; James, Judith A.; Sivils, Kathy L.; Alarcon-Riquelme, Marta E.; Scofield, R. Hal; Adrianto, Indra; Gaffney, Patrick M.; Stevens, Anne M.; Freedman, Barry I.; Langefeld, Carl D.; Tsao, Betty P.; Pons-Estel, Bernardo A.; Jacob, Chaim O.; Kamen, Diane L.; Gilkeson, Gary S.; Brown, Elizabeth E.; Alarcon, Graciela S.; Edberg, Jeffrey C.; Kimberly, Robert P.; Martin, Javier; Merrill, Joan T.; Harley, John B.; Kaufman, Kenneth M.; Reveille, John D.; Anaya, Juan-Manuel; Criswell, Lindsey A.; Vila, Luis M.; Petri, Michelle; Ramsey-Goldman, Rosalind; Bae, Sang-Cheol; Boackle, Susan A.; Vyse, Timothy J.; Niewold, Timothy B.; Cohen, Philip

2013-01-01

The genetic factors underlying the pathogenesis of lupus nephritis associated with systemic lupus erythematosus are largely unknown, although animal studies indicate that nuclear factor (NF)-κB is involved. We reported previously that a knockin mouse expressing an inactive form of ABIN1 (ABIN1[D485N]) develops lupus-like autoimmune disease and demonstrates enhanced activation of NF-κB and mitogen-activated protein kinases in immune cells after toll-like receptor stimulation. In the current study, we show that ABIN1[D485N] mice develop progressive GN similar to class III and IV lupus nephritis in humans. To investigate the clinical relevance of ABIN1 dysfunction, we genotyped five single-nucleotide polymorphisms in the gene encoding ABIN1, TNIP1, in samples from European-American, African American, Asian, Gullah, and Hispanic participants in the Large Lupus Association Study 2. Comparing cases of systemic lupus erythematosus with nephritis and cases of systemic lupus erythematosus without nephritis revealed strong associations with lupus nephritis at rs7708392 in European Americans and rs4958881 in African Americans. Comparing cases of systemic lupus erythematosus with nephritis and healthy controls revealed a stronger association at rs7708392 in European Americans but not at rs4958881 in African Americans. Our data suggest that variants in the TNIP1 gene are associated with the risk for lupus nephritis and could be mechanistically involved in disease development via aberrant regulation of NF-κB and mitogen-activated protein kinase activity. PMID:23970121

An atypical pattern of Epstein-Barr virus infection in a case with idiopathic tubulointerstitial nephritis.

PubMed

Okada, Hirokazu; Ikeda, Naofumi; Kobayashi, Tatsuya; Inoue, Tsutomu; Kanno, Yoshihiko; Sugahara, Souichi; Nakamoto, Hidetomo; Yamamoto, Takako; Suzuki, Hiromichi

2002-10-01

Recently, Epstein-Barr virus (EBV) received attention because a latent form of its infection in renal proximal tubular epithelial cells was found to cause idiopathic, chronic tubulointerstitial nephritis. In this report, we describe the case of a patient with a replicative form of EBV infection, chronic active EBV infection (CAEBV), who developed acute tubulointerstitial nephritis and minimal change nephrotic syndrome. A renal biopsy revealed papillary infoldings of atypical tubular epithelium and adjacent dense infiltration of lymphocytes. Using in situ polymerase chain reaction methods, we detected the EBV genome in some of the infiltrating lymphocytes, but not in the tubular epithelial cells. EBV-infected T cells are thought to activate other educated T cells, as well as secrete an unrestricted variety of cytokines, thus playing a pivotal role in CAEBV and its end organ disease. Therefore, in our case, the CAEBV activated, educated T cells may have followed the EBV-infected lymphocytes as they infiltrated into the peritubular interstitium, and promoted focal tubular epithelial atypia and minimal change nephrotic syndrome. The long-term observation of such patients is important because CAEBV may progress into lymphoproliferative diseases. Copyright 2002 S. Karger AG, Basel

Fatal suppurative nephritis caused by Pseudomonas in a chimpanzee

USGS Publications Warehouse

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

1979-01-01

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

Proliferative lupus nephritis in the absence of overt systemic lupus erythematosus: A historical study of 12 adult patients.

PubMed

Touzot, Maxime; Terrier, Cécile Saint-Pastou; Faguer, Stanislas; Masson, Ingrid; François, Hélène; Couzi, Lionel; Hummel, Aurélie; Quellard, Nathalie; Touchard, Guy; Jourde-Chiche, Noémie; Goujon, Jean-Michel; Daugas, Eric

2017-12-01

Severe lupus nephritis in the absence of systemic lupus erythematosus (SLE) is a rare condition with an unclear clinical presentation and outcome.We conducted a historical observational study of 12 adult (age >18 years) patients with biopsy-proven severe lupus nephritis or lupus-like nephritis without SLE immunological markers at diagnosis or during follow-up. Excluded were patients with chronic infections with HIV or hepatitis B or C; patients with a bacterial infectious disease; and patients with pure membranous nephropathy. Electron microscopy was retrospectively performed when the material was available. End points were the proportion of patients with a complete response (urine protein to creatinine ratio <0.5 g/day and a normal or near-normal eGFR), partial response (≥50% reduction in proteinuria to subnephrotic levels and a normal or near-normal eGFR), or nonresponse at 12 months or later after the initiation of the treatment.The study included 12 patients (66% female) with a median age of 36.5 years. At diagnosis, median creatinine and proteinuria levels were 1.21 mg/dL (range 0.5-11.6) and 7.5 g/day (1.4-26.7), respectively. Six patients had nephrotic syndrome and acute kidney injury. Renal biopsy examinations revealed class III or class IV A/C lupus nephritis in all cases. Electron microscopy was performed on samples from 5 patients. The results showed mesangial and subendothelial dense deposits consistent with LN in 4 cases, and a retrospective diagnosis of pseudo-amyloid fibrillary glomerulonephritis was made in 1 patient.Patients received immunosuppressive therapy consisting of induction therapy followed by maintenance therapy, similar to treatment for severe lupus nephritis. Remission was recorded in 10 patients at 12 months after the initiation of treatment. One patient reached end-stage renal disease. After a median follow-up of 24 months, 2 patients relapsed.Lupus nephritis in the absence of overt SLE is a nosological entity requiring

Predictors of long-term renal outcome in lupus nephritis trials: lessons learned from the Euro-Lupus Nephritis cohort.

PubMed

Dall'Era, Maria; Cisternas, Miriam G; Smilek, Dawn E; Straub, Laura; Houssiau, Frédéric A; Cervera, Ricard; Rovin, Brad H; Mackay, Meggan

2015-05-01

There is a need to determine which response measures in lupus nephritis trials are most predictive of good long-term renal function. We used data from the Euro-Lupus Nephritis Trial to evaluate the performance of proteinuria, serum creatinine (Cr), and urinary red blood cells (RBCs) as predictors of good long-term renal outcome. Patients from the Euro-Lupus Nephritis Trial with proteinuria, serum Cr, and urinary RBC measurements at 3, 6, or 12 months and with a minimum of 7 years of followup were included (n = 76). We assessed the ability of these clinical biomarkers at 3, 6, and 12 months after randomization to predict good long-term renal outcome (defined as a serum Cr value ≤1.0 mg/dl) at 7 years. Receiver operating characteristic curves were generated to assess parameter performance at these time points and to select the best cutoff for individual parameters. Sensitivity and specificity were calculated for the parameters alone and in combination. A proteinuria value of <0.8 gm/day at 12 months after randomization was the single best predictor of good long-term renal function (sensitivity 81% and specificity 78%). The addition of serum Cr to proteinuria as a composite predictor did not improve the performance of the outcome measure; addition of urinary RBCs as a predictor significantly decreased the sensitivity to 47%. This study demonstrates that the level of proteinuria at 12 months is the individual best predictor of long-term renal outcome in patients with lupus nephritis. Inclusion of urinary RBCs as part of a composite outcome measure actually undermined the predictive value of the trial data. We therefore suggest that urinary RBCs should not be included as a component of clinical trial response criteria in lupus nephritis. © 2015, American College of Rheumatology.

Validation of the Lupus Nephritis Clinical Indices in Childhood-Onset Systemic Lupus Erythematosus.

PubMed

Mina, Rina; Abulaban, Khalid; Klein-Gitelman, Marisa S; Eberhard, Barbara A; Ardoin, Stacy P; Singer, Nora; Onel, Karen; Tucker, Lori; O'neil, Kathleen; Wright, Tracey; Brooks, Elizabeth; Rouster-Stevens, Kelly; Jung, Lawrence; Imundo, Lisa; Rovin, Brad; Witte, David; Ying, Jun; Brunner, Hermine I

2016-02-01

To validate clinical indices of lupus nephritis activity and damage when used in children against the criterion standard of kidney biopsy findings. In 83 children requiring kidney biopsy, the Systemic Lupus Erythematosus Disease Activity Index renal domain (SLEDAI-R), British Isles Lupus Assessment Group index renal domain (BILAG-R), Systemic Lupus International Collaborating Clinics (SLICC) renal activity score (SLICC-RAS), and SLICC Damage Index renal domain (SDI-R) were measured. Fixed effects and logistic models were calculated to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low-to-moderate versus high lupus nephritis activity (National Institutes of Health [NIH] activity index [AI]) score: ≤10 versus >10; tubulointerstitial activity index (TIAI) score: ≤5 versus >5; or the absence versus presence of lupus nephritis chronicity (NIH chronicity index) score: 0 versus ≥1. There were 10, 50, and 23 patients with ISN/RPS class I/II, III/IV, and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with lupus nephritis activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between lupus nephritis activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture lupus nephritis chronicity was 23.5% and 91.7%, respectively. Despite being designed to measure lupus nephritis activity, SLICC-RAS and SLEDAI-R scores significantly differed with lupus nephritis chronicity status. Current clinical indices of lupus nephritis fail to discriminate ISN/RPS class in children. Despite its shortcomings, the SLEDAI-R appears best for measuring lupus nephritis activity in a clinical setting. The SDI-R is a poor correlate of lupus nephritis chronicity. © 2016, American College of Rheumatology.

Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient.

PubMed

Azar, Ibrahim; Esfandiarifard, Saghi; Sinai, Pedram; Wazir, Ali; Foulke, Llewellyn; Mehdi, Syed

2017-01-01

Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

A case of acute kidney injury caused by granulomatous interstitial nephritis associated with sarcoidosis.

PubMed

Horino, Taro; Matsumoto, Tatsuki; Inoue, Kosuke; Ichii, Osamu; Terada, Yoshio

2018-05-01

Sarcoidosis affects multiple organs including lung, heart and kidney. Sarcoidosis causes hypercalcemia, hypergammaglobulinemia, and rarely, granulomatous interstitial nephritis, resulting in renal stromal damage. Granulomatous interstitial nephritis is characterized as interstitial nephritis with noncaseating epithelioid granulomas. Diagnosing granulomatous interstitial nephritis before patient's death is challenging; hence, only few cases proven by renal biopsy have been reported till date. We present a case of acute kidney injury caused by granulomatous interstitial nephritis as a renal manifestation of sarcoidosis proven by renal biopsy, which can be confirmed by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Glucocorticoid therapy was helpful for improving and maintaining her renal function over a 6-year period.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-22

...] Guidance for Industry on Lupus Nephritis Caused By Systemic Lupus Erythematosus--Developing Medical... entitled ``Lupus Nephritis Caused By Systemic Lupus Erythematosus--Developing Medical Products for... biological products, and medical devices for the treatment of lupus nephritis (LN) caused by systemic lupus...

Childhood lupus nephritis: 12 years of experience from a developing country's perspective.

PubMed

Samanta, Moumita; Nandi, Madhumita; Mondal, Rakesh; Hazra, Avijit; Sarkar, Sumatra; Sabui, Tapas; Kundu, Chanchal Kumar; Biswas, Arnab

2017-09-01

To assess the long-term outcome of lupus nephritis in children with systemic lupus erythematosus followed up over 12 years at a tertiary care teaching hospital in Eastern India. This is a retrospective observational study of the clinicopathological presentation, management, and outcome in 46 children with lupus nephritis over a period of 12 years at a tertiary teaching hospital in Eastern India. Mortality was compared between different lupus classes and therapy groups with Kaplan-Meier analysis and log-rank test. The incidence of lupus nephritis was 58.97% [95% confidence interval (CI) 48.06%-59.89%] with the mean age at presentation being 10.2±2.43 years (range 5.5-14.5) years. Majority belonged to class IV (30.43%), followed by class II (26.91%), class III (23.91), and class V (8.70%). Outcome analysis of children with lupus nephritis over 12 years revealed that 24 (52.17%) achieved complete remission of disease activity, 5 attained partial remission, 4 continued to have active disease, 5 developed end-stage renal disease (ESRD), and 8 died. Overall mortality thus observed was 17.39% with septicemia in the background of ESRD being the commonest cause. No significant difference in mortality was observed between different lupus nephritis classes or therapy arm groups. The study throws light on various aspects of lupus nephritis and their long-term outcome patterns in children from developing countries such as India.

38 CFR 4.115 - Nephritis.

Code of Federal Regulations, 2012 CFR

2012-07-01

... hypertension or arteriosclerosis, develops slowly, with minimum laboratory findings, and is associated with... nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in the... coexisting hypertension or heart disease will be separately rated. [41 FR 34258, Aug. 13, 1976, as amended at...

38 CFR 4.115 - Nephritis.

Code of Federal Regulations, 2014 CFR

2014-07-01

... hypertension or arteriosclerosis, develops slowly, with minimum laboratory findings, and is associated with... nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in the... coexisting hypertension or heart disease will be separately rated. [41 FR 34258, Aug. 13, 1976, as amended at...

38 CFR 4.115 - Nephritis.

Code of Federal Regulations, 2013 CFR

2013-07-01

... hypertension or arteriosclerosis, develops slowly, with minimum laboratory findings, and is associated with... nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in the... coexisting hypertension or heart disease will be separately rated. [41 FR 34258, Aug. 13, 1976, as amended at...

38 CFR 4.115 - Nephritis.

Code of Federal Regulations, 2011 CFR

2011-07-01

... hypertension or arteriosclerosis, develops slowly, with minimum laboratory findings, and is associated with... nephritis, the absent kidney and any hypertension or heart disease will be separately rated. Also, in the... coexisting hypertension or heart disease will be separately rated. [41 FR 34258, Aug. 13, 1976, as amended at...

Mortality from nephritis and nephrosis in the fibreglass manufacturing industry

PubMed Central

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

1999-01-01

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

Acute radiation nephritis. Its evolution on sequential bone imaging

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

Palestro, C.; Fineman, D.; Goldsmith, S.J.

1988-11-01

Acute radiation nephritis typically affects the kidneys 3-12 months after radiation exposure and may occur with doses as low as 2500 rads. After an initial latent period, the affected portions of the kidneys become swollen and edematous, and develop multiple petechiae. Necrotizing vasculitis and interstitial hemorrhage occur, and the end stage is that of scarring. Two patients are presented in whom localized acute radiation nephritis developed, and whose kidneys demonstrated the characteristic sequential changes of this entity on serial bone imaging.

38 CFR 4.115 - Nephritis.

Code of Federal Regulations, 2010 CFR

2010-07-01

... disease; the onset is sudden, and the course marked by red blood cells, salt retention, and edema; it may... natural progress. Separate ratings are not to be assigned for disability from disease of the heart and any form of nephritis, on account of the close interrelationships of cardiovascular disabilities. If...

Anti-dsDNA Antibodies Bind to Mesangial Annexin II in Lupus Nephritis

PubMed Central

Yung, Susan; Cheung, Kwok Fan; Zhang, Qing

2010-01-01

Production of anti-dsDNA antibodies is a hallmark of lupus nephritis, but how these antibodies deposit in organs and elicit inflammatory damage remains unknown. In this study, we sought to identify antigens on the surface of human mesangial cells (HMC) that mediate the binding of human anti-dsDNA antibodies and the subsequent pathogenic processes. We isolated anti-dsDNA antibodies from patients with lupus nephritis by affinity chromatography. We used multiple methods to identify and characterize antigens from the plasma membrane fraction of mesangial cells that crossreacted with the anti-dsDNA antibodies. We found that annexin II mediated the binding of anti-dsDNA antibodies to HMC. After binding to the mesangial cell surface, anti-dsDNA antibodies were internalized into the cytoplasm and nucleus. This also led to induction of IL-6 secretion and annexin II synthesis, mediated through activation of p38 MAPK, JNK, and AKT. Binding of anti-dsDNA antibodies to annexin II correlated with disease activity in human lupus nephritis. Glomerular expression of annexin II correlated with the severity of nephritis, and annexin II colocalized with IgG and C3 deposits in both human and murine lupus nephritis. Gene silencing of annexin II in HMC reduced binding of anti-dsDNA antibody and partially decreased IL-6 secretion. In summary, our data demonstrate that annexin II mediates the binding of anti-dsDNA antibodies to mesangial cells, contributing to the pathogenesis of lupus nephritis. This interaction provides a potential target for therapeutic intervention. PMID:20847146

Blockade of CD354 (TREM-1) Ameliorates Anti-GBM-Induced Nephritis.

PubMed

Du, Yong; Wu, Tianfu; Zhou, Xin J; Davis, Laurie S; Mohan, Chandra

2016-06-01

CD354, Triggering Receptor of Myeloid Cells-1 (TREM-1), is a potent amplifier of myeloid immune responses. Our goal was to determine the expression and function of TREM-1 in immune-mediated nephritis. An anti-glomerular basement membrane antibody (anti-GBM)-induced nephritis model was employed, where mice were sensitized with rabbit IgG followed by anti-GBM serum to induce disease. Anti-GBM-treated 129x1/svJ mice developed severe nephritis whereas C57BL/6 (B6) mice were resistant to disease. Anti-GBM disease resulted in elevated renal TREM-1 messenger RNA (mRNA) and protein levels and increased urine TREM-1 levels in 129x1/svJ. TREM-1 blockade with an inhibitory peptide, LP17, inhibited proteinuria and renal disease as measured by glomerulonephritis class, severity of tubulointerstitial disease, crescent formation, and inflammatory cell infiltrates. In sum, TREM-1 is upregulated in renal inflammation and plays a vital role in driving disease. Thus, TREM-1 blockade emerges as a potential therapeutic avenue for immune-mediated renal diseases such as lupus nephritis.

The spectrum of renal thrombotic microangiopathy in lupus nephritis

PubMed Central

2013-01-01

Introduction Among various lupus renal vascular changes, thrombotic microangiopathy (TMA) presented with the most severe clinical manifestations and high mortality. The pathogenesis of TMA in systemic lupus erythematosus (SLE) was complicated. The aim of this study was to assess clinical manifestations, laboratory characteristics, pathological features and risk factors for clinical outcomes of lupus nephritis patients co-existing with renal TMA in a large cohort in China. Methods Clinical and renal histopathological data of 148 patients with biopsy-proven lupus nephritis were retrospectively analyzed. Serum complement factor H, A Disintegrin and Metalloprotease with Thrombospondin type I repeats 13 (ADAMTS-13) activity, antiphospholipid antibodies and C4d deposition on renal vessels were further detected and analyzed. Results In the 148 patients with lupus nephritis, 36 patients were diagnosed as co-existing with renal TMA based on pathological diagnosis. Among the 36 TMA patients, their clinical diagnoses of renal TMA were as followings: 2 patients combining with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 2 patients combining with anti-phospholipid syndrome, 2 patients with malignant hypertension, 1 patient with scleroderma and the other 29 patients presenting with isolated renal TMA. Compared with the non-renal TMA group, patients with renal TMA had significantly higher urine protein (7.09 ± 4.64 vs. 4.75 ± 3.13 g/24h, P = 0.007) and serum creatinine (159, 86 to 215 vs. 81, 68 to 112 μmol/l, P <0.001), higher scores of total activity indices (AI) (P <0.001), endocapillary hypercellularity (P <0.001), subendothelial hyaline deposits (P = 0.003), interstitial inflammation (P = 0.005), glomerular leukocyte infiltration (P = 0.006), total chronicity indices (CI) (P = 0.033), tubular atrophy (P = 0.004) and interstitial fibrosis (P = 0.018). Patients with renal TMA presented with poorer renal outcome (P = 0.005) compared with the non-TMA group

Assessment of premature atherosclerosis in systemic lupus erythematosus patients with and without nephritis.

PubMed

Sharma, S K; Rathi, M; Sahoo, S; Prakash, M; Dhir, V; Singh, S

2016-04-01

Risk of subclinical atherosclerosis is increased in patients with systemic lupus erythematosus (SLE). We correlated carotid intima media thickness (CIMT) and endothelial dysfunction through flow-mediated dilation (FMD) in SLE patients with the SLE Disease Activity Index (SLEDAI). This single-centre cross-sectional study recruited 100 consenting SLE outpatients (ACR 1997 criteria) out of which 50 had nephritis, with disease duration of ≥2 years for SLE and ≥6 months for lupus nephritis. We measured baseline laboratory levels, CIMT and FMD (after brachial BP cuff inflation up to 200 mmHg for five minutes), and calculated SLEDAI. Mean age was 29.88 ± 6.53 years; 95/100 were female. CIMT showed positive correlation (p = 0.037; rho = 0.209), and FMD showed inverse correlation with patient's age (p = 0.011; rho = -0.252). CIMT and FMD were more deranged in patients aged ≥25 years (p < 0.05). CIMT was not significantly different between SLE patients with and without nephritis (p > 0.05), whereas SLEDAI and FMD were more deranged in nephritis patients (p < 0.05). In patients without nephritis, FMD showed significant inverse correlation with disease duration (p = 0.043; rho = -0.288) and urine albumin (p = 0.045; rho = -0.285). In nephritis patients, the correlation between age of the patient was significantly positive with CIMT (p = 0.001; rho = 0.441) and significantly inverse with FMD (p = 0.028; rho = -0.312). SLE patients with nephritis are at a higher risk to develop arterial stiffening, leading to early end-organ damage. Early aggressive treatment may prevent endothelial dysfunction. FMD using vascular ultrasonography on the brachial artery represents a non-invasive, repeatable and useful method for the assessment of endothelial dysfunction. © The Author(s) 2015.

Pregnancy and renal outcomes in lupus nephritis: an update and guide to management.

PubMed

Bramham, K; Soh, M C; Nelson-Piercy, C

2012-10-01

Systemic lupus erythematosis (SLE) commonly affects women of child bearing-age, and advances in treatment have resulted in an increasing number of women with renal involvement becoming pregnant. Knowledge of the relationship of the condition with respect to fertility and pregnancy is important for all clinicians involved in the care of women with lupus nephritis because they have complicated pregnancies. Presentation of lupus nephritis can range from mild asymptomatic proteinuria to rapidly progressive renal failure and may occur before, during, or after pregnancy. The timing of diagnosis may influence pregnancy outcome. Pregnancy may also affect the course of lupus nephritis. All pregnancies in women with lupus nephritis should be planned, preferably after more than six-months of quiescent disease. Predictors of poor obstetric outcome include active disease at conception or early pregnancy, baseline poor renal function with Creatinine >100 μmol/L, proteinuria >0.5 g/24 hours, presence of concurrent antiphospholipid syndrome and hypertension. In this review the most recent studies of pregnancies in women with lupus nephritis are discussed and a practical approach to managing women prepregnancy, during pregnancy and post-partum is described.

Serum Vascular Endothelial Growth Factor (VEGF) as a Biomarker for Disease Activity in Lupus Nephritis.

PubMed

Ghazali, Wan Syamimee Wan; Iberahim, Rahimah; Ashari, Noor Suryani Mohd

2017-10-01

Previous studies have shown that serum VEGF levels were elevated in patients with active systemic lupus erythematosus (SLE), especially in those with lupus nephritis (LN). In this case control study, we aimed to compare serum levels of VEGF in SLE patients between LN, non-LN and healthy participants to determine the association between serum VEGF levels and the activity and histological classes of lupus nephritis. Blood samples were obtained from 92 SLE patients (46 LN and 46 non-LN) and 26 controls. Data were collected from medical records. Serum VEGF assays were performed by specific, enzyme-linked immunosorbent assay kits (ELISA). Laboratory investigations included urinalysis, urine protein-creatinine ratio, serum creatinine, albumin and VEGF levels. Blood pressure, renal biopsy result and treatment were recorded. LN activity was evaluated using the renal subscale of the British Isles Lupus Assessment Group (rBILAG, 2004). The rBILAG measures blood pressure (diastolic and systolic), urine protein, serum creatinine, calculated glomerular filtration rate (GFR), presence of active urinary sediments and histological evidence of active nephritis. Serum VEGF was elevated in SLE patients with LN compared with the non-LN group and healthy controls. The levels found were significantly higher in the sera of patients with active nephritis compared to those with quiescent nephritis ( P = 0.024). The study did not find a statistically significant relationship between serum VEGF levels and histological classes of LN. There was no significant difference of serum VEGF level between LN and non-LN SLE groups and between the non-LN group and healthy controls. However, there were increased levels of serum VEGF in the LN group, especially in patients with active nephritis as compared to quiescent nephritis group. This reflects the role of VEGF in the pathogenesis of lupus nephritis, however the clinical potential of this biomarker needs further study.

Biomarkers of IgA vasculitis nephritis in children

PubMed Central

Pillebout, Evangeline; Jamin, Agnès; Ayari, Hamza; Housset, Pierre; Pierre, Melissa; Sauvaget, Virginia; Viglietti, Denis; Deschenes, Georges

2017-01-01

Henoch–Schönlein purpura is a systemic vasculitis characterized by IgA deposits, which target the skin, joints, and kidneys, among other organs. In children, prognosis is often good but little is known about biomarkers of pediatric nephritis. We hypothesized that biological markers, including cytokines, immunoglobulins, IgA-immune complexes, IgA glycosylation and neutrophil gelatinase-associated lipocalin (NGAL), may discriminate IgA vasculitis (IgAV) pediatric patients with renal involvement from those without renal involvement. Fifty children at the time of IgAV rash between 2010 and 2015 were prospectively enrolled and compared to 21 controls. All patients were assessed for clinical and biological parameters at the time of diagnosis, including the levels of cytokines, immunoglobulins, immune complexes, IgA glycosylation and NGAL in serum and urine. Among IgAV patients, 33 patients exhibited nephritis (IgAV-N) and 17 children were without nephritis (IgAV-woN). The serum level of galactose-deficient (Gd)-IgA1 (p<0.01) and the urinary concentrations of IgA, IgG, IgM, IL-6, IL-8, IL-10, IgA-IgG complexes and IgA-sCD89 complexes (p<0.001 for all) were higher in the IgAV-N patients than in the IgAV-woN patients. Among those markers, urinary IgA and IgM had the highest AUC (0.86 and 0.87 respectively, p<0.0001). This prospective cohort study furthers our understanding of the pathophysiology of IgAV. We identified biomarkers that are able to distinguish patients initially with or without nephritis. To conclude, serum Gd-IgA1 and urinary IgA, IgG, IgM, IL-6, IL-8, IL-10, and IgA-IgG and IgA-sCD89 complexes could identify IgAV pediatric patients with renal involvement at the time of diagnosis. PMID:29190714

A rare and important case of Staphylococcus haemolyticus-associated ventricular atrial shunt nephritis.

PubMed

Suen, Kyle; Mashhadian, Ardavan; Figarsky, Ian; Payumo, Jeff; Liu, Antonio

2017-12-01

Shunt nephritis is a rare and relatively new diagnosis involving glomerular kidney damage following ventriculoperitoneal and ventriculoatrial shunt placement. Our case report summarizes the presentation, diagnostic workup, and management of a patient with shunt nephritis. We also review and discuss the current literature on the topic.

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

PubMed Central

2012-01-01

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

IgG4-related tubulointerstitial nephritis: A prospective analysis.

PubMed

Nada, Ritambhra; Ramachandran, Raja; Kumar, Ashwani; Rathi, Manish; Rawat, Amit; Joshi, Kusum; Kohli, Harbir Singh; Gupta, Krishan Lal

2016-07-01

Immunoglobulin-G4 (IgG4)-related tubulo-interstitial nephritis (IgG4TIN) could be the first presentation of IgG4-related systemic disease. Most of the data is from the West or Japan and retrospective, with good patient outcome. This study was carried out from April 2011 to July 2013. We report a prospective follow-up of 11 patients who presented with renal dysfunction and had histological diagnosis of IgG4TIN followed for a minimum period of 1 year or until end-stage renal disease. IgG4TIN constituted 0.28% of total renal biopsies and 6.5% of all tubulointerstitial nephritis. Patient ages ranged between 21 and 71 years with a male predominance. All the patients had renal dysfunction at presentation with a mean serum creatinine of 5.12 mg/dL. Proteinuria was subnephrotic except when there was coexisting membranous glomerulonephritis (36.4%). The mean 24-h urine protien excretion was 1.8 g. Serum IgG4 levels were elevated in 10 (90.9%) patients. Ten (90.9%) patients had renomegaly and one (9.1%) had focal renal mass. Extra-renal manifestations were present in seven (63.6%). Renal histology showed pattern A in five (45.5%), pattern B in four (36.3%) and pattern C in two (18.1%) patients. All but one patient (90.9%) received immunosuppressive therapy. Four (36.3%) achieved complete remission and three (27.2%) progressed to end stage renal disease. Two patients died due to infections while on steroid therapy. One patient with a mass had end stage renal disease for 12 months and did not improve with steroid therapy, and one (pattern C) had progressive chronic kidney disease on follow-up. IgG4TIN in an Indian cohort most often presents with rapidly progressive renal failure and less often has extra-renal organ involvement. On follow-up, patients can experience a more aggressive course with progression to end stage renal disease. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Impaired organic ion transport in proximal tubules of rats with Heymann nephritis.

PubMed

Park, E K; Hong, S K; Goldinger, J; Andres, G; Noble, B

1985-10-01

Organic ion transport across the basolateral membrane of proximal tubules was measured by means of the tissue slice technique in each of the four different stages of Heymann nephritis. Impairment of both organic anion and cation transport was detected early in Stage 2, and became more severe in Stage 3 of Heymann nephritis. The decreased transport function was associated with extensive damage to proximal tubule cells, including loss of brush border microvilli and basal infoldings. Despite these abnormalities of structure and function, oxygen consumption of proximal tubule cells remained essentially normal. Partial recovery of organic cation transport was noted late in Heymann nephritis (Stage 4). Recovery of the cation transport function was associated with a partial restoration of brush border microvilli and basal infoldings to proximal tubule cells. However, organic anion transport remained depressed throughout the entire course of disease. Impairment of organic ion transport in rats with Heymann nephritis appeared to result from damage to basolateral membrane transport elements rather than general deterioration of the metabolic machinery of proximal tubule cells. Decreased organic cation transport appeared to be the consequence of a reduction in the number of carrier sites, a phenomenon that could have resulted from decreased membrane surface area. However, the depression of organic anion transport was associated with decreased substrate affinity of the anion carrier, indicating that qualitative, rather than quantitative changes, were primarily responsible for that defect. Specific antibody-mediated damage to the anion transport elements in basolateral membranes of proximal tubules is postulated to occur in Heymann nephritis.

Epstein-Barr virus-associated hemophagocytic syndrome in a patient with lupus nephritis.

PubMed

Isome, Masato; Suzuki, Junzo; Takahashi, Ai; Murai, Hiromichi; Nozawa, Ruriko; Suzuki, Shigeo; Kawasaki, Yukihiko; Suzuki, Hitoshi

2005-02-01

Hemophagocytic syndrome (HPS) is an unusual but severe illness associated with a variety of infections, as well as genetic, malignant tumors, and autoimmune diseases. We report an 11-year-old girl with systemic lupus erythematosus and nephritis who developed HPS associated with Epstein-Barr virus reactivation. In our patient, the onset of reactive HPS might be related to immunosuppressive treatment during the course of lupus nephritis.

The role of antimalarial agents in the treatment of SLE and lupus nephritis.

PubMed

Lee, Senq-J; Silverman, Earl; Bargman, Joanne M

2011-10-18

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that affects various organs. Lupus nephritis is one of the most common, and most important, serious manifestations of SLE. Antimalarial agents are part of the immunomodulatory regimen used to treat patients with SLE; however, their role in the treatment of patients with lupus nephritis in particular is less well recognized, especially by nephrologists. Not all antimalarial agents have been used in the treatment of lupus; this Review will focus on studies using chloroquine and hydroxychloroquine. In addition, this Review will briefly describe the history of antimalarial drug use in patients with SLE, the theorized mechanisms of action of the agents chloroquine and hydroxychloroquine, their efficacy in patients with SLE and those with lupus nephritis, their use in pregnancy, and potential adverse effects. The Review will also cover the latest recommendations regarding monitoring for hydroxychloroquine-associated or chloroquine-associated retinopathy. Overall, antimalarial drugs have numerous beneficial effects in patients with SLE and lupus nephritis, and have a good safety profile.

Significance of anti-phospholipid antibodies in patients with lupus nephritis.

PubMed

Frampton, G; Hicks, J; Cameron, J S

1991-06-01

Anti-phospholipid antibodies (APA) as markers or mediators of thrombosis in lupus could be of pathogenetic significance in nephritis, since glomerular capillary thrombi are an indicator of subsequent renal dysfunction. Isotype specific APA antibodies were measured, using cardiolipin as the antigen, in 76 patients with lupus nephritis. Twenty-nine percent of the patients had elevated IgG APA. Overall, 43% of patients showed raised levels of at least one isotype. In general, APA had specificity for anionic phospholipids. In vitro lupus anticoagulant activity was associated with all three isotypes of APA, but only the IgM isotype correlated with the biological false positive test for syphilis. APA were not associated with thromboses or neurological involvement, and only the IgA isotype correlated with thrombocytopenia. We confirmed an association between the presence of intraglomerular thrombi and serum IgG APA. However, we found no association between APA and renal histological pattern, or long-term renal function. Our data, therefore, do not support a major pathogenetic role for APA in the nephritis of lupus in treated patients.

Neurological sequelae of bacterial meningitis.

PubMed

Lucas, Marjolein J; Brouwer, Matthijs C; van de Beek, Diederik

2016-07-01

We reported on occurrence and impact of neurological sequelae after bacterial meningitis. We reviewed occurrence of neurological sequelae in children and adults after pneumococcal and meningococcal meningitis. Most frequently reported sequelae are focal neurological deficits, hearing loss, cognitive impairment and epilepsy. Adults with pneumococcal meningitis have the highest risk of developing focal neurological deficits, which are most commonly caused by cerebral infarction, but can also be due to cerebritis, subdural empyema, cerebral abscess or intracerebral bleeding. Focal deficits may improve during clinical course and even after discharge, but a proportion of patients will have persisting focal neurological deficits that often interfere in patient's daily life. Hearing loss occurs in a high proportion of patients with pneumococcal meningitis and has been associated with co-existing otitis. Children and adults recovering from bacterial meningitis without apparent neurological deficits are at risk for long-term cognitive deficits. Early identification of neurological sequelae is important for children to prevent additional developmental delay, and for adults to achieve successful return in society after the disease. Neurological sequelae occur in a substantial amount of patients following bacterial meningitis. Most frequently reported sequelae are focal neurological deficits, hearing loss, cognitive impairment and epilepsy. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Outcomes in African Americans and Hispanics with lupus nephritis.

PubMed

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

2006-05-01

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

Pathogenesis of acute viral disease induced in fish by carp interstitial nephritis and gill necrosis virus.

PubMed

Pikarsky, Eli; Ronen, Ariel; Abramowitz, Julia; Levavi-Sivan, Berta; Hutoran, Marina; Shapira, Yechiam; Steinitz, Michael; Perelberg, Ayana; Soffer, Dov; Kotler, Moshe

2004-09-01

A lethal disease of koi and common carp (species Cyprinus carpio) has afflicted many fish farms worldwide since 1998, causing severe financial losses. Morbidity and mortality are restricted to common carp and koi and appear in spring and autumn, when water temperatures are 18 to 28 degrees C. We have isolated the virus causing the disease from sick fish, propagated it in koi fin cell culture, and shown that virus from a single clone causes lethal disease in carp and koi upon infection. Intraperitoneal virus injection or bathing the fish in virus-containing water kills 85 to 100% of the fish within 7 to 21 days. This virus is similar to the previously reported koi herpesvirus; however, it has characteristics inconsistent with the herpesvirus family, and thus we have called it carp interstitial nephritis and gill necrosis virus. We examined the pathobiology of this disease in carp by using immunohistochemistry and PCR. We found large amounts of the virus in the kidneys of sick fish and smaller amounts in liver and brain. A rapid increase in the viral load in the kidneys was detected by using both immunofluorescence and semiquantitative PCR. Histological analyses of fish at various times after infection revealed signs of interstitial nephritis as early as 2 days postinfection, which increased in severity up to 10 days postinfection. There was severe gill disease evidenced by loss of villi with accompanying inflammation in the gill rakers. Minimal focal inflammation was noted in livers and brains. This report describes the etiology and pathology of a recently described viral agent in fish.

Pathogenesis of Acute Viral Disease Induced in Fish by Carp Interstitial Nephritis and Gill Necrosis Virus

PubMed Central

Pikarsky, Eli; Ronen, Ariel; Abramowitz, Julia; Levavi-Sivan, Berta; Hutoran, Marina; Shapira, Yechiam; Steinitz, Michael; Perelberg, Ayana; Soffer, Dov; Kotler, Moshe

2004-01-01

A lethal disease of koi and common carp (species Cyprinus carpio) has afflicted many fish farms worldwide since 1998, causing severe financial losses. Morbidity and mortality are restricted to common carp and koi and appear in spring and autumn, when water temperatures are 18 to 28°C. We have isolated the virus causing the disease from sick fish, propagated it in koi fin cell culture, and shown that virus from a single clone causes lethal disease in carp and koi upon infection. Intraperitoneal virus injection or bathing the fish in virus-containing water kills 85 to 100% of the fish within 7 to 21 days. This virus is similar to the previously reported koi herpesvirus; however, it has characteristics inconsistent with the herpesvirus family, and thus we have called it carp interstitial nephritis and gill necrosis virus. We examined the pathobiology of this disease in carp by using immunohistochemistry and PCR. We found large amounts of the virus in the kidneys of sick fish and smaller amounts in liver and brain. A rapid increase in the viral load in the kidneys was detected by using both immunofluorescence and semiquantitative PCR. Histological analyses of fish at various times after infection revealed signs of interstitial nephritis as early as 2 days postinfection, which increased in severity up to 10 days postinfection. There was severe gill disease evidenced by loss of villi with accompanying inflammation in the gill rakers. Minimal focal inflammation was noted in livers and brains. This report describes the etiology and pathology of a recently described viral agent in fish. PMID:15308746

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-27

... ``Lupus Nephritis Caused By Systemic Lupus Erythematosus--Developing Medical Products for Treatment...] Guidance for Industry on Lupus Nephritis Caused by Systemic Lupus Erythematosus--Developing Medical Products for Treatment; Withdrawal of Guidance AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

Integrative medicine for managing the symptoms of lupus nephritis

PubMed Central

Choi, Tae-Young; Jun, Ji Hee; Lee, Myeong Soo

2018-01-01

Abstract Background: Integrative medicine is claimed to improve symptoms of lupus nephritis. No systematic reviews have been performed for the application of integrative medicine for lupus nephritis on patients with systemic lupus erythematosus (SLE). Thus, this review will aim to evaluate the current evidence on the efficacy of integrative medicine for the management of lupus nephritis in patients with SLE. Methods and analyses: The following electronic databases will be searched for studies published from their dates of inception February 2018: Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as 6 Korean medical databases (Korea Med, the Oriental Medicine Advanced Search Integrated System [OASIS], DBpia, the Korean Medical Database [KM base], the Research Information Service System [RISS], and the Korean Studies Information Services System [KISS]), and 1 Chinese medical database (the China National Knowledge Infrastructure [CNKI]). Study selection, data extraction, and assessment will be performed independently by 2 researchers. The risk of bias (ROB) will be assessed using the Cochrane ROB tool. Dissemination: This systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to inform and guide healthcare practice and policy. Trial registration number: PROSPERO 2018 CRD42018085205 PMID:29595669

Bacterial Sepsis in Patients with Visceral Leishmaniasis in Northwest Ethiopia

PubMed Central

Takele, Yegnasew; Woldeyohannes, Desalegn; Tiruneh, Moges; Mohammed, Rezika; Lynen, Lutgarde; van Griensven, Johan

2014-01-01

Background and Objectives. Visceral leishmaniasis (VL) is one of the neglected diseases affecting the poorest segment of world populations. Sepsis is one of the predictors for death of patients with VL. This study aimed to assess the prevalence and factors associated with bacterial sepsis, causative agents, and their antimicrobial susceptibility patterns among patients with VL. Methods. A cross-sectional study was conducted among parasitologically confirmed VL patients suspected of sepsis admitted to the University of Gondar Hospital, Northwest Ethiopia, from February 2012 to May 2012. Blood cultures and other clinical samples were collected and cultured following the standard procedures. Results. Among 83 sepsis suspected VL patients 16 (19.3%) had culture confirmed bacterial sepsis. The most frequently isolated organism was Staphylococcus aureus (68.8%; 11/16), including two methicillin-resistant isolates (MRSA). Patients with focal bacterial infection were more likely to have bacterial sepsis (P < 0.001). Conclusions. The prevalence of culture confirmed bacterial sepsis was high, predominantly due to S. aureus. Concurrent focal bacterial infection was associated with bacterial sepsis, suggesting that focal infections could serve as sources for bacterial sepsis among VL patients. Careful clinical evaluation for focal infections and prompt initiation of empiric antibiotic treatment appears warranted in VL patients. PMID:24895569

NITROGEN RETENTION IN THE BLOOD IN EXPERIMENTAL ACUTE NEPHRITIS OF THE CAT

PubMed Central

Folin, Otto; Karsner, Howard T.; Denis, W.

1912-01-01

It will be seen that uranium nephritis, which involves both tubules and glomeruli, the former more markedly than the latter, produces a marked accumulation of nitrogen in the blood. Chromate nephritis, which involves almost exclusively the tubules, produces only moderate retention of nitrogen. Cantharidin nephritis which involves both tubules and glomeruli, the latter more severely than does uranium, produces a marked accumulation of nitrogen, beginning early and persisting for a considerable period. The experiments were controlled by testing the blood of normal cats kept under the same conditions, these animals showing only slight variations from day to day. This general statement is in accordance with the physiological classification of these nephritides except that the retention in uranium occurs at an early stage, where, according to the physiological studies of Schlayer and his associates, and of Pearce, Hill, and Eisenbrey, the vascular changes have not as yet appeared. It must be noticed that in the three types of nephritis that form the subject of this investigation, anatomical study shows the glomerulus to be distinctly involved in the two forms where accumulation of nitrogen in the blood is most marked, a condition indicating that although almost pure tubular involvement produces only moderate accumulation, the additional involvement of the glomerulus is extremely important in leading to a retention of nitrogenous waste products. The accumulation of non-protein nitrogen in the blood and tissues is not large when compared with the total intake or elimination of nitrogen, and consequently it is practically impossible by means of ordinary nitrogen equilibrium experiments to demonstrate the fact of the retention, to say nothing of determining the degree of accumulation of waste products accompanying nephritis. That both can be demonstrated by the method employed in this research is clearly shown by the figures recorded ablove. PMID:19867613

NITROGEN RETENTION IN THE BLOOD IN EXPERIMENTAL ACUTE NEPHRITIS OF THE CAT.

PubMed

Folin, O; Karsner, H T; Denis, W

1912-12-01

It will be seen that uranium nephritis, which involves both tubules and glomeruli, the former more markedly than the latter, produces a marked accumulation of nitrogen in the blood. Chromate nephritis, which involves almost exclusively the tubules, produces only moderate retention of nitrogen. Cantharidin nephritis which involves both tubules and glomeruli, the latter more severely than does uranium, produces a marked accumulation of nitrogen, beginning early and persisting for a considerable period. The experiments were controlled by testing the blood of normal cats kept under the same conditions, these animals showing only slight variations from day to day. This general statement is in accordance with the physiological classification of these nephritides except that the retention in uranium occurs at an early stage, where, according to the physiological studies of Schlayer and his associates, and of Pearce, Hill, and Eisenbrey, the vascular changes have not as yet appeared. It must be noticed that in the three types of nephritis that form the subject of this investigation, anatomical study shows the glomerulus to be distinctly involved in the two forms where accumulation of nitrogen in the blood is most marked, a condition indicating that although almost pure tubular involvement produces only moderate accumulation, the additional involvement of the glomerulus is extremely important in leading to a retention of nitrogenous waste products. The accumulation of non-protein nitrogen in the blood and tissues is not large when compared with the total intake or elimination of nitrogen, and consequently it is practically impossible by means of ordinary nitrogen equilibrium experiments to demonstrate the fact of the retention, to say nothing of determining the degree of accumulation of waste products accompanying nephritis. That both can be demonstrated by the method employed in this research is clearly shown by the figures recorded ablove.

Annexin II-binding immunoglobulins in patients with lupus nephritis and their correlation with disease manifestations.

PubMed

Cheung, Kwok Fan; Yung, Susan; Chau, Mel K M; Yap, Desmond Y H; Chan, Kwok Wah; Lee, Cheuk Kwong; Tang, Colin S O; Chan, Tak Mao

2017-04-25

Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins (Igs) in patients with severe proliferative lupus nephritis, and renal annexin II expression in relation to progression of nephritis in New Zealand Black and White F1 mice (NZBWF1/J) mice. Annexin II-binding Igs in serum were measured by ELISA. Ultrastructural localization of annexin II was determined by electron microscopy. Seropositivity rates for annexin II-binding IgG and IgM in patients with active lupus nephritis were significantly higher compared with controls (8.9%, 1.3% and 0.9% for annexin II-binding IgG and 11.1%, 4.0% and 1.9% for annexin II-binding IgM for patients with active lupus nephritis, patients with non-lupus renal disease and healthy subjects respectively). In lupus patients, annexin II-binding IgM level was higher at disease flare compared with remission. Annexin II-binding IgG and IgM levels were associated with that of anti-dsDNA and disease activity. Annexin II-binding IgG and IgM levels correlated with histological activity index in lupus nephritis biopsy samples. In NZBWF1/J mice, serum annexin II-binding IgG and IgM levels and glomerular annexin II and p11 expression increased with progression of active nephritis. Annexin II expression was present on mesangial cell surface and in the mesangial matrix, and co-localized with electron-dense deposits along the glomerular basement membrane. Our results show that circulating annexin II-binding IgG and IgM levels are associated with clinical and histological disease activity in proliferative lupus nephritis. The co-localization of annexin II and p11 expression with immune deposition in the kidney suggests pathogenic relevance. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Lupus nephritis in Lebanon.

PubMed

Uthman, I W; Muffarij, A A; Mudawar, W A; Nasr, F W; Masri, A F

2001-01-01

This is a retrospective study of the clinicopathological characteristics of 50 systemic lupus erythematosus patients with nephritis who underwent a kidney biopsy and were admitted to the American University of Beirut Medical Center, in Lebanon, between 1979 and 1999. There were 43 females and seven males, with a median age of 24 y. Renal histology slides from these patients were assessed according to the World Health Organization classification, and were distributed as follows: class I (n = 3, 6%); class II (n = 14, 28%); class III (n = 11, 22%); class IV (n = 19, 38%); class V (n = 1, 2%); class VI (n = 2, 4%). All the patients received oral prednisone, in addition the following treatments were used: pulse intravenous (i.v.) cyclophosphamide (n = 23, 46%); azathioprine (n = 22, 44%); pulse i.v. steroids (n = 19, 38%); chloroquine sulfate (n = 17, 34%); methotrexate (n = 5, 10%); and plasmapheresis (n = 2, 4%). The median duration of follow-up was 5 y (range 1-33 y). On their last evaluation, out of 37 patients who were followed, 20 patients (54%) had controlled disease, eight patients (22%) were still on active medical treatment, four patients (11%) were on chronic hemodialysis, and five patients (13%) had died. Unlike three other Arab populations studies from Kuwait, United Arab Emirates and Saudi Arabia, where the most frequent histopathologic abnormality was class III, diffuse proliferative LN (class IV) was the most common type of lupus nephritis in Lebanon, similarly to reports from USA, France, Netherlands, South Africa, Thailand and Taiwan.

Tubulointerstitial Nephritis and Uveitis Syndrome in a Twelve-Year-Old Girl

PubMed Central

Paladini, Alessia; Venturoli, Vittorio; Mosconi, Giovanni; Zambianchi, Loretta; Serra, Luigi; Valletta, Enrico

2013-01-01

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disorder defined by the combination of biochemical abnormalities, tubulointerstitial nephritis, and uveitis. We describe a 12-year-old female, presented with a ten-day history of fever, characterized by sudden onset and rapid spontaneous resolution in few hours, accompanied by shivering, extreme fatigue, and loss of appetite. Laboratory values were consistent with renal failure of tubular origin. Renal biopsy confirmed a tubulointerstitial nephritis, with acute tubulitis, polymorphonuclear infiltration, and microabscesses. The renal interstitium was occupied by a dense inflammatory infiltrate, consisting of lymphocytes, plasma cells, and neutrophils. Glomerular structures were preserved. Ophthalmological examination that suggested a previous asymptomatic bilateral uveitis and HLA typing (HLA-DQA1∗0101/0201 and HLA-DQB1∗0303/0503) further supported the suspect of TINU syndrome. TINU syndrome is probably an underdiagnosed disorder, responsible for many cases of idiopathic anterior uveitis in young patients, especially in those who have asymptomatic renal disease and when proper diagnostic tests are not performed at the time of presentation. PMID:23691408

Tubulointerstitial nephritis and uveitis syndrome in a twelve-year-old girl.

PubMed

Paladini, Alessia; Venturoli, Vittorio; Mosconi, Giovanni; Zambianchi, Loretta; Serra, Luigi; Valletta, Enrico

2013-01-01

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disorder defined by the combination of biochemical abnormalities, tubulointerstitial nephritis, and uveitis. We describe a 12-year-old female, presented with a ten-day history of fever, characterized by sudden onset and rapid spontaneous resolution in few hours, accompanied by shivering, extreme fatigue, and loss of appetite. Laboratory values were consistent with renal failure of tubular origin. Renal biopsy confirmed a tubulointerstitial nephritis, with acute tubulitis, polymorphonuclear infiltration, and microabscesses. The renal interstitium was occupied by a dense inflammatory infiltrate, consisting of lymphocytes, plasma cells, and neutrophils. Glomerular structures were preserved. Ophthalmological examination that suggested a previous asymptomatic bilateral uveitis and HLA typing (HLA-DQA1∗0101/0201 and HLA-DQB1∗0303/0503) further supported the suspect of TINU syndrome. TINU syndrome is probably an underdiagnosed disorder, responsible for many cases of idiopathic anterior uveitis in young patients, especially in those who have asymptomatic renal disease and when proper diagnostic tests are not performed at the time of presentation.

Anti-pentraxin 3 auto-antibodies might be protective in lupus nephritis: a large cohort study.

PubMed

Yuan, Mo; Tan, Ying; Pang, Yun; Li, Yong-Zhe; Song, Yan; Yu, Feng; Zhao, Ming-Hui

2017-11-01

Anti-pentraxin 3 (PTX3) auto-antibodies were found to be associated with the absence of renal involvement in systemic lupus erythematosus (SLE). This study is to investigate the prevalence of anti-PTX3 auto-antibodies and their clinical significance based on a large Chinese lupus nephritis cohort. One hundred and ninety-six active lupus nephritis patients, 150 SLE patients without clinical renal involvement, and 100 healthy controls were enrolled. Serum anti-PTX3 auto-antibodies and PTX3 levels were screened by enzyme-linked immunosorbent assay (ELISA). The associations between anti-PTX3 auto-antibodies and clinicopathological parameters in lupus nephritis were further analyzed. Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement (19.4% (38/196) versus 40.7% (61/150), p < .001). The serum levels of anti-PTX3 auto-antibodies were negatively correlated with proteinuria in lupus nephritis (r = -.143, p = .047). The levels of proteinuria, serum creatinine, and the prevalence of thrombotic microangiopathy were significantly higher in patients with higher PTX3 levels (≥3.207 ng/ml) and without anti-PTX3 auto-antibodies compared with patients with lower PTX3 levels (<3.207 ng/ml) and with anti-PTX3 auto-antibodies (4.79 (3.39-8.28) versus 3.95 (1.78-7.0), p = .03; 168.84 ± 153.63 versus 101.44 ± 47.36, p = .01; 34.1% (14/41) versus 0% (0/9), p = .04; respectively). Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement and associated with less severe renal damage, especially with the combined evaluation of serum PTX3 levels.

Lupus nephritis with preserved kidney function associated with poorer cardiovascular risk control: A call for more awareness.

PubMed

Todolí-Parra, J A; Tung-Chen, Y; Micó, L; Gutiérrez, J; Hernández-Jaras, J; Ruiz-Cerda, J L

2018-01-27

Despite the improvement in the prognosis of lupus nephritis (LN), the cardiovascular morbimortality remains high. The early recognition and remission of flares, while trying to avoid the metabolic adverse effects of medication, must be mandatory. The aim of our study was to assess the cardiovascular (CV) risk profile in a cohort of lupus patients with preserved kidney function after a nephritis episode, compared to patients without a nephritis flare. 130 patients diagnosed of SLE (32 with previous nephritis flare and 98 without) were studied in order to evaluate the CV risk profile, despite the preserved kidney function. The most prevalent risk factors were sedentary lifestyle (57.6%), overweight/obesity (38.3%) and dyslipidemia (36%), followed by smoking (32%) and hypertension (16%). Though more than a half (53.1%) was taking CV medication, a high percentage did not reach a therapeutic target value, especially regarding obesity (11.5%) and cholesterol levels (LDL-C of 16%). The prevalence of dyslipidemia (53.1% vs 30.6%), smoking (46.6% vs 27.5%), left ventricular hypertrophy (LVH) (21.4% vs 6.4%) and lower HDL-C (48.6mg/dL vs 55.4mg/dL) were significantly different in the group with previous nephritis flare. Moreover, young patients with lupus nephritis, received more pulses of corticosteroids and cyclophosphamide, had higher prevalence of hypertension, LVH, higher proteinuria, hospital admissions and waist circumference, constituting the subgroup of patients with greater aggregation of CV risk factors. Patients with previous nephritis flare showed a poor control of CV risk factors despite the preserved renal function, these patients would require a closer therapeutic management. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

TUBULOINTERSTITIAL NEPHRITIS AND UVEITIS SYNDROME WITH A PRIMARY PRESENTATION OF ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY.

PubMed

Lee, Andrew R; Sharma, Sumit; Mahmoud, Tamer H

2017-01-01

To report a case of tubulointerstitial nephritis and uveitis syndrome with a primary presentation of acute posterior multifocal placoid pigment epitheliopathy after use of lamotrigine. Retrospective case report with ultra-widefield fundus imaging, optical coherence tomography, and fluorescein angiography. A 19-year-old woman presented with decreased visual acuity and acute renal failure after starting lamotrigine. Her examination demonstrated 1+ anterior chamber cell and numerous white deep retinal plaque-like lesions predominantly in the macula in both eyes. After extensive ophthalmic and systemic evaluation, the patient was diagnosed with tubulointerstitial nephritis and uveitis syndrome with a primary presentation of acute posterior multifocal placoid pigment epitheliopathy. She had excellent visual recovery with topical and systemic steroids. Acute posterior multifocal placoid pigment epitheliopathy is a rare but important clinical presentation of tubulointerstitial nephritis and uveitis syndrome. Oral corticosteroid treatment can be considered for tubulointerstitial nephritis but is generally not necessary for acute posterior multifocal placoid pigment epitheliopathy.

Modulation of interferon-induced genes by lipoxin analogue in anti-glomerular basement membrane nephritis.

PubMed

Ohse, Takamoto; Ota, Tatsuru; Kieran, Niamh; Godson, Catherine; Yamada, Koei; Tanaka, Tetsuhiro; Fujita, Toshiro; Nangaku, Masaomi

2004-04-01

Immune complex deposition is associated with the accumulation of neutrophils, which play an important role in the various immune-mediated diseases. A novel anti-inflammatory agent, the lipoxin A (LXA) analogue (15-epi-16-(FPhO)-LXA-Me)), a stable synthetic analogue of aspirin-triggered 15-epi-lipoxin A4 (ATLa), was used in experimental anti-glomerular basement membrane (GBM) antibody nephritis in mice. ATLa was administered before the induction of the disease, and 2 h later, the animals were killed. ATLa reduced the infiltrating neutrophils and nitrotyrosine staining in glomeruli. Subsequent changes of gene expression in the early phase were evaluated, and 5674 genes were present under the basal conditions in kidneys from normal mice; 54 upregulated genes and 25 downregulated genes were detected in anti-GBM nephritis. Eighteen of these upregulated genes were those induced by IFN-gamma. Real-time quantitative PCR analysis confirmed the results of the microarrays. To investigate a role of IFN-gamma in neutrophil infiltration, anti-GBM nephritis was induced in IFN-gamma knockout mice. The number of infiltrating neutrophils in these mice did not differ from those in wild-type mice. Also examined were CD11b expression on neutrophils from mice treated with ATLa by flow cytometry, but suppression of this adhesion molecule was not observed. Neutrophil infiltration was successfully inhibited by ATLa in the early phase of murine anti-GBM nephritis. Microarray analysis detected the change of mRNA expression in anti-GBM nephritis and demonstrated amelioration of various genes by ATLa, which may provide a clue to the development of novel therapeutic approaches in immune renal injury.

Renal Interstitial Arteriosclerotic Lesions in Lupus Nephritis Patients: A Cohort Study from China

PubMed Central

Qin, Dan-dan; Wu, Li-hua; Song, Yan; Yu, Feng; Wang, Su-xia; Liu, Gang; Zhao, Ming-hui

2015-01-01

Objective The aim of this study was to evaluate renal arteriosclerotic lesions in patients with lupus nephritis and investigate their associations with clinical and pathological characteristics, especially cardio-vascular features. Design A retrospective cohort study. Participants Seventy-nine patients with renal biopsy-proven lupus nephritis, diagnosed between January 2000 and June 2008 from Peking University First Hospital. Results In clinico-pathological data, patients with arteriosclerosis had higher ratio of hypertension and more severe renal injury indices compared with patients with no renal vascular lesions. More importantly, patients with renal arteriosclerosis had worse cardiac structure and function under transthoracic echocardiographic examination. Patients with renal arteriosclerosis tend to have higher ratios of combined endpoints compared with those of no renal vascular lesions, although the difference didn’t reach statistical meanings (P = 0.104). Conclusion Renal arteriosclerotic lesion was common and associated with vascular immune complex deposits in lupus nephritis. It might have a certain degree of association with poor outcomes and cardiovascular events, which needs further explorations. PMID:26544865

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

PubMed

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

2013-06-01

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

Immunologic findings, thrombocytopenia and disease activity in lupus nephritis.

PubMed Central

Clark, W. F.; Linton, A. L.; Cordy, P. E.; Keown, P. E.; Lohmann, R. C.; Lindsay, R. M.

1978-01-01

Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis. PMID:350367

Serum uric acid levels are associated with lupus nephritis in patients with normal renal function.

PubMed

Calich, Ana Luisa; Borba, Eduardo Ferreira; Ugolini-Lopes, Michelle Remião; da Rocha, Luiza Fuoco; Bonfá, Eloisa; Fuller, Ricardo

2018-05-01

Uric acid has been recognised as a potential marker of endothelial dysfunction and kidney disease but there are scarce data about its importance in systemic lupus erythematosus (SLE) nephritis. This study aimed to evaluate serum uric acid (UA) levels in lupus nephritis (LN), by comparing SLE patients with normal renal function, with and without nephritis. Forty-six female SLE patients were consecutively selected and divided in two groups according to renal activity at the evaluation: presence of a recently diagnosed lupus nephritis (LN+, n = 18) and absence of lupus nephritis (LN-, n = 28). Age-matched healthy women were selected (CONTROL, n = 28). Patients with gout, creatinine clearance lower than 80 ml/min and use of drugs that interfere in UA were excluded. Laboratory and clinical data were analysed by appropriate tests. A multivariate analysis was performed, and a receiver operating characteristic (ROC) curve was plotted, and the area under the curve was calculated to assess the diagnostic strength of UA in LN. The mean age was similar among LN+, LN- and CONTROL groups (32.44 ± 6.09 vs. 30.68 ± 5.36 vs. 30.86 ± 5.00 years, p = 0.52). UA was significantly higher in LN+ compared to LN- (5.54 ± 1.67 vs. 3.65 ± 1.090 mg/dL, p < 0.001) and CONTROL (5.54 ± 1.67 vs. 3.92 ± 0.95 mg/dL p < 0.001). Multivariate analysis confirmed that high UA was an independent variable related to LN (p < 0.001). The cut-off value for UA using the ROC curve was 4.47 mg/dL (AUC 0.86, p = 0.00004, CI 95% 0.75-0.96). Lupus nephritis was associated with higher UA. Hyperuricemia as a predictor of renal damage in SLE needs to be evaluated in further studies.

Economic outcomes in patients diagnosed with systemic lupus erythematosus with versus without nephritis: results from an analysis of data from a US claims database.

PubMed

Pelletier, Elise M; Ogale, Sarika; Yu, Elaine; Brunetta, Paul; Garg, Jay

2009-11-01

Based on a literature search, there are limited data on the economic burden of systemic lupus erythematosus (SLE), particularly in patients with lupus nephritis. The objective of this study was to compare health care resource utilization and direct medical care costs over a period of 12 months in patients with a history of SLE with or without nephritis. Patients aged >or=18 years with >or=1 claim for an immunosuppressive/disease-modifying antirheumatic drug, antimalarial agent, NSAID/cyclooxygenase-2 inhibitor, or other SLE-related treatment (eg, opioid and combination analgesic, antianxiety agent, antihyperlipidemic agent, antihypertensive agent, bisphosphonate, vitamin D) dated between January 1, 2007, and December 31, 2007, were identified using a nationally representative, US commercial insurance claims database. The date of the first dispensation of the treatment represented the index date. Patients were required to have >or=2 claims containing a diagnosis of SLE during a 6-month preindex period through 3 months postindex and to have continuous health plan enrollment for 6 months before and 12 months after the index date. Patients with >or=1 claim containing a diagnosis of nephritis during the preindex period were identified. Health care resource utilization and direct medical care cost data were assessed over a period of 12 months; paid amounts were used as a proxy for costs and were expressed in year-2008 US dollars. A total of 15,590 patients with SLE were identified (13,828 women, 1762 men; mean age, 48 years); 1068 (6.9%) had a history of nephritis. The mean age of patients with SLE without nephritis was significantly greater compared with the group with nephritis (47.9 vs 46.5 years, respectively; P < 0.001), and a greater proportion of this group were women (89.0% vs 84.7%; P < 0.001). Over a period of 12 months, 30.3% of patients with nephritis were hospitalized compared with 13.6% of those without nephritis (P < 0.001); the mean lengths of hospital

Therapeutic Effect of Dendrobium candidum on Lupus Nephritis in Mice.

PubMed

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

2017-01-01

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

Autoantigen microarrays reveal autoantibodies associated with proliferative nephritis and active disease in pediatric systemic lupus erythematosus.

PubMed

Haddon, D James; Diep, Vivian K; Price, Jordan V; Limb, Cindy; Utz, Paul J; Balboni, Imelda

2015-06-17

Pediatric systemic lupus erythematosus (pSLE) patients often initially present with more active and severe disease than adults, including a higher frequency of lupus nephritis. Specific autoantibodies, including anti-C1q, anti-DNA and anti-alpha-actinin, have been associated with kidney involvement in SLE, and DNA antibodies are capable of initiating early-stage lupus nephritis in severe combined immunodeficiency (SCID) mice. Over 100 different autoantibodies have been described in SLE patients, highlighting the need for comprehensive autoantibody profiling. Knowledge of the antibodies associated with pSLE and proliferative nephritis will increase the understanding of SLE pathogenesis, and may aid in monitoring patients for renal flare. We used autoantigen microarrays composed of 140 recombinant or purified antigens to compare the serum autoantibody profiles of new-onset pSLE patients (n = 45) to healthy controls (n = 17). We also compared pSLE patients with biopsy-confirmed class III or IV proliferative nephritis (n = 23) and without significant renal involvement (n = 18). We performed ELISA with selected autoantigens to validate the microarray findings. We created a multiple logistic regression model, based on the ELISA and clinical information, to predict whether a patient had proliferative nephritis, and used a validation cohort (n = 23) and longitudinal samples (88 patient visits) to test its accuracy. Fifty autoantibodies were at significantly higher levels in the sera of pSLE patients compared to healthy controls, including anti-B cell-activating factor (BAFF). High levels of anti-BAFF were associated with active disease. Thirteen serum autoantibodies were present at significantly higher levels in pSLE patients with proliferative nephritis than those without, and we confirmed five autoantigens (dsDNA, C1q, collagens IV and X and aggrecan) by ELISA. Our model, based on ELISA measurements and clinical variables, correctly identified patients with proliferative

BK virus induced nephritis in a boy with acute myeloid leukaemia undergoing bone marrow transplantation

PubMed Central

Hoefele, Julia; Rüssmann, Despina; Klein, Barbara; Weber, Lutz T.; Führer, Monika

2008-01-01

BK virus (BKV) is a human polyomavirus. The primary infection occurs typically without specific signs or symptoms. Almost 80% of adults are seropositive. Clinically relevant infections are usually limited to individuals who are immunosuppressed. After primary infection, BKV remains latent in the kidneys and can be reactivated in the setting of immunosuppression. BKV is associated with tubulointerstitial nephritis and ureteric stenosis in renal transplant recipients. Furthermore, BKV-induced haemorrhagic cystitis (HC) is a severe complication of bone marrow transplantation (BMT) in children and adults. A combination of HC and tubulointerstitial nephritis in a patient has not been reported so far. We report on an 11-year-old boy with acute myeloid leukaemia undergoing BMT. BKV infection was reactivated during post-transplant immunosuppressive therapy causing HC associated with tubulointerstitial nephritis. PMID:25983928

Appraisal of lupus nephritis by renal imaging with gallium-67

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

Bakir, A.A.; Lopez-Majano, V.; Hryhorczuk, D.O.

1985-08-01

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

Association of the osteopontin rs1126616 polymorphism and a higher serum osteopontin level with lupus nephritis

PubMed Central

SALIMI, SAEEDEH; NOORA, MEHRANGIZ; NABIZADEH, SIMA; REZAEI, MAHNAZ; SHAHRAKI, HOSSAIN; MILAD, MOHAMMADOO-KHORASSANI; NAGHAVI, ANOOSH; FARAJIAN-MASHHADI, FARZANEH; ZAKERI, ZAHRA; SANDOUGHI, MAHNAZ

2016-01-01

Osteopontin (OPN) is a chemokine-like glycoprotein that has a prominent role in regulating inflammation and immunity. OPN polymorphisms and elevated OPN levels are associated with systemic lupus erythematosus (SLE) in several populations. The aim of present study was to evaluate the association between the OPN rs1126616 polymorphism and OPN level with SLE susceptibility. A total of 163 SLE patients and 180 age-, gender- and ethnically matched controls were genotyped for the rs1126616 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism method. Serum OPN levels were assayed by the enzyme-linked immunosorbent assay. There was no association between the OPN rs1126616 C/T polymorphism and SLE. The frequency of the OPN rs1126616 CT genotype was significantly higher in SLE patients with nephritis compared to SLE patients without nephritis and controls. Additionally, the frequency of TT genotypes was higher in SLE patients with nephritis compared to controls. The serum OPN levels were significantly higher in SLE patients compared to controls (50.6±22 vs. 35.6±15.8 ng/ml, P<0.001). Increased serum OPN levels were observed in SLE patients with lupus nephritis and joint symptoms. There was no correlation between OPN levels and the OPN rs1126616 polymorphism. The present data suggest that the CT and TT genotypes of the OPN rs1126616 polymorphism could be a risk factor for lupus nephritis. The OPN level is associated with SLE and certain SLE manifestations. However, there was no association between the OPN rs1126616 C/T polymorphism and SLE susceptibility. PMID:26998275

Clinical profile of patients with biopsy proven lupus nephritis at a tertiary care hospital from Northern Pakistan, 1995 to 2012.

PubMed

Ali, Akhtar; Mehmood, Anjum; Ali, Muhammad Usman

2017-01-01

TTo highlight the clinical spectrum of biopsy-proven lupus nephritis by analysing any variations in its histological subtypes across gender, varying age groups, serum creatinine levels and anti-double stranded deoxyribonucleic acid levels. This retrospective, observational study was conducted at the Lady Reading Hospital in collaboration with the Fauji Foundation Hospital, Peshawar, Pakistan, and comprised patient records of biopsy-proven lupus nephritis from 1995 to 2012. The cases were analysed according to clinical presentations and histological pattern of systemic lupus erythematosus nephritis. EpiData 3.1 and SPSS 17 were used for data analyses. Of the 2,000 renal biopsies performed, lupus nephritis was found in 74(3.7%) cases. Of them, 63(85.1%) were females and 11(14.9%) males. The mean age of the cases was 23.88±9.73 years (range: 10-55 years). Class IV lupus nephritis was seen in 38(51.4%) patients, followed by Class II in 15(20.3%), Class III in 10(13.5%), Class V and VI in 4(5.4%) each and Class I in 3(4.1%). Out of the combined Class III and IV cases, 25(52.08%) had serum creatinine levels of >1.2 mg/dL, whereas positive anti-double stranded deoxyribonucleic acid titers up to 50 IU/L were seen in all of the 48(100%) such patients. Overall, microscopic haematuria was found in 52(70.3%) cases, followed by arthralgia in 40(54.1%). Moreover, 32(50.8%) females and 6(54.5%) males had Type IV nephritis. Class VI lupus nephritis, in particular, were significantly more prominent in 31-40 years of age group when compared to other histological subtypes and age groups (p=0.0096, odds ratio: 23.25, 95% confidence interval: 2.15-251.21). Female predominance was observed in all histological sub-types of lupus nephritis. Class IV lupus was the most common histological pattern. Microscopic haematuria was the most common clinical presentation.

Therapeutic Effect of Dendrobium candidum on Lupus Nephritis in Mice

PubMed Central

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

2017-01-01

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

An unusual case of crescentic lupus nephritis presenting with normal renal function.

PubMed

Manohar, Sandhya; Subramanian, Chamundeswari; Lakshmi, Kameswari

2015-11-01

Lupus nephritis is a life-threatening manifestation of systemic lupus erythematosus (SLE). This is commonly suspected when lupus patients present with elevated serum creatinine levels. But it is important to be aware that even patients with advanced disease in the kidney from SLE can have normal renal function, thus requiring a high index of suspicion. We present the case of a patient who presented with nonspecific musculoskeletal symptoms and was diagnosed with SLE. He also had nephrotic range proteinuria but his serum creatinine was normal. A renal biopsy revealed diffuse proliferative crescentic lupus nephritis. We have reviewed the literature for correlation between crescents; a sign of severe glomerular damage and creatinine levels.

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

PubMed

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

2012-05-01

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

Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis.

