Acute interstitial pneumonia (Hamman-Rich syndrome) in idiopathic pulmonary fibrosis and bronchoalveolar carcinoma: a case report.

PubMed

Plasek, Jiri; Dvorackova, Jana; Jahoda, Jan; Trulikova, Kristina; Mokosova, Radka; Danek, Tomas; Hrabovsky, Vladimir; Martinek, Arnost

2011-12-01

Acute interstitial pneumonia is characterized by rapid progressive dyspnoea degenerating into respiratory failure requiring mechanical ventilation. Acute interstitial pneumonia (AIP) and idiopathic pulmonary fibrosis (IPF) are separate clinic/pathological entities although overlap may be present. It is well-known that patients with IPF have increased risk of lung carcinoma; Adenocarcinoma in connection with IPF is less common. Moreover the subtype of adenocarcinoma, diffuse bronchoalveolar carcinoma has not yet been described. We report the case of 45 yr old former hockey player with increased bilateral reticular shadowing on chest radiograph, dyspnoea, velcro-like crackles, restrictive respiratory disease and mixed high-resolution computed tomography finding. During brief in-patient treatment the patient developed acute respiratory failure accompanied by multiorgan failure and disseminated coagulopathy. Deterioration of the microcirculation was followed by loss of peripheral vascular resistance, which was irreversible even with normalization of the blood gases achieved by extracorporeal membrane oxygenation. At autopsy, bronchoalveolar carcinoma in usual interstitial pneumonia (UIP) combined with areas of alveolar damage with hyaline membranes was found. This case alerts clinicians to unusual idiopathic pulmonary fibrosis manifestations and its complications. Close collaboration between clinicians, pathologists and laboratory physicians is highly recommended for early diagnosis and appropriate treatment.

Effects of dietary salt restriction on renal progression and interstitial fibrosis in adriamycin nephrosis.

PubMed

Park, Joon-Sung; Kim, Sua; Jo, Chor Ho; Oh, Il Hwan; Kim, Gheun-Ho

2014-01-01

Although high salt intake is thought to accelerate renal progression in proteinuric kidney disease, it is not known whether strict dietary salt restriction could delay renal inflammation and interstitial fibrosis. Here, we sought to answer this question in a rat model of adriamycin-induced nephrotic syndrome. Adriamycin was administered via the femoral vein in a single bolus (7.5 mg/kg), and the rats were put on a sodium-deficient rodent diet. Rats with intact kidneys were studied for 5 weeks (experiment 1), and uninephrectomized rats were studied for 6 weeks (experiment 2). In experiment 1, restricting salt intake improved renal tubulointerstitial histopathology in adriamycin-treated rats. Immunohistochemical and immunoblot results additionally showed that restricting dietary salt lowered adriamycin-induced expression of osteopontin, collagen III, and fibronectin. In experiment 2, salt restriction improved adriamycin-induced azotemia, although it did not affect proteinuria or blood pressure. Dietary salt restriction also reduced adriamycin-induced infiltration of ED1-positive cells and the upregulated expression of osteopontin and α-SMA. Masson's trichrome and Sirius red staining revealed that salt restriction slowed Adriamycin-induced progression of renal interstitial fibrosis. Finally, qPCR revealed that adriamycin-induced expression of TNF-α, IκB-α, gp91(phox), p47(phox), and p67(phox) mRNA was blocked by salt restriction. Our findings demonstrate that strict dietary salt restriction delays the progress of renal inflammation and fibrosis in proteinuric kidney disease, most likely via relieving the reactive oxygen species-mediated NF-κB activation. © 2014 S. Karger AG, Basel.

Fanconi's syndrome, interstitial fibrosis and renal failure by aristolochic acid in Chinese herbs.

PubMed

Hong, Yin-Tai; Fu, Lin-Shien; Chung, Lin-Huei; Hung, Shien-Chung; Huang, Yi-Ting; Chi, Chin-Shiang

2006-04-01

Aristolochic acid-associated nephropathy (AAN) has been identified as a separate entity of progressive tubulo-interstitial nephropathy. Its characteristic pathological findings, including hypocellular interstitial fibrosis, intimal thickening of interlobular and afferent arterioles with glomeruli sparing or mild sclerosis, have been identified. Many cases of AAN in adults have been reported in Taiwan as well as throughout the world, but it has seldom been described in children. We report on a 10-year-old boy who presented with severe anemia, Fanconi's syndrome, and progressive renal failure. Renal biopsy revealed typical findings of AAN. Aristolochic acids I and II were identified from a Chinese herb mixture ingested by the boy. AAN was diagnosed after other etiologies had been excluded. The case demonstrates the hazards of Chinese herbs with regard to children's health in Taiwan and suggests that more attention should be paid to this issue.

Lung Ultrasonography in the Evaluation of Interstitial Lung Disease in Systemic Connective Tissue Diseases: Criteria and Severity of Pulmonary Fibrosis - Analysis of 52 Patients.

PubMed

Buda, N; Piskunowicz, M; Porzezińska, M; Kosiak, W; Zdrojewski, Z

2016-08-01

Patients with a diagnosed systemic connective tissue disease require regular monitoring from the point of view of interstitial lung disease. The main aim of this work is a description of the criteria for pulmonary fibrosis and the degree of the severity of the fibrosis during the course of interstitial lung disease through the TLU (transthoracic lung ultrasound). 52 patients with diagnosed diffuse interstitial lung disease were qualified for this research, together with 50 volunteers in the control group. The patients in both groups were over 18 years of age and were of both sexes. The results of the TLU of the patients underwent statistical analysis and were compared to High-Resolution Computed Tomography (HRCT) results. As a consequence of the statistical analysis, we defined our own criteria for pulmonary fibrosis in TLU: irregularity of the pleura line, tightening of the pleura line, the fragmentary nature of the pleura line, blurring of the pleura line, thickening of the pleura line, artifacts of line B ≤ 3 and ≥ 4, artifacts of Am line and subpleural consolidations < 5 mm. As a result of the conducted research, a scale of severity of pulmonary fibrosis in TLU was devised (UFI - Ultrasound Fibrosis Index), enabling a division to be made into mild, moderate and severe cases. Transthoracic Lung Ultrasonography (TLU) gives a new outlook on the diagnostic possibilities, non-invasive and devoid of ionising radiation, of pulmonary fibrosis. This research work has allowed to discover two new ultrasound symptoms of pulmonary fibrosis (blurred pleural line and Am lines). © Georg Thieme Verlag KG Stuttgart · New York.

Ulinastatin inhibits renal tubular epithelial apoptosis and interstitial fibrosis in rats with unilateral ureteral obstruction.

PubMed

Zhang, Qing-Fang

2017-12-01

The effect of ulinastatin (UTI) on renal tubular epithelial apoptosis and interstitial fibrosis in rats with unilateral ureteral obstruction (UUO) was investigated. A total of 18 male Wistar rats were randomly divided into the following 3 groups: The Sham group (n=6), the UUO group (n=6), and the UTI group (n=6). In the UUO and UTI groups, the left ureter was ligated to establish a UUO model. Starting from day 1 after surgery, an intervention treatment was performed using normal saline (1 ml/kg/d) and UTI (40,000 unit/kg/d). On day 7 after surgery, 6 rats from each group were sacrificed. In the Sham group, the left ureter was only freed, not ligated; after 7 days of abdominal closure, all of the rats were sacrificed. Blood samples were collected prior to sacrificing the animals to measure the blood urea nitrogen (BUN) and serum creatinine (Scr). The incidence of renal interstitial lesions on the obstruction side was observed by hematoxylin and eosin, and Masson staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical detection of apoptosis regulator Bax (Bax), apoptosis regulator Bcl‑2 (Bcl‑2) and caspase‑3 were performed to observe the presence of renal tubular epithelial cell apoptosis. The UTI did not have a significant influence on the mouse BUN and Scr levels in any of the groups (P>0.05). Compared with that in the Sham group, renal tissue injury in the UUO group was significantly aggravated with renal tubular dilation, epithelial cell atrophy, renal interstitial inflammatory cell infiltration and fibrous tissue hyperplasia (P<0.01). Furthermore, the renal tubular epithelial TUNEL+ cell number and Bax and caspase‑3 levels were increased, and the expression of Bcl‑2 was decreased (P<0.01). Following the UTI treatment, the renal interstitial injury at the obstruction side was significantly attenuated (P<0.05), the renal tubular epithelial TUNEL+ cell number, and Bax and caspase‑3 levels

Identification of key metabolic changes in renal interstitial fibrosis rats using metabonomics and pharmacology.

PubMed

Zhao, Liangcai; Dong, Minjian; Liao, Shixian; Du, Yao; Zhou, Qi; Zheng, Hong; Chen, Minjiang; Ji, Jiansong; Gao, Hongchang

2016-06-03

Renal fibrosis is one of the important pathways involved in end-stage renal failure. Investigating the metabolic changes in the progression of disease may enhance the understanding of its pathogenesis and therapeutic information. In this study, (1)H-nuclear magnetic resonance (NMR)-based metabonomics was firstly used to screen the metabolic changes in urine and kidney tissues of renal interstitial fibrotic rats induced by unilateral ureteral obstruction (UUO), at 7, 14, 21, and 28 days after operation, respectively. The results revealed that reduced levels of bioenergy synthesis and branched chain amino acids (BCAAs), as well as elevated levels of indoxyl sulfate (IS) are involved in metabolic alterations of renal fibrosis rats. Next, by pharmacological treatment we found that reduction of IS levels could prevent the renal fibrotic symptoms. Therefore, we suggested that urinary IS may be used as a potential biomarker for the diagnosis of renal fibrosis, and a therapeutic target for drugs. Novel attempt combining metabonomics and pharmacology was established that have ability to provide more systematic diagnostic and therapeutic information of diseases.

High-resolution computed tomography findings of acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis.

PubMed

Ichikado, Kazuya

2014-02-01

Diffuse alveolar damage (DAD) is the pathologic feature of rapidly progressive lung diseases, including acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. The clinical significance and limitation of high-resolution computed tomography (HRCT) findings in these diseases were reviewed. The HRCT findings correlate well with pathologic phases (exudative, proliferative, and fibrotic) of DAD, although it cannot detect early exudative phase. Traction bronchiolectasis or bronchiectasis within areas of increased attenuation on HRCT scan is a sign of progression from the exudative to the proliferative and fibrotic phase of DAD. Extensive abnormalities seen on HRCT scans, which are indicative of fibroproliferative changes, were independently predictive of poor prognosis in patients with clinically early acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. © 2013 Published by Elsevier Inc.

[Effect of fluorofenidone on renal interstitial fibrosis in rats with unilateral ureteral obstruction].

PubMed

Tan, Wenqing; Wang, Wei; Zheng, Xuan; Chen, Jiying; Yuan, Xiangning; Zhang, Fangfang; Wang, Shuting; Tao, Lijian

2018-05-28

To investigate the effect of fluorofenidone on renal interstitial fibrosis in rats with unilateral ureteral obstruction (UUO) and to observe the effect of fluorofenidone on the expressions of collagen type I (Col I), collagen type III (Col III), α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), platelet derived growth factor (PDGF) in the renal tissues of UUO rats.
 Methods: Male Sprague-Dawley (SD) rats were randomly divided into a sham-operated group, a UUO group, and a flurofenidone group (n=5). UUO model was induced by ligating the left ureter in rats. The rats were treated with 125 mg/(kg.d) fluorofenidone by gastric gavage in the fluorofenidone group at 24 h before the operation, and the rats were treated with the identical dose of 0.5% sodium carboxyl methyl cellulose (CMC-Na) in the other 2 groups. The rats were sacrificed at 14 days after UUO. Pathological changes of the renal tissue were observed by HE and Masson staining, the mRNA expressions of Col I, Col III, α-SMA, PDGF and CTGF were detected by real-time PCR, and the protein expressions of Col I, Col III, PDGF and CTGF were detected by immunohistochemical staining.
 Results: The renal interstitial damage index, relative collagen area and mRNA and protein expressions of Col I and Col III in the renal tissues of the rats in the UUO group significantly increased (P<0.05), and fluorofenidone could reduce these indexes (P<0.05). Compared with the sham-operated group, the protein expressions of α-SMA, PDGF, CTGF and the mRNA expressions of PDGF and CTGF in the renal tissues of the rats in the UUO group were increased, but fluorofenidone could decrease the protein expressions of α-SMA, PDGF, CTGF and the mRNA expressions of PDGF and CTGF (P<0.05).
 Conclusion: Fluorofenidone (125 mg/kg.d) could attenuate renal interstitial fibrosis through inhibition of fibroblast proliferation, myofibroblastic activation, PDGF and CTGF expression.

Role of Semaphorin 7a signaling in TGF-β1 induced lung fibrosis and scleroderma-related interstitial lung disease

PubMed Central

Gan, Ye; Reilkoff, Ronald; Peng, Xueyan; Russell, Thomas; Chen, Qingsheng; Mathai, Susan K.; Homer, Robert; Gulati, Mridu; Siner, Jonathan; Elias, Jack; Bucala, Richard; Herzog, Erica

2012-01-01

Objective Semaphorin (Sema) 7a regulates TGF- β1 induced fibrosis. Using a murine model of pulmonary fibrosis in which an inducible, bioactive form of the human TGF- β1 gene is overexpressed in the lung, we tested the hypothesis that Sema-7a exerts its pro-fibrotic effects in part by promoting the tissue accumulation of CD45+ fibrocytes. Methods Fibrosis and fibrocytes were evaluated in TGF- β1 transgenic mice in which the Sema-7a locus had been disrupted. The effect of replacement or deletion of Sema-7a on bone marrow derived cells was ascertained using bone marrow transplantation. The role of the Sema-7a receptor β1 integrin was assessed using neutralizing antibodies. The applicability of these findings to TGF-β1-driven fibrosis in humans was examined in patients with scleroderma-related interstitial lung disease. Results The appearance of fibrocytes in the lungs in TGF- β1 transgenic mice requires Sema-7a. Replacement of Sema-7a in bone marrow derived cells restores lung fibrosis and fibrocytes. Immunoneutralization of β1 integrin reduces pulmonary fibrocytes and fibrosis. Peripheral blood mononuclear cells from patients with scleroderma-related interstitial lung disease show increased mRNA for Sema-7a and the β1 integrin, with Sema-7a located on collagen producing fibrocytes and CD19+ lymphocytes. Peripheral blood fibrocyte outgrowth is enhanced in these patients. Stimulation of normal human peripheral blood mononuclear cells with recombinant Sema-7a enhances fibrocyte differentiation; these effects are attenuated by β1 integrin neutralization. Conclusion Interventions that reduce Sema-7a expression or prevent the Sema-7a - β1 integrin interaction may be ameliorative in TGF- β1-driven or fibrocyte-associated autoimmune fibroses. PMID:21484765

Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFβ1 and miR-29 pathways.

PubMed

Zhang, Yang; Wang, Jing-Hao; Zhang, Yi-Yuan; Wang, Ying-Zhe; Wang, Jin; Zhao, Yue; Jin, Xue-Xin; Xue, Gen-Long; Li, Peng-Hui; Sun, Yi-Lin; Huang, Qi-He; Song, Xiao-Tong; Zhang, Zhi-Ren; Gao, Xu; Yang, Bao-Feng; Du, Zhi-Min; Pan, Zhen-Wei

2016-03-14

Interleukin 6 (IL-6) has been shown to be an important regulator of cardiac interstitial fibrosis. In this study, we explored the role of interleukin-6 in the development of diabetic cardiomyopathy and the underlying mechanisms. Cardiac function of IL-6 knockout mice was significantly improved and interstitial fibrosis was apparently alleviated in comparison with wildtype (WT) diabetic mice induced by streptozotocin (STZ). Treatment with IL-6 significantly promoted the proliferation and collagen production of cultured cardiac fibroblasts (CFs). High glucose treatment increased collagen production, which were mitigated in CFs from IL-6 KO mice. Moreover, IL-6 knockout alleviated the up-regulation of TGFβ1 in diabetic hearts of mice and cultured CFs treated with high glucose or IL-6. Furthermore, the expression of miR-29 reduced upon IL-6 treatment, while increased in IL-6 KO hearts. Overexpression of miR-29 blocked the pro-fibrotic effects of IL-6 on cultured CFs. In summary, deletion of IL-6 is able to mitigate myocardial fibrosis and improve cardiac function of diabetic mice. The mechanism involves the regulation of IL-6 on TGFβ1 and miR-29 pathway. This study indicates the therapeutic potential of IL-6 suppression on diabetic cardiomyopathy disease associated with fibrosis.

Genetic susceptibility to interstitial pulmonary fibrosis in mice induced by vanadium pentoxide (V2O5)

PubMed Central

Walters, Dianne M.; White, Kevin M.; Patel, Ushma; Davis, Martin J.; Veluci-Marlow, Roberta M.; Bhupanapadu Sunkesula, Solomon Raju; Bonner, James C.; Martin, Jessica R.; Gladwell, Wes; Kleeberger, Steven R.

2014-01-01

Interstitial lung diseases (ILDs) are characterized by injury, inflammation, and scarring of alveoli, leading to impaired function. The etiology of idiopathic forms of ILD is not understood, making them particularly difficult to study due to the lack of appropriate animal models. Consequently, few effective therapies have emerged. We developed an inbred mouse model of ILD using vanadium pentoxide (V2O5), the most common form of a transition metal found in cigarette smoke, fuel ash, mineral ores, and steel alloys. Pulmonary responses to V2O5, including dose-dependent increases in lung permeability, inflammation, collagen content, and dysfunction, were significantly greater in DBA/2J mice compared to C57BL/6J mice. Inflammatory and fibrotic responses persisted for 4 mo in DBA/2J mice, while limited responses in C57BL/6J mice resolved. We investigated the genetic basis for differential responses through genetic mapping of V2O5-induced lung collagen content in BXD recombinant inbred (RI) strains and identified significant linkage on chromosome 4 with candidate genes that associate with V2O5-induced collagen content across the RI strains. Results suggest that V2O5 may induce pulmonary fibrosis through mechanisms distinct from those in other models of pulmonary fibrosis. These findings should further advance our understanding of mechanisms involved in ILD and thereby aid in identification of new therapeutic targets.—Walters, D. M., White, K. M., Patel, U., Davis, M. J., Veluci-Marlow, R. M., Bhupanapadu Sunkesula, S. R., Bonner, J. C., Martin, J. R., Gladwell, W., Kleeberger, S. R. Genetic susceptibility to interstitial pulmonary fibrosis in mice induced by vanadium pentoxide (V2O5). PMID:24285090

Aspirin Reduces Cardiac Interstitial Fibrosis by Inhibiting Erk1/2-Serpine2 and P-Akt Signalling Pathways.

PubMed

Li, Xuelian; Wang, GuoYuan; QiLi, MuGe; Liang, HaiHai; Li, TianShi; E, XiaoQiang; Feng, Ying; Zhang, Ying; Liu, Xiao; Qian, Ming; Xu, BoZhi; Shen, ZhiHang; Gitau, Samuel Chege; Zhao, DanDan; Shan, HongLi

2018-01-01

Cardiac interstitial fibrosis is an abnormality of various cardiovascular diseases, including myocardial infarction, hypertrophy, and atrial fibrillation, and it can ultimately lead to heart failure. However, there is a lack of practical therapeutic approaches to treat fibrosis and reverse the damage to the heart. The purpose of this study was to investigate the effect of long-term aspirin administration on pressure overload-induced cardiac fibrosis in mice and reveal the underlying mechanisms of aspirin treatment. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 10 mg·kg-1·day-1 of aspirin for 4 weeks. Masson staining and a collagen content assay were used to detect the effects of aspirin on cardiac fibrosis in vivo and in vitro. Western blot and qRT-PCR were applied to examine the impact of aspirin on extracellular signal-regulated kinases (Erks), p-Akt/β-catenin, SerpinE2, collagen I, and collagen III levels in the mice heart. Aspirin significantly suppressed the expression of α-smooth muscle actin (α-SMA; 1.19±0.19-fold) and collagen I (0.95±0.09-fold) in TAC mice. Aspirin, at doses of 100 and 1000 µM, also significantly suppressed angiotensin II-induced α-SMA and collagen I in cultured CFs. The enhanced phosphorylation of Erk1/2 caused by TAC (p-Erk1, 1.49±0.19-fold; p-Erk2, 1.96±0.68-fold) was suppressed by aspirin (p-Erk1, 1.04±0.15-fold; p-Erk2, 0.87±0.06-fold). SerpinE2 levels were suppressed via the Erk1/2 signalling pathway following treatment with aspirin (1.36±0.12-fold for TAC; 1.06±0.07-fold for aspirin+TAC). The p-Akt and β-catenin levels were also significantly inhibited in vivo and in vitro. Our study reveals a novel mechanism by which aspirin alleviates pressure overload-induced cardiac interstitial fibrosis in TAC mice by suppressing the p-Erk1/2 and p-Akt/β-catenin signalling pathways. © 2018 The Author(s). Published by S. Karger AG, Basel.

Angiotensin II type 1 and 2 receptors and lymphatic vessels modulate lung remodeling and fibrosis in systemic sclerosis and idiopathic pulmonary fibrosis.

PubMed

Parra, Edwin Roger; Ruppert, Aline Domingos Pinto; Capelozzi, Vera Luiza

2014-01-01

To validate the importance of the angiotensin II receptor isotypes and the lymphatic vessels in systemic sclerosis and idiopathic pulmonary fibrosis. We examined angiotensin II type 1 and 2 receptors and lymphatic vessels in the pulmonary tissues obtained from open lung biopsies of 30 patients with systemic sclerosis and 28 patients with idiopathic pulmonary fibrosis. Their histologic patterns included cellular and fibrotic non-specific interstitial pneumonia for systemic sclerosis and usual interstitial pneumonia for idiopathic pulmonary fibrosis. We used immunohistochemistry and histomorphometry to evaluate the number of cells in the alveolar septae and the vessels stained by these markers. Survival curves were also used. We found a significantly increased percentage of septal and vessel cells immunostained for the angiotensin type 1 and 2 receptors in the systemic sclerosis and idiopathic pulmonary fibrosis patients compared with the controls. A similar percentage of angiotensin 2 receptor positive vessel cells was observed in fibrotic non-specific interstitial pneumonia and usual interstitial pneumonia. A significantly increased percentage of lymphatic vessels was present in the usual interstitial pneumonia group compared with the non-specific interstitial pneumonia and control groups. A Cox regression analysis showed a high risk of death for the patients with usual interstitial pneumonia and a high percentage of vessel cells immunostained for the angiotensin 2 receptor in the lymphatic vessels. We concluded that angiotensin II receptor expression in the lung parenchyma can potentially control organ remodeling and fibrosis, which suggests that strategies aimed at preventing high angiotensin 2 receptor expression may be used as potential therapeutic target in patients with pulmonary systemic sclerosis and idiopathic pulmonary fibrosis.

Hypothalamic digoxin, hemispheric chemical dominance, and interstitial lung disease.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2003-10-01

The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. This was assessed in patients with idiopathic pulmonary fibrosis and in individuals of differing hemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of idiopathic pulmonary fibrosis. All 15 cases of interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. The isoprenoidal metabolites--digoxin, dolichol, and ubiquinone, RBC membrane Na(+)-K+ ATPase activity, serum magnesium, tyrosine/tryptophan catabolic patterns, free radical metabolism, glycoconjugate metabolism, and RBC membrane composition--were assessed in idiopathic pulmonary fibrosis as well as in individuals with differing hemispheric dominance. In patients with idiopathic pulmonary fibrosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in patients with idiopathic pulmonary fibrosis. Isoprenoid pathway dysfunction con tributes to the pathogenesis of idiopathic pulmonary fibrosis. The biochemical patterns obtained in interstitial lung disease are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. However, all the patients with interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Interstitial lung disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Correlation of pulmonary function and usual interstitial pneumonia computed tomography patterns in idiopathic pulmonary fibrosis.

PubMed

Arcadu, Antonella; Byrne, Suzanne C; Pirina, Pietro; Hartman, Thomas E; Bartholmai, Brian J; Moua, Teng

2017-08-01

Little is known about presenting 'inconsistent' or 'possible' usual interstitial pneumonia (UIP) computed tomography (CT) patterns advancing to 'consistent' UIP as disease progresses in idiopathic pulmonary fibrosis (IPF). We hypothesized that if 'consistent' UIP represented more advanced disease, such a pattern on presentation should also correlate with more severe pulmonary function test (PFT) abnormalities. Consecutive IPF patients (2005-2013) diagnosed by international criteria with baseline PFT and CT were included. Presenting CTs were assessed by three expert radiologists for consensus UIP pattern ('consistent', 'possible', and 'inconsistent'). Approximation of individual and combined interstitial abnormalities was also performed with correlation of interstitial abnormalities and UIP CT pattern made with PFT findings and survival. Three-hundred and fifty patients (70% male) were included with a mean age of 68.3 years. Mean percent predicted forced vital capacity (FVC%) and diffusion capacity (DLCO%) was 64% and 45.5% respectively. Older age and male gender correlated more with 'consistent' UIP CT pattern. FVC% was not associated with any UIP pattern but did correlate with total volume of radiologist assessed interstitial abnormalities. DLCO% was lower in those with 'consistent' UIP pattern. A 'consistent' UIP CT pattern was also not independently predictive of survival after correction for age, gender, FVC%, and DLCO%. PFT findings appear to correlate with extent of radiologic disease but not specific morphologic patterns. Whether such UIP patterns represent different stages of disease severity or radiologic progression is not supported by coinciding pulmonary function decline. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interleukin-18 deficiency protects against renal interstitial fibrosis in aldosterone/salt-treated mice.

PubMed

Tanino, Akiko; Okura, Takafumi; Nagao, Tomoaki; Kukida, Masayoshi; Pei, Zuowei; Enomoto, Daijiro; Miyoshi, Ken-Ichi; Okamura, Haruki; Higaki, Jitsuo

2016-10-01

Interleukin (IL)-18 is a member of the IL-1 family of cytokines and was described originally as an interferon γ-inducing factor. Aldosterone plays a central role in the regulation of sodium and potassium homoeostasis by binding to the mineralocorticoid receptor and contributes to kidney and cardiovascular damage. Aldosterone has been reported to induce IL-18, resulting in cardiac fibrosis with induced IL-18-mediated osteopontin (OPN). We therefore hypothesized that aldosterone-induced renal fibrosis via OPN may be mediated by IL-18. To verify this hypothesis, we compared mice deficient in IL-18 and wild-type (WT) mice in a model of aldosterone/salt-induced hypertension. IL-18(-/-) and C57BL/6 WT mice were used for the uninephrectomized aldosterone/salt hypertensive model, whereas NRK-52E cells (rat kidney epithelial cells) were used in an in vitro model. In the present in vivo study, IL-18 protein expression was localized in medullary tubules in the WT mice, whereas in aldosterone-infused WT mice this expression was up-regulated markedly in the proximal tubules, especially in injured and dilated tubules. This renal damage caused by aldosterone was attenuated significantly by IL-18 knockout with down-regulation of OPN expression. In the present in vitro study, aldosterone directly induced IL-18 gene expression in renal tubular epithelial cells in a concentration- and time-dependent manner. These effects were inhibited completely by spironolactone. IL-18 may be a key mediator of aldosterone-induced renal fibrosis by inducing OPN, thereby exacerbating renal interstitial fibrosis. Inhibition of IL-18 may therefore provide a potential target for therapeutic intervention aimed at preventing the progression of renal injury. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Epimorphin expression in interstitial pneumonia

PubMed Central

Terasaki, Yasuhiro; Fukuda, Yuh; Suga, Moritaka; Ikeguchi, Naoki; Takeya, Motohiro

2005-01-01

Epimorphin modulates epithelial morphogenesis in embryonic mouse organs. We previously suggested that epimorphin contributes to repair of bleomycin-induced pulmonary fibrosis in mice via epithelium-mesenchyme interactions. To clarify the role of epimorphin in human lungs, we evaluated epimorphin expression and localization in normal lungs, lungs with nonspecific interstitial pneumonia (NSIP), and lungs with usual interstitial pneumonia (UIP); we also studied the effect of recombinant epimorphin on cultured human alveolar epithelial cells in vitro. Northern and Western blotting analyses revealed that epimorphin expression in NSIP samples were significantly higher than those in control lungs and lungs with UIP. Immunohistochemistry showed strong epimorphin expression in mesenchymal cells of early fibrotic lesions and localization of epimorphin protein on mesenchymal cells and extracellular matrix of early fibrotic lesions in the nonspecific interstitial pneumonia group. Double-labeled fluorescent images revealed expression of matrix metalloproteinase 2 in re-epithelialized cells overlying epimorphin-positive early fibrotic lesions. Immunohistochemistry and metalloproteinase activity assay demonstrated augmented expression of metalloproteinase induced by recombinant epimorphin in human alveolar epithelial cells. These findings suggest that epimorphin contributes to repair of pulmonary fibrosis in nonspecific interstitial pneumonia, perhaps partly by inducing expression of matrix metalloproteinase 2, which is an important proteolytic factor in lung remodeling. PMID:15651999

Epigenetic regulation of cardiac fibrosis

PubMed Central

Stratton, Matthew S.; McKinsey, Timothy A.

2016-01-01

Fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In the heart, fibrosis may be reparative, replacing areas of myocyte loss with a structural scar following infarction, or reactive, which is triggered in the absence of cell death and involves interstitial ECM deposition in response to long-lasting stress. Interstitial fibrosis can increase the passive stiffness of the myocardium, resulting in impaired relaxation and diastolic dysfunction. Additionally, fibrosis can lead to disruption of electrical conduction in the heart, causing arrhythmias, and can limit myocyte oxygen availability and thus exacerbate myocardial ischemia. Here, we review recent studies that have illustrated key roles for epigenetic events in the control of pro-fibrotic gene expression, and highlight the potential of small molecules that target epigenetic regulators as a means of treating fibrotic cardiac diseases. PMID:26876451

CSF1R inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages.

PubMed

Meziani, Lydia; Mondini, Michele; Petit, Benoît; Boissonnas, Alexandre; Thomas de Montpreville, Vincent; Mercier, Olaf; Vozenin, Marie-Catherine; Deutsch, Eric

2018-03-01

Radiation-induced lung fibrosis (RIF) is a delayed side-effect of chest radiotherapy, frequently associated with macrophage infiltration.We aimed to characterise the role of pulmonary macrophages in RIF using human lung biopsies from patients receiving radiotherapy for thorax malignancies and a RIF model developed in C57BL/6 mice after 16-Gy thorax irradiation.High numbers of macrophages (both interstitial and alveolar) were detected in clinical and preclinical RIF. In the preclinical model, upregulation of T-helper (Th)2 cytokines was measured, whereas Th1 cytokines were downregulated in RIF tissue lysate. Bronchoalveolar lavage demonstrated upregulation of both types of cytokines. At steady state, tissue-infiltrating macrophages (IMs) expressed 10-fold more arginase (Arg)-1 than alveolar macrophages (AMs), and a 40-fold upregulation of Arg-1 was found in IMs isolated from RIF. IMs, but not AMs, were able to induce myofibroblast activation in vitro In addition, whereas depletion of AMs using Clodrosome didn't affect RIF score, depletion of IMs using a clinically available colony-stimulating factor receptor-1 (CSF1R) neutralising antibody was antifibrotic.These findings suggest differential contributions of alveolar versus interstitial macrophages in RIF, highlighting the fibrogenic role of IMs. The CSF1/CSF1R pathway was identified as a new therapeutic target to inhibit RIF. Copyright ©ERS 2018.

Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis.

PubMed

Juge, Pierre-Antoine; Borie, Raphaël; Kannengiesser, Caroline; Gazal, Steven; Revy, Patrick; Wemeau-Stervinou, Lidwine; Debray, Marie-Pierre; Ottaviani, Sébastien; Marchand-Adam, Sylvain; Nathan, Nadia; Thabut, Gabriel; Richez, Christophe; Nunes, Hilario; Callebaut, Isabelle; Justet, Aurélien; Leulliot, Nicolas; Bonnefond, Amélie; Salgado, David; Richette, Pascal; Desvignes, Jean-Pierre; Lioté, Huguette; Froguel, Philippe; Allanore, Yannick; Sand, Olivier; Dromer, Claire; Flipo, René-Marc; Clément, Annick; Béroud, Christophe; Sibilia, Jean; Coustet, Baptiste; Cottin, Vincent; Boissier, Marie-Christophe; Wallaert, Benoit; Schaeverbeke, Thierry; Dastot le Moal, Florence; Frazier, Aline; Ménard, Christelle; Soubrier, Martin; Saidenberg, Nathalie; Valeyre, Dominique; Amselem, Serge; Boileau, Catherine; Crestani, Bruno; Dieudé, Philippe

2017-05-01

Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT , RTEL1 , PARN or SFTPC coding regions . The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT , RTEL1 , PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12; p=9.45×10 -4 ). Telomeres were shorter in RA-ILD patients with a TERT , RTEL1 or PARN mutation than in controls (p=2.87×10 -2 ).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility. Copyright ©ERS 2017.

Idiopathic pulmonary fibrosis.

PubMed

Xaubet, Antoni; Ancochea, Julio; Molina-Molina, María

2017-02-23

Idiopathic pulmonary fibrosis is a fibrosing interstitial pneumonia associated with the radiological and/or histological pattern of usual interstitial pneumonia. Its aetiology is unknown, but probably comprises the action of endogenous and exogenous micro-environmental factors in subjects with genetic predisposition. Its diagnosis is based on the presence of characteristic findings of high-resolution computed tomography scans and pulmonary biopsies in absence of interstitial lung diseases of other aetiologies. Its clinical evolution is variable, although the mean survival rate is 2-5 years as of its clinical presentation. Patients with idiopathic pulmonary fibrosis may present complications and comorbidities which modify the disease's clinical course and prognosis. In the mild-moderate disease, the treatment consists of the administration of anti-fibrotic drugs. In severe disease, the best therapeutic option is pulmonary transplantation. In this paper we review the diagnostic and therapeutic aspects of the disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Hypersensitivity pneumonia-nonspecific interstitial pneumonia/fibrosis histopathologic presentation: a study in diagnosis and long-term management.

PubMed

Jacobs, Robert L; Andrews, Charles P

2003-02-01

Nonspecific interstitial pneumonia/fibrosis (NSIP) has been classified a form of idiopathic interstitial pneumonia/fibrosis. We have shown that cases of NSIP without demonstrable serum precipitins may be caused by inhalation of high levels of mold and/or bacteria in closed environments. We report a patient with a clinical and histopathologic diagnosis of NSIP without serum precipitins caused by a microbial contamination in her home. Her case was converted from an acute to an insidious clinical presentation by inadequate remediation. A prolonged avoidance-challenge technique demonstrated that this case of NSIP was a form of hypersensitivity pneumonia that was reversible by effective remediation. The patient was identified by compatible signs and symptoms, roentgenographic studies, pulmonary function tests, and a transbronchial lung biopsy. She was further evaluated with a detailed environmental history, serologic tests, and investigation of the home environment. An environmental avoidance and challenge technique was performed to confirm cause and effect and to determine that remediation had been effective. Review of the biopsy showed NSIP and failed to reveal any non-caseating granuloma formation. Investigation of the home revealed a Cladosporium species contamination of the air conditioning system and Penicillium species beneath an entryway carpet. Serum precipitins to commercial antigens of common mold to the south Texas area were negative. Avoidance and challenge techniques confirmed the home as the causative environment in this case of NSIP. The patient has been free of signs and symptoms and has taken no medication for interstitial lung disease over the past 30 months. Some cases of NSIP may be caused by inhalation of microbial antigen(s) in a closed environment. An environmental challenge technique was an effective method to determine the causative environment and confirm that remediation had been effective. Inadequate remediation may lead to symptomatic

Overview of the cellular and molecular basis of kidney fibrosis

PubMed Central

Eddy, Allison A

2014-01-01

The common pathogenetic pathway of progressive injury in patients with chronic kidney disease (CKD) is epitomized as normal kidney parenchymal destruction due to scarring (fibrosis). Understanding the fundamental pathways that lead to renal fibrosis is essential in order to develop better therapeutic options for human CKD. Although complex, four cellular responses are pivotal. (1) An interstitial inflammatory response that has multiple consequences—some harmful and others healing. (2) The appearance of a unique interstitial cell population of myofibroblasts, primarily derived from kidney stromal cells (fibroblasts and pericytes), that are the primary source of the various extracellular matrix proteins that form interstitial scars. (3) Tubular epithelial cells that have variable and time-dependent roles as early responders to injury and later as victims of fibrosis due to the loss of their regenerative abilities. (4) Loss of interstitial capillary integrity that compromises oxygen delivery and leads to a vicious cascade of hypoxia–oxidant stress that accentuates injury and fibrosis. In the absence of adequate angiogenic responses, a healthy interstitial capillary network is not maintained. The fibrotic ‘scar' that typifies CKD is an interesting consortium of multifunctional macromolecules that not only change in composition and structure over time, but can be degraded via extracellular and intracellular proteases. Although transforming growth factor beta appears to be the primary driver of kidney fibrosis, a vast array of additional molecules may have modulating roles. The importance of genetic and epigenetic factors is increasingly appreciated. An intriguing but incompletely understood cardiorenal syndrome underlies the high morbidity and mortality rates that develop in association with progressive kidney fibrosis. PMID:25401038

Progression of fibrosis in usual interstitial pneumonia: serial evaluation of the native lung after single lung transplantation.

PubMed

Grgic, Aleksandar; Lausberg, Henning; Heinrich, Marc; Koenig, Jochem; Uder, Michael; Sybrecht, Gerhard W; Wilkens, Heinrike

2008-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Usual interstitial pneumonia (UIP) is the histopathological pattern identifying patients with the clinical entity of IPF. Despite aggressive immunosuppressive therapy the clinical course is usually dismal. For selected patients only lung transplantation improves prognosis and quality of life. After lung transplantation patients often receive a potent cyclosporine-based immunosuppressive therapy. Some reports suggest that cyclosporine has the potential to prevent progression of fibrosis. In patients with single lung transplantation (sLTx) for UIP we evaluated the effect of cyclosporine-based immunosuppressive therapy on progression of fibrosis using a high-resolution computed tomography (HRCT) scoring system. This retrospective observational study included 13 patients (24-64 years old) with histologically confirmed UIP who had HRCT scans preceding and following sLTx and who survived at least 6 months after sLTx. All patients were initially treated with cyclosporin A, prednisone and azathioprine. Three radiologists analyzed HRCT scans by setting a score regarding fibrosis [fibrosis score (FS); range 0-5 for each lobe] and ground-glass opacity [ground-glass score (GGS); range 0-5 for each lobe]. A comparison of serial changes (interval: 12-96 months posttransplant, 2-4 HRCT examinations/patient) was performed with the sign test. Mean pretransplant FS and GGS of the nontransplanted lung were 1.80 and 1.61, respectively. Comparing pre- and posttransplant HRCT scans, mean lung FS significantly increased (0.35 +/- 0.15/year; p = 0.00024), while GGS tended to decrease (0.06 +/- 0.26/year; p = 0.5). A cyclosporin A based triple immunosuppressive regimen following sLTx does not seem to prevent progression of the fibrotic changes of the native lung in patients with IPF. Copyright 2007 S. Karger AG, Basel.

Rheb/mTORC1 Signaling Promotes Kidney Fibroblast Activation and Fibrosis

PubMed Central

Jiang, Lei; Xu, Lingling; Mao, Junhua; Li, Jianzhong; Fang, Li; Zhou, Yang; Liu, Wei; He, Weichun; Zhao, Allan Zijian

2013-01-01

Ras homolog enriched in brain (Rheb) is a small GTPase that regulates cell growth, differentiation, and survival by upregulating mammalian target of rapamycin complex 1 (mTORC1) signaling. The role of Rheb/mTORC1 signaling in the activation of kidney fibroblasts and the development of kidney fibrosis remains largely unknown. In this study, we found that Rheb/mTORC1 signaling was activated in interstitial myofibroblasts from fibrotic kidneys. Treatment of rat kidney interstitial fibroblasts (NRK-49F cell line) with TGFβ1 also activated Rheb/mTORC1 signaling. Blocking Rheb/mTORC1 signaling with rapamycin or Rheb small interfering RNA abolished TGFβ1-induced fibroblast activation. In a transgenic mouse, ectopic expression of Rheb activated kidney fibroblasts. These Rheb transgenic mice exhibited increased activation of mTORC1 signaling in both kidney tubular and interstitial cells as well as progressive interstitial renal fibrosis; rapamycin inhibited these effects. Similarly, mice with fibroblast-specific deletion of Tsc1, a negative regulator of Rheb, exhibited activated mTORC1 signaling in kidney interstitial fibroblasts and increased renal fibrosis, both of which rapamycin abolished. Taken together, these results suggest that Rheb/mTORC1 signaling promotes the activation of kidney fibroblasts and contributes to the development of interstitial fibrosis, possibly providing a therapeutic target for progressive renal disease. PMID:23661807

Familial Pulmonary Fibrosis

MedlinePlus

... called Familial Pulmonary Fibrosis (FPF) or Familial Interstitial Pneumonia (FIP). The most common definition of FPF is two or more primary biological family members (parent, child, or sibling) with the diagnosis of IPF or ...

Idiopathic pulmonary fibrosis in a Staffordshire bull terrier with hypothyroidism.

PubMed

Corcoran, B M; Dukes-McEwan, J; Rhind, S; French, A

1999-04-01

Radiographic evidence of chronic interstitial lung changes, usually believed to be attributable to lung fibrosis, is readily recognised in canine practice. Furthermore, there is a body of anecdotal evidence suggesting that a specific clinical entity consistent with chronic lung fibrosis occurs in specific breeds of terrier dogs. However, there is little pathological data to confirm these radiographic and clinical findings and, therefore, chronic interstitial lung disease of dogs is poorly characterised. In this report, a case of chronic pulmonary fibrosis is described in which histopathological confirmation was possible, and suggested that the condition might be analogous to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in humans.

Elsholtzia ciliata (Thunb.) Hylander attenuates renal inflammation and interstitial fibrosis via regulation of TGF-ß and Smad3 expression on unilateral ureteral obstruction rat model.

PubMed

Kim, Tae-Won; Kim, Young-Jung; Seo, Chang-Seob; Kim, Hyun-Tae; Park, Se-Ra; Lee, Mee-Young; Jung, Ju-Young

2016-04-15

Renal interstitial fibrosis is characterized by excessive accumulation of extracellular matrix, which leads to end-stage renal failure. The aim of this study was to explore the effect of Elsholtzia ciliata (Thunb.) Hylander ethanol extract (ECE) on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). After quantitative analysis of ECE using the high performance liquid chromatography-photodiode array (HPLC-PDA) method, an in vitro study was performed to assess the anti-inflammatory and anti-fibrotic effects of ECE, using lipopolysaccharide (LPS) and transforming growth factor-ß (TGF-ß), respectively. For in vivo study, all male Sprague Dawley (SD) rats (n=10/group), except for those in the control group, underwent UUO. The rats were orally treated with water (control), captopril (positive control, 200 mg/kg), and ECE (300 and 500 mg/kg) for 14 days. In ECE, luteolin and rosmarinic acid were relatively abundant among the other flavonoids and phenolic acids. ECE treatment ameliorated LPS-induced overexpression of nuclear factor-κB, tumor necrosis factor (TNF-α), and interleukin-6 and improved oxidative stress in RAW 264.7 cells. Furthermore, ECE treatment suppressed TGF-ß-induced α-smooth muscle actin and matrix metalloproteinase 9 expression in human renal mesangial cells. In the UUO model, 14 consecutive days of ECE treatment improved UUO-induced renal damage and attenuated histopathological alterations and interstitial fibrosis. Moreover, the renal expression of TNF-α, TGF-ß, and Smad 3 were inhibited by ECE treatment. Taken together, the effects of ECE may be mediated by blocking the activation of TGF-ß and inflammatory cytokines, leading subsequently to degradation of the ECM accumulation pathway. Based on these findings, ECE might serve as an improved treatment strategy for renal fibrotic disease. Copyright © 2016 Elsevier GmbH. All rights reserved.

Myostatin induces interstitial fibrosis in the heart via TAK1 and p38.

PubMed

Biesemann, Nadine; Mendler, Luca; Kostin, Sawa; Wietelmann, Astrid; Borchardt, Thilo; Braun, Thomas

2015-09-01

Myostatin, a member of the TGF-β superfamily of secreted growth factors, is a negative regulator of skeletal muscle growth. In the heart, it is expressed at lower levels compared to skeletal muscle but up-regulated under disease conditions. Cre recombinase-mediated inactivation of myostatin in adult cardiomyocytes leads to heart failure and increased mortality but cardiac function of surviving mice is restored after several weeks probably due to compensatory expression in non-cardiomyocytes. To study long-term effects of increased myostatin expression in the heart and to analyze the putative crosstalk between cardiomyocytes and fibroblasts, we overexpressed myostatin in cardiomyocytes. Increased expression of myostatin in heart muscle cells caused interstitial fibrosis via activation of the TAK-1-MKK3/6-p38 signaling pathway, compromising cardiac function in older mice. Our results uncover a novel role of myostatin in the heart and highlight the necessity for tight regulation of myostatin to maintain normal heart function.

Coxiella burnetii, a hidden pathogen in interstitial lung disease?

PubMed

Melenotte, Cléa; Izaaryene, Jalal-Jean; Gomez, Carine; Delord, Marion; Prudent, Elsa; Lepidi, Hubert; Mediannikov, Oleg; Lacoste, Marion; Djossou, Felix; Mania, Alexandre; Bernard, Noelle; Huchot, Eric; Mège, Jean-Louis; Brégeon, Fabienne; Raoult, Didier

2018-04-06

We report 7 patients with interstitial lung disease (ILD) on CT-scan reviewing. C. burnetii was diagnosed in situ in one lung biopsy performed. All patients had advanced interstitial lung fibrosis and persistent C. burnetii infection. Q fever may be a cofactor of ILD, especially in endemic areas.

Smoking-related interstitial fibrosis combined with pulmonary emphysema: computed tomography-pathologic correlative study using lobectomy specimens.

PubMed

Otani, Hideji; Tanaka, Tomonori; Murata, Kiyoshi; Fukuoka, Junya; Nitta, Norihisa; Nagatani, Yukihiro; Sonoda, Akinaga; Takahashi, Masashi

2016-01-01

To evaluate the incidence and pathologic correlation of thin-section computed tomography (TSCT) findings in smoking-related interstitial fibrosis (SRIF) with pulmonary emphysema. Our study included 172 consecutive patients who underwent TSCT and subsequent lobectomy. TSCT findings including clustered cysts with visible walls (CCVW) and ground-glass attenuation with/without reticulation (GGAR) were evaluated and compared in nonsmokers and smokers and among lung locations. TSCT findings, especially CCVW, were also compared with histological findings using lobectomy specimens. The incidence of CCVW and GGAR was significantly higher in smokers than in nonsmokers (34.1% and 40.7%, respectively, vs 2.0% and 12.2%). CCVW and GGAR were frequently found in the lower and peripheral zones. Histologically, CCVW corresponded more often with SRIF with emphysema than usual interstitial pneumonia (UIP, 63.3% vs 30%). CCVW of irregular size and shape were seen in 19 of 20 SRIF with emphysema and in seven of nine UIP-manifested areas with similar round cysts. A less-involved subpleural parenchyma was observed more frequently in SRIF with emphysema. SRIF with emphysema is a more frequent pathological finding than UIP in patients with CCVW on TSCT. The irregular size and shape of CCVW and a less-involved subpleural parenchyma may be a clue suggesting the presence of SRIF with emphysema.

Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive

PubMed Central

Newton, Chad A.; Batra, Kiran; Torrealba, Jose; Kozlitina, Julia; Glazer, Craig S.; Aravena, Carlos; Meyer, Keith; Raghu, Ganesh; Collard, Harold R.; Garcia, Christine Kim

2017-01-01

Heterozygous mutations in four telomere-related genes have been linked to pulmonary fibrosis, but little is known about similarities or differences of affected individuals. 115 patients with mutations in telomerase reverse transcriptase (TERT) (n=75), telomerase RNA component (TERC) (n=7), regulator of telomere elongation helicase 1 (RTEL1) (n=14) and poly(A)-specific ribonuclease (PARN) (n=19) were identified and clinical data were analysed. Approximately one-half (46%) had a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF); others had unclassifiable lung fibrosis (20%), chronic hypersensitivity pneumonitis (12%), pleuroparenchymal fibroelastosis (10%), interstitial pneumonia with autoimmune features (7%), an idiopathic interstitial pneumonia (4%) and connective tissue disease-related interstitial fibrosis (3%). Discordant interstitial lung disease diagnoses were found in affected individuals from 80% of families. Patients with TERC mutations were diagnosed at an earlier age than those with PARN mutations (51±11 years versus 64±8 years; p=0.03) and had a higher incidence of haematological comorbidities. The mean rate of forced vital capacity decline was 300 mL·year−1 and the median time to death or transplant was 2.87 years. There was no significant difference in time to death or transplant for patients across gene mutation groups or for patients with a diagnosis of IPF versus a non-IPF diagnosis. Genetic mutations in telomere related genes lead to a variety of interstitial lung disease (ILD) diagnoses that are universally progressive. PMID:27540018

Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.