PubMed

Mistry, Pragnesh; Kaplan, Mariana J

2017-12-01

Nephritis is one of the most severe complications of systemic lupus erythematosus (SLE). One key characteristic of lupus nephritis (LN) is the deposition of immune complexes containing nucleic acids and/or proteins binding to nucleic acids and autoantibodies recognizing these molecules. A variety of cell death processes are implicated in the generation and externalization of modified nuclear autoantigens and in the development of LN. Among these processes, apoptosis, primary and secondary necrosis, NETosis, necroptosis, pyroptosis, and autophagy have been proposed to play roles in tissue damage and immune dysregulation. Cell death occurs in healthy individuals during conditions of homeostasis yet autoimmunity does not develop, at least in part, because of rapid clearance of dying cells. In SLE, accelerated cell death combined with a clearance deficiency may lead to the accumulation and externalization of nuclear autoantigens and to autoantibody production. In addition, specific types of cell death may modify autoantigens and alter their immunogenicity. These modified molecules may then become novel targets of the immune system and promote autoimmune responses in predisposed hosts. In this review, we examine various cell death pathways and discuss how enhanced cell death, impaired clearance, and post-translational modifications of proteins could contribute to the development of lupus nephritis. Published by Elsevier Inc.

The treatment of systemic lupus proliferative nephritis.

PubMed

Punaro, Marilynn G

2013-11-01

Lupus nephritis is one of the most common and serious complications of systemic lupus erythematosus (SLE) in childhood affecting more than 80% of patients. Treatment of this complication has undergone significant evolution in recent years. A series of randomized controlled trials has clarified the role of a variety of immunomodulating regimens including some novel biologic medications. This review touches on the major trials that have influenced practice and shaped current thinking about the treatment of proliferative lupus glomerulonephritis.

Early Prediction of Lupus Nephritis Using Advanced Proteomics

DTIC Science & Technology

2008-06-01

Structure of the Conserved Hypothetical Protein Rv2302 from Mycobacterium tuberculosis ” 188, 5993-6001, J. Bacteriology, 2006. 11. T.A. Ramelot, A. Yee...currently elusive renal biomarkers crucial for the prognosis of SLE. A well-defined cohort of patients with SLE (n=150), disease and healthy...enhanced various TOF- MS, we discovered a set urinary lupus nephritis candidate biomarkers ; namely transferrin, ceruloplasmin, alpha1-acid

[Tubulointerstitial nephritis with uveitis (TINU) syndrome. A relatively rare rheumatological differential diagnosis with unexplained uveitis].

PubMed

Häusler, U; Guminski, B; Helmchen, U; Kisters, K; Heinz, C; Braun, J

2013-05-01

The tubulo-interstitial nephritis and uveitis (TINU) syndrome, first described in 1975, is a rare disease most probably of autoimmune origin that is characterized by unilateral or bilateral uveitis and tubulointerstitial nephritis. Most patients are adolescents and it is sometimes associated with other autoimmune diseases, such as spondyloarthritis, rheumatoid arthritis and hyperthyroidosis. This article reports the case of a 43-year-old female patient who presented with refractory recurrent bilateral uveitis despite therapy with high doses of corticosteroids in combination with cyclosporin. When the patient was referred to this hospital for rheumatological examination after almost 1 year of therapy, mild renal insufficiency and proteinuria were found. The kidney biopsy revealed interstitial nephritis, partly crescent-shaped and partly chronic. A diagnosis of TINU syndrome was made and treatment with adalimumab in combination with methotrexate was started. The favorable clinical outcome indicated that tumor necrosis factor (TNF) alpha may play an important role in the pathogenesis of TINU syndrome.

Early detection of acute tubulointerstitial nephritis in the genesis of Mesoamerican nephropathy.

PubMed

Fischer, Rebecca S B; Vangala, Chandan; Truong, Luan; Mandayam, Sreedhar; Chavarria, Denis; Granera Llanes, Orlando M; Fonseca Laguna, Marcos U; Guerra Baez, Alvaro; Garcia, Felix; García-Trabanino, Ramón; Murray, Kristy O

2018-03-01

Mesoamerican nephropathy is a devastating disease of unknown etiology that affects mostly young agricultural workers in Central America. An understanding of the mechanism of injury and the early disease process is urgently needed and will aid in identification of the underlying cause and direct treatment and prevention efforts. We sought to describe the renal pathology in Mesoamerican nephropathy at its earliest clinical appearance in prospectively identified acute case patients in Nicaragua. We considered those with elevated (or increased at least 0.3 mg/dL or 1.5-fold from baseline) serum creatinine, leukocyturia, and either leukocytosis or neutrophilia for inclusion in this biopsy study. Renal tissue was obtained by ultrasound-guided biopsy for examination by light, immunofluorescence, and electron microscopy. All 11 individuals who underwent renal biopsy showed tubulointerstitial nephritis, with varying degrees of inflammation and chronicity. Interstitial cellular infiltrates (predominantly T lymphocytes and monocytes), mostly in the corticomedullary junction; neutrophilic accumulation in the tubular lumens; largely preserved glomeruli; few mild ischemic changes; and no immune deposits were noted. The acute components of tubulointerstitial nephritis were acute tubular cell injury, interstitial edema, and early fibrosis. Chronic tubulointerstitial nephritis included severe tubular atrophy, thickened tubular basement membrane, and interstitial fibrosis. Thus, renal histopathology in Mesoamerican nephropathy reveals primary interstitial disease with intact glomeruli. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Crescentic glomerular nephritis associated with rheumatoid arthritis: a case report.

PubMed

Balendran, K; Senarathne, L D S U; Lanerolle, R D

2017-07-21

Rheumatoid arthritis is a systemic disorder where clinically significant renal involvement is relatively common. However, crescentic glomerular nephritis is a rarely described entity among the rheumatoid nephropathies. We report a case of a patient with rheumatoid arthritis presenting with antineutrophil cytoplasmic antibody-negative crescentic glomerular nephritis. A 54-year-old Sri Lankan woman who had recently been diagnosed with rheumatoid arthritis was being treated with methotrexate 10 mg weekly and infrequent nonsteroidal anti-inflammatory drugs. She presented to our hospital with worsening generalized body swelling and oliguria of 1 month's duration. Her physical examination revealed that she had bilateral pitting leg edema and periorbital edema. She was not pale or icteric. She had evidence of mild synovitis of the small joints of the hand bilaterally with no deformities. No evidence of systemic vasculitis was seen. Her blood pressure was 170/100 mmHg, and her jugular venous pressure was elevated to 7 cm with an undisplaced cardiac apex. Her urine full report revealed 2+ proteinuria with active sediment (dysmorphic red blood cells [17%] and granular casts). Her 24-hour urinary protein excretion was 2 g. Her serum creatinine level was 388 μmol/L. Abdominal ultrasound revealed normal-sized kidneys with acute parenchymal changes and mild ascites. Her renal biopsy showed renal parenchyma containing 20 glomeruli showing diffuse proliferative glomerular nephritis, with 14 of 20 glomeruli showing cellular crescents, and the result of Congo red staining was negative. Her rheumatoid factor was positive with a high titer (120 IU/ml), but results for antinuclear antibody, double-stranded deoxyribonucleic acid, and antineutrophil cytoplasmic antibody (perinuclear and cytoplasmic) were negative. Antistreptolysin O titer <200 U/ml and cryoglobulins were not detected. The results of her hepatitis serology, retroviral screening, and malignancy screening were

FcγRIIIa SNPs and haplotypes affect human IgG binding and association with lupus nephritis in African Americans

PubMed Central

Dong, Chaoling; Ptacek, Travis S; Redden, David T; Zhang, Kui; Brown, Elizabeth E.; Edberg, Jeffrey C.; McGwin, Gerald; Alarcón, Graciela S.; Ramsey-Goldman, Rosalind; Reveille, John D.; Vilá, Luis M.; Petri, Michelle; Qin, Aijian; Wu, Jianming; Kimberly, Robert P.

2014-01-01

Objective To investigate whether the FcγRIIIa-66R/H/L polymorphism influences net effective receptor function and to assess if the FCGR3A combined genotypes formed by FcγRIIIa-66R/H/L and FcγRIIIa-176F/V as well as copy number variation (CNV) confer risk for development of SLE and lupus nephritis. Methods FcγRIIIa variants, expressed on A20 IIA1.6 cells, were used in flow cytometry-based human IgG binding assays. FCGR3A SNP and CNV genotypes were determined by Pyrosequencing methodology in a cohort of 1728 SLE patients and 2404 healthy controls. Results The FcγRIIIa-66L/H/R (rs10127939) polymorphism influences ligand binding capacity in the context of the FcγRIIIa-176V (rs396991) allele. The low binding FcγRIIIa-176F allele was associated with SLE nephritis (p = 0.0609) in African Americans but not in European Americans (p > 0.10). Nephritis among African American SLE subjects was associated with FcγRIIIa low binding haplotypes containing the 66R/H/L and 176F variants (p = 0.03) and with low binding genotype combinations (p = 0.002). No association was observed in European American SLE patients. The distribution of FCGR3A CNV was not significantly different between controls and SLE patients with or without nephritis. Conclusion FcγRIIIa-66R/H/L influences ligand binding. The low binding haplotypes formed by 66R/H/L and 176F confer enhanced risk for lupus nephritis in African Americans. FCGR3A CNVs are not associated with SLE or SLE nephritis in either African Americans or European Americans. PMID:24782186

Mechanisms involved in the p62-73 idiopeptide-modulated delay of lupus nephritis in SNF(1) mice.

PubMed

Nyland, J F; Stoll, M L; Jiang, F; Feng, F; Gavalchin, J

2012-12-01

The F(1) progeny of the (SWR × NZB) cross develop a lupus-like disease with high serum titers of autoantibodies, and increased frequency and severity of immune complex-mediated glomerulonephritis in females. In previous work, we found that an idiotypic peptide corresponding to aa62-73 (p62-73) of the heavy chain variable region of autoantibody 540 (Id(LN)F(1)) induced the proliferation of p62-73 idiotype-reactive T cell clones. Further, monthly immunization of pre-nephritic SNF(1) female mice with p62-73 resulted in decreased nephritis and prolonged life spans. Here we show that this treatment modulated proliferative responses to Id(LN)F(1) antigen, including a reduction in the population of idiopeptide-presenting antigen-presenting cells (APCs), as early as two weeks after immunization (10 weeks of age). Th1-type cytokine production was increased at 12 weeks of age. The incidence and severity of nephritis was reduced by 14 weeks compared to controls. Clinical indicators of nephritis, specifically histological evidence of glomerulonephritis and urine protein levels, were reduced by 20 weeks. Together these data suggest that events involved in the mechanism(s) whereby p62-73 immunization delayed nephritis occurred early after immunization, and involved modulation of APCs, B and T cell populations.

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.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with systemic lupus erythematosus: a possible relation to proliferative nephritis.

PubMed

Hammad, A; Yahia, S; Laimon, W; Hamed, S M; Shouma, A; Shalaby, N M; Abdel-Hady, D; Ghanem, R; El-Farahaty, R M; El-Bassiony, S R; Hammad, E M

2017-06-01

Introduction Angiotensin-converting enzyme (ACE) is crucial in the pathogenesis of systemic lupus erythematosus through angiotensin II which regulates vascular tone and endothelial functions. Objectives To study the frequency of ACE insertion/deletion (I/D) gene polymorphism in Egyptian children with systemic lupus erythematosus and its possible relation to the renal pathology in cases with lupus nephritis. Subjects and methods The frequency of ACE gene insertion/deletion polymorphism genotypes was determined in 78 Egyptian children with systemic lupus erythematosus and compared to a matched group of 140 healthy controls using polymerase chain reaction. Results The DD genotype of the ACE gene was higher in systemic lupus erythematosus patients when compared to controls ( P<0.0001; odds ratio (OR) 2.4; 95% confidence interval (CI) 1.7-3.3) and the D allele was more frequent than the I allele in systemic lupus erythematosus patients in comparison to controls ( P < 0.0001; OR = 2.2; 95% CI = (1.6-3.1). In the lupus nephritis group, the DD genotype was significantly higher in those with proliferative lupus nephritis when compared to those with non-proliferative lupus nephritis ( P = 0.02; OR = 1.45; 95% CI = 1.4-1.6). Also, patients with proliferative lupus nephritis showed a higher frequency of the D allele ( P < 0.001; OR = 1.98; 95% CI = 1.3-2.9). Conclusion The D allele and DD genotype of the ACE gene appear to be a risk factor for the susceptibility of systemic lupus erythematosus and occurrence of proliferative nephritis in Egyptian children.

The serum levels of connective tissue growth factor in patients with systemic lupus erythematosus and lupus nephritis.

PubMed

Wang, F-M; Yu, F; Tan, Y; Liu, G; Zhao, M-H

2014-06-01

The expression of connective tissue growth factor mRNA in human kidneys may serve as an early marker for lupus nephritis progression. Therefore, we speculated that connective tissue growth factor may be involved in the pathogenesis of systemic lupus erythematosus and lupus nephritis. In this study, we set out to investigate the associations between serum connective tissue growth factor levels and clinicopathological features of patients with systemic lupus erythematosus and lupus nephritis. Serum samples from patients with non-renal systemic lupus erythematosus, renal biopsy-proven lupus nephritis and healthy control subjects were detected by enzyme-linked immunosorbent assay for serum connective tissue growth factor levels. The associations between connective tissue growth factor levels and clinicopathological features of the patients were further analysed. The levels of serum connective tissue growth factor in patients with non-renal systemic lupus erythematosus and lupus nephritis were both significantly higher than those in the normal control group (34.14 ± 12.17 ng/ml vs. 22.8 ± 3.0 ng/ml, p<0.001; 44.1 ± 46.8 ng/ml vs. 22.8 ± 3.0 ng/ml, p = 0.035, respectively). There was no significant difference of the serum connective tissue growth factor levels between non-renal systemic lupus erythematosus and lupus nephritis group (34.14 ± 12.17 ng/ml vs. 44.1 ± 46.8 ng/ml, p = 0.183). Serum connective tissue growth factor levels were significantly higher in lupus nephritis patients with the following clinical manifestations, including anaemia (51.3 ± 51.4 ng/ml vs. 23.4 ± 9.7 ng/ml, p<0.001) and acute renal failure (85.5 ± 75.0 ng/ml vs. 31.2 ± 21.8 ng/ml, p = 0.002). Serum connective tissue growth factor levels in class IV were significantly higher than that in class II, III and V (57.6 ± 57.5 ng/ml vs. 18.7 ± 6.4 ng/ml, p = 0.019; 57.6 ± 57.5 ng/ml vs. 25.2�

Outcome of childhood lupus nephritis in Saudi children.

PubMed

Al-Mayouf, Sulaiman Mohammed; AlAmeer, Ali; Alfattani, Areej; Alsonbul, Abdullah

2017-01-01

Our aim in this study is to report the long-term renal outcome of a cohort of Saudi children with systemic lupus erythematosus (SLE). All patients with childhood lupus nephritis (cLN) proved by renal biopsy seen between January 2000 and June 2015 were reviewed. The renal outcome was assessed according to serum creatinine level, protein/creatinine ratio at the last follow-up visit, and/or evidence of renal impairment during follow-up period and end-stage renal disease (ESRD). Additional outcome measures include accrual damage measured by pediatric adaptation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (pSDI), and death related to SLE was determined. A total of 84 (72 females) cLN patients with follow-up duration of 9.3 years (±5.2) were included in this study. The mean current age was 19.4 years (±5.5) and mean age at onset was 9.2 years (±2.4). The most frequent histopathological class was proliferative glomerulonephritis (64.3%) followed by membranous nephritis (27.4%). The mean activity and chronicity indices were 5.9 (±3.9) and 2.9 (±2.2), respectively. Renal microthrombosis was found in 9 (10.7%) patients. All patients treated with immunosuppressive medications; cyclophosphamide used in 64 followed by mycophenolate mofetil in 42, then azathioprine in 19 patients, while rituximab used in 24 patients. At the last follow-up visit, the mean serum creatinine was 147 umol/L (±197) and the mean protein/ creatinine ratio was 0.8 (± 1.1) while the mean total pSDI was 1.9 (±1.9) and mean renal SDI was 0.7 (±1.1). Sixteen (19%) patients had ESRD and eight of them had class IV nephritis. However, there was no significant difference in ESRD by histological class. The overall survival rates were five years: 94% and 10 years: 87%. Infection was the leading cause of mortality. Our patients had severe cLN and required intensive treatment. Despite the survival rate is comparable to other studies, ESRD is more

Subdural empyema in bacterial meningitis.

PubMed

Jim, Kin K; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik

2012-11-20

To evaluate the occurrence, treatment, and outcome of subdural empyema complicating community-acquired bacterial meningitis in adults. Case series from a prospective nationwide cohort study from Dutch hospitals from 2006 to 2011. Subdural empyema was diagnosed in 28 of 1,034 episodes (2.7%), and was present on admission in 10 episodes and diagnosed during admission in 18. Predisposing conditions were present in 26 patients (93%), and consisted of otitis or sinusitis in 21 patients (75%). In all these patients the otitis or sinusitis spread to the subdural space. Twenty-three patients (82%) presented with neurologic symptoms (paresis, focal seizures, dysesthesia contralateral to the empyema). Streptococcus pneumoniae was identified in 26 patients (93%) and Streptococcus pyogenes in 1 (3%); 1 patient had negative CSF cultures. Clinical course was frequently complicated with seizures (50%), focal neurologic abnormalities (54%), and hearing impairment (39%), causing an unfavorable outcome in 19 episodes (68%). Neurosurgical evacuation of the empyema was performed in 5 patients, all with considerable midline shift. Although rare, subdural empyema must be considered in patients with community-acquired bacterial meningitis and otitis or sinusitis, focal neurologic deficits, or epileptic seizures. S pneumoniae is the predominant causative organism and neurosurgical intervention should be regarded as first-choice therapy in patients with empyema causing midline shift and focal neurologic abnormalities or a decreased level of consciousness.

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

USDA-ARS?s Scientific Manuscript database

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

IRF4 Deficiency Abrogates Lupus Nephritis Despite Enhancing Systemic Cytokine Production

PubMed Central

Lech, Maciej; Weidenbusch, Marc; Kulkarni, Onkar P.; Ryu, Mi; Darisipudi, Murthy Narayana; Susanti, Heni Eka; Mittruecker, Hans-Willi; Mak, Tak W.

2011-01-01

The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice, resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4 deficiency completely protected these mice from glomerulonephritis and lung disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti-dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of plasma cells. As a consequence, Irf4-deficient C57BL/6-(Fas)lpr mice neither developed immune complex disease nor glomerular activation of complement. In addition, lack of IRF4 impaired the maturation of Th17 effector T cells and reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic inflammation and the activation of antigen-presenting cells but also prevents the maturation of plasma cells and effector T cells. Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells. PMID:21742731

Levetiracetam-induced interstitial nephritis in a patient with glioma.

PubMed

Mahta, Ali; Kim, Ryan Y; Kesari, Santosh

2012-01-01

A 45-year-old man with a new diagnosis of low grade glioma was started on an escalating dose of levetiracetam (Lev) for seizure management. He gradually developed intractable nausea/vomiting and a high creatinine concentration due to acute renal failure which was attributed to Lev-induced interstitial nephritis. The medication was changed and his renal function rapidly improved to his baseline. Copyright © 2011 Elsevier Ltd. All rights reserved.

Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis.

PubMed

Nielsen, C T; Østergaard, O; Rekvig, O P; Sturfelt, G; Jacobsen, S; Heegaard, N H H

2015-10-01

A high level of galectin-3-binding protein (G3BP) appears to distinguish circulating cell-derived microparticles in systemic lupus erythematosus (SLE). The aim of this study is to characterize the population of G3BP-positive microparticles from SLE patients compared to healthy controls, explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis. Numbers of annexin V-binding and G3BP-exposing plasma microparticles from 56 SLE patients and 36 healthy controls were determined by flow cytometry. Quantitation of microparticle-associated G3BP, C1q and immunoglobulins was obtained by liquid chromatography tandem mass spectrometry (LC-MS/MS). Correlations between microparticle-G3BP data and clinical parameters were analyzed. Co-localization of G3BP with in vivo-bound IgG was examined in kidney biopsies from one non-SLE control and from patients with class IV (n = 2) and class V (n = 1) lupus nephritis using co-localization immune electron microscopy. Microparticle-G3BP, microparticle-C1q and microparticle-immunoglobulins were significantly (P < 0.01) increased in SLE patients by LC-MS/MS. Three G3BP-exposing microparticle populations could be discerned by flow cytometry, including two subpopulations that were significantly increased in SLE samples (P = 0.01 and P = 0.0002, respectively). No associations of G3BP-positive microparticles with clinical manifestations or disease activity were found. Immune electron microscopy showed co-localization of G3BP with in vivo-bound IgG in glomerular electron dense immune complex deposits in all lupus nephritis biopsies. Both circulating microparticle-G3BP numbers as well as G3BP expression are increased in SLE patients corroborating G3BP being a feature of SLE microparticles. By demonstrating G3BP co-localized with deposited immune complexes in lupus nephritis, the study supports cell-derived microparticles as a major

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

PubMed

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

2010-10-01

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

Necrotizing suppurative nephritis in a Japanese black feedlot steer due to Proteus mirabilis infection.

PubMed

Abe, Tadatsugu; Iizuka, Ayako; Kojima, Hirokazu; Kimura, Kumiko; Shibahara, Tomoyuki; Haritani, Makoto

2017-04-05

A Japanese black feedlot steer suddenly died after exhibiting astasia and cramping of the extremities. Necropsy of the animal revealed that the right kidney was enlarged and pale with severe nephrolithiasis. The urinary bladder displayed mucosal hemorrhage. Upon bacteriological investigation, Proteus mirabilis was isolated from the liver, spleen, right kidney, lungs and urine. Histopathological examination revealed necrotizing suppurative nephritis with the presence of numerous gram-negative bacilli and fibrinous suppurative cystitis with no bacilli. Immunohistochemical analysis revealed that the bacteria and cytoplasm of the macrophages stained positively with P. mirabilis antiserum. Electron microscopy revealed the presence of numerous bacteria in the renal tubules. To our knowledge, this is the first report describing the histopathological aspects of nephritis caused by P. mirabilis in cattle.

Therapeutic potential of DCB-SLE1, an extract of a mixture of Chinese medicinal herbs, for severe lupus nephritis.

PubMed

Tsai, Pei-Yi; Ka, Shuk-Man; Chang, Jia-Ming; Chang, Wen-Liang; Huang, Yuan-Jen; Hung, Le-Mei; Jheng, Huei-Lin; Wu, Rey-Yuh; Chen, Ann

2011-10-01

The pathogenesis of lupus nephritis is mainly attributable to a complex interaction between the innate and adaptive immune systems, including T and B cell function abnormalities. In addition to autoantibody production and immune complex deposition, Th1 and Th17 cytokines may play key roles in the development and progression of lupus nephritis. Acute onset of severe lupus nephritis remains a challenge in terms of prevention and treatment. In the present study, we evaluated the therapeutic effects of DCB-SLE1, an extract of a mixture of four traditional Chinese medicinal herbs (Atractylodis macrocephalae Rhizoma, Eucommiae cortex, Lonicerae caulis, and Hedyotidis diffusae Herba), on an accelerated severe lupus nephritis model, characterized by acute onset of proteinuria, azotemia, autoantibody production, and development of severe nephritis, induced by twice weekly injection of New Zealand black/white F1 mice with Salmonella-type lipopolysaccharide. DCB-SLE1 was administered daily by gavage starting 2 days after the first dose of induction of lipopolysaccharide, and the mice were euthanized at week 1 or week 5. The results showed that DCB-SLE1 significantly ameliorated the hematuria, proteinuria, renal dysfunction, and severe renal lesions by 1) suppression of B cell activation and decreased autoantibody production; 2) negative regulation of T cell activation/proliferation and natural killer cell activity; 3) suppression of IL-18, IL-6, and IL-17 production and blocking of NF-κB activation in the kidney; and 4) prevention of lymphoid and renal apoptosis. These results show that DCB-SLE1 can protect the kidney from autoimmune response-mediated acute and severe damage through systemic immune modulation and anti-inflammation pathways.

Urinary Angiostatin - A Novel Putative Marker of Renal Pathology Chronicity in Lupus Nephritis*

PubMed Central

Wu, Tianfu; Du, Yong; Han, Jie; Singh, Sandeep; Xie, Chun; Guo, Yuyuan; Zhou, Xin J.; Ahn, Chul; Saxena, Ramesh; Mohan, Chandra

2013-01-01

There is a critical need to identify biomarkers for Systemic Lupus Erythematosus (SLE) which has a high prevalence of renal failure. When urine from patients with lupus nephritis was recently screened for the levels of ∼280 molecules using an exploratory array-based proteomic platform, elevated angiostatin levels were noted. Angiostatin is a bioactive fragment of plasminogen, and has been known to have modulatory function in angiogenesis and inflammation. The significant elevation in urinary angiostatin was next validated in an independent cohort of SLE patients (n = 100) using ELISA. Among patients with SLE, urine angiostatin was significantly increased in active SLE compared with inactive SLE, correlating well with the SLEDAI disease activity index and SLICC renal activity score (r = 0.66, p < 0.0001). ROC curve analysis further confirmed that urinary angiostatin had the capacity to discriminate patients with active SLE from those with inactive disease. Patients with Class IV lupus nephritis exhibited the highest levels of urinary angiostatin. Immunohistochemistry staining localized angiostatin expression to the renal tubular cells in these patients. Finally, when paired urine-kidney samples procured concurrently from patients with LN were next examined, urine angiostatin levels correlated strongly with the renal pathology chronicity index, but not with the activity index. Given that Class IV lupus nephritis and renal pathology chronicity changes forebode poor renal and patient survival, urinary angiostatin emerges as a novel noninvasive marker of renal disease in SLE. Longitudinal studies are in progress to further assess the disease-predictive potential of urinary angiostatin. PMID:23345539

Dentistry and internal medicine: from the focal infection theory to the periodontal medicine concept.

PubMed

Pizzo, Giuseppe; Guiglia, Rosario; Lo Russo, Lucio; Campisi, Giuseppina

2010-12-01

During past decades the relationship between dentistry and internal medicine and especially the concept of the so-called focal infection theory have long been a matter of debate. The pathogenesis of focal diseases has been classically attributed to dental pulp pathologies and periapical infections. Nonetheless, in recent years, their role is being dismissed while increasing interest is being devoted to the possible associations between periodontal infection and systemic diseases. In fact, periodontal pathogens and their products, as well as inflammatory mediators produced in periodontal tissues, might enter the bloodstream, causing systemic effects and/or contributing to systemic diseases. On the basis of this mechanism, chronic periodontitis has been suggested as a risk factor for cardiovascular diseases associated with atherosclerosis, bacterial endocarditis, diabetes mellitus, respiratory disease, preterm delivery, rheumatoid arthritis, and, recently, osteoporosis, pancreatic cancer, metabolic syndrome, renal diseases and neurodegenerative diseases such as Alzheimer's disease. Various hypotheses, including common susceptibility, systemic inflammation, direct bacterial infection and cross-reactivity, or molecular mimicry, between bacterial antigens and self-antigens, have been postulated to explain these relationships. In this scenario, the association of periodontal disease with systemic diseases has set the stage for introducing the concept of periodontal medicine. This narrative review summarizes the evolution of focal infection theory up to the current pathophysiology of periodontal disease, and presents an update on the relationships between chronic periodontitis and systemic diseases. Copyright © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Complement in Lupus Nephritis: New Perspectives.

PubMed

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

2015-09-01

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

Fcγ receptor IIIa single-nucleotide polymorphisms and haplotypes affect human IgG binding and are associated with lupus nephritis in African Americans.

PubMed

Dong, Chaoling; Ptacek, Travis S; Redden, David T; Zhang, Kui; Brown, Elizabeth E; Edberg, Jeffrey C; McGwin, Gerald; Alarcón, Graciela S; Ramsey-Goldman, Rosalind; Reveille, John D; Vilá, Luis M; Petri, Michelle; Qin, Aijian; Wu, Jianming; Kimberly, Robert P

2014-05-01

To investigate whether the Fcγ receptor IIIa-66L/R/H (FcγRIIIa-66L/R/H) polymorphism influences net effective receptor function and to assess if the FCGR3A combined genotypes formed by FcγRIIIa-66L/R/H and FcγRIIIa-176F/V, as well as copy number variation (CNV), confer risk of developing systemic lupus erythematosus (SLE) and lupus nephritis. FcγRIIIa variants, expressed on A20 IIA1.6 cells, were used in flow cytometry-based human IgG-binding assays. Using Pyrosequencing methodology, FCGR3A single-nucleotide polymorphism and CNV genotypes were determined in a cohort of 1,728 SLE patients and 2,404 healthy controls. The FcγRIIIa-66L/R/H (rs10127939) polymorphism influenced ligand binding capacity in the presence of the FcγRIIIa-176V (rs396991) allele. There was a trend toward an association of the low-binding FcγRIIIa-176F allele with lupus nephritis among African Americans (P = 0.0609) but not among European Americans (P > 0.10). Nephritis among African American patients with SLE was associated with FcγRIIIa low-binding haplotypes containing the 66L/R/H and 176F variants (P = 0.03) and with low-binding genotype combinations (P = 0.002). No association was observed among European American patients with SLE. The distribution of FCGR3A CNV was not significantly different among controls and SLE patients with or without nephritis. FcγRIIIa-66L/R/H influences ligand binding. The low-binding haplotypes formed by 66L/R/H and 176F confer enhanced risk of lupus nephritis in African Americans. FCGR3A CNVs are not associated with SLE or lupus nephritis in either African Americans or European Americans. Copyright © 2014 by the American College of Rheumatology.

Inducible nitric oxide synthase gene polymorphisms are associated with a risk of nephritis in Henoch-Schönlein purpura children.

PubMed

Jiang, Jue; Duan, Wuqiong; Shang, Xu; Wang, Hua; Gao, Ya; Tian, Peijun; Zhou, Qi

2017-08-01

Henoch-Schönlein purpura (HSP) is the most common form of systemic small-vessel vasculitis in children, and HSP nephritis (HSPN) is a major complication of HSP and is the primary cause of morbidity and mortality. Previous studies have suggested that inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of HSP. In this study, we performed a detailed analysis to investigate the potential association between iNOS polymorphisms and the risk of HSP and the tendency for children with HSP to develop HSPN in a Chinese Han population. A promoter pentanucleotide repeat (CCTTT)n and 10 functional single-nucleotide polymorphisms (SNPs) from 532 healthy controls and 513 children with HSP were genotyped using the MassARRAY system and GeneScan. The results suggested that the allelic and genotypic frequencies of the rs3729508 polymorphism were nominally associated with susceptibility to HSP. In addition, there was a significant difference in the allelic distribution of the (CCTTT)12 repeats and rs2297518 between the HSP children with and without nephritis; the HSP children with nephritis exhibited a significantly higher frequency of the (CCTTT)12 repeats and A allele of rs2297518 than the HSP children without nephritis (P FDR  = 0.033, OR = 1.624, 95% CI = 1.177-2.241 and P FDR  = 0.030, OR = 1.660, 95% CI = 1.187-2.321, respectively). Our results support that iNOS polymorphisms are associated with the risk of HSP and may strongly contribute to the genetic basis of individual differences in the progression to nephritis among children with HSP in the Chinese Han population. What is Known: • The etiology of HSP is unknown, but the genetic factors may play an important role in the pathogenesis of HSP. • iNOS could contribute to the development and clinical manifestations of HSP, and this has not been studied extensively so far. What is New: • Our results support that iNOS polymorphisms not only are associated with HSP risk but also

Barriers to Medication Decision Making in Women with Lupus Nephritis: A Formative Study using Nominal Group Technique.

PubMed

Singh, Jasvinder A; Qu, Haiyan; Yazdany, Jinoos; Chatham, Winn; Dall'era, Maria; Shewchuk, Richard M

2015-09-01

To assess the perspectives of women with lupus nephritis on barriers to medication decision making. We used the nominal group technique (NGT), a structured process to elicit ideas from participants, for a formative assessment. Eight NGT meetings were conducted in English and moderated by an expert NGT researcher at 2 medical centers. Participants responded to the question: "What sorts of things make it hard for people to decide to take the medicines that doctors prescribe for treating their lupus kidney disease?" Patients nominated, discussed, and prioritized barriers to decisional processes involving medications for treating lupus nephritis. Fifty-one women with lupus nephritis with a mean age of 40.6 ± 13.3 years and disease duration of 11.8 ± 8.3 years participated in 8 NGT meetings: 26 African Americans (4 panels), 13 Hispanics (2 panels), and 12 whites (2 panels). Of the participants, 36.5% had obtained at least a college degree and 55.8% needed some help in reading health materials. Of the 248 responses generated (range 19-37 responses/panel), 100 responses (40%) were perceived by patients as having relatively greater importance than other barriers in their own decision-making processes. The most salient perceived barriers, as indicated by percent-weighted votes assigned, were known/anticipated side effects (15.6%), medication expense/ability to afford medications (8.2%), and the fear that the medication could cause other diseases (7.8%). Women with lupus nephritis identified specific barriers to decisions related to medications. Information relevant to known/anticipated medication side effects and medication cost will form the basis of a patient guide for women with systemic lupus erythematosus, currently under development.

Toward a Comprehensive Hypothesis of Chronic Interstitial Nephritis in Agricultural Communities.

PubMed

Orantes-Navarro, Carlos Manuel; Herrera-Valdés, Raúl; Almaguer-López, Miguel; López-Marín, Laura; Vela-Parada, Xavier Fernando; Hernandez-Cuchillas, Marcelo; Barba, Lilly M

2017-03-01

Over the past 20 years, there has been an increase in chronic interstitial nephritis in agricultural communities (CINAC) not associated with traditional risk factors. This disease has become an important public health problem and is observed in several countries in Central America and Asia. CINAC predominantly affects young male farmers between the third and fifth decades of life with women, children, and adolescents less often affected. Clinically, CINAC behaves like a chronic tubulointerstitial nephropathy but with systemic manifestations not attributable to kidney disease. Kidney biopsy reveals chronic tubulointerstitial nephritis with variable glomerulosclerosis and mild chronic vascular damage, with the severity depending on sex, occupation, and CKD stage. The presence of toxicological, occupational, and environmental risk factors within these communities suggests a multifactorial etiology for CINAC. This may include exposure to agrochemicals, a contaminated environment, repeated episodes of dehydration with heat stress, and an underlying genetic predisposition. An understanding of these interacting factors using a multidisciplinary approach with international cooperation and the formulation of a comprehensive hypothesis are essential for the development of public health programs to prevent this devastating epidemic. Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.

Interobserver agreement on histopathological lesions in class III or IV lupus nephritis.

PubMed

Wilhelmus, Suzanne; Cook, H Terence; Noël, Laure-Hélène; Ferrario, Franco; Wolterbeek, Ron; Bruijn, Jan A; Bajema, Ingeborg M

2015-01-07

To treat lupus nephritis effectively, proper identification of the histologic class is essential. Although the classification system for lupus nephritis is nearly 40 years old, remarkably few studies have investigated interobserver agreement. Interobserver agreement among nephropathologists was studied, particularly with respect to the recognition of class III/IV lupus nephritis lesions, and possible causes of disagreement were determined. A link to a survey containing pictures of 30 glomeruli was provided to all 360 members of the Renal Pathology Society; 34 responses were received from 12 countries (a response rate of 9.4%). The nephropathologist was asked whether glomerular lesions were present that would categorize the biopsy as class III/IV. If so, additional parameters were scored. To determine the interobserver agreement among the participants, κ or intraclass correlation values were calculated. The intraclass correlation or κ-value was also calculated for two separate levels of experience (specifically, nephropathologists who were new to the field or moderately experienced [less experienced] and nephropathologists who were highly experienced). Intraclass correlation for the presence of a class III/IV lesion was 0.39 (poor). The κ/intraclass correlation values for the additional parameters were as follows: active, chronic, or both: 0.36; segmental versus global: 0.39; endocapillary proliferation: 0.46; influx of inflammatory cells: 0.32; swelling of endothelial cells: 0.46; extracapillary proliferation: 0.57; type of crescent: 0.46; and wire loops: 0.35. The highly experienced nephropathologists had significantly less interobserver variability compared with the less experienced nephropathologists (P=0.004). There is generally poor agreement in terms of recognizing class III/IV lesions. Because experience clearly increases interobserver agreement, this agreement may be improved by training nephropathologists. These results also underscore the importance of

Induction of passive Heymann nephritis in complement component 6-deficient PVG rats.

PubMed

Spicer, S Timothy; Tran, Giang T; Killingsworth, Murray C; Carter, Nicole; Power, David A; Paizis, Kathy; Boyd, Rochelle; Hodgkinson, Suzanne J; Hall, Bruce M

2007-07-01

Passive Heymann nephritis (PHN), a model of human membranous nephritis, is induced in susceptible rat strains by injection of heterologous antisera to rat renal tubular Ag extract. PHN is currently considered the archetypal complement-dependent form of nephritis, with the proteinuria resulting from sublytic glomerular epithelial cell injury induced by the complement membrane attack complex (MAC) of C5b-9. This study examined whether C6 and MAC are essential to the development of proteinuria in PHN by comparing the effect of injection of anti-Fx1A antisera into PVG rats deficient in C6 (PVG/C6(-)) and normal PVG rats (PVG/c). PVG/c and PVG/C6(-) rats developed similar levels of proteinuria at 3, 7, 14, and 28 days following injection of antisera. Isolated whole glomeruli showed similar deposition of rat Ig and C3 staining in PVG/c and PVG/C6(-) rats. C9 deposition was abundant in PVG/c but was not detected in PVG/C6(-) glomeruli, indicating C5b-9/MAC had not formed in PVG/C6(-) rats. There was also no difference in the glomerular cellular infiltrate of T cells and macrophages nor the size of glomerular basement membrane deposits measured on electron micrographs. To examine whether T cells effect injury, rats were depleted of CD8+ T cells which did not affect proteinuria in the early heterologous phase but prevented the increase in proteinuria associated with the later autologous phase. These studies showed proteinuria in PHN occurs without MAC and that other mechanisms, such as immune complex size, early complement components, CD4+ and CD8+ T cells, disrupt glomerular integrity and lead to proteinuria.

Integrative medicine for managing the symptoms of lupus nephritis: A protocol for systematic review and meta-analysis.

PubMed

Choi, Tae-Young; Jun, Ji Hee; Lee, Myeong Soo

2018-03-01

Integrative medicine is claimed to improve symptoms of lupus nephritis. No systematic reviews have been performed for the application of integrative medicine for lupus nephritis on patients with systemic lupus erythematosus (SLE). Thus, this review will aim to evaluate the current evidence on the efficacy of integrative medicine for the management of lupus nephritis in patients with SLE. The following electronic databases will be searched for studies published from their dates of inception February 2018: Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as 6 Korean medical databases (Korea Med, the Oriental Medicine Advanced Search Integrated System [OASIS], DBpia, the Korean Medical Database [KM base], the Research Information Service System [RISS], and the Korean Studies Information Services System [KISS]), and 1 Chinese medical database (the China National Knowledge Infrastructure [CNKI]). Study selection, data extraction, and assessment will be performed independently by 2 researchers. The risk of bias (ROB) will be assessed using the Cochrane ROB tool. This systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to inform and guide healthcare practice and policy. PROSPERO 2018 CRD42018085205.

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

PubMed

Houssiau, Frédéric A

2016-01-01

Treatment of lupus nephritis is more evidenced-based than ever. Yet many areas of uncertainty persist. The article by Rathi et al. brings a piece to the puzzle by comparing, in a group of Indian patients, the Euro-Lupus low-dose i.v. cyclophosphamide regimen with mycophenolate mofetil. Although some caveats must be raised, the results suggest that, after crossing the Atlantic, the Euro-Lupus regimen may well be moving East. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Prevalence, incidence, and demographics of systemic lupus erythematosus and lupus nephritis from 2000 to 2004 among children in the US Medicaid beneficiary population.

PubMed

Hiraki, Linda T; Feldman, Candace H; Liu, Jun; Alarcón, Graciela S; Fischer, Michael A; Winkelmayer, Wolfgang C; Costenbader, Karen H

2012-08-01

To investigate the nationwide prevalence, incidence, and sociodemographics of systemic lupus erythematosus (SLE) and lupus nephritis among children in the US Medicaid beneficiary population. Children ages 3 years to <18 years with a diagnosis of SLE (defined as ≥3 claims with an International Classification of Diseases, Ninth Revision [ICD-9] code of 710.0 for SLE, each >30 days apart) were identified from the US Medicaid Analytic eXtract database from 2000 to 2004. This database contains all inpatient and outpatient Medicaid claims for 47 US states and the District of Columbia. Lupus nephritis was identified from ≥2 ICD-9 billing codes for glomerulonephritis, proteinuria, or renal failure, each recorded >30 days apart. The prevalence and incidence of SLE and lupus nephritis were calculated among Medicaid-enrolled children overall and within sociodemographic groups. Of the 30,420,597 Medicaid-enrolled children during these years, 2,959 were identified as having SLE. The prevalence of SLE was 9.73 (95% confidence interval [95% CI] 9.38-10.08) per 100,000 Medicaid-enrolled children. Among the children with SLE, 84% were female, 40% were African American, 25% were Hispanic, 21% were White, and 42% resided in the South region of the US. Moreover, of the children with SLE, 1,106 (37%) had lupus nephritis, representing a prevalence of 3.64 (95% CI 3.43-3.86) per 100,000 children. The average annual incidence of SLE was 2.22 cases (95% CI 2.05-2.40) and that of lupus nephritis was 0.72 cases (95% CI 0.63-0.83) per 100,000 Medicaid enrollees per year. The prevalence and incidence rates of SLE and lupus nephritis increased with age, were higher in girls than in boys, and were higher in all non-White racial/ethnic groups. In the current study, the prevalence and incidence rates of SLE among Medicaid-enrolled children in the US are high compared to studies in other populations. In addition, these data represent the first population-based estimates of the prevalence and

Systemic Staphylococcus pseudintermedius infection in an arctic fox (Vulpes lagopus) with severe multifocal suppurative meningoencephalitis and nephritis.

PubMed

Iwata, Kei; Kasuya, Kazufumi; Takayama, Kou; Nakahara, Yusuke; Kobayashi, Yoshifumi; Kato, Asako; Senba, Hironobu; Yanagisawa, Masae; Shibahara, Tomoyuki

2018-06-11

A 2-year-female arctic fox (Vulpes lagopus) developed anorexia, dehydration, and emaciation during the quarantine period for importation from Norway, and died 17 days later. At necropsy, a fistula was observed on the left gluteal region, and the left eye, left brain, and kidneys were discolored. Histologically, severe diffuse suppurative meningoencephalitis and renal abscesses were detected. Numerous Gram-positive cocci were detected in these lesions. Multidrug-susceptible Staphylococcus pseudintermedius were isolated from the lesions. These results suggest that S. pseudintermedius can cause severe multifocal suppurative meningoencephalitis and nephritis in foxes. This is the first report of multidrug-susceptible S. pseudintermedius meningoencephalitis and nephritis in a fox.

Predictive risk factors for failure to induction therapy of lupus nephritis in a cohort of Colombian patients.

PubMed

Pinto Peñaranda, Luis Fernando; Castro Mercado, Inis Lizeth; Duque Caballero, Vladimir; Márquez Hernández, Javier Darío; Velásquez Franco, Carlos Jaime

2014-01-01

To determine the predictors of failure to obtain remission after induction therapy for proliferative lupus nephritis in a group of northwestern Colombian patients. A retrospective study was conducted. We included patients with systemic lupus erythematosus according to the American College of Rheumatology criteria who had nephritis confirmed by renal biopsy. We followed 84 patients: 88.1% female, and 11.9% male. The mean age at diagnosis of systemic lupus erythematosus was 27.5±11.8 years (9-70). The average time between diagnosis of systemic lupus erythematosus and proliferative nephritis onset was 13.6 months (0-168). Histopathologic type: iv (78.57%), iii (15.47%), iii-iv/v (5.96%). Activity index: 6.7±4.6. Chronicity index: 2±2.7. 24-hour proteinuria (mg): 6,164 (130-18,100). Baseline creatinine: 1.14 mg/dL (0.43-7.4). Induction therapy: Steroids (100%), cyclophosphamide (76.2%) and mycophenolate mofetil (23.8%). At six months, 56% of individuals failed to achieve partial or complete remission. Predictors of failure to induction therapy were, in accordance with the bivariate analysis (OR; 95%CI): creatinine level more than 1.2mg/dL (10.8; 3.18-36.84; P<.005), nephrotic range proteinuria (11.9; 3.09-45.8; P<.001), and an activity index above 8 (5.04; 1.7-14.3; P<.001). In the multivariate analysis, only baseline creatinine higher than 1.2mg/dL (10.92; 2.65-45.02; P=.001), and nephrotic range proteinuria (9.81; 1.85-52.04; P=.007) were significant. A significant percentage of Colombian patients fail to achieve remission of proliferative lupus nephritis after six months of treatment. Copyright © 2013 Elsevier España, S.L. All rights reserved.

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

PubMed

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

2015-09-01

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

Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis.

PubMed

Szeto, C-C; Kwan, B C-H; Lai, F M-M; Tam, L-S; Li, E K-M; Chow, K-M; Gang, W; Li, P K-T

2008-11-01

The treatment of pure membranous (class V) lupus nephropathy remains unsatisfactory. We studied the efficacy and safety of tacrolimus in the treatment of membranous nephritis secondary to SLE. We recruited 18 consecutive SLE patients (tacrolimus group) with recently confirmed biopsy-proven class V lupus nephritis. They were treated with a tailing dose of oral prednisolone and tacrolimus 0.1-0.2 mg/kg/day for 6 months, followed by maintenance prednisolone and AZA. The rate of resolution of proteinuria and SLEDAI were compared with 19 historical controls treated with oral cyclophosphamide or AZA (control group). All patients were followed for 12 months. Baseline clinical characteristics were comparable between the groups. For the tacrolimus group, the complete and partial remission rates were 27.8 and 50.0%, respectively at 12 weeks; for the control group, they were 15.8 and 47.4%, respectively (overall chi-square test, P = 0.5). However, tacrolimus group had faster resolution of proteinuria than the control group by the general linear model with repeated measures (P = 0.032). At 12 weeks, proteinuria was reduced by 76.2 +/- 17.0% for the tacrolimus group and 47.1 +/- 51.1% for the control group (P = 0.028). Serial change in renal function and SLEDAI score did not differ between the groups. During the study period, four patients of the tacrolimus group, and 11 of the control group, developed lupus flare (P = 0.027). There was no serious adverse effect in the tacrolimus group. A 6-month course of tacrolimus is a safe and effective treatment of pure class V (membranous) lupus nephritis. As compared with conventional cytotoxic treatment, tacrolimus possibly results in a faster resolution of proteinuria, and a lower risk of lupus flare within 1 yr. The long-term effect and optimal regimen of tacrolimus require further study.

Anti-Myeloperoxidase Antibodies Associate with Future Proliferative Lupus Nephritis

PubMed Central

Lee, J. J.; Poirier, M.; Little, D. J.; Prince, L. K.; Baker, T. P.; Edison, J. D.; Abbott, K. C.

2017-01-01

Background The subclinical pathophysiology of proliferative lupus nephritis (PLN) has not been fully elucidated. Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) is associated with PLN, but prediagnostic levels have not been reported. Methods We performed a retrospective case-control Department of Defense Serum Repository (DoDSR) study comparing MPO-ANCA levels in longitudinal prediagnostic serum samples for 23 biopsy confirmed proliferative lupus nephritis (PLN) patients to DoDSR identified age, sex, race, and age of serum matched healthy and SLE without LN disease controls. We also compared the temporal relationship of MPO-ANCA to anti-double stranded DNA antibodies (dsDNAab). Results A greater proportion of PLN patients had prediagnostic MPO-ANCA levels above ≥3 U/mL and ≥6 U/mL compared to SLE without LN (91% versus 43%, p < 0.001; 57% versus 5%, p < 0.001, resp.). In subgroup analysis, the MPO-ANCA threshold of ≥3 U/mL was significant at <1 year (88% versus 39%, p = 0.007) and 1–4 years (87% versus 38%, p = 0.009) prior to diagnosis. Statistically significant subclinical MPO-ANCA levels (≥3 U/mL) occurred prior to statistically significant dsDNAab ≥ 3 IU/ml (89% versus 11%, p = 0.003). Conclusions Subclinical MPO-ANCA levels could distinguish future PLN from SLE without LN. MPO-ANCA manifests prior to clinical disease and subclinical dsDNAab to suggest that it may contribute directly to PLN pathogenicity. PMID:29435367

Lamotrigine-induced tubulointerstitial nephritis and uveitis-atypical Cogan syndrome.

PubMed

Kolomeyer, Anton M; Kodati, Shyam

2015-12-01

To report a case of lamotrigine-induced tubulointerstitial nephritis and uveitis (TINU)-atypical Cogan syndrome. Case report. A 16-year-old boy with traumatic brain injury and seizures presented to the emergency department with facial swelling, rash, and back pain several days after increasing lamotrigine dose secondary to a breakthrough seizure. Creatinine, urine β2 microglobulin, and eosinophils were elevated. Antinuclear antibodies, antineutrophil cytoplasmic antibodies, angiotensin-converting enzyme, and complement were normal. Renal biopsy showed acute granulomatous tubulointerstitial nephritis. Lamotrigine was discontinued, intravenous steroids were initiated, and the patient was discharged on Ativan and prednisone. Subsequently, he was diagnosed with bilateral anterior uveitis (vision 20/30 bilaterally) and started on prednisolone and cyclopentolate. Two months later, he developed a branch retinal artery occlusion in the right eye (vision 20/70) and bilateral ocular hypertension for which timolol-brimonidine and dorzolamide were added. Neuroimaging and hypercoagulability workup was unremarkable. Vision and intraocular pressure improved, while uveitis remained recalcitrant. Several months later, the patient developed central serous retinopathy in the right eye (vision 20/30). Prednisone was stopped but restarted due to methotrexate intolerance. A month later, he reported dizziness and was diagnosed with severe bilateral sensorineural hearing loss. Brain magnetic resonance imaging showed foci of perivascular, subcortical, and cochlear enhancement. Transtympanic Decadron injections and infliximab infusions were initiated. At the final visit, vision remained at 20/30 with trace anterior chamber reaction bilaterally while on timolol-brimonidine, dorzolamide, and prednisolone. An idiosyncratic drug reaction should be considered in the differential diagnosis of TINU-atypical Cogan syndrome.

Significance of mast cell renal infiltration in patients with anti-GBM nephritis.

PubMed

Wu, Xiao-Mei; Zhang, Yi-Yan; Zhang, Ming-Chao; Zhang, Li-Hua; Zeng, Cai-Hong; Liu, Zhi-Hong; Tang, Zheng

2016-07-01

To investigate the role of mast cells (MCs) renal infiltration in the progression of human anti-GBM nephritis, 38 patients diagnosed with anti-GBM nephritis were enrolled. Renal biopsies were performed. Immunohistochemistry was conducted to detect MCs in renal tissues. Patients were divided into group 1 (MCs <50 mm(-2), n = 18) and group 2 (MCs ≥50 mm(-2), n = 20) according to the infiltrating renal MC count. The clinical-pathological indices were compared. And, correlation between MCs and the clinical-pathological indices was analyzed. Patients of group 2 had more severe renal dysfunctions, expressed as higher levels of serum creatinine (SCr 8.95 ± 3.66 vs. 4.75 ± 2.73 mg/dL, p < 0.001), urine retinol-binding protein (RBP 29.8 ± 13.9 vs. 15.7 ± 11.5 mg/dL, p = 0.005), and lower urinary osmotic pressure. Pathologically, patients of group 2 had a higher percentage of fibrous/fibrocellular crescents (66.7 ± 21.9 vs. 47.0 ± 33.6%, p = 0.037) but a lower percentage of cellular crescents. More CD8 (268 mm(-2) vs. 180 mm(-2), p = 0.045) and CD68 (268 mm(-2) vs. 180 mm(-2), p = 0.045) positive cells infiltrating the interstitium were observed in group 2. Furthermore, renal MCs correlated significantly with the total number of crescents and the tubular interstitial CD8 and CD68 positive cells. And, the number of MCs was associated with the histological types. The renal function was significantly different between the two groups at presentation. However, at 3 and 6 month follow-up, the patient outcome was associated with the histological types. Our study showed that MC infiltrations were associated with chronic lesions in anti-GBM nephritis and may be involved in the loss of renal function with pathological changes.

Acute interstitial nephritis due to nicergoline (Sermion).

PubMed

Kim, Mi Jeong; Chang, Jae Hyuck; Lee, Suk Kyeong; Park, Joo Hyun; Choi, Yeong Jin; Yang, Chul Woo; Kim, Yong Soo; Park, Sung Hak; Bang, Byung Kee

2002-01-01

We report a case of acute interstitial nephritis (AIN) due to nicergoline (Sermion). A 50-year-old patient admitted to our hospital for fever and acute renal failure. Before admission, he had been taking nicergoline and bendazac lysine due to retinal vein occlusion at ophthalmologic department. Thereafter, he experienced intermittent fever and skin rash. On admission, clinical symptoms (i.e. arthralgia and fever) and laboratory findings (i.e. eosinophilia and renal failure) suggested AIN, and which was confirmed by pathologic findings on renal biopsy. A lymphocyte transformation test demonstrated a positive result against nicergoline. Treatment was consisted of withdrawal of nicergoline and intravenous methylprednisolone, and his renal function was completely recovered. To our knowledge, this is the first report of nicergoline-associated AIN. Copyright 2002 S. Karger AG, Basel

A proteinuria cut-off level of 0.7 g/day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: data from the MAINTAIN Nephritis Trial

PubMed Central

Tamirou, Farah; Lauwerys, Bernard R; Dall'Era, Maria; Mackay, Meggan; Rovin, Brad; Cervera, Ricard; Houssiau, Frédéric A

2015-01-01

Background Although an early decrease in proteinuria has been correlated with good long-term renal outcome in lupus nephritis (LN), studies aimed at defining a cut-off proteinuria value are missing, except a recent analysis performed on patients randomised in the Euro-Lupus Nephritis Trial, demonstrating that a target value of 0.8 g/day at month 12 optimised sensitivity and specificity for the prediction of good renal outcome. The objective of the current work is to validate this target in another LN study, namely the MAINTAIN Nephritis Trial (MNT). Methods Long-term (at least 7 years) renal function data were available for 90 patients randomised in the MNT. Receiver operating characteristic curves were built to test the performance of proteinuria measured within the 1st year as short-term predictor of long-term renal outcome. We calculated the positive and negative predictive values (PPV, NPV). Results After 12 months of treatment, achievement of a proteinuria <0.7 g/day best predicted good renal outcome, with a sensitivity and a specificity of 71% and 75%, respectively. The PPV was high (94%) but the NPV low (29%). Addition of the requirement of urine red blood cells ≤5/hpf as response criteria at month 12 reduced sensitivity from 71% to 41%. Conclusions In this cohort of mainly Caucasian patients suffering from a first episode of LN in most cases, achievement of a proteinuria <0.7 g/day at month 12 best predicts good outcome at 7 years and inclusion of haematuria in the set of criteria at month 12 undermines the sensitivity of early proteinuria decrease for the prediction of good outcome. The robustness of these conclusions stems from the very similar results obtained in two distinct LN cohorts. Trial registration number: NCT00204022. PMID:26629352

The cause of death in smallpox: an examination of the pathology record.

PubMed

Martin, David Barrett

2002-07-01

Because the cause of death in smallpox remains controversial, the human pathology record was examined. The surviving case series of smallpox pathology in humans as well as other review articles from English language journals written during the last 200 years were reviewed. The skin lesions in smallpox developed as a result of viral damage and inflammation. Secondary bacterial infection did not occur until the scabs started shedding. During the papular stage of skin eruption, a secondary viremia caused focal lesions in the pharynx, larynx, tongue, trachea, and esophagus in descending frequency. The virus also caused potentially lethal interstitial pneumonitis as well as tubulointerstitial nephritis. The cytopathic effects of smallpox cause death. The data did not support previously promulgated theories attributing death to a bacterial sepsis syndrome seeded from the pustules or immune complex deposition. In a future outbreak, antibiotic therapy would minimally influence mortality.

Epistatic effect of plasminogen activator inhibitor 1 and beta-fibrinogen genes on risk of glomerular microthrombosis in lupus nephritis: interaction with environmental/clinical factors.

PubMed

Gong, Rujun; Liu, Zhihong; Li, Leishi

2007-05-01

Glomerular microthrombosis (GMT) is not uncommon in lupus nephritis and has been associated with active renal injury and progressive kidney destruction. We undertook this study to determine whether genetic variations of hemostasis factors, such as plasminogen activator inhibitor 1 (PAI-1) and fibrinogen, affect the risk of GMT. A cross-sectional cohort of 101 lupus nephritis patients with or without GMT was genotyped for PAI-1 -675 4G/5G and beta-fibrinogen (FGB) -455 G/A gene polymorphisms and analyzed. PAI-1 4G/4G homozygotes and FGB A allele carriers were both at increased risk for GMT. When the data were stratified for both gene polymorphisms, an epistatic effect was detected. The PAI-1 4G/4G genotype was found to predispose to GMT not equally in all lupus nephritis patients, but only in FGB A allele carriers. Likewise, the association between the FGB A allele and GMT was restricted to lupus nephritis patients homozygous for the PAI-1 4G allele. This epistatic effect was revalidated by the multifactor dimensionality reduction (MDR) analysis and further assessed by incorporating a variety of environmental and clinical factors into the MDR analysis. The most parsimonious model that had a cross-validation consistency of 100% included joint effects of PAI-1 and FGB gene polymorphisms and anticardiolipin antibody (aCL) status and yielded the best prediction of GMT, with 66.6% accuracy. Our findings suggest that risk of GMT in lupus nephritis is attributable, at least in part, to an epistatic effect of PAI-1 and FGB genes, likely via an interaction with environmental/clinical factors, such as aCL.

[Yersiniosis as a cause of acute tubulointerstitial nephritis and acute renal failure--case report].

PubMed

Runowski, Dariusz; Szymoniak, Norbert; Zaniew, Marcin; Piatkowska-Kopczyk, Małgorzata; Wozniak, Aldona; Kroll, Paweł; Zachwieja, Jacek

2005-01-01

Tubulointerstitial nephritis (TN) is a heterogenous disease, where disturbances of the interstitial tissue and renal tubules are found. Different immunological and nonimmunological mechanisms initiated by infectious and non-infectious factors may lead to TN. A case of 13-years-old girl with primary diagnosis of acute pyelonephritis is presented. The abdominal pain, headache, pain in lumbar region and intermittent fever with loss of appetite were observed in this girl a few weeks before admission. Microcytic anemia, proteinuria and glucosuria, azotemia and elevated markers of inflammatory response were found. In ultrasound examination heterogenous cortex echogenicity of both kidneys and disturbances in parenchymal blood flow were observed. In renal scintigraphy the discriminated catch index was found. Kidney biopsy revealed the edema of the interstitial space with mononuclear and lymphocyte infiltration. The diagnosis of TN was established upon the history, clinical examination, results of laboratory tests, kidney imaging and biopsy. After steroid and doxycycline treatment an improvement and normalization of the results of laboratory tests were observed. It seems to be justified to consider Yersinia infection as a cause of acute tubulointerstitial nephritis.

The Leptospira outer membrane protein LipL32 induces tubulointerstitial nephritis-mediated gene expression in mouse proximal tubule cells.

PubMed

Yang, Chih-Wei; Wu, Mai-Szu; Pan, Ming-Jeng; Hsieh, Wang-Ju; Vandewalle, Alain; Huang, Chiu-Ching

2002-08-01

Tubulointerstitial nephritis is a main renal manifestation caused by pathogenic leptospira that accumulate mostly in the proximal tubules, thereby inducing tubular injury and tubulointerstitial nephritis. To elucidate the role of leptospira outer membrane proteins in tubulointerstitial nephritis, outer membrane proteins from pathogenic Leptospira shermani and nonpathogenic Leptospira patoc extracted by Triton X-114 were administered to cultured mouse proximal tubule cells. A dose-dependent increase of monocyte chemoattractant protein-1 (MCP-1), RANTES, nitrite, and tumor necrosis factor-alpha (TNF-alpha) in the culture supernatant was observed 48 h after incubating Leptospira shermani outer membrane proteins with mouse proximal tubule cells. RT competitive-PCR experiments showed that Leptospira shermani outer membrane proteins (0.2 microg/ml) increased the expression of MCP-1, nitric oxide synthase (iNOS), RANTES, and TNF-alpha mRNA by 3.0-, 9.4-, 2.5-, and 2.5-fold, respectively, when compared with untreated cells. Outer membrane proteins extract from avirulent Leptospira patoc did not induce significant effects. The pathogenic outer membrane proteins extract contain a major component of a 32-kD lipoprotein (LipL32), which is absent in the nonpathogenic leptospira outer membrane. An antibody raised against LipL32 prevented the stimulatory effect of Leptospira shermani outer membrane proteins extract on MCP-1 and iNOS mRNA expression in cultured proximal tubule cells, whereas recombinant LipL32 significantly stimulated the expression of MCP-1 and iNOS mRNAs and augmented nuclear binding of nuclear factor-kappaB (NF-kappaB) and AP-1 transcription factors in proximal tubule cells. An antibody raised against LipL32 also blunted the effects induced by the recombinant LipL32. This study demonstrates that LipL32 is a major component of pathogenic leptospira outer membrane proteins involved in the pathogenesis of tubulointerstitial nephritis.

Activated protein C attenuates systemic lupus erythematosus and lupus nephritis in MRL-Fas(lpr) mice.

PubMed

Lichtnekert, Julia; Rupanagudi, Khader Valli; Kulkarni, Onkar P; Darisipudi, Murthy Narayana; Allam, Ramanjaneyulu; Anders, Hans-Joachim

2011-09-15

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease leading to inflammatory tissue damage in multiple organs (e.g., lupus nephritis). Current treatments including steroids, antimalarials, and immunosuppressive drugs have significant side effects. Activated protein C is a natural protein with anticoagulant and immunomodulatory effects, and its recombinant version has been approved by the U.S. Food and Drug Administration to treat severe sepsis. Given the similarities between overshooting immune activation in sepsis and autoimmunity, we hypothesized that recombinant activated protein C would also suppress SLE and lupus nephritis. To test this concept, autoimmune female MRL-Fas(lpr) mice were injected with either vehicle or recombinant human activated protein C from week 14-18 of age. Activated protein C treatment significantly suppressed lupus nephritis as evidenced by decrease in activity index, glomerular IgG and complement C3 deposits, macrophage counts, as well as intrarenal IL-12 expression. Further, activated protein C attenuated cutaneous lupus and lung disease as compared with vehicle-treated MRL-Fas(lpr) mice. In addition, parameters of systemic autoimmunity, such as plasma cytokine levels of IL-12p40, IL-6, and CCL2/MCP-1, and numbers of B cells and plasma cells in spleen were suppressed by activated protein C. The latter was associated with lower total plasma IgM and IgG levels as well as lower titers of anti-dsDNA IgG and rheumatoid factor. Together, recombinant activated protein C suppresses the abnormal systemic immune activation in SLE of MRL-Fas(lpr) mice, which prevents subsequent kidney, lung, and skin disease. These results implicate that recombinant activated protein C might be useful for the treatment of human SLE.

Prognostic factors for treatment response in patients with lupus nephritis.

PubMed

Miranda-Hernández, Dafhne; Cruz-Reyes, Claudia; Angeles, Ulises; Jara, Luis Javier; Saavedra, Miguel Angel

2014-01-01

To identify prognostic factors associated with response to induction therapy in lupus nephritis (LN) according to the stage of treatment. We analyzed a retrospective cohort of patients of systemic lupus erythematosus (SLE) with biopsy-proven LN from January 2001 to December 2008. LN was classified according to WHO. All patients received induction therapy and had a minimum follow-up period of two years. We analyzed 18 clinical and laboratory variables that potentially have predictive value for response to therapy. We identified predictors of therapeutic response at 6, 12 and 24 months by univariate and multivariate analysis; odds ratios (OR) with confidence intervals (CI) 95% were also calculated. We reviewed the clinical records of 168 patients, 141 female (84%). The response rate was 69% at 6 months, 86.9% at 12 months and 79.7% at 24 months. Multivariate analysis found that > 25 years of age at diagnosis of LN and the presence of microhematuria were factors associated with good response to induction treatment. At 12 months, baseline creatinine clearance < 30ml/min was associated with a poor response to treatment. Finally at 24 months, delay in treatment was a predictor of poor response to treatment and the presence of a histological proliferative NL and low C3 were associated with good response to treatment. There are treatment-modifiable factors that can alter aberrant immunologic activity of NF. Therefore, intensive early treatment of lupus nephritis is associated with favorable response to two years. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Kidney-targeted inhibition of protein kinase C-α ameliorates nephrotoxic nephritis with restoration of mitochondrial dysfunction.

PubMed

Kvirkvelia, Nino; McMenamin, Malgorzata; Warren, Marie; Jadeja, Ravirajsinh N; Kodeboyina, Sai Karthik; Sharma, Ashok; Zhi, Wenbo; O'Connor, Paul M; Raju, Raghavan; Lucas, Rudolf; Madaio, Michael P

2018-05-04

To investigate the role of protein kinase C-α (PKC-α) in glomerulonephritis, the capacity of PKC-α inhibition to reverse the course of established nephrotoxic nephritis (NTN) was evaluated. Nephritis was induced by a single injection of nephrotoxic serum and after its onset, a PKC-α inhibitor was administered either systemically or by targeted glomerular delivery. By day seven, all mice with NTN had severe nephritis, whereas mice that received PKC-α inhibitors in either form had minimal evidence of disease. To further understand the underlying mechanism, label-free shotgun proteomic analysis of the kidney cortexes were performed, using quantitative mass spectrometry. Ingenuity pathway analysis revealed 157 differentially expressed proteins and mitochondrial dysfunction as the most modulated pathway. Functional protein groups most affected by NTN were mitochondrial proteins associated with respiratory processes. These proteins were down-regulated in the mice with NTN, while their expression was restored with PKC-α inhibition. This suggests a role for proteins that regulate oxidative phosphorylation in recovery. In cultured glomerular endothelial cells, nephrotoxic serum caused a decrease in mitochondrial respiration and membrane potential, mitochondrial morphologic changes and an increase in glycolytic lactic acid production; all normalized by PKC-α inhibition. Thus, PKC-α has a critical role in NTN progression, and the results implicate mitochondrial processes through restoring oxidative phosphorylation, as an essential mechanism underlying recovery. Importantly, our study provides additional support for targeted therapy to glomeruli to reverse the course of progressive disease. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

[Cerebral aneurysms complicating bacterial endocarditis. Seven cases (author's transl)].

PubMed

Pecker, J; Vallée, B; Camuzet, J P; Faivre, J; Javalet, A

The authors report seven cases of cerebral aneurysms complicating bacterial endocarditis. The evolution was good in three cases, two of which without sequelae. The bacteries involved were staphylococcus, streptococcus, and enterobacter. The cardiopathy was mitral in four cases. Two patients presented an isolated focal neurological impairment, while the other five presented a severe coma either isolated (one case) or associated with focal neurological deficits (four cases). An intracerebral hematoma was diagnosed in five cases (four died). Only one patient was not operated. The surgical treatment was as follows: one carotid ligation (good result), two evacuations of intracerebral hematomas (both died), two evacuations of intracerebral hematomas with clipping of the aneurysms (one died, one had a fair result in despite of residual hemiplegia), one clipping of aneurysm (good result). Repeated cerebral angiographies should be systematically performed in cases of bacterial endocarditis in order to disclose and follow up cerebral aneurysms which may occur in this condition. Except in cases of emergency, surgery should be differed, in particular, in cases of proximal or multiple aneurysms. Aneurysms of the peripheral cortical arteries are more accessible to treatment and may be operated in the acute phase.

Control of lupus nephritis by changes of gut microbiota.

PubMed

Mu, Qinghui; Zhang, Husen; Liao, Xiaofeng; Lin, Kaisen; Liu, Hualan; Edwards, Michael R; Ahmed, S Ansar; Yuan, Ruoxi; Li, Liwu; Cecere, Thomas E; Branson, David B; Kirby, Jay L; Goswami, Poorna; Leeth, Caroline M; Read, Kaitlin A; Oestreich, Kenneth J; Vieson, Miranda D; Reilly, Christopher M; Luo, Xin M

2017-07-11

Systemic lupus erythematosus, characterized by persistent inflammation, is a complex autoimmune disorder with no known cure. Immunosuppressants used in treatment put patients at a higher risk of infections. New knowledge of disease modulators, such as symbiotic bacteria, can enable fine-tuning of parts of the immune system, rather than suppressing it altogether. Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Here we report a role of gut microbiota in the pathogenesis of renal dysfunction in lupus. Using a classical model of lupus nephritis, MRL/lpr, we found a marked depletion of Lactobacillales in the gut microbiota. Increasing Lactobacillales in the gut improved renal function of these mice and prolonged their survival. We used a mixture of 5 Lactobacillus strains (Lactobacillus oris, Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus johnsonii, and Lactobacillus gasseri), but L. reuteri and an uncultured Lactobacillus sp. accounted for most of the observed effects. Further studies revealed that MRL/lpr mice possessed a "leaky" gut, which was reversed by increased Lactobacillus colonization. Lactobacillus treatment contributed to an anti-inflammatory environment by decreasing IL-6 and increasing IL-10 production in the gut. In the circulation, Lactobacillus treatment increased IL-10 and decreased IgG2a that is considered to be a major immune deposit in the kidney of MRL/lpr mice. Inside the kidney, Lactobacillus treatment also skewed the Treg-Th17 balance towards a Treg phenotype. These beneficial effects were present in female and castrated male mice, but not in intact males, suggesting that the gut microbiota controls lupus nephritis in a sex hormone-dependent manner. This work demonstrates essential mechanisms on how changes of the gut microbiota regulate lupus-associated immune responses in mice. Future studies are warranted to determine if these results can be replicated in human subjects.

The Non-Muscle Myosin Heavy Chain 9 Gene (MYH9) Is Not Associated with Lupus Nephritis in African Americans

PubMed Central

Freedman, Barry I.; Edberg, Jeffrey C.; Comeau, Mary E.; Murea, Mariana; Bowden, Donald W.; Divers, Jasmin; Alarcón, Graciela S.; Brown, Elizabeth E.; McGwin, Gerald; Kopp, Jeffrey B.; Winkler, Cheryl A.; Nelson, George W.; Illei, Gabor; Petri, Michelle; Ramsey-Goldman, Rosalind; Reveille, John D.; Vilá, Luis M.; Langefeld, Carl D.; Kimberly, Robert P.

2010-01-01

Background African Americans (AA) disproportionately develop lupus nephritis (LN) relative to European Americans and familial clustering supports causative genes. Since MYH9 underlies approximately 40% of end-stage renal disease (ESRD) in AA, we tested for genetic association with LN. Methods Seven MYH9 single nucleotide polymorphisms (SNPs) and the E1 risk haplotype were tested for association with LN in three cohorts of AA. Results A preliminary analysis revealed that the MYH9 E1 risk haplotype was associated with ESRD in 25 cases with presumed systemic lupus erythematosus (SLE)-associated ESRD, compared to 735 non-SLE controls (odds ratio 3.1; p = 0.010 recessive). Replication analyses were performed in 583 AA with SLE in the PROFILE cohort (318 with LN; 265 with SLE but without nephropathy) and 60 AA from the NIH (39 with LN; 21 with SLE but without nephropathy). Analysis of the NIH and larger PROFILE cohorts, as well as a combined analysis, did not support this association. Conclusions These results suggest that AA with ESRD and coincident SLE who were recruited from dialysis clinics more likely have kidney diseases in the MYH9-associated spectrum of focal segmental glomerulosclerosis. PROFILE and NIH participants, recruited from rheumatology practices, demonstrate that MYH9 does not contribute substantially to the development of LN in AA. PMID:20523037

The prevalence of leptospirosis and its association with multifocal interstitial nephritis in swine at slaughter.