PubMed

Newton, Chad A; Batra, Kiran; Torrealba, Jose; Kozlitina, Julia; Glazer, Craig S; Aravena, Carlos; Meyer, Keith; Raghu, Ganesh; Collard, Harold R; Garcia, Christine Kim

2016-12-01

Heterozygous mutations in four telomere-related genes have been linked to pulmonary fibrosis, but little is known about similarities or differences of affected individuals.115 patients with mutations in telomerase reverse transcriptase (TERT) (n=75), telomerase RNA component (TERC) (n=7), regulator of telomere elongation helicase 1 (RTEL1) (n=14) and poly(A)-specific ribonuclease (PARN) (n=19) were identified and clinical data were analysed.Approximately one-half (46%) had a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF); others had unclassifiable lung fibrosis (20%), chronic hypersensitivity pneumonitis (12%), pleuroparenchymal fibroelastosis (10%), interstitial pneumonia with autoimmune features (7%), an idiopathic interstitial pneumonia (4%) and connective tissue disease-related interstitial fibrosis (3%). Discordant interstitial lung disease diagnoses were found in affected individuals from 80% of families. Patients with TERC mutations were diagnosed at an earlier age than those with PARN mutations (51±11 years versus 64±8 years; p=0.03) and had a higher incidence of haematological comorbidities. The mean rate of forced vital capacity decline was 300 mL·year -1 and the median time to death or transplant was 2.87 years. There was no significant difference in time to death or transplant for patients across gene mutation groups or for patients with a diagnosis of IPF versus a non-IPF diagnosis.Genetic mutations in telomere related genes lead to a variety of interstitial lung disease (ILD) diagnoses that are universally progressive. Copyright ©ERS 2016.

Therapeutic Targeting of CC Ligand 21 or CC Chemokine Receptor 7 Abrogates Pulmonary Fibrosis Induced by the Adoptive Transfer of Human Pulmonary Fibroblasts to Immunodeficient Mice

PubMed Central

Pierce, Elizabeth M.; Carpenter, Kristin; Jakubzick, Claudia; Kunkel, Steven L.; Flaherty, Kevin R.; Martinez, Fernando J.; Hogaboam, Cory M.

2007-01-01

Idiopathic interstitial pneumonias (IIPs) are a collection of pulmonary fibrotic diseases of unknown etiopathogenesis. CC chemokine receptor 7 (CCR7) is expressed in IIP biopsies and primary fibroblast lines, but its role in pulmonary fibrosis was not previously examined. To study the in vivo role of CCR7 in a novel model of pulmonary fibrosis, 1.0 × 106 primary fibroblasts grown from idiopathic pulmonary fibrosis/usual interstitial pneumonia, nonspecific interstitial pneumonia, or histologically normal biopsies were injected intravenously into C.B-17 severe combined immunodeficiency (SCID)/beige (bg) mice. At days 35 and 63 after idiopathic pulmonary fibrosis/usual interstitial pneumonia fibroblast injection, patchy interstitial fibrosis and increased hydroxyproline were present in the lungs of immunodeficient mice. Adoptively transferred nonspecific interstitial pneumonia fibroblasts caused a more diffuse interstitial fibrosis and increased hydroxyproline levels at both times, but injected normal human fibroblasts did not induce interstitial remodeling changes in C.B-17SCID/bg mice. Systemic therapeutic immunoneutralization of either human CCR7 or CC ligand 21, its ligand, significantly attenuated the pulmonary fibrosis in groups of C.B-17SCID/bg mice that received either type of IIP fibroblasts. Thus, the present study demonstrates that pulmonary fibrosis is initiated by the intravenous introduction of primary human fibroblast lines into immunodeficient mice, and this fibrotic response is dependent on the interaction between CC ligand 21 and CCR7. PMID:17392156

Antioxidants as Potential Therapeutics for Lung Fibrosis

PubMed Central

DAY, BRIAN J.

2009-01-01

Interstitial lung disease encompasses a large group of chronic lung disorders associated with excessive tissue remodeling, scarring, and fibrosis. The evidence of a redox imbalance in lung fibrosis is substantial, and the rationale for testing antioxidants as potential new therapeutics for lung fibrosis is appealing. Current animal models of lung fibrosis have clear involvement of ROS in their pathogenesis. New classes of antioxidant agents divided into catalytic antioxidant mimetics and antioxidant scavengers are being developed. The catalytic antioxidant class is based on endogenous antioxidant enzymes and includes the manganese-containing macrocyclics, porphyrins, salens, and the non–metal-containing nitroxides. The antioxidant scavenging class is based on endogenous antioxidant molecules and includes the vitamin E analogues, thiols, lazaroids, and polyphenolic agents. Numerous studies have shown oxidative stress to be associated with many interstitial lung diseases and that these agents are effective in attenuating fibroproliferative responses in the lung of animals and humans. PMID:17999627

[Nonspecific interstitial pneumonitis: a clinicopathologic entity, histologic pattern or unclassified group of heterogeneous interstitial pneumonitis?].

PubMed

Morais, António; Moura, M Conceição Souto; Cruz, M Rosa; Gomes, Isabel

2004-01-01

Nonspecific interstitial pneumonitis (NSIP) initially described by Katzenstein and Fiorelli in 1994, seems to be a distinct clinicopathologic entity among idiopathic interstitial pneumonitis (IIP). Besides different histologic features from other IIP, NSIP is characterized by a better long-term outcome, associated with a better steroids responsiveness than idiopathic pulmonar fibrosis (IPF), where usually were included. Thus, differentiating NSIP from other IIP, namely IPF is very significant, since it has important therapeutic and prognostic implications. NSIP encloses different pathologies, namely those with inflammatory predominance (cellular subtype) or fibrous predominance (fibrosing subtype). NSIP is reviewed and discussed by the authors, after two clinical cases description.

Myositis-associated usual interstitial pneumonia has a better survival than idiopathic pulmonary fibrosis.

PubMed

Aggarwal, Rohit; McBurney, Christine; Schneider, Frank; Yousem, Samuel A; Gibson, Kevin F; Lindell, Kathleen; Fuhrman, Carl R; Oddis, Chester V

2017-03-01

To compare the survival outcomes between myositis-associated usual interstitial pneumonia (MA-UIP) and idiopathic pulmonary fibrosis (IPF-UIP). Adult MA-UIP and IPF-UIP patients were identified using CTD and IPF registries. The MA-UIP cohort included myositis or anti-synthetase syndrome patients with interstitial lung disease while manifesting UIP on high-resolution CT chest and/or a lung biopsy revealing UIP histology. IPF subjects met American Thoracic Society criteria and similarly had UIP histopathology. Kaplan-Meier survival curves compared cumulative and pulmonary event-free survival (event = transplant or death) between (i) all MA-UIP and IPF-UIP subjects, (ii) MA-UIP with biopsy proven UIP (n = 25) vs IPF-UIP subjects matched for age, gender and baseline forced vital capacity (±10%). Cox proportional hazards ratios compared the survival controlling for co-variates. Eighty-one IPF-UIP and 43 MA-UIP subjects were identified. The median cumulative and event-free survival time in IPF vs MA-UIP was 5.25/1.8 years vs 16.2/10.8 years, respectively. Cumulative and event-free survival was significantly worse in IPF-UIP vs MA-UIP [hazards ratio of IPF-UIP was 2.9 (95% CI: 1.5, 5.6) and 5.0 (95% CI: 2.8, 8.7) (P < 0.001), respectively]. IPF-UIP event-free survival (but not cumulative) remained significantly worse than MA-UIP with a hazards ratio of 6.4 (95% CI: 3.0, 13.8) after controlling for age at interstitial lung disease diagnosis, gender, ethnicity and baseline forced vital capacity%. Respiratory failure was the most common cause of death in both groups. A sub-analysis of 25 biopsy-proven MA-UIP subjects showed similar results. MA-UIP patients demonstrated a significant survival advantage over a matched IPF cohort, suggesting that despite similar histological and radiographic findings at presentation, the prognosis of MA-UIP is superior to that of IPF-UIP. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology

Sequential occurrence of combined pulmonary fibrosis and emphysema syndrome in a non-smoker female patient.

PubMed

Gupta, Pawan; Dash, Devijyoti; Mittal, Richa; Chhabra, Sunil K

2017-05-01

The combined pulmonary fibrosis and emphysema (CPFE) syndrome is a unique and an under-recognized disorder characterized by emphysema in the upper lobes and interstitial fibrosis in the lower lobes of the lung. It occurs predominantly in males and almost exclusively in smokers. This rare combination of a restrictive and an obstructive mechanical defect carries a poorer prognosis than either of the two components. We present a case of CPFE syndrome in a non-smoker female patient who developed lower lobe emphysema subsequent to development of interstitial fibrosis. The case was remarkable for the extreme rarity of several presenting features, namely, a lower lobe occurrence of emphysema subsequent to pre-existent interstitial fibrosis, female gender and absence of a history of smoking. © 2015 John Wiley & Sons Ltd.

Smoking-related interstitial fibrosis combined with pulmonary emphysema: computed tomography-pathologic correlative study using lobectomy specimens

PubMed Central

Otani, Hideji; Tanaka, Tomonori; Murata, Kiyoshi; Fukuoka, Junya; Nitta, Norihisa; Nagatani, Yukihiro; Sonoda, Akinaga; Takahashi, Masashi

2016-01-01

Purpose To evaluate the incidence and pathologic correlation of thin-section computed tomography (TSCT) findings in smoking-related interstitial fibrosis (SRIF) with pulmonary emphysema. Patients and methods Our study included 172 consecutive patients who underwent TSCT and subsequent lobectomy. TSCT findings including clustered cysts with visible walls (CCVW) and ground-glass attenuation with/without reticulation (GGAR) were evaluated and compared in nonsmokers and smokers and among lung locations. TSCT findings, especially CCVW, were also compared with histological findings using lobectomy specimens. Results The incidence of CCVW and GGAR was significantly higher in smokers than in nonsmokers (34.1% and 40.7%, respectively, vs 2.0% and 12.2%). CCVW and GGAR were frequently found in the lower and peripheral zones. Histologically, CCVW corresponded more often with SRIF with emphysema than usual interstitial pneumonia (UIP, 63.3% vs 30%). CCVW of irregular size and shape were seen in 19 of 20 SRIF with emphysema and in seven of nine UIP-manifested areas with similar round cysts. A less-involved subpleural parenchyma was observed more frequently in SRIF with emphysema. Conclusion SRIF with emphysema is a more frequent pathological finding than UIP in patients with CCVW on TSCT. The irregular size and shape of CCVW and a less-involved subpleural parenchyma may be a clue suggesting the presence of SRIF with emphysema. PMID:27445472

Serum metalloproteinases 1 and 7 in the diagnosis of idiopathic pulmonary fibrosis and other interstitial pneumonias.

PubMed

Morais, António; Beltrão, Marília; Sokhatska, Oksana; Costa, Diogo; Melo, Natalia; Mota, Patricia; Marques, Agostinho; Delgado, Luís

2015-08-01

Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) has important therapeutic and prognostic implications and would be greatly aided by reliable diagnostic biomarkers as IPF has sometimes overlapping features with other interstitial lung diseases (ILD). To explore the value of serum metalloproteinases (MMP) 1 and 7 levels in the differential diagnosis of IPF with other ILD. MMP-1/7 serum levels were measured using Luminex xMAP technology in 139 patients- 47 IPF, 36 non-IPF Usual Interstitial Pneumonia (UIP), 14 idiopathic Nonspecific Interstitial Pneumonia (iNSIP), 29 secondary NSIP (secNSIP), 13 stage IV sarcoidosis- and 20 healthy controls, and compared using the Mann-Whitney U test. MMP-1 was significantly higher in IPF than non-IPF UIP (P = .042) and sarcoidosis (P = .027). MMP-7 was significantly higher in IPF than controls (P < .001), non-IPF UIP (P = .003), secNSIP (P < .001), and sarcoidosis (P < .001). The Area Under the Curve for IPF versus other ILD was 0.63 (95%CI, 0.53-0.73) for MMP-1, 0.73 (95%CI, 0.65-0.81) for MMP-7, and 0.74 (95%CI, 0.66-0.82) for MMP-1/MMP-7 combined. Sensitivity and specificity for MMP-7 cutoff = 3.91 ng/mL was 72.3% and 66.3%, respectively, Positive Predictive Values = 52.3% and Negative Predictive Values = 82.4%. MMP-1 and particularly MMP-7 serum levels were significantly higher in IPF than in non-IPF UIP, the main entity in differential diagnosis. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF diagnosis needs to be considered and further explored. Copyright © 2015 Elsevier Ltd. All rights reserved.

Smoking-related interstitial lung diseases.

PubMed

Caminati, A; Graziano, P; Sverzellati, N; Harari, S

2010-12-01

In pulmonary pathology, a wide spectrum of morphological changes is related to the consequences of smoking, and recognizing them on surgical specimens and on small transbronchial biopsies represents a challenge for the pathologist. Respiratory bronchiolitis, also referred to as smoker's bronchiolitis, is a common histologic feature found in the lung tissue of cigarette smokers. When identified as the sole histopathologic finding in the clinical setting of symptomatic interstitial lung disease, a diagnosis of respiratory bronchiolitis-interstitial lung disease is made. Since smoking is recognized to cause a variety of histologic patterns encompassing respiratory bronchiolitis, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia and pulmonary Langerhans cell hystiocytosis, smoking-related interstitial lung disease may be a useful concept to keep in mind for the pathologists. The relationship of smoking with each of these entities has been largely established on the basis of epidemiologic evidence. Although they have been retained as distinct and separate conditions in various classifications of interstitial lung diseases, these entities share a number of clinical, radiologic, and pathologic features suggesting that they represent a spectrum of patterns of interstitial lung disease occurring in predisposed individuals who smoke. Evaluation of histologic features, particularly in surgical lung biopsy samples, is important in making the distinction between these disorders. However, even after tissue biopsy, it may sometimes be difficult to clearly separate these entities. Recently, respiratory bronchiolitis-interstitial lung disease with fibrosis has been described and postulated that this is a smoking-related condition distinct from fibrotic non-specific interstitial pneumonia.

Idiopathic pulmonary fibrosis: current understanding of the pathogenesis and the status of treatment.

PubMed

Khalil, Nasreen; O'Connor, Robert

2004-07-20

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary fibrotic lung disease. The diagnostic histological changes are called usual interstitial pneumonia and are characterized by histological temporal heterogeneity, whereby normal lung tissue is interspersed with interstitial fibrosis, honeycomb cysts and fibroblast foci. Pulmonary functions show restricted volumes and capacities, preserved flows and evidence of decreased gas exchange. High-resolution computed axial tomography demonstrates evidence of fibrosis and lung remodelling such as honeycomb cysts and traction bronchiectasis. There is no known effective treatment for IPF, but lung transplantation improves survival.

Acute Exacerbation in Interstitial Lung Disease

PubMed Central

Leuschner, Gabriela; Behr, Jürgen

2017-01-01

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has been defined as an acute, clinically significant deterioration that develops within less than 1 month without obvious clinical cause like fluid overload, left heart failure, or pulmonary embolism. Pathophysiologically, damage of the alveoli is the predominant feature of AE-IPF which manifests histopathologically as diffuse alveolar damage and radiologically as diffuse, bilateral ground-glass opacification on high-resolution computed tomography. A growing body of literature now focuses on acute exacerbations of interstitial lung disease (AE-ILD) other than idiopathic pulmonary fibrosis. Based on a shared pathophysiology it is generally accepted that AE-ILD can affect all patients with interstitial lung disease (ILD) but apparently occurs more frequently in patients with an underlying usual interstitial pneumonia pattern. The etiology of AE-ILD is not fully understood, but there are distinct risk factors and triggers like infection, mechanical stress, and microaspiration. In general, AE-ILD has a poor prognosis and is associated with a high mortality within 6–12 months. Although there is a lack of evidence based data, in clinical practice, AE-ILD is often treated with a high dose corticosteroid therapy and antibiotics. This article aims to provide a summary of the clinical features, diagnosis, management, and prognosis of AE-ILD as well as an update on the current developments in the field. PMID:29109947

Renalase Protects against Renal Fibrosis by Inhibiting the Activation of the ERK Signaling Pathways

PubMed Central

Wu, Yiru; Wang, Liyan; Deng, Dai; Zhang, Qidong; Liu, Wenhu

2017-01-01

Renal interstitial fibrosis is a common pathway for the progression of chronic kidney disease (CKD) to end-stage renal disease. Renalase, acting as a signaling molecule, has been reported to have cardiovascular and renal protective effects. However, its role in renal fibrosis remains unknown. In this study, we evaluated the therapeutic efficacy of renalase in rats with complete unilateral ureteral obstruction (UUO) and examined the inhibitory effects of renalase on transforming growth factor-β1 (TGF-β1)-induced epithelial–mesenchymal transition (EMT) in human proximal renal tubular epithelial (HK-2) cells. We found that in the UUO model, the expression of renalase was markedly downregulated and adenoviral-mediated expression of renalase significantly attenuated renal interstitial fibrosis, as evidenced by the maintenance of E-cadherin expression and suppressed expression of α-smooth muscle actin (α-SMA), fibronectin and collagen-I. In vitro, renalase inhibited TGF-β1-mediated upregulation of α-SMA and downregulation of E-cadherin. Increased levels of Phospho-extracellular regulated protein kinases (p-ERK1/2) in TGF-β1-stimulated cells were reversed by renalase cotreatment. When ERK1 was overexpressed, the inhibition of TGF-β1-induced EMT and fibrosis mediated by renalase was attenuated. Our study provides the first evidence that renalase can ameliorate renal interstitial fibrosis by suppression of tubular EMT through inhibition of the ERK pathway. These results suggest that renalase has potential renoprotective effects in renal interstitial fibrosis and may be an effective agent for slowing CKD progression. PMID:28448446

Advances in the treatment of rheumatic interstitial lung disease.

PubMed

Vassallo, Robert; Thomas, Charles F

2004-05-01

Interstitial lung disease frequently complicates the rheumatic diseases. The purpose of this review is to outline recent advances and current concepts regarding the management of these interstitial lung diseases. Several histologic lesions cause interstitial lung disease in rheumatic diseases, including nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia, lymphocytic interstitial pneumonia, desquamative interstitial pneumonia, and acute interstitial pneumonia. Although the relative frequency of occurrence of these histopathologic lesions is not definitively established, it seems that nonspecific interstitial pneumonia accounts for a large proportion of rheumatic disease-associated interstitial lung diseases. Although usual interstitial pneumonia generally responds poorly to corticosteroid therapy, other forms of interstitial pneumonia are often steroid responsive and have a more favorable long-term prognosis. Pulmonary hypertension is increasingly recognized as a complication of these interstitial lung diseases. Treatment of pulmonary hypertension in these patients provides clinical benefit and may suppress pulmonary inflammation and fibrosis. Lung transplantation is a treatment option for selected patients with severe pulmonary involvement and limited life expectancy. Interstitial lung disease is common in the rheumatic diseases, may be caused by a variety of lesions that respond differently to treatment, and may lead to the development of pulmonary hypertension. Whether the prognosis of interstitial lung disease associated with rheumatic disease is similar to that associated with the idiopathic interstitial pneumonias is not known. Treatment of these interstitial lung diseases should take into account the specific histologic lesion, the activity of the underlying rheumatic disease, and associated pulmonary hypertension, if present. The diagnosis of a rheumatic disease is no longer an absolute contraindication to lung

[Lung transplantation in pulmonary fibrosis and other interstitial lung diseases].

PubMed

Berastegui, Cristina; Monforte, Victor; Bravo, Carlos; Sole, Joan; Gavalda, Joan; Tenório, Luis; Villar, Ana; Rochera, M Isabel; Canela, Mercè; Morell, Ferran; Roman, Antonio

2014-09-15

Interstitial lung disease (ILD) is the second indication for lung transplantation (LT) after emphysema. The aim of this study is to review the results of LT for ILD in Hospital Vall d'Hebron (Barcelona, Spain). We retrospectively studied 150 patients, 87 (58%) men, mean age 48 (r: 20-67) years between August 1990 and January 2010. One hundred and four (69%) were single lung transplants (SLT) and 46 (31%) bilateral-lung transplants (BLT). The postoperative diagnoses were: 94 (63%) usual interstitial pneumonia, 23 (15%) nonspecific interstitial pneumonia, 11 (7%) unclassifiable interstitial pneumonia and 15% miscellaneous. We describe the functional results, complications and survival. The actuarial survival was 87, 70 and 53% at one, 3 and 5 years respectively. The most frequent causes of death included early graft dysfunction and development of chronic rejection in the form of bronchiolitis obliterans (BOS). The mean postoperative increase in forced vital capacity and forced expiratory volume in the first second (FEV1) was similar in SLT and BLT. The best FEV1 was reached after 10 (r: 1-36) months. Sixteen percent of patients returned to work. At some point during the evolution, proven acute rejection was diagnosed histologically in 53 (35%) patients. The prevalence of BOS among survivors was 20% per year, 45% at 3 years and 63% at 5 years. LT is the best treatment option currently available for ILD, in which medical treatment has failed. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Cadherin-11 Regulation of Fibrosis through Modulation of Epithelial-to-Mesenchymal Transition: Implications for Pulmonary Fibrosis in Scleroderma

DTIC Science & Technology

2014-10-01

fibrosis, interstitial lung diseases 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON...cadherin-11 in scleroderma patients with interstitial lung disease . We have been working with our collaborators at UTHSC to identify and sera that...83% female, avg age 49, avg disease duration 2.5 years, 59% with diffuse SSc, 28% with ILD and avg skin score of 16 at enrollment). Since there is

Toll-Like Receptor Signaling and SIGIRR in Renal Fibrosis upon Unilateral Ureteral Obstruction

PubMed Central

Allam, Ramanjaneyulu; Ryu, Mi; Clauss, Sebastian; Susanti, Heni Eka; Römmele, Christoph; Garlanda, Cecilia; Mantovani, Alberto; Anders, Hans-Joachim

2011-01-01

Innate immune activation via IL-1R or Toll-like receptors (TLR) contibutes to acute kidney injury but its role in tissue remodeling during chronic kidney disease is unclear. SIGIRR is an inhibitor of TLR-induced cytokine and chemokine expression in intrarenal immune cells, therefore, we hypothesized that Sigirr-deficiency would aggravate postobstructive renal fibrosis. The expression of TLRs as well as endogenous TLR agonists increased within six days after UUO in obstructed compared to unobstructed kidneys while SIGIRR itself was downregulated by day 10. However, lack of SIGIRR did not affect the intrarenal mRNA expression of proinflammatory and profibrotic mediators as well as the numbers of intrarenal macrophages and T cells or morphometric markers of tubular atrophy and interstitial fibrosis. Because SIGIRR is known to block TLR/IL-1R signaling at the level of the intracellular adaptor molecule MyD88 UUO experiments were also performed in mice deficient for either MyD88, TLR2 or TLR9. After UUO there was no significant change of tubular interstitial damage and interstitial fibrosis in neither of these mice compared to wildtype counterparts. Additional in-vitro studies with CD90+ renal fibroblasts revealed that TLR agonists induce the expression of IL-6 and MCP-1/CCL2 but not of TGF-β, collagen-1α or smooth muscle actin. Together, postobstructive renal interstitial fibrosis and tubular atrophy develop independent of SIGIRR, TLR2, TLR9, and MyD88. These data argue against a significant role of these molecules in renal fibrosis. PMID:21544241

Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia

PubMed Central

Parra, E.R.; Pincelli, M.S.; Teodoro, W.R.; Velosa, A.P.P.; Martins, V.; Rangel, M.P.; Barbas-Filho, J.V.; Capelozzi, V.L.

2014-01-01

Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis. PMID:24919172

Idiopathic pulmonary fibrosis: evolving concepts.

PubMed

Ryu, Jay H; Moua, Teng; Daniels, Craig E; Hartman, Thomas E; Yi, Eunhee S; Utz, James P; Limper, Andrew H

2014-08-01

Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older adults and accounts for 20% to 30% of interstitial lung diseases. It is usually progressive, resulting in respiratory failure and death. Diagnostic criteria for IPF have evolved over the years, and IPF is currently defined as a disease characterized by the histopathologic pattern of usual interstitial pneumonia occurring in the absence of an identifiable cause of lung injury. Understanding of the pathogenesis of IPF has shifted away from chronic inflammation and toward dysregulated fibroproliferative repair in response to alveolar epithelial injury. Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by various interactions between genetic components and environmental exposures. High-resolution computed tomography can be diagnostic in the presence of typical findings such as bilateral reticular opacities associated with traction bronchiectasis/bronchiolectasis in a predominantly basal and subpleural distribution, along with subpleural honeycombing. In other circumstances, a surgical lung biopsy may be needed. The clinical course of IPF can be unpredictable and may be punctuated by acute deteriorations (acute exacerbation). Although progress continues in unraveling the mechanisms of IPF, effective therapy has remained elusive. Thus, clinicians and patients need to reach informed decisions regarding management options including lung transplant. The findings in this review were based on a literature search of PubMed using the search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia, limited to human studies in the English language published from January 1, 2000, through December 31, 2013, and supplemented by key references published before the year 2000. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Mannose Receptor 2 Attenuates Renal Fibrosis

PubMed Central

López-Guisa, Jesús M.; Cai, Xiaohe; Collins, Sarah J.; Yamaguchi, Ikuyo; Okamura, Daryl M.; Bugge, Thomas H.; Isacke, Clare M.; Emson, Claire L.; Turner, Scott M.; Shankland, Stuart J.

2012-01-01

Mannose receptor 2 (Mrc2) expresses an extracellular fibronectin type II domain that binds to and internalizes collagen, suggesting that it may play a role in modulating renal fibrosis. Here, we found that Mrc2 levels were very low in normal kidneys but subsets of interstitial myofibroblasts and macrophages upregulated Mrc2 after unilateral ureteral obstruction (UUO). Renal fibrosis and renal parenchymal damage were significantly worse in Mrc2-deficient mice. Similarly, Mrc2-deficient Col4α3−/− mice with hereditary nephritis had significantly higher levels of total kidney collagen, serum BUN, and urinary protein than Mrc2-sufficient Col4α3−/− mice. The more severe phenotype seemed to be the result of reduced collagen turnover, because procollagen III (α1) mRNA levels and fractional collagen synthesis in the wild-type and Mrc2-deficient kidneys were similar after UUO. Although Mrc2 associates with the urokinase receptor, differences in renal urokinase activity did not account for the increased fibrosis in the Mrc2-deficient mice. Treating wild-type mice with a cathepsin inhibitor, which blocks proteases implicated in Mrc2-mediated collagen degradation, worsened UUO-induced renal fibrosis. Cathepsin mRNA profiles were similar in Mrc2-positive fibroblasts and macrophages, and Mrc2 genotype did not alter relative cathepsin mRNA levels. Taken together, these data establish an important fibrosis-attenuating role for Mrc2-expressing renal interstitial cells and suggest the involvement of a lysosomal collagen turnover pathway. PMID:22095946

Pulmonary fibrosis in rheumatoid arthritis: a review of clinical features and therapy.

PubMed

Roschmann, R A; Rothenberg, R J

1987-02-01

During the past four decades there has been a growing appreciation of the frequency of pulmonary abnormalities associated with RA. Approximately 30% to 40% of patients with RA demonstrate either radiographic or pulmonary function abnormalities indicative of interstitial fibrosis or restrictive lung disease. The severity of pulmonary fibrosis is not associated with rheumatologic symptoms or the duration of the associated RA, nor is there any clear relation to the extraarticular features of RA or serologic findings. Survival rates in patients with coexisting RA and pulmonary fibrosis are similar to those of patients with idiopathic pulmonary fibrosis. However, the spectrum of disease activity is quite variable. The majority of patients with progressive pulmonary symptomatology, when treated with corticosteroids, will have equivocal results. Some patients appear to respond to immunosuppressive or cytotoxic medications. The role of macrophages may be central to the injury to lung. Recent studies suggest a potential treatment role for cyclosporine, which may be able to interrupt lymphocyte-stimulated macrophage activation, and thus, fibroblast-mediated fibrosis in patients with pulmonary interstitial fibrosis. Bronchoalveolar lavage studies may delineate subgroups of patients who are more likely to respond to immunosuppressive agents, especially when treatment is started early.

Pulmonary fibrosis in asbestos insulation workers with lung cancer: a radiological and histopathological evaluation.

PubMed Central

Kipen, H M; Lilis, R; Suzuki, Y; Valciukas, J A; Selikoff, I J

1987-01-01

This study was undertaken to determine the relation between radiographic and histological manifestations of pulmonary asbestosis (interstitial fibrosis) in insulation workers who had died of lung cancer. Of 450 confirmed deaths from lung cancer a chest radiograph suitable for determining evidence of pneumoconiosis was obtained in 219. Of these cases, 138 also had a tissue specimen submitted that was suitable for histological study to determine the extent of histological fibrosis. There was a significant albeit limited correlation between the radiographic and histological findings (r = 0.27, p less than 0.0013). All 138 cases had histological evidence of parenchymal fibrosis; in 25 (18%), however, there was no radiographic evidence of parenchymal fibrosis. In 10 cases (7%) both parenchymal and pleural disease were undetectable on the radiograph. Thus a negative chest radiograph does not exclude the presence of interstitial fibrosis (asbestosis) in a substantial proportion of insulation workers previously exposed to asbestos who develop lung cancer. PMID:3814551

Desquamative interstitial pneumonia associated with chrysotile asbestos fibres.

PubMed Central

Freed, J A; Miller, A; Gordon, R E; Fischbein, A; Kleinerman, J; Langer, A M

1991-01-01

The drywall construction trade has in the past been associated with exposure to airborne asbestos fibres. This paper reports a drywall construction worker with 32 years of dust exposure who developed dyspnoea and diminished diffusing capacity, and showed diffuse irregular opacities on chest radiography. He did not respond to treatment with corticosteroids. Open lung biopsy examination showed desquamative interstitial pneumonia. Only a single ferruginous body was seen on frozen section, but tissue examination by electron microscopy showed an extraordinary pulmonary burden of mineral dust with especially high concentrations of chrysotile asbestos fibres. This report emphasises the need to consider asbestos fibre as an agent in the aetiology of desquamative interstitial pneumonia. The coexistent slight interstitial fibrosis present in this case is also considered to have resulted from exposure to mineral dust, particularly ultramicroscopic asbestos fibres. Images PMID:1645584

Diffusing capacity and forced vital capacity in 5,003 asbestos-exposed workers: relationships to interstitial fibrosis (ILO profusion score) and pleural thickening.

PubMed

Miller, Albert; Warshaw, Raphael; Nezamis, James

2013-12-01

Asbestosis is an interstitial lung disease whose radiographic severity has long been graded by the International Labour Office (ILO) profusion score. Its effect on pulmonary function is further impacted by asbestos related pleural thickening. This report aims to describe the relationships between radiographic grading of interstitial and pleural fibrosis and a key test of pulmonary function, the diffusing capacity, which measures gas exchange and has rarely been assessed in large groups, and to confirm the relationship to an independent test of pulmonary function, the vital capacity, which measures a mechanical property of the lungs. The data were derived from a survey during the period 1997-2004 of 5,003 workers (all white males) exposed to asbestos in various trades. Tests included chest radiographs read by a certified expert ("B") reader, forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLco). Cigarette smoking was adjusted for in the predictive equation for DLCO . Workers were evaluated at a mobile facility at work sites in four southern states. Both diffusing capacity and vital capacity were negatively correlated with profusion score over the full spectrum of radiographic severity. ILO profusion scores 0/1 (conventionally classified as normal) and 1/0 (conventionally classified as abnormal) were associated with similar diffusing capacity and vital capacity values. The highest profusion scores were associated with a greater proportionate decrease in diffusing capacity than in FVC. Both tests showed an effect of pleural fibrosis. Both radiographic severity graded by the profusion score and pleural thickening are correlated with two independent measures of pulmonary function. FVC (which had been reported in smaller work forces) and DLCO (which has not been reported). Both measures show a decrease from normal to intermediate (0/1, 1/0) scores and a further decrease with greater scores, demonstrating the consistency of radiographic and functional

Inhibition mechanism of compound ethanol extracts from wuweizi (fructus schisandrae chinensis) on renal interstitial fibrosis in diabetic nephropathy model mice.

PubMed

Zhang, Yanqiu; Zhang, Daning; Zhang, Mianzhi

2012-12-01

To evaluate inhibition effect and mechanism of compound ethanol extracts from Wuweizi (Fructus Schisandrae Chinensis), Chuanxiong (Rhizoma Chuanxiong) and Muli (Cocha Ostreae) (FRC) on glomerular and tubular interstitial fibrosis in streptozocin (STZ)-induced diabetic nephropathy (ND) model mice. Twenty-seven male C57BL/6 mice were divided randomly into 3 groups: nondibetic (ND), STZ-induced diabetic (D), and STZ-induced diabetic that were treated with 5 g x kg(-1) x day(-1) of FRC by oral gavage (D(FRC)), with 9 in each group. The protein expressions of E-cadherin, alpha-smooth muscle actin (alpha-SMA), Plasminogen Activator Inhibitor-1 (PAL-1) in renal tissues were investigated by Western blotting. The expressions of fibronectin (FN) and alpha-SMA were detected by immunohistochemical method. The morphological changes of renal tissues were observed under a microscope. Renal tissues in the D(FRC) group showed a lessened degree of fibrosis. Meanwhile, the expressions of FN, alpha-SMA and PAI-1 were significantly lower in the D(FRC) group than those in the D group (all P < 0.05). FRC can ameliorate the DN in the C57BL/6 mice, and its mechanism may relate to inhibition on the epithelial to mesenchymal transdifferentiation, endothelial-myofibroblast transition and PAL-1 expression.

The study on serum and urine of renal interstitial fibrosis rats induced by unilateral ureteral obstruction based on metabonomics and network analysis methods.

PubMed

Xiang, Zheng; Sun, Hao; Cai, Xiaojun; Chen, Dahui

2016-04-01

Transmission of biological information is a biochemical process of multistep cascade from genes/proteins to metabolites. However, because most metabolites reflect the terminal information of the biochemical process, it is difficult to describe the transmission process of disease information in terms of the metabolomics strategy. In this paper, by incorporating network and metabolomics methods, an integrated approach was proposed to systematically investigate and explain the molecular mechanism of renal interstitial fibrosis. Through analysis of the network, the cascade transmission process of disease information starting from genes/proteins to metabolites was putatively identified and uncovered. The results indicated that renal fibrosis was involved in metabolic pathways of glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and arachidonic acid metabolism, riboflavin metabolism, tyrosine metabolism, and sphingolipid metabolism. These pathways involve kidney disease genes such as TGF-β1 and P2RX7. Our results showed that combining metabolomics and network analysis can provide new strategies and ideas for the interpretation of pathogenesis of disease with full consideration of "gene-protein-metabolite."

Increased Lymphatic Vessel Length Is Associated With the Fibroblast Reticulum and Disease Severity in Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia

PubMed Central

Cosgrove, Gregory P.; Janssen, William J.; Huie, Tristan J.; Burnham, Ellen L.; Heinz, David E.; Curran-Everett, Douglas; Sahin, Hakan; Schwarz, Marvin I.; Cool, Carlyne D.; Groshong, Steve D.; Geraci, Mark W.; Tuder, Rubin M.; Hyde, Dallas M.; Henson, Peter M.

2012-01-01

Background: Lymphangiogenesis responds to tissue injury as a key component of normal wound healing. The development of fibrosis in the idiopathic interstitial pneumonias may result from abnormal wound healing in response to injury. We hypothesize that increased lymphatic vessel (LV) length, a marker of lymphangiogenesis, is associated with parenchymal components of the fibroblast reticulum (organizing collagen, fibrotic collagen, and fibroblast foci), and its extent correlates with disease severity. Methods: We assessed stereologically the parenchymal structure of fibrotic lungs and its associated lymphatic network, which was highlighted immunohistochemically in age-matched samples of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) with FVC < 80%, COPD with a Global Initiative for Obstructive Lung Disease stage 0, and normal control lungs. Results: LV length density, as opposed to vessel volume density, was found to be associated with organizing and fibrotic collagen density (P < .0001). Length density of LVs and the volume density of organizing and fibrotic collagen were significantly associated with severity of both % FVC (P < .001) and diffusing capacity of the lung for carbon monoxide (P < .001). Conclusions: Severity of disease in UIP and NSIP is associated with increased LV length and is strongly associated with components of the fibroblast reticulum, namely organizing and fibrotic collagen, which supports a pathogenic role of LVs in these two diseases. Furthermore, the absence of definable differences between UIP and NSIP suggests that LVs are a unifying mechanism for the development of fibrosis in these fibrotic lung diseases. PMID:22797508

Pathogenesis of occult chronic hepatitis B virus infection

PubMed Central

de la Fuente, Rocio Aller; Gutiérrez, María L; Garcia-Samaniego, Javier; Fernández-Rodriguez, Conrado; Lledó, Jose Luis; Castellano, Gregorio

2011-01-01

Occult hepatitis B infection (OBI) is characterized by hepatitis B virus (HBV) DNA in serum in the absence of hepatitis B surface antigen (HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns. Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays; but more frequently it is due to a strong suppression of viral replication and gene expression. OBI is an entity with world-wide diffusion. The failure to detect HBsAg, despite the persistence of the viral DNA, is due in most cases to the strong suppression of viral replication and gene expression that characterizes this “occult” HBV infection; although the mechanisms responsible for suppression of HBV are not well understood. The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection. Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma. PMID:21472118

Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies.

PubMed

Mariani, Laura H; Martini, Sebastian; Barisoni, Laura; Canetta, Pietro A; Troost, Jonathan P; Hodgin, Jeffrey B; Palmer, Matthew; Rosenberg, Avi Z; Lemley, Kevin V; Chien, Hui-Ping; Zee, Jarcy; Smith, Abigail; Appel, Gerald B; Trachtman, Howard; Hewitt, Stephen M; Kretzler, Matthias; Bagnasco, Serena M

2018-02-01

Interstitial fibrosis (IF), tubular atrophy (TA) and interstitial inflammation (II) are known determinants of progression of renal disease. Standardized quantification of these features could add value to current classification of glomerulopathies. We studied 315 participants in the Nephrotic Syndrome Study Network (NEPTUNE) study, including biopsy-proven minimal change disease (MCD = 98), focal segmental glomerulosclerosis (FSGS = 121), membranous nephropathy (MN = 59) and IgA nephropathy (IgAN = 37). Cortical IF, TA and II were quantified (%) on digitized whole-slide biopsy images, by five pathologists with high inter-reader agreement (intra-class correlation coefficient >0.8). Tubulointerstitial messenger RNA expression was measured in a subset of patients. Multivariable Cox proportional hazards models were fit to assess association of IF with the composite of 40% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease (ESRD) and separately as well, and with complete remission (CR) of proteinuria. IF was highly correlated with TA (P < 0.001) and II (P < 0.001). Median IF varied by diagnosis: FSGS 17, IgAN 21, MN 7, MCD 1 (P < 0.001). IF was strongly correlated with baseline eGFR (P < 0.001) and proteinuria (P = 0.002). After adjusting for clinical pathologic diagnosis, age, race, global glomerulosclerosis, baseline proteinuria, eGFR and medications, each 10% increase in IF was associated with a hazard ratio of 1.29 (P < 0.03) for ESRD/40% eGFR decline, but was not significantly associated with CR. A total of 981 genes were significantly correlated with IF (|r| > 0.4, false discovery rate (FDR) < 0.01), including upstream regulators such as tumor necrosis factor, interferon gamma (IFN-gamma), and transforming growth factor beta 1 (TGF-B1), and signaling pathways for antigen presentation and hepatic fibrosis. The degree of IF is associated with risk of eGFR decline across different types of proteinuric

Stable expression of HIF-1α in tubular epithelial cells promotes interstitial fibrosis

PubMed Central

Kimura, Kuniko; Iwano, Masayuki; Higgins, Debra F.; Yamaguchi, Yukinari; Nakatani, Kimihiko; Harada, Koji; Kubo, Atsushi; Akai, Yasuhiro; Rankin, Erinn B.; Neilson, Eric G.; Haase, Volker H.; Saito, Yoshihiko

2008-01-01

Chronic hypoxia accelerates renal fibrosis. The chief mediator of the hypoxic response is hypoxia-inducible factor 1 (HIF-1) and its oxygen-sensitive component HIF-1α. HIF-1 regulates a wide variety of genes, some of which are closely associated with tissue fibrosis. To determine the specific role of HIF-1 in renal fibrosis, we generated a knockout mouse in which tubular epithelial expression of von Hippel-Lindau tumor suppressor (VHL), which acts as a ubiquitin ligase to promote proteolysis of HIF-1α, was targeted. We investigated the effect of VHL deletion (i.e., stable expression of HIF-1α) histologically and used the anti-HIF-1α agent [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] (YC-1) to test whether inhibition of HIF-1α could represent a novel approach to treating renal fibrosis. The area of renal fibrosis was significantly increased in a 5/6 renal ablation model of VHL−/− mice and in all VHL−/− mice at least 60 wk of age. Injection of YC-1 inhibited the progression of renal fibrosis in unilateral ureteral obstruction model mice. In conclusion, HIF-1α appears to be a critical contributor to the progression of renal fibrosis and could be a useful target for its treatment. PMID:18667485

Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis

PubMed Central

Morelle, Johann; Sow, Amadou; Hautem, Nicolas; Bouzin, Caroline; Crott, Ralph

2015-01-01

Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport. PMID:25636412

Reflective Occultation Mask for Evaluation of Occulter Designs for Planet Finding

NASA Technical Reports Server (NTRS)

Hagopian, John; Lyon, Richard; Shiri, Shahram; Roman, Patrick

2011-01-01

Advanced formation flying occulter designs utilize a large occulter mask flying in formation with an imaging telescope to block and null starlight to allow imaging of faint planets in exosolar systems. A paper describes the utilization of subscale reflective occultation masks to evaluate formation flying occulter designs. The use of a reflective mask allows mounting of the occulter by conventional means and simplifies the test configuration. The innovation alters the test set-up to allow mounting of the mask using standard techniques to eliminate the problems associated with a standard configuration. The modified configuration uses a reflective set-up whereby the star simulator reflects off of a reflective occulting mask and into an evaluation telescope. Since the mask is sized to capture all rays required for the imaging test, it can be mounted directly to a supporting fixture without interfering with the beam. Functionally, the reflective occultation mask reflects light from the star simulator instead of transmitting it, with a highly absorptive carbon nanotube layer simulating the occulter blocking mask. A subscale telescope images the star source and companion dim source that represents a planet. The primary advantage of this is that the occulter can be mounted conventionally instead of using diffractive wires or magnetic levitation.

Endothelial Dysfunction Exacerbates Renal Interstitial Fibrosis through Enhancing Fibroblast Smad3 Linker Phosphorylation in the Mouse Obstructed Kidney

PubMed Central

Sun, Yu Bo Yang; Qu, Xinli; Li, Xueling; Nikolic-Paterson, David J.; Li, Jinhua

2013-01-01

Endothelial dysfunction and enhanced transforming growth factor-β (TGF-β)/Smad3 signalling are common features of progressive renal fibrosis. This study investigated a potential link between these mechanisms. In unilateral ureteric obstruction (UUO) we observed an acute (6 hr) down-regulation of nitric oxide synthase 3 (NOS3/eNOS) levels and increased phosphorylation of the linker region of Smad3 at T179 and S208 in Smad3/JNK complexes. These events preceded Smad3 C-terminal domain phosphorylation and the induction of myofibroblast proliferation at 48 hrs. Mice deficient in NOS3 showed enhanced myofibroblast proliferation and collagen accumulation compared to wild type mice in a 7 day UUO model. This was associated with enhanced phosphorylation of Smad3 T179 and S208 by 92% and 88%, respectively, whereas Smad3-C-terminal phosphorylation was not affected. Resolvin D1 (RvD1) can suppress renal fibrosis in the UUO model, and further analysis herein showed that RvD1 protected against endothelial dysfunction and suppressed Smad3/JNK complex formation with a consequent reduction in phosphorylation of Smad3 T179 and S208 by 78% and 65%, respectively, while Smad3 C-terminal phosphorylation was unaltered. In vitro, conditioned media from mouse microvascular endothelial cells (MMEC) treated with a general inhibitor of nitric oxide synthase (L-NAME) augmented the proliferation and collagen production of renal fibroblasts (NRK49F cells) compared to control MMEC media and this was associated with increased phosphorylation of JNK and Smad3 T179 and S208, whereas Smad3-C-terminal domain phosphorylation was unaffected. The addition of RvD1 to L-NAME treated MMEC abrogated these effects of the conditioned media on renal fibroblasts. Finally, Smad3 T179/V and S208/A mutations significantly inhibit TGF-β1 induced up-regulation collagen I promoter. In conclusion, these data suggest that endothelial dysfunction can exacerbate renal interstitial fibrosis through increased fibroblast

Endothelial dysfunction exacerbates renal interstitial fibrosis through enhancing fibroblast Smad3 linker phosphorylation in the mouse obstructed kidney.

PubMed

Sun, Yu Bo Yang; Qu, Xinli; Li, Xueling; Nikolic-Paterson, David J; Li, Jinhua

2013-01-01

Endothelial dysfunction and enhanced transforming growth factor-β (TGF-β)/Smad3 signalling are common features of progressive renal fibrosis. This study investigated a potential link between these mechanisms. In unilateral ureteric obstruction (UUO) we observed an acute (6 hr) down-regulation of nitric oxide synthase 3 (NOS3/eNOS) levels and increased phosphorylation of the linker region of Smad3 at T179 and S208 in Smad3/JNK complexes. These events preceded Smad3 C-terminal domain phosphorylation and the induction of myofibroblast proliferation at 48 hrs. Mice deficient in NOS3 showed enhanced myofibroblast proliferation and collagen accumulation compared to wild type mice in a 7 day UUO model. This was associated with enhanced phosphorylation of Smad3 T179 and S208 by 92% and 88%, respectively, whereas Smad3-C-terminal phosphorylation was not affected. Resolvin D1 (RvD1) can suppress renal fibrosis in the UUO model, and further analysis herein showed that RvD1 protected against endothelial dysfunction and suppressed Smad3/JNK complex formation with a consequent reduction in phosphorylation of Smad3 T179 and S208 by 78% and 65%, respectively, while Smad3 C-terminal phosphorylation was unaltered. In vitro, conditioned media from mouse microvascular endothelial cells (MMEC) treated with a general inhibitor of nitric oxide synthase (L-NAME) augmented the proliferation and collagen production of renal fibroblasts (NRK49F cells) compared to control MMEC media and this was associated with increased phosphorylation of JNK and Smad3 T179 and S208, whereas Smad3-C-terminal domain phosphorylation was unaffected. The addition of RvD1 to L-NAME treated MMEC abrogated these effects of the conditioned media on renal fibroblasts. Finally, Smad3 T179/V and S208/A mutations significantly inhibit TGF-β1 induced up-regulation collagen I promoter. In conclusion, these data suggest that endothelial dysfunction can exacerbate renal interstitial fibrosis through increased fibroblast

Expression of bone morphogenetic proteins 4, 6 and 7 is downregulated in kidney allografts with interstitial fibrosis and tubular atrophy.

PubMed

Furic-Cunko, Vesna; Kes, Petar; Coric, Marijana; Hudolin, Tvrtko; Kastelan, Zeljko; Basic-Jukic, Nikolina

2015-07-01

Bone morphogenetic proteins (BMPs) are pleiotropic growth factors. This paper investigates the connection between the expression pattern of BMPs in kidney allograft tissue versus the cause of allograft dysfunction. The expression pattern of BMP2, BMP4, BMP6 and BMP7 in 50 kidney allografts obtained by transplant nephrectomy is investigated. Immunohistochemical staining is semiquantitatively evaluated for intensity to identify the expression pattern of BMPs in normal and allograft kidney tissues. The expression of BMP4 is unique between different tubular cell types in grafts without signs of fibrosis. This effect is not found in specimens with high grades of interstitial fibrosis and tubular atrophy (IFTA). In samples with IFTA grades II and III, the BMP7 expression is reduced in a significant fraction of specimens relative to those without signs of IFTA. The expression pattern of BMP6 indicates that its activation may be triggered by the act of transplantation and subsequent reperfusion injury. The expression of BMP2 is strong in all types of tubular epithelial cells and does not differ between the compared allografts and control kidney specimens. The intensity and expression pattern of BMP4, BMP6 and BMP7 in transplanted kidney tissue are found to be dependent upon the length of the transplanted period, the clinical indication for transplant nephrectomy and signs of IFTA in kidney tissue.

Diffuse Alveolar Damage: A Common Phenomenon in Progressive Interstitial Lung Disorders

PubMed Central

Kaarteenaho, Riitta; Kinnula, Vuokko L.

2011-01-01

It has become obvious that several interstitial lung diseases, and even viral lung infections, can progress rapidly, and exhibit similar features in their lung morphology. The final histopathological feature, common in these lung disorders, is diffuse alveolar damage (DAD). The histopathology of DAD is considered to represent end stage phenomenon in acutely behaving interstitial pneumonias, such as acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (IPF). Acute worsening and DAD may occur also in patients with nonspecific interstitial pneumonias (NSIPs), and even in severe viral lung infections where there is DAD histopathology in the lung. A better understanding of the mechanisms underlying the DAD reaction is needed to clarify the treatment for these serious lung diseases. There is an urgent need for international efforts for studying DAD-associated lung diseases, since the prognosis of these patients has been and is still dismal. PMID:21637367

Rheumatoid arthritis-associated interstitial lung disease: lung inflammation evaluated with high resolution computed tomography scan is correlated to rheumatoid arthritis disease activity.