PubMed Central

Baker, T F; McEwen, S A; Prescott, J F; Meek, A H

1989-01-01

An abattoir survey was undertaken to determine the prevalence of leptospirosis and its association with lesions of multifocal interstitial nephritis (so-called "white spotted kidneys") in swine at slaughter. Both cross-sectional and case-control study designs were used. Of 197 kidneys from hogs randomly selected at slaughter, 11 (5.6%) had generalized grey-white foci typical of multifocal interstitial nephritis (MFIN). Antibody titers greater than or equal to 1:80 against Leptospira pomona were detected in nine (4.6%) hogs and against L. bratislava in 63 (32%) of these hogs. Leptospira pomona (kennewicki) was detected by immunofluorescence in 5/197 (2.5%) of randomly selected hogs. Leptospires identified as genotype kennewicki were isolated from six (9.8%) of 61 kidneys cultured. Leptospira bratislava was not detected by immunofluorescence or culture. There was a highly significant (p = 0.00) and strong association (odds ratio (OR) = 195) between high L. pomona titer (greater than or equal to 1:80) and the presence of leptospires in the kidneys, as detected by culture. There was also a significant (p = 0.046) and strong (OR = 8.10) association between multifocal interstitial nephritis and the presence of renal leptospires as detected by culture. The association between leptospiral titer and MFIN lesions in the prevalence survey group of animals was statistically significant (p = 0.031), but this association was not significant in the case-control study group (p = 0.071) The failure to identify L. bratislava despite serological evidence of infection suggests that some of these seropositive animals may have been transiently infected at an early age, that serological findings were falsely positive, or that immunofluorescence and isolation attempts failed to detect L. bratislava if they were indeed present in the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2766150

Mild and moderate Mannose Binding Lectin deficiency are associated with systemic lupus erythematosus and lupus nephritis in Brazilian patients.

PubMed

Perazzio, Sandro Félix; Silva, Neusa Pereira da; Carneiro-Sampaio, Magda; Andrade, Luis Eduardo Coelho

2016-01-01

The potential association of mannose binding lectin (MBL) deficiency and systemic lupus erythematosus (SLE) has been investigated in several studies, but results have been mixed. One explanation for the conflicting results could be differences in ethnic background of study subjects. In this study we investigated the association of MBL deficiency and SLE in a large cohort of Brazilian SLE patients and controls. Serum MBL and Complement levels were determined for 286 Brazilian adult SLE patients and 301 healthy Brazilian adults as controls. MBL deficiency was classified as mild (<1000 and ≥500μg/L), moderate (<500 and ≥100μg/L) or severe (<100μg/L). SLE patients presented higher frequency of mild and moderate MBL deficiency compared to controls. SLE patients with MBL deficiency presented higher frequency of lupus nephritis compared to those without MBL deficiency. MBL deficiency was not associated with any other clinical manifestation, use of immunosuppressant therapy, disease activity, disease severity serum or Complement levels. This study shows that an association between MBL deficiency and SLE does exist in the Brazilian population. We also found an association between MBL deficiency and lupus nephritis. These findings support the hypothesis that MBL deficiency contributes to the development of SLE and lupus nephritis. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Focal Contacts as Mechanosensors

PubMed Central

Riveline, Daniel; Zamir, Eli; Balaban, Nathalie Q.; Schwarz, Ulrich S.; Ishizaki, Toshimasa; Narumiya, Shuh; Kam, Zvi; Geiger, Benjamin; Bershadsky, Alexander D.

2001-01-01

The transition of cell–matrix adhesions from the initial punctate focal complexes into the mature elongated form, known as focal contacts, requires GTPase Rho activity. In particular, activation of myosin II–driven contractility by a Rho target known as Rho-associated kinase (ROCK) was shown to be essential for focal contact formation. To dissect the mechanism of Rho-dependent induction of focal contacts and to elucidate the role of cell contractility, we applied mechanical force to vinculin-containing dot-like adhesions at the cell edge using a micropipette. Local centripetal pulling led to local assembly and elongation of these structures and to their development into streak-like focal contacts, as revealed by the dynamics of green fluorescent protein–tagged vinculin or paxillin and interference reflection microscopy. Inhibition of Rho activity by C3 transferase suppressed this force-induced focal contact formation. However, constitutively active mutants of another Rho target, the formin homology protein mDia1 (Watanabe, N., T. Kato, A. Fujita, T. Ishizaki, and S. Narumiya. 1999. Nat. Cell Biol. 1:136–143), were sufficient to restore force-induced focal contact formation in C3 transferase-treated cells. Force-induced formation of the focal contacts still occurred in cells subjected to myosin II and ROCK inhibition. Thus, as long as mDia1 is active, external tension force bypasses the requirement for ROCK-mediated myosin II contractility in the induction of focal contacts. Our experiments show that integrin-containing focal complexes behave as individual mechanosensors exhibiting directional assembly in response to local force. PMID:11402062

Lupus Nephritis: An Overview of Recent Findings

PubMed Central

de Zubiria Salgado, Alberto; Herrera-Diaz, Catalina

2012-01-01

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) since it is the major predictor of poor prognosis. In susceptible individuals suffering of SLE, in situ formation and deposit of immune complexes (ICs) from apoptotic bodies occur in the kidneys as a result of an amplified epitope immunological response. IC glomerular deposits generate release of proinflammatory cytokines and cell adhesion molecules causing inflammation. This leads to monocytes and polymorphonuclear cells chemotaxis. Subsequent release of proteases generates endothelial injury and mesangial proliferation. Presence of ICs promotes adaptive immune response and causes dendritic cells to release type I interferon. This induces maturation and activation of infiltrating T cells, and amplification of Th2, Th1 and Th17 lymphocytes. Each of them, amplify B cells and activates macrophages to release more proinflammatory molecules, generating effector cells that cannot be modulated promoting kidney epithelial proliferation and fibrosis. Herein immunopathological findings of LN are reviewed. PMID:22536486

Minorities with lupus nephritis and medications: a study of facilitators to medication decision-making.

PubMed

Singh, Jasvinder A; Qu, Haiyan; Yazdany, Jinoos; Chatham, Winn; Shewchuk, Richard

2015-12-17

Medication decision-making poses a challenge for a significant proportion of patients. This is an even more challenging for patients who have complex, rare, immune conditions that affect them at a young age and are associated with the use of life-long treatment, perceived by some as having significant risk of side effects and toxicity. The aim of our study was to examine the perspectives of women with lupus nephritis on facilitators to medication decision-making. We used the nominal group technique (NGT), a structured formative process to elicit patient perspectives. An NGT expert moderated eight patient group meetings. Participants (n = 52) responded to the question "What sorts of things make it easier for people to decide to take the medicines that doctors prescribe for treating their lupus kidney disease?" Patients nominated, discussed, and prioritized facilitators to medication decisional processes. Fifty-two women with lupus nephritis participated in eight NGT meetings (27 African-American, 13 Hispanic, and 12 Caucasian). Average age was 40.6 years (standard deviation (SD) = 13.3), and disease duration was 11.8 years (SD = 8.3); 36.5 % obtained at least a college education, and 55.8 % had difficulty in reading health materials. Patients generated 280 decision-making facilitators (range of 26 to 42 per panel). Of these, 102 (36 %) facilitators were perceived by patients as having relatively more influence in decision-making processes than others. Prioritized facilitators included effective patient-physician communication regarding benefits/harms, patient desire to live a normal life and improve quality of life, concern for their dependents, experiencing benefits and few/infrequent/no harms with lupus medications, and their affordability. Relative to African-Americans, Caucasian and Hispanic patients endorsed a smaller percentage of facilitators as influential. Level of agreement with which patients within panels independently agreed in their

Focal retinal phlebitis.

PubMed

Hoang, Quan V; Freund, K Bailey; Klancnik, James M; Sorenson, John A; Cunningham, Emmett T; Yannuzzi, Lawrence A

2012-01-01

To report three cases of solitary, focal retinal phlebitis. An observational case series. Three eyes in three patients were noted to have unilateral decreased vision, macular edema, and a focal retinal phlebitis, which was not at an arteriovenous crossing. All three patients developed a branch retinal vein occlusion at the site of inflammation. These patients had no other evidence of intraocular inflammation, including vitritis, retinitis, retinal vasculitis, or choroiditis, nor was there any systemic disorder associated with inflammation, infection, or coagulation identified. Focal retinal phlebitis appears to be an uncommon and unique entity that produces macular edema and ultimately branch retinal vein occlusion. In our patients, the focal phlebitis and venous occlusion did not occur at an arteriovenous crossing, which is the typical site for branch retinal venous occlusive disease. This suggests that our cases represent a distinct clinical entity, which starts with a focal abnormality in the wall of a retinal venule, resulting in surrounding exudation and, ultimately, ends with branch retinal vein occlusion.

Semaphorin3A: A Potential Therapeutic Tool for Lupus Nephritis.

PubMed

Bejar, Jacob; Kessler, Ofra; Sabag, Adi D; Sabo, Edmond; Itzhak, Ofer Ben; Neufeld, Gera; Vadasz, Zahava

2018-01-01

The immune regulatory properties of semaphorin3A (sema3A) (both innate and adaptive) are well established in many in vitro studies. The injection of sema3A into a mice model of rheumatoid arthritis was proven to be highly beneficial, both in attenuating clinical symptoms and in decreasing inflammatory mechanisms. This study was designed in order to assess the possible therapeutic benefits of sema3A following its injection into female NZB/W mice. Forty-eight NZB/W mice were recruited for this study. Thirty mice were treated as a "prevention group" and 18 were used as a "treatment group." Eight-week-old mice were acclimated and then divided into the two abovementioned groups. The injection of sema3A into young mice (at week 12) before the onset of disease (the prevention group) delayed the appearance of proteinuria. Here, the median time to severe proteinuria was 110 days, 95% CI: 88-131. However, in mice in which the empty vector was injected, the median time to severe proteinuria was 63 days, 95% CI: 0-139. sema3A treatment, significantly reduced renal damage, namely, it prevented the deposition of immune complexes in the glomeruli. When sema3A was injected at the onset of proteinuria (the treatment group), aiming to treat rather than to prevent disease in these mice, survival was increased and the deterioration of proteinuria was delayed. Semaphorin3A is highly beneficial in reducing lupus nephritis in NZB/W mice. It delays the appearance and deterioration of proteinuria, and increases the survival rates in these mice. The regulatory mechanisms of sema3A involve both innate and adaptive immune responses. Further studies will establish the idea of applying sema3A in the treatment of lupus nephritis.

Characterization of Novel PI3Kδ Inhibitors as Potential Therapeutics for SLE and Lupus Nephritis in Pre-Clinical Studies

PubMed Central

Haselmayer, Philipp; Camps, Montserrat; Muzerelle, Mathilde; El Bawab, Samer; Waltzinger, Caroline; Bruns, Lisa; Abla, Nada; Polokoff, Mark A.; Jond-Necand, Carole; Gaudet, Marilène; Benoit, Audrey; Bertschy Meier, Dominique; Martin, Catherine; Gretener, Denise; Lombardi, Maria Stella; Grenningloh, Roland; Ladel, Christoph; Petersen, Jørgen Søberg; Gaillard, Pascale; Ji, Hong

2014-01-01

SLE is a complex autoimmune inflammatory disease characterized by pathogenic autoantibody production as a consequence of uncontrolled T–B cell activity and immune-complex deposition in various organs, including kidney, leading to tissue damage and function loss. There is a high unmet need for better treatment options other than corticosteroids and immunosuppressants. Phosphoinositol-3 kinase δ (PI3Kδ) is a promising target in this respect as it is essential in mediating B- and T-cell function in mouse and human. We report the identification of selective PI3Kδ inhibitors that blocked B-, T-, and plasmacytoid dendritic cell activities in human peripheral blood and in primary cell co-cultures (BioMAP®) without detecting signs of undesired toxicity. In an IFNα-accelerated mouse SLE model, our PI3Kδ inhibitors blocked nephritis development, whether administered at the onset of autoantibody appearance or the onset of proteinuria. Disease amelioration correlated with normalized immune cell numbers in the spleen, reduced immune-complex deposition as well as reduced inflammation, fibrosis, and tissue damage in the kidney. Improvements were similar to those achieved with a frequently prescribed drug for lupus nephritis, the potent immunosuppressant mycophenolate mofetil. Finally, we established a pharmacodynamics/pharmacokinetic/efficacy model that revealed that a sustained PI3Kδ inhibition of 50% is sufficient to achieve full efficacy in our disease model. These data demonstrate the therapeutic potential of PI3Kδ inhibitors in SLE and lupus nephritis. PMID:24904582

Characterization of Novel PI3Kδ Inhibitors as Potential Therapeutics for SLE and Lupus Nephritis in Pre-Clinical Studies.

PubMed

Haselmayer, Philipp; Camps, Montserrat; Muzerelle, Mathilde; El Bawab, Samer; Waltzinger, Caroline; Bruns, Lisa; Abla, Nada; Polokoff, Mark A; Jond-Necand, Carole; Gaudet, Marilène; Benoit, Audrey; Bertschy Meier, Dominique; Martin, Catherine; Gretener, Denise; Lombardi, Maria Stella; Grenningloh, Roland; Ladel, Christoph; Petersen, Jørgen Søberg; Gaillard, Pascale; Ji, Hong

2014-01-01

SLE is a complex autoimmune inflammatory disease characterized by pathogenic autoantibody production as a consequence of uncontrolled T-B cell activity and immune-complex deposition in various organs, including kidney, leading to tissue damage and function loss. There is a high unmet need for better treatment options other than corticosteroids and immunosuppressants. Phosphoinositol-3 kinase δ (PI3Kδ) is a promising target in this respect as it is essential in mediating B- and T-cell function in mouse and human. We report the identification of selective PI3Kδ inhibitors that blocked B-, T-, and plasmacytoid dendritic cell activities in human peripheral blood and in primary cell co-cultures (BioMAP(®)) without detecting signs of undesired toxicity. In an IFNα-accelerated mouse SLE model, our PI3Kδ inhibitors blocked nephritis development, whether administered at the onset of autoantibody appearance or the onset of proteinuria. Disease amelioration correlated with normalized immune cell numbers in the spleen, reduced immune-complex deposition as well as reduced inflammation, fibrosis, and tissue damage in the kidney. Improvements were similar to those achieved with a frequently prescribed drug for lupus nephritis, the potent immunosuppressant mycophenolate mofetil. Finally, we established a pharmacodynamics/pharmacokinetic/efficacy model that revealed that a sustained PI3Kδ inhibition of 50% is sufficient to achieve full efficacy in our disease model. These data demonstrate the therapeutic potential of PI3Kδ inhibitors in SLE and lupus nephritis.

Evaluation of TGF-β1 and MCP-1 expression and tubulointerstitial fibrosis in children with Henoch-Schönlein purpura nephritis and IgA nephropathy: A clinical correlation.

PubMed

Shuiai, Zhao; Huijun, Shen; Weizhong, Gu; Aimin, Liu; Jianhua, Mao

2017-02-01

Henoch-Schönlein purpura nephritis and immunoglobulin A nephropathy are two diseases with similar clinical presentations but very different prognoses. Transforming growth factor β1 and monocyte chemoattractant protein-1 have been associated with the development of tissue fibrosis. We examined the development of tubulointerstitial fibrosis and its relationship with Transforming growth factor β1 and monocyte chemoattractant protein-1 expression in these patients. Renal tissue samples were collected by renal biopsy from 50 children with Henoch-Schönlein purpura nephritis and 50 children with immunoglobulin A nephropathy. Hematoxylin and eosin and Masson's trichrome-stained tissues were examined using light microscopy. Tubulointerstitial fibrosis was graded using the method described by Bohle et al. (1). The immunohistochemical detection of Transforming growth factor β1 and monocyte chemoattractant protein-1 expression was correlated with the tubulointerstitial fibrosis grade. Clinical Trial registration number: ZJCH-2012-0105. Transforming growth factor β1 and monocyte chemoattractant protein-1 expression in the renal tissues was significantly greater in the patients with immunoglobulin A nephropathy than in the patients with Henoch-Schönlein purpura nephritis (both p<0.001). The immunoglobulin A nephropathy patients had a higher tubulointerstitial fibrosis grade than the Henoch-Schönlein purpura nephritis patients (p<0.001). The tubulointerstitial fibrosis grade was in accordance with the Transforming growth factor β1 and monocyte chemoattractant protein-1 expression levels in both diseases (both p<0.001). Transforming growth factor β1 and monocyte chemoattractant protein-1 expression was associated with the development of immunoglobulin A nephropathy and Henoch-Schönlein purpura nephritis. Further studies are needed to better evaluate this association.

Mesangial cell Fas ligand: upregulation in human lupus nephritis and NF-kappaB-mediated expression in cultured human mesangial cells.

PubMed

Tsukinoki, Tomoko; Sugiyama, Hitoshi; Sunami, Reiko; Kobayashi, Mizuho; Onoda, Tetsuya; Maeshima, Yohei; Yamasaki, Yasushi; Makino, Hirofumi

2004-09-01

Fas ligand (FasL) is a well-known death factor; however, the role of FasL in the regulation of human glomerulonephritis remains unclear. We investigated the renal expression and localization of FasL in various forms of human glomerulonephritis by immunohistochemistry, utilizing confocal laser scanning microscopy. We further evaluated cytokine-induced FasL expression via nuclear factor (NF)kappaB in cultured human mesangial cells (HMC). The level of soluble FasL was measured by a specific enzyme-linked immunosorbent assay (ELISA). The frequency of glomerular FasL-positive cases was higher in lupus nephritis (37.9%) as compared with other forms of glomerulonephritis (8.7%). The glomerular FasL score in proliferative lupus nephritis was significantly higher than that in nonproliferative forms. Patients with a high apoptosis score, severe microhematuria, proteinuria, or decreased renal function had a high FasL score. Double immunolabelling demonstrated that the most prevalent phenotypes of FasL-positive cells were mesangial cells. In cultured HMC, interleukin (IL)1beta, lipopolysaccharide (LPS), or gamma interferon (IFN) upregulated membrane-bound FasL. IL1beta significantly, and LPS or gammaIFN weakly activated NFkappaB, but none of these agents activated NFkappaB/Rel-related nuclear factor of activated T cells (NFATc) or IFN regulatory factor-1. IL1beta-mediated NFkappaB was completely inhibited in the presence of lactacystin, a potent inhibitor of NFkappaB. Lactacystin-mediated inhibition of NFkappaB reduced FasL protein levels. Matrix metalloproteinase (MMP)-7, but not other MMPs (1, 2, 3, 8, or 9), significantly sensitized HMC to release soluble FasL after IL1beta stimulation. The results suggest that: (1) upregulation of mesangial FasL may contribute to the glomerular inflammation in proliferative lupus nephritis in vivo; (2) proinflammatory cytokines, in particular IL1beta, produced in nephritis can upregulate FasL via the transcription factor NFkappaB in HMC

Toll-like receptor activation in the pathogenesis of lupus nephritis.

PubMed

Lorenz, Georg; Lech, Maciej; Anders, Hans-Joachim

2017-12-01

The pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis is complex but no longer enigmatic. Much progress has been made to on the polygenetic origin of lupus in identifying gene variants that permit the loss of tolerance against nuclear autoantigens. Along the same line in about 50% of lupus patients additional genetic weaknesses promote immune complex glomerulonephritis and filtration barrier dysfunction. Here we briefly summarize the pathogenesis of SLE with a focus on loss of tolerance and the role of toll-like receptors in the "pseudo"-antiviral immunity concept of systemic lupus. In addition, we discuss the local role of Toll-like receptors in intrarenal inflammation and kidney remodeling. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed Central

Uttl, Bob

2011-01-01

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

Focal cryotherapy for prostate cancer.

PubMed

Tsivian, Matvey; Polascik, Thomas J

2010-05-01

Focal therapy for prostate cancer has emerged an interesting concept as a less morbid option for the treatment of localized low-risk disease. Despite the growing interest in focal therapy, this approach has not yet gained sufficient popularity nor provided enough data to be discussed outside the experimental application. Herein we summarize the available data on focal cryotherapy and focus on the targets to be achieved in order to increase the applicability of focal cryotherapy to clinical practice. A cautious approach to candidate selection and generation of solid scientific data that would result in wide consensus on patient selection strategies and follow-up schemes would provide the tools necessary to take the path of focal therapy. Currently available focal cryotherapy data demonstrate excellent short-term results and a favorable quality-of-life profile. Although the future role of focal treatment is debated, a growing amount of science is generated in support of this minimally invasive approach.

Preeclampsia in pregnancies complicated by systemic lupus erythematosus (SLE) nephritis: prophylactic treatment with multidisciplinary approach are important keys to prevent adverse obstetric outcomes.

PubMed

Mecacci, Federico; Simeone, Serena; Cirami, Calogero Lino; Cozzolino, Mauro; Serena, Caterina; Rambaldi, Marianna Pina; Gallo, Pamela; Emmi, Lorenzo; Cammelli, Daniele; Mello, Giorgio; Matucci Cerinic, Marco

2017-11-27

Systemic lupus erythematosus (SLE) commonly affects women of childbearing age. Hypertension, antiphospholipid syndrome, and lupus nephritis are risk factors for adverse maternal/fetal outcome. The aim of this retrospective cohort study is to compare pregnancy outcomes in patients with and without SLE nephritis, using a multidisciplinary approach and a broad prophylaxis protocol. Data were collected from 86 pregnancies complicated by SLE. Twenty-seven women with nephropathy before pregnancy stated as the study group and 59 formed the control group. Each group received a prophylactic treatment based on their clinical characteristics. Results were expressed as mean ± SD, percentage and χ 2 -test (significant values when p < .05). The prophylactic treatment (60.4% of the patients) significantly controlled the complications related to some risk factors, such as antiphospholipid antibodies (aPL) and nephritis. Preeclampsia occurred in 14.8% of patients. Patients with pregestational hypertension showed a 2.75 odds ratio of adverse events when compared to the group without chronic hypertension. The presence of proteinuria was associated with a risk of preeclampsia 2.45 times greater, as well as serum creatinine >1.2 mg/dL, which was related to a risk 1.25 times higher than the risk observed in patients with serum creatinine <1.2 mg/dL. A 6-month inactive disease was associated with a better outcome. A value of Estimated Glomerular Filtration Rate (eGFR) < 90 mL/min/1.73 m 2 resulted in a 18.73 times greater risk of preeclampsia, intrauterine growth restriction (IUGR), and preterm delivery. A multidisciplinary approach in a tertiary care center and a broad prophylactic treatment protocol to patients affected by SLE and complicated by nephritis may definitively foster a successful pregnancy.

Dual-layer electrode-driven liquid crystal lens with electrically tunable focal length and focal plane

NASA Astrophysics Data System (ADS)

Zhang, Y. A.; Lin, C. F.; Lin, J. P.; Zeng, X. Y.; Yan, Q.; Zhou, X. T.; Guo, T. L.

2018-04-01

Electric-field-driven liquid crystal (ELC) lens with tunable focal length and their depth of field has been extensively applied in 3D display and imaging systems. In this work, a dual-layer electrode-driven liquid crystal (DELC) lens with electrically tunable focal length and controllable focal plane is demonstrated. ITO-SiO2-AZO electrodes with the dual-layer staggered structure on the top substrate are used as driven electrodes within a LC cell, which permits the establishment of an alternative controllability. The focal length of the DELC lens can be adjusted from 1.41 cm to 0.29 cm when the operating voltage changes from 15 V to 40 V. Furthermore, the focal plane of the DELC lens can selectively move by changing the driving method of the applied voltage to the next driven electrodes. This work demonstrates that the DELC lens has potential applications in imaging systems because of electrically tunable focal length and controllable focal plane.

Mycophenolate mofetil as maintenance therapy for childhood-onset systemic lupus erythematosus patients with severe lupus nephritis.

PubMed

Kizawa, Toshitaka; Nozawa, Tomo; Kikuchi, Masako; Nagahama, Kiyotaka; Okudela, Koji; Miyamae, Takako; Imagawa, Tomoyuki; Nakamura, Tomoko; Mori, Masaaki; Yokota, Shumpei; Tsutsumi, Hiroyuki

2015-03-01

We evaluated histological changes occurring in renal biopsy specimens, between the time before initial induction therapy and after 12 months' maintenance therapy, as well as changes in laboratory parameters, SLE disease activity (SLEDAI), and dosage of corticosteroid (CS) in childhood-onset systemic lupus erythematosus (SLE) patients treated with mycophenolate mofetil (MMF). A retrospective analysis was performed on nine patients diagnosed with childhood-onset SLE and lupus nephritis. They were treated with pulsed mPSL and intravenous cyclophosphamide as induction therapy and MMF (500-1500 mg/day) plus CS as maintenance therapy. Renal biopsy was performed before the initial induction therapy and after 12 months' maintenance therapy. Pathological findings at second biopsy were improved in eight of nine patients (89%). The findings of SLEDAI, urinalysis, and blood tests also showed improvement. CS doses could be tapered satisfactorily. Adverse events were observed in two patients. No patients treated with MMF experienced any disease flares during maintenance therapy. MMF as maintenance therapy might be useful in that not only the histological findings of lupus nephritis were improved, but also CS doses could be beneficially tapered. Nonetheless, this is a retrospective report of only nine cases and further prospective multicenter studies are necessary.

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.

Bacillus cereus Certhrax ADP-ribosylates Vinculin to Disrupt Focal Adhesion Complexes and Cell Adhesion*

PubMed Central

Simon, Nathan C.; Barbieri, Joseph T.

2014-01-01

Bacillus cereus is often associated with mild to moderate gastroenteritis; however, some recent isolates cause inhalational anthrax-like diseases and death. These potential emerging human pathogens express multiple virulence factors. B. cereus strain G9241 expresses anthrax toxin, several polysaccharide capsules, and the novel ADP-ribosyltransferase, Certhrax. In this study, we show that Certhrax ADP-ribosylates Arg-433 of vinculin, a protein that coordinates actin cytoskeleton and extracellular matrix interactions. ADP-ribosylation of vinculin disrupted focal adhesion complexes and redistributed vinculin to the cytoplasm. Exogenous vinculin rescued these phenotypes. This provides a mechanism for strain G9241 to breach host barrier defenses and promote bacterial growth and spread. Certhrax is the first bacterial toxin to add a post-translational modification to vinculin to disrupt the actin cytoskeleton. PMID:24573681

Approach to Membranous Lupus Nephritis: A Survey of Pediatric Nephrologists and Pediatric Rheumatologists.

PubMed

Boneparth, Alexis; Radhakrishna, Suhas M; Greenbaum, Larry A; Yen, Eric; Okamura, Daryl M; Cooper, Jennifer C; Mason, Sherene; Levy, Deborah M; Sule, Sangeeta D; Jensen, Paul T; Yildirim-Toruner, Cagri; Ardoin, Stacy P; Wenderfer, Scott E

2017-11-01

To describe treatment practices for childhood pure membranous lupus nephritis (MLN). Survey study of Childhood Arthritis and Rheumatology Research Alliance and American Society of Pediatric Nephrology members. There were 117 respondents who completed the survey (60 pediatric nephrologists, 57 pediatric rheumatologists). Steroids and nonsteroid immunosuppression (NSI) were routinely used by the majority for MLN. Mycophenolate mofetil was the favored initial NSI. Nephrologists used steroids (60% vs 93%) and NSI (53% vs 87%) less often than did rheumatologists for MLN without nephrotic syndrome (NS). Pediatric rheumatologists and nephrologists both recommend steroids and NSI for children with MLN, with or without NS.

Focal surfaces of hyperbolic cylinders

NASA Astrophysics Data System (ADS)

Georgiev, Georgi Hristov; Pavlov, Milen Dimov

2017-12-01

Cylindrical surfaces have many applications in geometric modeling, architecture and other branches of engineering. In this paper, we describe two cylindrical surfaces associated to a given hyperbolic cylinder. The first one is a focal surface which is determined by reciprocal principle curvature of the hyperbolic cylinder. The second one is a generalized focal surface obtained by reciprocal mean curvature of the same hyperbolic cylinder. In particular, we show that each of these surfaces admits three different parametric representations. As consequence, it is proved that the focal and generalized focal surfaces of the hyperbolic cylinder are rational surfaces. An illustrative example is included.

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

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

Strober, S.; Farinas, M.C.; Field, E.H.

1988-07-01

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

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.

Classification of Focal and Non Focal Epileptic Seizures Using Multi-Features and SVM Classifier.

PubMed

Sriraam, N; Raghu, S

2017-09-02

Identifying epileptogenic zones prior to surgery is an essential and crucial step in treating patients having pharmacoresistant focal epilepsy. Electroencephalogram (EEG) is a significant measurement benchmark to assess patients suffering from epilepsy. This paper investigates the application of multi-features derived from different domains to recognize the focal and non focal epileptic seizures obtained from pharmacoresistant focal epilepsy patients from Bern Barcelona database. From the dataset, five different classification tasks were formed. Total 26 features were extracted from focal and non focal EEG. Significant features were selected using Wilcoxon rank sum test by setting p-value (p < 0.05) and z-score (-1.96 > z > 1.96) at 95% significance interval. Hypothesis was made that the effect of removing outliers improves the classification accuracy. Turkey's range test was adopted for pruning outliers from feature set. Finally, 21 features were classified using optimized support vector machine (SVM) classifier with 10-fold cross validation. Bayesian optimization technique was adopted to minimize the cross-validation loss. From the simulation results, it was inferred that the highest sensitivity, specificity, and classification accuracy of 94.56%, 89.74%, and 92.15% achieved respectively and found to be better than the state-of-the-art approaches. Further, it was observed that the classification accuracy improved from 80.2% with outliers to 92.15% without outliers. The classifier performance metrics ensures the suitability of the proposed multi-features with optimized SVM classifier. It can be concluded that the proposed approach can be applied for recognition of focal EEG signals to localize epileptogenic zones.

Serum levels of adiponectin and leptin as biomarkers of proteinuria in lupus nephritis.

PubMed

Diaz-Rizo, Valeria; Bonilla-Lara, David; Gonzalez-Lopez, Laura; Sanchez-Mosco, Dalia; Fajardo-Robledo, Nicte S; Perez-Guerrero, Edsaul E; Rodriguez-Jimenez, N Alejandra; Saldaña-Cruz, A Miriam; Vazquez-Villegas, M Luisa; Gomez-Bañuelos, Eduardo; Vazquez-Del Mercado, Monica; Cardona-Muñoz, E German; Cardona-Muller, David; Trujillo, Xochitl; Huerta, Miguel; Salazar-Paramo, Mario; Gamez-Nava, Jorge I

2017-01-01

There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis. The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN). In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE) were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN). A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN. We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02), whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07). Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001), but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01-1.12; p = 0.02). Instead, leptin was not associated with LN. These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse.

Statistical Earthquake Focal Mechanism Forecasts

NASA Astrophysics Data System (ADS)

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

2013-12-01

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

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

DOEpatents

Crandall, David Lynn [Idaho Falls, ID

2011-08-01

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

Focal stimulation of the brain by entirely extracranial means. An example of radiation controlled focal pharmacology

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

Remler, M.P.

A method for focal stimulation of the brain by entirely extracranial means is presented. A focal x ray lesion of cortex was made that reduces the blood-brain barrier in that area. Then parenteral penicillin was administered. Penicillin is primarily confined to the vascular space by the blood-brain barrier in all parts of the brain except for some leakage into the brain at higher doses. An increased concentration of penicillin is created in the irradiated cortex. The penicillin creates a focal epileptic lesion in the irradiated area. This is an example of radiation-controlled focal pharmacology in the central nervous system. (auth)

Blood oxygen level dependent magnetic resonance imaging for detecting pathological patterns in lupus nephritis patients: a preliminary study using a decision tree model.

PubMed

Shi, Huilan; Jia, Junya; Li, Dong; Wei, Li; Shang, Wenya; Zheng, Zhenfeng

2018-02-09

Precise renal histopathological diagnosis will guide therapy strategy in patients with lupus nephritis. Blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) has been applicable noninvasive technique in renal disease. This current study was performed to explore whether BOLD MRI could contribute to diagnose renal pathological pattern. Adult patients with lupus nephritis renal pathological diagnosis were recruited for this study. Renal biopsy tissues were assessed based on the lupus nephritis ISN/RPS 2003 classification. The Blood oxygen level dependent magnetic resonance imaging (BOLD-MRI) was used to obtain functional magnetic resonance parameter, R2* values. Several functions of R2* values were calculated and used to construct algorithmic models for renal pathological patterns. In addition, the algorithmic models were compared as to their diagnostic capability. Both Histopathology and BOLD MRI were used to examine a total of twelve patients. Renal pathological patterns included five classes III (including 3 as class III + V) and seven classes IV (including 4 as class IV + V). Three algorithmic models, including decision tree, line discriminant, and logistic regression, were constructed to distinguish the renal pathological pattern of class III and class IV. The sensitivity of the decision tree model was better than that of the line discriminant model (71.87% vs 59.48%, P < 0.001) and inferior to that of the Logistic regression model (71.87% vs 78.71%, P < 0.001). The specificity of decision tree model was equivalent to that of the line discriminant model (63.87% vs 63.73%, P = 0.939) and higher than that of the logistic regression model (63.87% vs 38.0%, P < 0.001). The Area under the ROC curve (AUROCC) of the decision tree model was greater than that of the line discriminant model (0.765 vs 0.629, P < 0.001) and logistic regression model (0.765 vs 0.662, P < 0.001). BOLD MRI is a useful non-invasive imaging technique

Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices.

PubMed

Bajema, Ingeborg M; Wilhelmus, Suzanne; Alpers, Charles E; Bruijn, Jan A; Colvin, Robert B; Cook, H Terence; D'Agati, Vivette D; Ferrario, Franco; Haas, Mark; Jennette, J Charles; Joh, Kensuke; Nast, Cynthia C; Noël, Laure-Hélène; Rijnink, Emilie C; Roberts, Ian S D; Seshan, Surya V; Sethi, Sanjeev; Fogo, Agnes B

2018-04-01

We present a consensus report pertaining to the improved clarity of definitions and classification of glomerular lesions in lupus nephritis that derived from a meeting of 18 members of an international nephropathology working group in Leiden, Netherlands, in 2016. Here we report detailed recommendations on issues for which we can propose adjustments based on existing evidence and current consensus opinion (phase 1). New definitions are provided for mesangial hypercellularity and for cellular, fibrocellular, and fibrous crescents. The term "endocapillary proliferation" is eliminated and the definition of endocapillary hypercellularity considered in some detail. We also eliminate the class IV-S and IV-G subdivisions of class IV lupus nephritis. The active and chronic designations for class III/IV lesions are replaced by a proposal for activity and chronicity indices that should be applied to all classes. In the activity index, we include fibrinoid necrosis as a specific descriptor. We also make recommendations on issues for which there are limited data at present and that can best be addressed in future studies (phase 2). We propose to proceed to these investigations, with clinicopathologic studies and tests of interobserver reproducibility to evaluate the applications of the proposed definitions and to classify lupus nephritis lesions. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Clinical outcomes in children with Henoch-Schönlein purpura nephritis without crescents.

PubMed

Delbet, Jean Daniel; Hogan, Julien; Aoun, Bilal; Stoica, Iulia; Salomon, Rémi; Decramer, Stéphane; Brocheriou, Isabelle; Deschênes, Georges; Ulinski, Tim

2017-07-01

Henoch-Schönlein purpura is the most common vasculitis in children. Its long-term prognosis depends on renal involvement. The management of Henoch-Schönlein purpura nephritis (HSPN) remains controversial. This study reports the prognosis of children with HSPN presenting with class 2 International Study of Kidney Disease in Children (ISKDC) nephritis. All children with HSPN class 2 diagnosed between 1995 and 2015 in four pediatric nephrology centers were included, and clinical and biological data were collected from the medical files. The primary endpoint was proteinuria remission defined as a proteinuria <200 mg/L. Ninety-two children were included in the study with a median follow-up of 36 (6-120) months; 28% had nephrotic syndrome, 31% proteinuria >3 g/L, 52% proteinuria between 1 and 3 g/L, and 18% proteinuria <1 g/L. Forty-seven percent of patients received orally treatment with steroids alone, 37% received methylprednisolone pulses followed by steroids orally, 18% received no steroids. Although 85% reached remission during follow-up, 12% did not maintain complete remission over time so that only 75% remained in complete remission by the end of the follow-up. Univariate analysis found a higher likelihood of remission in patients with higher proteinuria at disease onset (p = 0.009). This trend was not found in the multivariate analysis after adjusting for treatments, as patients with higher proteinuria were most often treated with steroids. Our study shows that one fourth of patients with HSPN class 2 remain proteinuric and thus carry the risk of developing chronic kidney disease over the long term. This finding, together with the better outcome of patients treated with steroids, is in favor of using high-dose steroids orally or IV in these patients.

Serum levels of adiponectin and leptin as biomarkers of proteinuria in lupus nephritis

PubMed Central

Sanchez-Mosco, Dalia; Fajardo-Robledo, Nicte S.; Perez-Guerrero, Edsaul E.; Rodriguez-Jimenez, N. Alejandra; Saldaña-Cruz, A. Miriam; Vazquez-Villegas, M. Luisa; Gomez-Bañuelos, Eduardo; Vazquez-Del Mercado, Monica; Cardona-Muñoz, E. German; Cardona-Muller, David; Trujillo, Xochitl; Huerta, Miguel; Salazar-Paramo, Mario

2017-01-01

Introduction There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis. Objective The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN). Methods In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE) were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN). A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN. Results We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02), whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07). Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001), but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01–1.12; p = 0.02). Instead, leptin was not associated with LN. Conclusion These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse. PMID:28898254

Btk-specific inhibition blocks pathogenic plasma cell signatures and myeloid cell-associated damage in IFNα-driven lupus nephritis.

PubMed

Katewa, Arna; Wang, Yugang; Hackney, Jason A; Huang, Tao; Suto, Eric; Ramamoorthi, Nandhini; Austin, Cary D; Bremer, Meire; Chen, Jacob Zhi; Crawford, James J; Currie, Kevin S; Blomgren, Peter; DeVoss, Jason; DiPaolo, Julie A; Hau, Jonathan; Johnson, Adam; Lesch, Justin; DeForge, Laura E; Lin, Zhonghua; Liimatta, Marya; Lubach, Joseph W; McVay, Sami; Modrusan, Zora; Nguyen, Allen; Poon, Chungkee; Wang, Jianyong; Liu, Lichuan; Lee, Wyne P; Wong, Harvey; Young, Wendy B; Townsend, Michael J; Reif, Karin

2017-04-06

Systemic lupus erythematosus (SLE) is often associated with exaggerated B cell activation promoting plasma cell generation, immune-complex deposition in the kidney, renal infiltration of myeloid cells, and glomerular nephritis. Type-I IFNs amplify these autoimmune processes and promote severe disease. Bruton's tyrosine kinase (Btk) inhibitors are considered novel therapies for SLE. We describe the characterization of a highly selective reversible Btk inhibitor, G-744. G-744 is efficacious, and superior to blocking BAFF and Syk, in ameliorating severe lupus nephritis in both spontaneous and IFNα-accelerated lupus in NZB/W_F1 mice in therapeutic regimens. Selective Btk inhibition ablated plasmablast generation, reduced autoantibodies, and - similar to cyclophosphamide - improved renal pathology in IFNα-accelerated lupus. Employing global transcriptional profiling of spleen and kidney coupled with cross-species human modular repertoire analyses, we identify similarities in the inflammatory process between mice and humans, and we demonstrate that G-744 reduced gene expression signatures essential for splenic B cell terminal differentiation, particularly the secretory pathway, as well as renal transcriptional profiles coupled with myeloid cell-mediated pathology and glomerular plus tubulointerstitial disease in human glomerulonephritis patients. These findings reveal the mechanism through which a selective Btk inhibitor blocks murine autoimmune kidney disease, highlighting pathway activity that may translate to human SLE.

Btk-specific inhibition blocks pathogenic plasma cell signatures and myeloid cell–associated damage in IFNα-driven lupus nephritis

PubMed Central

Katewa, Arna; Wang, Yugang; Hackney, Jason A.; Huang, Tao; Suto, Eric; Ramamoorthi, Nandhini; Bremer, Meire; Chen, Jacob Zhi; Crawford, James J.; Currie, Kevin S.; Blomgren, Peter; DeVoss, Jason; DiPaolo, Julie A.; Hau, Jonathan; Lesch, Justin; DeForge, Laura E.; Lin, Zhonghua; Liimatta, Marya; Lubach, Joseph W.; McVay, Sami; Modrusan, Zora; Nguyen, Allen; Poon, Chungkee; Wang, Jianyong; Liu, Lichuan; Lee, Wyne P.; Wong, Harvey; Young, Wendy B.; Townsend, Michael J.

2017-01-01

Systemic lupus erythematosus (SLE) is often associated with exaggerated B cell activation promoting plasma cell generation, immune-complex deposition in the kidney, renal infiltration of myeloid cells, and glomerular nephritis. Type-I IFNs amplify these autoimmune processes and promote severe disease. Bruton’s tyrosine kinase (Btk) inhibitors are considered novel therapies for SLE. We describe the characterization of a highly selective reversible Btk inhibitor, G-744. G-744 is efficacious, and superior to blocking BAFF and Syk, in ameliorating severe lupus nephritis in both spontaneous and IFNα-accelerated lupus in NZB/W_F1 mice in therapeutic regimens. Selective Btk inhibition ablated plasmablast generation, reduced autoantibodies, and — similar to cyclophosphamide — improved renal pathology in IFNα-accelerated lupus. Employing global transcriptional profiling of spleen and kidney coupled with cross-species human modular repertoire analyses, we identify similarities in the inflammatory process between mice and humans, and we demonstrate that G-744 reduced gene expression signatures essential for splenic B cell terminal differentiation, particularly the secretory pathway, as well as renal transcriptional profiles coupled with myeloid cell–mediated pathology and glomerular plus tubulointerstitial disease in human glomerulonephritis patients. These findings reveal the mechanism through which a selective Btk inhibitor blocks murine autoimmune kidney disease, highlighting pathway activity that may translate to human SLE. PMID:28405610

Krüppel-like factor 5 associates with melamine-cyanurate crystal-induced nephritis in rats.

PubMed

Huang, Hsin-Lei; Yang, Wen-Ying; Pu, Hsiao-Fung; Tsai, Tung-Hu; Lin, Chi-Hung; Chen, Nien-Jung; Tarng, Der-Cherng

2013-10-01

Melamine and cyanuric acid (M/CA), when orally administered together to rats, can induce crystal formation within renal tubules and cause acute kidney injury. To investigate the pathomechanism of crystal-induced nephritis, melamine and/or cyanuric acid were administered to 3-week-old (young) and 8-week-old (adult) rats, respectively. Crystal formation, blood urea nitrogen elevation, tubular cell injury and macrophage infiltration were noted in rats fed with M/CA, but not in rats fed with vehicle, melamine or CA alone. These parameters were significantly higher in young rats than those in adult rats fed with M/CA 200 mg/kg body weight (BW) for 3 days. Krüppel-like factor 5 (KLF5) was expressed on distal tubule cells, especially when crystals deposited within the lumens. Both mRNA and protein levels were higher in young rats than those in adult rats fed with M/CA (200 mg/kg BW). KLF5 expression has been shown to modulate renal tissue cytokine production, and we found that proinflammatory cytokines like monocyte chemoattractant protein-1 and interlukin-6 were increased in kidney tissues of young rats fed with M/CA for 3 days. In contrast, interlukin-10, an anti-inflammatory cytokine, was upregulated in kidneys of adult rats fed with M/CA for 3 days. Crystals are prone to deposition in distal tubules of young rats fed with M/CA. M/CA Crystal-related nephritis might be induced by the KLF5 expression, which modulated macrophage recruitment and proinflammatory cytokine production, subsequently leading to renal tubular injury and interstitial inflammation.

Henoch-Schönlein purpura nephritis occurring postpartum in a patient with anti-PL-7 anti-synthetase syndrome.

PubMed

Nagai, Kojiro; Kishi, Jun; Morizumi, Shun; Minakuchi, Jun; Bando, Yoshimi; Nishioka, Yasuhiko; Doi, Toshio

2017-09-01

A 37-year-old pregnant woman developed purpura which was subsequently diagnosed as Henoch-Schönlein purpura (HSP). After childbirth, the patient developed proteinuria and hematuria. Further examination revealed that the HSP nephritis (HSPN) was associated with anti-threonyl-tRNA synthetase anti-synthetase syndrome. The onset of HSPN during pregnancy or after childbirth is rare. Moreover, to our knowledge, this is the first case to describe renal involvement in anti-synthetase syndrome.

Focal brainstem gliomas

PubMed Central

Sabbagh, Abdulrahman J.; Alaqeel, Ahmed M.

2015-01-01

Improved neuronavigation guidance as well as intraoperative imaging and neurophysiologic monitoring technologies have enhanced the ability of neurosurgeons to resect focal brainstem gliomas. In contrast, diffuse brainstem gliomas are considered to be inoperable lesions. This article is a continuation of an article that discussed brainstem glioma diagnostics, imaging, and classification. Here, we address open surgical treatment of and approaches to focal, dorsally exophytic, and cervicomedullary brainstem gliomas. Intraoperative neuronavigation, intraoperative neurophysiologic monitoring, as well as intraoperative imaging are discussed as adjunctive measures to help render these procedures safer, more acute, and closer to achieving surgical goals. PMID:25864061

Exposure–effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis

PubMed Central

Abd Rahman, Azrin N; Tett, Susan E; Abdul Gafor, Halim A; McWhinney, Brett C; Staatz, Christine E

2015-01-01

Aims The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis. Methods Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0), maximum concentration (Cmax) and area under the concentration–time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events. Results Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l–1 h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l–1, P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l–1 h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l–1 h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l–1 h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023). Conclusions This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis. PMID:25959850

Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis.

PubMed

Abd Rahman, Azrin N; Tett, Susan E; Abdul Gafor, Halim A; McWhinney, Brett C; Staatz, Christine E

2015-11-01

The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis. Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0 ), maximum concentration (Cmax ) and area under the concentration-time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events. Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l(-1) h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l(-1) , P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l(-1) h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l(-1) h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l(-1) h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023). This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis. © 2015 The British Pharmacological Society.

The dispersion-focalization theory of sound systems

NASA Astrophysics Data System (ADS)

Schwartz, Jean-Luc; Abry, Christian; Boë, Louis-Jean; Vallée, Nathalie; Ménard, Lucie

2005-04-01

The Dispersion-Focalization Theory states that sound systems in human languages are shaped by two major perceptual constraints: dispersion driving auditory contrast towards maximal or sufficient values [B. Lindblom, J. Phonetics 18, 135-152 (1990)] and focalization driving auditory spectra towards patterns with close neighboring formants. Dispersion is computed from the sum of the inverse squared inter-spectra distances in the (F1, F2, F3, F4) space, using a non-linear process based on the 3.5 Bark critical distance to estimate F2'. Focalization is based on the idea that close neighboring formants produce vowel spectra with marked peaks, easier to process and memorize in the auditory system. Evidence for increased stability of focal vowels in short-term memory was provided in a discrimination experiment on adult French subjects [J. L. Schwartz and P. Escudier, Speech Comm. 8, 235-259 (1989)]. A reanalysis of infant discrimination data shows that focalization could well be the responsible for recurrent discrimination asymmetries [J. L. Schwartz et al., Speech Comm. (in press)]. Recent data about children vowel production indicate that focalization seems to be part of the perceptual templates driving speech development. The Dispersion-Focalization Theory produces valid predictions for both vowel and consonant systems, in relation with available databases of human languages inventories.

Focal Cryotherapy for Localized Prostate Cancer.

PubMed

Tay, K J; Polascik, T J

2016-07-01

To systematically review the oncological and functional outcomes of contemporary primary prostate focal cryotherapy for localized prostate cancer in the context of current developments in prostate focal therapy. We performed a systematic search of the Pubmed, Cochrane and Embase databases to identify studies where primary prostate focal cryotherapy was performed to treat prostate cancer. These included reports on focal/ lesion/ sector ablation, hemi-ablation and partial prostate ablation. We excluded salvage focal therapy studies. Where multiple reports were published over time from a single cohort, the latest one was used. Our search yielded 290 publications, including 17 primary reports on eight single-center cohort studies and one multi-center registry report. Of 1,595 men identified, mean age was 60.5-69.5 years and mean PSA 5.1-7.8 ng/ml. When stratified by D'Amico risk criteria, 52% of the aggregate total number of men were low-risk, 38% intermediate-risk and 10% high-risk. Besides 12-core TRUS biopsy, 3 cohorts reported using TTMB and one included mpMRI to select men for focal treatment. Median follow-up ranged from 13-63 months. BPFS ranged from 71-98%. The overall post-treatment positive biopsy rate was 8-25%. Among 5 cohorts with a mandatory 6-12 month posttreatment biopsy, 216 of 272 men (79%) did undergo biopsy, with 47 positive (21.8%). Of these, 15 were infield, 26 outfield, 2 bilateral and 4 undeclared. Ten upgraded to Gleason≥7. Overall, two men had metastatic disease and none died of prostate cancer. Post-treatment continence rates were 96-100% and rates of erectile dysfunction ranged from 0-42%. The rate of post-treatment urinary retention ranged from 0-15%. The rate of recto-urethral fistula was 0-0.1%. Focal cryotherapy for localized prostate cancer is a safe and provides good preservation of sexual and urinary function. Accurate cancer localization and risk stratification is key to patient selection. In highly selected patients, focal therapy

Expansive focal cemento-osseous dysplasia.

PubMed

Bulut, Emel Uzun; Acikgoz, Aydan; Ozan, Bora; Zengin, Ayse Zeynep; Gunhan, Omer

2012-01-01

To present a case of expansive focal cemento-osseous dysplasia and emphasize the importance of differential diagnosis. Cemento-osseous dysplasia is categorized into three subtypes on the basis of the clinical and radiographic features: Periapical, focal and florid. The focal type exhibits a single site of involvement in any tooth-bearing or edentulous area of the jaws. These lesions are usually asymptomatic; therefore, they are frequently diagnosed incidentally during routine radiographic examinations. Lesions are usually benign, show limited growth, and do not require further surgical intervention, but periodic follow-up is recommended because occasionally, this type of dysplasia progresses into florid osseous dysplasia and simple bone cysts are formed. A 24-year-old female patient was referred to our clinic for swelling in the left edentulous mandibular premolarmolar region and felt discomfort when she wore her prosthetics. She had no pain, tenderness or paresthesia. Clinical examination showed that the swelling in the posterior mandible that was firm, nonfluctuant and covered by normal mucosa. On panoramic radiography and computed tomography, a well defined lesion of approximately 1.5 cm in diameter of mixed density was observed. The swelling increased slightly in size over 2 years making it difficult to use prosthetics and, therefore, the lesion was totally excised under local anesthesia, and surgical specimens were submitted for histopathological examination. The histopathological diagnosis was focal cemento-osseous dysplasia. In the present case, because of the increasing size of the swelling making it difficult to use prosthetics, young age of the patient and localization of the lesion, in the initial examination, cemento-ossifying fibroma was suspected, and the lesion was excised surgically; the histopathological diagnosis confirmed it as focal cemento-osseous dysplasia. We present a case of expansive focal cemento-osseous dysplasia. Differential diagnosis

Biomarkers identification by a combined clinical and metabonomics analysis in Henoch-Schonlein purpura nephritis children

PubMed Central

Sun, Lin; Xie, Biao; Zhang, Qiuju; Wang, Yupeng; Wang, Xinyu; Gao, Bing; Liu, Meina; Wang, Maoqing

2017-01-01

Background In children with Henoch-Schonlein purpura (HSP), the severity of Henoch-Schonlein purpura nephritis (HSPN) is considered responsible for the prognosis of HSP. The pathological process from HSP to HSPN is not clear yet and current diagnostic tools have shortcomings in accurate diagnosis of HSPN. This study aims to assess clinical characteristics of HSP and HSPN, to identify metabolic perturbations involved in HSP progress, and to combine metabolic biomarkers and clinical features into a better prediction for HSPN. Methods A total of 162 children were recruited, including 109 HSP patients and 53 healthy children (HC). The clinical characteristics were compared between HSPN and HSP without nephritis (HSPWN). The serum metabonomics analysis was performed to determine the metabolic differences in HSP and HC. Results Among 109 HSP children, 57 progressed to HSPN. The increased D-dimer level was significantly associated with renal damage in HSP. The metabonomic profiles revealed alterations between various subgroups of HSP and HC, making it possible to investigate small-molecule metabolites related to the pathological process of HSP. In total, we identified 9 biomarkers for HSP vs. HC, 7 for HSPWN vs. HC, 9 for HSPN vs. HC, and 3 for HSPN vs. HSPWN. Conclusions (S)-3-hydroxyisobutyric acid, p-Cresol sulfate, and 3-carboxy-4-methyl-5-pentyl-2-furanpropanoic acid were found associated with the progress of HSP to HSPN. Moreover, resulting biomarkers, when combined with D-dimer, allowed improving the HSPN prediction with high sensitivity (94.7%) and specificity (80.8%). Together these findings highlighted the strength of the combination of metabonomics and clinical analysis in the research of HSP. PMID:29371982

Chronic kidney disease of uncertain etiology in Sri Lanka is a possible sequel of interstitial nephritis!

PubMed

Badurdeen, Zeid; Nanayakkara, Nishantha; Ratnatunga, Neelakanthi V I; Wazil, Abdul W M; Abeysekera, Tilak D J; Rajakrishna, Premil N; Thinnarachchi, Jalitha P; Kumarasiri, Ranjith; Welagedera, Dulani D; Rajapaksha, Needika; Alwis, Adambarage P D

The majority of published data on chronic kidney disease of uncertain etiology (CKDu) is on asymptomatic patients who were detected in screening programs. The clinicopathological profile of a group of patients presenting with acute symptoms and renal dysfunction from CKDu endemic regions in Sri Lanka was studied. 59 patients > 10 years of age with backache, feverish fatigue feeling, dysuria, joint pain, or dyspepsia, singly or in combination with elevated serum creatinine (> 116 and > 98 µmol/L for male and females, respectively) were included in the study. Those patients who had normal-sized kidneys were biopsied after excluding clinically detectable causes for renal dysfunction. Histology was scored with activity and chronicity indices. These patients' urinary sediment and inflammatory markers were checked. Patients were stratified into three groups based on duration of symptom onset to the time of biopsy. The natural course of the disease was described using serial mean serum creatinine and histological activity as well as chronicity indices in these 3 groups. These patients' mean age, occupation, and sex ratio were 44 (9) years, 57 farmers, and male : female 55 : 4, respectively. Mean serum creatinine at biopsy was 143.8 (47.9) µmol/L. Elevated inflammatory markers and active urine sediment were reported. Histology was compatible with an interstitial nephritis with a mixture of acute and chronic tubulointerstitial lesions and glomerular scarring. In the natural course of an acute episode of CKDu, serum creatinine and histological activity were reduced while histological chronicity increased. CKDu may be preceded by an acute episode of tubulointerstitial nephritis (TIN).

Focal segmental glomerulosclerosis

MedlinePlus

... Alternative Names Segmental glomerulosclerosis; Focal sclerosis with hyalinosis Images Male urinary system References Appel GB, Radhakrishnan J. Glomerular disorders and nephrotic syndromes In: Goldman L, ...

An empirical assessment of the focal species hypothesis.

PubMed

Lindenmayer, D B; Lane, P W; Westgate, M J; Crane, M; Michael, D; Okada, S; Barton, P S

2014-12-01

Biodiversity surrogates and indicators are commonly used in conservation management. The focal species approach (FSA) is one method for identifying biodiversity surrogates, and it is underpinned by the hypothesis that management aimed at a particular focal species will confer protection on co-occurring species. This concept has been the subject of much debate, in part because the validity of the FSA has not been subject to detailed empirical assessment of the extent to which a given focal species actually co-occurs with other species in an assemblage. To address this knowledge gap, we used large-scale, long-term data sets of temperate woodland birds to select focal species associated with threatening processes such as habitat isolation and loss of key vegetation attributes. We quantified co-occurrence patterns among focal species, species in the wider bird assemblage, and species of conservation concern. Some, but not all, focal species were associated with high levels of species richness. One of our selected focal species was negatively associated with the occurrence of other species (i.e., it was an antisurrogate)-a previously undescribed property of nominated focal species. Furthermore, combinations of focal species were not associated with substantially elevated levels of bird species richness, relative to levels associated with individual species. Our results suggest that although there is some merit to the underpinning concept of the FSA, there is also a need to ensure that actions are sufficiently flexible because management tightly focused on a given focal species may not benefit some other species, including species of conservation concern, such of which might not occur in species-rich assemblages. © 2014 Society for Conservation Biology.

Complementary bodybuilding: A potential risk for permanent kidney disease.

PubMed

El-Reshaid, Wael; El-Reshaid, Kamel; Al-Bader, Shaikha; Ramadan, Ahmad; Madda, John Patrick

2018-01-01

We report our experience of renal disease associated with bodybuilders who had been on high-protein diet, anabolic androgenic steroids (AASs), and growth hormone (GH) for years. A total of 22 adult males who volunteered information about use of high protein diet and AAS or GH were seen over a six-year period with renal disease. Kidney biopsy revealed focal segmental glomerulosclerosis (FSGS) in eight, nephroangiosclerosis in four, chronic interstitial nephritis in three, acute interstitial nephritis in two, nephrocalcinosis with chronic interstitial nephritis in two, and single patients with membranous glomerulopathy, crescentic glomerulopathy, and sclerosing glomerulonephritis. Patients with FSGS had a longer duration of exposure, late presentation, and worse prognosis. Those with interstitial disease had shorter exposure time and earlier presentation and had improved or stabilized after discontinuation of their practice. There is a need for health education for athletes and bodybuilders to inform them about the risks of renal disease involved with the use of high-protein diet, AAS, and GH.

Changes in the aetiology, clinical presentation and management of acute interstitial nephritis, an increasingly common cause of acute kidney injury.

PubMed

Praga, Manuel; Sevillano, Angel; Auñón, Pilar; González, Ester

2015-09-01

Acute interstitial nephritis (AIN) is an important cause of acute kidney injury that has experienced significant epidemiological and clinical changes in the last years. The classical presentation, mostly induced by antibiotics and accompanied by evident hypersensitivity manifestations (skin rash, eosinophilia, fever) has been largely replaced by oligosymptomatic presentations that require a higher index of suspicion and are increasingly recognized in the elderly, having non-steroidal anti-inflammatory agents and proton pump inhibitors as frequent offending drugs. Drug-induced AIN continues to be the commonest type, but it requires a careful differential diagnosis with other entities (tubulointerstitial nephritis with uveitis syndrome, IgG4-related disease, drug reaction with eosinophilia and systemic symptom syndrome, sarcoidosis and other systemic diseases) that can also induce AIN. Cortico-dependant, relapsing AIN is a recently recognized entity that poses an important therapeutic challenge. Although corticosteroids are widely used in drug-induced AIN to speed kidney function recovery and avoid chronic kidney disease, their efficacy has not been tested by randomized controlled trials. New diagnostic tests and biomarkers, as well as prospective therapeutic studies are needed to improve AIN diagnosis and management. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

[A boy with cervical focal myositis].

PubMed

Prop, Serge; van Vuurden, Dannis; van der Kuip, Martijn; van der Voorn, J Patrick; Plötz, Frans B

2014-01-01

Focal myositis is a rare idiopathic pseudotumour that mostly occurs in the extremities in adults. An 8-year-old boy presented with a few months history of swelling in the neck and fever. Ultrasound investigation revealed an inhomogenous mass consistent with lymphadenitis. After nine days of antibiotic therapy, the clinical picture of fever and swelling was unchanged. MRI imaging revealed continuity of the swelling in the sternocleidomastoid muscle and a malignant process was suspected. Microscopy showed no malignant cells, however, but a lymphoplasmocytic infiltration with fibrosis and degeneration of muscle fibres, consistent with focal myositis. No intervention was undertaken and one year after presentation the tumour had regressed almost entirely. Focal myositis can present as a cervical tumour. On ultrasound, the condition is hard to distinguish from lymphadenopathy or malignancy. In cases of insufficient response to empirical antibiotic therapy, focal myositis should be considered.

Sighting optics including an optical element having a first focal length and a second focal length and methods for sighting

DOEpatents

Crandall, David Lynn

2011-08-16

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

Do focal colors look particularly "colorful"?

PubMed

Witzel, Christoph; Franklin, Anna

2014-04-01

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

Partial (focal) seizure

MedlinePlus

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

Inverse-designed stretchable metalens with tunable focal distance

NASA Astrophysics Data System (ADS)

Callewaert, Francois; Velev, Vesselin; Jiang, Shizhou; Sahakian, Alan Varteres; Kumar, Prem; Aydin, Koray

2018-02-01

In this paper, we present an inverse-designed 3D-printed all-dielectric stretchable millimeter wave metalens with a tunable focal distance. A computational inverse-design method is used to design a flat metalens made of disconnected polymer building blocks with complex shapes, as opposed to conventional monolithic lenses. The proposed metalens provides better performance than a conventional Fresnel lens, using lesser amount of material and enabling larger focal distance tunability. The metalens is fabricated using a commercial 3D-printer and attached to a stretchable platform. Measurements and simulations show that the focal distance can be tuned by a factor of 4 with a stretching factor of only 75%, a nearly diffraction-limited focal spot, and with a 70% relative focusing efficiency, defined as the ratio between power focused in the focal spot and power going through the focal plane. The proposed platform can be extended for design and fabrication of multiple electromagnetic devices working from visible to microwave radiation depending on scaling of the devices.

A benzenediamine derivate FC-99 attenuates lupus nephritis in MRL/lpr mice via inhibiting myeloid dendritic cell-secreted BAFF

PubMed Central

Ji, Jianjian; Xu, Jingjing; Li, Fanlin; Li, Xiaojing; Gong, Wei; Song, Yuxian; Dou, Huan; Hou, Yayi

2016-01-01

Myeloid dendritic cells (DCs) can produce B-cell-activating factor (BAFF) that modulates survival and differentiation of B cells and plays a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). Toll-like receptor 4 (TLR4) signaling has important functions in the process of BAFF production. Our previous study showed that a benzenediamine derivate FC-99 possesses anti-inflammation activity and directly interacts with interleukin-1 receptor-associated kinase 4 (IRAK4), which was a pivotal molecule in TLR4 signaling. In this study, we demonstrated that FC-99 attenuated lupus nephritis in the MRL/lpr mice. FC-99 also decreased the levels of total immunoglobulin G (IgG), total IgG2a and IgM in sera, as well as the activation of B cells in the spleens of MRL/lpr mice. Moreover, FC-99 inhibited abnormal activation of myeloid DCs in spleens and reduced the levels of BAFF in sera, spleens, and kidneys of MRL/lpr mice. Furthermore, upon TLR4 stimulation with lipopolysaccharide in vitro, FC-99 inhibited IRAK4 phosphorylation, as well as the activation and BAFF production in murine bone marrow-derived DCs. These data indicate that FC-99 attenuates lupus nephritis in MRL/lpr mice via inhibiting DC-secreted BAFF, suggesting that FC-99 may be a potential therapeutic candidate for the treatment of SLE. PMID:27121231

Focal mechanisms of earthquakes in Mongolia

NASA Astrophysics Data System (ADS)

Sodnomsambuu, D.; Natalia, R.; Gangaadorj, B.; Munkhuu, U.; Davaasuren, G.; Danzansan, E.; Yan, R.; Valentina, M.; Battsetseg, B.

2011-12-01

Focal mechanism data provide information on the relative magnitudes of the principal stresses, so that a tectonic regime can be assigned. Especially such information is useful for the study of intraplate seismic active regions. A study of earthquake focal mechanisms in the territory of Mongolia as landlocked and intraplate region was conducted. We present map of focal mechanisms of earthquakes with M4.5 which occurred in Mongolia and neighboring regions. Focal mechanisms solutions were constrained by the first motion solutions, as well as by waveform modeling, particularly CMT solutions. Four earthquakes have been recorded in Mongolia in XX century with magnitude more than 8, the 1905 M7.9 Tsetserleg and M8.4 Bolnai earthquakes, the 1931 M8.0 Fu Yun earthquake, the 1957 M8.1 Gobi-Altai earthquake. However the map of focal mechanisms of earthquakes in Mongolia allows seeing all seismic active structures: Gobi Altay, Mongolian Altay, active fringe of Hangay dome, Hentii range etc. Earthquakes in the most of Mongolian territory and neighboring China regions are characterized by strike-slip and reverse movements. Strike-slip movements also are typical for earthquakes in Altay Range in Russia. The north of Mongolia and south part of the Baikal area is a region where have been occurred earthquakes with different focal mechanisms. This region is a zone of the transition between compressive regime associated to India-Eurasian collision and extensive structures localized in north of the country as Huvsgul area and Baykal rift. Earthquakes in the Baikal basin itself are characterized by normal movements. Earthquakes in Trans-Baikal zone and NW of Mongolia are characterized dominantly by strike-slip movements. Analysis of stress-axis orientations, the tectonic stress tensor is presented. The map of focal mechanisms of earthquakes in Mongolia could be useful tool for researchers in their study on Geodynamics of Central Asia, particularly of Mongolian and Baikal regions.

Thick lens chromatic effective focal length variation versus bending

NASA Astrophysics Data System (ADS)

Sparrold, Scott

2017-11-01

Longitudinal chromatic aberration (LCA) can limit the optical performance in refractive optical systems. Understanding a singlet's chromatic change of effective focal leads to insights and methods to control LCA. Long established, first order theory, shows the chromatic change in focal length for a zero thickness lens is proportional to it's focal length divided by the lens V number or inverse dispersion. This work presents the derivation of an equation for a thick singlet's chromatic change in effective focal length as a function of center thickness, t, dispersion, V, index of refraction, n, and the Coddington shape factor, K. A plot of bending versus chromatic focal length variation is presented. Lens thickness does not influence chromatic variation of effective focal length for a convex plano or plano convex lens. A lens's center thickness'influence on chromatic focal length variation is more pronounced for lower indices of refraction.

Nephrotic-range proteinuria and interstitial nephritis associated with the use of a topical loxoprofen patch.

PubMed

Kikuchi, Hiroaki; Aoyagi, Makoto; Nagahama, Kiyotaka; Yajima, Yu; Yamamura, Chisato; Arai, Yohei; Hirasawa, Suguru; Aki, Shota; Inaba, Naoto; Tanaka, Hiroyuki; Tamura, Teiichi

2014-01-01

A 76-year-old woman with a history of lumbar fracture and marked proteinuria, bilateral pitting edema, malaise and pruritus was referred for an evaluation of an impaired renal function. A renal biopsy led to a tentative diagnosis of acute interstitial nephritis (AIN) with minimal change disease caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Following the discontinuation of oral NSAIDs, the patient's symptoms disappeared spontaneously. However, nephrotic-range proteinuria relapsed one month after discharge, following loxoprofen patch use. The withdrawal of the topical loxoprofen patches once again resulted in the disappearance of all symptoms. This is the first case report of nephrotic-range proteinuria and AIN secondary to topical NSAID patch use.

Temperature variation, bacterial diversity and fungal infection dynamics in the amphibian skin.

PubMed

Longo, Ana V; Zamudio, Kelly R

2017-09-01

Host-associated bacterial communities on the skin act as the first line of defence against invading pathogens. Yet, for most natural systems, we lack a clear understanding of how temperature variability affects structure and composition of skin bacterial communities and, in turn, promotes or limits the colonization of opportunistic pathogens. Here, we examine how natural temperature fluctuations might be related to changes in skin bacterial diversity over time in three amphibian populations infected by the pathogenic fungus Batrachochytrium dendrobatidis (Bd). Our focal host species (Eleutherodactylus coqui) is a direct-developing frog that has suffered declines at some populations in the last 20 years, while others have not experienced any changes. We quantified skin bacterial alpha- and beta-diversity at four sampling time points, a period encompassing two seasons and ample variation in natural infections and environmental conditions. Despite the different patterns of infection across populations, we detected an overall increase in bacterial diversity through time, characterized by the replacement of bacterial operational taxonomic units (OTUs). Increased frog body temperatures possibly allowed the colonization of bacteria as well as the recruitment of a subset of indicator OTUs, which could have promoted the observed changes in diversity patterns. Our results suggest that natural environmental fluctuations might be involved in creating opportunities for bacterial replacement, potentially attenuating pathogen transmission and thus contributing to host persistence in E. coqui populations. © 2017 John Wiley & Sons Ltd.

Focal Adhesion-Independent Cell Migration.

PubMed

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

2016-10-06

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

Statistical earthquake focal mechanism forecasts

NASA Astrophysics Data System (ADS)

Kagan, Yan Y.; Jackson, David D.

2014-04-01

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

Physical Activity Performance of Focal Middle School Students

ERIC Educational Resources Information Center

Erfle, Stephen E.; Gelbaugh, Corey M.

2013-01-01

Histograms of push-ups and curl-ups from a sample of more than 9,000 students show periodic spikes at five and 10 unit intervals. This article argues that these spikes are related to focal points, a game theoretic concept popularized by Nobel Laureate Thomas Schelling. Being focal on one test makes one more likely to be focal on the other. Focal…

Recurrent Bilateral Focal Myositis.

PubMed

Nagafuchi, Hiroko; Nakano, Hiromasa; Ooka, Seido; Takakuwa, Yukiko; Yamada, Hidehiro; Tadokoro, Mamoru; Shimojo, Sadatomo; Ozaki, Shoichi

This report describes a rare case of recurrent bilateral focal myositis and its successful treatment via methotrexate. A 38-year-old man presented myalgia of the right gastrocnemius in May 2005. Magnetic resonance imaging showed very high signal intensity in the right gastrocnemius on short-tau inversion recovery images. A muscle biopsy revealed inflammatory CD4+ cell-dominant myogenic change. Focal myositis was diagnosed. The first steroid treatment was effective. Tapering of prednisolone, however, repeatedly induced myositis relapse, which progressed to multiple muscle lesions of both lower limbs. Initiation of methotrexate finally allowed successful tapering of prednisolone, with no relapse in the past 4 years.

Recurrent Bilateral Focal Myositis

PubMed Central

Nagafuchi, Hiroko; Nakano, Hiromasa; Ooka, Seido; Takakuwa, Yukiko; Yamada, Hidehiro; Tadokoro, Mamoru; Shimojo, Sadatomo; Ozaki, Shoichi

2016-01-01

This report describes a rare case of recurrent bilateral focal myositis and its successful treatment via methotrexate. A 38-year-old man presented myalgia of the right gastrocnemius in May 2005. Magnetic resonance imaging showed very high signal intensity in the right gastrocnemius on short-tau inversion recovery images. A muscle biopsy revealed inflammatory CD4+ cell-dominant myogenic change. Focal myositis was diagnosed. The first steroid treatment was effective. Tapering of prednisolone, however, repeatedly induced myositis relapse, which progressed to multiple muscle lesions of both lower limbs. Initiation of methotrexate finally allowed successful tapering of prednisolone, with no relapse in the past 4 years. PMID:27853086

Obstetric nephrology: lupus and lupus nephritis in pregnancy.