PubMed

Pérez-Dórame, Renzo; Mejía, Mayra; Mateos-Toledo, Heidegger; Rojas-Serrano, Jorge

2015-01-01

To describe the association between rheumatoid arthritis disease activity (RA) and interstitial lung damage (inflammation and fibrosis), in a group of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). A retrospective study of RA patients with interstitial lung disease (restrictive pattern in lung function tests and evidence of interstitial lung disease in high resolution computed tomography (HRCT)). Patients were evaluated to exclude other causes of pulmonary disease. RA disease activity was measured with the CDAI index. Interstitial lung inflammation and fibrosis were determined by Kazerooni scale. We compared Kazerooni ground-glass score with the nearest CDAI score to HRCT date scan of the first medical evaluation at our institution. In nine patients, we compared the first ground-glass score with a second one after treatment with DMARDs and corticosteroids. Spearman's rank correlation coefficient was used to evaluate association between RA disease activity and the Kazerooni ground-glass and fibrosis scores. Thirty-four patients were included. A positive correlation between CDAI and ground-glass scores was found (rs=0.3767, P<0.028). Fibrosis and CDAI scores were not associated (rs=-0.0747, P<0.6745). After treatment, a downward tendency in the ground-glass score was observed (median [IQR]): (2.33 [2,3] vs. 2 [1.33-2.16]), P<0.056, along with a lesser CDAI score (27 [8-43] vs. 9 [5-12]), P<0.063. There is a correlation between RA disease activity and ground-glass appearance in the HRCT of RA-ILD patients. These results suggest a positive association between RA disease activity and lung inflammation in RA-ILD. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF-α and TGF-β1/ERK1/2 signaling pathways

PubMed Central

Zhang, Changyi; Zhou, Guichi; Chen, Yezeng; Liu, Sizheng; Chen, Fen; Xie, Lichun; Wang, Wei; Zhang, Yonggang; Wang, Tianyou; Lai, Xiulan; Ma, Lian

2018-01-01

Dilated cardiomyopathy (DCM) is a disease of the heart characterized by pathological remodeling, including patchy interstitial fibrosis and degeneration of cardiomyocytes. In the present study, the beneficial role of human umbilical cord-derived mesenchymal stem cells (HuMSCs) derived from Wharton's jelly was evaluated in the myosin-induced rat model of DCM. Male Lewis rats (aged 8-weeks) were injected with porcine myosin to induce DCM. Cultured HuMSCs (1×106 cells/rat) were intravenously injected 28 days after myosin injection and the effects on myocardial fibrosis and the underlying signaling pathways were investigated and compared with vehicle-injected and negative control rats. Myosin injections in rats (vehicle group and experimental group) for 28 days led to severe fibrosis and significant deterioration of cardiac function indicative of DCM. HuMSC treatment reduced fibrosis as determined by Masson's staining of collagen deposits, as well as quantification of molecular markers of myocardial fibrosis such as collagen I/III, profibrotic factors transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and connective tissue growth factor (CTGF). HuMSC treatment restored cardiac function as observed using echocardiography. In addition, western blot analysis indicated that HuMSC injections in DCM rats inhibited the expression of TNF-α, extracellular-signal regulated kinase 1/2 (ERK1/2) and TGF-β1, which is a master switch for inducing myocardial fibrosis. These findings suggested that HuMSC injections attenuated myocardial fibrosis and dysfunction in a rat model of DCM, likely by inhibiting TNF-α and the TGF-β1/ERK1/2 fibrosis pathways. Therefore, HuMSC treatment may represent a potential therapeutic method for treatment of DCM. PMID:29115435

Peptidylarginine deiminase 4 promotes age-related organ fibrosis

PubMed Central

Erpenbeck, Luise; Savchenko, Alexander; Hayashi, Hideki; Cherpokova, Deya; Gallant, Maureen; Mauler, Maximilian; Cifuni, Stephen M.

2017-01-01

Aging promotes inflammation, a process contributing to fibrosis and decline in organ function. The release of neutrophil extracellular traps (NETs [NETosis]), orchestrated by peptidylarginine deiminase 4 (PAD4), damages organs in acute inflammatory models. We determined that NETosis is more prevalent in aged mice and investigated the role of PAD4/NETs in age-related organ fibrosis. Reduction in fibrosis was seen in the hearts and lungs of aged PAD4−/− mice compared with wild-type (WT) mice. An increase in left ventricular interstitial collagen deposition and a decline in systolic and diastolic function were present only in WT mice, and not in PAD4−/− mice. In an experimental model of cardiac fibrosis, cardiac pressure overload induced NETosis and significant platelet recruitment in WT but not PAD4−/− myocardium. DNase 1 was given to assess the effects of extracellular chromatin. PAD4 deficiency or DNase 1 similarly protected hearts from fibrosis. We propose a role for NETs in cardiac fibrosis and conclude that PAD4 regulates age-related organ fibrosis and dysfunction. PMID:28031479

ECG strain pattern in hypertension is associated with myocardial cellular expansion and diffuse interstitial fibrosis: a multi-parametric cardiac magnetic resonance study

PubMed Central

Rodrigues, Jonathan C.L.; Amadu, Antonio Matteo; Ghosh Dastidar, Amardeep; McIntyre, Bethannie; Szantho, Gergley V.; Lyen, Stephen; Godsave, Cattleya; Ratcliffe, Laura E.K.; Burchell, Amy E.; Hart, Emma C.; Hamilton, Mark C.K.; Nightingale, Angus K.; Paton, Julian F.R.; Manghat, Nathan E.; Bucciarelli-Ducci, Chiara

2017-01-01

Aims In hypertension, the presence of left ventricular (LV) strain pattern on 12-lead electrocardiogram (ECG) carries adverse cardiovascular prognosis. The underlying mechanisms are poorly understood. We investigated whether hypertensive ECG strain is associated with myocardial interstitial fibrosis and impaired myocardial strain, assessed by multi-parametric cardiac magnetic resonance (CMR). Methods and results A total of 100 hypertensive patients [50 ± 14 years, male: 58%, office systolic blood pressure (SBP): 170 ± 30 mmHg, office diastolic blood pressure (DBP): 97 ± 14 mmHg) underwent ECG and 1.5T CMR and were compared with 25 normotensive controls (46 ± 14 years, 60% male, SBP: 124 ± 8 mmHg, DBP: 76 ± 7 mmHg). Native T1 and extracellular volume fraction (ECV) were calculated with the modified look-locker inversion-recovery sequence. Myocardial strain values were estimated with voxel-tracking software. ECG strain (n = 20) was associated with significantly higher indexed LV mass (LVM) (119 ± 32 vs. 80 ± 17 g/m2, P < 0.05) and ECV (30 ± 4 vs. 27 ± 3%, P < 0.05) compared with hypertensive subjects without ECG strain (n = 80). ECG strain subjects had significantly impaired circumferential strain compared with hypertensive subjects without ECG strain and controls (−15.2 ± 4.7 vs. −17.0 ± 3.3 vs. −17.3 ± 2.4%, P < 0.05, respectively). In subgroup analysis, comparing ECG strain subjects to hypertensive subjects with elevated LVM but no ECG strain, a significantly higher ECV (30 ± 4 vs. 28 ± 3%, P < 0.05) was still observed. Indexed LVM was the only variable independently associated with ECG strain in multivariate logistic regression analysis [odds ratio (95th confidence interval): 1.07 (1.02–1.12), P < 0.05). Conclusion In hypertension, ECG strain is a marker of advanced LVH associated with increased interstitial fibrosis and associated with significant myocardial circumferential strain impairment. PMID:27334442

ECG strain pattern in hypertension is associated with myocardial cellular expansion and diffuse interstitial fibrosis: a multi-parametric cardiac magnetic resonance study.

PubMed

Rodrigues, Jonathan C L; Amadu, Antonio Matteo; Ghosh Dastidar, Amardeep; McIntyre, Bethannie; Szantho, Gergley V; Lyen, Stephen; Godsave, Cattleya; Ratcliffe, Laura E K; Burchell, Amy E; Hart, Emma C; Hamilton, Mark C K; Nightingale, Angus K; Paton, Julian F R; Manghat, Nathan E; Bucciarelli-Ducci, Chiara

2017-04-01

In hypertension, the presence of left ventricular (LV) strain pattern on 12-lead electrocardiogram (ECG) carries adverse cardiovascular prognosis. The underlying mechanisms are poorly understood. We investigated whether hypertensive ECG strain is associated with myocardial interstitial fibrosis and impaired myocardial strain, assessed by multi-parametric cardiac magnetic resonance (CMR). A total of 100 hypertensive patients [50 ± 14 years, male: 58%, office systolic blood pressure (SBP): 170 ± 30 mmHg, office diastolic blood pressure (DBP): 97 ± 14 mmHg) underwent ECG and 1.5T CMR and were compared with 25 normotensive controls (46 ± 14 years, 60% male, SBP: 124 ± 8 mmHg, DBP: 76 ± 7 mmHg). Native T1 and extracellular volume fraction (ECV) were calculated with the modified look-locker inversion-recovery sequence. Myocardial strain values were estimated with voxel-tracking software. ECG strain (n = 20) was associated with significantly higher indexed LV mass (LVM) (119 ± 32 vs. 80 ± 17 g/m2, P < 0.05) and ECV (30 ± 4 vs. 27 ± 3%, P < 0.05) compared with hypertensive subjects without ECG strain (n = 80). ECG strain subjects had significantly impaired circumferential strain compared with hypertensive subjects without ECG strain and controls (-15.2 ± 4.7 vs. -17.0 ± 3.3 vs. -17.3 ± 2.4%, P < 0.05, respectively). In subgroup analysis, comparing ECG strain subjects to hypertensive subjects with elevated LVM but no ECG strain, a significantly higher ECV (30 ± 4 vs. 28 ± 3%, P < 0.05) was still observed. Indexed LVM was the only variable independently associated with ECG strain in multivariate logistic regression analysis [odds ratio (95th confidence interval): 1.07 (1.02-1.12), P < 0.05). In hypertension, ECG strain is a marker of advanced LVH associated with increased interstitial fibrosis and associated with significant myocardial circumferential strain impairment. © The Author 2016. Published by Oxford University Press on behalf of the European Society

Calcium channel blockers and esophageal sclerosis: should we expect exacerbation of interstitial lung disease?

PubMed

Seretis, Charalampos; Seretis, Fotios; Gemenetzis, George; Liakos, Nikolaos; Pappas, Apostolos; Gourgiotis, Stavros; Lagoudianakis, Emmanuel; Keramidaris, Dimitrios; Salemis, Nikolaos

2012-01-01

Esophageal sclerosis is the most common visceral manifestation of systemic sclerosis, resulting in impaired esophageal clearance and retention of ingested food; in addition, co-existence of lung fibrosis with esophageal scleroderma is not uncommon. Both the progression of generalized connective tissue disorders and the damaging effect of chronic aspiration due to esophageal dysmotility appear to be involved in this procedure of interstitial fibrosis. Nifedipine is a widely prescribed calcium antagonist in a significant percentage of rheumatologic patients suffering from Raynaud syndrome, in order to inhibit peripheral vasospasm. Nevertheless, blocking calcium channels has proven to contribute to exacerbation of gastroesophageal reflux, which consequently can lead to chronic aspiration. We describe the case of severe exacerbation of interstitial lung disease in a 76-year-old female with esophageal sclerosis who was treated with oral nifedipine for Raynaud syndrome.

The Interplay between inflammation and fibrosis in kidney transplantation.

PubMed

Torres, Irina B; Moreso, Francesc; Sarró, Eduard; Meseguer, Anna; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis.

The Interplay between Inflammation and Fibrosis in Kidney Transplantation

PubMed Central

Torres, Irina B.; Moreso, Francesc; Sarró, Eduard; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis. PMID:24991565

Pathogenesis of Idiopathic Pulmonary Fibrosis

PubMed Central

Wolters, Paul J.; Collard, Harold R.; Jones, Kirk D.

2014-01-01

Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated. PMID:24050627

Common threads in cardiac fibrosis, infarct scar formation, and wound healing.

PubMed

Czubryt, Michael P

2012-11-01

Wound healing, cardiac fibrosis, and infarct scar development, while possessing distinct features, share a number of key functional similarities, including extracellular matrix synthesis and remodeling by fibroblasts and myofibroblasts. Understanding the underlying mechanisms that are common to these processes may suggest novel therapeutic approaches for pathologic situations such as fibrosis, or defective wound healing such as hypertrophic scarring or keloid formation. This manuscript will briefly review the major steps of wound healing, and will contrast this process with how cardiac infarct scar formation or interstitial fibrosis occurs. The feasibility of targeting common pro-fibrotic growth factor signaling pathways will be discussed. Finally, the potential exploitation of novel regulators of wound healing and fibrosis (ski and scleraxis), will be examined.

Predicted occultation of Regulus

NASA Astrophysics Data System (ADS)

Waagen, Elizabeth O.

2014-03-01

The predicted occultation of Regulus (alpha Leo) by the magnitude-12.4 V asteroid (163) Erigone on 2014 March 20 at approximately 02:06 a.m. EDT (06:06 UT) is discussed. The occultation track includes Bermuda and northwest along a corridor stretching from the mid-Atlantic USA through Ontario, Canada. Unusual things about this occultation include the facts that the track includes major metropolitan areas such as New York City, and the star being occulted is one of the brightest in the Northern sky and is in a constellation pattern that makes it easy to find. The International Occultation Timing Association (IOTA) website (http://occultations.org/Regulus2014/) has comprehensive information about this predicted occultation and observing and reporting instructions, as well as links to other resources. In addition to witnessing a very rare event (Regulus is the brightest star ever to be predicted to be occulted from the USA), the possibilities for science include these three:! determining the shape of Erigone, detecting a possible companion of Erigone, and detecting the suspected white dwarf companion of Regulus. See the Alert Notice for details.

Fibrosis of the pancreas: the initial tissue damage and the resulting pattern.

PubMed

Klöppel, Günter; Detlefsen, Sönke; Feyerabend, Bernd

2004-07-01

Fibrosis in the pancreas is caused by such processes as necrosis/apoptosis, inflammation or duct obstruction. The initial event that induces fibrogenesis in the pancreas is an injury that may involve the interstitial mesenchymal cells, the duct cells and/or the acinar cells. Damage to any one of these tissue compartments of the pancreas is associated with cytokine-triggered transformation of resident fibroblasts/pancreatic stellate cells into myofibroblasts and the subsequent production and deposition of extracellular matrix. Depending on the site of injury in the pancreas and the involved tissue compartment, predominantly inter(peri)lobular fibrosis (as in alcoholic chronic pancreatitis), periductal fibrosis (as in hereditary pancreatitis), periductal and interlobular fibrosis (as in autoimmune pancreatitis) or diffuse inter- and intralobular fibrosis (as in obstructive chronic pancreatitis) develops.

Deep shadow occulter

NASA Technical Reports Server (NTRS)

Cash, Webster (Inventor)

2010-01-01

Methods and apparatus are disclosed for occulting light. The occulter shape suppresses diffraction at any given size or angle and is practical to build because it can be made binary to avoid scatter. Binary structures may be fully opaque or fully transmitting at specific points. The diffraction suppression is spectrally broad so that it may be used with incoherent white light. An occulter may also include substantially opaque inner portion and an at least partially transparent outer portion. Such occulters may be used on the ground to create a deep shadow in a short distance, or may be used in space to suppress starlight and reveal exoplanets.

Novel therapeutic approaches for pulmonary fibrosis

PubMed Central

Datta, Arnab; Scotton, Chris J; Chambers, Rachel C

2011-01-01

Pulmonary fibrosis represents the end stage of a number of heterogeneous conditions and is, to a greater or lesser degree, the hallmark of the interstitial lung diseases. It is characterized by the excessive deposition of extracellular matrix proteins within the pulmonary interstitium leading to the obliteration of functional alveolar units and in many cases, respiratory failure. While a small number of interstitial lung diseases have known aetiologies, most are idiopathic in nature, and of these, idiopathic pulmonary fibrosis is the most common and carries with it an appalling prognosis – median survival from the time of diagnosis is less than 3 years. This reflects the lack of any effective therapy to modify the course of the disease, which in turn is indicative of our incomplete understanding of the pathogenesis of this condition. Current prevailing hypotheses focus on dysregulated epithelial–mesenchymal interactions promoting a cycle of continued epithelial cell injury and fibroblast activation leading to progressive fibrosis. However, it is likely that multiple abnormalities in a myriad of biological pathways affecting inflammation and wound repair – including matrix regulation, epithelial reconstitution, the coagulation cascade, neovascularization and antioxidant pathways – modulate this defective crosstalk and promote fibrogenesis. This review aims to offer a pathogenetic rationale behind current therapies, briefly outlining previous and ongoing clinical trials, but will focus on recent and exciting advancements in our understanding of the pathogenesis of idiopathic pulmonary fibrosis, which may ultimately lead to the development of novel and effective therapeutic interventions for this devastating condition. LINKED ARTICLES This article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-1 PMID:21265830

Guidelines for the medical treatment of idiopathic pulmonary fibrosis.

PubMed

Xaubet, Antoni; Molina-Molina, María; Acosta, Orlando; Bollo, Elena; Castillo, Diego; Fernández-Fabrellas, Estrella; Rodríguez-Portal, José Antonio; Valenzuela, Claudia; Ancochea, Julio

2017-05-01

Idiopathic pulmonary fibrosis is defined as chronic fibrosing interstitial pneumonia limited to the lung, with poor prognosis. The incidence has been rising in recent years probably due to improved diagnostic methods and increased life expectancy. In 2013, the SEPAR guidelines for the diagnosis and treatment for idiopathic pulmonary fibrosis were published. Since then, clinical trials and meta-analyses have shown strong scientific evidence for the use of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis. In 2015, the international consensus of 2011 was updated and new therapeutic recommendations were established, prompting us to update our recommendation for the medical treatment of idiopathic pulmonary fibrosis accordingly. Diagnostic aspects and non-pharmacological treatment will not be discussed as no relevant developments have emerged since the 2013 guidelines. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Idiopathic Pulmonary Fibrosis: Diagnosis and Clinical Manifestations

PubMed Central

Nakamura, Yutaro; Suda, Takafumi

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is a parenchymal lung disease characterized by progressive interstitial fibrosis. The clinical course of IPF can be unpredictable and may be punctuated by acute exacerbations. Although much progress is being made in unraveling the mechanisms underlying IPF, effective therapy for improving survival remains elusive. Longitudinal disease profiling, especially in terms of clinical manifestations in a large cohort of patients, should lead to proper management of the patients and development of new treatments for IPF. Appropriate multidisciplinary assessment in ongoing registries is required to achieve this. This review summarizes the current status of the diagnosis and clinical manifestations of IPF. PMID:27625576

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials.

PubMed

Saketkoo, Lesley Ann; Mittoo, Shikha; Huscher, Dörte; Khanna, Dinesh; Dellaripa, Paul F; Distler, Oliver; Flaherty, Kevin R; Frankel, Sid; Oddis, Chester V; Denton, Christopher P; Fischer, Aryeh; Kowal-Bielecka, Otylia M; LeSage, Daphne; Merkel, Peter A; Phillips, Kristine; Pittrow, David; Swigris, Jeffrey; Antoniou, Katerina; Baughman, Robert P; Castelino, Flavia V; Christmann, Romy B; Christopher-Stine, Lisa; Collard, Harold R; Cottin, Vincent; Danoff, Sonye; Highland, Kristin B; Hummers, Laura; Shah, Ami A; Kim, Dong Soon; Lynch, David A; Miller, Frederick W; Proudman, Susanna M; Richeldi, Luca; Ryu, Jay H; Sandorfi, Nora; Sarver, Catherine; Wells, Athol U; Strand, Vibeke; Matteson, Eric L; Brown, Kevin K; Seibold, James R

2014-05-01

Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.

Usual interstitial pneumonia: typical, possible, and “inconsistent” patterns

PubMed Central

Torres, Pedro Paulo Teixeira e Silva; Rabahi, Marcelo Fouad; Moreira, Maria Auxiliadora Carmo; Meirelles, Gustavo de Souza Portes; Marchiori, Edson

2017-01-01

ABSTRACT Idiopathic pulmonary fibrosis is a severe and progressive chronic fibrosing interstitial lung disease, a definitive diagnosis being established by specific combinations of clinical, radiological, and pathological findings. According to current international guidelines, HRCT plays a key role in establishing a diagnosis of usual interstitial pneumonia (UIP). Current guidelines describe three UIP patterns based on HRCT findings: a typical UIP pattern; a pattern designated “possible UIP”; and a pattern designated “inconsistent with UIP”, each pattern having important diagnostic implications. A typical UIP pattern on HRCT is highly accurate for the presence of histopathological UIP, being currently considered to be diagnostic of UIP. The remaining patterns require further diagnostic investigation. Other known causes of a UIP pattern include drug-induced interstitial lung disease, chronic hypersensitivity pneumonitis, occupational diseases (e.g., asbestosis), and connective tissue diseases, all of which should be included in the clinical differential diagnosis. Given the importance of CT studies in establishing a diagnosis and the possibility of interobserver variability, the objective of this pictorial essay was to illustrate all three UIP patterns on HRCT. PMID:29160385

Overexpression of SerpinE2/protease nexin-1 Contribute to Pathological Cardiac Fibrosis via increasing Collagen Deposition

PubMed Central

Li, Xuelian; Zhao, Dandan; Guo, Zhenfeng; Li, Tianshi; Qili, Muge; Xu, Bozhi; Qian, Ming; Liang, Haihai; E, Xiaoqiang; Chege Gitau, Samuel; Wang, Lu; Huangfu, Longtao; Wu, Qiuxia; Xu, Chaoqian; Shan, Hongli

2016-01-01

Although increases in cardiovascular load (pressure overload) are known to elicit ventricular remodeling including cardiomyocyte hypertrophy and interstitial fibrosis, the molecular mechanisms of pressure overload or AngII -induced cardiac interstitial fibrosis remain elusive. In this study, serpinE2/protease nexin-1 was over-expressed in a cardiac fibrosis model induced by pressure-overloaded via transverse aortic constriction (TAC) in mouse. Knockdown of serpinE2 attenuates cardiac fibrosis in a mouse model of TAC. At meantime, the results showed that serpinE2 significantly were increased with collagen accumulations induced by AngII or TGF-β stimulation in vitro. Intriguingly, extracellular collagen in myocardial fibroblast was reduced by knockdown of serpinE2 compared with the control in vitro. In stark contrast, the addition of exogenous PN-1 up-regulated the content of collagen in myocardial fibroblast. The MEK1/2- ERK1/2 signaling probably promoted the expression of serpinE2 via transcription factors Elk1 in myocardial fibroblast. In conclusion, stress-induced the ERK1/2 signaling pathway activation up-regulated serpinE2 expression, consequently led accumulation of collagen protein, and contributed to cardiac fibrosis. PMID:27876880

Halofuginone reduces the occurrence of renal fibrosis in 5/6 nephrectomized rats.

PubMed

Benchetrit, Sydney; Yarkoni, Shy; Rathaus, Mauro; Pines, Marc; Rashid, Gloria; Bernheim, Joelle; Bernheim, Jacques

2007-01-01

Halofuginone is a novel antifibrotic agent that can reverse the fibrotic process by specific inhibition of collagen type I synthesis. To evaluate the effect of Halo on the development of glomerulosclerosis and interstitial fibrosis in the 5/6 nephrectomy rat model Male Wistar rats were assigned to undergo 5/6 NX or sham operation, and then divided into three groups: 5/6 NX rats (NX-Halo and NX-Control) and sham. Systolic blood pressure, proteinuria and body weight were determined every 2 weeks. At sacrifice (10 weeks) creatinine clearance was evaluated and remnant kidneys removed for histologic examination, sirius red staining and in situ hybridization Systolic blood pressure increased progressively in both 5/6 NX groups. Halo slowed the increase in proteinuria in 5/6 NX rats. As expected, creatinine clearance was lower in 5/6 NX groups when compared to sham rats. Creatinine clearance was significantly higher in the NX-Halo group at the end of the study period. Histologic examination by light microscopy showed significantly less severe interstitial fibrosis and glomerulosclerosis in Halo-treated rats. The increase in collagen alpha1 (I) gene expression and collagen staining after nephrectomy was almost completely abolished by Halo. Halofuginone reduced proteinuria as well as the severity of interstitial fibrosis and glomerulosclerosis in 5/6 NX rats. The renal beneficial effect of Halo was also demonstrated by the blunted decrease in creatinine clearance observed in the treated animals.

Accumulation of BDCA1⁺ dendritic cells in interstitial fibrotic lung diseases and Th2-high asthma.

PubMed

Greer, Alexandra M; Matthay, Michael A; Kukreja, Jasleen; Bhakta, Nirav R; Nguyen, Christine P; Wolters, Paul J; Woodruff, Prescott G; Fahy, John V; Shin, Jeoung-Sook

2014-01-01

Dendritic cells (DCs) significantly contribute to the pathology of several mouse lung disease models. However, little is known of the contribution of DCs to human lung diseases. In this study, we examined infiltration with BDCA1⁺ DCs of human lungs in patients with interstitial lung diseases or asthma. Using flow cytometry, we found that these DCs increased by 5∼6 fold in the lungs of patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis, which are both characterized by extensive fibrosis in parenchyma. The same DC subset also significantly increased in the lung parenchyma of patients with chronic obstructive pulmonary disease, although the degree of increase was relatively modest. By employing immunofluorescence microscopy using FcεRI and MHCII as the specific markers for BDCA1⁺ DCs, we found that the numbers of BDCA1⁺ DCs also significantly increased in the airway epithelium of Th2 inflammation-associated asthma. These findings suggest a potential contribution of BDCA1⁺ DCs in human lung diseases associated with interstitial fibrosis or Th2 airway inflammation.

Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities.

PubMed

Ho, Jennifer E; Gao, Wei; Levy, Daniel; Santhanakrishnan, Rajalakshmi; Araki, Tetsuro; Rosas, Ivan O; Hatabu, Hiroto; Latourelle, Jeanne C; Nishino, Mizuki; Dupuis, Josée; Washko, George R; O'Connor, George T; Hunninghake, Gary M

2016-07-01

Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis. We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis. We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54% women; 14% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography. Higher Gal-3 concentrations were associated with lower lung volumes (1.4% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95% confidence interval [CI], 0.8-2.0%; P < 0.001; 1.2% decrease in percentage of predicted FVC; 95% CI, 0.6-1.8%; P < 0.001) and decreased diffusing capacity of the lung for carbon monoxide (2.1% decrease; 95% CI, 1.3-2.9%; P < 0.001). These associations remained significant after multivariable adjustment (P ≤ 0.008 for all). Compared with the lowest quartile, participants in the highest Gal-3 quartile were more than twice as likely to have interstitial lung abnormalities visualized by computed tomography (multivariable-adjusted odds ratio, 2.67; 95% CI, 1.49-4.76; P < 0.001). Elevated Gal-3 concentrations are associated with interstitial lung abnormalities coupled with a restrictive pattern, including decreased lung volumes and altered gas exchange. These findings suggest a potential role for Gal-3 in early stages of pulmonary fibrosis.

Mineralogic correlates of fibrosis in chrysotile miners and millers

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

Churg, A.; Wright, J.L.; DePaoli, L.

1989-04-01

To determine which mineral parameters relate to the degree of interstitial fibrosis (asbestosis) in the lungs of chrysotile miners and millers, we graded fibrosis histologically and correlated fibrosis grades with fiber concentration and mean size, surface area, and mass, and with total sample fiber length, surface area, and mass in 21 cases. A positive correlation of fibrosis grade with tremolite concentration and a lesser correlation with chrysotile concentration was found for whole lungs, specific sites within lungs, and, for tremolite, single microscopic fields. No correlations were found for measures of chrysotile fiber size, surface area, or mass, but tremolite meanmore » fiber length, aspect ratio, and surface area were, surprisingly, negatively correlated with fibrosis grade. Measures based on total rather than on mean case or site parameters failed to show correlations with fibrosis. We conclude that: (1) degree of pulmonary fibrosis reflects fiber concentration at both a bulk and a microscopic level; (2) mean fiber length and parameters related to mean fiber length also correlate with fibrosis grade, but, contrary to predictions from animal studies, this correlation is negative, suggesting that short fibers may be more important in the genesis of pulmonary fibrosis than is commonly believed; (3) there is no evidence that parameters such as total fiber length, surface area, or mass provide predictors of degree of fibrosis.« less

Comparative study of two models of combined pulmonary fibrosis and emphysema in mice.

PubMed

Zhang, Wan-Guang; Wu, Si-Si; He, Li; Yang, Qun; Feng, Yi-Kuan; Chen, Yue-Tao; Zhen, Guo-Hua; Xu, Yong-Jian; Zhang, Zhen-Xiang; Zhao, Jian-Ping; Zhang, Hui-Lan

2017-04-01

Combined pulmonary fibrosis and emphysema (CPFE) is an "umbrella term" encompassing emphysema and pulmonary fibrosis, but its pathogenesis is not known. We established two models of CPFE in mice using tracheal instillation with bleomycin (BLM) or murine gammaherpesvirus 68 (MHV-68). Experimental mice were divided randomly into four groups: A (normal control, n=6), B (emphysema, n=6), C (emphysema+MHV-68, n=24), D (emphysema+BLM, n=6). Group C was subdivided into four groups: C1 (sacrificed on day 367, 7 days after tracheal instillation of MHV-68); C2 (day 374; 14days); C3 (day 381; 21days); C4 (day 388; 28days). Conspicuous emphysema and interstitial fibrosis were observed in BLM and MHV-68 CPFE mouse models. However, BLM induced diffuse pulmonary interstitial fibrosis with severely diffuse pulmonary inflammation; MHV-68 induced relatively modest inflammation and fibrosis, and the inflammation and fibrosis were not diffuse, but instead around bronchioles. Inflammation and fibrosis were detectable in the day-7 subgroup and reached a peak in the day-28 subgroup in the emphysema + MHV-68 group. Levels of macrophage chemoattractant protein-1, macrophage inflammatory protein-1α, interleukin-13, and transforming growth factor-β1 in bronchoalveolar lavage fluid were increased significantly in both models. Percentage of apoptotic type-2 lung epithelial cells was significantly higher; however, all four types of cytokine and number of macrophages were significantly lower in the emphysema+MHV-68 group compared with the emphysema +BLM group. The different changes in pathology between BLM and MHV-68 mice models demonstrated different pathology subtypes of CPFE: macrophage infiltration and apoptosis of type-II lung epithelial cells increased with increasing pathology score for pulmonary fibrosis. Copyright © 2017 Elsevier GmbH. All rights reserved.

Interstitial inflammation in Alport syndrome.

PubMed

Jedlicka, Jan; Soleiman, Afschin; Draganovici, Dan; Mandelbaum, Jana; Ziegler, Urs; Regele, Heinz; Wüthrich, Rudolf P; Gross, Oliver; Anders, Hans-Joachim; Segerer, Stephan

2010-04-01

The Alport syndrome is a hereditary glomerular disease linked to structural abnormalities of collagen IV. In a mouse model of Alport syndrome, the interstitial lymphocyte influx was important for disease progression. CXCR3 is a chemokine receptor involved in lymphocyte recruitment to the kidney. We hypothesized that CXCR3-positive T cells might be involved in human Alport syndrome. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded biopsies from 17 patients with Alport syndrome, 10 with immunoglobulin A (IgA) nephropathy, and 11 healthy donor kidneys. We investigated the expression of the alpha5 chain of collagen IV to confirm the morphologic diagnosis, the chemokine receptor CXCR3 and CD3-positive T cells. Alport syndrome biopsies demonstrated a complete loss of the alpha5 chain of collagen IV from the glomerular basement membrane and the morphologic features consistent with Alport syndrome on electron microscopy. A prominent number of CXCR3-positive cells were found in the tubulointerstitium. Most of the CXCR3-positive cells were CD3-positive T cells, demonstrated by double-labeling in selected biopsies. The number of CXCR3-positive cells in kidneys with Alport syndrome correlated with serum creatinine (P < .05) and with morphologic features of a progressive disease (eg, interstitial fibrosis, glomerulosclerosis, and tubular atrophy). The severity of interstitial CXCR3-positive cell influx was similar in Alport syndrome as compared to immunoglobulin A nephropathy. The noninflammatory glomerular lesion of Alport syndrome is associated with prominent interstitial accumulation of CD3- and CXCR3-positive lymphocytes. The degree of infiltration correlated with renal function. We speculate that targeting T lymphocytes, for example, by CXCR3 blocking agents, might be a novel approach to inhibit disease progression in patients with Alport syndrome. Copyright 2010 Elsevier Inc.

020. Coexistence of lung adenocarcinoma and usual interstitial pneumonia: a case report

PubMed Central

Baliaka, Aggeliki; Papaemmanouil, Styliani; Spyratos, Dionysis; Zarogoulidis, Paul; Sakkas, Leonidas

2015-01-01

Background Usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause. The most common symptoms are progressively increased shortness of breath and dry cough. Some studies suggest an association between usual interstitial pneumonia and lung cancer through different pathogenetic mechanisms. Objective The case presentation of a patient with lung adenocarcinoma and UIP. Methods A 66-year-old male presented with persistent dry cough, hemoptysis and dyspnea. The chest radiographs revealed a mass in the lower lobe of the left lung, measuring 3 cm, as well as diffuse interstitial changes in the same lobe. Two partial lobectomies were performed. Results Histological examination of the mass showed moderately differentiated adenocarcinoma, focally with bronchoalveolar pattern (Immunohistochemical detection of EGFR: positive). The rest lung parenchyma presented histological appearance of UIP. Conclusions According to clinicopathological studies, the prevalence of lung cancer among patients with UIP/IPF varies between 4% and 9%. The overall median survival of IPF-Ca patients is seven months in comparison with IPF only patients (14 months).

Inflammation and Fibrosis in Polycystic Kidney Disease.

PubMed

Song, Cheng Jack; Zimmerman, Kurt A; Henke, Scott J; Yoder, Bradley K

Polycystic kidney disease (PKD) is a commonly inherited disorder characterized by cyst formation and fibrosis (Wilson, N Engl J Med 350:151-164, 2004) and is caused by mutations in cilia or cilia-related proteins, such as polycystin 1 or 2 (Oh and Katsanis, Development 139:443-448, 2012; Kotsis et al., Nephrol Dial Transplant 28:518-526, 2013). A major pathological feature of PKD is the development of interstitial inflammation and fibrosis with an associated accumulation of inflammatory cells (Grantham, N Engl J Med 359:1477-1485, 2008; Zeier et al., Kidney Int 42:1259-1265, 1992; Ibrahim, Sci World J 7:1757-1767, 2007). It is unclear whether inflammation is a driving force for cyst formation or a consequence of the pathology (Ta et al., Nephrology 18:317-330, 2013) as in some murine models cysts are present prior to the increase in inflammatory cells (Phillips et al., Kidney Blood Press Res 30:129-144, 2007; Takahashi et al., J Am Soc Nephrol JASN 1:980-989, 1991), while in other models the increase in inflammatory cells is present prior to or coincident with cyst initiation (Cowley et al., Kidney Int 43:522-534, 1993, Kidney Int 60:2087-2096, 2001). Additional support for inflammation as an important contributor to cystic kidney disease is the increased expression of many pro-inflammatory cytokines in murine models and human patients with cystic kidney disease (Karihaloo et al., J Am Soc Nephrol JASN 22:1809-1814, 2011; Swenson-Fields et al., Kidney Int, 2013; Li et al., Nat Med 14:863-868, 2008a). Based on these data, an emerging model in the field is that disruption of primary cilia on tubule epithelial cells leads to abnormal cytokine cross talk between the epithelium and the inflammatory cells contributing to cyst growth and fibrosis (Ta et al., Nephrology 18:317-330, 2013). These cytokines are produced by interstitial fibroblasts, inflammatory cells, and tubule epithelial cells and activate multiple pathways including the JAK-STAT and NF-κB signaling (Qin

Uranus occults SAO158687. [stellar occultation and planetary parametric observation

NASA Technical Reports Server (NTRS)

Elliot, J. L.; Veverka, J.; Millis, R. L.

1977-01-01

Experience gained in obtaining atmospheric parameters, oblatenesses, and diameters of Jupiter and Mars from recent stellar occultations by these planets is used to predict what can be learned from the March 1977 occultation of the star SAO158687 by Uranus. The spectra of this star and Uranus are compared to indicate the relative instrument intensities of the two objects, the four passbands where the relative intensities are most nearly equal are listed, and expected photon fluxes from the star are computed on the assumption that it has UBVRI colors appropriate for a K5 main-sequence object. It is shown that low photon noise errors can be achieved by choosing appropriate passbands for observation, and the rms error expected for the Uranus temperature profiles obtained from the occultation light curves is calculated. It is suggested that observers of this occultation should record their data digitally for optimum time resolution.

The Occult Today: Why?

ERIC Educational Resources Information Center

Kessler, Gary E.

1975-01-01

Author offered some reflections on the "why" of the contemporary interest in the occult. He attempted to convince the reader that, if he or she has been surprised by the recent rise of occultism, sober reflection will dispell some fears and, perhaps, even convince him or her that occultism is not merely superstition. (Author/RK)

Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias.

PubMed

Barisione, Giovanni; Brusasco, Claudia; Garlaschi, Alessandro; Baroffio, Michele; Brusasco, Vito

2016-05-01

Lung diffusing capacity for carbon monoxide (DLCO) is decreased in both usual interstitial pneumonia-idiopathic pulmonary fibrosis (UIP-IPF) and nonspecific interstitial pneumonia (NSIP), but is moderately related to computed tomography (CT)-determined fibrotic changes. This may be due to the relative insensitivity of DLCO to changes in alveolar membrane diffusive conductance (DMCO). The purpose of this study was to determine whether measurement of lung diffusing capacity for nitric oxide (DLNO) better reflects fibrotic changes than DLCO DLNO-DLCO were measured simultaneously in 30 patients with UIP-IPF and 30 with NSIP. Eighty-one matched healthy subjects served as a control group. The amount of pulmonary fibrosis was estimated by CT volumetric analysis of visually bounded areas showing reticular opacities and honeycombing. DMCO and pulmonary capillary volume (VC) were calculated. DLNO was below the lower limit of normal in all patients irrespective of extent and nature of disease, whereas DLCO was within the normal range in a nonnegligible number of patients. Both DLNO and DLCO were significantly correlated with visual assessment of fibrosis but DLNO more closely than DLCO DMCO was also below the lower limit of normal in all UIP-IPF and NSIP patients and significantly correlated with fibrosis extent in both diseases, whereas VC was weakly correlated with fibrosis in UIP-IPF and uncorrelated in NSIP, with normal values in half of patients. In conclusion, measurement of DLNO may provide a more sensitive evaluation of fibrotic changes than DLCO in either UIP-IPF or NSIP, because it better reflects DMCO. Copyright © 2016 the American Physiological Society.

Pulmonary fibrosis and exposure to steel welding fume.

PubMed

Cosgrove, M P

2015-12-01

Arc welders who have been exposed to high concentrations of steel welding fume for prolonged periods of time may develop pulmonary fibrosis but the nature of the fibrotic changes has been debated over the last 80 years without any clear international consensus. To characterize the nature of the pulmonary fibrosis that develops in response to steel welding fume exposure and to provide a working hypothesis that would explain the findings of the existing research, to provide a platform for future research and to inform future occupational and clinical management of welders with pulmonary effects from welding fume. Review of the world literature on pulmonary fibrosis and welding of steel in all languages using PubMed, with further secondary search of references in the articles found in the primary search. Google and Reference Manager were used as further confirmatory search tools. Only case series and case reports were found but these provided consistent evidence that the consequence of exposure to steel welding fume at high levels for a prolonged period of time is a type of pulmonary fibrosis similar to, and possibly the same as, respiratory bronchiolitis which eventually develops into desquamative interstitial pneumonia with ongoing exposure. Steel welding fume may cause an occupational respiratory bronchiolitis which may develop into de squamative interstitial pneumonia with ongoing exposure. This concept may explain the difficulties in interpreting the wider literature on welding fume and lung function at lower exposures and may also explain the increased risk of lung cancer in welders. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Computed tomography findings in liver fibrosis and cirrhosis.

PubMed

Huber, A; Ebner, L; Montani, M; Semmo, N; Roy Choudhury, K; Heverhagen, J; Christe, A

2014-02-19

Computed tomography (CT) is inferior to the fibroscan and laboratory testing in the noninvasive diagnosis of liver fibrosis. On the other hand, CT is a frequently used diagnostic tool in modern medicine. The auxiliary finding of clinically occult liver fibrosis in CT scans could result in an earlier diagnosis. The aim of this study was to analyse quantifiable direct signs of liver remodelling in CT scans to depict liver fibrosis in a precirrhotic stage. Retrospective review of 148 abdominal CT scans (80 liver cirrhosis, 35 precirrhotic fibrosis and 33 control patients). Fibrosis and cirrhosis were histologically proven. The diameters of the three main hepatic veins were measured 1-2 cm before their aperture into the inferior caval vein. The width of the caudate and the right hepatic lobe were divided, and measured horizontally at the level of the first bifurcation of the right portal vein in axial planes (caudate-right-lobe ratio). A combination of both (sum of liver vein diameters divided by the caudate-right lobe ratio) was defined as the ld/crl ratio. These metrics were analysed for the detection of liver fibrosis and cirrhosis. An ld/crl-r <24 showed a sensitivity of 83% and a specificity of 76% for precirrhotic liver fibrosis. Liver cirrhosis could be detected with a sensitivity of 88% and a specificity of 82% if ld/crl-r <20. An ld/crl-r <24 justifies laboratory testing and a fibroscan. This could bring forward the diagnosis and patients would profit from early treatment in a potentially reversible stage of disease.

Update on diagnosis and treatment of idiopathic pulmonary fibrosis

PubMed Central

Baddini-Martinez, José; Baldi, Bruno Guedes; da Costa, Cláudia Henrique; Jezler, Sérgio; Lima, Mariana Silva; Rufino, Rogério

2015-01-01

Idiopathic pulmonary fibrosis is a type of chronic fibrosing interstitial pneumonia, of unknown etiology, which is associated with a progressive decrease in pulmonary function and with high mortality rates. Interest in and knowledge of this disorder have grown substantially in recent years. In this review article, we broadly discuss distinct aspects related to the diagnosis and treatment of idiopathic pulmonary fibrosis. We list the current diagnostic criteria and describe the therapeutic approaches currently available, symptomatic treatments, the action of new drugs that are effective in slowing the decline in pulmonary function, and indications for lung transplantation. PMID:26578138

Time course of polyhexamethyleneguanidine phosphate-induced lung inflammation and fibrosis in mice.

PubMed

Song, Jeongah; Kim, Woojin; Kim, Yong-Bum; Kim, Bumseok; Lee, Kyuhong

2018-04-15

Pulmonary fibrosis is a chronic progressive disease with unknown etiology and has poor prognosis. Polyhexamethyleneguanidine phosphate (PHMG-P) causes acute interstitial pneumonia and pulmonary fibrosis in humans when it exposed to the lung. In a previous study, when rats were exposed to PHMG-P through inhalation for 3 weeks, lung inflammation and fibrosis was observed even after 3 weeks of recovery. In this study, we aimed to determine the time course of PHMG-P-induced lung inflammation and fibrosis. We compared pathological action of PHMG-P with that of bleomycin (BLM) and investigated the mechanism underlying PHMG-P-induced lung inflammation and fibrosis. PHMG-P (0.9 mg/kg) or BLM (1.5 mg/kg) was intratracheally administered to mice. At weeks 1, 2, 4 and 10 after instillation, the levels of inflammatory and fibrotic markers and the expression of inflammasome proteins were measured. The inflammatory and fibrotic responses were upregulated until 10 and 4 weeks in the PHMG-P and BLM groups, respectively. Immune cell infiltration and considerable collagen deposition in the peribronchiolar and interstitial areas of the lungs, fibroblast proliferation, and hyperplasia of type II epithelial cells were observed. NALP3 inflammasome activation was detected in the PHMG-P group until 4 weeks, which is suspected to be the main reason for the persistent inflammatory response and exacerbation of fibrotic changes. Most importantly, the pathological changes in the PHMG-P group were similar to those observed in humidifier disinfectant-associated patients. A single exposure of PHMG-P led to persistent pulmonary inflammation and fibrosis for at least 10 weeks. Copyright © 2018. Published by Elsevier Inc.

Studies in occultation astronomy

NASA Technical Reports Server (NTRS)

Veverka, J.

1980-01-01

Major scientific results are summarized for the following studies: (1) observations of the 8 April 1976 occultation of epsilon Geminorum by Mars; (2) studies in occultation techniques; and (3) the March 1974 occultation of Saturn by the Moon. A re-analysis of the 1974 lunar occultation of the Titan indicates that Titan is strongly limb darkened, with D approximately greater than 5800km; there is internal evidence in the data that Titan's atmosphere is inhomogeneous; and that observations are inconsistent with any sample homogeneous model atmosphere which matches the P (lambda) and Beta (lambda) observations of Titan.

Predicting survival across chronic interstitial lung disease: the ILD-GAP model.

PubMed

Ryerson, Christopher J; Vittinghoff, Eric; Ley, Brett; Lee, Joyce S; Mooney, Joshua J; Jones, Kirk D; Elicker, Brett M; Wolters, Paul J; Koth, Laura L; King, Talmadge E; Collard, Harold R

2014-04-01

Risk prediction is challenging in chronic interstitial lung disease (ILD) because of heterogeneity in disease-specific and patient-specific variables. Our objective was to determine whether mortality is accurately predicted in patients with chronic ILD using the GAP model, a clinical prediction model based on sex, age, and lung physiology, that was previously validated in patients with idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis (n=307), chronic hypersensitivity pneumonitis (n=206), connective tissue disease-associated ILD (n=281), idiopathic nonspecific interstitial pneumonia (n=45), or unclassifiable ILD (n=173) were selected from an ongoing database (N=1,012). Performance of the previously validated GAP model was compared with novel prediction models in each ILD subtype and the combined cohort. Patients with follow-up pulmonary function data were used for longitudinal model validation. The GAP model had good performance in all ILD subtypes (c-index, 74.6 in the combined cohort), which was maintained at all stages of disease severity and during follow-up evaluation. The GAP model had similar performance compared with alternative prediction models. A modified ILD-GAP Index was developed for application across all ILD subtypes to provide disease-specific survival estimates using a single risk prediction model. This was done by adding a disease subtype variable that accounted for better adjusted survival in connective tissue disease-associated ILD, chronic hypersensitivity pneumonitis, and idiopathic nonspecific interstitial pneumonia. The GAP model accurately predicts risk of death in chronic ILD. The ILD-GAP model accurately predicts mortality in major chronic ILD subtypes and at all stages of disease.

Occultation studies of the Solar System

NASA Technical Reports Server (NTRS)

Millis, Robert L.

1987-01-01

The planetary occultation program began at Lowell Observatory in 1973 with a worldwide campaign to observe mutual occultations and eclipses of the Galilean Satellites. Then the temperature profile of the Martian atmosphere was measured from data taken during the occultation of epsilon Geminorum, the Rings of Uranus were discovered as they occulted SAO 158687, and the dimensions of Pallas were measured when that minor planet occulted SAO 85009. In 1979 the present grant was initiated, providing funds for portable photometric instrumentation used to observe occultations by asteroids as well as by Uranus and Neptune. Software for predicting occultations of catalog stars by asteroids, planets, and comets was written in 1983. Lowell currently provides most of the available predictions for asteroid occultations. Realizing in 1983 that the lack of a high-quality astrometric telescope dedicated to occultation work was limiting progress, an 18-inch, F/8 lens was acquired and adapted to an existing mounting at Lowell. Although acquisition of the lens and implementation of the new telescope has been accomplished primarily with non-grant funds, the instrument makes a major contribution to occultation research.

New Occultation Systems and the 2005 July 11 Charon Occultation

NASA Astrophysics Data System (ADS)

Young, L. A.; French, R. G.; Gregory, B.; Olkin, C. B.; Ruhland, C.; Shoemaker, K.; Young, E. F.

2005-08-01

Charon's density is an important input to models of its formation and internal structure. Estimates range from 1.59 to 1.83 g/cm3 (Olkin et al. 2003. Icarus 164, 254), with Charon's radius as the main source of uncertainty. Reported values of Charon's radius from mutual events range from 593±13 (Buie et al. 1992, Icarus 97, 211) to 621±21 km (Young & Binzel 1994, Icarus 108), while an occultation observed from a single site gives a lower limit on the radius of 601.5 km (Walker 1980 MNRAS 192, 47; Elliot & Young 1991, Icarus 89, 244). On 2005 July 11 UT (following this abstract submission date), Charon is predicted to occult the star C313.2. If successful, this event will be the first Charon occultation observed since 1980, and the first giving multiple chords across Charon's disk. This event is expected to measure Charon's radius to 1 km. Our team is observing from three telescopes in Chile, the 4.0-m Blanco and the 0.9-m telescopes at Cerro Tololo and the 4.2-m SOAR telescope at Cerro Pachon. At SOAR, we will be using the camera from our new PHOT systems (Portable High-speed Occultation Telescopes). The PHOT camera is a Princeton Instrument MicroMAX:512BFT from Roper Scientific, a 512×512 frame-transfer CCD with a readnoise of only 3 electrons at the 100 kHz digitization rate. The camera's exposures are triggered by a custom built, compact, stand-alone GPS-based pulse-train generator. A PHOT camera and pulse-train generator were used to observe the occultation of 2MASS 1275723153 by Pluto on 2005 June 15 UT from Sommers-Bausch Observatory in Boulder Colorado; preliminary analysis shows this was at best a grazing occultation from this site and a successful engineering run for the July 11 Charon occultation. The work was supported, in part, by NSF AST-0321338 (EFY) and NASA NNG-05GF05G (LAY).

IDENTIFICATION AND CHARACTERIZATION OF AN IDIOPATHIC PULMONARY FIBROSIS-LIKE CONDITION IN CATS

EPA Science Inventory

Interstitial lung diseases are a heterogeneous group of disorders due to a variety of causes. In veterinary medicine, those with a prominent fibrotic component of unknown etiology are often called idiopathic pulmonary fibrosis (IPF). In human medicine, this term is reserved for ...