PubMed

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

2012-12-01

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

Differences of serum procalcitonin levels between bacterial infection and flare in systemic lupus erythematosus patients

NASA Astrophysics Data System (ADS)

Patrick, J.; Marpaung, B.; Ginting, Y.

2018-03-01

Differentiate bacterial infections from flare in SLE patients is difficult to do because clinical symptoms of infection is similar to flare. SLE patients with infection require antibiotic therapy with decreased doses of immunosuppressant while in flare diseases require increased immunosuppressant. Procalcitonin (PCT), a biological marker, increased in serum patients with bacterial infections and expected to be a solution of problem. The aim of this study was to examine the function of PCT serum as marker to differentiate bacterial infection and flare in SLE patients. This cross-sectional study was conducted in Adam Malik Hospital from January-July 2017. We examined 80 patients SLE flare (MEX-SLEDAI>5), screen PCT and culture according to focal infection. Data were statistically analyzed. 80 SLE patients divided into 2 groups: bacterial infection group (31 patients) and non-infection/flare group (49 patients). Median PCT levels of bacterial infection group was 1.66 (0.04-8.45)ng/ml while flare group was 0.12 (0.02-0.81)ng/ml. There was significant difference of serum Procalcitonin level between bacterial infection and flare group in SLE patients (p=0.001). Procalcitonin serum levels can be used as a biomarker to differentiate bacterial infections and flare in SLE patients.

Continuously variable focal length lens

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

Adams, Bernhard W; Chollet, Matthieu C

2013-12-17

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

A large-sized bubbling appearance of the glomerular basement membrane in a patient with pulmonary limited AL amyloidosis and a past history of lupus nephritis.

PubMed

Suga, Norihiro; Miura, Naoto; Uemura, Yuko; Nakamura, Toshinobu; Morita, Hiroyuki; Banno, Shogo; Imai, Hirokazu

2011-12-01

We report an unusual pathological finding, a large-sized bubbling appearance of the glomerular basement membrane (GBM), in a patient with pulmonary limited AL amyloidosis and a past history of lupus nephritis. The first renal biopsy specimen from 10 years ago, when systemic lupus erythematosus was diagnosed, demonstrated mild mesangial proliferation and subepithelial deposits (WHO classification: III + V). Light microscopy of the current biopsy using periodic acid methenamine silver (PAMS) stain demonstrated a large-sized bubbling appearance of the GBM; however, very weak immunoglobulin and complement deposition was observed in immunofluorescence studies. Routine electron microscopy demonstrated partial subendothelial expansion with electron-lucent materials, but no electron-dense deposits or amyloid fibrils. Electron microscopy with PAMS stain revealed electron-lucent endothelial scalloping, including some cellular components and microspheres in the GBM; however, it is not clear if these materials are derived from endothelial cells. One possibility is that these unique findings represent a recovery phase of lupus membranous nephritis; another is that these findings correspond to a new disease entity.

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

PubMed Central

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

2016-01-01

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

[Consensus of the Brazilian Society of Rheumatology for the diagnosis, management and treatment of lupus nephritis].

PubMed

Klumb, Evandro Mendes; Silva, Clovis Artur Almeida; Lanna, Cristina Costa Duarte; Sato, Emilia Inoue; Borba, Eduardo Ferreira; Brenol, João Carlos Tavares; de Albuquerque, Elisa Martins das Neves; Monticielo, Odirlei Andre; Costallat, Lilian Tereza Lavras; Latorre, Luiz Carlos; Sauma, Maria de Fátima Lobato da Cunha; Bonfá, Eloisa Silva Dutra de Oliveira; Ribeiro, Francinne Machado

2015-01-01

To develop recommendations for the diagnosis, management and treatment of lupus nephritis in Brazil. Extensive literature review with a selection of papers based on the strength of scientific evidence and opinion of the Commission on Systemic Lupus Erythematosus members, Brazilian Society of Rheumatology. 1) Renal biopsy should be performed whenever possible and if this procedure is indicated; and, when the procedure is not possible, the treatment should be guided with the inference of histologic class. 2) Ideally, measures and precautions should be implemented before starting treatment, with emphasis on attention to the risk of infection. 3) Risks and benefits of treatment should be shared with the patient and his/her family. 4) The use of hydroxychloroquine (preferably) or chloroquine diphosphate is recommended for all patients (unless contraindicated) during induction and maintenance phases. 5) The evaluation of the effectiveness of treatment should be made with objective criteria of response (complete remission/partial remission/refractoriness). 6) ACE inhibitors and/or ARBs are recommended as antiproteinuric agents for all patients (unless contraindicated). 7) The identification of clinical and/or laboratory signs suggestive of proliferative or membranous glomerulonephritis should indicate an immediate implementation of specific therapy, including steroids and an immunosuppressive agent, even though histological confirmation is not possible. 8) Immunosuppressives must be used during at least 36 months, but these medications can be kept for longer periods. Its discontinuation should only be done when the patient achieve and maintain a sustained and complete remission. 9) Lupus nephritis should be considered as refractory when a full or partial remission is not achieved after 12 months of an appropriate treatment, when a new renal biopsy should be considered to assist in identifying the cause of refractoriness and in the therapeutic decision. Copyright © 2014

Effect of genetic background on the contribution of New Zealand Black loci to autoimmune lupus nephritis

PubMed Central

Rozzo, Stephen J.; Vyse, Timothy J.; Drake, Charles G.; Kotzin, Brian L.

1996-01-01

Autoimmune diseases such as systemic lupus erythematosus are complex genetic traits with contributions from major histocompatibility complex (MHC) genes and multiple unknown non-MHC genes. Studies of animal models of lupus have provided important insight into the immunopathogenesis of disease, and genetic analyses of these models overcome certain obstacles encountered when studying human patients. Genome-wide scans of different genetic crosses have been used to map several disease-linked loci in New Zealand hybrid mice. Although some consensus exists among studies mapping the New Zealand Black (NZB) and New Zealand White (NZW) loci that contribute to lupus-like disease, considerable variability is also apparent. A variable in these studies is the genetic background of the non-autoimmune strain, which could influence genetic contributions from the affected strain. A direct examination of this question was undertaken in the present study by mapping NZB nephritis-linked loci in backcrosses involving different non-autoimmune backgrounds. In a backcross with MHC-congenic C57BL/6J mice, H2z appeared to be the strongest genetic determinant of severe lupus nephritis, whereas in a backcross with congenic BALB/cJ mice, H2z showed no influence on disease expression. NZB loci on chromosomes 1, 4, 11, and 14 appeared to segregate with disease in the BALB/cJ cross, but only the influence of the chromosome 1 locus spanned both crosses and showed linkage with disease when all mice were considered. Thus, the results indicate that contributions from disease-susceptibility loci, including MHC, may vary markedly depending on the non-autoimmune strain used in a backcross analysis. These studies provide insight into variables that affect genetic heterogeneity and add an important dimension of complexity for linkage analyses of human autoimmune disease. PMID:8986781

Antithyroid drug-associated MPO-ANCA-positive tubulointerstitial nephritis in a type 2 diabetes patient: a case report.

PubMed

Nishimura, Shinsuke; Nakao, Kazushi; Takeda, Masaya; Matsuura, Ikuko; Nomura, Yoshihisa; Shojima, Sonei; Yamamura, Yuriko; Fujita, Kazuyuki; Momoki, Noriya; Maruyama, Keisuke; Yamamura, Masahiro; Hiramatsu, Makoto

2017-05-01

A 54-year-old man diagnosed with type 2 diabetes and hyperthyroidism was prescribed propylthiouracil (PTU) after the patient developed hepatic dysfunction on thiamazole. At 50 mg/day of PTU, he was stable with thyroid-stimulating hormone receptor and thyrotropic antibody titers remaining stable. After four years of taking PTU, he was referred to the Department of Nephrology due to a rapid increase in his serum creatinine (Cr) level. He showed impaired renal function (Cr 2.26 mg/dL; estimated glomerular filtration rate (eGFR), 25 mL/min). In addition, urinary β2-microglobulin (β2 MG) was increased to 71,980 μg/L and was positive for myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) (33.9 U/mL). Gallium scintigraphy demonstrated a remarkable accumulation in both kidneys. The patient was diagnosed with tubulointerstitial nephritis based on a renal biopsy, the results of which suggested that it might have been induced by PTU. He was treated with prednisolone (PSL) at 30 mg/day. As a result, within two weeks, Cr, eGFR, and urinary β2 MG levels were progressively improved to 1.72 mg/dL, 34 mL/min, and 22,020 μg/L, respectively. Therefore, we tapered off the PSL with a dose of 5 mg/day after approximately one year. There have been no exacerbated renal function parameters. Although there are many reports on patients developing MPO-ANCA-positive crescentic glomerulonephritis after the administration of PTU, we report on a relatively rare case in which interstitial nephritis occurred after the administration of PTU.

Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism.

PubMed

Riveline, D; Zamir, E; Balaban, N Q; Schwarz, U S; Ishizaki, T; Narumiya, S; Kam, Z; Geiger, B; Bershadsky, A D

2001-06-11

The transition of cell-matrix adhesions from the initial punctate focal complexes into the mature elongated form, known as focal contacts, requires GTPase Rho activity. In particular, activation of myosin II-driven contractility by a Rho target known as Rho-associated kinase (ROCK) was shown to be essential for focal contact formation. To dissect the mechanism of Rho-dependent induction of focal contacts and to elucidate the role of cell contractility, we applied mechanical force to vinculin-containing dot-like adhesions at the cell edge using a micropipette. Local centripetal pulling led to local assembly and elongation of these structures and to their development into streak-like focal contacts, as revealed by the dynamics of green fluorescent protein-tagged vinculin or paxillin and interference reflection microscopy. Inhibition of Rho activity by C3 transferase suppressed this force-induced focal contact formation. However, constitutively active mutants of another Rho target, the formin homology protein mDia1 (Watanabe, N., T. Kato, A. Fujita, T. Ishizaki, and S. Narumiya. 1999. Nat. Cell Biol. 1:136-143), were sufficient to restore force-induced focal contact formation in C3 transferase-treated cells. Force-induced formation of the focal contacts still occurred in cells subjected to myosin II and ROCK inhibition. Thus, as long as mDia1 is active, external tension force bypasses the requirement for ROCK-mediated myosin II contractility in the induction of focal contacts. Our experiments show that integrin-containing focal complexes behave as individual mechanosensors exhibiting directional assembly in response to local force.

Urinary angiostatin, CXCL4 and VCAM-1 as biomarkers of lupus nephritis.

PubMed

Mok, Chi Chiu; Soliman, Samar; Ho, Ling Yin; Mohamed, Fatma A; Mohamed, Faten Ismail; Mohan, Chandra

2018-01-11

-proliferative types of lupus nephritis. Urinary CXCL4 and VCAM-1 correlated significantly with the histologic activity score, and urinary angiostatin correlated significantly with proteinuria in this subgroup. Urinary angiostatin, CXCL4 and VCAM-1 are potential biomarkers for SLE, in particular lupus nephritis. Further longitudinal studies are necessary to delineate the performance of these markers in predicting renal flares and prognosis in SLE patients.

Long-term post-marketing surveillance of mizoribine for the treatment of lupus nephritis: Safety and efficacy during a 3-year follow-up

PubMed Central

Okada, Kenya; Sudo, Yohei; Itoh, Hiromichi; Yoshida, Hisao; Kuroda, Tatsuhiko

2014-01-01

Objective: To determine the safety and efficacy of long-term use of mizoribine by undertaking a 3-year post-marketing surveillance study. Methods: Subjects were all lupus nephritis patients newly treated with mizoribine between 1 October 2003 and 30 September 2005 at contracted study sites. Results: Mizoribine was administered to 881 lupus nephritis patients in the safety analysis set consisting of 946 patients recruited from 281 contracted study sites after satisfying the eligibility criteria. There were 301 events of adverse drug reactions that were observed in 196 (20.7%) of the 946 subjects. There were 34 events of serious adverse drug reactions in 31 patients (3.2%). No deterioration in hematological and biochemical test values was observed, but immunological testing showed significant improvements in C3, CH50, and anti-DNA antibody titers. The negative rate of proteinuria also increased over time. The median steroid dosage was 15 mg/day at the commencement of treatment, but was reduced to 10 mg/day at 12 months and 8 mg/day at 36 months. Conclusion: The findings of the 3-year long-term drug use surveillance study indicated that mizoribine can be used over the long term with relatively few adverse drug reactions, suggesting its suitability for use in maintenance drug therapy. PMID:26770729

Focal myositis: A review.

PubMed

Devic, P; Gallay, L; Streichenberger, N; Petiot, P

2016-11-01

Amongst the heterogeneous group of inflammatory myopathies, focal myositis stands as a rare and benign dysimmune disease. Although it can be associated with root and/or nerve lesions, traumatic muscle lesions and autoimmune diseases, its triggering factors remain poorly understood. Defined as an isolated inflammatory pseudotumour usually restricted to one skeletal muscle, clinical presentation of focal myositis is that of a rapidly growing solitary mass within a single muscle, usually in the lower limbs. Electromyography shows spontaneous activity associated with a myopathic pattern. MRI reveals a contrast enhanced enlarged muscle appearing hyper-intense on FAT-SAT T2 weighted images. Adjacent structures are spared and there are no calcifications. Serum creatine kinase (CK) levels are usually moderately augmented and biological markers of systemic inflammation are absent in most cases. Pathological histological features include marked variation in fibre size, inflammatory infiltrates mostly composed of T CD4+ lymphocytes and macrophages, degenerating/regenerating fibres and interstitial fibrosis. Differential diagnoses are numerous and include myositis of other origin with focal onset. Steroid treatment should be reserved for patients who present with major pain, nerve lesions, associated autoimmune disease, or elevated C reactive protein or CK. Copyright © 2016 Elsevier B.V. All rights reserved.

Invasion of Epithelial Cells and Proteolysis of Cellular Focal Adhesion Components by Distinct Types of Porphyromonas gingivalis Fimbriae

PubMed Central

Nakagawa, Ichiro; Inaba, Hiroaki; Yamamura, Taihei; Kato, Takahiro; Kawai, Shinji; Ooshima, Takashi; Amano, Atsuo

2006-01-01

Porphyromonas gingivalis fimbriae are classified into six types (types I to V and Ib) based on the fimA genes encoding FimA (a subunit of fimbriae), and they play a critical role in bacterial interactions with host tissues. In this study, we compared the efficiencies of P. gingivalis strains with distinct types of fimbriae for invasion of epithelial cells and for degradation of cellular focal adhesion components, paxillin, and focal adhesion kinase (FAK). Six representative strains with the different types of fimbriae were tested, and P. gingivalis with type II fimbriae (type II P. gingivalis) adhered to and invaded epithelial cells at significantly greater levels than the other strains. There were negligible differences in gingipain activities among the six strains; however, type II P. gingivalis apparently degraded intracellular paxillin in association with a loss of phosphorylation 30 min after infection. Degradation was blocked with cytochalasin D or in mutants with fimA disrupted. Paxillin was degraded by the mutant with Lys-gingipain disrupted, and this degradation was prevented by inhibition of Arg-gingipain activity by Nα-p-tosyl-l-lysine chloromethyl ketone. FAK was also degraded by type II P. gingivalis. Cellular focal adhesions with green fluorescent protein-paxillin macroaggregates were clearly destroyed, and this was associated with cellular morphological changes and microtubule disassembly. In an in vitro wound closure assay, type II P. gingivalis significantly inhibited cellular migration and proliferation compared to the cellular migration and proliferation observed with the other types. These results suggest that type II P. gingivalis efficiently invades epithelial cells and degrades focal adhesion components with Arg-gingipain, which results in cellular impairment during wound healing and periodontal tissue regeneration. PMID:16790749

Solid-state curved focal plane arrays

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

Seven tesla MRI improves detection of focal cortical dysplasia in patients with refractory focal epilepsy.

PubMed

Veersema, Tim J; Ferrier, Cyrille H; van Eijsden, Pieter; Gosselaar, Peter H; Aronica, Eleonora; Visser, Fredy; Zwanenburg, Jaco M; de Kort, Gerard A P; Hendrikse, Jeroen; Luijten, Peter R; Braun, Kees P J

2017-06-01

The aim of this study is to determine whether the use of 7 tesla (T) MRI in clinical practice leads to higher detection rates of focal cortical dysplasias in possible candidates for epilepsy surgery. In our center patients are referred for 7 T MRI if lesional focal epilepsy is suspected, but no abnormalities are detected at one or more previous, sufficient-quality lower-field MRI scans, acquired with a dedicated epilepsy protocol, or when concealed pathology is suspected in combination with MR-visible mesiotemporal sclerosis-dual pathology. We assessed 40 epilepsy patients who underwent 7 T MRI for presurgical evaluation and whose scans (both 7 T and lower field) were discussed during multidisciplinary epilepsy surgery meetings that included a dedicated epilepsy neuroradiologist. We compared the conclusions of the multidisciplinary visual assessments of 7 T and lower-field MRI scans. In our series of 40 patients, multidisciplinary evaluation of 7 T MRI identified additional lesions not seen on lower-field MRI in 9 patients (23%). These findings were guiding in surgical planning. So far, 6 patients underwent surgery, with histological confirmation of focal cortical dysplasia or mild malformation of cortical development. Seven T MRI improves detection of subtle focal cortical dysplasia and mild malformations of cortical development in patients with intractable epilepsy and may therefore contribute to identification of surgical candidates and complete resection of the epileptogenic lesion, and thus to postoperative seizure freedom.

Intranuclear delivery of the transcription modulation domain of Tbet-improved lupus nephritis in (NZB/NZW) F1 lupus-prone mice.

PubMed

Moon, Jae-Seung; Mun, Chin Hee; Kim, Jung-Ho; Cho, Jen-Young; Park, Sung-Dong; Park, Tae-Yoon; Shin, Jin-Su; Ho, Chun-Chang; Park, Yong-Beom; Ghosh, Sankar; Bothwell, Alfred L M; Lee, Sang-Won; Lee, Sang-Kyou

2018-05-01

Excessive expression of Tbet and IFNγ is evidence of systemic lupus erythematosus (SLE) in lupus patients. In this study, the nucleus-transducible form of Transcription Modulation Domain (TMD) of Tbet (ntTbet-TMD), which is a fusion protein between Protein Transduction Domain Hph-1 (Hph-1-PTD) and the TMD of Tbet comprising DNA binding domain and isotype-specific domain, was generated to inhibit Tbet-mediated transcription in the interactomic manner. ntTbet-TMD was effectively delivered into the nucleus of the cells and specifically inhibited Tbet-mediated transcription without influencing the differentiation of other T cell subsets and signaling events for T cell activation. The severity of nephritis was significantly reduced by ntTbet-TMD as effectively as methylprednisolone in lupus-prone mice. The number of Th1, Th2 or Th17 cells and the secretion of their cytokines substantially decreased in the spleen and kidney of lupus-prone mice by ntTbet-TMD treatment. In contrast to methylprednisolone, the marked increase of Treg cells and the secretion of their immunosuppressive cytokine were detected in the spleen of (NZB/NZW) F1 mice treated with ntTbet-TMD. Thus, ntTbet-TMD can improve nephritis in lupus-prone mice by modulating the overall proinflammatory microenvironment and rebalancing T cell subsets, leading to new immune therapeutics for Th1-mediated autoimmune diseases. Copyright © 2017 International Society of Nephrology. All rights reserved.

A benzenediamine derivate FC-99 attenuates lupus nephritis in MRL/lpr mice via inhibiting myeloid dendritic cell-secreted BAFF.

PubMed

Ji, Jianjian; Xu, Jingjing; Li, Fanlin; Li, Xiaojing; Gong, Wei; Song, Yuxian; Dou, Huan; Hou, Yayi

2016-05-01

Myeloid dendritic cells (DCs) can produce B-cell-activating factor (BAFF) that modulates survival and differentiation of B cells and plays a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). Toll-like receptor 4 (TLR4) signaling has important functions in the process of BAFF production. Our previous study showed that a benzenediamine derivate FC-99 possesses anti-inflammation activity and directly interacts with interleukin-1 receptor-associated kinase 4 (IRAK4), which was a pivotal molecule in TLR4 signaling. In this study, we demonstrated that FC-99 attenuated lupus nephritis in the MRL/lpr mice. FC-99 also decreased the levels of total immunoglobulin G (IgG), total IgG2a and IgM in sera, as well as the activation of B cells in the spleens of MRL/lpr mice. Moreover, FC-99 inhibited abnormal activation of myeloid DCs in spleens and reduced the levels of BAFF in sera, spleens, and kidneys of MRL/lpr mice. Furthermore, upon TLR4 stimulation with lipopolysaccharide in vitro, FC-99 inhibited IRAK4 phosphorylation, as well as the activation and BAFF production in murine bone marrow-derived DCs. These data indicate that FC-99 attenuates lupus nephritis in MRL/lpr mice via inhibiting DC-secreted BAFF, suggesting that FC-99 may be a potential therapeutic candidate for the treatment of SLE. © The Author 2016. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Towards dualband megapixel QWIP focal plane arrays

NASA Astrophysics Data System (ADS)

Gunapala, S. D.; Bandara, S. V.; Liu, J. K.; Mumolo, J. M.; Hill, C. J.; Rafol, S. B.; Salazar, D.; Woolaway, J.; LeVan, P. D.; Tidrow, M. Z.

2007-04-01

Mid-wavelength infrared (MWIR) and long-wavelength infrared (LWIR) 1024 × 1024 pixel quantum well infrared photodetector (QWIP) focal planes have been demonstrated with excellent imaging performance. The MWIR QWIP detector array has demonstrated a noise equivalent differential temperature (NEΔT) of 17 mK at a 95 K operating temperature with f/2.5 optics at 300 K background and the LWIR detector array has demonstrated a NEΔT of 13 mK at a 70 K operating temperature with the same optical and background conditions as the MWIR detector array after the subtraction of system noise. Both MWIR and LWIR focal planes have shown background limited performance (BLIP) at 90 K and 70 K operating temperatures respectively, with similar optical and background conditions. In addition, we have demonstrated MWIR and LWIR pixel co-registered simultaneously readable dualband QWIP focal plane arrays. In this paper, we will discuss the performance in terms of quantum efficiency, NEΔT, uniformity, operability, and modulation transfer functions of the 1024 × 1024 pixel arrays and the progress of dualband QWIP focal plane array development work.

Chemical–genetic attenuation of focal neocortical seizures

PubMed Central

Kätzel, Dennis; Nicholson, Elizabeth; Schorge, Stephanie; Walker, Matthew C.; Kullmann, Dimitri M.

2014-01-01

Focal epilepsy is commonly pharmacoresistant, and resective surgery is often contraindicated by proximity to eloquent cortex. Many patients have no effective treatment options. Gene therapy allows cell-type specific inhibition of neuronal excitability, but on-demand seizure suppression has only been achieved with optogenetics, which requires invasive light delivery. Here we test a combined chemical–genetic approach to achieve localized suppression of neuronal excitability in a seizure focus, using viral expression of the modified muscarinic receptor hM4Di. hM4Di has no effect in the absence of its selective, normally inactive and orally bioavailable agonist clozapine-N-oxide (CNO). Systemic administration of CNO suppresses focal seizures evoked by two different chemoconvulsants, pilocarpine and picrotoxin. CNO also has a robust anti-seizure effect in a chronic model of focal neocortical epilepsy. Chemical–genetic seizure attenuation holds promise as a novel approach to treat intractable focal epilepsy while minimizing disruption of normal circuit function in untransduced brain regions or in the absence of the specific ligand. PMID:24866701

Focal Adhesion Induction at the Tip of a Functionalized Nanoelectrode

PubMed Central

Fuentes, Daniela E.; Bae, Chilman; Butler, Peter J.

2012-01-01

Cells dynamically interact with their physical micro-environment through the assembly of nascent focal contacts and focal adhesions. The dynamics and mechanics of these contact points are controlled by transmembrane integrins and an array of intracellular adaptor proteins. In order to study the mechanics and dynamics of focal adhesion assembly, we have developed a technique for the timed induction of a nascent focal adhesion. Bovine aortic endothelial cells were approached at the apical surface by a nanoelectrode whose position was controlled with a resolution of 10s of nanometers using changes in electrode current to monitor distance from the cell surface. Since this probe was functionalized with fibronectin, a focal contact formed at the contact location. Nascent focal adhesion assembly was confirmed using time-lapse confocal fluorescent images of red fluorescent protein (RFP) – tagged talin, an adapter protein that binds to activated integrins. Binding to the cell was verified by noting a lack of change of electrode current upon retraction of the electrode. This study demonstrates that functionalized nanoelectrodes can enable precisely-timed induction and 3-D mechanical manipulation of focal adhesions and the assay of the detailed molecular kinetics of their assembly. PMID:22247742

The semiology of febrile seizures: Focal features are frequent.

PubMed

Takasu, Michihiko; Kubota, Tetsuo; Tsuji, Takeshi; Kurahashi, Hirokazu; Numoto, Shingo; Watanabe, Kazuyoshi; Okumura, Akihisa

2017-08-01

To clarify the semiology of febrile seizures (FS) and to determine the frequency of FS with symptoms suggestive of focal onset. FS symptoms in children were reported within 24h of seizure onset by the parents using a structured questionnaire consisting principally of closed-ended questions. We focused on events at seizure commencement, including changes in behavior and facial expression, and ocular and oral symptoms. We also investigated the autonomic and motor symptoms developing during seizures. The presence or absence of focal and limbic features was determined for each patient. The associations of certain focal and limbic features with patient characteristics were assessed. Information was obtained on FS in 106 children. Various events were recorded at seizure commencement. Behavioral changes were observed in 35 children, changes in facial expression in 53, ocular symptoms in 78, and oral symptoms in 90. In terms of events during seizures, autonomic symptoms were recognized in 78, and convulsive motor symptoms were recognized in 68 children. Focal features were evident in 81 children; 38 children had two or more such features. Limbic features were observed in 44 children, 9 of whom had two or more such features. There was no significant relationship between any patient characteristic and the numbers of focal or limbic features. The semiology of FS varied widely among children, and symptoms suggestive of focal onset were frequent. FS of focal onset may be more common than is generally thought. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of Intravenous Cyclophosphamide Pulse Therapy for P-Glycoprotein-expressing B Cell-associated Active True Renal Lupus Vasculitis in Lupus Nephritis

PubMed Central

Kawabe, Akio; Tsujimura, Shizuyo; Saito, Kazuyoshi; Tanaka, Yoshiya

2017-01-01

True renal lupus vasculitis (TRLV), a vascular lesion usually associated with proliferative lupus nephritis (LN), is resistant to conventional treatments. The expression of P-glycoprotein (P-gp) on activated lymphocytes causes drug resistance. We herein report a patient with TRLV, minimal change LN, overexpression of P-gp on peripheral B cells, and accumulation of P-gp+ B cells at the site of TRLV. High-dose corticosteroids combined with intravenous cyclophosphamide pulse therapy resulted in clinical remission and the long-term normal renal function. PMID:28626187

The flexible engagement of monitoring processes in non-focal and focal prospective memory tasks with salient cues.

PubMed

Hefer, Carmen; Cohen, Anna-Lisa; Jaudas, Alexander; Dreisbach, Gesine

2017-09-01

Prospective memory (PM) refers to the ability to remember to perform a delayed intention. Here, we aimed to investigate the ability to suspend such an intention and thus to confirm previous findings (Cohen, Gordon, Jaudas, Hefer, & Dreisbach, 2016) demonstrating the ability to flexibly engage in monitoring processes. In the current study, we presented a perceptually salient PM cue (bold and red) to rule out that previous findings were limited to non-salient and, thus, easy to ignore PM cues. Moreover, we used both a non-focal (Experiment 1) and a focal PM (Experiment 2) cue. In both Experiments, three groups of participants performed an Eriksen flanker task as an ongoing task with an embedded PM task (they had to remember to press the F1 key if a pre-specified cue appeared). Participants were assigned to either a control condition (performed solely the flanker task), a standard PM condition (performed the flanker task along with the PM task), or a PM delayed condition (performed the flanker task but were instructed to postpone their PM task intention). The results of Experiment 1 with the non-focal PM cue closely replicated those of Cohen et al. (2016) and confirmed that participants were able to successfully postpone the PM cue intention without additional costs even when the PM cue was a perceptually salient one. However, when the PM cue was focal (Experiment 2), it was much more difficult for participants to ignore it as evidenced by commission errors and slower latencies on PM cue trials. In sum, results showed that the focality of the PM cue plays a more crucial role in the flexibility of the monitoring process whereas the saliency of the PM cue does not. Copyright © 2017 Elsevier B.V. All rights reserved.

Combined scanning transmission electron microscopy tilt- and focal series.

PubMed

Dahmen, Tim; Baudoin, Jean-Pierre; Lupini, Andrew R; Kübel, Christian; Slusallek, Philipp; de Jonge, Niels

2014-04-01

In this study, a combined tilt- and focal series is proposed as a new recording scheme for high-angle annular dark-field scanning transmission electron microscopy (STEM) tomography. Three-dimensional (3D) data were acquired by mechanically tilting the specimen, and recording a through-focal series at each tilt direction. The sample was a whole-mount macrophage cell with embedded gold nanoparticles. The tilt-focal algebraic reconstruction technique (TF-ART) is introduced as a new algorithm to reconstruct tomograms from such combined tilt- and focal series. The feasibility of TF-ART was demonstrated by 3D reconstruction of the experimental 3D data. The results were compared with a conventional STEM tilt series of a similar sample. The combined tilt- and focal series led to smaller "missing wedge" artifacts, and a higher axial resolution than obtained for the STEM tilt series, thus improving on one of the main issues of tilt series-based electron tomography.

[Prospective study of drug-induced interstitial nephritis in eleven French nephrology units].

PubMed

Leven, Cyril; Hudier, Laurent; Picard, Sylvie; Longuet, Hélène; Lorcy, Nolwenn; Cam, Gérard; Boukerroucha, Zakaria; Dolley-Hitze, Thibault; Le Cacheux, Philippe; Halimi, Jean-Michel; Cornec Le Gall, Emilie; Hanrotel-Saliou, Catherine; Arreule, Audrey; Massad, Michel; Duveau, Agnès; Couvrat-Desvergnes, Grégoire; Renaudineau, Eric

2014-11-01

Certain medications have been associated with drug-induced acute interstitial nephritis (AIN), but few prospective studies have been published. This prospective observational study aims to record and assess incidents of drug-induced AIN observed over a period of one year in nephrology units in France. The goal is to determine which medications are involved in AIN and to expound the clinical and biological presentation, management, and evolution of AIN. Between April 2012 and April 2013, drug-associated cases of AIN were prospectively recorded in 24 patients registered in 11 nephrology units that belong to the Société de Néphrologie de l'Ouest (SNO). Data sheets, including suspected and concomitant drug(s), kidney function assessment, biological disturbances, clinical signs, histological data, management, and evolution, were collected by the Rennes Regional Pharmacovigilance Center and recorded in the French pharmacovigilance database. In order, the most frequently involved medications in the AIN cases were: vitamin K antagonists (33.3% of the cases, almost exclusively fluindione), antibiotics (20.8% of cases) non-steroidal anti-inflammatory drugs (20.8% of cases), and proton pump inhibitors (16.7% of cases). The mean delay of onset to AIN was 8.3 weeks. At the time of diagnosis, mean serum creatinine was 366 μM, higher for vitamin K antagonists (VKAs), except in the case of warfarin. During the course of an AIN event, 70% of patients had complete blood count and/or urine analysis abnormalities, 55% had clinical signs of systemic hypersensitivity, and 13% of patients had hepatic disorders. Renal biopsies were performed in 54% of patients; however, only 37% of patients requiring therapeutic anticoagulation underwent a biopsy. Suspected drugs were discontinued in all patients and the majority was treated with oral corticosteroids. Renal function often continued to be impaired after an AIN event. At baseline, 25% of patients had chronic kidney disease (CKD); after

Focal necrotizing pneumonia is a distinct entity from lung abscess.

PubMed

Seo, Hyewon; Cha, Seung-Ick; Shin, Kyung-Min; Lim, Jaekwang; Yoo, Seung-Soo; Lee, Jaehee; Lee, Shin-Yup; Kim, Chang-Ho; Park, Jae-Yong

2013-10-01

'Focal necrotizing pneumonia' was defined as a localized type of necrotizing pneumonia characterized by a single or few cavities of low density without rim enhancement on computed tomography (CT) scan. The purpose of this study was to investigate the clinical features and course of patients with focal necrotizing pneumonia, thereby elucidating its clinical relevance. The present study was conducted retrospectively in patients who had been interpreted as having lung abscess or necrotizing pneumonia on CT scan. Clinical and radiological characteristics were compared between the focal necrotizing pneumonia and lung abscess groups. Overall, 68 patients with focal necrotizing pneumonia (n = 35) or lung abscess (n = 33) were included in the present study. The frequency of risk factors for aspiration was significantly lower in the focal necrotizing group, compared with the lung abscess group (14.3% vs 45.5%, P = 0.005). Compared with lung abscess, focal necrotizing pneumonia was observed more commonly in non-gravity-dependent segments (66% vs 36%, P < 0.001). In addition, a trend towards more common isolation of aerobes as potential pathogens was observed in the focal necrotizing pneumonia group, compared with the lung abscess group (31% vs 12%, P = 0.08). However, in terms of treatment outcomes, a similar high rate of success was observed in both groups: 97%, respectively. Compared to lung abscess, focal necrotizing pneumonia occurs more commonly in non-gravity-dependent segments with lower incidence of risk factors for aspiration. Similar to lung abscess, the rate of success for treatment of focal necrotizing pneumonia was high. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Diabetic Macular Edema: What is Focal and What is Diffuse?

PubMed Central

Browning, David J.; Altaweel, Michael M.; Bressler, Neil M.; Bressler, Susan B.; Scott, Ingrid U.

2009-01-01

Purpose To review the available information on classification of diabetic macular edema (DME) as focal or diffuse. Design Interpretive essay. Methods Literature review and interpretation. Results The terms focal and diffuse diabetic macular edema are frequently used without clear definitions. Published definitions often use different examination modalities and are often inconsistent. Evaluating published information on prevalence of focal and diffuse DME, response of focal and diffuse DME to treatments, and importance of focal and diffuse DME in assessing prognosis is hindered because the terms are inconsistently employed. A newer vocabulary may be more constructive, one that describes discrete components of the concepts such as extent and location of macular thickening, involvement of the center of the macula, quantity and pattern of lipid exudates, source of fluorescein leakage, and regional variation in macular thickening, and that distinguishes these terms from the use of the term focal when describing one type of photocoagulation technique. Developing methods for assessing component variables that can be used in clinical practice and establishing reproducibility of the methods will be important tasks. Conclusion Little evidence exists that characteristics of DME described by the terms focal and diffuse help to explain variation in visual acuity or response to treatment. It is unresolved whether a concept of focal and diffuse DME will prove clinically useful despite frequent usage of the terms when describing management of DME. Further studies to address the issues are needed. PMID:18774122

The Focal Surface of the JEM-EUSO Instrument

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

Kawasaki, Y.; EUSO Team, ASI, RIKEN; Casolino, M.

The Extreme Universe Space Observatory on JEM/EF (JEM-EUSO) is a space mission to study extremely high-energy cosmic rays. The JEM-EUSO instrument is a wide-angle refractive telescope in the near-ultraviolet wavelength region which will be mounted to the International Space Station. Its goal is to measure time-resolved fluorescence images of extensive air showers in the atmosphere. In this paper we describe in detail the main features and technological aspects of the focal surface of the instrument. The JEM-EUSO focal surface is a spherically curved surface, with an area of about 4.5m{sup 2}. The focal surface detector is made of more thanmore » 5,000 multi-anode photomultipliers (MAPMTs). Current baseline is Hamamatsu R11265-03-M64. The approach to the focal surface detector is highly modular. Photo-Detector-Modules (PDM) are the basic units that drive the mechanical structure and data acquisition. Each PDM consists of 9 Elementary Cells (ECs). The EC, which is the basic unit of the MAPMT support structure and of the front-end electronics, contains 4 units of MAPMTs. In total, about 1,200 ECs or about 150 PDMs are arranged on the whole of the focal surface of JEM-EUSO.« less

Implementation of focal zooming on the Nike KrF laser

NASA Astrophysics Data System (ADS)

Kehne, D. M.; Karasik, M.; Aglitsky, Y.; Smyth, Z.; Terrell, S.; Weaver, J. L.; Chan, Y.; Lehmberg, R. H.; Obenschain, S. P.

2013-01-01

In direct drive inertial confinement laser fusion, a pellet containing D-T fuel is imploded by ablation arising from absorption of laser energy at its outer surface. For optimal coupling, the focal spot of the laser would continuously decrease to match the reduction in the pellet's diameter, thereby minimizing wasted energy. A krypton-fluoride laser (λ = 248 nm) that incorporates beam smoothing by induced spatial incoherence has the ability to produce a high quality focal profile whose diameter varies with time, a property known as focal zooming. A two-stage focal zoom has been demonstrated on the Nike laser at the Naval Research Laboratory. In the experiment, a 4.4 ns laser pulse was created in which the on-target focal spot diameter was 1.3 mm (full width at half maximum) for the first 2.4 ns and 0.28 mm for the final 2 ns. These two diameters appear in time-integrated focal plane equivalent images taken at several locations in the amplification chain. Eight of the zoomed output beams were overlapped on a 60 μm thick planar polystyrene target. Time resolved images of self-emission from the rear of the target show the separate shocks launched by the two corresponding laser focal diameters.

New advances in focal therapy for early stage prostate cancer.

PubMed

Tay, Kae Jack; Schulman, Ariel A; Sze, Christina; Tsivian, Efrat; Polascik, Thomas J

2017-08-01

Prostate focal therapy offers men the opportunity to achieve oncological control while preserving sexual and urinary function. The prerequisites for successful focal therapy are to accurately identify, localize and completely ablate the clinically significant cancer(s) within the prostate. We aim to evaluate the evidence for current and upcoming technologies that could shape the future of prostate cancer focal therapy in the next five years. Areas covered: Current literature on advances in patient selection using imaging, biopsy and biomarkers, ablation techniques and adjuvant treatments for focal therapy are summarized. A literature search of major databases was performed using the search terms 'focal therapy', 'focal ablation', 'partial ablation', 'targeted ablation', 'image guided therapy' and 'prostate cancer'. Expert commentary: Advanced radiological tools such as multiparametric magnetic resonance imaging (mpMRI), multiparametric ultrasound (mpUS), prostate-specific-membrane-antigen positron emission tomography (PSMA-PET) represent a revolution in the ability to understand cancer function and biology. Advances in ablative technologies now provide a menu of modalities that can be rationalized based on lesion location, size and perhaps in the near future, pre-determined resistance to therapy. However, these need to be carefully studied to establish their safety and efficacy parameters. Adjuvant strategies to enhance focal ablation are under development.

Implementation of focal zooming on the Nike KrF laser.

PubMed

Kehne, D M; Karasik, M; Aglitsky, Y; Smyth, Z; Terrell, S; Weaver, J L; Chan, Y; Lehmberg, R H; Obenschain, S P

2013-01-01

In direct drive inertial confinement laser fusion, a pellet containing D-T fuel is imploded by ablation arising from absorption of laser energy at its outer surface. For optimal coupling, the focal spot of the laser would continuously decrease to match the reduction in the pellet's diameter, thereby minimizing wasted energy. A krypton-fluoride laser (λ = 248 nm) that incorporates beam smoothing by induced spatial incoherence has the ability to produce a high quality focal profile whose diameter varies with time, a property known as focal zooming. A two-stage focal zoom has been demonstrated on the Nike laser at the Naval Research Laboratory. In the experiment, a 4.4 ns laser pulse was created in which the on-target focal spot diameter was 1.3 mm (full width at half maximum) for the first 2.4 ns and 0.28 mm for the final 2 ns. These two diameters appear in time-integrated focal plane equivalent images taken at several locations in the amplification chain. Eight of the zoomed output beams were overlapped on a 60 μm thick planar polystyrene target. Time resolved images of self-emission from the rear of the target show the separate shocks launched by the two corresponding laser focal diameters.

Outcome of the acute glomerular injury in proliferative lupus nephritis

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

Chagnac, A.; Kiberd, B.A.; Farinas, M.C.

1989-09-01

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

DESI focal plate mechanical integration and cooling

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

The Focal Surface of the JEM-EUSO Telescope

NASA Technical Reports Server (NTRS)

Kawasaki, Yoshiya

2007-01-01

Extreme Universe Space Observatory onboard JEM/EP (JEM-EUSO) is a space mission to study extremely high-energy cosmic rays. The JEM-EUSO instrument is a wide-angle refractive telescope in near-ultraviolet wavelength region to observe time-resolved atmospheric fluorescence images of the extensive air showers from the International Space Station. The focal surface is a spherical curved surface, and its area amounts to about 4.5 square m. The focal surface detector is covered with about 6,000 multi-anode photomultipliers (MAPMTs). The focal surface detector consists of Photo-Detector-Modules, each of which consists of 9 Elementary Cells (ECs). The EC contains 4 units of the MAPMTs. Therefore, about 1,500 ECs or about 160 PDMS are arranged on the whole of the focal surface of JEM- EUSO. The EC is a basic unit of the front-end electronics. The PDM is a, basic unit of the data acquisition system

Variable focal length deformable mirror

DOEpatents

Headley, Daniel [Albuquerque, NM; Ramsey, Marc [Albuquerque, NM; Schwarz, Jens [Albuquerque, NM

2007-06-12

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

Focal cemento-osseous dysplasia: review and a case report.

PubMed

Salem, Y M Y; Osman, Y I; Norval, E J G

2010-10-01

Focal cemento-osseous dysplasia is a benign fibro-osseous condition that can be seen in dentate and edentulous patients. It is an asymptomatic lesion and needs no treatment; however follow-up is essential due to the possibility that focal cemento-osseous dysplasia can progress to a condition called florid osseous dysplasia that involves multiple sites. A case report is presented here, along with a review of the differential diagnoses considered in order to reach a final diagnosis of focal cemento-osseous dysplasia.

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

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

Macconi, D.; Noris, M.; Benfenati, E.

1991-01-01

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

Infrared fiber optic focal plane dispersers

NASA Technical Reports Server (NTRS)

Goebel, J. H.

1981-01-01

Far infrared transmissive fiber optics as a component in the design of integrated far infrared focal plane array utilization is discussed. A tightly packed bundle of fibers is placed at the focal plane, where an array of infrared detectors would normally reside, and then fanned out in two or three dimensions to individual detectors. Subsequently, the detectors are multiplexed by cryogenic electronics for relay of the data. A second possible application is frequency up-conversion (v sub 1 + v sub 2 = v sub 3), which takes advantage of the nonlinear optical index of refraction of certain infrared transmissive materials in fiber form. Again, a fiber bundle is utilized as above, but now a laser of frequency v sub 1 is mixed with the incoming radiation of frequency v sub 1 within the nonlinear fiber material. The sum, v sub 2 is then detected by near infrared or visible detectors which are more sensitive than those available at v sub 2. Due to the geometrical size limitations of detectors such as photomultipliers, the focal plane dispersal technique is advantageous for imaging up-conversion.

Up regulation of serum tumor necrosis factor-related apoptosis inducing ligand in juvenile-onset systemic lupus erythematosus: relations with disease activity, antibodies to double -stranded DNA, nephritis and neutropenia.

PubMed

Ezzat, Mohamed H M; El-Gammasy, Tarek M A; Shaheen, Kareem Y A; El-Mezdawi, Ramzi A M; Youssef, Mervat S M

2013-06-01

Apoptosis is induced by binding of death receptor ligands, members of the tumor necrosis factor (TNF) superfamily, to their cognate receptors. It is suggested that TNF-related apoptosis inducing ligand (TRAIL) is involved in pathogenesis of juvenile-onset systemic lupus erythematosus (JSLE). This study aimed to assess TRAIL concentrations in sera of JSLE children and to determine their potential relationship with disease activity, anti-double-stranded DNA (anti-dsDNA) levels, neutropenia and renal involvement. Circulating levels of TRAIL were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples obtained from 40 JSLE patients (20 with active and 20 with inactive disease) and 20 controls. The mean (SEM) serum TRAIL concentration in JSLE was 1750.7 (440.2) pg/mL. Serum TRAIL concentrations in patients were higher than those in controls (P < 0.01). Serum TRAIL concentrations for children with inactive disease (1854.8 [485.4] pg/mL) and those with activity (1646.6 [390.6] pg/mL) were statistically comparable. JSLE children with positive anti-dsDNA antibodies had significantly higher TRAIL levels (mean = 1846 [456] vs. 1455 [325] pg/mL; P < 0.05). Serum TRAIL concentrations were significantly higher in classes III and IV nephritis compared to classes I and II nephritis (1970 [512] vs. 1330 [331] pg/mL; P < 0.01). Serum TRAIL concentrations in patients with neutropenia were higher than those without neutropenia (1805 [505] vs. 1516 [400] pg/mL; P = 0.042) and in controls (P = 0.024). Our data indicate that an increased level of TRAIL is a feature of JSLE that correlates with disease activity, anti-dsDNA titers neutropenia and lupus nephritis. © 2013 The Authors International Journal of Rheumatic Diseases © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Association of polymorphic variants of PTPN22, TNF and VDR genes in children with lupus nephritis: A study in Colombian family triads.

PubMed

Garavito, Gloria; Egea, Eduardo; Fang, Luis; Malagón, Clara; Olmos, Carlos; González, Luz; Guarnizo, Pilar; Aroca, Gustavo; López, Guillermo; Iglesias, Antonio

2017-06-01

Systemic lupus erythematosus is an autoimmune disease in which the severity varies according to race, sex and age of onset. This variation is also observed in the genetic markers associated with the disease, including PTPN22, VDR and TNF genes. The genetic stratification in different populations worldwide can influence the variability. To analyze the heritability of PTPN22, VDR and TNF genetic variants and their association with pediatric lupus nephritis in Colombian families. We conducted a family-based study including 46 triads (case, father and mother). The variants rs2476601 of PTPN22; rs361525 and rs1800629 of TNF, and TaqI [rs731236], ApaI [rs7975232], BsmI [rs1544410] and FokI [rs2228570] of VDR were genotyped by qPCR. The effects of overtransmission of the risk allele from parents to children and linkage disequilibrium at the VDR and TNF loci were estimated. We found that allele A of rs2476601 in PTPN22 was distributed among 8.69 % (n=16) of the parents and 19.5 % (n=18) of the cases; this allele was overtransmitted from parents to children 17 times more often than the G allele (p=0.028). TNF and VDR polymorphisms did not exhibit transmission disequilibrium. VDR TaqI, ApaI and BsmI variants exhibited linkage disequilibrium. These findings showed an association between the PTPN22 rs2476601 polymorphism and pediatric lupus nephritis due to its overtransmission in the group of families studied.

Outcome of epilepsy surgery in focal cortical dysplasia

PubMed Central

Kral, T; Clusmann, H; Blumcke, I; Fimmers, R; Ostertun, B; Kurthen, M; Schramm, J

2003-01-01

Objective: To describe the outcome of surgery in patients with drug resistant epilepsy and a histopathological diagnosis of focal cortical dysplasia. Methods and subjects: Analysis of histories and presurgical and follow up data was carried out in 53 patients with a histological diagnosis of focal cortical dysplasia. Their mean age was 24.0 years (range 5 to 46), and they included 14 children and adolescents. Mean age at seizure onset was 12.4 years (0.4 to 36) and mean seizure duration was 11.6 years (1 to 45). Results: The presurgical detection rate of focal cortical dysplasia with magnetic resonance imaging (MRI) was 96%. There were 24 temporal and 29 extratemporal resections; additional multiple subpial transections were done in 12 cases to prevent spread of seizure discharges. There was a 6% rate of complications with permanent neurological deficit, but no deaths. All resected specimens were classified by neuropathological criteria as focal cortical dysplasia. Balloon cells were seen in most cases of extratemporal focal cortical dysplasia. After a mean follow up of 50 months, 38 patients (72%) were seizure-free, two (4%) had less than two seizures a year, nine (17%) had a reduction of seizure frequency of more than 75%, and four (8%) had no improvement. Seizure outcome was similar after temporal and extratemporal surgery. The patients in need of multilobar surgery had the poorest outcome. Conclusions: Circumscribed lesionectomy of focal dysplastic lesions provides seizure relief in patients with chronic drug resistant temporal and extratemporal epilepsy. There was a trend for the best seizure outcome to be in patients with early presurgical evaluation and early surgery, and in whom lesions were identified on the preoperative MRI studies. PMID:12531945

Focal therapy in prostate cancer: the current situation

PubMed Central

Jácome-Pita, FX; Sánchez-Salas, R; Barret, E; Amaruch, N; Gonzalez-Enguita, C; Cathelineau, X

2014-01-01

Prostate cancer is one of the most significant pathologies in the field of urology. The adoption of screening strategies and improvements in biopsies have resulted in an increase in early-stage tumour detection. Radical global therapies provide very good oncological results in localised prostate cancer. However, excess treatment in low- and, in some cases, intermediate-risk groups affects the quality of life of these patients. In the case of localised prostate cancer, focal therapies offer a minimally invasive option with good results with respect to established treatments. Although this is currently not a standard treatment, it represents the therapeutic approach with the greatest potential. This literature review has the following objectives: to define selection criteria for patients who are candidates for focal therapy, to assess the current situation and results of the different therapeutic options, and to define procedures in cases of recurrence and for follow-ups. We concluded that focal therapy is a viable therapeutic alternative for localised prostate cancer, specifically cryosurgery and high-intensity targeted ultrasound, which have acceptable oncologic results and a lower comorbidity compared with global treatments. Studies with a high level of scientific evidence are still needed to validate these results. Acquisition of evidence A search was carried out on the Medline (PubMed), EMBASE, Web of Science and Cochrane databases of all papers published before 31 July 2013. We included clinical studies and literature reviews that evaluated primary focal therapy for prostate cancer confirmed by biopsy and excluded focal rescue therapy studies. The keywords used were focal therapy and prostate cancer. Initially, we found 42 articles; 15 studies were excluded because they did not meet the minimum criteria for inclusion. A total of 1350 cases were treated throughout 27 studies. PMID:24944577

Fabrication of three-focal diffractive lenses by two-photon polymerization technique

NASA Astrophysics Data System (ADS)

Osipov, Vladimir; Doskolovich, Leonid L.; Bezus, Evgeni A.; Cheng, Wei; Gaidukeviciute, Arune; Chichkov, Boris

2012-06-01

Fabrication of submicron-height relief of three-focal diffractive lenses using two-photon polymerization is studied. Optical properties of the designed lenses are investigated theoretically and experimentally. The proposed design of the combined diffractive-refractive lenses is promising for the realization of three-focal optical ophthalmological implants with predetermined light intensity distribution between the foci. The realized three-focal optical element has a diameter size of 2.7 mm with the focal distances in the range of 27-34 mm.

Testing of focal plane arrays at the AEDC

NASA Astrophysics Data System (ADS)

Nicholson, Randy A.; Mead, Kimberly D.; Smith, Robert W.

1992-07-01

A facility was developed at the Arnold Engineering Development Center (AEDC) to provide complete radiometric characterization of focal plane arrays (FPAs). The highly versatile facility provides the capability to test single detectors, detector arrays, and hybrid FPAs. The primary component of the AEDC test facility is the Focal Plane Characterization Chamber (FPCC). The FPCC provides a cryogenic, low-background environment for the test focal plane. Focal plane testing in the FPCC includes flood source testing, during which the array is uniformly irradiated with IR radiation, and spot source testing, during which the target radiation is focused onto a single pixel or group of pixels. During flood source testing, performance parameters such as power consumption, responsivity, noise equivalent input, dynamic range, radiometric stability, recovery time, and array uniformity can be assessed. Crosstalk is evaluated during spot source testing. Spectral response testing is performed in a spectral response test station using a three-grating monochromator. Because the chamber can accommodate several types of testing in a single test installation, a high throughput rate and good economy of operation are possible.

Positive focal shift of gallium nitride high contrast grating focusing reflectors

NASA Astrophysics Data System (ADS)

He, Shumin; Wang, Zhenhai; Liu, Qifa

2016-09-01

We design a type of metasurfaces capable of serving as a visible-light focusing reflector based on gallium nitride (GaN) high contrast gratings (HCGs). The wavefront of the reflected light is precisely manipulated by spatial variation of the grating periods along the subwavelength ridge array to achieve light focusing. Different from conventional negative focal shift effect, a positive focal shift is observed in such focusing reflectors. Detailed investigations of the influence of device size on the focusing performance, especially the focal length, are preformed via a finite element method . The results show that all performance parameters are greatly affected by the reflector size. A more concentrated focal point, or a better focusing capability, can be achieved by larger size. With increasing reflector size, the achieved focal length decreases and gradually approaches to the design, thus the corresponding positive focal shift decreases. Our results are helpful for understanding the visible-light control of the planar HCG-based focusing reflectors.

Tubulointerstitial nephritis and uveitis syndrome associated with hyperthyroidism.

PubMed

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

2006-09-01

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

Natural-focal diseases: mapping experience in Russia.

PubMed

Malkhazova, Svetlana M; Mironova, Varvara A; Kotova, Tatiana V; Shartova, Natalia V; Orlov, Dmitry S

2014-06-14

Natural-focal diseases constitute a serious hazard for human health. Agents and vectors of such diseases belong to natural landscapes. The aim of this study is to identify the diversity and geography of natural-focal diseases in Russia and to develop cartographic approaches for their mapping, including mathematical-cartographical modeling. Russian medico-geographical mapping of natural-focal diseases is highly developed regionally and locally but extremely limited at the national level. To solve this problem, a scientific team of the Faculty of Geography at Lomonosov Moscow State University has developed and implemented a project of a medico-geographical Atlas of Russia "Natural-Focal Diseases". The mapping is based on medical statistics data. The Atlas contains a series of maps on disease incidence, long-term dynamics of disease morbidity, etc. In addition, other materials available to the authors were used: mapping of the natural environment, field data, archival materials, analyzed satellite images, etc. The maps are processed using ArcGIS (ESRI) software application. Different methods of rendering of mapped phenomena are used (geographical ranges, diagrams, choropleth maps etc.). A series of analytical, integrated, and synthetic maps shows disease incidence in the population at both the national and regional levels for the last 15 years. Maps of the mean annual morbidity of certain infections and maps of morbidity dynamics and nosological profiles allow for a detailed analysis of the situation for each of 83 administrative units of the Russian Federation. The degree of epidemic hazard in Russia by natural-focal diseases is reflected in a synthetic medico-geographical map that shows the degree of epidemic risks due to such diseases in Russia and allows one to estimate the risk of disease manifestation in a given region. This is the first attempt at aggregation and public presentation of diverse and multifaceted information about natural-focal diseases in Russia

Ertapenem-Induced Acute Interstitial Nephritis (AIN) in a Case of Protein S Deficiency and Factor V Leiden Mutation with Deep Vein Thrombosis.

PubMed

Rathod, Nitin; Pai, Pavan

2016-03-01

We present a case of 58 years old male patient, who presented with high fever for which injection Ertapenem was started empirically at Dubai hospital. Patient was a known case of Deep vein thrombosis of left leg since 5 years on warfarin therapy. Patient came to India for high fever and further management. Patient developed proteinuria with high creatinine and urinary abnormalities. Renal biopsy revealed acute interstitial nephritis (AIN). In addition, he was diagnosed to have protein S deficiency with Factor V Leiden mutation. © Journal of the Association of Physicians of India 2011.

[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.

A targeted resequencing gene panel for focal epilepsy.

PubMed

Hildebrand, Michael S; Myers, Candace T; Carvill, Gemma L; Regan, Brigid M; Damiano, John A; Mullen, Saul A; Newton, Mark R; Nair, Umesh; Gazina, Elena V; Milligan, Carol J; Reid, Christopher A; Petrou, Steven; Scheffer, Ingrid E; Berkovic, Samuel F; Mefford, Heather C

2016-04-26

We report development of a targeted resequencing gene panel for focal epilepsy, the most prevalent phenotypic group of the epilepsies. The targeted resequencing gene panel was designed using molecular inversion probe (MIP) capture technology and sequenced using massively parallel Illumina sequencing. We demonstrated proof of principle that mutations can be detected in 4 previously genotyped focal epilepsy cases. We searched for both germline and somatic mutations in 251 patients with unsolved sporadic or familial focal epilepsy and identified 11 novel or very rare missense variants in 5 different genes: CHRNA4, GRIN2B, KCNT1, PCDH19, and SCN1A. Of these, 2 were predicted to be pathogenic or likely pathogenic, explaining ∼0.8% of the cohort, and 8 were of uncertain significance based on available data. We have developed and validated a targeted resequencing panel for focal epilepsies, the most important clinical class of epilepsies, accounting for about 60% of all cases. Our application of MIP technology is an innovative approach that will be advantageous in the clinical setting because it is highly sensitive, efficient, and cost-effective for screening large patient cohorts. Our findings indicate that mutations in known genes likely explain only a small proportion of focal epilepsy cases. This is not surprising given the established clinical and genetic heterogeneity of these disorders and underscores the importance of further gene discovery studies in this complex syndrome. © 2016 American Academy of Neurology.

Myxococcus xanthus Gliding Motors Are Elastically Coupled to the Substrate as Predicted by the Focal Adhesion Model of Gliding Motility

PubMed Central

Balagam, Rajesh; Litwin, Douglas B.; Czerwinski, Fabian; Sun, Mingzhai; Kaplan, Heidi B.; Shaevitz, Joshua W.; Igoshin, Oleg A.

2014-01-01

Myxococcus xanthus is a model organism for studying bacterial social behaviors due to its ability to form complex multi-cellular structures. Knowledge of M. xanthus surface gliding motility and the mechanisms that coordinated it are critically important to our understanding of collective cell behaviors. Although the mechanism of gliding motility is still under investigation, recent experiments suggest that there are two possible mechanisms underlying force production for cell motility: the focal adhesion mechanism and the helical rotor mechanism, which differ in the biophysics of the cell–substrate interactions. Whereas the focal adhesion model predicts an elastic coupling, the helical rotor model predicts a viscous coupling. Using a combination of computational modeling, imaging, and force microscopy, we find evidence for elastic coupling in support of the focal adhesion model. Using a biophysical model of the M. xanthus cell, we investigated how the mechanical interactions between cells are affected by interactions with the substrate. Comparison of modeling results with experimental data for cell-cell collision events pointed to a strong, elastic attachment between the cell and substrate. These results are robust to variations in the mechanical and geometrical parameters of the model. We then directly measured the motor-substrate coupling by monitoring the motion of optically trapped beads and find that motor velocity decreases exponentially with opposing load. At high loads, motor velocity approaches zero velocity asymptotically and motors remain bound to beads indicating a strong, elastic attachment. PMID:24810164

Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults

PubMed Central

Legendre, Mathieu; Devilliers, Hervé; Perard, Laurent; Groh, Matthieu; Nefti, Habdelamid; Dussol, Bertrand; Trad, Salim; Touré, Fatouma; Abad, Sébastien; Boffa, Jean-Jacques; Frimat, Luc; Torner, Stéphane; Seidowsky, Alexandre; Massy, Ziad André; Saadoun, David; Rieu, Virginie; Schoindre, Yoland; Heron, Emmanuel; Frouget, Thierry; Lionet, Arnaud; Glowacki, François; Arnaud, Laurent; Mousson, Christiane; Besancenot, Jean-François; Rebibou, Jean-Michel; Bielefeld, Philip

2016-01-01

Abstract Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis. We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015. Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8–77.4) with a median serum creatinine level at 207 μmol/L (range 100–1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m2 (range 2–73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10–2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m2 (range 17–119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = −0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = −0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated

[Familial focal and segmentary hyalinosis].

PubMed

Sánchez de la Nieta, M D; Arias, L F; Alcázar, R; de la Torre, M; González, L; Rivera, F; Blanco, J; Ferreras, I

2003-01-01

Focal segmental glomerulosclerosis represents a finding in several renal disorders, characterized by proteinuria and sometimes by arterial hypertension and progressive decline in renal function. There are primary (idiopathic and familial) and secundary forms. In the last 20 years several familial cases has been reported, with a great genetic heterogeneity (dominant and recessive forms) and with multiple associations with particular MHC class-I and class-II gene loci, being Al, DR3 o DR7 the most frequently reported. We described three members of same family with focal segmental hyalinosis that shared the HLA haplotype A31 B61 DR13. This association has not been described previously. We highlight that genetic and acquired factors (obesity, hypertension...) could have importance in the development of progressive renal failure in these patients.

In vivo epidermal migration requires focal adhesion targeting of ACF7

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

Yue, Jiping; Zhang, Yao; Liang, Wenguang G.

Turnover of focal adhesions allows cell retraction, which is essential for cell migration. The mammalian spectraplakin protein, ACF7 (Actin-Crosslinking Factor 7), promotes focal adhesion dynamics by targeting of microtubule plus ends towards focal adhesions. However, it remains unclear how the activity of ACF7 is regulated spatiotemporally to achieve focal adhesion-specific guidance of microtubule. To explore the potential mechanisms, we resolve the crystal structure of ACF7's NT (amino-terminal) domain, which mediates F-actin interactions. Structural analysis leads to identification of a key tyrosine residue at the calponin homology (CH) domain of ACF7, whose phosphorylation by Src/FAK (focal adhesion kinase) complex is essentialmore » for F-actin binding of ACF7. Using skin epidermis as a model system, we further demonstrate that the phosphorylation of ACF7 plays an indispensable role in focal adhesion dynamics and epidermal migration in vitro and in vivo. Altogether, our findings provide critical insights into the molecular mechanisms underlying coordinated cytoskeletal dynamics during cell movement.« less

In vivo epidermal migration requires focal adhesion targeting of ACF7

DOE PAGES

Yue, Jiping; Zhang, Yao; Liang, Wenguang G.; ...

2016-05-24

Turnover of focal adhesions allows cell retraction, which is essential for cell migration. The mammalian spectraplakin protein, ACF7 (Actin-Crosslinking Factor 7), promotes focal adhesion dynamics by targeting of microtubule plus ends towards focal adhesions. However, it remains unclear how the activity of ACF7 is regulated spatiotemporally to achieve focal adhesion-specific guidance of microtubule. To explore the potential mechanisms, we resolve the crystal structure of ACF7's NT (amino-terminal) domain, which mediates F-actin interactions. Structural analysis leads to identification of a key tyrosine residue at the calponin homology (CH) domain of ACF7, whose phosphorylation by Src/FAK (focal adhesion kinase) complex is essentialmore » for F-actin binding of ACF7. Using skin epidermis as a model system, we further demonstrate that the phosphorylation of ACF7 plays an indispensable role in focal adhesion dynamics and epidermal migration in vitro and in vivo. Altogether, our findings provide critical insights into the molecular mechanisms underlying coordinated cytoskeletal dynamics during cell movement.« less

Managing focal fields of vector beams with multiple polarization singularities.

PubMed

Han, Lei; Liu, Sheng; Li, Peng; Zhang, Yi; Cheng, Huachao; Gan, Xuetao; Zhao, Jianlin

2016-11-10

We explore the tight focusing behavior of vector beams with multiple polarization singularities, and analyze the influences of the number, position, and topological charge of the singularities on the focal fields. It is found that the ellipticity of the local polarization states at the focal plane could be determined by the spatial distribution of the polarization singularities of the vector beam. When the spatial location and topological charge of singularities have even-fold rotation symmetry, the transverse fields at the focal plane are locally linearly polarized. Otherwise, the polarization state becomes a locally hybrid one. By appropriately arranging the distribution of the polarization singularities in the vector beam, the polarization distributions of the focal fields could be altered while the intensity maintains unchanged.

Analysis of Rapid Multi-Focal Zone ARFI Imaging

PubMed Central

Rosenzweig, Stephen; Palmeri, Mark; Nightingale, Kathryn

2015-01-01

Acoustic radiation force impulse (ARFI) imaging has shown promise for visualizing structure and pathology within multiple organs; however, because the contrast depends on the push beam excitation width, image quality suffers outside of the region of excitation. Multi-focal zone ARFI imaging has previously been used to extend the region of excitation (ROE), but the increased acquisition duration and acoustic exposure have limited its utility. Supersonic shear wave imaging has previously demonstrated that through technological improvements in ultrasound scanners and power supplies, it is possible to rapidly push at multiple locations prior to tracking displacements, facilitating extended depth of field shear wave sources. Similarly, ARFI imaging can utilize these same radiation force excitations to achieve tight pushing beams with a large depth of field. Finite element method simulations and experimental data are presented demonstrating that single- and rapid multi-focal zone ARFI have comparable image quality (less than 20% loss in contrast), but the multi-focal zone approach has an extended axial region of excitation. Additionally, as compared to single push sequences, the rapid multi-focal zone acquisitions improve the contrast to noise ratio by up to 40% in an example 4 mm diameter lesion. PMID:25643078

Smart focal-plane technology for micro-instruments and micro-rovers

NASA Technical Reports Server (NTRS)

Fossum, Eric R.

1993-01-01

It is inevitable that micro-instruments and micro-rovers for space exploration will contain one or more focal-plane arrays for imaging, spectroscopy, or navigation. In this paper, we explore the state-of-the-art in focal-plane technology for visible sensors. Also discussed is present research activity in advanced focal-plane technology with particular emphasis on the development of smart sensors. The paper concludes with a discussion of possible future directions for the advancement of the technology.

Focus in Grade 8: Teaching with Curriculum Focal Points

ERIC Educational Resources Information Center

Schielack, Jane

2010-01-01

This book describes and illustrates learning paths for the mathematical concepts and skills of each grade 8 Focal Point as presented in Curriculum Focal Points for Prekindergarten through Grade 8 Mathematics. It includes representational supports for teaching and learning that can facilitate understanding, stimulate productive discussions about…

The contribution of the programmed cell death machinery in innate immune cells to lupus nephritis.

PubMed

Tsai, FuNien; Perlman, Harris; Cuda, Carla M

2017-12-01

Systemic lupus erythematosus (SLE) is a chronic multi-factorial autoimmune disease initiated by genetic and environmental factors, which in combination trigger disease onset in susceptible individuals. Damage to the kidney as a consequence of lupus nephritis (LN) is one of the most prevalent and severe outcomes, as LN affects up to 60% of SLE patients and accounts for much of SLE-associated morbidity and mortality. As remarkable strides have been made in unlocking new inflammatory mechanisms associated with signaling molecules of programmed cell death pathways, this review explores the available evidence implicating the action of these pathways specifically within dendritic cells and macrophages in the control of kidney disease. Although advancements into the underlying mechanisms responsible for inducing cell death inflammatory pathways have been made, there still exist areas of unmet need. By understanding the molecular mechanisms by which dendritic cells and macrophages contribute to LN pathogenesis, we can improve their viability as potential therapeutic targets to promote remission. Copyright © 2016 Elsevier Inc. All rights reserved.

NeuroSeek dual-color image processing infrared focal plane array

NASA Astrophysics Data System (ADS)

McCarley, Paul L.; Massie, Mark A.; Baxter, Christopher R.; Huynh, Buu L.

1998-09-01

Several technologies have been developed in recent years to advance the state of the art of IR sensor systems including dual color affordable focal planes, on-focal plane array biologically inspired image and signal processing techniques and spectral sensing techniques. Pacific Advanced Technology (PAT) and the Air Force Research Lab Munitions Directorate have developed a system which incorporates the best of these capabilities into a single device. The 'NeuroSeek' device integrates these technologies into an IR focal plane array (FPA) which combines multicolor Midwave IR/Longwave IR radiometric response with on-focal plane 'smart' neuromorphic analog image processing. The readout and processing integrated circuit very large scale integration chip which was developed under this effort will be hybridized to a dual color detector array to produce the NeuroSeek FPA, which will have the capability to fuse multiple pixel-based sensor inputs directly on the focal plane. Great advantages are afforded by application of massively parallel processing algorithms to image data in the analog domain; the high speed and low power consumption of this device mimic operations performed in the human retina.

Context cue focality influences strategic prospective memory monitoring.

PubMed

Hunter Ball, B; Bugg, Julie M

2018-02-12

Monitoring the environment for the occurrence of prospective memory (PM) targets is a resource-demanding process that produces cost (e.g., slower responding) to ongoing activities. However, research suggests that individuals are able to monitor strategically by using contextual cues to reduce monitoring in contexts in which PM targets are not expected to occur. In the current study, we investigated the processes supporting context identification (i.e., determining whether or not the context is appropriate for monitoring) by testing the context cue focality hypothesis. This hypothesis predicts that the ability to monitor strategically depends on whether the ongoing task orients attention to the contextual cues that are available to guide monitoring. In Experiment 1, participants performed an ongoing lexical decision task and were told that PM targets (TOR syllable) would only occur in word trials (focal context cue condition) or in items starting with consonants (nonfocal context cue condition). In Experiment 2, participants performed an ongoing first letter judgment (consonant/vowel) task and were told that PM targets would only occur in items starting with consonants (focal context cue condition) or in word trials (nonfocal context cue condition). Consistent with the context cue focality hypothesis, strategic monitoring was only observed during focal context cue conditions in which the type of ongoing task processing automatically oriented attention to the relevant features of the contextual cue. These findings suggest that strategic monitoring is dependent on limited-capacity processing resources and may be relatively limited when the attentional demands of context identification are sufficiently high.

Earthquake focal mechanism forecasting in Italy for PSHA purposes

NASA Astrophysics Data System (ADS)

Roselli, Pamela; Marzocchi, Warner; Mariucci, Maria Teresa; Montone, Paola

2018-01-01

In this paper, we put forward a procedure that aims to forecast focal mechanism of future earthquakes. One of the primary uses of such forecasts is in probabilistic seismic hazard analysis (PSHA); in fact, aiming at reducing the epistemic uncertainty, most of the newer ground motion prediction equations consider, besides the seismicity rates, the forecast of the focal mechanism of the next large earthquakes as input data. The data set used to this purpose is relative to focal mechanisms taken from the latest stress map release for Italy containing 392 well-constrained solutions of events, from 1908 to 2015, with Mw ≥ 4 and depths from 0 down to 40 km. The data set considers polarity focal mechanism solutions until to 1975 (23 events), whereas for 1976-2015, it takes into account only the Centroid Moment Tensor (CMT)-like earthquake focal solutions for data homogeneity. The forecasting model is rooted in the Total Weighted Moment Tensor concept that weighs information of past focal mechanisms evenly distributed in space, according to their distance from the spatial cells and magnitude. Specifically, for each cell of a regular 0.1° × 0.1° spatial grid, the model estimates the probability to observe a normal, reverse, or strike-slip fault plane solution for the next large earthquakes, the expected moment tensor and the related maximum horizontal stress orientation. These results will be available for the new PSHA model for Italy under development. Finally, to evaluate the reliability of the forecasts, we test them with an independent data set that consists of some of the strongest earthquakes with Mw ≥ 3.9 occurred during 2016 in different Italian tectonic provinces.

Nonlinear Focal Modulation Microscopy.