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

PubMed Central

Saketkoo, Lesley Ann; Mittoo, Shikha; Huscher, Dörte; Khanna, Dinesh; Dellaripa, Paul F; Distler, Oliver; Flaherty, Kevin R; Frankel, Sid; Oddis, Chester V; Denton, Christopher P; Fischer, Aryeh; Kowal-Bielecka, Otylia M; LeSage, Daphne; Merkel, Peter A; Phillips, Kristine; Pittrow, David; Swigris, Jeffrey; Antoniou, Katerina; Baughman, Robert P; Castelino, Flavia V; Christmann, Romy B; Christopher-Stine, Lisa; Collard, Harold R; Cottin, Vincent; Danoff, Sonye; Highland, Kristin B; Hummers, Laura; Shah, Ami A; Kim, Dong Soon; Lynch, David A; Miller, Frederick W; Proudman, Susanna M; Richeldi, Luca; Ryu, Jay H; Sandorfi, Nora; Sarver, Catherine; Wells, Athol U; Strand, Vibeke; Matteson, Eric L; Brown, Kevin K; Seibold, James R

2014-01-01

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field. PMID:24368713

The Pinhole/Occulter Facility

NASA Technical Reports Server (NTRS)

Tandberg-Hanssen, E. A. (Editor); Hudson, H. S. (Editor); Dabbs, J. R. (Editor); Baity, W. A. (Editor)

1983-01-01

Scientific objectives and requirements are discussed for solar X-ray observations, coronagraph observations, studies of coronal particle acceleration, and cosmic X-ray observations. Improved sensitivity and resolution can be provided for these studies using the pinhole/occulter facility which consists of a self-deployed boom of 50 m length separating an occulter plane from a detector plane. The X-ray detectors and coronagraphic optics mounted on the detector plane are analogous to the focal plane instrumentation of an ordinary telescope except that they use the occulter only for providing a shadow pattern. The occulter plane is passive and has no electrical interface with the rest of the facility.

Mefunidone Attenuates Tubulointerstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction

PubMed Central

Liu, Chunyan; Mei, Wenjuan; Tang, Juan; Yuan, Qiongjing; Huang, Ling; Lu, Miaomiao; Wu, Lin; Peng, Zhangzhe; Meng, Jie; Yang, Huixiang; Shen, Hong; Lv, Ben; Hu, Gaoyun; Tao, Lijian

2015-01-01

Background Inflammation has a crucial role in renal interstitial fibrosis, which is the common pathway of chronic kidney diseases. Mefunidone (MFD) is a new compound which could effectively inhibit the proliferation of renal fibroblasts in vitro. However, the overall effect of Mefunidone in renal fibrosis remains unknown. Methods Sprague-Dawley rats were randomly divided intro 6 groups: sham operation, unilateral ureteral obstruction (UUO), UUO/Mefunidone (25, 50, 100mg/kg/day) and UUO/PFD (500mg/kg/day). The rats were sacrificed respectively on days 3, 7, and 14 after the operation. Tubulointerstitial injury index, interstitial collagen deposition, expression of fibronectin (FN), α-smooth muscle actin (α-SMA), type I and III collagen and the number of CD3+ and CD68+ cells were determined. The expressions of proinflammatory cytokines, p-ERK, p-IκB, and p-STAT3 were measured in human renal proximal tubular epithelial cells of HK-2 or macrophages. Results Mefunidone treatment significantly attenuated tubulointerstitial injury, interstitial collagen deposition, expression of FN, α-SMA, type I and III collagen in the obstructive kidneys, which correlated with significantly reduced the number of T cells and macrophages in the obstructive kidneys. Mechanistically, Mefunidone significantly inhibited tumor necrosis factor-α (TNF-α-) or lipopolysaccharide (LPS)-induced production of proinflammatory cytokines. This effect is possibly due to the inhibition of phosphorylation of ERK, IκB, and STAT3. Conclusion Mefunidone treatment attenuated tubulointerstitial fibrosis in a rat model of UUO, at least in part, through inhibition of inflammation. PMID:26042668

Measurement of stellar occultations

NASA Astrophysics Data System (ADS)

Eberle, Andreas

2008-09-01

Whenever an asteroid occults a star, we have the opportunity to study that asteroid in great detail. As frequently shown in the past, amateur astronomers1 have the necessary equipment to measure such events successfully2. Combined with the dense net of amateur observatories and online coordination tools3 for movable stations, they can create fine grids to detect even small bodies. The analysis of these events gives us the possibility to receive high precision astrometry data, to determine the asteroids size and shape (and therefore its albedo), and even to collect information on the star itself.4 While usually a set of several light curves is required to do so, a single recording5 of (10734) Wieck's occultation of HIP 22157 on 2008 Feb 08 was sufficient to retrieve the necessary data6. 1 Observation campaigns are organized by the International Occultation Timing Association (IOTA), http://www.iota-es.de/ 2 for results see e.g. euraster.net by E. Frappa, http://www.euraster.net/ 3 Occult Watcher by H. Pavlov, http://www.hristopavlov.net/OccultWatcher/OccultWatcher.html 4 see K. Miyashita's analysis of the observation of the occultation of TYC 1886-01206-1 by Kalliope and Linus, http://www005.upp.so-net.ne.jp/k miyash/occ02/kalliope/doublestar en.html 5 recording obtained by H. Michels, MPC Station Code 240 6 using Limovie by K. Miyashita

Lung adenocarcinoma mimicking pulmonary fibrosis-a case report.

PubMed

Mehić, Bakir; Duranović Rayan, Lina; Bilalović, Nurija; Dohranović Tafro, Danina; Pilav, Ilijaz

2016-09-13

Lung cancer is usually presented with cough, dyspnea, pain and weight loss, which is overlapping with symptoms of other lung diseases such as pulmonary fibrosis. Pulmonary fibrosis shows characteristic reticular and nodular pattern, while lung cancers are mostly presented with infiltrative mass, thick-walled cavitations or a solitary nodule with spiculated borders. If the diagnosis is established based on clinical symptoms and CT findings, it would be a misapprehension. We report a case of lung adenocarcinoma whose symptoms as well as clinical images overlapped strongly with pulmonary fibrosis. The patient's non-productive cough, progressive dyspnea, restrictive pattern of pulmonary function test and CT scans (showing reticular interstitial opacities) were all indicative of pulmonary fibrosis. The patient underwent a treatment consisting of corticosteroids and antibiotics, to no avail. Histopathology of the lung showed that the patient suffered from mucinous adenocarcinoma. Albeit the immunohistochemical staining was not consistent with lung adenocarcinoma, tumor's morphological characteristics were consistent, and were used to make the definitive diagnosis. Given the fact that radiography cannot always make a clear-cut difference between pulmonary fibrosis and lung adenocarcinomas, and that clinical symptoms often overlap, histological examination should be considered as gold standard for diagnosis of lung adenocarcinoma.

Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities

PubMed Central

Gao, Wei; Levy, Daniel; Santhanakrishnan, Rajalakshmi; Araki, Tetsuro; Rosas, Ivan O.; Hatabu, Hiroto; Latourelle, Jeanne C.; Nishino, Mizuki; Dupuis, Josée; Washko, George R.; O’Connor, George T.; Hunninghake, Gary M.

2016-01-01

Rationale: Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis. Objectives: We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis. Methods: We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54% women; 14% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography. Measurements and Main Results: Higher Gal-3 concentrations were associated with lower lung volumes (1.4% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95% confidence interval [CI], 0.8–2.0%; P < 0.001; 1.2% decrease in percentage of predicted FVC; 95% CI, 0.6–1.8%; P < 0.001) and decreased diffusing capacity of the lung for carbon monoxide (2.1% decrease; 95% CI, 1.3–2.9%; P < 0.001). These associations remained significant after multivariable adjustment (P ≤ 0.008 for all). Compared with the lowest quartile, participants in the highest Gal-3 quartile were more than twice as likely to have interstitial lung abnormalities visualized by computed tomography (multivariable-adjusted odds ratio, 2.67; 95% CI, 1.49–4.76; P < 0.001). Conclusions: Elevated Gal-3 concentrations are associated with interstitial lung abnormalities coupled with a restrictive pattern, including decreased lung volumes and altered gas exchange. These findings suggest a potential role for Gal-3 in early stages of pulmonary fibrosis. PMID:26771117

EMMPRIN expression is involved in the development of interstitial fibrosis and tubular atrophy in human kidney allografts.

PubMed

Kemmner, Stephan; Schulte, Christian; von Weyhern, Claus Hann; Schmidt, Roland; Baumann, Marcus; Heemann, Uwe; Renders, Lutz; Schmaderer, Christoph

2016-03-01

Matrix metalloproteinases (MMP) are involved in the development of interstitial fibrosis and tubular atrophy (IF/TA) in renal disease. The synthesis of MMP is activated by the extracellular matrix metalloproteinases inducer protein (EMMPRIN). To analyze the role of EMMPRIN in IF/TA, we retrospectively detected EMMPRIN expression in specimens of human renal allografts with various levels of IF/TA. Immunohistochemistry was performed to detect EMMPRIN expression. In a retrospective analysis, a total cohort of 50 specimens were divided according to BANFF-classification into four subgroups (0-3): no, mild (≤ 25%), moderate (26-50%), or severe (>50%) IF/TA. Among other parameters, renal function was analyzed and compared to EMMPRIN expression. In 24 of 38 biopsies, we detected positive EMMPRIN staining. All nephrectomy (n = 12) samples were negative for EMMPRIN. Positive staining in the biopsy samples was detectable on the basolateral side of tubular epithelial cells. EMMPRIN staining was negatively correlated with IF/TA (p < 0.001). We found significant differences between the mean EMMPRIN expression in IF/TA groups 0 and 3 (p = 0.021) and groups 1 and 3 (p = 0.004). Furthermore, we found significant correlations between EMMPRIN staining and renal function. Our data suggest that EMMPRIN is involved in the pathophysiology of IF/TA. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Spherical Occulter Coronagraph Cubesat

NASA Technical Reports Server (NTRS)

Davila, Joseph M. (Inventor); Rabin, Douglas M. (Inventor); Reginald, Nelson (Inventor); Gong, Qian (Inventor); Shah, Neerav (Inventor); Chamberlin, Phillip C. (Inventor)

2018-01-01

The present invention relates to a space-based instrument which provides continuous coronal electron temperature and velocity images, for a predetermined period of time, thereby improving the understanding of coronal evolution and how the solar wind and Coronal Mass Ejection transients evolve from the low solar atmosphere through the heliosphere for an entire solar rotation. Specifically, the present invention relates to using a 6U spherical occulter coronagraph CubeSat, and a relative navigational system (RNS) that controls the position of the spacecraft relative to the occulting sphere. The present invention innovatively deploys a free-flying spherical occulter, and after deployment, the actively controlled CubeSat will provide an inertial formation flying with the spherical occulter and Sun.

Mesenchymal stem cell-derived inflammatory fibroblasts mediate interstitial fibrosis in the aging heart.

PubMed

Trial, JoAnn; Entman, Mark L; Cieslik, Katarzyna A

2016-02-01

Pathologic fibrosis in the aging mouse heart is associated with dysregulated resident mesenchymal stem cells (MSC) arising from reduced stemness and aberrant differentiation into dysfunctional inflammatory fibroblasts. Fibroblasts derived from aging MSC secrete higher levels of 1) collagen type 1 (Col1) that directly contributes to fibrosis, 2) monocyte chemoattractant protein-1 (MCP-1) that attracts leukocytes from the blood and 3) interleukin-6 (IL-6) that facilitates transition of monocytes into myeloid fibroblasts. The transcriptional activation of these proteins is controlled via the farnesyltransferase (FTase)-Ras-Erk pathway. The intrinsic change in the MSC phenotype acquired by advanced age is specific for the heart since MSC originating from bone wall (BW-MSC) or fibroblasts derived from them were free of these defects. The potential therapeutic interventions other than clinically approved strategies based on findings presented in this review are discussed as well. This article is a part of a Special Issue entitled "Fibrosis and Myocardial Remodeling". Copyright © 2015 Elsevier Ltd. All rights reserved.

Unilateral Renal Ischemia as a Model of Acute Kidney Injury and Renal Fibrosis in Cats.

PubMed

Schmiedt, C W; Brainard, B M; Hinson, W; Brown, S A; Brown, C A

2016-01-01

The objectives of this study were to define the acute and chronic effects of 1-hour unilateral in vivo renal ischemia on renal function and histology in cats. Twenty-one adult purpose-bred research cats were anesthetized, and 1 kidney underwent renal artery and vein occlusion for 1 hour. Serum creatinine and urea concentrations, urine protein:creatinine ratio, urine-specific gravity, glomerular filtration rate, hematocrit, platelet concentration and function, and white blood cell count were measured at baseline and variable time points after ischemia. Renal histopathology was evaluated on days 3, 6, 12, 21, 42, and 70 postischemia; changes in smooth muscle actin and interstitial collagen were examined. Following ischemia, whole animal glomerular filtration rate was significantly reduced (57% of baseline on day 6; P < .05). At the early time points, the ischemic kidneys exhibited severe acute epithelial necrosis accompanied by evidence of regeneration of tubules predominantly within the corticomedullary junction. At later periods, postischemic kidneys had evidence of tubular atrophy and interstitial inflammation with significantly more smooth muscle actin and interstitial collagen staining and interstitial fibrosis when compared with the contralateral control kidneys. This study characterizes the course of ischemic acute kidney injury in cats and demonstrates that ischemic acute kidney injury triggers chronic fibrosis, interstitial inflammation, and tubular atrophy in feline kidneys. These late changes are typical of those observed in cats with naturally occurring chronic kidney disease. © The Author(s) 2015.

Primary proximal tubule injury leads to epithelial cell cycle arrest, fibrosis, vascular rarefaction, and glomerulosclerosis

PubMed Central

Bonventre, Joseph V

2014-01-01

Tubular injury has a major etiological role in fibrosis. For many years, this relationship has been dominated by the perception that epithelial cells are transformed into myofibroblasts that proliferate and generate fibrotic matrix—the so-called epithelial-to-mesenchymal transition. Here we focus on mechanisms by which injury to the tubule results in fibrosis because of paracrine mechanisms. Specific injury to the proximal tubule results in inflammation, reversible injury, and adaptive repair if the insult is mild, self-limited in time, and occurs in a background of a normal kidney. Repeated injury, in contrast, leads to maladaptive repair with sustained tubule injury, chronic inflammation, proliferation of interstitial myofibroblasts, vascular rarefaction, interstitial fibrosis, and glomerular sclerosis. During the maladaptive repair process after the renal insult, many tubular cells become arrested in the G2/M phase of the cell cycle. This results in activation of the DNA repair response with the resultant synthesis and secretion of pro-fibrotic factors. Pharmacologic interventions that enhance the movement through G2/M or facilitate apoptosis of cells that otherwise would be blocked in G2/M may reduce the development of fibrosis after kidney injury and reduce the progression of chronic kidney disease. PMID:26310195

Protein S is protective in pulmonary fibrosis.

PubMed

Urawa, M; Kobayashi, T; D'Alessandro-Gabazza, C N; Fujimoto, H; Toda, M; Roeen, Z; Hinneh, J A; Yasuma, T; Takei, Y; Taguchi, O; Gabazza, E C

2016-08-01

Essentials Epithelial cell apoptosis is critical in the pathogenesis of idiopathic pulmonary fibrosis. Protein S, a circulating anticoagulant, inhibited apoptosis of lung epithelial cells. Overexpression of protein S in lung cells reduced bleomycin-induced pulmonary fibrosis. Intranasal therapy with exogenous protein S ameliorated bleomycin-induced pulmonary fibrosis. Background Pulmonary fibrosis is the terminal stage of interstitial lung diseases, some of them being incurable and of unknown etiology. Apoptosis plays a critical role in lung fibrogenesis. Protein S is a plasma anticoagulant with potent antiapoptotic activity. The role of protein S in pulmonary fibrosis is unknown. Objectives To evaluate the clinical relevance of protein S and its protective role in pulmonary fibrosis. Methods and Results The circulating level of protein S was measured in patients with pulmonary fibrosis and controls by the use of enzyme immunoassays. Pulmonary fibrosis was induced with bleomycin in transgenic mice overexpressing human protein S and wild-type mice, and exogenous protein S or vehicle was administered to wild-type mice; fibrosis was then compared in both models. Patients with pulmonary fibrosis had reduced circulating levels of protein S as compared with controls. Inflammatory changes, the levels of profibrotic cytokines, fibrosis score, hydroxyproline content in the lungs and oxygen desaturation were significantly reduced in protein S-transgenic mice as compared with wild-type mice. Wild-type mice treated with exogenous protein S showed significant decreases in the levels of inflammatory and profibrotic markers and fibrosis in the lungs as compared with untreated control mice. After bleomycin infusion, mice overexpressing human protein S showed significantly low caspase-3 activity, enhanced expression of antiapoptotic molecules and enhanced Akt and Axl kinase phosphorylation as compared with wild-type counterparts. Protein S also inhibited apoptosis of alveolar

A Histologically Distinctive Interstitial Pneumonia Induced by Overexpression of the Interleukin 6, Transforming Growth Factor β1, or Platelet-Derived Growth Factor B Gene

NASA Astrophysics Data System (ADS)

Yoshida, Mitsuhiro; Sakuma, Junko; Hayashi, Seiji; Abe, Kin'ya; Saito, Izumu; Harada, Shizuko; Sakatani, Mitsunoir; Yamamoto, Satoru; Matsumoto, Norinao; Kaneda, Yasufumi; Kishmoto, Tadamitsu

1995-10-01

Interstitial pneumonia is characterized by alveolitis with resulting fibrosis of the interstitium. To determine the relevance of humoral factors in the pathogenesis of interstitial pneumonia, we introduced expression vectors into Wistar rats via the trachea to locally overexpress humoral factors in the lungs. Human interleukin (IL) 6 and IL-6 receptor genes induced lymphocytic alveolitis without marked fibroblast proliferation. In contrast, overexpression of human transforming growth factor β1 or human platelet-derived growth factor B gene induced only mild or apparent cellular infiltration in the alveoli, respectively. However, both factors induced significant proliferation of fibroblasts and deposition of collagen fibrils. These histopathologic changes induced by the transforming growth factor β1 and platelet-derived growth factor B gene are partly akin to those changes seen in lung tissues from patients with pulmonary fibrosis and markedly contrast with the changes induced by overexpression of the IL-6 and IL-6 receptor genes that mimics lymphocytic interstitial pneumonia.

[Clinical assessment of occult infections in children].

PubMed

Sporisević, L; Bajraktarević, A; Begić, Z

2000-01-01

Children's occult infections are characterised presenting pathogenic bacteries in blood of children in age 3 to 36 months, but they are good general aspect and orderly immunologic status and they don't have signs of focal infection. Manifestation of occult infections determined: age of child, increasing bodies temperature, testsphysical observance and clinical-biochemistry tests. Prevalence of manifestation occult infections is 3-8%, but they manifest ni a form occult bacteremia, occult pneumonia nad occult urinary infection. Methodic, systematic admission and adequate clinical-biochemical monitoring, we minimise sequeles of occult infections. Risk of serious sequeles at occult infections is importantly decreasing by epidemiological changes that it rises by using vaccination against Haemophilus influenzae and Streptococcus pneumoniae is leading ethiological source. Many contraversal opinions are presented in glance of therapeutic strategy at children's occult infection. Future of solutions at many hesitations ni context diagnosis and therapy of occult infections is established in using recent detectional tests /pneumococcus PCR, plasmas tumor reaction, interleukin lâ/ and preventive intervetions activities /conjugated pneumococcus vaccination/.

21 CFR 864.6550 - Occult blood test.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Occult blood test. 864.6550 Section 864.6550 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6550 Occult blood test. (a) Identification. An occult blood test is a device used to detect occult blood in urine or feces. (Occult blood is...

21 CFR 864.6550 - Occult blood test.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Occult blood test. 864.6550 Section 864.6550 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6550 Occult blood test. (a) Identification. An occult blood test is a device used to detect occult blood in urine or feces. (Occult blood is...

21 CFR 864.6550 - Occult blood test.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Occult blood test. 864.6550 Section 864.6550 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6550 Occult blood test. (a) Identification. An occult blood test is a device used to detect occult blood in urine or feces. (Occult blood is...

21 CFR 864.6550 - Occult blood test.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Occult blood test. 864.6550 Section 864.6550 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6550 Occult blood test. (a) Identification. An occult blood test is a device used to detect occult blood in urine or feces. (Occult blood is...

21 CFR 864.6550 - Occult blood test.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Occult blood test. 864.6550 Section 864.6550 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6550 Occult blood test. (a) Identification. An occult blood test is a device used to detect occult blood in urine or feces. (Occult blood is...

Febuxostat Prevents Renal Interstitial Fibrosis by the Activation of BMP-7 Signaling and Inhibition of USAG-1 Expression in Rats.

PubMed

Cao, Jing; Li, Yong; Peng, Yingxian; Zhang, Yaqian; Li, Huanhuan; Li, Ran; Xia, Anzhou

2015-01-01

Renal interstitial fibrosis (RIF) is a common pathology associated with end-stage renal diseases. The activation of bone morphogenetic protein-7 (BMP-7)-Smad1/5/8 pathway seems to alleviate RIF. Uterine sensitization-associated gene-1 (USAG-1), a kidney-specific BMPs antagonist, is associated with the development and prognosis of several renal diseases. Febuxostat is a xanthine oxidase inhibitor that can attenuate the renal dysfunction of patients. The purpose of this study was to investigate the effects of febuxostat on renal fibrosis and to clarify the mechanisms underlying these effects. Rats were randomly divided into 6 groups termed a sham-operated group, a unilateral ureteral obstruction (UUO) group, 3 doses of febuxostat groups (low, intermediate and high doses) and a sham group treated with high-dose febuxostat. After 14 days, renal function, relative kidney weight, accumulation of glycogen and collagens were examined by different methods. Expression of α-SMA, transforming growth factor-β1 (TGF-β1), BMP-7 and USAG-1 was detected by western blotting and RT-PCR, respectively. The phosphorylation level of Smad1/5/8 was also quantified by western blotting. The renal function was declined, and large amounts of glycogen and collagens were deposited in the kidneys of UUO rats compared with the rats in the sham group. Besides, expression of α-SMA and USAG-1 in these kidneys was elevated, and the TGF-β1 was also activated, while the BMP-7-Smad1/5/8 pathway was inhibited. Febuxostat reversed the changes stated earlier, exhibiting protective effects on RIF induced by UUO. Febuxostat was able to attenuate RIF caused by UUO, which was associated with the activation of BMP-7-Smad1/5/8 pathway and the inhibition of USAG-1 expression in the kidneys of UUO rats. © 2015 S. Karger AG, Basel.

Macrophage migration inhibitory factor in lung tissue of idiopathic pulmonary fibrosis patients.

PubMed

Olivieri, Carmela; Bargagli, Elena; Inghilleri, Simona; Campo, Ilaria; Cintorino, Marcella; Rottoli, Paola

2016-06-01

Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disorder characterized by a pattern of Usual Interstitial Pneumonia where the presence of fibroblastic foci is the hallmark of the disease. In the present study, we analyzed the migration inhibitory factor (MIF) expression in lung tissue of IPF patients compared with healthy controls and organizing pneumonia (OP) patients focusing into MIF potential role in fibroblastic foci development. The immunohistochemical analysis was performed in 10 IPF patients (7 male), 3 OP patients (2 male), and 3 healthy controls (all male) using the streptavidin-biotin method (Dako). In IPF samples, MIF resulted overexpressed in the areas of active fibrosis and, in particular, in the alveolar epithelium, bronchiolar epithelium, and in the peripheral zones of fibroblastic foci. Bronchiolar epithelium from organizing pneumonia patients resulted only weakly positive for MIF while no evidence of MIF expression was reported for alveolar epithelium. In the control subject group, MIF was unexpressed except for a weak presence in the bronchiolar epithelium. In conclusion, MIF is a pleiotropic cytokine involved in the pathogenesis of IPF being mainly expressed in the areas of remodeling and active fibrosis, in bronchiolar and alveolar epithelium, and in the peripheral zone of fibroblastic foci.

Idiopathic pulmonary fibrosis misdiagnosed as sputum-negative pulmonary tuberculosis.

PubMed

Isah, Muhammad Danasabe; Abbas, Aminu; Abba, Abdullahi A; Umar, Mohammed

2016-01-01

Idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis, is one of a spectrum of idiopathic interstitial pneumonia. IPF is an increasingly common condition which poses many diagnostic and therapeutic challenges leading to misdiagnosis and mismanagement. We presented a 55-year-old male textile trader who was initially managed as sputum-negative pulmonary tuberculosis before histology report. He presented to our clinic with Breathlessness and cough of 3 years and 2.5 years, respectively. He had commenced anti-tuberculosis two months before presentation without significant relief. General Physical examination and vital signs were essentially normal. SPO2 was 96% on room air. Chest Examination revealed end-inspiratory bi-basal velcro-like crackles. Other systemic examinations were normal. Radiological examination by way of chest X- ray and chest CT showed features suggestive of IPF. The patient also had open Lung biopsy for histology and spirometry which demonstrated restrictive ventilatory function pattern. A diagnosis of Interstitial lung disease probably Idiopathic Pulmonary Fibrosis was entertained. He was commenced on Tab prednisolone, Tab Rabeprazole, with minimal improvement. IPF have often been misdiagnosed and treated as pulmonary tuberculosis with unfavorable outcome.

Sonic hedgehog signaling in kidney fibrosis: a master communicator.