PubMed

Zhao, Guangyuan; Zheng, Cheng; Kuang, Cuifang; Zhou, Renjie; Kabir, Mohammad M; Toussaint, Kimani C; Wang, Wensheng; Xu, Liang; Li, Haifeng; Xiu, Peng; Liu, Xu

2018-05-11

We demonstrate nonlinear focal modulation microscopy (NFOMM) to achieve superresolution imaging. Traditional approaches to superresolution that utilize point scanning often rely on spatially reducing the size of the emission pattern by directly narrowing (e.g., through minimizing the detection pinhole in Airyscan, Zeiss) or indirectly peeling its outer profiles [e.g., through depleting the outer emission region in stimulated emission depletion (STED) microscopy]. We show that an alternative conceptualization that focuses on maximizing the optical system's frequency shifting ability offers advantages in further improving resolution while reducing system complexity. In NFOMM, a spatial light modulator and a suitably intense laser illumination are used to implement nonlinear focal-field modulation to achieve a transverse spatial resolution of ∼60  nm (∼λ/10). We show that NFOMM is comparable with STED microscopy and suitable for fundamental biology studies, as evidenced in imaging nuclear pore complexes, tubulin and vimentin in Vero cells. Since NFOMM is readily implemented as an add-on module to a laser-scanning microscope, we anticipate wide utility of this new imaging technique.

Nonlinear Focal Modulation Microscopy

NASA Astrophysics Data System (ADS)

Zhao, Guangyuan; Zheng, Cheng; Kuang, Cuifang; Zhou, Renjie; Kabir, Mohammad M.; Toussaint, Kimani C.; Wang, Wensheng; Xu, Liang; Li, Haifeng; Xiu, Peng; Liu, Xu

2018-05-01

We demonstrate nonlinear focal modulation microscopy (NFOMM) to achieve superresolution imaging. Traditional approaches to superresolution that utilize point scanning often rely on spatially reducing the size of the emission pattern by directly narrowing (e.g., through minimizing the detection pinhole in Airyscan, Zeiss) or indirectly peeling its outer profiles [e.g., through depleting the outer emission region in stimulated emission depletion (STED) microscopy]. We show that an alternative conceptualization that focuses on maximizing the optical system's frequency shifting ability offers advantages in further improving resolution while reducing system complexity. In NFOMM, a spatial light modulator and a suitably intense laser illumination are used to implement nonlinear focal-field modulation to achieve a transverse spatial resolution of ˜60 nm (˜λ /10 ). We show that NFOMM is comparable with STED microscopy and suitable for fundamental biology studies, as evidenced in imaging nuclear pore complexes, tubulin and vimentin in Vero cells. Since NFOMM is readily implemented as an add-on module to a laser-scanning microscope, we anticipate wide utility of this new imaging technique.

Focal hyperhidrosis: diagnosis and management

PubMed Central

Haider, Aamir; Solish, Nowell

2005-01-01

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

DEPDC5 takes a second hit in familial focal epilepsy.

PubMed

Anderson, Matthew P

2018-04-30

Loss-of-function mutations in a single allele of the gene encoding DEP domain-containing 5 protein (DEPDC5) are commonly linked to familial focal epilepsy with variable foci; however, a subset of patients presents with focal cortical dysplasia that is proposed to result from a second-hit somatic mutation. In this issue of the JCI, Ribierre and colleagues provide several lines of evidence to support second-hit DEPDC5 mutations in this disorder. Moreover, the authors use in vivo, in utero electroporation combined with CRISPR-Cas9 technology to generate a murine model of the disease that recapitulates human manifestations, including cortical dysplasia-like changes, focal seizures, and sudden unexpected death. This study provides important insights into familial focal epilepsy and provides a preclinical model for evaluating potential therapies.

Magnetic electroanatomical mapping for ablation of focal atrial tachycardias.

PubMed

Marchlinski, F; Callans, D; Gottlieb, C; Rodriguez, E; Coyne, R; Kleinman, D

1998-08-01

Uniform success for ablation of focal atrial tachycardias has been difficult to achieve using standard catheter mapping and ablation techniques. In addition, our understanding of the complex relationship between atrial anatomy, electrophysiology, and surface ECG P wave morphology remains primitive. The magnetic electroanatomical mapping and display system (CARTO) offers an on-line display of electrical activation and/or signal amplitude related to the anatomical location of the recorded sites in the mapped chamber. A window of electrical interest is established based on signals timed from an electrical reference that usually represents a fixed electrogram recording from the coronary sinus or the atrial appendage. This window of electrical interest is established to include atrial activation prior to the onset of the P wave activity associated with the site of origin of a focal atrial tachycardia. Anatomical and electrical landmarks are defined with limited fluoroscopic imaging support and more detailed global chamber and more focal atrial mapping can be performed with minimal fluoroscopic guidance. A three-dimensional color map representing atrial activation or voltage amplitude at the magnetically defined anatomical sites is displayed with on-line data acquisition. This display can be manipulated to facilitate viewing from any angle. Altering the zoom control, triangle fill threshold, clipping plane, or color range can all enhance the display of a more focal area of interest. We documented the feasibility of using this single mapping catheter technique for localizing and ablating focal atrial tachycardias. In a consecutive series of 8 patients with 9 focal atrial tachycardias, the use of the single catheter CARTO mapping system was associated with ablation success in all but one patient who had a left atrial tachycardia localized to the medial aspect of the orifice of the left atrial appendage. Only low power energy delivery was used in this patient because of the

Very delayed lupus nephritis: a report of three cases and literature review.

PubMed

Alexandre, André R; Carreira, Pedro L; Isenberg, David A

2018-01-01

Lupus nephritis (LN) affects up to 50% of patients with Systemic Lupus Erythematosus (SLE) and is associated with a worse prognosis. LN usually develops within the first 5 years of the onset of the disease. We report three patients with very delayed LN (DLN) diagnosed after 15 or more years after SLE diagnosis. The three patients were non-Caucasian women with adolescent or adult-onset SLE. Each had antinuclear, anti-dsDNA and anti-Ro antibodies. Hydroxychloroquine was prescribed for each. Their disease courses were characterised by sporadic non-renal flares controlled by steroids and, in two cases, by one cycle of rituximab. Unexpectedly, they developed proteinuria, haematuria and lowering of estimated glomerular filtration rate with clinical signs of renal disease. LN was confirmed by renal biopsy. Reviewing them, each showed serological signs of increasing disease activity (rising levels of anti-dsDNA antibodies and fall in C3) that predated clinical or laboratory signs of LN by 1-3 years. Reviewing the literature, we found a lack of knowledge about DLN starting more than 15 years after SLE diagnosis. With the increasing life expectancy of patients with SLE it is likely that more cases of very DLN will emerge.

Crystal diffraction lens with variable focal length

DOEpatents

Smither, R.K.

1991-04-02

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

Rasmussen's encephalitis presenting as focal cortical dysplasia

PubMed Central

O'Rourke, D.J.; Bergin, A.; Rotenberg, A.; Peters, J.; Gorman, M.; Poduri, A.; Cryan, J.; Lidov, H.; Madsen, J.; Harini, C.

2014-01-01

Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD) and discuss the literature on this topic. PMID:25667877

Gallbladder adenoma with focal adenocarcinoma.

PubMed

Ciurea, S; Matei, E; Petrisor, P; Luca, L; Boros, Mirela; Herlea, V; Popescu, I

2008-01-01

The majority of polypoid lesions of the gallbladder are cholesterolosis pseudopolyps. True neoplastic GB polyps are represented mainly by adenomas. The case of a 52-year old male patient with an adenomatous polyp of the GB with focal adenocarcinoma is presented.

Primary focal hyperhidrosis: diagnosis and management. .

PubMed

Wang, Rena; Solish, Nowell; Murray, Christian A

2008-12-01

Primary focal hyperhidrosis is a common and serious medical condition that causes considerable psychosocial morbidity. Diagnostic and effective management strategies can improve patients' quality of living dramatically.

Heterogeneity of Focal Adhesions and Focal Contacts in Motile Fibroblasts.

PubMed

Gladkikh, Aleena; Kovaleva, Anastasia; Tvorogova, Anna; Vorobjev, Ivan A

2018-01-01

Cell-extracellular matrix (ECM) adhesion is an important property of virtually all cells in multicellular organisms. Cell-ECM adhesion studies, therefore, are very significant both for biology and medicine. Over the last three decades, biomedical studies resulted in a tremendous advance in our understanding of the molecular basis and functions of cell-ECM adhesion. Based on morphological and molecular criteria, several different types of model cell-ECM adhesion structures including focal adhesions, focal complexes, fibrillar adhesions, podosomes, and three-dimensional matrix adhesions have been described. All the subcellular structures that mediate cell-ECM adhesion are quite heterogeneous, often varying in size, shape, distribution, dynamics, and, to a certain extent, molecular constituents. The morphological "plasticity" of cell-ECM adhesion perhaps reflects the needs of cells to sense, adapt, and respond to a variety of extracellular environments. In addition, cell type (e.g., differentiation status, oncogenic transformation, etc.) often exerts marked influence on the structure of cell-ECM adhesions. Although molecular, genetic, biochemical, and structural studies provide important maps or "snapshots" of cell-ECM adhesions, the area of research that is equally valuable is to study the heterogeneity of FA subpopulations within cells. Recently time-lapse observations on the FA dynamics become feasible, and behavior of individual FA gives additional information on cell-ECM interactions. Here we describe a robust method of labeling of FA using plasmids with fluorescent markers for paxillin and vinculin and quantifying the morphological and dynamical parameters of FA.

Focal fibrous hyperplasia: A review of 193 cases.

PubMed

de Santana Santos, Thiago; Martins-Filho, Paulo Ricardo Saquete; Piva, Marta Rabello; de Souza Andrade, Emanuel Sávio

2014-09-01

Focal fibrous hyperplasia, also known as irritation or traumatic fibroma, is a reactive, inflammatory hyperplastic lesion of the connective tissue. The aim of this study is to perform a retrospective study of a focal fibrous hyperplasia of 18 years. We retrospectively reviewed 193 cases of focal fibrous hyperplasia of the oral cavity from the medical and histological reports of the Department of Oral Pathology, Pernambuco University, Brazil, during the period between January 1992 and December 2009. Data with regard to age, gender, location, size of the lesion (equal to or less than 1 cm, between 1 and 2 cm and greater than 2 cm), pain, history of trauma, treatment, length of follow-up (from diagnosis to release or last review) and recurrence, were collected. The most commonly affected site was the buccal mucosa (n = 119, 61.7%). Almost two-thirds of the cases were concentrated from the second to the fifth decade of life. Females were more affected than men and a history of trauma was related by 90.7% of the patients. Two recurrences were notified (1.0%). Further studies are needed on the distribution of the lesion in different ethnic and geographical populations. The influence of sex hormones on the development of focal fibrous hyperplasia must be clarified.

Focal mechanism determination for induced seismicity using the neighbourhood algorithm

NASA Astrophysics Data System (ADS)

Tan, Yuyang; Zhang, Haijiang; Li, Junlun; Yin, Chen; Wu, Furong

2018-06-01

Induced seismicity is widely detected during hydraulic fracture stimulation. To better understand the fracturing process, a thorough knowledge of the source mechanism is required. In this study, we develop a new method to determine the focal mechanism for induced seismicity. Three misfit functions are used in our method to measure the differences between observed and modeled data from different aspects, including the waveform, P wave polarity and S/P amplitude ratio. We minimize these misfit functions simultaneously using the neighbourhood algorithm. Through synthetic data tests, we show the ability of our method to yield reliable focal mechanism solutions and study the effect of velocity inaccuracy and location error on the solutions. To mitigate the impact of the uncertainties, we develop a joint inversion method to find the optimal source depth and focal mechanism simultaneously. Using the proposed method, we determine the focal mechanisms of 40 stimulation induced seismic events in an oil/gas field in Oman. By investigating the results, we find that the reactivation of pre-existing faults is the main cause of the induced seismicity in the monitored area. Other observations obtained from the focal mechanism solutions are also consistent with earlier studies in the same area.

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

Focal Length Controllable Ultrasonic Transducer Using Bimorph-Type Bending Actuator

NASA Astrophysics Data System (ADS)

Chae, Min-Ku; Kim, Moo-Joon; Ha, Kang-Lyeol; Lee, Chai-Bong

2003-05-01

Using a bimorph-type bending actuator, we propose a new method for controlling the focal length of a transducer by electric DC voltage. We designed two focal length controllable ultrasonic transducers with actuators, a line-focus and a point-focus transducer. The polyvinylidene fluoride (PVDF) piezoelectric type polymer film is used for transmitting and receiving of ultrasonic signals. Using the new method, it is confirmed by investigation of the underwater acoustic field that the focal length can be controlled to within 10% of the radius of the transducer curvature.

Expression of advanced glycation end products and their cellular receptor RAGE in diabetic nephropathy and nondiabetic renal disease.

PubMed

Tanji, N; Markowitz, G S; Fu, C; Kislinger, T; Taguchi, A; Pischetsrieder, M; Stern, D; Schmidt, A M; D'Agati, V D

2000-09-01

Advanced glycation end products (AGE) contribute to diabetic tissue injury by two major mechanisms, i.e., the alteration of extracellular matrix architecture through nonenzymatic glycation, with formation of protein crosslinks, and the modulation of cellular functions through interactions with specific cell surface receptors, the best characterized of which is the receptor for AGE (RAGE). Recent evidence suggests that the AGE-RAGE interaction may also be promoted by inflammatory processes and oxidative cellular injury. To characterize the distributions of AGE and RAGE in diabetic kidneys and to determine their specificity for diabetic nephropathy, an immunohistochemical analysis of renal biopsies from patients with diabetic nephropathy (n = 26), hypertensive nephrosclerosis (n = 7), idiopathic focal segmental glomerulosclerosis (n = 11), focal sclerosis secondary to obesity (n = 7), and lupus nephritis (n = 11) and from normal control subjects (n = 2) was performed, using affinity-purified antibodies raised to RAGE and two subclasses of AGE, i.e., N(epsilon)-(carboxymethyl)-lysine (CML) and pentosidine (PENT). AGE were detected equally in diffuse and nodular diabetic nephropathy. CML was the major AGE detected in diabetic mesangium (96%), glomerular basement membranes (GBM) (42%), tubular basement membranes (85%), and vessel walls (96%). In diabetic nephropathy, PENT was preferentially located in interstitial collagen (90%) and was less consistently observed in vessel walls (54%), mesangium (77%), GBM (4%), and tubular basement membranes (31%). RAGE was expressed on normal podocytes and was upregulated in diabetic nephropathy. The restriction of RAGE mRNA expression to glomeruli was confirmed by reverse transcription-PCR analysis of microdissected renal tissue compartments. The extent of mesangial and GBM immunoreactivity for CML, but not PENT, was correlated with the severity of diabetic glomerulosclerosis, as assessed pathologically. CML and PENT were also

A 1.3 giga pixels focal plane for GAIA

NASA Astrophysics Data System (ADS)

Laborie, Anouk; Pouny, Pierre; Vetel, Cyril; Collados, Emmanuel; Rougier, Gilles; Davancens, Robert; Zayer, Igor; Perryman, Michael; Pace, Oscar

2004-06-01

The astrometric mission GAIA is a cornerstone mission of the European Space Agency, due for launch in the 2010 time frame. Requiring extremely demanding performance GAIA calls for the development of an unprecedented large focal plane featuring innovative technologies. For securing the very challenging GAIA development, a significant number of technology activities have been initiated by ESA through a competitive selection process. In this context, an industrial consortium led by EADS-Astrium (France) with e2v technologies (UK) as major subcontractor was selected for the GAIA CCD and Focal Plane Technology Demonstrators programme, which is by far the most significant and the most critical GAIA pre-development for all aspects: science performance, development schedule and cost. This programme has started since August 2002 and will end early 2005 prior to commencement of the GAIA Phase B. While the GAIA payload will host three instruments and related focal planes, the major mission objectives are assigned to the Astrometric (ASTRO) Focal Plane, which is the subject of this presentation.

The challenge of diagnosing focal hand dystonia in musicians.

PubMed

Rosset-Llobet, J; Candia, V; Fàbregas i Molas, S; Dolors Rosinés i Cubells, D; Pascual-Leone, A

2009-07-01

To most clinicians, medical problems in musicians, particularly those concerning focal hand dystonia, constitute an unfamiliar domain difficult to manage. The latter can importantly influence diagnostics and the course of treatment. The purpose of this study was to enlighten the issue and to identify possible problems in diagnosing musicians' cramp within the Spanish medical community. We used a brief questions' catalog and clinical histories of 665 musicians seen at our clinic for performing artists. We analyzed patients' diagnosis records in 87 cases of focal hand dystonia (13.1%). In so doing, we surveyed previous diagnoses and diverse treatments prescriptions prior to referral to our clinic. Referrals came primarily from orthopaedists and neurologists. The 52.9% arrived at our clinic without a diagnosis or a suspicion of suffering from focal dystonia. The most frequently attempted diagnoses other than musicians' dystonia included nerve compression, tendonitis and trigger fingers. Commonly prescribed treatments included rest, various surgical procedures, physiotherapy and oral anti-inflammatory medication. This data depicts the diagnostic challenges of medical professionals may encounter when confronted with musician's focal dystonia.

Surface nanoporosity has a greater influence on osteogenic and bacterial cell adhesion than crystallinity and wettability

NASA Astrophysics Data System (ADS)

Rodriguez-Contreras, Alejandra; Guadarrama Bello, Dainelys; Nanci, Antonio

2018-07-01

There has been much emphasis on the influence of crystallinity and wettability for modulating cell activity, particularly for bone biomaterials. In this context, we have generated titanium oxide layers with similar mesoporous topography and surface roughness but with amorphous or crystalline oxide layers and differential wettability. We then investigated their influence on the behavior of MC3T3 osteoblastic and bacterial cells. There was no difference in cell adhesion, spreading and growth on amorphous and crystalline surfaces. The number of focal adhesions was similar, however, cells on the amorphous surface exhibited a higher frequency of mature adhesions. The crystallinity of the surface layers also had no bearing on bacterial adhesion. While it cannot be excluded that surface crystallinity, roughness and wettability contribute to some degree to determining cell behavior, our data suggest that physical characteristics of surfaces represent the major determinant.

anisotropic microseismic focal mechanism inversion by waveform imaging matching

NASA Astrophysics Data System (ADS)

Wang, L.; Chang, X.; Wang, Y.; Xue, Z.

2016-12-01

The focal mechanism is one of the most important parameters in source inversion, for both natural earthquakes and human-induced seismic events. It has been reported to be useful for understanding stress distribution and evaluating the fracturing effect. The conventional focal mechanism inversion method picks the first arrival waveform of P wave. This method assumes the source as a Double Couple (DC) type and the media isotropic, which is usually not the case for induced seismic focal mechanism inversion. For induced seismic events, the inappropriate source and media model in inversion processing, by introducing ambiguity or strong simulation errors, will seriously reduce the inversion effectiveness. First, the focal mechanism contains significant non-DC source type. Generally, the source contains three components: DC, isotropic (ISO) and the compensated linear vector dipole (CLVD), which makes focal mechanisms more complicated. Second, the anisotropy of media will affect travel time and waveform to generate inversion bias. The common way to describe focal mechanism inversion is based on moment tensor (MT) inversion which can be decomposed into the combination of DC, ISO and CLVD components. There are two ways to achieve MT inversion. The wave-field migration method is applied to achieve moment tensor imaging. This method can construct elements imaging of MT in 3D space without picking the first arrival, but the retrieved MT value is influenced by imaging resolution. The full waveform inversion is employed to retrieve MT. In this method, the source position and MT can be reconstructed simultaneously. However, this method needs vast numerical calculation. Moreover, the source position and MT also influence each other in the inversion process. In this paper, the waveform imaging matching (WIM) method is proposed, which combines source imaging with waveform inversion for seismic focal mechanism inversion. Our method uses the 3D tilted transverse isotropic (TTI) elastic

Mechanical design and analysis of focal plate for gravity deformation

NASA Astrophysics Data System (ADS)

Wang, Jianping; Chu, Jiaru; Hu, Hongzhuan; Li, Kexuan; Zhou, Zengxiang

2014-07-01

The surface accuracy of astronomical telescope focal plate is a key indicator to precision stellar observation. To conduct accurate deformation measurement for focal plate in different status, a 6-DOF hexapod platform was used for attitude adjustment. For the small adjustment range of a classic 6-DOF hexapod platform, an improved structural arrangement method was proposed in the paper to achieve ultimate adjustment of the focal plate in horizontal and vertical direction. To validate the feasibility of this method, an angle change model which used ball hinge was set up for the movement and base plate. Simulation results in MATLAB suggested that the ball hinge angle change of movement and base plate is within the range of the limiting angle in the process of the platform plate adjusting to ultimate attitude. The proposed method has some guiding significance for accurate surface measurement of focal plate.

Familial aggregation of focal seizure semiology in the Epilepsy Phenome/Genome Project.

PubMed

Tobochnik, Steven; Fahlstrom, Robyn; Shain, Catherine; Winawer, Melodie R

2017-07-04

To improve phenotype definition in genetic studies of epilepsy, we assessed the familial aggregation of focal seizure types and of specific seizure symptoms within the focal epilepsies in families from the Epilepsy Phenome/Genome Project. We studied 302 individuals with nonacquired focal epilepsy from 149 families. Familial aggregation was assessed by logistic regression analysis of relatives' traits (dependent variable) by probands' traits (independent variable), estimating the odds ratio for each symptom in a relative given presence vs absence of the symptom in the proband. In families containing multiple individuals with nonacquired focal epilepsy, we found significant evidence for familial aggregation of ictal motor, autonomic, psychic, and aphasic symptoms. Within these categories, ictal whole body posturing, diaphoresis, dyspnea, fear/anxiety, and déjà vu/jamais vu showed significant familial aggregation. Focal seizure type aggregated as well, including complex partial, simple partial, and secondarily generalized tonic-clonic seizures. Our results provide insight into genotype-phenotype correlation in the nonacquired focal epilepsies and a framework for identifying subgroups of patients likely to share susceptibility genes. © 2017 American Academy of Neurology.

Renal transplantation in lupus nephritis: a Brazilian cohort.

PubMed

Oliveira, C S; d Oliveira, I; Bacchiega, A B S; Klumb, E M; Albuquerque, E M M; Souza, E; Suassuna, J H S; Ribeiro, F M

2012-04-01

To determine the epidemiological profile and outcome of patients with lupus nephritis (LN) undergoing renal transplantation. The archival records of 50 patients with LN and end-stage renal disease (ESRD) treated by kidney transplantation from March 1992 to December 2010 were reviewed. All patients met the American College of Rheumatology criteria for systemic lupus erythematosus (SLE). Fourteen patients were included in the study. The majority were women (85.7%) and non-Caucasian (85.7%); the mean age at diagnosis of SLE and LN was 24 ± 8 and 25 ± 8 years, respectively. Renal biopsy was performed in 12 patients, with 75% of them showing proliferative lesions (class III and IV according to the World Health Organization and International Society of Nephrology/Renal Pathology Society classification). Thirteen patients (93%) underwent intermittent hemodialysis or peritoneal dialysis before transplantation. The median time between the start of dialysis and transplantation was 30 months (range 3-103 months); 67% of the procedures involved deceased donors and 33% involved living-related donors. The graft survival rates were 93.3%, 90.9%, and 85.7% at 1, 5 and 10 years, respectively. Post-transplant immunosuppressive agents were mycophenolate mofetil (84%), azathioprine (17%), tacrolimus (25%), sirolimus (58%) and cyclosporine (8%). Eight episodes of acute rejection were noted in six patients. There was a graft loss due to renal vein thrombosis in the one patient with secondary antiphospholipid syndrome. The mean SLICC by the time of kidney transplantation was 5 ± 2. In total, 13 patients (92.8%) developed at least one infectious event during the follow-up, with one dying in the immediate post-transplant period because of sepsis. Two patients (14%) had a lupus flare. There was no clinical or histological evidence of LN recurrence. LN is the major cause of morbidity in SLE, with progression to ESRD in 10-22% of cases. Despite concerns about LN recurrence

Alignment of x-ray tube focal spots for spectral measurement.

PubMed

Nishizawa, K; Maekoshi, H; Kamiya, Y; Kobayashi, Y; Ohara, K; Sakuma, S

1982-01-01

A general method to align a diagnostic x-ray machine for x-ray spectrum measurement purpose was theoretically and experimentally investigated by means of the optical alignment of focal pinhole images. Focal pinhole images were obtained by using a multi-pinholed lead plate. the vertical plane, including the central axis and tube axis, was decided upon by observing the symmetry of focal images. the central axis was designated as a line through the center of focus parallel to the target surface lying in the vertical plane. A method to determine the manipulation of the central axis in any direction is presented.

EEG dynamical correlates of focal and diffuse causes of coma.

PubMed

Kafashan, MohammadMehdi; Ryu, Shoko; Hargis, Mitchell J; Laurido-Soto, Osvaldo; Roberts, Debra E; Thontakudi, Akshay; Eisenman, Lawrence; Kummer, Terrance T; Ching, ShiNung

2017-11-15

Rapidly determining the causes of a depressed level of consciousness (DLOC) including coma is a common clinical challenge. Quantitative analysis of the electroencephalogram (EEG) has the potential to improve DLOC assessment by providing readily deployable, temporally detailed characterization of brain activity in such patients. While used commonly for seizure detection, EEG-based assessment of DLOC etiology is less well-established. As a first step towards etiological diagnosis, we sought to distinguish focal and diffuse causes of DLOC through assessment of temporal dynamics within EEG signals. We retrospectively analyzed EEG recordings from 40 patients with DLOC with consensus focal or diffuse culprit pathology. For each recording, we performed a suite of time-series analyses, then used a statistical framework to identify which analyses (features) could be used to distinguish between focal and diffuse cases. Using cross-validation approaches, we identified several spectral and non-spectral EEG features that were significantly different between DLOC patients with focal vs. diffuse etiologies, enabling EEG-based classification with an accuracy of 76%. Our findings suggest that DLOC due to focal vs. diffuse injuries differ along several electrophysiological parameters. These results may form the basis of future classification strategies for DLOC and coma that are more etiologically-specific and therefore therapeutically-relevant.

Focal fibrous hyperplasia: A review of 193 cases

PubMed Central

de Santana Santos, Thiago; Martins-Filho, Paulo Ricardo Saquete; Piva, Marta Rabello; de Souza Andrade, Emanuel Sávio

2014-01-01

Context: Focal fibrous hyperplasia, also known as irritation or traumatic fibroma, is a reactive, inflammatory hyperplastic lesion of the connective tissue. Aim: The aim of this study is to perform a retrospective study of a focal fibrous hyperplasia of 18 years. Materials and Methods: We retrospectively reviewed 193 cases of focal fibrous hyperplasia of the oral cavity from the medical and histological reports of the Department of Oral Pathology, Pernambuco University, Brazil, during the period between January 1992 and December 2009. Settings and Design: Data with regard to age, gender, location, size of the lesion (equal to or less than 1 cm, between 1 and 2 cm and greater than 2 cm), pain, history of trauma, treatment, length of follow-up (from diagnosis to release or last review) and recurrence, were collected. Results: The most commonly affected site was the buccal mucosa (n = 119, 61.7%). Almost two-thirds of the cases were concentrated from the second to the fifth decade of life. Females were more affected than men and a history of trauma was related by 90.7% of the patients. Two recurrences were notified (1.0%). Conclusion: Further studies are needed on the distribution of the lesion in different ethnic and geographical populations. The influence of sex hormones on the development of focal fibrous hyperplasia must be clarified. PMID:25364187

[Focal myositis: An unknown disease].

PubMed

Gallay, L; Streichenberger, N; Benveniste, O; Allenbach, Y

2017-10-01

Focal myositis are inflammatory muscle diseases of unknown origin. At the opposite from the other idiopathic inflammatory myopathies, they are restricted to a single muscle or to a muscle group. They are not associated with extramuscular manifestations, and they have a good prognosis without any treatment. They are characterized by a localized swelling affecting mostly lower limbs. The pseudo-tumor can be painful, but is not associated with a muscle weakness. Creatine kinase level is normal. Muscle MRI shows an inflammation restricted to a muscle or a muscle group. Muscle biopsy and pathological analysis remain necessary for the diagnosis, showing inflammatory infiltrates composed by macrophages and lymphocytes without any specific distribution within the muscle. Focal overexpression of HLA-1 by the muscle fibers is frequently observed. The muscle biopsy permits to rule out differential diagnosis such a malignancy (sarcoma). Spontaneous remission occurs within weeks or months after the first symptoms, relapse is unusual. Copyright © 2017. Published by Elsevier SAS.

Focal spot motion of linear accelerators and its effect on portal image analysis.

PubMed

Sonke, Jan-Jakob; Brand, Bob; van Herk, Marcel

2003-06-01

The focal spot of a linear accelerator is often considered to have a fully stable position. In practice, however, the beam control loop of a linear accelerator needs to stabilize after the beam is turned on. As a result, some motion of the focal spot might occur during the start-up phase of irradiation. When acquiring portal images, this motion will affect the projected position of anatomy and field edges, especially when low exposures are used. In this paper, the motion of the focal spot and the effect of this motion on portal image analysis are quantified. A slightly tilted narrow slit phantom was placed at the isocenter of several linear accelerators and images were acquired (3.5 frames per second) by means of an amorphous silicon flat panel imager positioned approximately 0.7 m below the isocenter. The motion of the focal spot was determined by converting the tilted slit images to subpixel accurate line spread functions. The error in portal image analysis due to focal spot motionwas estimated by a subtraction of the relative displacement of the projected slit from the relative displacement of the field edges. It was found that the motion of the focal spot depends on the control system and design of the accelerator. The shift of the focal spot at the start of irradiation ranges between 0.05-0.7 mm in the gun-target (GT) direction. In the left-right (AB) direction the shift is generally smaller. The resulting error in portal image analysis due to focal spotmotion ranges between 0.05-1.1 mm for a dose corresponding to two monitor units (MUs). For 20 MUs, the effect of the focal spot motion reduces to 0.01-0.3 mm. The error in portal image analysis due to focal spot motion can be reduced by reducing the applied dose rate.

Focal myositis of lower extremity responsive to botulinum A toxin.

PubMed

Mitrovic, Josko; Prka, Zeljko; Zic, Rado; Marusic, Srecko; Morovic-Vergles, Jadranka

2014-01-01

Focal myositis is a rare, mostly benign disease (pseudotumor) of skeletal muscle, histopathologically characterized by interstitial myositis and tumorous enlargement of a single muscle. The etiology of focal myositis remains unknown; however, localized myopathy has been postulated to be caused by denervation lesions. This case report describes a patient that presented with clinical, laboratory, electromyoneurography, and magnetic resonance imaging features of focal myositis complicated with intervertebral disk protrusion in the lumbosacral spine affected with radicular distress. In most cases, focal myositic lesions show spontaneous regression, relapses are rare, and long-term prognosis is good. There is a wide spectrum of therapeutic options, from no therapy at all through nonsteroidal antirheumatics and glucocorticoids to radiotherapy, surgical excision, and immunosuppressants. In the patient presented, treatment with glucocorticoids, methotrexate, and surgical excision failed to produce satisfactory results. Clinical improvement, pain relief, and reduction in lower leg volume were only achieved by local infiltration of botulinum A toxin.

The challenge of diagnosing focal hand dystonia in musicians

PubMed Central

Rosset-Llobet, J.; Candia, V.; Molas, S. Fàbregas i; Dolors Rosinés i Cubells, D.; Pascual-Leone, A.

2012-01-01

Background and purpose To most clinicians, medical problems in musicians, particularly those concerning focal hand dystonia, constitute an unfamiliar domain difficult to manage. The latter can importantly influence diagnostics and the course of treatment. The purpose of this study was to enlighten the issue and to identify possible problems in diagnosing musicians’ cramp within the Spanish medical community. Methods We used a brief questions’ catalog and clinical histories of 665 musicians seen at our clinic for performing artists. We analyzed patients’ diagnosis records in 87 cases of focal hand dystonia (13.1%). In so doing, we surveyed previous diagnoses and diverse treatments prescriptions prior to referral to our clinic. Results Referrals came primarily from orthopaedists and neurologists. The 52.9% arrived at our clinic without a diagnosis or a suspicion of suffering from focal dystonia. The most frequently attempted diagnoses other than musicians’ dystonia included nerve compression, tendonitis and trigger fingers. Commonly prescribed treatments included rest, various surgical procedures, physiotherapy and oral anti-inflammatory medication. Conclusions This data depicts the diagnostic challenges of medical professionals may encounter when confronted with musician’s focal dystonia. PMID:19473363

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

PubMed Central

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

2015-01-01

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

Focal depth measurement of scanning helium ion microscope

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

Guo, Hongxuan, E-mail: Guo.hongxuan@nims.go.jp; Itoh, Hiroshi; Wang, Chunmei

2014-07-14

When facing the challenges of critical dimension measurement of complicated nanostructures, such as of the three dimension integrated circuit, characterization of the focal depth of microscopes is important. In this Letter, we developed a method for characterizing the focal depth of a scanning helium ion microscope (HIM) by using an atomic force microscope tip characterizer (ATC). The ATC was tilted in a sample chamber at an angle to the scanning plan. Secondary electron images (SEIs) were obtained at different positions of the ATC. The edge resolution of the SEIs shows the nominal diameters of the helium ion beam at differentmore » focal levels. With this method, the nominal shapes of the helium ion beams were obtained with different apertures. Our results show that a small aperture is necessary to get a high spatial resolution and high depth of field images with HIM. This work provides a method for characterizing and improving the performance of HIM.« less

Focal depth measurement of scanning helium ion microscope

NASA Astrophysics Data System (ADS)

Guo, Hongxuan; Itoh, Hiroshi; Wang, Chunmei; Zhang, Han; Fujita, Daisuke

2014-07-01

When facing the challenges of critical dimension measurement of complicated nanostructures, such as of the three dimension integrated circuit, characterization of the focal depth of microscopes is important. In this Letter, we developed a method for characterizing the focal depth of a scanning helium ion microscope (HIM) by using an atomic force microscope tip characterizer (ATC). The ATC was tilted in a sample chamber at an angle to the scanning plan. Secondary electron images (SEIs) were obtained at different positions of the ATC. The edge resolution of the SEIs shows the nominal diameters of the helium ion beam at different focal levels. With this method, the nominal shapes of the helium ion beams were obtained with different apertures. Our results show that a small aperture is necessary to get a high spatial resolution and high depth of field images with HIM. This work provides a method for characterizing and improving the performance of HIM.

Focal adhesions, stress fibers and mechanical tension

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

Burridge, Keith, E-mail: Keith_Burridge@med.unc.edu; Guilluy, Christophe, E-mail: christophe.guilluy@univ-nantes.fr

Stress fibers and focal adhesions are complex protein arrays that produce, transmit and sense mechanical tension. Evidence accumulated over many years led to the conclusion that mechanical tension generated within stress fibers contributes to the assembly of both stress fibers themselves and their associated focal adhesions. However, several lines of evidence have recently been presented against this model. Here we discuss the evidence for and against the role of mechanical tension in driving the assembly of these structures. We also consider how their assembly is influenced by the rigidity of the substratum to which cells are adhering. Finally, we discussmore » the recently identified connections between stress fibers and the nucleus, and the roles that these may play, both in cell migration and regulating nuclear function. - Highlights: • The different types of stress fiber and focal adhesion are described. • We discuss the controversy about tension and assembly of these structures. • We describe the different models used to investigate assembly of these structures. • The influence of substratum rigidity is discussed. • Stress fiber connections to the nucleus are reviewed.« less

Super-resolution links vinculin localization to function in focal adhesions.

PubMed

Giannone, Grégory

2015-07-01

Integrin-based focal adhesions integrate biochemical and biomechanical signals from the extracellular matrix and the actin cytoskeleton. The combination of three-dimensional super-resolution imaging and loss- or gain-of-function protein mutants now links the nanoscale dynamic localization of proteins to their activation and function within focal adhesions.

Focal length hysteresis of a double-liquid lens based on electrowetting

NASA Astrophysics Data System (ADS)

Peng, Runling; Wang, Dazhen; Hu, Zhiwei; Chen, Jiabi; Zhuang, Songlin

2013-02-01

In this paper, an extended Young equation especially suited for an ideal cylindrical double-liquid variable-focus lens is derived by means of an energy minimization method. Based on the extended Young equation, a kind of focal length hysteresis effect is introduced into the double-liquid variable-focus lens. Such an effect can be explained theoretically by adding a force of friction to the tri-phase contact line. Theoretical analysis shows that the focal length at a particular voltage can be different depending on whether the applied voltage is increasing or decreasing, that is, there is a focal length hysteresis effect. Moreover, the focal length at a particular voltage must be larger when the voltage is rising than when it is dropping. These conclusions are also verified by experiments.

Extensive Focal Epithelial Hyperplasia: A Case Report.

PubMed

Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

2015-01-01

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

[Antiperspirants for the therapy of focal hyperhidrosis].

PubMed

Streker, M; Kerscher, M

2012-06-01

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

Long-term survival of kidney grafts in lupus nephritis: a Mexican cohort.

PubMed

Ramirez-Sandoval, J C; Chavez-Chavez, H; Wagner, M; Vega-Vega, O; Morales-Buenrostro, L E; Correa-Rotter, R

2018-07-01

Kidney transplant for patients with lupus nephritis (LN) has satisfactory outcomes in studies with short-term or mid-term follow up. Nevertheless, information about long-term outcomes is scarce. We performed a retrospective matched-pair cohort study in 74 LN recipients compared with 148 non-LN controls matched by age, sex, immunosuppressive treatment, human leukocyte antigen (HLA) matches, and transplant period in order to evaluate long-term outcomes of kidney transplant in LN recipients. Matched pairs were predominantly females (83%), median age at transplant surgery of 32 years (interquartile range 23-38 years), and 66% received a graft from a living related donor. Among LN recipients, 5-, 10-, 15-, and 20-year graft survival was 81%, 79%, 57% and 51%, respectively, and it was similar to that observed in controls (89%, 78%, 64%, and 56%, respectively). Graft loss (27% vs. 21%, p = 0.24) and overall survival ( p = 0.15) were not different between LN recipients and controls. Also, there was no difference in episodes of immunological rejection, thrombosis, or infection. Only six LN recipients had biopsy-proven lupus recurrence and three of them had graft loss. In a cohort with a long follow up of kidney transplant recipients, LN recipients had similar long-term graft survival and overall outcomes compared with non-lupus recipients when predictors are matched between groups.

Determination of the paraxial focal length using Zernike polynomials over different apertures

NASA Astrophysics Data System (ADS)

Binkele, Tobias; Hilbig, David; Henning, Thomas; Fleischmann, Friedrich

2017-02-01

The paraxial focal length is still the most important parameter in the design of a lens. As presented at the SPIE Optics + Photonics 2016, the measured focal length is a function of the aperture. The paraxial focal length can be found when the aperture approaches zero. In this work, we investigate the dependency of the Zernike polynomials on the aperture size with respect to 3D space. By this, conventional wavefront measurement systems that apply Zernike polynomial fitting (e.g. Shack-Hartmann-Sensor) can be used to determine the paraxial focal length, too. Since the Zernike polynomials are orthogonal over a unit circle, the aperture used in the measurement has to be normalized. By shrinking the aperture and keeping up with the normalization, the Zernike coefficients change. The relation between these changes and the paraxial focal length are investigated. The dependency of the focal length on the aperture size is derived analytically and evaluated by simulation and measurement of a strong focusing lens. The measurements are performed using experimental ray tracing and a Shack-Hartmann-Sensor. Using experimental ray tracing for the measurements, the aperture can be chosen easily. Regarding the measurements with the Shack-Hartmann- Sensor, the aperture size is fixed. Thus, the Zernike polynomials have to be adapted to use different aperture sizes by the proposed method. By doing this, the paraxial focal length can be determined from the measurements in both cases.

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

PubMed Central

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

2016-01-01

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

Quantum-Well Infrared Photodetector (QWIP) Focal Plane Assembly

NASA Technical Reports Server (NTRS)

Jhabvala, Murzy; Jhabvala, Christine A.; Ewin, Audrey J.; Hess, Larry A.; Hartmann, Thomas M.; La, Anh T.

2012-01-01

A paper describes the Thermal Infrared Sensor (TIRS), a QWIP-based instrument intended to supplement the Operational Land Imager (OLI) for the Landsat Data Continuity Mission (LDCM). The TIRS instrument is a far-infrared imager operating in the pushbroom mode with two IR channels: 10.8 and 12 microns. The focal plane will contain three 640x512 QWIP arrays mounted on a silicon substrate. The silicon substrate is a custom-fabricated carrier board with a single layer of aluminum interconnects. The general fabrication process starts with a 4-in. (approx.10-cm) diameter silicon wafer. The wafer is oxidized, a single substrate contact is etched, and aluminum is deposited, patterned, and alloyed. This technology development is aimed at incorporating three large-format infrared detecting arrays based on GaAs QWIP technology onto a common focal plane with precision alignment of all three arrays. This focal plane must survive the rigors of flight qualification and operate at a temperature of 43 K (-230 C) for five years while orbiting the Earth. The challenges presented include ensuring thermal compatibility among all the components, designing and building a compact, somewhat modular system and ensuring alignment to very tight levels. The multi-array focal plane integrated onto a single silicon substrate is a new application of both QWIP array development and silicon wafer scale integration. The Invar-based assembly has been tested to ensure thermal reliability.

Genetics Home Reference: focal dermal hypoplasia

MedlinePlus

... in people with focal dermal hypoplasia is an omphalocele , which is an opening in the wall of ... Dermal Hypoplasia MedlinePlus Encyclopedia: Ectodermal dysplasia MedlinePlus Encyclopedia: Omphalocele General Information from MedlinePlus (5 links) Diagnostic Tests ...

Performance of an Achromatic Focal Plane Mask for Exoplanet Imaging Coronagraphy

NASA Technical Reports Server (NTRS)

Newman, Kevin; Belikov, Ruslan; Pluzhnik, Eugene; Balasubramanian, Kunjithapatham; Wilson, Dan

2014-01-01

Coronagraph technology combined with wavefront control is close to achieving the contrast and inner working angle requirements in the lab necessary to observe the faint signal of an Earth-like exoplanet in monochromatic light. An important remaining technological challenge is to achieve high contrast in broadband light. Coronagraph bandwidth is largely limited by chromaticity of the focal plane mask, which is responsible for blocking the stellar PSF. The size of a stellar PSF scales linearly with wavelength; ideally, the size of the focal plane mask would also scale with wavelength. A conventional hard-edge focal plane mask has a fixed size, normally sized for the longest wavelength in the observational band to avoid starlight leakage. The conventional mask is oversized for shorter wavelengths and blocks useful discovery space. Recently we presented a solution to the size chromaticity challenge with a focal plane mask designed to scale its effective size with wavelength. In this paper, we analyze performance of the achromatic size-scaling focal plane mask within a Phase Induced Amplitude Apodization (PIAA) coronagraph. We present results from wavefront control around the achromatic focal plane mask, and demonstrate the size-scaling effect of the mask with wavelength. The edge of the dark zone, and therefore the inner working angle of the coronagraph, scale with wavelength. The achromatic mask enables operation in a wider band of wavelengths compared with a conventional hard-edge occulter.

Butterfly Wings Are Three-Dimensional: Pupal Cuticle Focal Spots and Their Associated Structures in Junonia Butterflies.

PubMed

Taira, Wataru; Otaki, Joji M

2016-01-01

Butterfly wing color patterns often contain eyespots, which are developmentally determined at the late larval and early pupal stages by organizing activities of focal cells that can later form eyespot foci. In the pupal stage, the focal position of a future eyespot is often marked by a focal spot, one of the pupal cuticle spots, on the pupal surface. Here, we examined the possible relationships of the pupal focal spots with the underneath pupal wing tissues and with the adult wing eyespots using Junonia butterflies. Large pupal focal spots were found in two species with large adult eyespots, J. orithya and J. almana, whereas only small pupal focal spots were found in a species with small adult eyespots, J. hedonia. The size of five pupal focal spots on a single wing was correlated with the size of the corresponding adult eyespots in J. orithya. A pupal focal spot was a three-dimensional bulge of cuticle surface, and the underside of the major pupal focal spot exhibited a hollowed cuticle in a pupal case. Cross sections of a pupal wing revealed that the cuticle layer shows a curvature at a focal spot, and a positional correlation was observed between the cuticle layer thickness and its corresponding cell layer thickness. Adult major eyespots of J. orithya and J. almana exhibited surface elevations and depressions that approximately correspond to the coloration within an eyespot. Our results suggest that a pupal focal spot is produced by the organizing activity of focal cells underneath the focal spot. Probably because the focal cell layer immediately underneath a focal spot is thicker than that of its surrounding areas, eyespots of adult butterfly wings are three-dimensionally constructed. The color-height relationship in adult eyespots might have an implication in the developmental signaling for determining the eyespot color patterns.

Butterfly Wings Are Three-Dimensional: Pupal Cuticle Focal Spots and Their Associated Structures in Junonia Butterflies

PubMed Central

Taira, Wataru; Otaki, Joji M.

2016-01-01

Butterfly wing color patterns often contain eyespots, which are developmentally determined at the late larval and early pupal stages by organizing activities of focal cells that can later form eyespot foci. In the pupal stage, the focal position of a future eyespot is often marked by a focal spot, one of the pupal cuticle spots, on the pupal surface. Here, we examined the possible relationships of the pupal focal spots with the underneath pupal wing tissues and with the adult wing eyespots using Junonia butterflies. Large pupal focal spots were found in two species with large adult eyespots, J. orithya and J. almana, whereas only small pupal focal spots were found in a species with small adult eyespots, J. hedonia. The size of five pupal focal spots on a single wing was correlated with the size of the corresponding adult eyespots in J. orithya. A pupal focal spot was a three-dimensional bulge of cuticle surface, and the underside of the major pupal focal spot exhibited a hollowed cuticle in a pupal case. Cross sections of a pupal wing revealed that the cuticle layer shows a curvature at a focal spot, and a positional correlation was observed between the cuticle layer thickness and its corresponding cell layer thickness. Adult major eyespots of J. orithya and J. almana exhibited surface elevations and depressions that approximately correspond to the coloration within an eyespot. Our results suggest that a pupal focal spot is produced by the organizing activity of focal cells underneath the focal spot. Probably because the focal cell layer immediately underneath a focal spot is thicker than that of its surrounding areas, eyespots of adult butterfly wings are three-dimensionally constructed. The color-height relationship in adult eyespots might have an implication in the developmental signaling for determining the eyespot color patterns. PMID:26731532

System and method for generating a deselect mapping for a focal plane array

DOEpatents

Bixler, Jay V; Brandt, Timothy G; Conger, James L; Lawson, Janice K

2013-05-21

A method for generating a deselect mapping for a focal plane array according to one embodiment includes gathering a data set for a focal plane array when exposed to light or radiation from a first known target; analyzing the data set for determining which pixels or subpixels of the focal plane array to add to a deselect mapping; adding the pixels or subpixels to the deselect mapping based on the analysis; and storing the deselect mapping. A method for gathering data using a focal plane array according to another embodiment includes deselecting pixels or subpixels based on a deselect mapping; gathering a data set using pixels or subpixels in a focal plane array that are not deselected upon exposure thereof to light or radiation from a target of interest; and outputting the data set.

Multicolor megapixel QWIP focal plane arrays for remote sensing instruments

NASA Astrophysics Data System (ADS)

Gunapala, S. D.; Bandara, S. V.; Liu, J. K.; Hill, C. J.; Rafol, S. B.; Mumolo, J. M.; Trinh, J. T.; Tidrow, M. Z.; LeVan, P. D.

2006-08-01

Mid-wavelength infrared (MWIR) and long-wavelength infrared (LWIR) 1024x1024 pixel quantum well infrared photodetector (QWIP) focal planes have been demonstrated with excellent imaging performance. The MWIR QWIP detector array has demonstrated a noise equivalent differential temperature (NEΔT) of 17 mK at a 95K operating temperature with f/2.5 optics at 300K background and the LWIR detector array has demonstrated a NEΔT of 13 mK at a 70K operating temperature with the same optical and background conditions as the MWIR detector array after the subtraction of system noise. Both MWIR and LWIR focal planes have shown background limited performance (BLIP) at 90K and 70K operating temperatures respectively, with similar optical and background conditions. In addition, we have demonstrated MWIR and LWIR pixel co-registered simultaneously readable dualband QWIP focal plane arrays. In this paper, we will discuss the performance in terms of quantum efficiency, NEΔT, uniformity, operability, and modulation transfer functions of the 1024x1024 pixel arrays and the progress of dualband QWIP focal plane array development work.

A case of pathological rib fractures: focal osteolysis or osteoporosis?

PubMed

Vrbanić, T S L; Novak, S; Sestan, B; Tudor, A; Gulan, G

2008-03-01

This paper reports on a unique, previously unreported, successful outcome in the case of a patient with focal osteolytic lesions of the ribs as a first sign of osteoporosis. The lesions were detected by chance after acute cough-induced rib fractures were seen on plain chest radiographs. The diagnosis had to be approached as a diagnosis of exclusion since known causes of the osteolytic process had to be eliminated. The authors describe multiple focal osteolytic lesions with rib fractures appearing in a pattern that could be confused with metastases. Laboratory results were normal. Final diagnosis was based on plain radiography, bone scan and bone densitometry. Pharmacomedical treatments for osteoporosis were applied. The patient was observed between the year 2000 and 2005. Five years later radiological and bone scintigraphy revealed resolution of the lesion. We conclude that osteoporosis should be included in the differential diagnosis of asymptomatic focal osteolysis of the ribs with rib fractures as a complication of acute cough. The case suggests that focal osteolytic lesions of the ribs may regress over time and become scintigraphically inactive.

Out-of-focal plane imaging by leakage radiation microscopy

NASA Astrophysics Data System (ADS)

Zhu, Liangfu; Zhang, Douguo; Wang, Ruxue; Wen, Xiaolei; Wang, Pei; Ming, Hai; Badugu, Ramachandram; Lakowicz, Joseph R.

2017-09-01

Leakage radiation microscopy (LRM) is used to investigate the optical properties of surfaces. The front-focal plane (FFP) image with LRM reveals the structural features on the surfaces. A back-focal plane (BFP) image with LRM reveals the angular distribution of the radiation. Herein, we experimentally demonstrate that the out-of-focal plane (OFP) images present a link between the FFP and BFP images and provide optical information that cannot be resolved by either FFP or BFP images. The OFP image provides a link between the spatial location of the emission and the angular distribution from the same location, and thus information about the film’s discontinuity, nonuniformity or variable thickness can be uncovered. The use of OFP imaging will extend the scope and applications of the LRM and coupled emission imaging, which are powerful tools in nanophotonics and high throughput fluorescence screening.

The cheating liver: imaging of focal steatosis and fatty sparing.

PubMed

Dioguardi Burgio, Marco; Bruno, Onorina; Agnello, Francesco; Torrisi, Chiara; Vernuccio, Federica; Cabibbo, Giuseppe; Soresi, Maurizio; Petta, Salvatore; Calamia, Mauro; Papia, Giovanni; Gambino, Angelo; Ricceri, Viola; Midiri, Massimo; Lagalla, Roberto; Brancatelli, Giuseppe

2016-06-01

Focal steatosis and fatty sparing are a frequent finding in liver imaging, and can mimic solid lesions. Liver regional variations in the degree of fat accumulation can be related to vascular anomalies, metabolic disorders, use of certain drugs or coexistence of hepatic masses. CT and MRI are the modalities of choice for the noninvasive diagnosis of hepatic steatosis. Knowledge of CT and MRI appearance of focal steatosis and fatty sparing is crucial for an accurate diagnosis, and to rule-out other pathologic processes. This paper will review the CT and MRI techniques for the diagnosis of hepatic steatosis and the CT and MRI features of common and uncommon causes of focal steatosis and fatty sparing.

Simulation of the Focal Spot of the Accelerator Bremsstrahlung Radiation

NASA Astrophysics Data System (ADS)

Sorokin, V.; Bespalov, V.

2016-06-01

Testing of thick-walled objects by bremsstrahlung radiation (BR) is primarily performed via high-energy quanta. The testing parameters are specified by the focal spot size of the high-energy bremsstrahlung radiation. In determining the focal spot size, the high- energy BR portion cannot be experimentally separated from the low-energy BR to use high- energy quanta only. The patterns of BR focal spot formation have been investigated via statistical modeling of the radiation transfer in the target material. The distributions of BR quanta emitted by the target for different energies and emission angles under normal distribution of the accelerated electrons bombarding the target have been obtained, and the ratio of the distribution parameters has been determined.

Visible and shortwave infrared focal planes for remote sensing instruments

NASA Astrophysics Data System (ADS)

Tower, J. R.; McCarthy, B. M.; Pellon, L. E.; Strong, R. T.; Elabd, H.

1984-01-01

The development of solid-state sensor technology for multispectral linear array (MLA) instruments is described. A buttable four-spectral-band linear-format CCD and a buttable two-spectral band linear-format short-wave IR CCD have been designed, and first samples have been demonstrated. In addition, first-sample four-band interference filters have been fabricated, and hybrid packaging technology is being developed. Based on this development work, the design and construction of focal planes for a Shuttle sortie MLA instrument have begun. This work involves a visible and near-IR focal plane with 2048 pixels x 4 spectral bands and a short-wave IR focal plane with 1024 pixels x 2 spectral bands.

Vermont management in focal areas

Treesearch

Judy Rosovsky; Bruce L. Parker; Luke Curtis

1991-01-01

Following the 1979 outbreak of gypsy moths Lymantria dispar L. in Vermont, state personnel began monitoring a number of focal areas for signs of increase in gypsy moth populations. In 1986 data from this early warning system indicated an incipient outbreak. We took advantage of this increase to test an experimental management technique. Would...

Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration

PubMed Central

Wu, Jui-Chung; Chen, Yu-Chen; Kuo, Chih-Ting; Wenshin Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean-Cheng

2015-01-01

Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine-specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration. PMID:26681405

Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration.

PubMed

Wu, Jui-Chung; Chen, Yu-Chen; Kuo, Chih-Ting; Wenshin Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean-Cheng

2015-12-18

Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine-specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration.

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

PubMed

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

2015-07-20

In Myxococcus xanthus the gliding motility machinery is assembled at the leading cell pole to form focal adhesions, translocated rearward to propel the cell, and disassembled at the lagging pole. We show that MglA, a Ras-like small G-protein, is an integral part of this machinery. In this function, MglA stimulates the assembly of the motility complex by directly connecting it to the MreB actin cytoskeleton. Because the nucleotide state of MglA is regulated spatially and MglA only binds MreB in the guanosine triphosphate-bound form, the motility complexes are assembled at the leading pole and dispersed at the lagging pole where the guanosine triphosphatase activating protein MglB disrupts the MglA-MreB interaction. Thus, MglA acts as a nucleotide-dependent molecular switch to regulate the motility machinery spatially. The function of MreB in motility is independent of its function in peptidoglycan synthesis, representing a coopted function. Our findings highlight a new function for the MreB cytoskeleton and suggest that G-protein-cytoskeleton interactions are a universally conserved feature. © 2015 Treuner-Lange et al.

What proportions of focal liver lesions detected by unenhanced ultrasound are inconclusive?

PubMed Central

Willits, Iain; Burn, Julie; Cole, Helen; Hoare, Tim

2014-01-01

In August 2012, the National Institute for Health and Care Excellence produced positive diagnostics guidance on the ultrasound contrast agent SonoVue®, but recommended further research involving an estimation of the proportion of unenhanced ultrasound scans reporting, but not characterising, focal liver lesions, particularly in cirrhotic livers. Patient records from the Radiology Information System of an acute hospital trust were progressively filtered based on categorical fields and keywords in the free text reports, to obtain ultrasound records including the liver that were appropriate for manual analysis. In total, 21,731 records referred from general practice or out-patient clinics were analysed. Patients described as having cirrhosis were analysed as a subgroup. After automatic exclusion of records considered likely to be negative, 5812 records were manually read and categorised as focal liver lesion inconclusive, benign or malignant. In the general practice cohort of 9175 records, 746 reported the presence of one or more focal liver lesions, with 18.4% (95% CI 15.7% to 21.3%) of these records mentioning an inconclusive focal liver lesion. In the out-patient cohort of 12,556 records, 1437 reported one or more focal liver lesions, and 29.4% (95% CI 26.9% to 32.0%) of these were inconclusive. Cirrhosis was reported in 10.8% of the out-patient scans that also reported a focal liver lesion, and 47.4% (95% CI 39.3% to 55.6%) of these scans had an inconclusive focal liver lesion, compared with 27.3% (95% CI 24.9% to 29.8%) that were inconclusive in non-cirrhotic livers (odds ratio 2.4; 95% CI 1.7 to 3.4). This retrospective study indicates that unenhanced ultrasound scans, in which a focal liver lesion is detected, are frequently inconclusive, with the probability of an inconclusive scan being greater in out-patient than general practice referrals. Inconclusive focal liver lesions were also reported in greater proportions of cirrhotic than non-cirrhotic livers. The

Random spot urine protein to creatinine ratio is a reliable measure of proteinuria in lupus nephritis in Koreans.

PubMed

Choi, In Ah; Park, Jin Kyun; Lee, Eun Young; Song, Yeong Wook; Lee, Eun Bong

2013-01-01

The accurate assessment of proteinuria is critical for the management of lupus nephritis. Measuring the protein to creatinine (P/C) ratio in random spot urine (RSU) samples has been introduced as an alternative to the 24-hour (24h) urine collection method. However, it remains unclear as to whether the RSU P/C ratio is reliable for assessing lupus nephritis (LN) in routine clinical practice. In total, 275 pairs of 24h urine and RSU samples from 102 patients with biopsy-proven LN were analysed. The correlation and concordance between the P/C ratios in the two sample types were assessed by Pearson or Spearman correlation and intra-class correlation coefficient (ICC) using mixed models for repeated measurements, respectively. The mean 24h urine P/C ratio was 3.2 ± 4.9. Overall, RSU P/C ratio correlated strongly with the 24h urine P/C ratio (r=0.944, p<0.001) with an excellent agreement (ICC=0.949, 95% confidence interval [CI]: 0.69-1.00). Subgroup analyses revealed that the correlation remained high in class II, III, IV, and V LN (rho=0.868, p<0.001; rho=0.649, p=0.007; r=0.945, p<0.001; and rho=0.900, p=0.001, respectively). The correlation between the 24h urine and RSU P/C ratio in the range of 0.5 to 3 was good (r=0.720, p<0.001) with ICC of 0.659 (95%CI 0.554-0.812). RSU P/C ratio ≥0.5 could predict 24h PCR ≥0.5 with 91.7% sensitivity and 70.2% specificity, whereas RSU P/C ratio ≥1.0 increased specificity up to 94.7%. The RSU P/C ratio is an excellent alternative to the 24 hour P/C ratio for assessing the presence of clinically significant proteinuria in LN. RSU P/C ratio >1.0 may prompt directly to a renal biopsy, whereas RSU P/C ratio between 0.5-1.0 should be followed by a confirmatory 24h urine collection.

Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

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

Al-Qaisieh, Bashar; Mason, Josh, E-mail: joshua.mason@nhs.net; Bownes, Peter

2015-07-15

Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focalmore » (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a

Focal adhesions and Ras are functionally and spatially integrated to mediate IL-1 activation of ERK

PubMed Central

Wang, Qin; Downey, Gregory P.; McCulloch, Christopher A.

2011-01-01

In connective tissue cells, IL-1-induced ERK activation leading to matrix metalloproteinase (MMP)-3 expression is dependent on cooperative interactions between focal adhesions and the endoplasmic reticulum (ER). As Ras can be activated on the ER, we investigated the role of Ras in IL-1 signaling and focal adhesion formation. We found that constitutively active H-Ras, K-Ras or N-Ras enhanced focal adhesion maturation and β1-integrin activation. IL-1 promoted the accumulation of Ras isoforms in ER and focal adhesion fractions, as shown in cells cotransfected with GFP-tagged Ras isoforms and YFP-ER protein and by analysis of subcellular fractions enriched for ER or focal adhesion proteins. Dominant-negative H-Ras or K-Ras reduced accumulation of H-Ras and K-Ras in focal adhesions induced by IL-1 and also blocked ERK activation and focal adhesion maturation. Ras-GRF was enriched constitutively in focal adhesion fractions and was required for Ras recruitment to focal adhesions. We conclude that Ras activation and IL-1 signaling are interactive processes that regulate the maturation of focal adhesions, which, in turn, is required for ERK activation.—Wang, Q., Downey, G. P., McCulloch, C. A. Focal adhesions and Ras are functionally and spatially integrated to mediate IL-1 activation of ERK. PMID:21719512

[MRI/TRUS fusion-guided prostate biopsy : Value in the context of focal therapy].

PubMed

Franz, T; von Hardenberg, J; Blana, A; Cash, H; Baumunk, D; Salomon, G; Hadaschik, B; Henkel, T; Herrmann, J; Kahmann, F; Köhrmann, K-U; Köllermann, J; Kruck, S; Liehr, U-B; Machtens, S; Peters, I; Radtke, J P; Roosen, A; Schlemmer, H-P; Sentker, L; Wendler, J J; Witzsch, U; Stolzenburg, J-U; Schostak, M; Ganzer, R

2017-02-01

Several systems for MRI/TRUS fusion-guided biopsy of the prostate are commercially available. Many studies have shown superiority of fusion systems for tumor detection and diagnostic quality compared to random biopsy. The benefit of fusion systems in focal therapy of prostate cancer (PC) is less clear. Critical considerations of fusion systems for planning and monitoring of focal therapy of PC were investigated. A systematic literature review of available fusion systems for the period 2013-5/2016 was performed. A checklist of technical details, suitability for special anatomic situations and suitability for focal therapy was established by the German working group for focal therapy (Arbeitskreis fokale und Mikrotherapie). Eight fusion systems were considered (Artemis™, BioJet, BiopSee®, iSR´obot™ Mona Lisa, Hitachi HI-RVS, UroNav and Urostation®). Differences were found for biopsy mode (transrectal, perineal, both), fusion mode (elastic or rigid), navigation (image-based, electromagnetic sensor-based or mechanical sensor-based) and space requirements. Several consensus groups recommend fusion systems for focal therapy. Useful features are "needle tracking" and compatibility between fusion system and treatment device (available for Artemis™, BiopSee® and Urostation® with Focal One®; BiopSee®, Hitachi HI-RVS with NanoKnife®; BioJet, BiopSee® with cryoablation, brachytherapy). There are a few studies for treatment planning. However, studies on treatment monitoring after focal therapy are missing.

"Kill" the messenger: Targeting of cell-derived microparticles in lupus nephritis.

PubMed

Nielsen, Christoffer T; Rasmussen, Niclas S; Heegaard, Niels H H; Jacobsen, Søren

2016-07-01

Immune complex (IC) deposition in the glomerular basement membrane (GBM) is a key early pathogenic event in lupus nephritis (LN). The clarification of the mechanisms behind IC deposition will enable targeted therapy in the future. Circulating cell-derived microparticles (MPs) have been proposed as major sources of extracellular autoantigens and ICs and triggers of autoimmunity in LN. The overabundance of galectin-3-binding protein (G3BP) along with immunoglobulins and a few other proteins specifically distinguish circulating MPs in patients with systemic lupus erythematosus (SLE), and this is most pronounced in patients with active LN. G3BP co-localizes with deposited ICs in renal biopsies from LN patients supporting a significant presence of MPs in the IC deposits. G3BP binds strongly to glomerular basement membrane proteins and integrins. Accordingly, MP surface proteins, especially G3BP, may be essential for the deposition of ICs in kidneys and thus for the ensuing formation of MP-derived electron dense structures in the GBM, and immune activation in LN. This review focuses on the notion of targeting surface molecules on MPs as an entirely novel treatment strategy in LN. By targeting MPs, a double hit may be achieved by attenuating both the autoantigenic fueling of immune complexes and the triggering of the adaptive immune system. Thereby, early pathogenic events may be blocked in contrast to current treatment strategies that primarily target and modulate later events in the cellular and humoral immune response. Copyright © 2016 Elsevier B.V. All rights reserved.

Production of high energy, uniform focal profiles with the Nike laser

NASA Astrophysics Data System (ADS)

Lehecka, T.; Lehmberg, R. H.; Deniz, A. V.; Gerber, K. A.; Obenschain, S. P.; Pawley, C. J.; Pronko, M. S.; Sullivan, C. A.

1995-02-01

Nike, a KrF laser facility at the Naval Research Laboratory, is designed to produce high intensity, ultra-uniform focal profiles for experiments relating to direct drive inertial confinement fusion. We present measurements of focal profiles through the next-to-last amplifier, a 20 × 20 cm 2 aperture electron beam pumped amplifier capable of producing more than 120 J of output in a 120 ns pulse. Using echelon free induced spatial incoherence beam smoothing this system has produced focal profiles with less than 2% tilt and curvature and less than 2% rms variation from a flat top distribution.

Adult-onset Rasmussen encephalitis associated with focal cortical dysplasia.

PubMed

Hohenbichler, Katharina; Lelotte, Julie; Lhommel, Renaud; Tahry, Riëm El; Vrielynck, Pascal; Santos, Susana Ferrao

2017-12-01

Rasmussen encephalitis is a rare, devastating condition, typically presenting in childhood. Cases of adult-onset Rasmussen have also been described, but the clinical picture is less defined, rendering final diagnosis difficult. We present a case of adult-onset Rasmussen encephalitis with dual pathology, associated with focal cortical dysplasia and encephalitis. We interpreted the Rasmussen encephalitis to be caused by severe and continuous epileptic activity due to focal cortical dysplasia. The best therapeutic approach for such cases remains unclear.

Focal cryotherapy of localized prostate cancer: a systematic review of the literature.

PubMed

Shah, Taimur Tariq; Ahmed, Hashim; Kanthabalan, Abi; Lau, Benjamin; Ghei, Maneesh; Maraj, Barry; Arya, Manit

2014-11-01

Radical/whole gland treatment for prostate cancer has significant side-effects. Therefore focal treatments such as cryotherapy have been used to treat localized lesions whilst aiming to provide adequate cancer control with minimal side-effects. We performed a systematic review of Pubmed/Medline and Cochrane databases' to yield 9 papers for primary focal prostate cryotherapy and 2 papers for focal salvage treatment (radio-recurrent). The results of 1582 primary patients showed biochemical disease-free survival between 71-93% at 9-70 months follow-up. Incontinence rates were 0-3.6% and ED 0-42%. Recto-urethral fistula occurred in only 2 patients. Salvage focal cryotherapy had biochemical disease-free survival of 50-68% at 3 years. ED occurred in 60-71%. Focal cryotherapy appears to be an effective treatment for primary localized prostate cancer and compares favorably to radical/whole gland treatments in medium-term oncological outcomes and side-effects. Although more studies are needed it is also effective for radio-recurrent cancer with a low complications rates.

Analysis of Altered Micro RNA Expression Profiles in Focal Cortical Dysplasia IIB.

PubMed

Li, Lin; Liu, Chang-Qing; Li, Tian-Fu; Guan, Yu-Guang; Zhou, Jian; Qi, Xue-Ling; Yang, Yu-Tao; Deng, Jia-Hui; Xu, Zhi-Qing David; Luan, Guo-Ming

2016-04-01

Focal cortical dysplasia type IIB is a commonly encountered subtype of developmental malformation of the cerebral cortex and is often associated with pharmacoresistant epilepsy. In this study, to investigate the molecular etiology of focal cortical dysplasia type IIB, the authors performed micro ribonucleic acid (RNA) microarray on surgical specimens from 5 children (2 female and 3 male, mean age was 73.4 months, range 50-112 months) diagnosed of focal cortical dysplasia type IIB and matched normal tissue adjacent to the lesion. In all, 24 micro RNAs were differentially expressed in focal cortical dysplasia type IIB, and the microarray results were validated using quantitative real-time polymerase chain reaction (PCR). Then the putative target genes of the differentially expressed micro RNAs were identified by bioinformatics analysis. Moreover, biological significance of the target genes was evaluated by investigating the pathways in which the genes were enriched, and the Hippo signaling pathway was proposed to be highly related with the pathogenesis of focal cortical dysplasia type IIB. © The Author(s) 2015.

Focal plane for the next generation of earth observation instruments

NASA Astrophysics Data System (ADS)

Pranyies, P.; Toubhans, I.; Badoil, B.; Tanguy, F.; Descours, Francis

2017-09-01

Sodern is the French focal plane provider for Earth Observation (EO) satellites. Since the 1980's, Sodern has played an active role first in the SPOT program. Within the two-spacecraft constellation Pleiades 1A/1B over the next years, Sodern introduced advanced technologies as Silicon Carbide (SiC) focal plane structure and multispectral strip filters dedicated to multiple-lines detectors.

Starbugs: focal plane fiber positioning technology

NASA Astrophysics Data System (ADS)

Goodwin, Michael; Heijmans, Jeroen; Saunders, Ian; Brzeski, Jurek; Saunders, Will; Muller, Rolf; Haynes, Roger; Gilbert, James

2010-07-01

We report on the technological achievements of our latest Starbug prototypes and their implications for smart focal plane fiber positioning applications for wide-field astronomy. The Starbugs are innovative self-motile miniature robotic devices that can simultaneously and independently position fibers or payloads over a field plate located at the telescope's focal plane. The Starbugs concept overcomes many of the limitations associated with the traditional 'pick and place' positioners where a robot places fixed buttons onto the field plate. The new Starbug prototypes use piezoelectric actuators and have the following features: (i) new 'lift-and-step' method (discrete step) for accurate positioning over different surfaces; and (ii) operate in an inverted hanging position underneath a transparent field plate, removing the need for fibercable retractors. In this paper, we present aspects of the Starbug prototypes, including the theoretical model, mechanical design, experimental setup, algorithms, performance and applications for astronomical instrumentation.

Focal therapy: patients, interventions, and outcomes--a report from a consensus meeting.

PubMed

Donaldson, Ian A; Alonzi, Roberto; Barratt, Dean; Barret, Eric; Berge, Viktor; Bott, Simon; Bottomley, David; Eggener, Scott; Ehdaie, Behfar; Emberton, Mark; Hindley, Richard; Leslie, Tom; Miners, Alec; McCartan, Neil; Moore, Caroline M; Pinto, Peter; Polascik, Thomas J; Simmons, Lucy; van der Meulen, Jan; Villers, Arnauld; Willis, Sarah; Ahmed, Hashim U

2015-04-01

Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field. To gather expert opinion on patient selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design. Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health. Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level. Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging-targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3+3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus. The landscape of PCa treatment is rapidly evolving with new treatment technologies. This consensus meeting provides guidance to clinicians on current expert thinking in the field of focal therapy. In this

Measuring the Flatness of Focal Plane for Very Large Mosaic CCD Camera

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

Hao, Jiangang; Estrada, Juan; Cease, Herman

2010-06-08

Large mosaic multiCCD camera is the key instrument for modern digital sky survey. DECam is an extremely red sensitive 520 Megapixel camera designed for the incoming Dark Energy Survey (DES). It is consist of sixty two 4k x 2k and twelve 2k x 2k 250-micron thick fully-depleted CCDs, with a focal plane of 44 cm in diameter and a field of view of 2.2 square degree. It will be attached to the Blanco 4-meter telescope at CTIO. The DES will cover 5000 square-degrees of the southern galactic cap in 5 color bands (g, r, i, z, Y) in 5 yearsmore » starting from 2011. To achieve the science goal of constraining the Dark Energy evolution, stringent requirements are laid down for the design of DECam. Among them, the flatness of the focal plane needs to be controlled within a 60-micron envelope in order to achieve the specified PSF variation limit. It is very challenging to measure the flatness of the focal plane to such precision when it is placed in a high vacuum dewar at 173 K. We developed two image based techniques to measure the flatness of the focal plane. By imaging a regular grid of dots on the focal plane, the CCD offset along the optical axis is converted to the variation the grid spacings at different positions on the focal plane. After extracting the patterns and comparing the change in spacings, we can measure the flatness to high precision. In method 1, the regular dots are kept in high sub micron precision and cover the whole focal plane. In method 2, no high precision for the grid is required. Instead, we use a precise XY stage moves the pattern across the whole focal plane and comparing the variations of the spacing when it is imaged by different CCDs. Simulation and real measurements show that the two methods work very well for our purpose, and are in good agreement with the direct optical measurements.« less

[Liver ultrasound: focal lesions and diffuse diseases].

PubMed

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

2016-01-01

Liver ultrasound is frequently used as a first-line technique for the detection and characterization of the most common liver lesions, especially those incidentally found focal liver lesions, and for monitoring of chronic liver diseases. Ultrasound is not only used in the Bmode, but also with Doppler and, more recently, contrast-enhanced ultrasound. It is mainly used in the diagnosis of diffuse liver diseases, such as steatosis or cirrhosis. This article presents a practical approach for diagnosis workup, in which the different characteristics of the main focal liver lesions and diffuse liver diseases are reviewed. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Rituximab in systemic lupus erythematosus and lupus nephritis.

PubMed

Beckwith, Hannah; Lightstone, Liz

2014-01-01

Treatment options for systemic lupus erythematosus (SLE) and lupus nephritis (LN) have high associated morbidity and mortality. Side effects, particularly from long-term corticosteroid usage, limit patient adherence, with subsequent impacts on treatment efficacy. In addition, a subset of patients with SLE/LN fails to respond to current standard immunotherapy. There is an urgent need to develop steroid-sparing treatment regimens as well as novel therapies for the management of refractory disease. Rituximab is a chimeric mouse/human monoclonal antibody directed against the B cell CD20 receptor. It has been used in the treatment of non-Hodgkin's lymphoma for over 30 years and has an excellent safety profile. Recent work has demonstrated a role for B cell depletion therapy in the management of autoimmune disease, and the efficacy of rituximab in many observational studies in SLE and LN has been noted. Unfortunately, two large randomised controlled trials evaluating rituximab for the treatment of renal and non-renal lupus failed to meet their primary endpoints. Reasons for this have been discussed extensively within the medical community with a general consensus that trial design (steroid use, trial size and endpoints used) was the principal reason for the failures. Despite the lack of trial evidence, clinical experience means many physicians firmly believe in the value of rituximab in SLE/LN treatment and have continued to use it in their clinical practice. Recent work has demonstrated the efficacy of rituximab as a steroid-sparing agent and as an alternative therapeutic option for refractory SLE/LN. There are two further rituximab randomised controlled trials planned/started in LN – one using a steroid-minimising regimen with rituximab for induction and one evaluating rituximab for LN refractory to 6 months standard of care treatment. Rituximab remains a problematic drug in lupus and LN – it is a biologically plausible agent with a huge amount of supportive

Evolution of IgA nephropathy into anaphylactoid purpura in six cases--further evidence that IgA nephropathy and Henoch-Schonlein purpura nephritis share common pathogenesis.

PubMed

Kamei, Koichi; Ogura, Masao; Sato, Mai; Ito, Shuichi; Ishikura, Kenji

2016-05-01

As the morphological and immunohistochemical manifestations of immunoglobulin A (IgA) nephropathy and Henoch-Schonlein purpura nephritis (HSPN) are very similar, they are considered to share a common pathogenesis. Although HSPN usually develops after the appearance of anaphylactoid purpura, we have encountered patients whose renal symptoms preceded purpura. We reviewed the clinical courses of patients who were first diagnosed with IgA nephropathy, but developed purpura later, at the National Center for Child Health and Development in Tokyo, Japan. Of the 53 patients who were diagnosed with primary IgA nephropathy at our institute during the study period (March 2002 to July 2015), six (11 %) developed anaphylactoid purpura after the diagnosis of primary IgA nephropathy and therefore met the inclusion criteria. Duration between the onset of nephritis and subsequent appearance of purpura ranged from 5 months to 14 years. One patient reached end-stage renal failure due to IgA nephropathy and developed purpura after renal transplantation. All renal biopsies performed before the appearance of purpura showed mesangial proliferation with predominant IgA deposits. Urinary findings deteriorated in three patients after the appearance of purpura, including one patient who developed rapidly progressive glomerulonephritis. Renal biopsy findings worsened in two patients. At the last observation, two patients showed mild renal insufficiency. Our clinical experience and previous reports support the argument that IgA nephropathy and HSPN are different manifestations of a single disease. Hence, it is acceptable to consider that they are variants of a single disease.

TAC-TIC use of tacrolimus-based regimens in lupus nephritis

PubMed Central

Bredewold, Obbo W; Trompet, Stella; Huizinga, Tom W J; Rabelink, Ton J; de Craen, Anton J M; Teng, Y K Onno

2016-01-01

Current guidelines do not mention tacrolimus (TAC) as a treatment option and no consensus has been reported on the role of TAC in lupus nephritis (LN). The present study aimed to guide clinical judgement on the use of TAC in patients with LN. A meta-analysis was performed for clinical studies investigating TAC regimens in LN on the basis of treatment target (induction or maintenance), concomitant immunosuppression and quality of the data. 23 clinical studies performed in patients with LN were identified: 6 case series, 9 cohort studies, 2 case-control studies and 6 randomised controlled trials (RCTs). Of the 6 RCTs, 5 RCTs investigated TAC regimens as induction treatment and 1 RCT as maintenance treatment. Five RCTs investigated TAC in combination with steroids and 2 TAC with mycophenolate plus steroids. All RCTs were performed in patients of Asian ethnicity. In a meta-analysis, TAC regimens achieved a significantly higher total response (relative risk (RR) 1.23, 95% CI 1.12 to 1.34, p<0.05) and significantly higher complete response (RR 1.48, 95% CI 1.23 to 1.77, p<0.05). The positive outcome was predominantly defined by the largest RCT investigating TAC with mycophenolate plus steroids. Regarding safety, the occurrence of leucopoenia was significantly lower, while the occurrence of increased creatine was higher. Clinical studies on TAC regimens for LN are limited to patients of Asian ethnicity and hampered by significant heterogeneity. The positive results on clinical efficacy of TAC as induction treatment in LN cannot be extrapolated beyond Asian patients with LN. Therefore, further confirmation in multiethnic, randomised trials is mandatory. Until then, TAC can be considered in selected patients with LN. PMID:28123768

[A case of focal epilepsy manifesting multiple psychiatric auras].

PubMed

Ezura, Michinori; Kakisaka, Yosuke; Jin, Kazutaka; Kato, Kazuhiro; Iwasaki, Masaki; Fujikawa, Mayu; Aoki, Masashi; Nakasato, Nobukazu

2015-01-01

We present a case of epilepsy with multiple types of focal seizures that were misdiagnosed as psychiatric disorders. A 20-year-old female patient presented with a variety of episodes, including loss of consciousness, deja vu, fear, delusion of possession, violent movements, and generalized convulsions. Each of these symptoms appeared in a stereotypic manner. She was initially diagnosed with a psychiatric disorder and treated with psychoactive medications, which had no effect. Long-term video electroencephalography revealed that her episodes of violent movement with impaired consciousness and secondarily generalized seizure were epileptic events originating in the right hemisphere. High-field brain magnetic resonance imaging for detecting subtle lesions revealed bilateral lesions from periventricular nodular heterotopia. Her final diagnosis was right hemispheric focal epilepsy. Carbamazepine administration was started, which successfully controlled all seizures. The present case demonstrates the pitfall of diagnosing focal epilepsy when it presents with multiple types of psychiatric aura. Epilepsy should thus be included in differential diagnoses, considering the stereotypic nature of symptoms, to avoid misdiagnosis.

Role of inhibitory control in modulating focal seizure spread.

PubMed

Liou, Jyun-You; Ma, Hongtao; Wenzel, Michael; Zhao, Mingrui; Baird-Daniel, Eliza; Smith, Elliot H; Daniel, Andy; Emerson, Ronald; Yuste, Rafael; Schwartz, Theodore H; Schevon, Catherine A

2018-05-10

Focal seizure propagation is classically thought to be spatially contiguous. However, distribution of seizures through a large-scale epileptic network has been theorized. Here, we used a multielectrode array, wide field calcium imaging, and two-photon calcium imaging to study focal seizure propagation pathways in an acute rodent neocortical 4-aminopyridine model. Although ictal neuronal bursts did not propagate beyond a 2-3-mm region, they were associated with hemisphere-wide field potential fluctuations and parvalbumin-positive interneuron activity outside the seizure focus. While bicuculline surface application enhanced contiguous seizure propagation, focal bicuculline microinjection at sites distant to the 4-aminopyridine focus resulted in epileptic network formation with maximal activity at the two foci. Our study suggests that both classical and epileptic network propagation can arise from localized inhibition defects, and that the network appearance can arise in the context of normal brain structure without requirement for pathological connectivity changes between sites.

Focal cryotherapy in the treatment of localized prostate cancer.

PubMed

Nguyen, Huy D; Allen, Bryan J; Pow-Sang, Julio M

2013-07-01

The management choice for newly diagnosed localized prostate cancer presents a challenge to both the physician and the patient. Traditionally, surgery and radiation therapy have been the most commonly recommended options. More recently, active surveillance is recommended as the preferred management choice for a subset of men with localized, low-risk cancer. Recent reports also suggest that focal cryotherapy may be considered as a management option for selected cases of clinically localized prostate cancer. A review of the literature on focal cryotherapy from 2002 to 2012 was performed. Outcomes on cancer control, complications, and quality of life were extracted and assessed. The biochemical disease-free survival at 5 years is comparable to whole gland treatment modalities. Complications are minimal and comparable with other local treatment modalities. Focal cryotherapy is safe and effective, and it may improve failure rates in men who initially pursue active surveillance protocols. Early outcomes with cancer control are encouraging.

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.

Multi-focal HIFU reduces cavitation in mild-hyperthermia.

PubMed

Chaplin, Vandiver; Caskey, Charles F

2017-01-01

Mild-hyperthermia therapy (40-45 °C) with high-intensity focused ultrasound (HIFU) is a technique being considered in a number of different treatments such as thermally activated drug delivery, immune-stimulation, and as a chemotherapy adjuvant. Mechanical damage and loss of cell viability associated with HIFU-induced acoustic cavitation may pose a risk during these treatments or may hinder their success. Here we present a method that achieves mild heating and reduces cavitation by using a multi-focused HIFU beam. We quantify cavitation level and temperature rise in multi-focal sonications and compare it to single-focus sonications at the transducer geometric focus. Continuous wave sonications were performed with the Sonalleve V2 transducer in gel phantoms and pork at 5, 10, 20, 40, 60, 80 acoustic watts for 30 s. Cavitation activity was measured with two ultrasound (US) imaging probes, both by computing the raw channel variance and using passive acoustic mapping (PAM). Temperature rise was measured with MR thermometry at 3 T. Cavitation and heating were compared for single- and multi-focal sonication geometries. Multi-focal sonications used four points equally spaced on a ring of either 4 mm or 8 mm diameter. Single-focus sonications were not steered. Multi-focal sonication generated distinct foci that were visible in MRI thermal maps in both phantoms and pork, and visible in PAM images in phantoms only. Cavitation activity (measured by channel variance) and mean PAM image value were highly correlated (r > 0.9). In phantoms, cavitation exponentially decreased over the 30-second sonication, consistent with depletion of cavitation nuclei. In pork, sporadic spikes signaling cavitation were observed with single focusing only. In both materials, the widest beam reduced average and peak cavitation level by a factor of two or more at each power tested when compared to a single focus. The widest beam reduced peak temperature by at least 10 °C at powers above 5

The Sentinel 4 focal plane subsystem

NASA Astrophysics Data System (ADS)

Hohn, Rüdiger; Skegg, Michael P.; Hermsen, Markus; Hinger, Jürgen; Williges, Christian; Reulke, Ralf

2017-09-01

The Sentinel 4 instrument is an imaging spectrometer, developed by Airbus under ESA contract in the frame of the joint European Union (EU)/ESA COPERNICUS program with the objective of monitoring trace gas concentrations. Sentinel 4 will provide accurate measurements of key atmospheric constituents such as ozone, nitrogen dioxide, sulfur dioxide, formaldehyde, as well as aerosol and cloud properties. Sentinel 4 is unique in being the first geostationary UVN mission. The SENTINEL 4 space segment will be integrated on EUMETSAT's Meteosat Third Generation Sounder satellite (MTG-S). Sentinel 4 will provide coverage of Europe and adjacent regions. The Sentinel 4 instrument comprises as a major element two Focal Plane Subsystems (FPS) covering the wavelength ranges 305 nm to 500 nm (UVVIS) and 750 nm to 775 nm (NIR) respectively. The paper describes the Focal Plane Subsystems, comprising the detectors, the optical bench and the control electronics. Further the design and development approach will be presented as well as first measurement results of FPS Qualification Model.

Translocation of TRPV2 channel induced by focal administration of mechanical stress

PubMed Central

Nagasawa, Masahiro; Kojima, Itaru

2015-01-01

The effect of focal mechanical stress on the localization of TRPV2 was investigated in HT1080 cells, where only mRNA for TRPV2 was detected among members of the TRPV channel family. Mechanical stress was applied by adding negative pressure using a glass pipette. When focal mechanical stress was applied, subplasma membrane Ca2+ concentration ([Ca2+]s) was increased beneath the pipette, which propagated throughout the cell. The increase in [Ca2+]s was blocked by ruthenium red or by knocking down TRPV2. Elevation of [Ca2+]s was not observed by removal of extracellular Ca2+, by an addition of a phosphatidylinositol 3-kinase inhibitor LY29034, and by transfection of dominant-negative Rac. In cells expressing GFP-TRPV2 and RFP-Akt, administration of focal mechanical stress induced accumulation of GFP-TRPV2 beneath the pipette. RFP-Akt was also accumulated to the same site. Gadolinium blocked the elevation of [Ca2+]s induced by focal mechanical stress and also attenuated accumulation of TRPV2. When GFP-TRPV1, GFP-TRPV3, GFP-TRPV4, GFP-TRPV5, or GFP-TRPV6 was transfected ectopically in HT1080 cells, only GFP-TRPV4 was accumulated beneath the pipette in response to the focal mechanical stress. These results indicate that TRPV2 translocates to the site receiving a focal mechanical stress and increases [Ca2+]s. PMID:25677550

Average focal length and power of a section of any defined surface.

PubMed

Kaye, Stephen B

2010-04-01

To provide a method to allow calculation of the average focal length and power of a lens through a specified meridian of any defined surface, not limited to the paraxial approximations. University of Liverpool, Liverpool, United Kingdom. Functions were derived to model back-vertex focal length and representative power through a meridian containing any defined surface. Average back-vertex focal length was based on the definition of the average of a function, using the angle of incidence as an independent variable. Univariate functions allowed determination of average focal length and power through a section of any defined or topographically measured surface of a known refractive index. These functions incorporated aberrations confined to the section. The proposed method closely approximates the average focal length, and by inference power, of a section (meridian) of a surface to a single or scalar value. It is not dependent on the paraxial and other nonconstant approximations and includes aberrations confined to that meridian. A generalization of this method to include all orthogonal and oblique meridians is needed before a comparison with measured wavefront values can be made. Copyright (c) 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Low power, highly linear output buffer. [for infrared focal plane arrays

NASA Technical Reports Server (NTRS)

Foley, D.; Butler, N.; Stobie, J.

1992-01-01

A class AB CMOS output buffer has been designed for use on an IR focal plane array. Given the requirements for power dissipation and load capacitance a class A output, such as a source follower, would be unsuitable. The approach taken uses a class AB amplifier configured as a charge integrator. Thus it converts a charge packet in the focal plane multiplexer to a voltage which is then the output of the focal plane. With a quiescent current of 18 micro-a and a load capacitance of 100 pf, the amplifier has an open loop unity gain bandwidth of 900 khz. Integral nonlinearity is better than .03 percent over 5.5 volts when run with VDD-VSS = 6v.

Mutations in KCNT1 cause a spectrum of focal epilepsies

PubMed Central

Møller, Rikke S.; Heron, Sarah E.; Larsen, Line H. G.; Lim, Chiao Xin; Ricos, Michael G.; Bayly, Marta A.; van Kempen, Marjan J. A.; Klinkenberg, Sylvia; Andrews, Ian; Kelley, Kent; Ronen, Gabriel M.; Callen, David; McMahon, Jacinta M.; Yendle, Simone C.; Carvill, Gemma L.; Mefford, Heather C.; Nabbout, Rima; Poduri, Annapurna; Striano, Pasquale; Baglietto, Maria G.; Zara, Federico; Smith, Nicholas J.; Pridmore, Clair; Gardella, Elena; Nikanorova, Marina; Dahl, Hans Atli; Gellert, Pia; Scheffer, Ingrid E.; Gunning, Boudewijn; Kragh-Olsen, Bente; Dibbens, Leanne M.

2018-01-01

Summary Autosomal dominant mutations in the sodium-gated potassium channel subunit gene KCNT1 have been associated with two distinct seizure syndromes, nocturnal frontal lobe epilepsy (NFLE) and malignant migrating focal seizures of infancy (MMFSI). To further explore the phenotypic spectrum associated with KCNT1, we examined individuals affected with focal epilepsy or an epileptic encephalopathy for mutations in the gene. We identified KCNT1 mutations in 12 previously unreported patients with focal epilepsy, multifocal epilepsy, cardiac arrhythmia, and in a family with sudden unexpected death in epilepsy (SUDEP), in addition to patients with NFLE and MMFSI. In contrast to the 100% penetrance so far reported for KCNT1 mutations, we observed incomplete penetrance. It is notable that we report that the one KCNT1 mutation, p.Arg398Gln, can lead to either of the two distinct phenotypes, ADNFLE or MMFSI, even within the same family. This indicates that genotype–phenotype relationships for KCNT1 mutations are not straightforward. We demonstrate that KCNT1 mutations are highly pleiotropic and are associated with phenotypes other than ADNFLE and MMFSI. KCNT1 mutations are now associated with Ohtahara syndrome, MMFSI, and nocturnal focal epilepsy. They may also be associated with multifocal epilepsy and cardiac disturbances. PMID:26122718

Focal Therapy: Patients, Interventions, and Outcomes—A Report from a Consensus Meeting

PubMed Central

Donaldson, Ian A.; Alonzi, Roberto; Barratt, Dean; Barret, Eric; Berge, Viktor; Bott, Simon; Bottomley, David; Eggener, Scott; Ehdaie, Behfar; Emberton, Mark; Hindley, Richard; Leslie, Tom; Miners, Alec; McCartan, Neil; Moore, Caroline M.; Pinto, Peter; Polascik, Thomas J.; Simmons, Lucy; van der Meulen, Jan; Villers, Arnauld; Willis, Sarah; Ahmed, Hashim U.

2015-01-01

Background Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field. Objective To gather expert opinion on patient selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design. Design, setting, and participants Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health. Outcome measurements and statistical analysis Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level. Results and limitations Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging–targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5 mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3 + 3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus. Conclusions The landscape of PCa treatment is rapidly evolving with new

Warfarin-induced toxic epidermal necrolysis in combination therapy of Henoch-Schönlein purpura nephritis: a case report.

PubMed

Kasahara, Katsuaki; Gotoh, Yoshimitsu; Kuroyanagi, Yoshiyuki; Nagano, China

2017-07-14

Toxic epidermal necrolysis (TEN) is a rare life-threatening condition almost exclusively attributed to drugs. The main etiologic factors for TEN are sulphonamides, anticonvulsants, and antibiotics; however, there are no published reports of warfarin causing TEN. We present the case of a 3-year-old patient who developed TEN while receiving treatment for Henoch-Schönlein purpura nephritis (HSPN). With multiple-drug therapy comprising prednisolone, mizoribine, dipyridamole, and warfarin, it is difficult to detect which drug is the causative agent. While in most cases, diagnosis of the causative drug is based on clinical history without a lymphocyte transformation test (LTT), we performed the test three times and identified the causative drug as warfarin at the late phase. We continued HSPN treatment without warfarin, and results showed good renal function without life-threatening complications. To our knowledge, this is the first report about TEN caused by warfarin. Repeated LTTs could be useful for identifying TEN-causative drugs even in the late phase.

Approximate Evaluation of Acoustical Focal Beams by Phased Array Probes for Austenitic Weld Inspections

NASA Astrophysics Data System (ADS)

Kono, Naoyuki; Miki, Masahiro; Nakamura, Motoyuki; Ehara, Kazuya

2007-03-01

Phased array techniques are capable of the sensitive detection and precise sizing of flaws or cracks in components of nuclear power plants by using arbitrary focal beams with various depths, positions and angles. Aquantitative investigation of these focal beams is essential for the optimization of array probes, especially for austenitic weld inspection, in order to improve the detectability, sizing accuracy, and signal-to-noise ratio using these beams. In the present work, focal beams generated by phased array probes are calculated based on the Fresnel-Kirchhoff diffraction integral (FKDI) method, and an approximation formula between the actual focal depth and optical focal depth is proposed as an extension of the theory for conventional spherically focusing probes. The validity of the approximation formula for the array probes is confirmed by a comparison with simulation data using the FKDI method, and the experimental data.

Primary focal prostate radiotherapy: Do all patients really need whole-prostate irradiation?

PubMed

Jereczek-Fossa, Barbara Alicja; Ciardo, Delia; Petralia, Giuseppe; Bellomi, Massimo; De Bari, Berardino; De Cobelli, Ottavio; Orecchia, Roberto

2016-09-01

To review the available data about focal primary partial prostate irradiation (focal radiotherapy, FRT) for early prostate cancer. Medline search for English language full paper on primary FRT for early prostate cancer including review articles, planning studies or patient series (clinical outcome available) published before May 31, 2015. 22 papers have been found: 11 review articles, 4 planning studies and 7 patient series. Eleven review articles were dedicated to all types of focal therapy including FRT and 2 to FRT only. All planning studies included brachytherapy and showed excellent organ-at-risk sparing. Patient series included together 715 patients (99% treated with brachytherapy) and showed promising tumour control in low-risk cancer. In intermediate-risk tumours, FRT might be suboptimal. Primary FRT is feasible in early prostate cancer. As any other focal therapy, FRT remains investigational until numerous questions are answered. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

High intensity focused ultrasound (HIFU) focal spot localization using harmonic motion imaging (HMI).

PubMed

Han, Yang; Hou, Gary Yi; Wang, Shutao; Konofagou, Elisa

2015-08-07

Several ultrasound-based imaging modalities have been proposed for image guidance and monitoring of high-intensity focused ultrasound (HIFU) treatment. However, accurate localization and characterization of the effective region of treatment (focal spot) remain important obstacles in the clinical implementation of HIFU ablation. Harmonic motion imaging for focused ultrasound (HMIFU) is a HIFU monitoring technique that utilizes radiation-force-induced localized oscillatory displacement. HMIFU has been shown to correctly identify the formation and extent of HIFU thermal ablation lesions. However a significant problem remains in identifying the location of the HIFU focus, which is necessary for treatment planning. In this study, the induced displacement was employed to localize the HIFU focal spot inside the tissue prior to treatment. Feasibility was shown with two separate systems. The 1D HMIFU system consisted of a HIFU transducer emitting an amplitude-modulated HIFU beam for mechanical excitation and a confocal single-element, pulse-echo transducer for simultaneous RF acquisition. The 2D HIFU system consists of a HIFU phased array, and a co-axial imaging phased array for simultaneous imaging. Initial feasibility was first performed on tissue-mimicking gelatin phantoms and the focal zone was defined as the region corresponding to the -3dB full width at half maximum of the HMI displacement. Using the same parameters, in vitro experiments were performed in canine liver specimens to compare the defined focal zone with the lesion. In vitro measurements showed good agreement between the HMI predicted focal zone and the induced HIFU lesion location. HMIFU was experimentally shown to be capable of predicting and tracking the focal region in both phantoms and in vitro tissues. The accuracy of focal spot localization was evaluated by comparing with the lesion location in post-ablative tissues, with a R(2) = 0.821 at p < 0.002 in the 2D HMI system. We demonstrated the

High Intensity Focused Ultrasound (HIFU) Focal Spot Localization Using Harmonic Motion Imaging (HMI)

PubMed Central

Han, Yang; Hou, Gary Yi; Wang, Shutao; Konofagou, Elisa

2015-01-01

Several ultrasound-based imaging modalities have been proposed for image guidance and monitoring of High-Intensity Focused Ultrasound (HIFU) treatment. However, accurate localization and characterization of the effective region of treatment (focal spot) remain important obstacles in the clinical implementation of HIFU ablation. Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a HIFU monitoring technique that utilizes radiation-force-induced localized oscillatory displacement. HMIFU has been shown to correctly identify the formation and extent of HIFU thermal ablation lesions. However a significant problem remains in identifying the location of the HIFU focus, which is necessary for treatment planning. In this study, the induced displacement was employed to localize the HIFU focal spot inside the tissue prior to treatment. Feasibility was shown with two separate systems. The 1D HMIFU system consisted of a HIFU transducer emitting an amplitude-modulated HIFU beam for mechanical excitation and a confocal single-element, pulse-echo transducer for simultaneous RF acquisition. The 2D HIFU system consists of a HIFU phased array, and a co-axial imaging phased array for simultaneous imaging. Initial feasibility was first performed on tissue-mimicking gelatin phantoms and the focal zone was defined as the region corresponding to the −3 dB full width at half maximum of the HMI displacement. Using the same parameters, in vitro experiments were performed in canine liver specimens to compare the defined focal zone with the lesion. In vitro measurements showed good agreement between the HMI predicted focal zone and the induced HIFU lesion location. HMIFU was experimentally shown to be capable of predicting and tracking the focal region in both phantoms and in vitro tissues. The accuracy of focal spot localization was evaluated by comparing with the lesion location in post-ablative tissues, with a R2 = 0.821 at p<0.002 in the 2D HMI system. We demonstrated the

High intensity focused ultrasound (HIFU) focal spot localization using harmonic motion imaging (HMI)

NASA Astrophysics Data System (ADS)

Han, Yang; Hou, Gary Yi; Wang, Shutao; Konofagou, Elisa

2015-08-01

Several ultrasound-based imaging modalities have been proposed for image guidance and monitoring of high-intensity focused ultrasound (HIFU) treatment. However, accurate localization and characterization of the effective region of treatment (focal spot) remain important obstacles in the clinical implementation of HIFU ablation. Harmonic motion imaging for focused ultrasound (HMIFU) is a HIFU monitoring technique that utilizes radiation-force-induced localized oscillatory displacement. HMIFU has been shown to correctly identify the formation and extent of HIFU thermal ablation lesions. However a significant problem remains in identifying the location of the HIFU focus, which is necessary for treatment planning. In this study, the induced displacement was employed to localize the HIFU focal spot inside the tissue prior to treatment. Feasibility was shown with two separate systems. The 1D HMIFU system consisted of a HIFU transducer emitting an amplitude-modulated HIFU beam for mechanical excitation and a confocal single-element, pulse-echo transducer for simultaneous RF acquisition. The 2D HIFU system consists of a HIFU phased array, and a co-axial imaging phased array for simultaneous imaging. Initial feasibility was first performed on tissue-mimicking gelatin phantoms and the focal zone was defined as the region corresponding to the  -3dB full width at half maximum of the HMI displacement. Using the same parameters, in vitro experiments were performed in canine liver specimens to compare the defined focal zone with the lesion. In vitro measurements showed good agreement between the HMI predicted focal zone and the induced HIFU lesion location. HMIFU was experimentally shown to be capable of predicting and tracking the focal region in both phantoms and in vitro tissues. The accuracy of focal spot localization was evaluated by comparing with the lesion location in post-ablative tissues, with a R2 = 0.821 at p  <  0.002 in the 2D HMI system. We demonstrated

RESPONSE LATENCIES OF NORMAL AND FOCAL-HEAD IRRADIATED MONKEYS

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

McDowell, A.A.; Brown, W.L.

1963-12-01

This study was designed to determine whether focal-head irradiated rhesus monkeys differ from normal monkeys in a manner analogous to that previously found in whole-body irradiated monkeys with respect to response latencies under both familiar and novel stimulus conditions. Five control and four focal-head irradiated rhesus monkeys with nearly identical training histories were used; the latter were survivors of a focal-head irradiation study conducted four years earlier. They had received 3000 r x radiation to the inferior parietal lobule and posterior aspect of the temporal lobe of the brain, and 30 days later the same dosage to the same areamore » of the brain. The testing was conducted in a modified version of the Wisconsin General Test Apparatus, with 24 trials per day for two days, on response latency to a single food-rewarded wooden block placed randomly over either of the two extreme food-well positions. Then, 24 trials were conducted per day for two days on response latency to either the same food-rewarded wooden block or to a novel nonrewarded wooden block presented simultaneously. On the single-block condition, median response latencies of the two groups were comparable and the groups improved in a similar manner with practice. Optimal performance latencies were also comparable for the two groups. When the novel nonrewarded stimulus block was introduced, both groups manifested comparable disruption of median response latencies, but disruption of optimal response latencies was shown only by the focalhead irradiated group. The findings show that monkeys with previous focal-head irradiation of the posterior association areas, unlike relatively high-dose whole-body irradiated monkeys, manifest median response latencies comparable to those of controls. These data indicate the lasting effects of focal-head irradiation with x rays, and suggest that the sites of permanent damage for monkeys given sublethal whole-body radiation exposure differ from the sites

Multi-focal multiphoton lithography.

PubMed

Ritschdorff, Eric T; Nielson, Rex; Shear, Jason B

2012-03-07

Multiphoton lithography (MPL) provides unparalleled capabilities for creating high-resolution, three-dimensional (3D) materials from a broad spectrum of building blocks and with few limitations on geometry, qualities that have been key to the design of chemically, mechanically, and biologically functional microforms. Unfortunately, the reliance of MPL on laser scanning limits the speed at which fabrication can be performed, making it impractical in many instances to produce large-scale, high-resolution objects such as complex micromachines, 3D microfluidics, etc. Previously, others have demonstrated the possibility of using multiple laser foci to simultaneously perform MPL at numerous sites in parallel, but use of a stage-scanning system to specify fabrication coordinates resulted in the production of identical features at each focal position. As a more general solution to the bottleneck problem, we demonstrate here the feasibility for performing multi-focal MPL using a dynamic mask to differentially modulate foci, an approach that enables each fabrication site to create independent (uncorrelated) features within a larger, integrated microform. In this proof-of-concept study, two simultaneously scanned foci produced the expected two-fold decrease in fabrication time, and this approach could be readily extended to many scanning foci by using a more powerful laser. Finally, we show that use of multiple foci in MPL can be exploited to assign heterogeneous properties (such as differential swelling) to micromaterials at distinct positions within a fabrication zone.

Translocation of TRPV2 channel induced by focal administration of mechanical stress.

PubMed

Nagasawa, Masahiro; Kojima, Itaru

2015-02-01

The effect of focal mechanical stress on the localization of TRPV2 was investigated in HT1080 cells, where only mRNA for TRPV2 was detected among members of the TRPV channel family. Mechanical stress was applied by adding negative pressure using a glass pipette. When focal mechanical stress was applied, subplasma membrane Ca(2+) concentration ([Ca(2+)]s) was increased beneath the pipette, which propagated throughout the cell. The increase in [Ca(2+)]s was blocked by ruthenium red or by knocking down TRPV2. Elevation of [Ca(2+)]s was not observed by removal of extracellular Ca(2+), by an addition of a phosphatidylinositol 3-kinase inhibitor LY29034, and by transfection of dominant-negative Rac. In cells expressing GFP-TRPV2 and RFP-Akt, administration of focal mechanical stress induced accumulation of GFP-TRPV2 beneath the pipette. RFP-Akt was also accumulated to the same site. Gadolinium blocked the elevation of [Ca(2+)]s induced by focal mechanical stress and also attenuated accumulation of TRPV2. When GFP-TRPV1, GFP-TRPV3, GFP-TRPV4, GFP-TRPV5, or GFP-TRPV6 was transfected ectopically in HT1080 cells, only GFP-TRPV4 was accumulated beneath the pipette in response to the focal mechanical stress. These results indicate that TRPV2 translocates to the site receiving a focal mechanical stress and increases [Ca(2+)]s. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

A prospective study of risk factors for neurological complications in childhood bacterial meningitis.

PubMed

Namani, Sadie; Milenković, Zvonko; Koci, Bulëza

2013-01-01

To prospectively analyze the prognostic factors for neurological complications of childhood bacterial meningitis. This prospective study enrolled 77 children from 1 month until 16 years of age, treated for bacterial meningitis during the period of January 1, 2009 through December 31, 2010. 16 relevant predictors were chosen to analyze their association with the incidence of neurological complications. p-values < 0.05 were considered statistically significant. Of the 77 children treated for bacterial meningitis, 33 patients developed neurological complications (43%), and two children died (2.6%). The etiology of bacterial meningitis cases was proven in 57/77 (74%) cases: 32 meningococci, eight pneumococci, six Gram-negative bacilli, five H. influenzae, five staphylococci, and one S. viridans isolates were found. Factors found to be associated with increased risk of development of neurological complications were age < 12 months, altered mental status, seizures prior to admission, initial therapy with two antibiotics, dexamethasone use, presence of focal neurological deficit on admission and increased proteins in cerebrospinal fluid (CSF) (p < 0.05). Initial pleocytosis > 5,000 cells/mm(3), pleocytosis > 5,000 cells/mm(3) after 48 hours, CSF/blood glucose ratio < 0.20, female gender, previous treatment with antibiotics, community-acquired infection, duration of illness > 48 hours, presence of comorbidity, and primary focus of infection were not associated with increased risk for the development of neurological complications. Age < 12 months and severity of clinical presentation at admission were identified as the strongest predictors of neurological complications and may be of value in selecting patients for more intensive care and treatment. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Mechanisms underlying different onset patterns of focal seizures

PubMed Central

Trevelyan, Andrew J; Valentin, Antonio; Alarcon, Gonzalo

2017-01-01

Focal seizures are episodes of pathological brain activity that appear to arise from a localised area of the brain. The onset patterns of focal seizure activity have been studied intensively, and they have largely been distinguished into two types—low amplitude fast oscillations (LAF), or high amplitude spikes (HAS). Here we explore whether these two patterns arise from fundamentally different mechanisms. Here, we use a previously established computational model of neocortical tissue, and validate it as an adequate model using clinical recordings of focal seizures. We then reproduce the two onset patterns in their most defining properties and investigate the possible mechanisms underlying the different focal seizure onset patterns in the model. We show that the two patterns are associated with different mechanisms at the spatial scale of a single ECoG electrode. The LAF onset is initiated by independent patches of localised activity, which slowly invade the surrounding tissue and coalesce over time. In contrast, the HAS onset is a global, systemic transition to a coexisting seizure state triggered by a local event. We find that such a global transition is enabled by an increase in the excitability of the “healthy” surrounding tissue, which by itself does not generate seizures, but can support seizure activity when incited. In our simulations, the difference in surrounding tissue excitability also offers a simple explanation of the clinically reported difference in surgical outcomes. Finally, we demonstrate in the model how changes in tissue excitability could be elucidated, in principle, using active stimulation. Taken together, our modelling results suggest that the excitability of the tissue surrounding the seizure core may play a determining role in the seizure onset pattern, as well as in the surgical outcome. PMID:28472032

Tremor associated with focal and segmental dystonia.

PubMed

Rudzińska, M; Krawczyk, M; Wójcik-Pędziwiatr, M; Szczudlik, A; Wasielewska, A

2013-01-01

Tremor occurs in 10-85% of patients with focal dystonia as so-called dystonic tremor or tremor associated with dystonia. The aim of this study was to assess the incidence and to characterize parameters of tremor accompanying focal and segmental dystonia. One hundred and twenty-three patients with diagnosis of focal and segmental dystonia together with 51 healthy controls were included in the study. For each participant, clinical examination and objective assessment (accelerometer, electromyography, graphic tablet) of hand tremor was performed. Frequency and severity of tremor were assessed in three positions: at rest (rest tremor); with hands extended (postural tremor); during 'finger-to-nose' test and during Archimedes spiral drawing (kinetic tremor). Based on the mass load test, type of tremor was determined as essential tremor type or enhanced physiological type. The incidence of tremor was significantly higher in dystonic patients as compared to controls (p = 0.0001). In clinical examination, tremor was found in 50% of dystonic patients, and in instrumental assessment in an additional 10-20%. The most frequent type of tremor was postural and kinetic tremor with 7 Hz frequency and featured essential tremor type. In the control group, tremor was detected in about 10% of subjects as 9-Hz postural tremor of enhanced physiological tremor type. No differences were found between patients with different types of dystonia with respect to the tremor incidence, type and parameters (frequency and severity). No correlations between tremor severity and dystonia severity were found either.

Evaluation of focused ultrasound algorithms: Issues for reducing pre-focal heating and treatment time.

PubMed

Yiannakou, Marinos; Trimikliniotis, Michael; Yiallouras, Christos; Damianou, Christakis

2016-02-01

Due to the heating in the pre-focal field the delay between successive movements in high intensity focused ultrasound (HIFU) are sometimes as long as 60s, resulting to treatment time in the order of 2-3h. Because there is generally a requirement to reduce treatment time, we were motivated to explore alternative transducer motion algorithms in order to reduce pre-focal heating and treatment time. A 1 MHz single element transducer with 4 cm diameter and 10 cm focal length was used. A simulation model was developed that estimates the temperature, thermal dose and lesion development in the pre-focal field. The simulated temperature history that was combined with the motion algorithms produced thermal maps in the pre-focal region. Polyacrylimde gel phantom was used to evaluate the induced pre-focal heating for each motion algorithm used, and also was used to assess the accuracy of the simulation model. Three out of the six algorithms having successive steps close to each other, exhibited severe heating in the pre-focal field. Minimal heating was produced with the algorithms having successive steps apart from each other (square, square spiral and random). The last three algorithms were improved further (with small cost in time), thus eliminating completely the pre-focal heating and reducing substantially the treatment time as compared to traditional algorithms. Out of the six algorithms, 3 were successful in eliminating the pre-focal heating completely. Because these 3 algorithms required no delay between successive movements (except in the last part of the motion), the treatment time was reduced by 93%. Therefore, it will be possible in the future, to achieve treatment time of focused ultrasound therapies shorter than 30 min. The rate of ablated volume achieved with one of the proposed algorithms was 71 cm(3)/h. The intention of this pilot study was to demonstrate that the navigation algorithms play the most important role in reducing pre-focal heating. By evaluating in

Large format focal plane array integration with precision alignment, metrology and accuracy capabilities

NASA Astrophysics Data System (ADS)

Neumann, Jay; Parlato, Russell; Tracy, Gregory; Randolph, Max

2015-09-01

Focal plane alignment for large format arrays and faster optical systems require enhanced precision methodology and stability over temperature. The increase in focal plane array size continues to drive the alignment capability. Depending on the optical system, the focal plane flatness of less than 25μm (.001") is required over transition temperatures from ambient to cooled operating temperatures. The focal plane flatness requirement must also be maintained in airborne or launch vibration environments. This paper addresses the challenge of the detector integration into the focal plane module and housing assemblies, the methodology to reduce error terms during integration and the evaluation of thermal effects. The driving factors influencing the alignment accuracy include: datum transfers, material effects over temperature, alignment stability over test, adjustment precision and traceability to NIST standard. The FPA module design and alignment methodology reduces the error terms by minimizing the measurement transfers to the housing. In the design, the proper material selection requires matched coefficient of expansion materials minimizes both the physical shift over temperature as well as lowering the stress induced into the detector. When required, the co-registration of focal planes and filters can achieve submicron relative positioning by applying precision equipment, interferometry and piezoelectric positioning stages. All measurements and characterizations maintain traceability to NIST standards. The metrology characterizes the equipment's accuracy, repeatability and precision of the measurements.

Reactive astrocytes and therapeutic potential in focal ischemic stroke

PubMed Central

Choudhury, Gourav Roy; Ding, Shinghua

2015-01-01

Astrocytes are specialized and the most abundant cell type in the central nervous system (CNS). They play important roles in the physiology of the brain. Astrocytes are also critically involved in many CNS disorders including focal ischemic stroke, the leading cause of brain injury and death in patients. One of the prominent pathological features of a focal ischemic stroke is reactive astrogliosis and glial scar formation. Reactive astrogliosis is accompanied with changes in morphology, proliferation and gene expression in the reactive astrocytes. This study provides an overview of the most recent advances in astrocytic Ca2+ signaling, spatial and temporal dynamics of the morphology and proliferation of reactive astrocytes as well as signaling pathways involved in the reactive astrogliosis after ischemic stroke based on results from experimental studies performed in various animal models. This review also discusses the therapeutic potential of reactive astrocytes in a focal ischemic stroke. As reactive astrocytes exhibit high plasticity, we suggest that modulation of local reactive astrocytes is a promising strategy for cell-based stroke therapy. PMID:25982835

Epidemiological, clinical and genetic aspects of adult onset isolated focal dystonia in Ireland.

PubMed

Williams, L; McGovern, E; Kimmich, O; Molloy, A; Beiser, I; Butler, J S; Molloy, F; Logan, P; Healy, D G; Lynch, T; Walsh, R; Cassidy, L; Moriarty, P; Moore, H; McSwiney, T; Walsh, C; O'Riordan, S; Hutchinson, M

2017-01-01

Adult onset idiopathic isolated focal dystonia presents with a number of phenotypes. Reported prevalence rates vary considerably; well-characterized cohorts are important to our understanding of this disorder. To perform a nationwide epidemiological study of adult onset idiopathic isolated focal dystonia in the Republic of Ireland. Patients with adult onset idiopathic isolated focal dystonia were recruited from multiple sources. Diagnosis was based on assessment by a neurologist with an expertise in movement disorders. When consent was obtained, a number of clinical features including family history were assessed. On the prevalence date there were 592 individuals in Ireland with adult onset idiopathic isolated focal dystonia, a point prevalence of 17.8 per 100 000 (95% confidence interval 16.4-19.2). Phenotype numbers were cervical dystonia 410 (69.2%), blepharospasm 102 (17.2%), focal hand dystonia 39 (6.6%), spasmodic dysphonia 18 (3.0%), musician's dystonia 17 (2.9%) and oromandibular dystonia six (1.0%). Sixty-two (16.5%) of 375 consenting index cases had a relative with clinically confirmed adult onset idiopathic isolated focal dystonia (18 multiplex and 24 duplex families). Marked variations in the proportions of patients with tremor, segmental spread, sensory tricks, pain and psychiatric symptoms by phenotype were documented. The prevalence of adult onset idiopathic isolated focal dystonia in Ireland is higher than that recorded in many similar service-based epidemiological studies but is still likely to be an underestimate. The low proportion of individuals with blepharospasm may reflect reduced environmental exposure to sunlight in Ireland. This study will serve as a resource for international comparative studies of environmental and genetic factors in the pathogenesis of the disorder. © 2016 EAN.

A Micro-Thermal Sensor for Focal Therapy Applications

NASA Astrophysics Data System (ADS)

Natesan, Harishankar; Hodges, Wyatt; Choi, Jeunghwan; Lubner, Sean; Dames, Chris; Bischof, John

2016-02-01

There is an urgent need for sensors deployed during focal therapies to inform treatment planning and in vivo monitoring in thin tissues. Specifically, the measurement of thermal properties, cooling surface contact, tissue thickness, blood flow and phase change with mm to sub mm accuracy are needed. As a proof of principle, we demonstrate that a micro-thermal sensor based on the supported “3ω” technique can achieve this in vitro under idealized conditions in 0.5 to 2 mm thick tissues relevant to cryoablation of the pulmonary vein (PV). To begin with “3ω” sensors were microfabricated onto flat glass as an idealization of a focal probe surface. The sensor was then used to make new measurements of ‘k’ (W/m.K) of porcine PV, esophagus, and phrenic nerve, all needed for PV cryoabalation treatment planning. Further, by modifying the sensor use from traditional to dynamic mode new measurements related to tissue vs. fluid (i.e. water) contact, fluid flow conditions, tissue thickness, and phase change were made. In summary, the in vitro idealized system data presented is promising and warrants future work to integrate and test supported “3ω” sensors on in vivo deployed focal therapy probe surfaces (i.e. balloons or catheters).

The role of executive functioning in memory performance in pediatric focal epilepsy

PubMed Central

Sepeta, Leigh N.; Casaletto, Kaitlin Blackstone; Terwilliger, Virginia; Facella-Ervolini, Joy; Sady, Maegan; Mayo, Jessica; Gaillard, William D.; Berl, Madison M.

2016-01-01

Objective Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Methods Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (WASI/DAS), as well as visual (CMS Dot Locations) and verbal episodic memory (WRAML Story Memory and CVLT-C). Executive functioning was measured directly (WISC-IV Digit Span Backward; CELF-IV Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function (BRIEF)). Results Children with focal epilepsy had lower delayed free recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η2 = .12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η2 = .03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η2 = .08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9–19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9–10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extra-temporal, frontal vs. extra-frontal). Significance Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization

Active Focal Zone Sharpening for High-Precision Treatment Using Histotripsy

PubMed Central

Wang, Tzu-Yin; Xu, Zhen; Hall, Timothy L.; Fowlkes, J. Brian; Roberts, William W.; Cain, Charles A.

2011-01-01

The goal of this study is to develop a focal zone sharpening strategy that produces more precise lesions for pulsed cavitational ultrasound therapy, or histotripsy. Precise and well-confined lesions were produced by locally suppressing cavitation in the periphery of the treatment focus without affecting cavitation in the center. The local suppression of cavitation was achieved using cavitation nuclei preconditioning pulses to actively control cavitation in the periphery of the focus. A 1-MHz 513-element therapeutic array was used to generate both the therapy and the nuclei preconditioning pulses. For therapy, 10-cycle bursts at 100-Hz pulse repetition frequency with P−/P+ pressure of 21/76 MPa were delivered to the geometric focus of the therapeutic array. For nuclei preconditioning, a different pulse was delivered to an annular region immediately surrounding the focus before each therapy pulse. A parametric study on the effective pressure, pulse duration, and delivery time of the preconditioning pulse was conducted in red blood cell-gel phantoms, where cavitational damage was indicated by the color change resulting from local cell lysis. Results showed that a short-duration (20 µs) preconditioning pulse at a medium pressure (P−/P+ pressure of 7.2/13.6 MPa) delivered shortly before (30 µs) the therapy pulse substantially suppressed the peripheral damage by 77 ± 13% while complete fractionation in the focal center was maintained. High-speed imaging of the bubble cloud showed a substantial decrease in the maximum width of the bubble cloud by 48 ± 24% using focal zone sharpening. Experiments in ex vivo livers confirmed that highly confined lesions were produced in real tissues as well as in the phantoms. This study demonstrated the feasibility of active focal zone sharpening using cavitation nuclei preconditioning, allowing for increased treatment precision compared with the natural focal width of the therapy transducer. PMID:21342816

Active focal zone sharpening for high-precision treatment using histotripsy.

PubMed

Wang, Tzu-Yin; Xu, Zhen; Hall, Timothy; Fowlkes, J; Roberts, William; Cain, Charles

2011-02-01

The goal of this study is to develop a focal zone sharpening strategy that produces more precise lesions for pulsed cavitational ultrasound therapy, or histotripsy. Precise and well-confined lesions were produced by locally suppressing cavitation in the periphery of the treatment focus without affecting cavitation in the center. The local suppression of cavitation was achieved using cavitation nuclei preconditioning pulses to actively control cavitation in the periphery of the focus. A 1-MHz 513-element therapeutic array was used to generate both the therapy and the nuclei preconditioning pulses. For therapy, 10-cycle bursts at 100-Hz pulse repetition frequency with P-/P+ pressure of 21/76 MPa were delivered to the geometric focus of the therapeutic array. For nuclei preconditioning, a different pulse was delivered to an annular region immediately surrounding the focus before each therapy pulse. A parametric study on the effective pressure, pulse duration, and delivery time of the preconditioning pulse was conducted in red blood cell-gel phantoms, where cavitational damage was indicated by the color change resulting from local cell lysis. Results showed that a short-duration (20 μs) preconditioning pulse at a medium pressure (P-/P+ pressure of 7.2/13.6 MPa) delivered shortly before (30 μs) the therapy pulse substantially suppressed the peripheral damage by 77 ± 13% while complete fractionation in the focal center was maintained. High-speed imaging of the bubble cloud showed a substantial decrease in the maximum width of the bubble cloud by 48 ± 24% using focal zone sharpening. Experiments in ex vivo livers confirmed that highly confined lesions were produced in real tissues as well as in the phantoms. This study demonstrated the feasibility of active focal zone sharpening using cavitation nuclei preconditioning, allowing for increased treatment precision compared with the natural focal width of the therapy transducer.

DCEUS-based focal parametric perfusion imaging of microvessel with single-pixel resolution and high contrast.

PubMed

Wang, Diya; Xiao, Mengnan; Hu, Hong; Zhang, Yu; Su, Zhe; Xu, Shanshan; Zong, Yujin; Wan, Mingxi

2018-03-01

This study aimed to develop a focal microvascular contrast-enhanced ultrasonic parametric perfusion imaging (PPI) scheme to overcome the tradeoff between the resolution, contrast, and accuracy of focal PPI in the tumor. Its resolution was limited by the low signal-to-clutter ratio (SCR) of time-intensity-curves (TICs) induced by multiple limitations, which deteriorated the accuracy and contrast of focal PPI. The scheme was verified by the in-vivo perfusion experiments. Single-pixel TICs were first extracted to ensure PPI with the highest resolution. The SCR of focal TICs in the tumor was improved using respiratory motion compensation combined with detrended fluctuation analysis. The entire and focal PPIs of six perfusion parameters were then accurately created after filtrating the valid TICs and targeted perfusion parameters. Compared with those of the conventional PPIs, the axial and lateral resolutions of focal PPIs were improved by 30.29% (p < .05) and 32.77% (p < .05), respectively; the average contrast and accuracy evaluated by SCR improved by 7.24 ± 4.90 dB (p < .05) and 5.18 ± 1.28 dB (p < .05), respectively. The edge, morphostructure, inhomogeneous hyper-enhanced distribution, and ring-like perfusion features in intratumoral microvessel were accurately distinguished and highlighted by the focal PPIs. The developed focal PPI can assist clinicians in making confirmed diagnoses and in providing appropriate therapeutic strategies for liver tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

Focal posterior pole viral retinitis.

PubMed

Hazirolan, Dicle; Sungur, Gulten; Demir, Necati; Kasim, Remzi; Duman, Sunay

2010-01-01

To describe the clinical features of an atypical form of viral retinitis in immunocompetent patients. This was a retrospective noncomparative case series. The charts of 8 patients diagnosed with and treated for focal posterior viral retinitis were reviewed. Clinical and demographic features were evaluated. All the patients had extensive laboratory tests, fundus fluorescein angiography, optical coherence tomography of macula, and polymerase chain reaction of vitreous. All the patients were referred to our Uveitis Service from other hospitals, as their uveitis symptoms deteriorated in spite of treatment. The mean age of 4 male and 4 female patients was 32.1 years (range, 22-42 years). The mean follow-up period was 10 months (range, 6-18 months). All of the patients had unilateral disease. Polymerase chain reaction analysis of vitreous specimen was positive for herpes simplex virus-1 in 5 patients and varicella zoster virus in 3 patients. Retinitis resolved after systemic acyclovir treatment in all patients. Viral etiology must be borne in mind in the differential diagnosis of atypical retinitis. It can be a milder form of viral retinitis like focal viral retinitis, as mentioned in this study. The prognosis of this disease is better than the other forms of necrotizing retinopathies involving a larger area of retina.

The statistics of calcium-mediated focal excitations on a one-dimensional cable.

PubMed

Chen, Wei; Asfaw, Mesfin; Shiferaw, Yohannes

2012-02-08

It is well known that various cardiac arrhythmias are initiated by an ill-timed excitation that originates from a focal region of the heart. However, up to now, it is not known what governs the timing, location, and morphology of these focal excitations. Recent studies have shown that these excitations can be caused by abnormalities in the calcium (Ca) cycling system. However, the cause-and-effect relationships linking subcellular Ca dynamics and focal activity in cardiac tissue is not completely understood. In this article, we present a minimal model of Ca-mediated focal excitations in cardiac tissue. This model accounts for the stochastic nature of spontaneous Ca release on a one-dimensional cable of cardiac cells. Using this model, we show that the timing of focal excitations is equivalent to a first passage time problem in a spatially extended system. In particular, we find that for a short cable the mean first passage time increases exponentially with the number of cells in tissue, and is critically dependent on the ratio of inward to outward currents near the threshold for an action potential. For long cables excitations occurs due to ectopic foci that occur on a length scale determined by the minimum length of tissue that can induce an action potential. Furthermore, we find that for long cables the mean first passage time decreases as a power law in the number cells. These results provide precise criteria for the occurrence of focal excitations in cardiac tissue, and will serve as a guide to determine the propensity of Ca-mediated triggered arrhythmias in the heart. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

1024x1024 Pixel MWIR and LWIR QWIP Focal Plane Arrays and 320x256 MWIR:LWIR Pixel Colocated Simultaneous Dualband QWIP Focal Plane Arrays

NASA Technical Reports Server (NTRS)

Gunapala, Sarath D.; Bandara, Sumith V.; Liu, John K.; Hill, Cory J.; Rafol, S. B.; Mumolo, Jason M.; Trinh, Joseph T.; Tidrow, M. Z.; Le Van, P. D.

2005-01-01

Mid-wavelength infrared (MWIR) and long-wavelength infrared (LWIR) 1024x1024 pixel quantum well infrared photodetector (QWIP) focal planes have been demonstrated with excellent imaging performance. The MWIR QWIP detector array has demonstrated a noise equivalent differential temperature (NE(Delta)T) of 17 mK at a 95K operating temperature with f/2.5 optics at 300K background and the LWIR detector array has demonstrated a NE(Delta)T of 13 mK at a 70K operating temperature with the same optical and background conditions as the MWIR detector array after the subtraction of system noise. Both MWIR and LWIR focal planes have shown background limited performance (BLIP) at 90K and 70K operating-temperatures respectively, with similar optical and background conditions. In addition, we are in the process of developing MWIR and LWIR pixel collocated simultaneously readable dualband QWIP focal plane arrays.

Bacterial prostatitis.

PubMed

Gill, Bradley C; Shoskes, Daniel A

2016-02-01

The review provides the infectious disease community with a urologic perspective on bacterial prostatitis. Specifically, the article briefly reviews the categorization of prostatitis by type and provides a distillation of new findings published on bacterial prostatitis over the past year. It also highlights key points from the established literature. Cross-sectional prostate imaging is becoming more common and may lead to more incidental diagnoses of acute bacterial prostatitis. As drug resistance remains problematic in this condition, the reemergence of older antibiotics such as fosfomycin, has proven beneficial. With regard to chronic bacterial prostatitis, no clear clinical risk factors emerged in a large epidemiological study. However, bacterial biofilm formation has been associated with more severe cases. Surgery has a limited role in bacterial prostatitis and should be reserved for draining of a prostatic abscess or the removal of infected prostatic stones. Prostatitis remains a common and bothersome clinical condition. Antibiotic therapy remains the basis of treatment for both acute and chronic bacterial prostatitis. Further research into improving prostatitis treatment is indicated.

Complementarity of PALM and SOFI for super-resolution live-cell imaging of focal adhesions

PubMed Central

Deschout, Hendrik; Lukes, Tomas; Sharipov, Azat; Szlag, Daniel; Feletti, Lely; Vandenberg, Wim; Dedecker, Peter; Hofkens, Johan; Leutenegger, Marcel; Lasser, Theo; Radenovic, Aleksandra

2016-01-01

Live-cell imaging of focal adhesions requires a sufficiently high temporal resolution, which remains a challenge for super-resolution microscopy. Here we address this important issue by combining photoactivated localization microscopy (PALM) with super-resolution optical fluctuation imaging (SOFI). Using simulations and fixed-cell focal adhesion images, we investigate the complementarity between PALM and SOFI in terms of spatial and temporal resolution. This PALM-SOFI framework is used to image focal adhesions in living cells, while obtaining a temporal resolution below 10 s. We visualize the dynamics of focal adhesions, and reveal local mean velocities around 190 nm min−1. The complementarity of PALM and SOFI is assessed in detail with a methodology that integrates a resolution and signal-to-noise metric. This PALM and SOFI concept provides an enlarged quantitative imaging framework, allowing unprecedented functional exploration of focal adhesions through the estimation of molecular parameters such as fluorophore densities and photoactivation or photoswitching kinetics. PMID:27991512

Complementarity of PALM and SOFI for super-resolution live-cell imaging of focal adhesions

NASA Astrophysics Data System (ADS)

Deschout, Hendrik; Lukes, Tomas; Sharipov, Azat; Szlag, Daniel; Feletti, Lely; Vandenberg, Wim; Dedecker, Peter; Hofkens, Johan; Leutenegger, Marcel; Lasser, Theo; Radenovic, Aleksandra

2016-12-01

Live-cell imaging of focal adhesions requires a sufficiently high temporal resolution, which remains a challenge for super-resolution microscopy. Here we address this important issue by combining photoactivated localization microscopy (PALM) with super-resolution optical fluctuation imaging (SOFI). Using simulations and fixed-cell focal adhesion images, we investigate the complementarity between PALM and SOFI in terms of spatial and temporal resolution. This PALM-SOFI framework is used to image focal adhesions in living cells, while obtaining a temporal resolution below 10 s. We visualize the dynamics of focal adhesions, and reveal local mean velocities around 190 nm min-1. The complementarity of PALM and SOFI is assessed in detail with a methodology that integrates a resolution and signal-to-noise metric. This PALM and SOFI concept provides an enlarged quantitative imaging framework, allowing unprecedented functional exploration of focal adhesions through the estimation of molecular parameters such as fluorophore densities and photoactivation or photoswitching kinetics.

Complementarity of PALM and SOFI for super-resolution live-cell imaging of focal adhesions.

PubMed

Deschout, Hendrik; Lukes, Tomas; Sharipov, Azat; Szlag, Daniel; Feletti, Lely; Vandenberg, Wim; Dedecker, Peter; Hofkens, Johan; Leutenegger, Marcel; Lasser, Theo; Radenovic, Aleksandra

2016-12-19

Live-cell imaging of focal adhesions requires a sufficiently high temporal resolution, which remains a challenge for super-resolution microscopy. Here we address this important issue by combining photoactivated localization microscopy (PALM) with super-resolution optical fluctuation imaging (SOFI). Using simulations and fixed-cell focal adhesion images, we investigate the complementarity between PALM and SOFI in terms of spatial and temporal resolution. This PALM-SOFI framework is used to image focal adhesions in living cells, while obtaining a temporal resolution below 10 s. We visualize the dynamics of focal adhesions, and reveal local mean velocities around 190 nm min -1 . The complementarity of PALM and SOFI is assessed in detail with a methodology that integrates a resolution and signal-to-noise metric. This PALM and SOFI concept provides an enlarged quantitative imaging framework, allowing unprecedented functional exploration of focal adhesions through the estimation of molecular parameters such as fluorophore densities and photoactivation or photoswitching kinetics.

Formation of multiple focal spots using a high NA lens with a complex spiral phase mask

NASA Astrophysics Data System (ADS)

Lalithambigai, K.; Anbarasan, P. M.; Rajesh, K. B.

2014-07-01

The formation of a transversally polarized beam by transmitting a tightly focused double-ring-shaped azimuthally polarized beam through a complex spiral phase mask and high numerical aperture lens is presented based on vector diffraction theory. The generation of transversally polarized focal spot segment splitting and multiple focal spots is illustrated numerically. Moreover, we found that a properly designed complex spiral phase mask can move the focal spots along the optical axis in the z direction. Therefore, one can achieve a focal segment of two, three or multiple completely transversely polarized focal spots, which finds applications in optical trapping and in material processing technologies.

Bacterial Sialidase

NASA Technical Reports Server (NTRS)

2004-01-01

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

Taxonomy of multi-focal nematode image stacks by a CNN based image fusion approach.

PubMed

Liu, Min; Wang, Xueping; Zhang, Hongzhong

2018-03-01

In the biomedical field, digital multi-focal images are very important for documentation and communication of specimen data, because the morphological information for a transparent specimen can be captured in form of a stack of high-quality images. Given biomedical image stacks containing multi-focal images, how to efficiently extract effective features from all layers to classify the image stacks is still an open question. We present to use a deep convolutional neural network (CNN) image fusion based multilinear approach for the taxonomy of multi-focal image stacks. A deep CNN based image fusion technique is used to combine relevant information of multi-focal images within a given image stack into a single image, which is more informative and complete than any single image in the given stack. Besides, multi-focal images within a stack are fused along 3 orthogonal directions, and multiple features extracted from the fused images along different directions are combined by canonical correlation analysis (CCA). Because multi-focal image stacks represent the effect of different factors - texture, shape, different instances within the same class and different classes of objects, we embed the deep CNN based image fusion method within a multilinear framework to propose an image fusion based multilinear classifier. The experimental results on nematode multi-focal image stacks demonstrated that the deep CNN image fusion based multilinear classifier can reach a higher classification rate (95.7%) than that by the previous multilinear based approach (88.7%), even we only use the texture feature instead of the combination of texture and shape features as in the previous work. The proposed deep CNN image fusion based multilinear approach shows great potential in building an automated nematode taxonomy system for nematologists. It is effective to classify multi-focal image stacks. Copyright © 2018 Elsevier B.V. All rights reserved.

Temporal and Spatial Impact of Human Cadaver Decomposition on Soil Bacterial and Arthropod Community Structure and Function

PubMed Central

Singh, Baneshwar; Minick, Kevan J.; Strickland, Michael S.; Wickings, Kyle G.; Crippen, Tawni L.; Tarone, Aaron M.; Benbow, M. Eric; Sufrin, Ness; Tomberlin, Jeffery K.; Pechal, Jennifer L.

2018-01-01

As vertebrate carrion decomposes, there is a release of nutrient-rich fluids into the underlying soil, which can impact associated biological community structure and function. How these changes alter soil biogeochemical cycles is relatively unknown and may prove useful in the identification of carrion decomposition islands that have long lasting, focal ecological effects. This study investigated the spatial (0, 1, and 5 m) and temporal (3–732 days) dynamics of human cadaver decomposition on soil bacterial and arthropod community structure and microbial function. We observed strong evidence of a predictable response to cadaver decomposition that varies over space for soil bacterial and arthropod community structure, carbon (C) mineralization and microbial substrate utilization patterns. In the presence of a cadaver (i.e., 0 m samples), the relative abundance of Bacteroidetes and Firmicutes was greater, while the relative abundance of Acidobacteria, Chloroflexi, Gemmatimonadetes, and Verrucomicrobia was lower when compared to samples at 1 and 5 m. Micro-arthropods were more abundant (15 to 17-fold) in soils collected at 0 m compared to either 1 or 5 m, but overall, micro-arthropod community composition was unrelated to either bacterial community composition or function. Bacterial community structure and microbial function also exhibited temporal relationships, whereas arthropod community structure did not. Cumulative precipitation was more effective in predicting temporal variations in bacterial abundance and microbial activity than accumulated degree days. In the presence of the cadaver (i.e., 0 m samples), the relative abundance of Actinobacteria increased significantly with cumulative precipitation. Furthermore, soil bacterial communities and C mineralization were sensitive to the introduction of human cadavers as they diverged from baseline levels and did not recover completely in approximately 2 years. These data are valuable for understanding ecosystem

Temporal and Spatial Impact of Human Cadaver Decomposition on Soil Bacterial and Arthropod Community Structure and Function.

PubMed

Singh, Baneshwar; Minick, Kevan J; Strickland, Michael S; Wickings, Kyle G; Crippen, Tawni L; Tarone, Aaron M; Benbow, M Eric; Sufrin, Ness; Tomberlin, Jeffery K; Pechal, Jennifer L

2017-01-01

As vertebrate carrion decomposes, there is a release of nutrient-rich fluids into the underlying soil, which can impact associated biological community structure and function. How these changes alter soil biogeochemical cycles is relatively unknown and may prove useful in the identification of carrion decomposition islands that have long lasting, focal ecological effects. This study investigated the spatial (0, 1, and 5 m) and temporal (3-732 days) dynamics of human cadaver decomposition on soil bacterial and arthropod community structure and microbial function. We observed strong evidence of a predictable response to cadaver decomposition that varies over space for soil bacterial and arthropod community structure, carbon (C) mineralization and microbial substrate utilization patterns. In the presence of a cadaver (i.e., 0 m samples), the relative abundance of Bacteroidetes and Firmicutes was greater, while the relative abundance of Acidobacteria, Chloroflexi, Gemmatimonadetes, and Verrucomicrobia was lower when compared to samples at 1 and 5 m. Micro-arthropods were more abundant (15 to 17-fold) in soils collected at 0 m compared to either 1 or 5 m, but overall, micro-arthropod community composition was unrelated to either bacterial community composition or function. Bacterial community structure and microbial function also exhibited temporal relationships, whereas arthropod community structure did not. Cumulative precipitation was more effective in predicting temporal variations in bacterial abundance and microbial activity than accumulated degree days. In the presence of the cadaver (i.e., 0 m samples), the relative abundance of Actinobacteria increased significantly with cumulative precipitation. Furthermore, soil bacterial communities and C mineralization were sensitive to the introduction of human cadavers as they diverged from baseline levels and did not recover completely in approximately 2 years. These data are valuable for understanding ecosystem function

Rapid focal cooling attenuates cortical seizures in a primate epilepsy model.

PubMed

Ren, Guoping; Yan, Jiaqing; Tao, Guoxian; Gan, Yunmeng; Li, Donghong; Yan, Xi; Fu, Yongjuan; Wang, Leiming; Wang, Weimin; Zhang, Zhiming; Yue, Feng; Yang, Xiaofeng

2017-09-01

Rapid focal cooling is an attractive nondestructive strategy to control and possibly prevent focal seizures. However, the temperature threshold necessary to abort seizures in primates is still unknown. Here, we explored this issue in a primate epilepsy model and observed the effect of rapid cooling on different electroencephalogram frequency bands, aiming at providing necessary experimental data for future clinical translational studies and exploring the mechanism of focal cooling in terminating seizures. We induced focal neocortical seizures using microinjection of 4-aminopyridine into premotor cortex in five anesthetized cynomolgus monkeys. The rapid focal cooling was implemented by using a thermoelectric (Peltier) device. As a result, the average durations of seizures and interictal intervals before cooling were 94.3±4.0s and 62.3±6.9s, respectively. When the cortex was cooled to 20°C or 18°C, there was no effect on seizure duration (109.4±30.0s, 91.3±19.3s) or interictal duration (99.4±26.8s, 83.2±11.5s, P>0.05). But when the cortex was cooled to 16°C, the seizure duration was reduced to 54.1±4.9s and the interictal duration was extended to 175.0±16.7s (P<0.05). Electroencephalogram spectral analysis showed that the power of delta, alpha, beta, gamma and ripples bands in seizures were significantly reduced at 20°C and 18°C. At 16°C, the power of theta band in seizures was also significantly reduced along with the other bands. Our data reveal that the temperature threshold in rapid focal cooling required to significantly shorten neocortical seizures in nonhuman primates is 16°C, and inhibition of electroencephalogram broadband spectrum power, especially power of theta band, may be the underlying mechanism to control seizures. Copyright © 2017. Published by Elsevier Inc.

Focal application of low-dose-rate brachytherapy for prostate cancer: a pilot study

PubMed Central

Spadinger, Ingrid T.; Salcudean, Septimiu E.; Kozlowski, Piotr; Chang, Silvia D.; Ng, Tony; Lobo, Julio; Nir, Guy; Moradi, Hamid; Peacock, Michael; Morris, W. James

2017-01-01

Purpose To evaluate the feasibility and to report the early outcomes of focal treatment of prostate cancer using low-dose-rate brachytherapy (LDR-PB). Material and methods Seventeen patients were screened with multi-parametric magnetic resonance imaging (mpMRI), 14 of whom proceeded to receive trans-perineal template mapping biopsy (TTMB). Focal LDR-PB was performed on five eligible patients using dual air kerma strength treatment plans based on planning target volumes derived from cancer locations and determined by TTMB. Patient follow-up includes prostate specific antigen (PSA) measurements, urinary and sexual function questionnaires, repeated imaging and TTMB at specific intervals post-treatment. Results Feasibility of focal LDR-PB was shown and short-term outcomes are promising. While the detection rate of tumors, a majority of which were low grade GS 3 + 3, was found to be low on mpMRI (sensitivity of 37.5%), our results suggest the potential of mpMRI in detecting the presence of higher grade (GS ≥ 3 + 4), and bilateral disease indicating its usefulness as a screening tool for focal LDR-PB. Conclusions Low-dose-rate brachytherapy is a favorable ablation option for focal treatment of prostate cancer, requiring minimal modification to the standard (whole gland) LDR-PB treatment, and appears to have a more favorable side effect profile. Further investigation, in the form of a larger study, is needed to assess the methods used and the long-term outcomes of focal LDR-PB. PMID:28725242

Prior task experience and comparable stimulus exposure nullify focal and nonfocal prospective memory retrieval differences.

PubMed

Hicks, Jason L; Franks, Bryan A; Spitler, Samantha N

2017-10-01

We explored the nature of focal versus nonfocal event-based prospective memory retrieval. In the context of a lexical decision task, people received an intention to respond to a single word (focal) in one condition and to a category label (nonfocal) for the other condition. Participants experienced both conditions, and their order was manipulated. The focal instruction condition was a single word presented multiple times. In Experiment 1, the stimuli in the nonfocal condition were different exemplars from a category, each presented once. In the nonfocal condition retrieval was poorer and reaction times were slower during the ongoing task as compared to the focal condition, replicating prior findings. In Experiment 2, the stimulus in the nonfocal condition was a single category exemplar repeated multiple times. When this single-exemplar nonfocal condition followed in time the single-item focal condition, focal versus nonfocal performance was virtually indistinguishable. These results demonstrate that people can modify their stimulus processing and expectations in event-based prospective memory tasks based on experience with the nature of prospective cues and with the ongoing task.

Multiplexing of miniaturized planar antibody arrays for serum protein profiling--a biomarker discovery in SLE nephritis.

PubMed

Petersson, Linn; Dexlin-Mellby, Linda; Bengtsson, Anders A; Sturfelt, Gunnar; Borrebaeck, Carl A K; Wingren, Christer

2014-06-07

In the quest to decipher disease-associated biomarkers, miniaturized and multiplexed antibody arrays may play a central role in generating protein expression profiles, or protein maps, of crude serum samples. In this conceptual study, we explored a novel, 4-times larger pen design, enabling us to, in a unique manner, simultaneously print 48 different reagents (antibodies) as individual 78.5 μm(2) (10 μm in diameter) sized spots at a density of 38,000 spots cm(-2) using dip-pen nanolithography technology. The antibody array set-up was interfaced with a high-resolution fluorescent-based scanner for sensitive sensing. The performance and applicability of this novel 48-plex recombinant antibody array platform design was demonstrated in a first clinical application targeting SLE nephritis, a severe chronic autoimmune connective tissue disorder, as the model disease. To this end, crude, directly biotinylated serum samples were targeted. The results showed that the miniaturized and multiplexed array platform displayed adequate performance, and that SLE-associated serum biomarker panels reflecting the disease process could be deciphered, outlining the use of miniaturized antibody arrays for disease proteomics and biomarker discovery.

The use of waveform shapes to automatically determine earthquake focal depth

USGS Publications Warehouse

Sipkin, S.A.

2000-01-01

Earthquake focal depth is an important parameter for rapidly determining probable damage caused by a large earthquake. In addition, it is significant both for discriminating between natural events and explosions and for discriminating between tsunamigenic and nontsunamigenic earthquakes. For the purpose of notifying emergency management and disaster relief organizations as well as issuing tsunami warnings, potential time delays in determining source parameters are particularly detrimental. We present a method for determining earthquake focal depth that is well suited for implementation in an automated system that utilizes the wealth of broadband teleseismic data that is now available in real time from the global seismograph networks. This method uses waveform shapes to determine focal depth and is demonstrated to be valid for events with magnitudes as low as approximately 5.5.

Scanning metallic nanosphere microscopy for vectorial profiling of optical focal spots.

PubMed

Yi, Hui; Long, Jing; Li, Hongquan; He, Xiaolong; Yang, Tian

2015-04-06

Recent years have witnessed fast progress in the development of spatially variant states of polarization under high numerical aperture focusing, and intensive exploration of their applications. We report a vectorial, broadband, high contrast and subwavelength resolution method for focal spot profiling. In this experiment, a 100 nm diameter gold nanosphere on a silica aerogel substrate is raster scanned across the focal spots, and the orthogonal polarization components can be obtained simultaneously by measuring the scattering far field in a confocal manner. The metallic-nanosphere-on-aerogel structure ensures negligible distortion to the focal spots, low crosstalk between orthogonal polarization components (1/39 in experiment), and a low level background noise (1/80 of peak intensity in experiment), while high contrast imaging is not limited by the resonance bandwidth.

Fabrication of Transition Edge Sensor Microcalorimeters for X-Ray Focal Planes

NASA Technical Reports Server (NTRS)

Chervenak, James A.; Adams, Joseph S.; Audley, Heather; Bandler, Simon R.; Betancourt-Martinez, Gabriele; Eckart, Megan E.; Finkbeiner, Fred M.; Kelley, Richard L.; Kilbourne, Caroline; Lee, Sang Jun;

Pros and Cons of Focal Therapy for Localised Prostate Cancer

PubMed Central

Mearini, Luigi; Porena, Massimo

2011-01-01

In prostate cancer, an interesting and intriguing option to overcome the risks of whole-gland treatment is focal therapy, with the aim of eradicating known cancer foci and reducing collateral damages to the structures essential for maintaining normal urinary and sexual function. Ablation of all known lesions would favorably alter the natural history of the cancer without impacting health-related quality of life and allows for safe retreatment with repeated focal therapy or whole-gland approaches if necessary. Our objective is to reassess the possibilities and criticisms of such procedure: the rationale for focal therapy and the enthusiasm come from the success of conservative approaches in treating other malignancies and in the high incidence of overtreatment introduced by prostate cancer screening programs. One of the challenges in applying such an approach to the treatment of prostate cancer is the multifocal nature of the disease and current difficulties in accurate tumor mapmaking. PMID:22110990

The influence of focal spot blooming on high-contrast spatial resolution in CT imaging.

PubMed

Grimes, Joshua; Duan, Xinhui; Yu, Lifeng; Halaweish, Ahmed F; Haag, Nicole; Leng, Shuai; McCollough, Cynthia

2015-10-01

The objective of this work was to investigate focal spot blooming effects on the spatial resolution of CT images and to evaluate an x-ray tube that uses dynamic focal spot control for minimizing focal spot blooming. The influence of increasing tube current at a fixed tube potential of 80 kV on high-contrast spatial resolution of seven different CT scanner models (scanners A-G), including one scanner that uses dynamic focal spot control to reduce focal spot blooming (scanner A), was evaluated. Spatial resolution was assessed using a wire phantom for the modulation transfer function (MTF) calculation and a copper disc phantom for measuring the slice sensitivity profile (SSP). The impact of varying the tube potential was investigated on two scanner models (scanners A and B) by measuring the MTF and SSP and also by using the resolution bar pattern module of the ACR CT phantom. The phantoms were scanned at 70-150 kV on scanner A and 80-140 kV on scanner B, with tube currents from 100 mA up to the maximum tube current available on each scanner. The images were reconstructed using a slice thickness of 0.6 mm with both smooth and sharp kernels. Additionally, focal spot size at varying tube potentials and currents was directly measured using pinhole and slit camera techniques. Evaluation of the MTF and SSP data from the 7 CT scanner models evaluated demonstrated decreased focal spot blooming for newer scanners, as evidenced by decreasing deviations in MTF and SSP as tube current varied. For scanners A and B, where focal spot blooming effects as a function of tube potential were assessed, the spatial resolution variation in the axial plane was much smaller on scanner A compared to scanner B as tube potential and current changed. On scanner A, the 50% MTF never decreased by more than 2% from the 50% MTF measured at 100 mA. On scanner B, the 50% MTF decreased by as much as 19% from the 50% MTF measured at 100 mA. Assessments of the SSP, the bar patterns in the ACR phantom and

X-ray focal spot reconstruction by circular penumbra analysis-Application to digital radiography systems.

PubMed

Di Domenico, Giovanni; Cardarelli, Paolo; Contillo, Adriano; Taibi, Angelo; Gambaccini, Mauro

2016-01-01

The quality of a radiography system is affected by several factors, a major one being the focal spot size of the x-ray tube. In fact, the measurement of such size is recognized to be of primary importance during acceptance tests and image quality evaluations of clinical radiography systems. The most common device providing an image of the focal spot emission distribution is a pin-hole camera, which requires a high tube loading in order to produce a measurable signal. This work introduces an alternative technique to obtain an image of the focal spot, through the processing of a single radiograph of a simple test object, acquired with a suitable magnification. The radiograph of a magnified sharp edge is a well-established method to evaluate the extension of the focal spot profile along the direction perpendicular to the edge. From a single radiograph of a circular x-ray absorber, it is possible to extract simultaneously the radial profiles of several sharp edges with different orientations. The authors propose a technique that allows to obtain an image of the focal spot through the processing of these radial profiles by means of a pseudo-CT reconstruction technique. In order to validate this technique, the reconstruction has been applied to the simulated radiographs of an ideal disk-shaped absorber, generated by various simulated focal spot distributions. Furthermore, the method has been applied to the focal spot of a commercially available mammography unit. In the case of simulated radiographs, the results of the reconstructions have been compared to the original distributions, showing an excellent agreement for what regards both the overall distribution and the full width at half maximum measurements. In the case of the experimental test, the method allowed to obtain images of the focal spot that have been compared with the results obtained through standard techniques, namely, pin-hole camera and slit camera. The method was proven to be effective for simulated

Elevated Subclinical Double-Stranded DNA Antibodies and Future Proliferative Lupus Nephritis

PubMed Central

Lee, Jessica J.; Prince, Lisa K.; Baker, Thomas P.; Papadopoulos, Patricia; Edison, Jess; Abbott, Kevin C.

2013-01-01

Summary Background and objectives Elevated anti–double-stranded DNA (dsDNA) antibody and C-reactive protein are associated with proliferative lupus nephritis (PLN). Progression of quantitative anti-dsDNA antibody in patients with PLN has not been compared with that in patients with systemic lupus erythematosus (SLE) without LN before diagnosis. The temporal relationship between anti-dsDNA antibody and C-reactive protein elevation has also not been evaluated. Design, setting, participants, & measurements This case-control Department of Defense Serum Repository (established in 1985) study compared longitudinal prediagnostic quantitative anti-dsDNA antibody and C-reactive protein levels in 23 patients with biopsy-proven PLN (Walter Reed Army Medical Center, 1993–2009) with levels in 21 controls with SLE but without LN matched for patient age, sex, race, and age of serum sample. The oldest (median, 2601 days; 25%, 1245 days, 75%, 3075 days), the second to last (368; 212, 635 days), and the last (180; 135, 477 days) serum sample before diagnosis were analyzed. Results More patients with PLN had an elevated anti-dsDNA antibody level than did the matched controls at any point (78% versus 5%; P<0.001), <1 year (82% versus 8%; P<0.001), 1–4 years (53% versus 0%; P<0.001), and >4 years (33% versus 0%; P=0.04) before diagnosis. A rate of increase >1 IU/ml per year (70% versus 0%; P<0.001) was most specific for PLN. The anti-dsDNA antibody levels increased before C-reactive protein did in most patients with an antecedent elevation (92% versus 8%; P<0.001). Conclusions Elevated anti-dsDNA antibody usually precedes both clinical and subclinical evidence of proliferative LN, which suggests direct pathogenicity. Absolute anti-dsDNA antibody level and rate of increase could better establish risk of future PLN in patients with SLE. PMID:23833315

Loss of CD11b Exacerbates Murine Complement-Mediated Tubulointerstitial Nephritis

PubMed Central

Wang, Ying; Chang, Anthony; Haas, Mark; Quigg, Richard John

2014-01-01

Acute complement activation occurs in the tubulointerstitium (TI) of kidneys transplanted from Crry−/−C3−/− mice into complement-sufficient wildtype mice, followed by marked inflammatory cell infiltration, tubular damage and interstitial fibrosis. We postulated iC3b-CD11b interactions were critical in this TI nephritis model. We transplanted Crry−/−C3−/− mouse kidneys into CD11b−/− and wildtype C57BL/6 mice. Surprisingly, there was greater inflammation in Crry−/−C3−/− kidneys in CD11b−/− recipients compared to those in wildtype hosts. Kidneys in CD11b−/− recipients had large numbers of CD11b−Ly6ChiCCR2hiF4/80+ cells consistent with inflammatory (M1) macrophages recruited from circulating monocytes of the host CD11b−/− animal. There was also an expanded population of CD11b+CD11c+Ly6C−F4/80hi cells. Since these cells were CD11b+, they must have originated from the transplanted kidney; their surface protein expression and appearance within the kidney were consistent with the intrinsic renal mononuclear cellular population. These cells were markedly expanded relative to all relevant controls, including the contralateral donor kidney and Crry−/−C3−/− mouse kidneys in CD11b+/+ wildtype recipients. Direct evidence for their in situ proliferation was the presence of nuclear Ki67 and PCNA in CD11b+F4/80+ cells. Thus, in this experimental model in which there is unrestricted C3 activation, CD11b+ monocytes limit their own infiltration into the kidney and prevent proliferation of endogenous mononuclear cells. This suggests a role for outside-in iC3b-CD11b signals in limiting intrinsic organ inflammation. PMID:24632830

Increased calcineurin expression after pilocarpine-induced status epilepticus is associated with brain focal edema and astrogliosis.

PubMed

Liu, Jinzhi; Li, Xiaolin; Chen, Liguang; Xue, Ping; Yang, Qianqian; Wang, Aihua

2015-07-28

Calcineurin plays an important role in the development of neuronal excitability, modulation of receptor's function and induction of apoptosis in neurons. It has been established in kindling models that status epilepticus induces brain focal edema and astrocyte activation. However, the role of calcineurin in brain focal edema and astrocyte activation in status epilepticus has not been fully understood. In this study, we employed a model of lithium-pilocarpine-induced status epilepticus and detected calcineurin expression in hippocampus by immunoblotting, brain focal edema by non-invasive magnetic resonance imaging (MRI-7T) and astrocyte expression by immunohistochemistry. We found that the brain focal edema was seen at 24 h after status epilepticus, and astrocyte expression was obviously seen at 7 d after status epilepticus. Meanwhile, calcineurin expression was seen at24 h and retained to 7 d after status epilepticus. A FK506, a calcineurin inhibitor, remarkably suppressed the status epilepticus-induced brain focal edema and astrocyte expression. Our data suggested that calcineurin overexpression plays a very important role in brain focal edema and astrocyte expression. Therefore, calcineurin may be a novel candidate for brain focal edema occurring and intracellular trigger of astrogliosis in status epilepticus.

Achromatic Focal Plane Mask for Exoplanet Imaging Coronagraphy

NASA Technical Reports Server (NTRS)

Newman, Kevin Edward; Belikov, Ruslan; Guyon, Olivier; Balasubramanian, Kunjithapatham; Wilson, Dan

2013-01-01

Recent advances in coronagraph technologies for exoplanet imaging have achieved contrasts close to 1e10 at 4 lambda/D and 1e-9 at 2 lambda/D in monochromatic light. A remaining technological challenge is to achieve high contrast in broadband light; a challenge that is largely limited by chromaticity of the focal plane mask. The size of a star image scales linearly with wavelength. Focal plane masks are typically the same size at all wavelengths, and must be sized for the longest wavelength in the observational band to avoid starlight leakage. However, this oversized mask blocks useful discovery space from the shorter wavelengths. We present here the design, development, and testing of an achromatic focal plane mask based on the concept of optical filtering by a diffractive optical element (DOE). The mask consists of an array of DOE cells, the combination of which functions as a wavelength filter with any desired amplitude and phase transmission. The effective size of the mask scales nearly linearly with wavelength, and allows significant improvement in the inner working angle of the coronagraph at shorter wavelengths. The design is applicable to almost any coronagraph configuration, and enables operation in a wider band of wavelengths than would otherwise be possible. We include initial results from a laboratory demonstration of the mask with the Phase Induced Amplitude Apodization coronagraph.

Dual band QWIP focal plane array

NASA Technical Reports Server (NTRS)

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

2005-01-01

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

Impact of region contouring variability on image-based focal therapy evaluation

NASA Astrophysics Data System (ADS)

Gibson, Eli; Donaldson, Ian A.; Shah, Taimur T.; Hu, Yipeng; Ahmed, Hashim U.; Barratt, Dean C.

2016-03-01

Motivation: Focal therapy is an emerging low-morbidity treatment option for low-intermediate risk prostate cancer; however, challenges remain in accurately delivering treatment to specified targets and determining treatment success. Registered multi-parametric magnetic resonance imaging (MPMRI) acquired before and after treatment can support focal therapy evaluation and optimization; however, contouring variability, when defining the prostate, the clinical target volume (CTV) and the ablation region in images, reduces the precision of quantitative image-based focal therapy evaluation metrics. To inform the interpretation and clarify the limitations of such metrics, we investigated inter-observer contouring variability and its impact on four metrics. Methods: Pre-therapy and 2-week-post-therapy standard-of-care MPMRI were acquired from 5 focal cryotherapy patients. Two clinicians independently contoured, on each slice, the prostate (pre- and post-treatment) and the dominant index lesion CTV (pre-treatment) in the T2-weighted MRI, and the ablated region (post-treatment) in the dynamic-contrast- enhanced MRI. For each combination of clinician contours, post-treatment images were registered to pre-treatment images using a 3D biomechanical-model-based registration of prostate surfaces, and four metrics were computed: the proportion of the target tissue region that was ablated and the target:ablated region volume ratio for each of two targets (the CTV and an expanded planning target volume). Variance components analysis was used to measure the contribution of each type of contour to the variance in the therapy evaluation metrics. Conclusions: 14-23% of evaluation metric variance was attributable to contouring variability (including 6-12% from ablation region contouring); reducing this variability could improve the precision of focal therapy evaluation metrics.

Landsat 9 OLI 2 focal plane subsystem: design, performance, and status

NASA Astrophysics Data System (ADS)

Malone, Kevin J.; Schrein, Ronald J.; Bradley, M. Scott; Irwin, Ronda; Berdanier, Barry; Donley, Eric

2017-09-01

The Landsat 9 mission will continue the legacy of Earth remote sensing that started in 1972. The Operational Land Imager 2 (OLI 2) is one of two instruments on the Landsat 9 satellite. The OLI 2 instrument is essentially a copy of the OLI instrument flying on Landsat 8. A key element of the OLI 2 instrument is the focal plane subsystem, or FPS, which consists of the focal plane array (FPA), the focal plane electronics (FPE) box, and low-thermal conductivity cables. This paper presents design details of the OLI 2 FPS. The FPA contains 14 critically-aligned focal plane modules (FPM). Each module contains 6 visible/near-IR (VNIR) detector arrays and three short-wave infrared (SWIR) arrays. A complex multi-spectral optical filter is contained in each module. Redundant pixels for each array provide exceptional operability. Spare detector modules from OLI were recharacterized after six years of storage. Radiometric test results are presented and compared with data recorded in 2010. Thermal, optical, mechanical and structural features of the FPA will be described. Special attention is paid to the thermal design of the FPA since thermal stability is crucial to ensuring low-noise and low-drift operation of the detectors which operate at -63°C. The OLI 2 FPE provides power, timing, and control to the focal plane modules. It also digitizes the video data and formats it for the solid-state recorder. Design improvements to the FPA-FPE cables will be discussed and characterization data will be presented. The paper will conclude with the status of the flight hardware assembly and testing.

Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia.

PubMed

Dong, Beibei; Cai, Min; Fang, Zongping; Wei, Haidong; Zhu, Fangyun; Li, Guochao; Dong, Hailong; Xiong, Lize

2013-06-10

The plasma protein hemopexin (HPX) exhibits the highest binding affinity to free heme. In vitro experiments and gene-knock out technique have suggested that HPX may have a neuroprotective effect. However, the expression of HPX in the brain was not well elucidated and its expression after cerebral ischemia-reperfusion injury was also poorly studied. Furthermore, no in vivo data were available on the effect of HPX given centrally on the prognosis of focal cerebral ischemia. In the present study, we systematically investigated expression of HPX in normal rat brain by immunofluorescent staining. The results showed that HPX was mainly expressed in vascular system and neurons, as well as in a small portion of astrocytes adjacent to the vessels in normal rat brain. Further, we determined the role of HPX in the process of focal cerebral ischemic injury and explored the effects of HPX treatment in a rat model of transient focal cerebral ischemia. After 2 h' middle cerebral artery occlusion (MCAO) followed by 24 h' reperfusion, the expression of HPX was increased in the neurons and astrocytes in the penumbra area, as demonstrated by immunohistochemistry and Western blot techniques. Intracerebroventricular injection of HPX at the onset of reperfusion dose-dependently reduced the infarct volumes and improved measurements of neurological function of the rat subjected to transient focal cerebral ischemia. The neuroprotective effects of HPX sustained for up to 7 days after experiments. Our study provides a new insight into the potential neuroprotective role of HPX as a contributing factor of endogenous protective mechanisms against focal cerebral ischemia injury, and HPX might be developed as a potential agent for treatment of ischemic stroke.

Focal mechanisms of recent earthquakes in the Southern Korean Peninsula

NASA Astrophysics Data System (ADS)

Park, Jong-Chan; Kim, Woohan; Chung, Tae Woong; Baag, Chang-Eob; Ree, Jin-Han

2007-06-01

We evaluate the stress field in and around the southern Korean Peninsula with focal mechanism solutions, using the data collected from 71 earthquakes (ML = 1.9-5.2) between 1999 and 2004. For this, the hypocentres were relocated and well-constrained fault plane solutions were obtained from the data set of 1270 clear P-wave polarities and 46 SH/P amplitude ratios. The focal mechanism solutions indicate that the prevailing faulting types in South Korea are strike-slip-dominant-oblique-slip faultings with minor reverse-slip component. The maximum principal stresses (σ1) estimated from fault-slip inversion analysis of the focal mechanism solutions show a similar orientation with E-W trend (269° -275°) and low-angle plunge (10° -25°) for all tectonic provinces in South Korea, consistent with the E-W trending maximum horizontal stress (σHmax) of the Amurian microplate reported from in situ stress measurements and earthquake focal mechanisms. The directions of the intermediate (σ2) and minimum (σ3) principal stresses of the Gyeongsang Basin are, however, about 90 deg off from those of the other tectonic provinces on a common σ2-σ3 plane, suggesting a permutation of σ2 and σ3. Our results incorporated with those from the kinematic studies of the Quaternary faults imply that NNW- to NE-striking faults (dextral strike-slip or oblique-slip with a reverse-slip component) are highly likely to generate earthquakes in South Korea.

Imaging patterns and focal lesions in fatty liver: a pictorial review.

PubMed

Venkatesh, Sudhakar K; Hennedige, Tiffany; Johnson, Geoffrey B; Hough, David M; Fletcher, Joel G

2017-05-01

Non-alcoholic fatty liver disease is the most common cause of chronic liver disease and affects nearly one-third of US population. With the increasing trend of obesity in the population, associated fatty change in the liver will be a common feature observed in imaging studies. Fatty liver causes changes in liver parenchyma appearance on imaging modalities including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) and may affect the imaging characteristics of focal liver lesions (FLLs). The imaging characteristics of FLLs were classically described in a non-fatty liver. In addition, focal fatty change and focal fat sparing may also simulate FLLs. Knowledge of characteristic patterns of fatty change in the liver (diffuse, geographical, focal, subcapsular, and perivascular) and their impact on the detection and characterization of FLL is therefore important. In general, fatty change may improve detection of FLLs on MRI using fat suppression sequences, but may reduce sensitivity on a single-phase (portal venous) CT and conventional ultrasound. In patients with fatty liver, MRI is generally superior to ultrasound and CT for detection and characterization of FLL. In this pictorial essay, we describe the imaging patterns of fatty change in the liver and its effect on detection and characterization of FLLs on ultrasound, CT, MRI, and PET.

The role of executive functioning in memory performance in pediatric focal epilepsy.

PubMed

Sepeta, Leigh N; Casaletto, Kaitlin Blackstone; Terwilliger, Virginia; Facella-Ervolini, Joy; Sady, Maegan; Mayo, Jessica; Gaillard, William D; Berl, Madison M

2017-02-01

Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (Wechsler Abbreviated Scale of Intelligence [WASI]/Differential Ability Scales [DAS]), as well as visual Children's Memory Scale (CMS Dot Locations) and verbal episodic memory (Wide Range Assessment of Memory and Learning [WRAML] Story Memory and California Verbal Learning Test for Children [CVLT-C]). Executive functioning was measured directly (WISC-IV Digit Span Backward; Clinical Evaluation of Language Fundamentals, Fourth Edition (CELF-IV) Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function [BRIEF]). Children with focal epilepsy had lower delayed free-recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η 2 = 0.12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η 2 = 0.03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η 2 = 0.08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9-19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9-10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extratemporal, frontal vs. extrafrontal). Children with focal epilepsy demonstrated memory

Impact of functional focal versus diffuse coronary artery disease on bypass graft patency.

PubMed

Shiono, Yasutsugu; Kubo, Takashi; Honda, Kentaro; Katayama, Yosuke; Aoki, Hiroshi; Satogami, Keisuke; Kashiyama, Kuninobu; Taruya, Akira; Nishiguchi, Tsuyoshi; Kuroi, Akio; Orii, Makoto; Kameyama, Takeyoshi; Yamano, Takashi; Yamaguchi, Tomoyuki; Matsuo, Yoshiki; Ino, Yasushi; Tanaka, Atsushi; Hozumi, Takeshi; Nishimura, Yoshiharu; Okamura, Yoshitaka; Akasaka, Takashi

2016-11-01

Pressure guidewire pullback recording can differentiate between functional focal and diffuse disease types in coronary artery disease. The aim of this study was to compare the outcome of coronary artery bypass graft (CABG) patency between patients with functional focal versus diffuse disease types in recipient coronary arteries. We investigated 89 patients who underwent pressure guidewire pullback in the left anterior descending (LAD) artery before CABG using internal mammary artery (IMA). Based on the pressure guidewire pullback data, the LAD lesions were classified into functional focal disease (abrupt pressure step-up; n=58) or functional diffuse disease (gradual pressure increase; n=31). Follow-up computed tomography (CT) angiography was conducted within 1year after CABG to assess the bypass graft patency. Pre CABG, LAD angiographic percent diameter stenosis (57±10% vs. 54±12%, p=0.228) and fractional flow reserve (FFR) (0.68±0.07 vs. 0.69±0.07, p=0.244) were not different between the functional focal and diffuse disease groups. The CABG procedure characteristics were similarly comparable between the two groups. In the follow-up CT angiography after CABG, occlusion or string sign of the IMA graft to LAD was more frequently observed in the functional diffuse disease group than in the functional focal disease group (26% vs. 7%, p=0.021). In CABG, functional diffuse disease in the recipient coronary artery was associated with an increased risk of the graft failure in comparison with functional focal disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Low Temperature Plasma: A Novel Focal Therapy for Localized Prostate Cancer?

PubMed Central

Hirst, Adam M.; Frame, Fiona M.; Maitland, Norman J.; O'Connell, Deborah

2014-01-01

Despite considerable advances in recent years for the focal treatment of localized prostate cancer, high recurrence rates and detrimental side effects are still a cause for concern. In this review, we compare current focal therapies to a potentially novel approach for the treatment of early onset prostate cancer: low temperature plasma. The rapidly evolving plasma technology has the potential to deliver a wide range of promising medical applications via the delivery of plasma-induced reactive oxygen and nitrogen species. Studies assessing the effect of low temperature plasma on cell lines and xenografts have demonstrated DNA damage leading to apoptosis and reduction in cell viability. However, there have been no studies on prostate cancer, which is an obvious candidate for this novel therapy. We present here the potential of low temperature plasma as a focal therapy for prostate cancer. PMID:24738076

Low temperature plasma: a novel focal therapy for localized prostate cancer?

PubMed

Hirst, Adam M; Frame, Fiona M; Maitland, Norman J; O'Connell, Deborah

2014-01-01

Despite considerable advances in recent years for the focal treatment of localized prostate cancer, high recurrence rates and detrimental side effects are still a cause for concern. In this review, we compare current focal therapies to a potentially novel approach for the treatment of early onset prostate cancer: low temperature plasma. The rapidly evolving plasma technology has the potential to deliver a wide range of promising medical applications via the delivery of plasma-induced reactive oxygen and nitrogen species. Studies assessing the effect of low temperature plasma on cell lines and xenografts have demonstrated DNA damage leading to apoptosis and reduction in cell viability. However, there have been no studies on prostate cancer, which is an obvious candidate for this novel therapy. We present here the potential of low temperature plasma as a focal therapy for prostate cancer.

Core biopsy as a simple and effective diagnostic tool in head and neck focal myositis.

PubMed

Tan, Chun Yee; Chong, Sheldon; Shaw, Chi-Kee Leslie

2015-12-01

Most unilateral head and neck masses are benign, although malignancy is a possibility in some cases. However, there are other rare causes of unilateral neck masses, such as focal myositis, which is a rare, benign condition belonging to the family of inflammatory pseudotumors of the skeletal muscles, with rare presentations in the head and neck region. Focal myositis presents as a rapidly enlarging neck mass that can be misdiagnosed by fine-needle aspiration biopsy and/or radiologic imaging as either an infective or a neoplastic process. To date, there are only 5 reported cases of adult focal myositis of the sternocleidomastoid muscle in the medical literature. In this article, the authors present 2 cases involving patients with focal myositis of the sternocleidomastoid muscle that were successfully diagnosed with core-needle biopsy and managed conservatively. The pros and cons of fine-needle aspiration biopsy and core-needle biopsy are discussed. Based on the authors' results, fine-needle aspiration biopsy universally fails to provide the diagnosis of focal myositis. In contrast, core-needle biopsy successfully diagnosed focal myositis in both of our patients. Both of them had complete resolution with conservative management.

Oral focal epithelial hyperplasia: report of three cases.

PubMed

Ghalayani, Parichehr; Tavakoli, Payam; Eftekhari, Mehdi; Haghighi, Mohammad Akhondzadeh

2015-01-01

Focal epithelial hyperplasia or Heck's disease is an infrequent asymptomatic condition caused by human papillomavirus types 13 or 32 affecting the mucous membrane of the mouth and is commonly seen in young individuals. Firstly, it was described in Indians and Eskimos, but it exists in various populations. We present three cases of Heck's disease in an Afghan immigrant family group living in Iran that seem to have familial predominance. The disease was identified as oral focal epithelial hyperplasia on the basis of histopathologic and clinical findings. The lesions were reduced significantly after 4 months of good oral hygiene. Dentists should be familiar with the clinical manifestations of these types of lesions that affect the oral cavity. In fact, histopathologic assessment and clinical observation are necessary to establish the diagnosis.

Optofluidic lens with tunable focal length and asphericity

PubMed Central

Mishra, Kartikeya; Murade, Chandrashekhar; Carreel, Bruno; Roghair, Ivo; Oh, Jung Min; Manukyan, Gor; van den Ende, Dirk; Mugele, Frieder

2014-01-01

Adaptive micro-lenses enable the design of very compact optical systems with tunable imaging properties. Conventional adaptive micro-lenses suffer from substantial spherical aberration that compromises the optical performance of the system. Here, we introduce a novel concept of liquid micro-lenses with superior imaging performance that allows for simultaneous and independent tuning of both focal length and asphericity. This is achieved by varying both hydrostatic pressures and electric fields to control the shape of the refracting interface between an electrically conductive lens fluid and a non-conductive ambient fluid. Continuous variation from spherical interfaces at zero electric field to hyperbolic ones with variable ellipticity for finite fields gives access to lenses with positive, zero, and negative spherical aberration (while the focal length can be tuned via the hydrostatic pressure). PMID:25224851

Re-recognition of Age-dependent Reference Range for the Serum Creatinine Level in Teenagers - A Case of Slowly Progressive Tubulointerstitial Nephritis which Occurred in an Adolescent.

PubMed

Ono, Hiroyuki; Nagai, Kojiro; Shibata, Eriko; Matsuura, Motokazu; Kishi, Seiji; Inagaki, Taizo; Minato, Masanori; Yoshimoto, Sakiya; Ueda, Sayo; Obata, Fumiaki; Nishimura, Kenji; Tamaki, Masanori; Kishi, Fumi; Murakami, Taichi; Abe, Hideharu; Kinoshita, Yukiko; Urushihara, Maki; Kagami, Shoji; Doi, Toshio

2017-08-15

For the first time, a 15-year-old boy was found to have a slight degree of proteinuria and microscopic hematuria during annual school urinalysis screening. His kidney function had already severely deteriorated. A kidney biopsy revealed tubulointerstitial nephritis (TIN) with diffuse inflammatory cell infiltration. His medical records showed his serum creatinine level to be 0.98 mg/dL two years ago, which was abnormally high considering his age. Although the etiology of slowly progressive TIN was unclear, glucocorticoid and immunosuppressant therapy improved his kidney function. This case report suggests that all doctors should recognize the reference range for the serum creatinine level in teenagers.

Re-recognition of Age-dependent Reference Range for the Serum Creatinine Level in Teenagers - A Case of Slowly Progressive Tubulointerstitial Nephritis which Occurred in an Adolescent -

PubMed Central

Ono, Hiroyuki; Nagai, Kojiro; Shibata, Eriko; Matsuura, Motokazu; Kishi, Seiji; Inagaki, Taizo; Minato, Masanori; Yoshimoto, Sakiya; Ueda, Sayo; Obata, Fumiaki; Nishimura, Kenji; Tamaki, Masanori; Kishi, Fumi; Murakami, Taichi; Abe, Hideharu; Kinoshita, Yukiko; Urushihara, Maki; Kagami, Shoji; Doi, Toshio

2017-01-01

For the first time, a 15-year-old boy was found to have a slight degree of proteinuria and microscopic hematuria during annual school urinalysis screening. His kidney function had already severely deteriorated. A kidney biopsy revealed tubulointerstitial nephritis (TIN) with diffuse inflammatory cell infiltration. His medical records showed his serum creatinine level to be 0.98 mg/dL two years ago, which was abnormally high considering his age. Although the etiology of slowly progressive TIN was unclear, glucocorticoid and immunosuppressant therapy improved his kidney function. This case report suggests that all doctors should recognize the reference range for the serum creatinine level in teenagers. PMID:28781321

Focal plane AIT sequence: evolution from HRG-Spot 5 to Pleiades HR

NASA Astrophysics Data System (ADS)

Le Goff, Roland; Pranyies, Pascal; Toubhans, Isabelle

2017-11-01

Optical and geometrical image qualities of Focal Planes, for "push-broom" high resolution remote sensing satellites, require the implementation of specific means and methods for the AIT sequence. Indeed the geometric performances of the focal plane mainly axial focusing and transverse registration, are duly obtained on the basis of adjustment, setting and measurement of optical and CCD components with an accuracy of a few microns. Since the end of the 1970s, EADS-SODERN has developed a series of detection units for earth observation instruments like SPOT and Helios. And EADS-SODERN is now responsible for the development of the Pleiades High Resolution Focal Plane assembly. This paper presents the AIT sequences. We introduce all the efforts, innovative solutions and improvements made on the assembly facilities to match the technical evolutions and breakthrough of the Pleiades HR FP concept in comparison with the previous High Resolution Geometric SPOT 5 Focal Plane. The main evolution drivers are the implementation of strip filters and the realization of 400 mm continuous retinas. For Pleiades HR AIT sequence, three specific integration and measuring benches, corresponding with the different assembly stages, are used: a 3-D non-contact measurement machine for the assembly of detection module, a 3-D measurement machine for mirror integration on the main Focal Plane SiC structure, and a 3-D geometric coordinates control bench to focus detection module lines and to ensure they are well registered together.

Transcranial current stimulation focality using disc and ring electrode configurations: FEM analysis

NASA Astrophysics Data System (ADS)

Datta, Abhishek; Elwassif, Maged; Battaglia, Fortunato; Bikson, Marom

2008-06-01

We calculated the electric fields induced in the brain during transcranial current stimulation (TCS) using a finite-element concentric spheres human head model. A range of disc electrode configurations were simulated: (1) distant-bipolar; (2) adjacent-bipolar; (3) tripolar; and three ring designs, (4) belt, (5) concentric ring, and (6) double concentric ring. We compared the focality of each configuration targeting cortical structures oriented normal to the surface ('surface-radial' and 'cross-section radial'), cortical structures oriented along the brain surface ('surface-tangential' and 'cross-section tangential') and non-oriented cortical surface structures ('surface-magnitude' and 'cross-section magnitude'). For surface-radial fields, we further considered the 'polarity' of modulation (e.g. superficial cortical neuron soma hyper/depolarizing). The distant-bipolar configuration, which is comparable with commonly used TCS protocols, resulted in diffuse (un-focal) modulation with bi-directional radial modulation under each electrode and tangential modulation between electrodes. Increasing the proximity of the two electrodes (adjacent-bipolar electrode configuration) increased focality, at the cost of more surface current. At similar electrode distances, the tripolar-electrodes configuration produced comparable peak focality, but reduced radial bi-directionality. The concentric-ring configuration resulted in the highest spatial focality and uni-directional radial modulation, at the expense of increased total surface current. Changing ring dimensions, or use of two concentric rings, allow titration of this balance. The concentric-ring design may thus provide an optimized configuration for targeted modulation of superficial cortical neurons.

Treatment planning for prostate focal laser ablation in the face of needle placement uncertainty

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

Cepek, Jeremy, E-mail: jcepek@robarts.ca; Fenster, Aaron; Lindner, Uri

2014-01-15

Purpose: To study the effect of needle placement uncertainty on the expected probability of achieving complete focal target destruction in focal laser ablation (FLA) of prostate cancer. Methods: Using a simplified model of prostate cancer focal target, and focal laser ablation region shapes, Monte Carlo simulations of needle placement error were performed to estimate the probability of completely ablating a region of target tissue. Results: Graphs of the probability of complete focal target ablation are presented over clinically relevant ranges of focal target sizes and shapes, ablation region sizes, and levels of needle placement uncertainty. In addition, a table ismore » provided for estimating the maximum target size that is treatable. The results predict that targets whose length is at least 5 mm smaller than the diameter of each ablation region can be confidently ablated using, at most, four laser fibers if the standard deviation in each component of needle placement error is less than 3 mm. However, targets larger than this (i.e., near to or exceeding the diameter of each ablation region) require more careful planning. This process is facilitated by using the table provided. Conclusions: The probability of completely ablating a focal target using FLA is sensitive to the level of needle placement uncertainty, especially as the target length approaches and becomes greater than the diameter of ablated tissue that each individual laser fiber can achieve. The results of this work can be used to help determine individual patient eligibility for prostate FLA, to guide the planning of prostate FLA, and to quantify the clinical benefit of using advanced systems for accurate needle delivery for this treatment modality.« less

Next generation sub-millimeter wave focal plane array coupling concepts: an ESA TRP project to develop multichroic focal plane pixels for future CMB polarization experiments

NASA Astrophysics Data System (ADS)

Trappe, N.; Bucher, M.; De Bernardis, P.; Delabrouille, J.; Deo, P.; DePetris, M.; Doherty, S.; Ghribi, A.; Gradziel, M.; Kuzmin, L.; Maffei, B.; Mahashabde, S.; Masi, S.; Murphy, J. A.; Noviello, F.; O'Sullivan, C.; Pagano, L.; Piacentini, F.; Piat, M.; Pisano, G.; Robinson, M.; Stompor, R.; Tartari, A.; van der Vorst, M.; Verhoeve, P.

2016-07-01

The main objective of this activity is to develop new focal plane coupling array concepts and technologies that optimise the coupling from reflector optics to the large number of detectors for next generation sub millimetre wave telescopes particularly targeting measurement of the polarization of the cosmic microwave background (CMB). In this 18 month TRP programme the consortium are tasked with developing, manufacturing and experimentally verifying a prototype multichroic pixel which would be suitable for the large focal plane arrays which will be demanded to reach the required sensitivity of future CMB polarization missions. One major development was to have multichroic operation to potentially reduce the required focal plane size of a CMB mission. After research in the optimum telescope design and definition of requirements based on a stringent science case review, a number of compact focal plane architecture concepts were investigated before a pixel demonstrator consisting of a planar mesh lens feeding a backend Resonant Cold Electron Bolometer RCEB for filtering and detection of the dual frequency signal was planned for manufacture and test. In this demonstrator the frequencies of the channels was chosen to be 75 and 105 GHz in the w band close to the peak CMB signal. In the next year the prototype breadboards will be developed to test the beams produced by the manufactured flat lenses fed by a variety of antenna configurations and the spectral response of the RCEBs will also be verified.

The design and application of large area intensive lens array focal spots measurement system

NASA Astrophysics Data System (ADS)

Chen, Bingzhen; Yao, Shun; Yang, Guanghui; Dai, Mingchong; Wang, Zhiyong

2014-12-01

Concentrating Photovoltaic (CPV) modules are getting thinner and using smaller cells now days. Correspondingly, large area intensive lens arrays with smaller unit dimension and shorter focal length are wanted. However, the size and power center of lens array focal spots usually differ from the design value and are hard to measure, especially under large area situation. It is because the machining error and deformation of material of the lens array are hard to simulate in the optical design process. Thus the alignment error between solar cells and focal spots in the module assembly process will be hard to control. Under this kind of situation, the efficiency of CPV module with thinner body and smaller cells is much lower than expected. In this paper, a design of large area lens array focal spots automatic measurement system is presented, as well as its prototype application results. In this system, a four-channel parallel light path and its corresponding image capture and process modules are designed. These modules can simulate focal spots under sunlight and have the spots image captured and processed using charge coupled devices and certain gray level algorithm. Thus the important information of focal spots such as spot size and location will be exported. Motion control module based on grating scale signal and interval measurement method are also employed in this system in order to get test results with high speed and high precision on large area lens array no less than 1m×0.8m. The repeatability of the system prototype measurement is +/-10μm with a velocity of 90 spot/min. Compared to the original module assembled using coordinates from optical design, modules assembled using data exported from the prototype is 18% higher in output power, reaching a conversion efficiency of over 31%. This system and its design can be used in the focal spot measurement of planoconvex lens array and Fresnel lens array, as well as other kinds of large area lens array application

The Simbol-X Focal Plane

NASA Astrophysics Data System (ADS)

Laurent, P.

2009-05-01

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

BOLD responses related to focal spikes and widespread bilateral synchronous discharges generated in the frontal lobe.

PubMed

An, Dongmei; Dubeau, François; Gotman, Jean

2015-03-01

To investigate whether specific frontal regions have a tendency to generate widespread bilateral synchronous discharges (WBSDs) and others focal spikes and to determine the regions most involved when WBSDs occur; to assess the relationships between the extent of electroencephalography (EEG) discharges and the extent of metabolic changes measured by EEG/functional magnetic resonance imaging (fMRI). Thirty-seven patients with interictal epileptic discharges (IEDs) with frontocentral predominance underwent EEG/fMRI. Patients were divided into a Focal (20 patients) group with focal frontal spikes and a WBSD group (17 patients). Maps of hemodynamic responses related to IEDs were compared between the two groups. The mean number ± SD of IEDs in the Focal group was 137.5 ± 38.1 and in the WBSD group, 73.5 ± 16.6 (p = 0.07). The volume of hemodynamic responses in the WBSD group was significantly larger than in the Focal group (mean, 243.3 ± 41.1 versus 114.8 ± 27.4 cm(3), p = 0.01). Maximum hemodynamic responses occurred in both groups in the following regions: dorsolateral prefrontal, mesial prefrontal, cingulate, and supplementary motor cortices. Maxima in premotor and motor cortex, frontal operculum, frontopolar, and orbitofrontal regions were found only in the Focal group, and maxima in thalamus and caudate only occurred in the WBSD group. Thalamic responses were significantly more common in the WBSD group (14/17) than in the Focal group (7/20), p = 0.004. Deactivation in the default mode network was significantly more common in the WBSD group (14/17) than in the Focal group (10/20), p = 0.04. The spatial distribution and extent of blood oxygen level-dependent (BOLD) responses correlate well with electrophysiologic changes. Focal frontal spikes and WBSDs are not region specific in the frontal lobe, and the same frontal region can generate focal and generalized discharges. This suggests that widespread discharges reflect widespread epileptogenicity rather than a

Effects of cue focality on the neural mechanisms of prospective memory: A meta-analysis of neuroimaging studies.

PubMed

Cona, Giorgia; Bisiacchi, Patrizia Silvia; Sartori, Giuseppe; Scarpazza, Cristina

2016-05-17

Remembering to execute pre-defined intentions at the appropriate time in the future is typically referred to as Prospective Memory (PM). Studies of PM showed that distinct cognitive processes underlie the execution of delayed intentions depending on whether the cue associated with such intentions is focal to ongoing activity processing or not (i.e., cue focality). The present activation likelihood estimation (ALE) meta-analysis revealed several differences in brain activity as a function of focality of the PM cue. The retrieval of intention is supported mainly by left anterior prefrontal cortex (Brodmann Area, BA 10) in nonfocal tasks, and by cerebellum and ventral parietal regions in focal tasks. Furthermore, the precuneus showed increased activation during the maintenance phase of intentions compared to the retrieval phase in nonfocal tasks, whereas the inferior parietal lobule showed increased activation during the retrieval of intention compared to maintenance phase in the focal tasks. Finally, the retrieval of intention relies more on the activity in anterior cingulate cortex for nonfocal tasks, and on posterior cingulate cortex for focal tasks. Such focality-related pattern of activations suggests that prospective remembering is mediated mainly by top-down and stimulus-independent processes in nonfocal tasks, whereas by more automatic, bottom-up, processes in focal tasks.

Effects of cue focality on the neural mechanisms of prospective memory: A meta-analysis of neuroimaging studies

PubMed Central

Cona, Giorgia; Bisiacchi, Patrizia Silvia; Sartori, Giuseppe; Scarpazza, Cristina

2016-01-01

Remembering to execute pre-defined intentions at the appropriate time in the future is typically referred to as Prospective Memory (PM). Studies of PM showed that distinct cognitive processes underlie the execution of delayed intentions depending on whether the cue associated with such intentions is focal to ongoing activity processing or not (i.e., cue focality). The present activation likelihood estimation (ALE) meta-analysis revealed several differences in brain activity as a function of focality of the PM cue. The retrieval of intention is supported mainly by left anterior prefrontal cortex (Brodmann Area, BA 10) in nonfocal tasks, and by cerebellum and ventral parietal regions in focal tasks. Furthermore, the precuneus showed increased activation during the maintenance phase of intentions compared to the retrieval phase in nonfocal tasks, whereas the inferior parietal lobule showed increased activation during the retrieval of intention compared to maintenance phase in the focal tasks. Finally, the retrieval of intention relies more on the activity in anterior cingulate cortex for nonfocal tasks, and on posterior cingulate cortex for focal tasks. Such focality-related pattern of activations suggests that prospective remembering is mediated mainly by top-down and stimulus-independent processes in nonfocal tasks, whereas by more automatic, bottom-up, processes in focal tasks. PMID:27185531

Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis.

PubMed

Bastian, H M; Roseman, J M; McGwin, G; Alarcón, G S; Friedman, A W; Fessler, B J; Baethge, B A; Reveille, J D

2002-01-01

The purpose of this study was to determine the cumulative incidence of lupus nephritis (LN) and the factors predictive of its occurrence in a multiethnic systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African-Americans and 91 Caucasians). First, we determined the cumulative incidence of LN in all patients. Next, we determined the predictors for LN in those with nephritis occurring after diagnosis. The dependent variable, LN, was defined by: (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the following features also attributable to SLE and present on two or more visits, which were performed at least 6 months apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or > or = 3 granular or cellular casts per hpf. Independent variables assessed at diagnosis, and if absent, at baseline, were from four domains: sociodemographic, clinical, immunologic and immunogenetic (including the complete antibody profile and MHC class II alleles), and health habits. Variables with P < 0.05 by chi square analyses were entered into domain-specific stepwise logistic regression analyses controlling for disease duration, with LN as the dependent variable. Significant domain-specific regression variables (P < or = 0.1) were then entered into an overall model. The cumulative incidence of LN was 54.3% in all patients, and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in 43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians, P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/-2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71, 95

Study on observation planning of LAMOST focal plane positioning system and its simulation

NASA Astrophysics Data System (ADS)

Zhai, Chao; Jin, Yi; Peng, Xiaobo; Xing, Xiaozheng

2006-06-01

Fiber Positioning System of LAMOST focal plane based on subarea thinking, adopts a parallel controllable positioning plan, the structure is designed as a round area and overlapped each other in order to eliminate the un-observation region. But it also makes the observation efficiency of the system become an important problem. In this paper According to the system, the model of LAMOST focal plane Observation Planning including 4000 fiber positioning units is built, Stars are allocated using netflow algorithm and mechanical collisions are diminished through the retreat algorithm, then the simulation of the system's observation efficiency is carried out. The problem of observation efficiency of LAMOST focal plane is analysed systemic and all-sided from the aspect of overlapped region, fiber positioning units, observation radius, collisions and so on. The observation efficiency of the system in theory is describes and the simulation indicates that the system's observation efficiency is acceptable. The analyses play an indicative role on the design of the LAMOST focal plane structure.

Insight into bacterial virulence mechanisms against host immune response via the Yersinia pestis-human protein-protein interaction network.

PubMed

Yang, Huiying; Ke, Yuehua; Wang, Jian; Tan, Yafang; Myeni, Sebenzile K; Li, Dong; Shi, Qinghai; Yan, Yanfeng; Chen, Hui; Guo, Zhaobiao; Yuan, Yanzhi; Yang, Xiaoming; Yang, Ruifu; Du, Zongmin

2011-11-01

A Yersinia pestis-human protein interaction network is reported here to improve our understanding of its pathogenesis. Up to 204 interactions between 66 Y. pestis bait proteins and 109 human proteins were identified by yeast two-hybrid assay and then combined with 23 previously published interactions to construct a protein-protein interaction network. Topological analysis of the interaction network revealed that human proteins targeted by Y. pestis were significantly enriched in the proteins that are central in the human protein-protein interaction network. Analysis of this network showed that signaling pathways important for host immune responses were preferentially targeted by Y. pestis, including the pathways involved in focal adhesion, regulation of cytoskeleton, leukocyte transendoepithelial migration, and Toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling. Cellular pathways targeted by Y. pestis are highly relevant to its pathogenesis. Interactions with host proteins involved in focal adhesion and cytoskeketon regulation pathways could account for resistance of Y. pestis to phagocytosis. Interference with TLR and MAPK signaling pathways by Y. pestis reflects common characteristics of pathogen-host interaction that bacterial pathogens have evolved to evade host innate immune response by interacting with proteins in those signaling pathways. Interestingly, a large portion of human proteins interacting with Y. pestis (16/109) also interacted with viral proteins (Epstein-Barr virus [EBV] and hepatitis C virus [HCV]), suggesting that viral and bacterial pathogens attack common cellular functions to facilitate infections. In addition, we identified vasodilator-stimulated phosphoprotein (VASP) as a novel interaction partner of YpkA and showed that YpkA could inhibit in vitro actin assembly mediated by VASP.

European Genetic Ancestry is Associated with a Decreased Risk of Lupus Nephritis

PubMed Central

Richman, Ilana B.; Taylor, Kimberly E.; Chung, Sharon A.; Trupin, Laura; Petri, Michelle; Yelin, Edward; Graham, Robert R.; Lee, Annette; Behrens, Timothy W.; Gregersen, Peter K.; Seldin, Michael F.; Criswell, Lindsey A.

2013-01-01

Objective African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than SLE patients of European descent. We investigated whether European genetic ancestry protects against the development of lupus nephritis and explored genetic and socioeconomic factors that might explain this effect. Methods This was a cross-sectional study of 1906 adults with SLE. Participants were genotyped for 126 single nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. We used logistic regression to test the association between European ancestry and renal disease. Analyses adjusted for continental ancestries, socioeconomic status, and candidate genes. Results Participants (n=1906) had on average 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among participants, 34% (n=656) had renal disease. A 10% increase in European ancestry was associated with a 15% reduction in the odds of having renal disease after adjustment for disease duration and sex (OR 0.85, 95% CI 0.82-0.87, p=1.9 × 10−30). Adjusting for other genetic ancestries, measures of socioeconomic status, or SNPs in genes most associated with renal disease (IRF5 (rs4728142), BLK (rs2736340), STAT4 (rs3024912), ITGAM (rs9937837) and HLA-DRB1*0301 and DRB1*1501, p<0.05) did not substantively alter this relationship. Conclusion European ancestry is protective against the development of renal disease in SLE, an effect independent of other genetic ancestries, common risk alleles, and socioeconomic status. PMID:23023776

Seizure ending signs in patients with dyscognitive focal seizures.

PubMed

Gavvala, Jay R; Gerard, Elizabeth E; Macken, Mícheál; Schuele, Stephan U

2015-09-01

Signs indicating the end of a focal seizure with loss of awareness and/or responsiveness but without progression to focal or generalized motor symptoms are poorly defined and can be difficult to determine. Not recognizing the transition from ictal to postictal behaviour can affect seizure reporting accuracy by family members and may lead to delayed or a lack of examination during EEG monitoring, erroneous seizure localization and inadequate medical intervention for prolonged seizure duration. Our epilepsy monitoring unit database was searched for focal seizures without secondary generalization for the period from 2007 to 2011. The first focal seizure in a patient with loss of awareness and/or responsiveness and/or behavioural arrest, with or without automatisms, was included. Seizures without objective symptoms or inadequate video-EEG quality were excluded. A total of 67 patients were included, with an average age of 41.7 years. Thirty-six of the patients had seizures from the left hemisphere and 29 from the right. All patients showed an abrupt change in motor activity and resumed contact with the environment as a sign of clinical seizure ending. Specific ending signs (nose wiping, coughing, sighing, throat clearing, or laughter) were seen in 23 of 47 of temporal lobe seizures and 7 of 20 extra-temporal seizures. Seizure ending signs are often subtle and the most common finding is a sudden change in motor activity and resumption of contact with the environment. More distinct signs, such as nose wiping, coughing or throat clearing, are not specific to temporal lobe onset. A higher proportion of seizures during sleep went unexamined, compared to those during wakefulness. This demonstrates that seizure semiology can be very subtle and arousals from sleep during monitoring should alert staff. Patient accounts of seizure frequency appear to be unreliable and witness reports need to be taken into account. [Published with video sequences].

Connectome-Wide Phenotypical and Genotypical Associations in Focal Dystonia

PubMed Central

Fuertinger, Stefan

2017-01-01

Isolated focal dystonia is a debilitating movement disorder of unknown pathophysiology. Early studies in focal dystonias have pointed to segregated changes in brain activity and connectivity. Only recently has the notion that dystonia pathophysiology may lie in abnormalities of large-scale brain networks appeared in the literature. Here, we outline a novel concept of functional connectome-wide alterations that are linked to dystonia phenotype and genotype. Using a neural community detection strategy and graph theoretical analysis of functional MRI data in human patients with the laryngeal form of dystonia (LD) and healthy controls (both males and females), we identified an abnormally widespread hub formation in LD, which particularly affected the primary sensorimotor and parietal cortices and thalamus. Left thalamic regions formed a delineated functional community that highlighted differences in network topology between LD patients with and without family history of dystonia. Conversely, marked differences in the topological organization of parietal regions were found between phenotypically different forms of LD. The interface between sporadic genotype and adductor phenotype of LD yielded four functional communities that were primarily governed by intramodular hub regions. Conversely, the interface between familial genotype and abductor phenotype was associated with numerous long-range hub nodes and an abnormal integration of left thalamus and basal ganglia. Our findings provide the first comprehensive atlas of functional topology across different phenotypes and genotypes of focal dystonia. As such, this study constitutes an important step toward defining dystonia as a large-scale network disorder, understanding its causative pathophysiology, and identifying disorder-specific markers. SIGNIFICANCE STATEMENT The architecture of the functional connectome in focal dystonia was analyzed in a large population of patients with laryngeal dystonia. Breaking with the

How to diagnose and treat focal therapy failure and recurrence?

PubMed

Barret, Eric; Harvey-Bryan, Kadi-Ann; Sanchez-Salas, Rafael; Rozet, Francois; Galiano, Marc; Cathelineau, Xavier

2014-05-01

Focal therapy presents an alternative option for disease-targeted therapy while preserving erectile and urinary function without compromising oncological outcome. Such treatment, which preserves normal prostate parenchyma, presents a clinical challenge to the urologist, as typical disease surveillance parameters are not as reliable in post-ablation follow-up. We propose an integrated approach to post-ablation surveillance to identify treatment failure as well as recurrence. Post-ablation prostate-specific antigen kinetics, imaging based on multiparametric MRI and control biopsies are the tools currently used to follow patients after focal therapy. Good treatment response is indicated by a negative control biopsy, absence of persistent lesion on post-treatment imaging and a reduction in prostate-specific antigen of at least 50%. When histological evidence of therapeutic failure or recurrence is present, different options of management may be proposed to the patient including active surveillance, focal salvage therapy or radical salvage treatment, depending on the characteristics of the lesion found. A recommended post-ablation surveillance protocol is presented as well as a discussion of management strategies based on the data currently available.

Botulinum Toxin Treatment of Autonomic Disorders: Focal Hyperhidrosis and Sialorrhea.

PubMed

Hosp, Christine; Naumann, Markus K; Hamm, Henning

2016-02-01

Primary focal hyperhidrosis is a common autonomic disorder that significantly impacts quality of life. It is characterized by excessive sweating confined to circumscribed areas, such as the axillae, palms, soles, and face. Less frequent types of focal hyperhidrosis secondary to underlying causes include gustatory sweating in Frey's syndrome and compensatory sweating in Ross' syndrome and after sympathectomy. Approval of onabotulinumtoxinA for severe primary axillary hyperhidrosis in 2004 has revolutionized the treatment of this indication. Meanwhile further type A botulinum neurotoxins like abobotulinumtoxinA and incobotulinumtoxinA, as well as the type B botulinum neurotoxin rimabotulinumtoxinB are successfully used off-label for axillary and various other types of focal hyperhidrosis. For unexplained reasons, the duration of effect differs considerably at different sites. Beside hyperhidrosis, botulinum neurotoxin is also highly valued for the treatment of sialorrhea affecting patients with Parkinson's disease, cerebral palsy, amyotrophic lateral sclerosis, motor neuron disease, and other neurologic conditions. With correct dosing and application, side effects are manageable and transient. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Historical review: Autointoxication and focal infection theories of dementia praecox.

PubMed

Noll, Richard

2004-04-01

The popularity of theories of autointoxication and focal infection in general medicine and dentistry in the late nineteenth and early twentieth centuries led Emil Kraepelin and others to speculate that dementia praecox was caused by a poisoning of the brain from toxins produced in other parts of the body, notably the sex glands, the intestines and the mouth. Emil Kraepelin's commitment to the autointoxication theory is ignored in the literature on the history of psychiatry due to the focus of historians and clinicians on the major contributions of Kraepelin's methods of clinical psychopathology. Besides heredity, autointoxication and focal infection were the other most dominant theories of the organic aetiology of dementia praecox in the first three decades of its existence as a nosological entity in psychiatry. Rational treatments for dementia praecox that followed logically from these aetio-logical theories were colonic irrigations and major abdominal surgeries such as appendicostomies, colectomies and the removal of presumably infected ovaries, testes and other organs associated with reproduction. Autointoxication and focal infection theories disappeared from psychiatry by the mid-1930s.

Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults: A national retrospective strobe-compliant study.

PubMed

Legendre, Mathieu; Devilliers, Hervé; Perard, Laurent; Groh, Matthieu; Nefti, Habdelamid; Dussol, Bertrand; Trad, Salim; Touré, Fatouma; Abad, Sébastien; Boffa, Jean-Jacques; Frimat, Luc; Torner, Stéphane; Seidowsky, Alexandre; Massy, Ziad André; Saadoun, David; Rieu, Virginie; Schoindre, Yoland; Heron, Emmanuel; Frouget, Thierry; Lionet, Arnaud; Glowacki, François; Arnaud, Laurent; Mousson, Christiane; Besancenot, Jean-François; Rebibou, Jean-Michel; Bielefeld, Philip

2016-06-01

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8-77.4) with a median serum creatinine level at 207 μmol/L (range 100-1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m (range 2-73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10-2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m (range 17-119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = -0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = -0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated with fewer uveitis relapses

Design of transcranial magnetic stimulation coils with optimal trade-off between depth, focality, and energy.

PubMed

Gomez, Luis J; Goetz, Stefan M; Peterchev, Angel V

2018-08-01

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique used for research and clinical applications. Existent TMS coils are limited in their precision of spatial targeting (focality), especially for deeper targets. This paper presents a methodology for designing TMS coils to achieve optimal trade-off between the depth and focality of the induced electric field (E-field), as well as the energy required by the coil. A multi-objective optimization technique is used for computationally designing TMS coils that achieve optimal trade-offs between E-field focality, depth, and energy (fdTMS coils). The fdTMS coil winding(s) maximize focality (minimize the volume of the brain region with E-field above a given threshold) while reaching a target at a specified depth and not exceeding predefined peak E-field strength and required coil energy. Spherical and MRI-derived head models are used to compute the fundamental depth-focality trade-off as well as focality-energy trade-offs for specific target depths. Across stimulation target depths of 1.0-3.4 cm from the brain surface, the suprathreshold volume can be theoretically decreased by 42%-55% compared to existing TMS coil designs. The suprathreshold volume of a figure-8 coil can be decreased by 36%, 44%, or 46%, for matched, doubled, or quadrupled energy. For matched focality and energy, the depth of a figure-8 coil can be increased by 22%. Computational design of TMS coils could enable more selective targeting of the induced E-field. The presented results appear to be the first significant advancement in the depth-focality trade-off of TMS coils since the introduction of the figure-8 coil three decades ago, and likely represent the fundamental physical limit.

Optimal focal-plane restoration

NASA Technical Reports Server (NTRS)

Reichenbach, Stephen E.; Park, Stephen K.

1989-01-01

Image restoration can be implemented efficiently by calculating the convolution of the digital image and a small kernel during image acquisition. Processing the image in the focal-plane in this way requires less computation than traditional Fourier-transform-based techniques such as the Wiener filter and constrained least-squares filter. Here, the values of the convolution kernel that yield the restoration with minimum expected mean-square error are determined using a frequency analysis of the end-to-end imaging system. This development accounts for constraints on the size and shape of the spatial kernel and all the components of the imaging system. Simulation results indicate the technique is effective and efficient.

Luneburg lens with extended flat focal surface for electronic scan applications.

PubMed

Li, Ying; Zhu, Qi

2016-04-04

Luneburg lens with flat focal surface has been developed to work together with planar antenna feeds for beam steering applications. According to our analysis of the conventional flattened Luneburg lens, it cannot accommodate enough feeding elements which can cover its whole scan range with half power beamwidths (HPBWs). In this paper, a novel Luneburg lens with extended flat focal surface is proposed based on the theory of Quasi-Conformal Transformation Optics (QCTO), with its beam steering features reserved. To demonstrate this design, a three-dimensional (3D) prototype of this novel extend-flattened Luneburg lens working at Ku band is fabricated based on 3D printing techniques, whose flat focal surface is attached to a 9-element microstrip antenna array to achieve different scan angles. Our measured results show that, with different antenna elements being fed, the HPBWs can cover the whole scan range.

[Bacterial meningitis].

PubMed

Brouwer, M C; van de Beek, D

2012-05-01

Bacterial meningitis is a severe disease which affects 35.000 Europeans each year and has a mortality rate of about 20%. During the past 25 years the epidemiology of bacterial meningitis has changed significantly due to the implementation of vaccination against Haemophilus influenzae, Neisseria meningtidis group C and Streptococcus pneumoniae. Due to these vaccines, meningitis is now predominantly a disease occurring in adults, caused especially by Streptococcus pneumoniae, while it was formerly a child disease which was largely caused by Haemophilus influenzae. Bacterial meningitis is often difficult to recognize since the classical presentation with neck stiffness, reduced awareness and fever occurs in less than half of the patients. The only way to diagnose or exclude bacterial meningitis is by performing low-threshold cerebrospinal fluid examination with a suspicion of bacterial meningitis. The treatment consists of the prescription of antibiotics and dexamethasone.

Bacterial infection and acute lung injury in hamsters.

PubMed

Seidenfeld, J J; Mullins, R C; Fowler, S R; Johanson, W G

1986-07-01

Bacterial pneumonia is a common complication of lung injury that can be an important determinant of outcome. We studied experimental lung injury produced in hamsters by injecting 20 mg/kg paraquat (PQ) intraperitoneally; control animals received saline vehicle. Three days later, Pseudomonas aeruginosa (PAO1), 10(8) organisms in 0.25 ml, or saline, 0.25 ml, was inoculated intratracheally. Lung and systemic antibacterial defenses were studied at death 24 h later. Paraquat alone produced focal interstitial pneumonitis and neutrophilic alveolitis, and resulted in a 12% (3 of 26) mortality. PAO1 alone caused focal pneumonias and no deaths. Animals receiving both agents (PAO1/PQ) had extensive diffuse alveolar damage characterized by alveolar hemorrhage, edema, influx of neutrophils, and vasculitis; 50% (16 of 32) died within 96 h of PQ injection. Mean lung counts of PAO1 at death were 7.6 X 10(4) colony forming units/g in PAO1 and 2.8 X 10(7) in PAO1/PQ animals (p less than 0.05). PAO1 colony counts in liver were increased nearly 100-fold in PAO1/PQ animals (p less than 0.05). Half-time of clearance of P. aeruginosa from the blood was prolonged in PAO1 and in PAO1/PQ animals (p less than 0.05) but not in PQ animals. Phagocytosis of Staphylococcus aureus by leukocytes lavaged from the lung was not impaired in any group compared with that in control animals, but intracellular killing was impaired in PAO1 and PAO1/PQ but not in PQ animals. Paraquat injury impairs lung antibacterial defenses by uncertain mechanisms. Superinfection of PQ-injured lungs by PAO1 appears responsible for defects in intrapulmonary and systemic antibacterial defenses.

Adaptive metalenses with simultaneous electrical control of focal length, astigmatism, and shift.

PubMed

She, Alan; Zhang, Shuyan; Shian, Samuel; Clarke, David R; Capasso, Federico

2018-02-01

Focal adjustment and zooming are universal features of cameras and advanced optical systems. Such tuning is usually performed longitudinally along the optical axis by mechanical or electrical control of focal length. However, the recent advent of ultrathin planar lenses based on metasurfaces (metalenses), which opens the door to future drastic miniaturization of mobile devices such as cell phones and wearable displays, mandates fundamentally different forms of tuning based on lateral motion rather than longitudinal motion. Theory shows that the strain field of a metalens substrate can be directly mapped into the outgoing optical wavefront to achieve large diffraction-limited focal length tuning and control of aberrations. We demonstrate electrically tunable large-area metalenses controlled by artificial muscles capable of simultaneously performing focal length tuning (>100%) as well as on-the-fly astigmatism and image shift corrections, which until now were only possible in electron optics. The device thickness is only 30 μm. Our results demonstrate the possibility of future optical microscopes that fully operate electronically, as well as compact optical systems that use the principles of adaptive optics to correct many orders of aberrations simultaneously.

[Focal hyperhidrosis.Quality of life, socioeconomic importance and use of internal medicinal therapy].

PubMed

Rzany, B; Müller, C; Hund, M

2012-06-01

Focal hyperhidrosis can have a substantial influence on the professional, physical, emotional and social life of those affected. This becomes clear when the results of quality of life studies and Health Service Research studies are reviewed, e.g. affected patients were prepared to contribute additional money for treatment of hyperhidrosis. The systemic therapy of focal hyperhidrosis with oral anticholinergic agents is a quite economical treatment strategy. These products can be administered continuously or sporadically. However, only good clinical date for the continous treatment exists. Focal hyperhidrosis is a disease which requires our full attention. It should be discussed whether e.g. QoL questionnaires should be used routinelly.

Focal epilepsy recruiting a generalised network of juvenile myoclonic epilepsy: a case report.

PubMed

Khaing, Myo; Lim, Kheng-Seang; Tan, Chong-Tin

2014-09-01

We report a patient with juvenile myoclonic epilepsy who subsequently developed temporal lobe epilepsy, which gradually became clinically dominant. Video telemetry revealed both myoclonic seizures and temporal lobe seizures. The temporal lobe seizures were accompanied by a focal recruiting rhythm with rapid generalisation on EEG, in which the ictal EEG pattern during the secondary generalised phase was morphologically similar to the ictal pattern during myoclonic seizures. The secondary generalised seizures of the focal epilepsy responded to sodium valproate, similar to the myoclonic epilepsy. In this rare case of coexistent Juvenile Myoclonic Epilepsy and Temporal lobe epilepsy, the possibility of focal epilepsy recruiting a generalised epileptic network was proposed and discussed.

Focal adhesion kinase is involved in mechanosensing during fibroblast migration

NASA Technical Reports Server (NTRS)

Wang, H. B.; Dembo, M.; Hanks, S. K.; Wang, Y.

2001-01-01

Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase localized at focal adhesions and is believed to mediate adhesion-stimulated effects. Although ablation of FAK impairs cell movement, it is not clear whether FAK might be involved in the guidance of cell migration, a role consistent with its putative regulatory function. We have transfected FAK-null fibroblasts with FAK gene under the control of the tetracycline repression system. Cells were cultured on flexible polyacrylamide substrates for the detection of traction forces and the application of mechanical stimulation. Compared with control cells expressing wild-type FAK, FAK-null cells showed a decrease in migration speed and directional persistence. In addition, whereas FAK-expressing cells responded to exerted forces by reorienting their movements and forming prominent focal adhesions, FAK-null cells failed to show such responses. Furthermore, FAK-null cells showed impaired responses to decreases in substrate flexibility, which causes control cells to generate weaker traction forces and migrate away from soft substrates. Cells expressing Y397F FAK, which cannot be phosphorylated at a key tyrosine site, showed similar defects in migration pattern and force-induced reorientation as did FAK-null cells. However, other aspects of F397-FAK cells, including the responses to substrate flexibility and the amplification of focal adhesions upon mechanical stimulation, were similar to that of control cells. Our results suggest that FAK plays an important role in the response of migrating cells to mechanical input. In addition, phosphorylation at Tyr-397 is required for some, but not all, of the functions of FAK in cell migration.

Pictures of focal nodular hyperplasia and hepatocellular adenomas

PubMed Central

Sempoux, Christine; Balabaud, Charles; Bioulac-Sage, Paulette

2014-01-01

This practical atlas aims to help liver and non liver pathologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocellular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for paraffin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glutamine synthase and according to the above results additional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocellular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated. PMID:25232451

Design of a variable-focal-length optical system

NASA Technical Reports Server (NTRS)

Ricks, D.; Shannon, R. R.

1984-01-01

Requirements to place an entire optical system with a variable focal length ranging from 20 to 200 cm within a overall length somewhat less than 100 cm placed severe restrictions on the design of a zoom lens suitable for use on a comet explorer. The requirements of a wavelength range of 0.4 to 1.0 microns produced even greater limitations on the possibilities for a design that included a catadioptric (using mirrors and glass) front and followed by a zooming refractive portion. Capabilities available commercial zoom lenses as well as patents of optical systems are reviewed. Preliminary designs of the refractive optics zoom lens and the catadioptric system are presented and evaluated. Of the two, the latter probably has the best chance of success, so long as the shortest focal lengths are not really needed.

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.

Spectrum of PORCN mutations in Focal Dermal Hypoplasia

USDA-ARS?s Scientific Manuscript database

Focal Dermal Hypoplasia (FDH), also known as Goltz syndrome (OMIM 305600), is a genetic disorder that affects multiple organ systems early in development. Features of FDH include skin abnormalities, (hypoplasia, atrophy, linear pigmentation, and herniation of fat through dermal defects); papillomas...

Hematological changes in nephritis in poultry induced by diets high in protein, high in calcium, containing urea, or deficient in vitamin A.

PubMed

Chandra, M; Singh, B; Singh, N; Ahuja, S P

1984-04-01

Nephritis was induced in 300, 18-day-old male Arbor Acre broiler chicks by feeding diets high (42.28%) in protein, high (3.27%) in calcium, containing urea (5%), or deficient in vitamin A. Various hematological parameters were studied at weekly intervals. Normocytic-normochromic anemia, characterized by a decrease in total erythrocyte counts, hemoglobin, packed cell volume, and an increase in erythrocyte sedimentation rate, was evident in the birds kept on diets high in protein, high in calcium, or deficient in vitamin A. Increased total erythrocytes, hemoglobin packed cell volume, and erythrocyte sedimentation rate was observed in birds fed urea. Differential leucocyte counts revealed lymphopenia, heterophilia and monocytosis in birds kept on diets high in protein, containing urea, or deficient in vitamin A. However, lymphocytosis, heteropenia , and monocytosis were recorded in birds fed the high calcium diet.

Optimization of confocal laser induced fluorescence for long focal length applications

NASA Astrophysics Data System (ADS)

Jemiolo, Andrew J.; Henriquez, Miguel F.; Thompson, Derek S.; Scime, Earl E.

2017-10-01

Laser induced fluorescence (LIF) is a non-perturbative diagnostic for measuring ion and neutral particle velocities and temperatures in a plasma. The conventional method for single-photon LIF requires intersecting optical paths for light injection and collection. The multiple vacuum windows needed for such measurements are unavailable in many plasma experiments. Confocal LIF eliminates the need for perpendicular intersecting optical paths by using concentric injection and collection paths through a single window. One of the main challenges with using confocal LIF is achieving high resolution measurements at the longer focal lengths needed for many plasma experiments. We present confocal LIF measurements in HELIX, a helicon plasma experiment at West Virginia University, demonstrating spatial resolution dependence on focal length and spatial filtering. By combining aberration mitigating optics with spatial filtering, our results show high resolution measurements at focal lengths of 0.5 m, long enough to access the interiors of many laboratory plasma experiments. This work was supported by U.S. National Science Foundation Grant No. PHY-1360278.

Scalp EEG Ictal Gamma and Beta Activity during Infantile Spasms: Evidence of Focality

PubMed Central

Nariai, Hiroki; Beal, Jules; Galanopoulou, Aristea S.; Mowrey, Wenzhu B.; Bickel, Stephan; Sogawa, Yoshimi; Jehle, Rana; Shinnar, Shlomo; Moshé, Solomon L.

2017-01-01

Objective We investigated temporal and spatial characteristics of ictal gamma and beta activity on scalp EEG during spasms in patients with West syndrome (WS) to evaluate potential focal cortical onset. Methods A total of 1033 spasms from 34 patients with WS of various etiologies were analyzed in video-EEG using time-frequency analysis. Ictal gamma (35–90 Hz) and beta (15–30 Hz) activities were correlated with visual symmetry of spasms, objective EMG (electromyography) analysis, and etiology of WS. Results Prior to the ictal motor manifestation, focal ictal gamma activity emerged from one hemisphere (71%, 24/34) or from midline (26%, 9/34), and was rarely simultaneously bilateral (3%, 1/34). Focal ictal beta activity emerged from either one hemisphere (68%, 23/34) or from midline (32%, 11/34). Onsets of focal ictal gamma and beta activity were most commonly observed around the parietal areas. Focal ictal gamma activity propagated faster than ictal beta activity to adjacent electrodes (median: 65 vs. 170 ms, p<0.01), and to contralateral hemisphere (median: 100 vs. 170 ms, p=0.01). Asymmetric peak amplitude of ictal gamma activity in the centroparietal areas (C3-P3 vs. C4-P4) correlated with asymmetric semiology. On the other hand, the majority of visually symmetric spasms showed asymmetry in peak amplitude and interhemispheric onset latency difference in both ictal gamma and beta activity. Significance Spasms may be a seizure with focal electrographic onset regardless of visual symmetry. Asymmetric involvement of ictal gamma activity to the centroparietal areas may determine the motor manifestations in WS. Scalp EEG ictal gamma and beta activity may be useful to demonstrate localized seizure onset in infants with WS. PMID:28397999

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Activates Type I Interferon Signals in Lupus Nephritis.

PubMed

Xue, Leixi; Liu, Lei; Huang, Jun; Wen, Jian; Yang, Ru; Bo, Lin; Tang, Mei; Zhang, Yi; Liu, Zhichun

2017-01-01

Type I interferon (IFN) plays a central role in pathogenesis of systemic lupus erythematosus (SLE); tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been associated with a pathogenic role in lupus nephritis (LN). Thus we investigated whether TWEAK could induce the activation of type I IFN pathway in LN. We examined this in patient-derived peripheral blood mononuclear cells (PBMCs) as well as MRL/lpr mice, a murine LN model. Relative to the control cohorts, MRL/lpr mice showed severe histological changes, high index levels of renal damage, and elevated expression of type I IFN-inducible genes. After shRNA suppression of TWEAK, we observed that renal damage was significantly attenuated and expression of type I IFN-inducible genes was reduced in MRL/lpr mice. In parallel, siRNA of TWEAK also significantly reduced the expression of type I IFN-inducible genes in PBMCs relative to control transfections. In PBMCs, TWEAK stimulation also led to expression of type I IFN-inducible genes. Our results illustrate a novel regulatory role of TWEAK, in which its activity positively regulates type I IFN pathway in LN based on preclinical models. Our findings suggest TWEAK could act as a critical target in preventing renal damage in patients with LN.

The Piriform Cortex and Human Focal Epilepsy

PubMed Central

Vaughan, David N.; Jackson, Graeme D.

2014-01-01

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

Ultrasound elastographic techniques in focal liver lesions

PubMed Central

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

2016-01-01

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

Ultrasound elastographic techniques in focal liver lesions.

PubMed

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

2016-03-07

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

Performance of the QWIP Focal Plane Arrays for NASA's Landsat Data Continuity Mission

NASA Technical Reports Server (NTRS)

Jhabvala, M.; Choi, K.; Waczynski, A.; La, A.; Sundaram, M.; Costard, E.; Jhabvala, C.; Kan, E.; Kahle, D.; Foltz, R.;

Development and Testing of an Innovative Two-Arm Focal-Plane Thermal Strap (TAFTS)

NASA Technical Reports Server (NTRS)

Urquiza, E.; Vasquez, C.; Rodriguez, J.; Van Gorp, B.

2011-01-01

Maintaining temperature stability in optical focal planes comes with the intrinsic challenge of creating a pathway that is both extremely flexible mechanically and highly conductive thermally. The task is further complicated because science-caliber optical focal planes are extremely delicate, yet their mechanical resiliency is rarely tested and documented. The mechanical engineer tasked with the thermo-mechanical design must then create a highly conductive thermal link that minimizes the tensile and shear stresses transmitted to the focal plane without design parameters on an acceptable stiffness. This paper will describe the development and testing of the thermal link developed for the Portable Remote Imaging Spectrometer (PRISM) instrument. It will provide experimentally determined mechanical stiffness plots in the three axes of interest. Analytical and experimental thermal conductance results for the two-arm focal-plane thermal strap (TAFTS), from cryogenic to room temperatures, are also presented. The paper also briefly describes some elements of the fabrication process followed in developing a novel design solution, which provides high conductance and symmetrical mechanical loading, while providing enhanced flexibility in all three degrees of freedom.

The Power of Poincaré: Elucidating the Hidden Symmetries in Focal Conic Domains

NASA Astrophysics Data System (ADS)

Matsumoto, Elisabetta A.; Alexander, Gareth P.; Chen, Bryan Gin-Ge; Kamien, Randall D.

2011-03-01

Focal conic domains are typically the ``smoking gun'' by which smectic liquid crystalline phases are identified. The geometry of the equally spaced smectic layers is highly generic but, at the same time, difficult to work with. We develop an approach to the study of focal sets in smectics which exploits a hidden Poincaré symmetry revealed only by viewing the smectic layers as projections from one-higher dimension. We use this perspective to shed light upon the concentric cyclides of Dupin and several classic focal conic textures which exhibit a more widespread level of geometric organization as in Friedel's law of corresponding cones, the networks and trellises expounded by Bouligand, or Apollonian packings.

Uncooled infrared focal plane array imaging in China

NASA Astrophysics Data System (ADS)

Lei, Shuyu

2015-06-01

This article reviews the development of uncooled infrared focal plane array (UIFPA) imaging in China in the past decade. Sensors based on optical or electrical read-out mechanism were developed but the latter dominates the market. In resistive bolometers, VOx and amorphous silicon are still the two major thermal-sensing materials. The specifications of the IRFPA made by different manufactures were collected and compared. Currently more than five Chinese companies and institutions design and fabricate uncooled infrared focal plane array. Some devices have sensitivity as high as 30 mK; the largest array for commercial products is 640×512 and the smallest pixel size is 17 μm. Emphasis is given on the pixel MEMS design, ROIC design, fabrication, and packaging of the IRFPA manufactured by GWIC, especially on design for high sensitivities, low noise, better uniformity and linearity, better stabilization for whole working temperature range, full-digital design, etc.

Power of the Poincaré group: elucidating the hidden symmetries in focal conic domains.

PubMed

Alexander, Gareth P; Chen, Bryan Gin-Ge; Matsumoto, Elisabetta A; Kamien, Randall D

2010-06-25

Focal conic domains are typically the "smoking gun" by which smectic liquid crystalline phases are identified. The geometry of the equally spaced smectic layers is highly generic but, at the same time, difficult to work with. In this Letter we develop an approach to the study of focal sets in smectics which exploits a hidden Poincaré symmetry revealed only by viewing the smectic layers as projections from one-higher dimension. We use this perspective to shed light upon several classic focal conic textures, including the concentric cyclides of Dupin, polygonal textures, and tilt-grain boundaries.

Acute bacterial skin infections in pediatric medicine: current issues in presentation and treatment.

PubMed

Hedrick, James

2003-01-01

Bacterial skin and skin structure infections commonly encountered in children include impetigo, folliculitis, furunculosis, carbuncles, wound infections, abscesses, cellulitis, erysipelas, scarlet fever, acute paronychia, and staphylococcal scalded skin syndrome. If diagnosed early and treated appropriately, these infections are almost always curable, but some have the potential to cause serious complications such as septicemia, nephritis, carditis and arthritis if diagnosis is delayed and/or treatment is inadequate. During the initial evaluation, it is important to determine whether the infection is superficial or deep, and whether it is localized or spreading. Prompt treatment is essential if the infection appears to be spreading, as the sequelae can be life threatening. Once the proper diagnosis is made, the next important step is selecting the most appropriate therapy. In children presenting with mild or moderately severe bacterial skin and skin structure infections and not requiring inpatient management or urgent operative débridement, prompt provision of oral antimicrobial therapy avoids the risk of worsening infection or hospitalization. Empiric antimicrobial therapy should be directed at the most likely pathogens, (e.g. Staphylococcus aureus or Streptococcus pyogenes), although some infections (e.g. subcutaneous abscesses and cellulitis following animal or human bites) may have a polymicrobial origin. In choosing the appropriate antimicrobial therapy, one must take into account the resistance profile of the target pathogen, the agent's antibacterial profile and intrinsic activity against the target pathogen, and its pharmacokinetic properties (including absorption, elimination, and extent of tissue penetration). Other factors to consider include tolerability of the drug, convenience of the dosing regimen, and acceptability and palatability of the oral formulation administered. Any treatment plan for bacterial skin and skin structure infections should aim

Kalman Filter for Calibrating a Telescope Focal Plane

NASA Technical Reports Server (NTRS)

Kang, Bryan; Bayard, David

2006-01-01

The instrument-pointing frame (IPF) Kalman filter, and an algorithm that implements this filter, have been devised for calibrating the focal plane of a telescope. As used here, calibration signifies, more specifically, a combination of measurements and calculations directed toward ensuring accuracy in aiming the telescope and determining the locations of objects imaged in various arrays of photodetectors in instruments located on the focal plane. The IPF Kalman filter was originally intended for application to a spaceborne infrared astronomical telescope, but can also be applied to other spaceborne and ground-based telescopes. In the traditional approach to calibration of a telescope, (1) one team of experts concentrates on estimating parameters (e.g., pointing alignments and gyroscope drifts) that are classified as being of primarily an engineering nature, (2) another team of experts concentrates on estimating calibration parameters (e.g., plate scales and optical distortions) that are classified as being primarily of a scientific nature, and (3) the two teams repeatedly exchange data in an iterative process in which each team refines its estimates with the help of the data provided by the other team. This iterative process is inefficient and uneconomical because it is time-consuming and entails the maintenance of two survey teams and the development of computer programs specific to the requirements of each team. Moreover, theoretical analysis reveals that the engineering/ science iterative approach is not optimal in that it does not yield the best estimates of focal-plane parameters and, depending on the application, may not even enable convergence toward a set of estimates.

Finger-specific loss of independent control of movements in musicians with focal dystonia.

PubMed

Furuya, S; Altenmüller, E

2013-09-05

The loss of independent control of finger movements impairs the dexterous use of the hand. Focal hand dystonia is characterised by abnormal structural and functional changes at the cortical and subcortical regions responsible for individuated finger movements and by the loss of surround inhibition in the finger muscles. However, little is known about the pathophysiological impact of focal dystonia on the independent control of finger movements. Here we addressed this issue by asking pianists with and without focal dystonia to repetitively strike a piano key with one of the four fingers as fast as possible while the remaining digits kept the adjacent keys depressed. Using principal component analysis and cluster analysis to the derived keystroke data, we successfully classified pianists according to the presence or absence of dystonic symptoms with classification rates and cross-validation scores of approximately 90%. This confirmed the effects of focal dystonia on the individuated finger movements. Interestingly, the movement features that contributed to successful classification differed across fingers. Compared to healthy pianists, pianists with an affected index finger were characterised predominantly by stronger keystrokes, whereas pianists with affected middle or ring fingers exhibited abnormal temporal control of the keystrokes, such as slowness and rhythmic inconsistency. The selective alternation of the movement features indicates a finger-specific loss of the independent control of finger movements in focal dystonia of musicians. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Radio Telescope Focal Container for the Russian VLBI Network of New Generation

NASA Technical Reports Server (NTRS)

Ipatov, Alexander; Mardyshkin, Vyacheslav; Cherepanov, Andrey; Chernov, Vitaly; Diky, Dmitry; Khvostov, Evgeny; Yevstigneyev, Alexander

2010-01-01

This article considers the development of the structure of receivers for Russian radio telescopes. The development of these radio telescopes is undertaken within the project for creating a Russian small-antenna-based radio interferometer of new generation. It is shown that for small antennas (10. 12 meter) the principal unit, which provides the best SNR, is the so-called focal container placed at primary focus. It includes the primary feed, HEMT LNA, and cryogenic cooling system down to 20. K. A new multi-band feed based on traveling wave resonators is used. It has small dimensions, low weight, and allows working with circular polarizations. Thus it can be placed into focal container and cooled with the LNA. A sketch of the focal container, with traveling-wave-resonator feed, and calculations of the expected parameters of the multi-band receiver are presented.

Optimizing focal plane electric field estimation for detecting exoplanets

NASA Astrophysics Data System (ADS)

Groff, T.; Kasdin, N. J.; Riggs, A. J. E.

Detecting extrasolar planets with angular separations and contrast levels similar to Earth requires a large space-based observatory and advanced starlight suppression techniques. This paper focuses on techniques employing an internal coronagraph, which is highly sensitive to optical errors and must rely on focal plane wavefront control techniques to achieve the necessary contrast levels. To maximize the available science time for a coronagraphic mission we demonstrate an estimation scheme using a discrete time Kalman filter. The state estimate feedback inherent to the filter allows us to minimize the number of exposures required to estimate the electric field. We also show progress including a bias estimate into the Kalman filter to eliminate incoherent light from the estimate. Since the exoplanets themselves are incoherent to the star, this has the added benefit of using the control history to gain certainty in the location of exoplanet candidates as the signal-to-noise between the planets and speckles improves. Having established a purely focal plane based wavefront estimation technique, we discuss a sensor fusion concept where alternate wavefront sensors feedforward a time update to the focal plane estimate to improve robustness to time varying speckle. The overall goal of this work is to reduce the time required for wavefront control on a target, thereby improving the observatory's planet detection performance by increasing the number of targets reachable during the lifespan of the mission.

Renal alpha-smooth muscle actin: a new prognostic factor for lupus nephritis.

PubMed

Makni, Kaouthar; Jarraya, Faïçal; Khabir, Abdelmajid; Hentati, Basma; Hmida, Mohamed Ben; Makni, Hafedh; Boudawara, Tahia; Jlidi, Rchid; Hachicha, Jamil; Ayadi, Hammadi

2009-08-01

Systemic lupus erythematosus (SLE) is the prototype of autoimmune disease where renal involvement is frequent and always severe. Histological prognostic factors proposed for lupus nephritis (LN) including the World Health Organization and International Society of Nephrology/Renal Pathology Society--Working Group on the Classification classifications, active (AI) and chronicity (CI) indices may not predict response to treatment. The aim of this study was to correlate alpha-smooth muscle actin (alpha-SMA) expression, an early marker of glomerular and interstitial response to injury, to AI and CI, renal scarring progression and response to treatment. Fifty-seven kidney biopsy specimens obtained from 32 patients suffering from LN were studied. Twenty patients with class IV LN at first biopsy were identified to study renal progression to chronic renal failure until the use of immunosuppressive treatment. Interstitial alpha-SMA (I-alpha-SMA) was correlated only with CI (P < 0.001) whereas mesangial alpha-SMA (M-alpha-SMA) was correlated with neither LN activity (P = 0.126) nor sclerosis (P = 0.297). Only I-alpha-SMA was correlated with renal failure (P = 0.01). We divided patients with class IV LN into progressors and non-progressors based on the slope of serum creatinine. At first biopsy, M-alpha-SMA and I-alpha-SMA, but not AI and CI, were correlated with renal failure progression (M-alpha-SMA, 9.7b1.1 vs 7.8b1.4, P = 0.004; and I-alpha-SMA, 9.3b1.1 vs 6.5b3.2, P = 0.011). The study data highlight that I-alpha-SMA immunostain in class IV LN patients was correlated with chronicity indices. Moreover, M-alpha-SMA and I-alpha-SMA expression in first biopsy predicted renal progression modality. alpha-SMA expression may therefore be a useful marker to predict renal prognosis in LN.

Granulomatous nephritis in psittacines associated with parasitism by the trematode Paratanaisia spp.

PubMed

Luppi, Marcela M; de Melo, Alan L; Motta, Rafael O C; Malta, Marcelo C C; Gardiner, C H; Santos, Renato L

2007-05-31

Trematodes belonging to the family Eucotylidae are parasites of the kidney and ureter, and affect several bird species. However, psittacines have not been identified as hosts of these parasites. Three birds, an adult female blue and gold macaw (Ara ararauna), an adult female blue-winged macaw (Propyrrhura maracana) and an adult male white-eared parakeet (Pyrrhura leucotis) were admitted at the Veterinary Hospital of the Fundação Zoo-Botânica de Belo Horizonte, Brazil (FZB/BH). All three birds had severe dehydration and cachexia. The blue and gold macaw presented with dyspnea, apathy, and incoordination. Blood cell counts indicated discrete anemia and leucopenia. Blood biochemistry revealed significant increase in levels of uric acid (61 mg/dl) and blood urea nitrogen (22 mg/dl). The bird died within 24 h after admission. The other two birds were admitted with similar clinical signs, but died prior to a complete clinical examination. At the necropsy, in all the three birds, the kidneys were enlarged with brown-yellowish discoloration and irregular cortical surface. On the cut surface, there was a brown-yellowish material with few visible parasites flowing out of the parenchyma. When fragments of the kidneys were placed in 10% formalin, a large number of trematodes came out of the renal parenchyma. The parasites were identified as Paratanaisia robusta infecting all three birds, and P. bragai infecting the blue-winged macaw and the white-eared parakeet. Histologically, there was an interstitial, multifocal to coalescent, lymphoplasmacytic infiltrate with some epithelioid macrophages, and a few heterophils, characterizing a granulomatous nephritis. Adult worms and eggs were observed within dilated tubules and in the renal pelvis. In the blue and gold macaw, some parasite eggs were located interstitially associated with an intense adjacent granulomatous reaction.

European genetic ancestry is associated with a decreased risk of lupus nephritis.

PubMed

Richman, Ilana B; Taylor, Kimberly E; Chung, Sharon A; Trupin, Laura; Petri, Michelle; Yelin, Edward; Graham, Robert R; Lee, Annette; Behrens, Timothy W; Gregersen, Peter K; Seldin, Michael F; Criswell, Lindsey A

2012-10-01

African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than are SLE patients of European descent. This study was undertaken to investigate whether European genetic ancestry protects against the development of lupus nephritis, with the aim of exploring the genetic and socioeconomic factors that might explain this effect. This was a cross-sectional study of SLE patients from a multiethnic case collection. Participants were genotyped for 126 single-nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. Logistic regression was used to test the association between European ancestry and renal disease. Analyses were adjusted for continental ancestries, socioeconomic status (SES), and candidate genes. Participants (n = 1,906) had, on average, 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among the participants, 656 (34%) had renal disease. A 10% increase in the proportion of European ancestry estimated in each participant was associated with a 15% reduction in the odds of having renal disease, after adjustment for disease duration and sex (odds ratio 0.85, 95% confidence interval 0.82-0.87; P = 1.9 × 10(-30) ). Adjustment for other genetic ancestries, measures of SES, or SNPs in the genes most associated with renal disease (IRF5 [rs4728142], BLK [rs2736340], STAT4 [rs3024912], and HLA-DRB1*0301 and DRB1*1501) did not substantively alter this relationship. European ancestry is protective against the development of renal disease in SLE, an effect that is independent of other genetic ancestries, candidate risk alleles, and socioeconomic factors. Copyright © 2012 by the American College of Rheumatology.

Large-format InGaAs focal plane arrays for SWIR imaging

NASA Astrophysics Data System (ADS)

Hood, Andrew D.; MacDougal, Michael H.; Manzo, Juan; Follman, David; Geske, Jonathan C.

2012-06-01

FLIR Electro Optical Components will present our latest developments in large InGaAs focal plane arrays, which are used for low light level imaging in the short wavelength infrared (SWIR) regime. FLIR will present imaging from their latest small pitch (15 μm) focal plane arrays in VGA and High Definition (HD) formats. FLIR will present characterization of the FPA including dark current measurements as well as the use of correlated double sampling to reduce read noise. FLIR will show imagery as well as FPA-level characterization data.

Losigamone add-on therapy for focal epilepsy.

PubMed

Xiao, Yousheng; Luo, Man; Wang, Jin; Luo, Hongye

2018-01-22

Epilepsy is a common neurologic disorder, affecting approximately 50 million people worldwide; nearly a third of these people have epilepsy that is not well controlled by a single antiepileptic drug (AED) and they usually require treatment with a combination of two or more AEDs. In recent years, many newer AEDs have been investigated as add-on therapy for focal epilepsy; losigamone is one of these drugs and is the focus of this systematic review. This is an update of a Cochrane review first published in 2012 (Cochrane Database of Systematic Reviews 2012, Issue 6) and updated in 2015. To investigate the efficacy and safety of losigamone when used as an add-on therapy for focal epilepsy. For the latest update on 9 February 2017, we searched the Cochrane Epilepsy Specialized Register, CENTRAL and MEDLINE . We searched trials registers and contacted the manufacturer of losigamone and authors of included studies for additional information. We did not impose any language restrictions. Randomized controlled, add-on trials comparing losigamone with placebo for focal epilepsy. Two review authors independently assessed trial quality and extracted data. The primary outcomes were 50% or greater reduction in seizure frequency and seizure freedom; the secondary outcomes were treatment withdrawal and adverse events. Results are presented as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs (for the individual listed adverse events to make an allowance for multiple testing). Two trials involving a total of 467 participants, aged over 18 years, were eligible for inclusion. Both trials assessed losigamone 1200 mg/day or 1500 mg/day as an add-on therapy for focal epilepsy. We assessed one trial as being of good methodological quality while the other was of uncertain quality. For the efficacy outcomes, results did show that participants taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.76, 95% CI 1.14 to 2

Selecting focal species as surrogates for imperiled species using relative sensitivities derived from occupancy analysis

USGS Publications Warehouse

Silvano, Amy; Guyer, Craig; Steury, Todd; Grand, James B.

2017-01-01

Most imperiled species are rare or elusive and difficult to detect, which makes gathering data to estimate their response to habitat restoration a challenge. We used a repeatable, systematic method for selecting focal species using relative sensitivities derived from occupancy analysis. Our objective was to select suites of focal species that would be useful as surrogates when predicting effects of restoration of habitat characteristics preferred by imperiled species. We developed 27 habitat profiles that represent general habitat relationships for 118 imperiled species. We identified 23 regularly encountered species that were sensitive to important aspects of those profiles. We validated our approach by examining the correlation between estimated probabilities of occupancy for species of concern and focal species selected using our method. Occupancy rates of focal species were more related to occupancy rates of imperiled species when they were sensitive to more of the parameters appearing in profiles of imperiled species. We suggest that this approach can be an effective means of predicting responses by imperiled species to proposed management actions. However, adequate monitoring will be required to determine the effectiveness of using focal species to guide management actions.

ESRD from lupus nephritis in the United States, 1995-2010.

PubMed

Sexton, Donal J; Reule, Scott; Solid, Craig; Chen, Shu-Cheng; Collins, Allan J; Foley, Robert N

2015-02-06

While ESRD from lupus nephritis (ESLN) increased in the United States after the mid-1990s and racial disparities were apparent, current trends are unknown. Retrospective US Renal Data System data (n=1,557,117) were used to calculate standardized incidence ratios (standardized to 1995-1996) and outcomes of ESLN (n=16,649). For events occurring after initiation of RRT, follow-up ended on June 30, 2011. Overall ESLN rates (95% confidence intervals [95% CIs]) in 1995-1996 were 3.1 (2.9 to 3.2) cases per million per year. Rates were higher for subgroups characterized by African-American race (11.1 [95% CI, 10.3 to 11.9]); other race (4.9 [95% CI, 4.0 to 5.8]); female sex (4.9 [95% CI, 4.6 to 5.2]); and ages 20-29 years (4.9 [95% CI, 4.4 to 5.4]), 30-44 years (4.6 [95% CI, 4.2 to 5.0]), and 45-64 years (4.0 [95% CI, 3.7 to 4.4]). Standardized incidence ratios for the overall population in subsequent biennia were 1.19 (1.14 to 1.24) in 1997-1998, 1.17 (1.12 to 1.22) in 1999-2000, 1.17 (1.12 to 1.22) in 2001-2002, 1.21 (1.16 to 1.26) in 2003-2004, 1.18 (1.13 to 1.23) in 2005-2006, 1.16 (1.11 to 1.21) in 2007-2008, and 1.05 (1.01 to 1.09) in 2009-2010, respectively. During a median (interquartile range) follow-up of 4.4 (6.3) years, 42.6% of patients with ESLN died, 45.3% were listed for renal transplant, and 28.7% underwent transplantation. Patients with ESLN were more likely than matched controls to be listed for and to undergo transplantation, and mortality rates were similar. Among patients with ESLN, African Americans were less likely to undergo transplantation (adjusted hazard ratio, 0.54 [0.51 to 0.58]) and more likely to die prematurely (adjusted hazard ratio, 1.23 [1.17 to 1.30]). While ESLN appears to have stopped increasing in the last decade, racial disparities in outcomes persist. Copyright © 2015 by the American Society of Nephrology.

High operating temperature interband cascade focal plane arrays

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

Tian, Z.-B.; Godoy, S. E.; Kim, H. S.

2014-08-04

In this paper, we report the initial demonstration of mid-infrared interband cascade (IC) photodetector focal plane arrays with multiple-stage/junction design. The merits of IC photodetectors include low noise and efficient photocarrier extraction, even for zero-bias operation. By adopting enhanced electron barrier design and a total absorber thickness of 0.7 μm, the 5-stage IC detectors show very low dark current (1.10 × 10{sup −7} A/cm{sup 2} at −5 mV and 150 K). Even with un-optimized fabrication and standard commercial (mis-matched) read-out circuit technology, infrared images are obtained by the 320 × 256 IC focal plane array up to 180 K with f/2.3 optics. The minimum noise equivalent temperature differencemore » of 28 mK is obtained at 120 K. These initial results indicate great potential of IC photodetectors, particularly for high operating temperature applications.« less

Multispecies, Integrative GWAS for Focal Segmental Glomerulosclerosis

DTIC Science & Technology

2017-09-01

project are to identify genetic determinants of focal segmental glomerulosclerosis (FSGS) using genomewide association studies in mouse strains. We have... methodology used shall be provided. As the project progresses to completion, the emphasis in reporting in this section should shift from reporting...development” activities result in increased knowledge or skill in one’s area of expertise and may include workshops, conferences, seminars, study

Angiotensin II effects on ischemic focal ventricular tachycardia are predominantly mediated through myocardial AT(2) receptor.

PubMed

Gopinathannair, Rakesh; Chaudhary, Ashok K; Xing, Dezhi; Ely, Debra; Zheng, Wei; Martins, James B

2009-11-01

Ischemic focal ventricular tachycardia (VT) occurs in animals and humans. Angiotensin-converting enzyme inhibitors and receptor blockers reduce sudden death in patients with ischemic heart disease. In our dog model of coronary artery occlusion (CAO), we tested the hypothesis that angiotensin II (AGII) will selectively promote focal VT and that the specific AT(2) blocker PD-123319 (PD), or AT(1) blocker losartan, will affect this VT. Anesthetized dogs (n = 90) underwent CAO, followed by three-dimensional activation mapping of inducible VT. Dogs without VT in 1-3 h after CAO received AGII, and those with VT received either PD or losartan. Focal endocardium excised from ischemic sites was studied in vitro with standard microelectrode. Of 33 dogs with no inducible VT, AGII infusion resulted in sustained VT of only focal Purkinje origin in 13 (39%) compared with 0 of 20 dogs with saline. Of 26 dogs with inducible VT at baseline, given PD, reinduction was blocked in 8 of 10 (P < 0.05) focal VT, but only 1 of 15 with reentry. In contrast, of 11 dogs given losartan, reinduction of either mechanism was not blocked. In vitro triggered activity in Purkinje was blocked by PD in 13 of 19 (P < 0.05), but not by losartan in 8. Also, triggered activity was promoted by AGII, losartan, or the combination in 9 of 12 tissues. AGII promotes only focal, mainly Purkinje ischemic VT. PD, but not losartan, preferentially blocked focal VT, which is likely due to triggered activity due to delayed afterdepolarizations in Purkinje.

An Integrated Optimal Estimation Approach to Spitzer Space Telescope Focal Plane Survey

NASA Technical Reports Server (NTRS)

Bayard, David S.; Kang, Bryan H.; Brugarolas, Paul B.; Boussalis, D.

2004-01-01

This paper discusses an accurate and efficient method for focal plane survey that was used for the Spitzer Space Telescope. The approach is based on using a high-order 37-state Instrument Pointing Frame (IPF) Kalman filter that combines both engineering parameters and science parameters into a single filter formulation. In this approach, engineering parameters such as pointing alignments, thermomechanical drift and gyro drifts are estimated along with science parameters such as plate scales and optical distortions. This integrated approach has many advantages compared to estimating the engineering and science parameters separately. The resulting focal plane survey approach is applicable to a diverse range of science instruments such as imaging cameras, spectroscopy slits, and scanning-type arrays alike. The paper will summarize results from applying the IPF Kalman Filter to calibrating the Spitzer Space Telescope focal plane, containing the MIPS, IRAC, and the IRS science Instrument arrays.

Application of preconditioned alternating direction method of multipliers in depth from focal stack

NASA Astrophysics Data System (ADS)

Javidnia, Hossein; Corcoran, Peter

2018-03-01

Postcapture refocusing effect in smartphone cameras is achievable using focal stacks. However, the accuracy of this effect is totally dependent on the combination of the depth layers in the stack. The accuracy of the extended depth of field effect in this application can be improved significantly by computing an accurate depth map, which has been an open issue for decades. To tackle this issue, a framework is proposed based on a preconditioned alternating direction method of multipliers for depth from the focal stack and synthetic defocus application. In addition to its ability to provide high structural accuracy, the optimization function of the proposed framework can, in fact, converge faster and better than state-of-the-art methods. The qualitative evaluation has been done on 21 sets of focal stacks and the optimization function has been compared against five other methods. Later, 10 light field image sets have been transformed into focal stacks for quantitative evaluation purposes. Preliminary results indicate that the proposed framework has a better performance in terms of structural accuracy and optimization in comparison to the current state-of-the-art methods.

Combining PALM and SOFI for quantitative imaging of focal adhesions in living cells

NASA Astrophysics Data System (ADS)

Deschout, Hendrik; Lukes, Tomas; Sharipov, Azat; Feletti, Lely; Lasser, Theo; Radenovic, Aleksandra

2017-02-01

Focal adhesions are complicated assemblies of hundreds of proteins that allow cells to sense their extracellular matrix and adhere to it. Although most focal adhesion proteins have been identified, their spatial organization in living cells remains challenging to observe. Photo-activated localization microscopy (PALM) is an interesting technique for this purpose, especially since it allows estimation of molecular parameters such as the number of fluorophores. However, focal adhesions are dynamic entities, requiring a temporal resolution below one minute, which is difficult to achieve with PALM. In order to address this problem, we merged PALM with super-resolution optical fluctuation imaging (SOFI) by applying both techniques to the same data. Since SOFI tolerates an overlap of single molecule images, it can improve the temporal resolution compared to PALM. Moreover, an adaptation called balanced SOFI (bSOFI) allows estimation of molecular parameters, such as the fluorophore density. We therefore performed simulations in order to assess PALM and SOFI for quantitative imaging of dynamic structures. We demonstrated the potential of our PALM-SOFI concept as a quantitative imaging framework by investigating moving focal adhesions in living cells.

Focal shift and the axial optical coordinate for high-aperture systems of finite Fresnel number.

PubMed

Sheppard, Colin J R; Török, Peter

2003-11-01

Analytic expressions are given for the on-axis intensity predicted by the Rayleigh-Sommerfeld and Kirchhoff diffraction integrals for a scalar optical system of high numerical aperture and finite value of Fresnel number. A definition of the axial optical coordinate is introduced that is valid for finite values of Fresnel number, for high-aperture systems, and for observation points distant from the focus. The focal shift effect is reexamined. For the case when the focal shift is small, explicit expressions are given for the focal shift and the axial peak in intensity.

A new measurement method of profile tolerance for the LAMOST focal plane

NASA Astrophysics Data System (ADS)

Zhou, Zengxiang; Jin, Yi; Zhai, Chao; Xing, Xiaozheng

2008-07-01

There were a few methods taken in the profile tolerance measurement of the LAMOST Focal Plane Plate. One of the methods was to use CMM (Coordinate Measurement Machine) to measure the points on the small Focal Plane Plate and calculate the points whether or not in the tolerance zone. In this process there are some small shortcomings. The measuring point positions on the Focal Plane Plate are not the actual installation location of the optical fiber positioning system. In order to eliminate these principle errors, a measuring mandrel is inserted into the unit-holes, and the precision for the mandrel with the hole is controlled in the high level. Then measure the center of the precise target ball which is placed on the measuring mandrel by CMM. At last, fit a sphere surface with the measuring center points of the target ball and analyze the profile tolerance of the Focal Plane Plate. This process will be more in line with the actual installation location of the optical fiber positioning system. When use this method to judge the profile tolerance can provide the reference date for maintaining the ultra error unit-holes on the Focal Plane Plate. But when insert the measuring mandrel into the unit hole, there are manufacturing errors in the measuring mandrel, target ball and assembly errors. All these errors will bring the influence in the measurement. In the paper, an impact evaluation assesses the intermediate process with all these errors through experiments. And the experiment results show that there are little influence when use the target ball and the measuring mandrel in the measurement of the profile tolerance. Instead, there are more advantages than many past use of measuring methods.

Global and regional functional connectivity maps of neural oscillations in focal epilepsy

PubMed Central

Englot, Dario J.; Hinkley, Leighton B.; Kort, Naomi S.; Imber, Brandon S.; Mizuiri, Danielle; Honma, Susanne M.; Findlay, Anne M.; Garrett, Coleman; Cheung, Paige L.; Mantle, Mary; Tarapore, Phiroz E.; Knowlton, Robert C.; Chang, Edward F.; Nagarajan, Srikantan S.

2015-01-01

Intractable focal epilepsy is a devastating disorder with profound effects on cognition and quality of life. Epilepsy surgery can lead to seizure freedom in patients with focal epilepsy; however, sometimes it fails due to an incomplete delineation of the epileptogenic zone. Brain networks in epilepsy can be studied with resting-state functional connectivity analysis, yet previous investigations using functional magnetic resonance imaging or electrocorticography have produced inconsistent results. Magnetoencephalography allows non-invasive whole-brain recordings, and can be used to study both long-range network disturbances in focal epilepsy and regional connectivity at the epileptogenic zone. In magnetoencephalography recordings from presurgical epilepsy patients, we examined: (i) global functional connectivity maps in patients versus controls; and (ii) regional functional connectivity maps at the region of resection, compared to the homotopic non-epileptogenic region in the contralateral hemisphere. Sixty-one patients were studied, including 30 with mesial temporal lobe epilepsy and 31 with focal neocortical epilepsy. Compared with a group of 31 controls, patients with epilepsy had decreased resting-state functional connectivity in widespread regions, including perisylvian, posterior temporo-parietal, and orbitofrontal cortices (P < 0.01, t-test). Decreased mean global connectivity was related to longer duration of epilepsy and higher frequency of consciousness-impairing seizures (P < 0.01, linear regression). Furthermore, patients with increased regional connectivity within the resection site (n = 24) were more likely to achieve seizure postoperative seizure freedom (87.5% with Engel I outcome) than those with neutral (n = 15, 64.3% seizure free) or decreased (n = 23, 47.8% seizure free) regional connectivity (P < 0.02, chi-square). Widespread global decreases in functional connectivity are observed in patients with focal epilepsy, and may reflect deleterious

Bacterial meningitis.

PubMed

Heckenberg, Sebastiaan G B; Brouwer, Matthijs C; van de Beek, Diederik

2014-01-01

Bacterial meningitis is a neurologic emergency. Vaccination against common pathogens has decreased the burden of disease. Early diagnosis and rapid initiation of empiric antimicrobial and adjunctive therapy are vital. Therapy should be initiated as soon as blood cultures have been obtained, preceding any imaging studies. Clinical signs suggestive of bacterial meningitis include fever, headache, meningismus, and an altered level of consciousness but signs may be scarce in children, in the elderly, and in meningococcal disease. Host genetic factors are major determinants of susceptibility to meningococcal and pneumococcal disease. Dexamethasone therapy has been implemented as adjunctive treatment of adults with pneumococcal meningitis. Adequate and prompt treatment of bacterial meningitis is critical to outcome. In this chapter we review the epidemiology, pathophysiology, and management of bacterial meningitis. © 2014 Elsevier B.V. All rights reserved.

High Frequency High Spectral Resolution Focal Plane Arrays for AtLAST

NASA Astrophysics Data System (ADS)

Baryshev, Andrey

2018-01-01

Large collecting area single dish telescope such as ATLAST will be especially effective for medium (R 1000) and high (R 50000) spectral resolution observations. Large focal plane array is a natural solution to increase mapping speed. For medium resolution direct detectors with filter banks (KIDs) and or heterodyne technology can be employed. We will analyze performance limits of comparable KID and SIS focal plane array taking into account quantum limit and high background condition of terrestrial observing site. For large heterodyne focal plane arrays, a high current density AlN junctions open possibility of large instantaneous bandwidth >40%. This and possible multi frequency band FPSs presents a practical challenge for spatial sampling and scanning strategies. We will discuss phase array feeds as a possible solution, including a modular back-end system, which can be shared between KID and SIS based FPA. Finally we will discuss achievable sensitivities and pixel co unts for a high frequency (>500 GHz) FPAs and address main technical challenges: LO distribution, wire counts, bias line multiplexing, and monolithic vs. discrete mixer component integration.

Colonoscopic Findings in Patients With Incidental Colonic Focal FDG Uptake.

PubMed

Keyzer, Caroline; Dhaene, Benjamin; Blocklet, Didier; De Maertelaer, Viviane; Goldman, Serge; Gevenois, Pierre Alain

2015-05-01

The purpose of this study was to investigate the nature of FDG-avid and non-FDG-avid lesions detected at colonoscopy in patients presenting with incidental focal colonic FDG uptake at PET/CT. Among 9073 patients who underwent PET/CT over a 4-year period, 82 patients without a history of colonic disease had focal colonic FDG uptake and underwent colonoscopy. In consensus, a radiologist and a nuclear physician read images from these PET/CT examinations. They recorded the location of focal FDG uptake in the colon and associated CT abnormalities and measured maximum standardized uptake value (SUVmax) and metabolic volume (MV). Readings were performed twice--first without and second with knowledge of lesion location at colonoscopy. The final diagnosis was based on colonoscopic findings and histopathologic results categorized into benign, premalignant, or malignant. One hundred seven foci of colonic FDG uptake at PET/CT and 150 lesions at colonoscopy were detected. Among 107 foci of FDG uptake, 65 (61%) corresponded to a lesion at colonoscopy (true-positive findings), and 42 (39%) did not (false-positive findings). Among 150 lesions found at colonoscopy, 85 (57%) were not FDG avid (false-negative findings). The MV of true-positive findings was lower than that of false-positive findings (4.0 ± 0.4 cm(3) vs 6.2 ± 0.7 cm(3); p = 0.006), but SUVmax did not differ (7.4 ± 0.5 vs 7.7 ± 0.5; p = 0.649). Considering the histopathologic categories of the lesions and the false-positive findings, there was no difference in SUVmax (p = 0.103), but MV was lower in premalignant lesions than in false-positive findings (p = 0.005). Focal colonic FDG uptake may indicate the presence of a benign, pre-malignant, or malignant lesion. Subsequent colonoscopy should not be restricted to the colonic site of FDG uptake.

Recurrent Focal Myositis in Childhood: A Case Report and Systematic Review of the Literature.

PubMed

Milani, Gregorio P; Mazzoni, Marta B M; Gatti, Helga; Bertolozzi, Giuseppe; Fossali, Emilio F

2017-06-01

Recurrent focal myositis in adulthood has been documented in case reports and case series. Existing textbooks and reviews do not mention or mention only in passing this entity in childhood. We present a patient with recurrent focal myositis and summarize available clinical, laboratory, management, and outcome data on this entity in the pediatric ages. We describe a nine-year-old patient with recurrent myositis of the left biceps. The terms "myositis" and "relapsing" or "recurrent" or "recurrence" were searched using the United States National Library of Medicine and the Excerpta Medica Database. Pertinent secondary references were also screened. Another seven pediatric patients (five males and two females, median age ten years, interquartile range 7-14 years) with recurrent focal myositis were identified. In children, the calf was the most frequently involved muscle. Unlike adults, the myositis in children was usually painful. Episodes could be associated with normal or elevated erythrocyte sedimentation rate and blood levels of C-reactive protein, creatine kinase, and aspartate aminotransferase. Abnormalities of the creatine kinase value did not seem to be associated with a higher risk of recurrences. Focal myositis has a favorable outcome in children. Recurrent focal myositis is rare and usually benign in childhood. More data are needed to improve the understanding of this condition. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetics Home Reference: familial focal epilepsy with variable foci

MedlinePlus

... SF, Dibbens LM. Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations. ... caused by mutation in the mammalian target of rapamycin regulator NPRL3. Ann Neurol. 2016 Jan;79(1): ...

Validation of the Lupus Nephritis Clinical Indices in Childhood-Onset Systemic Lupus Erythematosus

PubMed Central

Mina, Rina; Abulaban, Khalid; Klein-Gitelman, Marisa; Eberhard, Anne; Ardoin, Stacy; Singer, Nora; Onel, Karen; Tucker, Lori; O’Neil, Kathleen; Wright, Tracey; Brooks, Elizabeth; Rouster-Stevens, Kelly; Jung, Lawrence; Imundo, Lisa; Rovin, Brad; Witte, David; Ying, Jun; Brunner, Hermine I.

2015-01-01

Objective To validate clinical indices of lupus nephritis (LN) activity and damage when used in children against the criterion standard of kidney biopsy findings. Methods In 83 children requiring kidney biopsy the SLE Disease Activity Index Renal Domain (SLEDAI-R); British Isles Lupus Assessment Group index Renal Domain (BILAG-R), Systemic Lupus International Collaborating Clinics Renal Activity (SLICC-RAS) and Damage Index Renal Domain (SDI-R) were measured. Fixed effect and logistic models were done to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low/moderate vs. high LN-activity [NIH Activity Index (NIH-AI) score: ≤ 10 vs. > 10; Tubulointerstitial Activity Index (TIAI) score: ≤ 5 vs. > 5) or the absence vs. presence of LN chronicity [NIH Chronicity Index (NIH-CI) score: 0 vs. ≥ 1]. Results There were 10, 50 and 23 patients with class I/II, III/IV and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with LN-activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between LN-activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture LN chronicity was 23.5% and 91.7%, respectively. Despite designed to measure LN-activity, SLICC-RAS and SLEDAI-R scores significantly differed with LN chronicity status. Conclusion Current clinical indices of LN fail to discriminate ISN/RPS Class in children. Despite its shortcomings, the SLEDAI-R appears to best for measuring LN activity in a clinical setting. The SDI-R is a poor correlate of LN chronicity. PMID:26213987

Automatic test comes to focal plane array production

NASA Astrophysics Data System (ADS)

Skaggs, Frank L.; Barton, T. D.

1992-08-01

To meet the needs of military and commercial markets, the infrared focal plane array industry must develop new, effective and low cost methods of fabricating and testing imaging detectors. This paper describes Texas Instruments new concepts in automated testing and cold probe technology as they apply to volume production.

The use of integrated focal plane array technologies in laser microsatellite networks

NASA Astrophysics Data System (ADS)

Arnon, Shlomi

2004-10-01

Clustering micro satellites in cooperative fly formation constellations leads to high-performance space systems. The only way to achieve high-speed communication between the satellites is by a laser beam with a narrow divergence angle. In order to make the communication successful three types of focal plane detector arrays are required in the communication terminal: acquisition, tracking and communication detector arrays. The acquisition detector array is used to acquire the neighbor satellite using a wide field-of-view telescope. The tracking detector provides fast, real time and accurate direction location of the neighbor satellite. Based on the information from the acquisition and tracking detectors the receiver and transmitter maintain line of sight. The development of large, fast and very sensitive focal plane detector arrays makes it possible to implement the acquisition, tracking and communication with only one focal plane detector array. By doing so it is possible to reduce dramatically the size, weight, and cost of the optics and electronics which leads to lightweight communication terminals. As a result, the satellites are smaller and lighter, which reduces the space mission cost and increases the booster efficiency. In this paper we will present an overview of the concept of integrated focal plane arrays for laser satellite communication. We also present simulation results based on real system parameters and compare different implementation options.

Prediction of secondary generalization from a focal onset seizure in intracerebral EEG.

PubMed

Karthick, P A; Tanaka, Hideaki; Khoo, Hui Ming; Gotman, Jean

2018-05-01

We propose a system based on the first five seconds of intracerebrally recorded focal seizures to predict their evolution from focal to bilateral tonic-clonic seizure (FTC), to spread outside the onset zone but without tonic-clonic component (FS), or to a seizure remaining focal (F). Nineteen time and frequency domain features were extracted from 39 seizures of 32 patients and were subjected to support vector machine based classification. Three prediction approaches regarding seizure evolution were (1) FTC vs FS vs F, (2) FTC vs FS or F and (3) FTC or FS vs F. We used 21 seizures for training. Most features had significantly different distributions in the three seizure types (p < 0.05). Eighteen seizures were used for testing. We predicted the evolution of 12 seizures in FTC vs FS vs F, 13 seizures in FTC vs FS or F and 14 seizures in FTC or FS vs F. The first five seconds of a focal seizure contains information regarding the eventual evolution of the seizure, which could be predicted in most seizures. The proposed system could alert the health care team when a patient is hospitalized for intracerebral EEG and improve safety and eventually result in an implantable device. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Focal nodular hyperplasia with major sinusoidal dilatation: a misleading entity

PubMed Central

Laumonier, Hervé; Frulio, Nora; Laurent, Christophe; Balabaud, Charles; Zucman-Rossi, Jessica; Bioulac-Sage, Paulette

2010-01-01

Focal nodular hyperplasia (FNH) is a benign liver lesion thought to be a non-specific response to locally increased blood flow. Although the diagnosis of FNH and hepatocellular adenoma (HCA) has made great progress over the last few years using modern imaging techniques, there are still in daily practice some difficulties concerning some atypical nodules. Here, the authors report the case of a 47-year-old woman with a single liver lesion thought to be, by imaging, an inflammatory HCA with major sinusoidal congestion. This nodule was revealed to be, at the microscopical level and after specific immunostaining and molecular analysis, an FNH with sinusoidal dilatation (so-called telangiectatic focal nodular hyperplasia). PMID:22798311

Thermal Effects on Camera Focal Length in Messenger Star Calibration and Orbital Imaging

NASA Astrophysics Data System (ADS)

Burmeister, S.; Elgner, S.; Preusker, F.; Stark, A.; Oberst, J.

2018-04-01

We analyse images taken by the MErcury Surface, Space ENviorment, GEochemistry, and Ranging (MESSENGER) spacecraft for the camera's thermal response in the harsh thermal environment near Mercury. Specifically, we study thermally induced variations in focal length of the Mercury Dual Imaging System (MDIS). Within the several hundreds of images of star fields, the Wide Angle Camera (WAC) typically captures up to 250 stars in one frame of the panchromatic channel. We measure star positions and relate these to the known star coordinates taken from the Tycho-2 catalogue. We solve for camera pointing, the focal length parameter and two non-symmetrical distortion parameters for each image. Using data from the temperature sensors on the camera focal plane we model a linear focal length function in the form of f(T) = A0 + A1 T. Next, we use images from MESSENGER's orbital mapping mission. We deal with large image blocks, typically used for the production of a high-resolution digital terrain models (DTM). We analyzed images from the combined quadrangles H03 and H07, a selected region, covered by approx. 10,600 images, in which we identified about 83,900 tiepoints. Using bundle block adjustments, we solved for the unknown coordinates of the control points, the pointing of the camera - as well as the camera's focal length. We then fit the above linear function with respect to the focal plane temperature. As a result, we find a complex response of the camera to thermal conditions of the spacecraft. To first order, we see a linear increase by approx. 0.0107 mm per degree temperature for the Narrow-Angle Camera (NAC). This is in agreement with the observed thermal response seen in images of the panchromatic channel of the WAC. Unfortunately, further comparisons of results from the two methods, both of which use different portions of the available image data, are limited. If leaving uncorrected, these effects may pose significant difficulties in the photogrammetric analysis

Stereotactic radiosurgery for focal leptomeningeal disease in patients with brain metastases.

PubMed

Wolf, Amparo; Donahue, Bernadine; Silverman, Joshua S; Chachoua, Abraham; Lee, Jean K; Kondziolka, Douglas

2017-08-01

Leptomeningeal disease (LMD) is well described in patients with brain metastases, presenting symptomatically in approximately 5% of patients. Conventionally, the presence of LMD is an indication for whole brain radiation therapy (WBRT) and not suitable for stereotactic radiosurgery (SRS). The purpose of the study was to evaluate the local control and overall survival of patients who underwent SRS to focal LMD. We reviewed our prospective registry and identified 32 brain metastases patients with LMD, from a total of 465 patients who underwent SRS between 2013 and 2015. Focal LMD was targeted with SRS in 16 patients. The median imaging follow-up time was 7 months. The median volume of LMD was 372 mm 3 and the median margin dose was 16 Gy. Five patients underwent prior WBRT. Histology included non-small cell lung (8), breast (5), melanoma (1), gastrointestinal (1) and ovarian cancer (1). Follow-up MR imaging was available for 14 patients. LMD was stable in 5 and partially regressed in 8 patients at follow-up. One patient had progression of LMD with hemorrhage 5 months after SRS. Seven patients developed distant LMD at a median time of 7 months. The median actuarial overall survival from SRS for LMD was 10.0 months. The 6-month and 1-year actuarial overall survival was 60% and 26% respectively. Six patients underwent WBRT after SRS for focal LMD at a median time of 6 months. Overall, focal LMD may be may be treated successfully with radiosurgery, potentially delaying WBRT in some patients.

FMC: a one-liner Python program to manage, classify and plot focal mechanisms

NASA Astrophysics Data System (ADS)

Álvarez-Gómez, José A.

2014-05-01

The analysis of earthquake focal mechanisms (or Seismic Moment Tensor, SMT) is a key tool on seismotectonics research. Each focal mechanism is characterized by several location parameters of the earthquake hypocenter, the earthquake size (magnitude and scalar moment tensor) and some geometrical characteristics of the rupture (nodal planes orientations, SMT components and/or SMT main axes orientations). The aim of FMC is to provide a simple but powerful tool to manage focal mechanism data. The data should be input to the program formatted as one of two of the focal mechanisms formatting options of the GMT (Generic Mapping Tools) package (Wessel and Smith, 1998): the Harvard CMT convention and the single nodal plane Aki and Richards (1980) convention. The former is a SMT format that can be downloaded directly from the Global CMT site (http://www.globalcmt.org/), while the later is the simplest way to describe earthquake rupture data. FMC is programmed in Python language, which is distributed as Open Source GPL-compatible, and therefore can be used to develop Free Software. Python runs on almost any machine, and has a wide support and presence in any operative system. The program has been conceived with the modularity and versatility of the classical UNIX-like tools. Is called from the command line and can be easily integrated into shell scripts (*NIX systems) or batch files (DOS/Windows systems). The program input and outputs can be done by means of ASCII files or using standard input (or redirection "<"), standard output (screen or redirection ">") and pipes ("|"). By default FMC will read the input and write the output as a Harvard CMT (psmeca formatted) ASCII file, although other formats can be used. Optionally FMC will produce a classification diagram representing the rupture type of the focal mechanisms processed. In order to count with a detailed classification of the focal mechanisms I decided to classify the focal mechanism in a series of fields that include

TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility

PubMed Central

Cáceres, Mónica; Ortiz, Liliana; Recabarren, Tatiana; Romero, Anibal; Colombo, Alicia; Leiva-Salcedo, Elías; Varela, Diego; Rivas, José; Silva, Ian; Morales, Diego; Campusano, Camilo; Almarza, Oscar; Simon, Felipe; Toledo, Hector; Park, Kang-Sik; Trimmer, James S.; Cerda, Oscar

2015-01-01

Cellular migration and contractility are fundamental processes that are regulated by a variety of concerted mechanisms such as cytoskeleton rearrangements, focal adhesion turnover, and Ca2+ oscillations. TRPM4 is a Ca2+-activated non-selective cationic channel (Ca2+-NSCC) that conducts monovalent but not divalent cations. Here, we used a mass spectrometry-based proteomics approach to identify putative TRPM4-associated proteins. Interestingly, the largest group of these proteins has actin cytoskeleton-related functions, and among these nine are specifically annotated as focal adhesion-related proteins. Consistent with these results, we found that TRPM4 localizes to focal adhesions in cells from different cellular lineages. We show that suppression of TRPM4 in MEFs impacts turnover of focal adhesions, serum-induced Ca2+ influx, focal adhesion kinase (FAK) and Rac activities, and results in reduced cellular spreading, migration and contractile behavior. Finally, we demonstrate that the inhibition of TRPM4 activity alters cellular contractility in vivo, affecting cutaneous wound healing. Together, these findings provide the first evidence, to our knowledge, for a TRP channel specifically localized to focal adhesions, where it performs a central role in modulating cellular migration and contractility. PMID:26110647

Focal mechanisms and the stress regime in NE and SW Tanzania, East Africa

NASA Astrophysics Data System (ADS)

Brazier, Richard A.; Nyblade, Andrew A.; Florentin, Juliette

2005-07-01

We report 12 new focal mechanisms from earthquakes in NE and SW Tanzania where the stress regime within the East African rift system is not well constrained. Focal mechanisms for events at the intersection of the Lake Tanganyika and Rukwa rifts in SW Tanzania indicate a complicated stress pattern with possible dextral strike-slip motion on some faults but oblique motion on others (either sinistral on NW striking faults or dextral on NE striking faults). Within the Rukwa rift, focal mechanisms indicate normal dip-slip motion with NE-SW opening. In NE Tanzania where the Eastern rift impinges on the margin of the Tanzania Craton, fault motions are consistent with a zone of distributed block faults and sub E-W extension. All twelve earthquakes likely nucleated within the crust.

TES is a novel focal adhesion protein with a role in cell spreading.

PubMed

Coutts, Amanda S; MacKenzie, Elaine; Griffith, Elen; Black, Donald M

2003-03-01

Previously, we identified TES as a novel candidate tumour suppressor gene that mapped to human chromosome 7q31.1. In this report we demonstrate that the TES protein is localised at focal adhesions, actin stress fibres and areas of cell-cell contact. TES has three C-terminal LIM domains that appear to be important for focal adhesion targeting. Additionally, the N-terminal region is important for targeting TES to actin stress fibres. Yeast two-hybrid and biochemical analyses yielded interactions with several focal adhesion and/or cytoskeletal proteins including mena, zyxin and talin. The fact that TES localises to regions of cell adhesion suggests that it functions in events related to cell motility and adhesion. In support of this, we demonstrate that fibroblasts stably overexpressing TES have an increased ability to spread on fibronectin.

Focal Point Inside the Vacuum Chamber for Solar Thermal Propulsion

NASA Technical Reports Server (NTRS)

1999-01-01

Researchers at the Marshall Space Flight Center (MSFC) have designed, fabricated, and tested the first solar thermal engine, a non-chemical rocket engine that produces lower thrust but has better thrust efficiency than a chemical combustion engine. MSFC turned to solar thermal propulsion in the early 1990s due to its simplicity, safety, low cost, and commonality with other propulsion systems. Solar thermal propulsion works by acquiring and redirecting solar energy to heat a propellant. The 20- by 24-ft heliostat mirror (not shown in this photograph) has dual-axis control that keeps a reflection of the sunlight on an 18-ft diameter concentrator mirror, which then focuses the sunlight to a 4-in focal point inside the vacuum chamber. The focal point has 10 kilowatts of intense solar power. This photograph is a close-up view of a 4-in focal point inside the vacuum chamber at the MSFC Solar Thermal Propulsion Test facility. As part of MSFC's Space Transportation Directorate, the Propulsion Research Center serves as a national resource for research of advanced, revolutionary propulsion technologies. The mission is to move the Nation's capabilities beyond the confines of conventional chemical propulsion into an era of aircraft-like access to Earth orbit, rapid travel throughout the solar system, and exploration of interstellar space.

Focal Cortical Dysplasia (FCD) lesion analysis with complex diffusion approach.

PubMed

Rajan, Jeny; Kannan, K; Kesavadas, C; Thomas, Bejoy

2009-10-01

Identification of Focal Cortical Dysplasia (FCD) can be difficult due to the subtle MRI changes. Though sequences like FLAIR (fluid attenuated inversion recovery) can detect a large majority of these lesions, there are smaller lesions without signal changes that can easily go unnoticed by the naked eye. The aim of this study is to improve the visibility of focal cortical dysplasia lesions in the T1 weighted brain MRI images. In the proposed method, we used a complex diffusion based approach for calculating the FCD affected areas. Based on the diffused image and thickness map, a complex map is created. From this complex map; FCD areas can be easily identified. MRI brains of 48 subjects selected by neuroradiologists were given to computer scientists who developed the complex map for identifying the cortical dysplasia. The scientists were blinded to the MRI interpretation result of the neuroradiologist. The FCD could be identified in all the patients in whom surgery was done, however three patients had false positive lesions. More lesions were identified in patients in whom surgery was not performed and lesions were seen in few of the controls. These were considered as false positive. This computer aided detection technique using complex diffusion approach can help detect focal cortical dysplasia in patients with epilepsy.

Outcome of lupus nephritis in childhood onset SLE in North and Central India: single-centre experience over 25 years.

PubMed

Srivastava, P; Abujam, B; Misra, R; Lawrence, A; Agarwal, V; Aggarwal, A

2016-04-01

Childhood SLE (cSLE) has a higher prevalence of lupus nephritis (LN), and there are ethnic variations in response to treatment as well as outcome of LN. There are limited data on long-term outcome of LN in cSLE from the Indian subcontinent. Retrospective analysis of case records of patients with cSLE (satisfying revised American College of Rheumatology (ACR) 1997 criteria for diagnosis) and age of onset <18 years was conducted from 1989 to 2013. Data on clinical features, renal involvement and biopsy findings, treatment, renal outcome, damage accrual and mortality were collected. End-stage renal disease (ESRD) was defined as the need for renal replacement therapy. Actuarial ESRD-free survival was studied as the primary outcome measure using Kaplan-Meier analysis. Among 205 children with cSLE, 134 (121 girls) had evidence of LN. The mean age at disease onset was 13.7 ± 3.5 years and the mean disease duration at presentation was 1.9 ± 2.5 years. Kidney biopsy was available for 92 patients, and histology included: 13 (14.2%) Class II, 24 (26%) Class III, 43 (46.7%) Class IV and 12 (13.1%) Class V LN. The mean follow-up period was 6.75 ± 5.7 years. At last visit, 81 (60.4%) children were in complete remission, 28 (20.9%) were in partial remission, 15 (11.2%) still had active nephritis and 10 (7.4%) had progressed to ESRD. Almost two-thirds (62.9%) of patients experienced lupus flares, and mean flare rate was 0.09 flares/patient follow-up year. Fifty-six (43.8%) children accrued damage and the mean Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage score was 0.79 ± 1.13. Actuarial ESRD-free survival at five, 10 and 15 years was 91.1%, 79% and 76.2%, and five-, 10- and 15-year renal survival was 93.8%, 87.1% and 84%, respectively. Although multiple factors individually predicted poor outcome (death/ESRD), only raised serum creatinine at onset (R square = 0.65, p ≤ 0.0001) and damage accrual (R square = 0.62, p�

Observations of marine wildlife tourism effects on a non-focal species.

PubMed

Rizzari, J R; Semmens, J M; Fox, A; Huveneers, C

2017-09-01

A radio-acoustic positioning system was used to assess the effects of shark cage-diving operators (SCDO) on the fine-scale movements of a non-focal species, the smooth stingray Bathytoshia brevicaudata. The results revealed that the time spent in the array was individually variable, but generally increased when SCDO were present and that the presence of SCDO may have the capacity to elicit changes in the space use of B. brevicaudata. These results indicate that the effects of marine wildlife tourism may extend beyond the focal species of interest. © 2017 The Fisheries Society of the British Isles.

[Laparoscopy findings of the yellow spot, a focal fatty liver infiltration].

PubMed

Koch, H; Henning, H; Friedrich, K; Lüders, C J

1984-05-01

From 1976 to 1982 in 279 patients amongst 3719 laparoscopies focal fatty liver infiltrates were found at the right and/or left liver edge next to the insertion point of the round ligament. These so-called "yellow spots" mainly could be recognized in case of normal liver tissue and in cases suffering from chronic hepatitis insofar as a cirrhotic transformation or a significant fibrosis had not taken place. The localization and the shape of these focal lesions indicate, that an abnormality in the portal blood supply of the corresponding area may play an etiologic role for the development of the fatty infiltration.

Effect of controlled offset of focal position in cavitation-enhanced high-intensity focused ultrasound treatment

NASA Astrophysics Data System (ADS)

Goto, Kota; Takagi, Ryo; Miyashita, Takuya; Jimbo, Hayato; Yoshizawa, Shin; Umemura, Shin-ichiro

2015-07-01

High-intensity focused ultrasound (HIFU) is a noninvasive treatment for tumors such as cancer. In this method, ultrasound is generated outside the body and focused to the target tissue. Therefore, physical and mental stresses on the patient are minimal. A drawback of the HIFU treatment is a long treatment time for a large tumor due to the small therapeutic volume by a single exposure. Enhancing the heating effect of ultrasound by cavitation bubbles may solve this problem. However, this is rather difficult because cavitation clouds tend to be formed backward from the focal point while ultrasonic intensity for heating is centered at the focal point. In this study, the focal points of the trigger pulses to generate cavitation were offset forward from those of the heating ultrasound to match the cavitation clouds with the heating patterns. Results suggest that the controlled offset of focal points makes the thermal coagulation more predictable.

Intracoronary infusion of catecholamines causes focal arrhythmias in pigs.

PubMed

Doppalapudi, Harish; Jin, Qi; Dosdall, Derek J; Qin, Hao; Walcott, Gregory P; Killingsworth, Cheryl R; Smith, William M; Ideker, Raymond E; Huang, Jian

2008-09-01

Acute ischemia causes myriad changes including increased catecholamines. We tested the hypothesis that elevated catecholamines alone are arrhythmogenic. A 504 electrode sock was placed over both ventricles in six open-chest pigs. During control infusion of saline through a catheter in the left anterior descending coronary artery (LAD), no sustained arrhythmias occurred, and the refractory period estimated by the activation recovery interval (ARI) was 175 +/- 14 ms in the LAD bed below the catheter. After infusion of isoproterenol at 0.1 microg/kg/min through the catheter, the ARI in this bed was significantly reduced to 109 +/- 10 ms. A sharp gradient of refractoriness of 43 +/- 10 ms was at the border of the perfused bed. Sustained monomorphic ventricular tachycardia occurred after drug infusion in the perfused bed or near its boundary in all animals with a cycle length of 329 +/- 26 ms and a focal origin. The maximum slope of the ARI restitution curve at the focal origins of the tachyarrhythmias was always <1 (0.62 +/- 0.15). Similar results with a focal arrhythmia origin occurred in two additional pigs in which intramural mapping was performed with 36 plunge needle electrodes in the left ventricular perfused bed. Regional elevation of a catecholamine, which is one of the alterations produced by acute ischemia, can by itself cause tachyarrhythmias. These arrhythmias are closely associated with a shortened refractory period and a large gradient of the spatial distribution of refractoriness but not with a steep restitution curve.

The localizing value of ictal EEG in focal epilepsy.

PubMed

Foldvary, N; Klem, G; Hammel, J; Bingaman, W; Najm, I; Lüders, H

2001-12-11

To investigate the lateralization and localization of ictal EEG in focal epilepsy. A total of 486 ictal EEG of 72 patients with focal epilepsy arising from the mesial temporal, neocortical temporal, mesial frontal, dorsolateral frontal, parietal, and occipital regions were analyzed. Surface ictal EEG was adequately localized in 72% of cases, more often in temporal than extratemporal epilepsy. Localized ictal onsets were seen in 57% of seizures and were most common in mesial temporal lobe epilepsy (MTLE), lateral frontal lobe epilepsy (LFLE), and parietal lobe epilepsy, whereas lateralized onsets predominated in neocortical temporal lobe epilepsy and generalized onsets in mesial frontal lobe epilepsy (MFLE) and occipital lobe epilepsy. Approximately two-thirds of seizures were localized, 22% generalized, 4% lateralized, and 6% mislocalized/lateralized. False localization/lateralization occurred in 28% of occipital and 16% of parietal seizures. Rhythmic temporal theta at ictal onset was seen exclusively in temporal lobe seizures, whereas localized repetitive epileptiform activity was highly predictive of LFLE. Seizures arising from the lateral convexity and mesial regions were differentiated by a high incidence of repetitive epileptiform activity at ictal onset in the former and rhythmic theta activity in the latter. With the exception of mesial frontal lobe epilepsy, ictal recordings are very useful in the localization/lateralization of focal seizures. Some patterns are highly accurate in localizing the epileptogenic lobe. One limitation of ictal EEG is the potential for false localization/lateralization in occipital and parietal lobe epilepsies.

SIRTF Focal Plane Survey: A Pre-flight Error Analysis

NASA Technical Reports Server (NTRS)

Bayard, David S.; Brugarolas, Paul B.; Boussalis, Dhemetrios; Kang, Bryan H.

2003-01-01

This report contains a pre-flight error analysis of the calibration accuracies expected from implementing the currently planned SIRTF focal plane survey strategy. The main purpose of this study is to verify that the planned strategy will meet focal plane survey calibration requirements (as put forth in the SIRTF IOC-SV Mission Plan [4]), and to quantify the actual accuracies expected. The error analysis was performed by running the Instrument Pointing Frame (IPF) Kalman filter on a complete set of simulated IOC-SV survey data, and studying the resulting propagated covariances. The main conclusion of this study is that the all focal plane calibration requirements can be met with the currently planned survey strategy. The associated margins range from 3 to 95 percent, and tend to be smallest for frames having a 0.14" requirement, and largest for frames having a more generous 0.28" (or larger) requirement. The smallest margin of 3 percent is associated with the IRAC 3.6 and 5.8 micron array centers (frames 068 and 069), and the largest margin of 95 percent is associated with the MIPS 160 micron array center (frame 087). For pointing purposes, the most critical calibrations are for the IRS Peakup sweet spots and short wavelength slit centers (frames 019, 023, 052, 028, 034). Results show that these frames are meeting their 0.14" requirements with an expected accuracy of approximately 0.1", which corresponds to a 28 percent margin.

Focal adhesion kinase is required for actin polymerization and remodeling of the cytoskeleton during sperm capacitation

PubMed Central

Roa-Espitia, Ana L.; Hernández-Rendón, Eva R.; Baltiérrez-Hoyos, Rafael; Muñoz-Gotera, Rafaela J.; Cote-Vélez, Antonieta; Jiménez, Irma; González-Márquez, Humberto

2016-01-01

ABSTRACT Several focal adhesion proteins are known to cooperate with integrins to link the extracellular matrix to the actin cytoskeleton; as a result, many intracellular signaling pathways are activated and several focal adhesion complexes are formed. However, how these proteins function in mammalian spermatozoa remains unknown. We confirm the presence of focal adhesion proteins in guinea pig spermatozoa, and we explore their role during capacitation and the acrosome reaction, and their relationship with the actin cytoskeleton. Our results suggest the presence of a focal adhesion complex formed by β1-integrin, focal adhesion kinase (FAK), paxillin, vinculin, talin, and α-actinin in the acrosomal region. Inhibition of FAK during capacitation affected the protein tyrosine phosphorylation associated with capacitation that occurs within the first few minutes of capacitation, which caused the acrosome reaction to become increasingly Ca2+ dependent and inhibited the polymerization of actin. The integration of vinculin and talin into the complex, and the activation of FAK and paxillin during capacitation, suggests that the complex assembles at this time. We identify that vinculin and α-actinin increase their interaction with F-actin while it remodels during capacitation, and that during capacitation focal adhesion complexes are structured. FAK contributes to acrosome integrity, likely by regulating the polymerization and the remodeling of the actin cytoskeleton. PMID:27402964

Shared Focal Plane Investigation for Serial Frame Cameras.

DTIC Science & Technology

1980-03-01

capability will be restored. 41. -.. TrABLE 1-1 SYSTEM LEADING P) ARTICULARS Lens Focal Length (inches) Range (ft) Contrast 12 18 24 Coverage 22.1...can be expected that signature bands will be apparent in the imagery. Such bands are at best distracting and at worst hindrances to image interpretation

Generalized onset seizures with focal evolution (GOFE) - A unique seizure type in the setting of generalized epilepsy.

PubMed

Linane, Avriel; Lagrange, Andre H; Fu, Cary; Abou-Khalil, Bassel

2016-01-01

We report clinical and electrographic features of generalized onset seizures with focal evolution (GOFE) and present arguments for the inclusion of this seizure type in the seizure classification. The adult and pediatric Epilepsy Monitoring Unit databases at Vanderbilt Medical Center and Children's Hospital were screened to identify generalized onset seizures with focal evolution. We reviewed medical records for epilepsy characteristics, epilepsy risk factors, MRI abnormalities, neurologic examination, antiepileptic medications before and after diagnosis, and response to medications. We also reviewed ictal and interictal EEG tracings, as well as video-recorded semiology. Ten patients were identified, 7 males and 3 females. All of the patients developed generalized epilepsy in childhood or adolescence (ages 3-15years). Generalized onset seizures with focal evolution developed years after onset in 9 patients, with a semiology concerning for focal seizures or nonepileptic events. Ictal discharges had a generalized onset on EEG, described as either generalized spike-and-wave and/or polyspike-and-wave discharges, or generalized fast activity. This electrographic activity then evolved to focal rhythmic activity most commonly localized to one temporal or frontal region; five patients had multiple seizures evolving to focal activity in different regions of both hemispheres. The predominant interictal epileptiform activity included generalized spike-and-wave and/or polyspike-and-wave discharges in all patients. Taking into consideration all clinical and EEG data, six patients were classified with genetic (idiopathic) generalized epilepsy, and four were classified with structural/metabolic (symptomatic) generalized epilepsy. All of the patients had modifications to their medications following discharge, with three becoming seizure-free and five responding with >50% reduction in seizure frequency. Generalized onset seizures may occasionally have focal evolution with semiology