PubMed

Zhou, Dong; Tan, Roderick J; Liu, Youhua

2016-09-01

The hedgehog signaling cascade is an evolutionarily conserved pathway that regulates multiple aspects of embryonic development and plays a decisive role in tissue homeostasis. As the best studied member of three hedgehog ligands, sonic hedgehog (Shh) is known to be associated with kidney development and tissue repair after various insults. Recent studies uncover an intrinsic link between dysregulated Shh signaling and renal fibrogenesis. In various types of chronic kidney disease (CKD), Shh is upregulated specifically in renal tubular epithelium but targets interstitial fibroblasts, thereby mediating a dynamic epithelial- mesenchymal communication (EMC). Tubule-derived Shh acts as a growth factor for interstitial fibroblasts and controls a hierarchy of fibrosis-related genes, which lead to the excessive deposition of extracellular matrix in renal interstitium. In this review, we recapitulate the principle of Shh signaling, its activation and regulation in a variety of kidney diseases. We also discuss the potential mechanisms by which Shh promotes renal fibrosis and assess the efficacy of blocking this signaling in preclinical settings. Continuing these lines of investigations will provide novel opportunities for designing effective therapies to improve CKD prognosis in patients.

Sonic hedgehog signaling in kidney fibrosis: a master communicator

PubMed Central

Zhou, Dong; Tan, Roderick J.; Liu, Youhua

2017-01-01

The hedgehog signaling cascade is an evolutionarily conserved pathway that regulates multiple aspects of embryonic development and plays a decisive role in tissue homeostasis. As the best studied member of three hedgehog ligands, sonic hedgehog (Shh) is known to be associated with kidney development and tissue repair after various insults. Recent studies uncover an intrinsic link between dysregulated Shh signaling and renal fibrogenesis. In various types of chronic kidney disease (CKD), Shh is upregulated specifically in renal tubular epithelium but targets interstitial fibroblasts, thereby mediating a dynamic epithelial-mesenchymal communication (EMC). Tubule-derived Shh acts as a growth factor for interstitial fibroblasts and controls a hierarchy of fibrosis-related genes, which lead to the excessive deposition of extracellular matrix in renal interstitium. In this review, we recapitulate the principle of Shh signaling, its activation and regulation in a variety of kidney diseases. We also discuss the potential mechanisms by which Shh promotes renal fibrosis and assess the efficacy of blocking this signaling in preclinical settings. Continuing these lines of investigations will provide novel opportunities for designing effective therapies to improve CKD prognosis in patients. PMID:27333788

On the reduction of occultation light curves. [stellar occultations by planets

NASA Technical Reports Server (NTRS)

Wasserman, L.; Veverka, J.

1973-01-01

The two basic methods of reducing occultation light curves - curve fitting and inversion - are reviewed and compared. It is shown that the curve fitting methods have severe problems of nonuniqueness. In addition, in the case of occultation curves dominated by spikes, it is not clear that such solutions are meaningful. The inversion method does not suffer from these drawbacks. Methods of deriving temperature profiles from refractivity profiles are then examined. It is shown that, although the temperature profiles are sensitive to small errors in the refractivity profile, accurate temperatures can be obtained, particularly at the deeper levels of the atmosphere. The ambiguities that arise when the occultation curve straddles the turbopause are briefly discussed.

β-Arrestin-1 deficiency ameliorates renal interstitial fibrosis by blocking Wnt1/β-catenin signaling in mice.

PubMed

Xu, Huiyan; Li, Quanxin; Liu, Jiang; Zhu, Jiaqing; Li, Liang; Wang, Ziying; Zhang, Yan; Sun, Yu; Sun, Jinpeng; Wang, Rong; Yi, Fan

2018-01-01

Despite substantial progress being made in understanding the mechanisms contributing to the pathogenesis of renal fibrosis, there are only a few therapies available to treat or prevent renal fibrosis in clinical use today. Therefore, identifying the key cellular and molecular mediators involved in the pathogenesis of renal fibrosis will provide new therapeutic strategy for treating patients with chronic kidney disease (CKD). β-Arrestin-1, a member of β-arrestin family, not only is a negative adaptor of G protein-coupled receptors (GPCRs), but also acts as a scaffold protein and regulates a diverse array of cellular functions independent of GPCR activation. In this study, we identified for the first time that β-arrestin-1 was upregulated in the kidney from mice with unilateral ureteral obstruction nephropathy as well as in the paraffin-embedded sections of human kidneys from the patients with diabetic nephropathy, polycystic kidney, or uronephrosis, which normally causes renal fibrosis. Deficiency of β-arrestin-1 in mice significantly alleviated renal fibrosis by the regulation of inflammatory responses, kidney fibroblast activation, and epithelial-mesenchymal transition (EMT) in both in vivo and in vitro studies. Furthermore, we found that among the major isoforms of Wnts, Wnt1 was regulated by β-arrestin-1 and gene silencing of Wnt1 inhibited the activation of β-catenin and suppressed β-arrestin-1-mediated renal fibrosis. Collectively, our results indicate that β-arrestin-1 is one of the critical components of signal transduction pathways in the development of renal fibrosis. Modulation of these pathways may be an innovative therapeutic strategy for treating patients with renal fibrosis. β-Arrestin-1 was upregulated in the kidney from mice with UUO nephropathy. β-Arrestin-1 regulated kidney fibroblast activation and epithelial-mesenchymal transition. β-Arrestin-1 exacerbated renal fibrosis via mediating Wnt1/β-catenin signaling.

Clinical features of usual interstitial pneumonia with anti-neutrophil cytoplasmic antibody in comparison with idiopathic pulmonary fibrosis.

PubMed

Hosoda, Chiaki; Baba, Tomohisa; Hagiwara, Eri; Ito, Hiroyuki; Matsuo, Norikazu; Kitamura, Hideya; Iwasawa, Tae; Okudela, Koji; Takemura, Tamiko; Ogura, Takashi

2016-07-01

Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) is occasionally positive in patients with usual interstitial pneumonia (UIP). However, the differences from idiopathic pulmonary fibrosis (IPF/UIP) have not been well documented. We aimed to clarify the clinical, radiological and pathological features of UIP associated with MPO-ANCA (ANCA/UIP). We retrospectively reviewed the medical records of 12 consecutive ANCA/UIP patients not manifesting microscopic polyangiitis and 108 IPF/UIP patients with no autoantibodies, both diagnosed by surgical lung biopsy. There was no significant difference in clinical background, laboratory results and pulmonary function tests between ANCA/UIP patients and IPF/UIP patients except for the percentage of bronchoalveolar lavage neutrophils. HRCT showed subpleural reticulation in both groups. Increased attenuation around honeycombing and cysts was significantly observed in ANCA/UIP. Pathologically, ANCA/UIP had more prominent inflammatory cell infiltration, lymphoid follicles with germinal centres and cellular bronchiolitis. During the disease course, three of 12 patients (25%) developed microscopic polyangiitis. Immunosuppressive treatment tended to be more effective in ANCA/UIP patients, and the survival time in ANCA/UIP patients tended to be longer than those with IPF/UIP. ANCA/UIP may be distinguishable from IPF/UIP with a combination of HRCT findings of increased attenuation around honeycombing and cysts and some of the characteristic pathological findings. In contrast to IPF/UIP, immunosuppressive treatment could be a therapeutic option for ANCA/UIP. © 2016 Asian Pacific Society of Respirology.

Triton stellar occultation candidates - 1992-1994

NASA Technical Reports Server (NTRS)

Mcdonald, S. W.; Elliot, J. T.

1992-01-01

A search for Triton stellar occultation candidates for the period 1992-1994 has been completed with CCD strip-scanning observations. The search reached an R magnitude of about 17.4 and found 129 candidates within 1.5 arcsec of Triton's ephemeris during this period. Of these events, around 30 occultations are expected to be visible from the earth, indicating that a number of Triton occultation events should be visible from major observatories. Even the faintest of the present candidate events could produce useful occultation data if observed with a large enough telescope. The present astrometric accuracy is inadequate to identify which of these appulse events will produce occultations on the earth; further astrometry is needed to refine the predictions for positive occultation identification. To aid in selecting candidates for additional astrometric and photometric studies, finder charts and earth-based visibility charts for each event are included.

Fibroblast growth factor represses Smad-mediated myofibroblast activation in aortic valvular interstitial cells

PubMed Central

Cushing, Melinda C.; Mariner, Peter D.; Liao, Jo-Tsu; Sims, Evan A.; Anseth, Kristi S.

2008-01-01

This study aimed to identify signaling pathways that oppose connective tissue fibrosis in the aortic valve. Using valvular interstitial cells (VICs) isolated from porcine aortic valve leaflets, we show that basic fibroblast growth factor (FGF-2) effectively blocks transforming growth factor-β1 (TGF-β1)-mediated myofibroblast activation. FGF-2 prevents the induction of α-smooth muscle actin (αSMA) expression and the exit of VICs from the cell cycle, both of which are hallmarks of myofibroblast activation. By blocking the activity of the Smad transcription factors that serve as the downstream nuclear effectors of TGF-β1, FGF-2 treatment inhibits fibrosis in VICs. Using an exogenous Smad-responsive transcriptional promoter reporter, we show that Smad activity is repressed by FGF-2, likely an effect of the fact that FGF-2 treatment prevents the nuclear localization of Smads in these cells. This appears to be a direct effect of FGF signaling through mitogen-activated protein kinase (MAPK) cascades as the treatment of VICs with the MAPK/extracellular regulated kinase (MEK) inhibitor U0126 acted to induce fibrosis and blocked the ability of FGF-2 to inhibit TGF-β1 signaling. Furthermore, FGF-2 treatment of VICs blocks the development of pathological contractile and calcifying phenotypes, suggesting that these pathways may be utilized in the engineering of effective treatments for valvular disease.—Cushing, M. C., Mariner, P. D., Liao, J. T., Sims, E. A., Anseth, K. S. Fibroblast growth factor represses Smad-mediated myofibroblast activation in aortic valvular interstitial cells. PMID:18218921

Rheumatoid Arthritis (RA) associated interstitial lung disease (ILD).

PubMed

O'Dwyer, David N; Armstrong, Michelle E; Cooke, Gordon; Dodd, Jonathan D; Veale, Douglas J; Donnelly, Seamas C

2013-10-01

Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lung disease (ILD) has been recognised as a complication of RA but its potential for mortality and morbidity has arguably been under appreciated for decades. New studies have underscored a significant lifetime risk of ILD development in RA. Contemporary work has identified an increased risk of mortality associated with the Usual Interstitial Pneumonia (UIP) pattern which shares similarity with the most devastating of the interstitial pulmonary diseases, namely Idiopathic Pulmonary Fibrosis (IPF). In this paper, we discuss recent studies highlighting the associated increase in mortality in RA-UIP. We explore associations between radiological and histopathological features of RA-ILD and the prognostic implications of same. We emphasise the need for translational research in this area given the growing burden of RA-ILD. We highlight the importance of the respiratory physician as a key stakeholder in the multidisciplinary management of this disorder. RA-ILD focused research offers the opportunity to identify early asymptomatic disease and define the natural history of this extra articular manifestation. This may provide a unique opportunity to define key regulatory fibrotic events driving progressive disease. We also discuss some of the more challenging and novel aspects of therapy for RA-ILD. © 2013.

Progression of renal fibrosis in congenital CKD model rats with reduced number of nephrons.

PubMed

Yasuda, Hidenori; Tochigi, Yuki; Katayama, Kentaro; Suzuki, Hiroetsu

2017-06-14

A congenital reduction in the number of nephrons is a critical risk factor for both onset of chronic kidney disease (CKD) and its progression to end-stage kidney disease (ESKD). Hypoplastic kidney (HPK) rats have only about 20% of the normal number of nephrons and show progressive CKD. This study used an immunohistological method to assess glomerular and interstitial pathogenesis in male HPK rats aged 35-210days. CD68 positive-macrophages were found to infiltrate into glomeruli in HPK rats aged 35 and 70days and to infiltrate into interstitial tissue in rats aged 140 and 210days. HPK rats aged 35 and 70days showed glomerular hypertrophy, loss of normal linear immunostaining of podocine, and increased expression of PDGFr-β, TGF-β, collagens, and fibronectin, with all of these alterations gradually deteriorating with age. α-SMA-positive myofibroblasts were rarely detected in glomerular tufts, whereas α-SMA-positive glomerular parietal epithelium (GPE) cells were frequently observed along Bowman's capsular walls. The numbers of PDGFr-β-positive fibroblasts in interstitial tissue were increased in rats aged 35days and older, whereas interstitial fibrosis, characterized by the increased expression of tubular PDGF-BB, the appearance of myofibroblasts doubly positive for PDGFr-β and α-SMA, and increased expression of collagens and fibronectin, were observed in rats aged 70 and older. These results clearly indicate that congenital CKD with only 20% of nephrons cause renal fibrosis in rats. Copyright © 2017 Elsevier GmbH. All rights reserved.

Poricoic acid ZA, a novel RAS inhibitor, attenuates tubulo-interstitial fibrosis and podocyte injury by inhibiting TGF-β/Smad signaling pathway.

PubMed

Wang, Ming; Chen, Dan-Qian; Wang, Min-Chang; Chen, Hua; Chen, Lin; Liu, Dan; Zhao, Hui; Zhao, Ying-Yong

2017-12-01

The pathogenesis of tubulo-interstitial fibrosis and glomerulosclerosisis was characterized by cellular hypertrophy, extracellular matrix accumulation and podocyte detachment. Poricoic acid ZA (PZA) is a tetracyclic triterpenoid compound extracted from the surface layer of Poria cocos (LPC), which have been used extensively for diuretic and renoprotective effects. The anti-fibrotic effect of PZA is investigated in HK-2 cells and podocytes induced by TGF-β1 and angiotensin II (ANGII). qRT-PCR, siRNA, immunofluorescence staining, co-immunoprecipitation and Western blot analyses are used to evaluate the expression of RAS signaling, TGF-β/Smad pathway, epithelial-to-mesenchymal transition (EMT) and podocyte markers. PZA restores the mRNA and protein expression of EMT in HK-2 cells. Specific TGF-β1-siRNA efficiently blocks ANGII-induced protein expression of TGF-β1 and further inhibits activated Smad signaling. PZA significantly attenuates up-regulation of angiotensinogen, renin, ACE and AT1. Further, PZA reverses up-regulation of TGFβRII and suppresses Smad proteins. Simultaneously, PZA inhibits the protein interaction of TGF-β receptor and Smads and PZA also inhibits activated RAS and TGF-β/Smad signaling cascade and up-regulates protein expression of podocyte markers and mitigates podocyte injury. This study demonstrated the beneficial role of PZA in renal fibrosis and podocyte injury. Our study highlighted that PZA inhibits RAS and further suppresses TGF-β/Smad pathway through inhibiting Smad2/3 phosphorylation via blocking Smad2/3-TGFβRI protein interaction. PZA is implicated in activation of RAS/TGF-β/Smad axis in HK-2 cells and podocytes. PZA could be considered as a novel RAS inhibitor for treating CKD. Copyright © 2017 Elsevier GmbH. All rights reserved.

Identification of Clinical Phenotypes in Idiopathic Interstitial Pneumonia with Pulmonary Emphysema.

PubMed

Sato, Suguru; Tanino, Yoshinori; Misa, Kenichi; Fukuhara, Naoko; Nikaido, Takefumi; Uematsu, Manabu; Fukuhara, Atsuro; Wang, Xintao; Ishida, Takashi; Munakata, Mitsuru

2016-01-01

Objective Since the term "combined pulmonary fibrosis and emphysema" (CPFE) was first proposed, the co-existence of pulmonary fibrosis and pulmonary emphysema (PE) has drawn considerable attention. However, conflicting results on the clinical characteristics of patients with both pulmonary fibrosis and PE have been published because of the lack of an exact definition of CPFE. The goal of this study was thus to clarify the clinical characteristics and phenotypes of idiopathic interstitial pneumonia (IIP) with PE. Methods We retrospectively analyzed IIP patients who had been admitted to our hospital. Their chest high-resolution computed tomography images were classified into two groups according to the presence of PE. We then performed a cluster analysis to identify the phenotypes of IIP patients with PE. Results Forty-four (53.7%) out of 82 patients had at least mild emphysema in their bilateral lungs. The cluster analysis separated the IIP patients with PE into three clusters. The overall survival rate of one cluster that consisted of mainly idiopathic pulmonary fibrosis (IPF) patients was significantly worse than those of the other clusters. Conclusion Three different phenotypes can be identified in IIP patients with PE, and IPF with PE is a distinct clinical phenotype with a poor prognosis.

Chronic active interstitial pancreatitis as a cause of transverse colonic obstruction and colic in a horse

PubMed Central

Lohmann, Katharina L.; Allen, Andrew L.

2015-01-01

A mature Quarter horse was euthanized following colic of 3 days duration. Postmortem, the large intestine, except the descending colon, was diffusely distended and associated with adhesion of the transverse colon to the pancreas, which had changes consistent with chronic active interstitial pancreatitis. Other lesions included hepatic fibrosis, erosive gastritis, and bilateral adrenal cortical hyperplasia. PMID:26538675

An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features

PubMed Central

2014-01-01

Background Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients. As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients. Methods Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients. Results All patients had a history of heavy smoking. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups. The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups. Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups. Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs). Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs. The cystic lesions were always larger than the cysts of honeycombing. The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema

Progress on the occulter experiment at Princeton

NASA Astrophysics Data System (ADS)

Cady, Eric; Balasubramanian, Kunjithapatham; Carr, Michael; Dickie, Matthew; Echternach, Pierre; Groff, Tyler; Kasdin, Jeremy; Laftchiev, Christian; McElwain, Michael; Sirbu, Dan; Vanderbei, Robert; White, Victor

2009-08-01

An occulter is used in conjunction with a separate telescope to suppress the light of a distant star. To demonstrate the performance of this system, we are building an occulter experiment in the laboratory at Princeton. This experiment will use an etched silicon mask as the occulter, with some modifications to try to improve the performance. The occulter is illuminated by a diverging laser beam to reduce the aberrations from the optics before the occulter. We present the progress of this experiment and expectations for future work.

Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats.

PubMed

Li, Longkai; Shen, Nan; Wang, Nan; Wang, Weidong; Tang, Qingzhu; Du, Xiangning; Carrero, Juan Jesus; Wang, Keping; Deng, Yiyao; Li, Zhitong; Lin, Hongli; Wu, Taihua

2018-06-01

Ultrafiltration failure is a major complication of long-term peritoneal dialysis, resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure to high glucose dialysate is the major contributor of ultrafiltration failure, for which there is no effective treatment. Overactivation of several signaling pathways, including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) pathways, contribute to the development of peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling pathways might be a potential novel method of treating peritoneal fibrosis. Previously, we showed that core fucosylation, an important posttranslational modification of the TGF-β1 receptors, can regulate the activation of TGF-β1 signaling in renal interstitial fibrosis. However, it remains unclear whether core fucosylation affects the progression of peritoneal fibrosis. Herein, we show that core fucosylation was enriched in the peritoneal membrane of rats accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking core fucosylation dramatically attenuated peritoneal fibrosis in the rat model achieved by simultaneously inactivating the TGF-β1 and PDGF signaling pathways. Next the protective effects of blocking core fucosylation and imatinib (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and found to exhibit a greater inhibitory effect over imatinib alone, suggesting that blocking activation of multiple signaling pathways may have superior inhibitory effects on the development of peritoneal fibrosis. Thus, core fucosylation is essential for the development of peritoneal fibrosis by regulating the activation of multiple signaling pathways. This may be a potential novel target for drug development to treat peritoneal fibrosis. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Pulmonary fibrosis in a carpenter with long-lasting exposure to fiberglass.

PubMed

Takahashi, T; Munakata, M; Takekawa, H; Homma, Y; Kawakami, Y

1996-11-01

A 56-year-old male carpenter had a history of glass fiber inhalation for 41 years without any protective device. His chest radiograph showed small nodular opacities in lower lung fields and multiple cystic lesions and low attenuation areas in upper lung fields. Light and polarizing microscopic examinations of his transbronchial lung biopsy specimen revealed mild interstitial fibrosis and mononuclear cell infiltration in alveolar walls without birefringent substances. However, widespread depositions of small glass fibers (< 2.5 microns in length and 0.3 micron in diameter) were detected by analytical electron microscopy, which suggested their possible contribution to the development of his pulmonary fibrosis.

Several Well-observed Asteroidal Occultations in 2010

NASA Astrophysics Data System (ADS)

Timerson, Brad; Durech, J.; Abramson, H.; Brooks, J.; Caton, D.; Clark, D.; Conard, S.; Cooke, B.; Dunham, D. W.; Dunham, J.; Edberg, S.; Ellington, C.; Faircloth, J.; Herchak, S.; Iverson, E.; Jones, R.; Lucas, G.; Lyzenga, G.; Maley, P.; Martinez, L.; Menke, J.; Mroz, G.; Nolan, P.; Peterson, R.; Preston, S.; Rattley, G.; Ray, J.; Scheck, A.; Stamm, J.; Stanton, R.; Suggs, R.; Tatum, R.; Thomas, W.

2011-10-01

During 2010 IOTA observers in North America reported about 190 positive observations for 106 asteroid occultation events. For several asteroids, this included observations with multiple chords. For two events, an inversion model was available. An occultation by 16 Psyche on 2010 August 21 yielded a best-fit ellipse of 235.4 x 230.4 km. On 2010 December 24, an occultation by 93 Minerva produced a best-fit ellipse of 179.4 x 133.4 km. An occultation by 96 Aegle on 2010 October 29 yielded a best-fit ellipse of 124.9 x 88.0 km. An occultation by 105 Artemis on 2010 June 24 showed a best-fit ellipse of 125.0 x 92.0 km. An occultation by 375 Ursula on 2010 December 4 produced a best-fit ellipse of 125.0 km x 135.0 km. Of note are two events not summarized in this article. On 2010 August 31, an occultation by 695 Bella yielded a new double star. That event will be summarized in the JDSO. Finally, on 2010 April 6, an occultation of zeta Ophiuchi by 824 Anastasia was observed by 65 observers at 69 locations. Unfortunately a large shift in the path yielded only 4 chords. Results of that event, and all the events mentioned here, can be found on the North American Asteroidal Occultation Results web page.

Stellar Occultation Studies of the Solar System

NASA Technical Reports Server (NTRS)

Elliot, James L.

1998-01-01

Earth-based observations of stellar occultations provide extremely high spatial resolution for bodies in the outer solar system, about 10,000 times better than that of traditional imaging observations. Stellar occultation data can be used to establish the structure of atmospheres and rings of solar system bodies at high spatial resolution. Airborne occultation observations are particularly effective, since the controlled mobility of the observing platform allows the observer to fly within the optimum part of the occultation shadow for most events that are visible from Earth. Airborne observations are carried out above any clouds and are nearly free of scintillation noise from the Earth's atmosphere. KAO occultation observations resulted in the first detection of gravity waves in the Martian atmosphere, discovery of the Uranian rings, the first detection of Pluto's atmosphere, the first Earth-based investigations of Triton's atmosphere, and the discovery of narrow jets from Chiron's nucleus. The first SOFIA occultation opportunity will be an investigation of Pluto's atmospheric structure in November, 2002, and will resolve a problem that has lingered since the KAO discovery observation fourteen years earlier. We plan to continue our successful airborne occultation program with the greatly enhanced capability provided by SOFIA. We propose here to replace our KAO occultation photometer with one having twice the throughput, half the noise, a somewhat wider wavelength range, four times the field of view, and ten times the frame rate to optimize its performance and to capitalize on the larger collecting area offered by SOFIA. It will also allow for simultaneous visible and IR occultation observations, greatly enriching the results that we can obtain from occultations. We call this new imaging occultation photometer HOPI (High-speed Occultation Photometer and Imager). HOPI will provide a signal-to-noise ratio two to four times that of our present photometer for a given

Changes in urinary microbiome populations correlate in kidney transplants with interstitial fibrosis and tubular atrophy documented in early surveillance biopsies

PubMed Central

Modena, Brian D; Milam, Rachel; Harrison, Frank; Cheeseman, Jennifer A; Abecassis, Michael M; Friedewald, John; Kirk, Allan D.; Salomon, Daniel R

2016-01-01

An unbalanced microbiome may lead to disease by creating aberrant immune responses. A recent association of cellular rejection with the development of interstitial fibrosis and tubular atrophy (IFTA) suggests the role of immune-mediated tissue injury. We hypothesized that developing IFTA correlates with altered urinary tract microbiomes (UMBs). UMBs at two serial time points, 1 and 6-8 months post-transplant, were assessed by 16S microbial ribosomal gene sequencing in 25 patients developing biopsy-proven IFTA compared to 23 transplant patients with normal biopsies and excellent function (TX) and 20 healthy non-transplant controls (HC). Streptococcus, the dominant genera in HC males, was lower in IFTA and TX males at 1 month compared to HCs. At 6-8 months, Streptococcus was further decreased in IFTA males, but normalized in TX. IFTA males and females had increases in number of genera per sample at 6-8 months. UMB composition varied substantially between individuals in all groups. Despite the wide variation in UMBs between individuals, IFTA associated with a loss in dominant resident urinary microbes in males, and a parallel increase in non-resident, pathogenic bacteria in males and females. UMB changes may contribute to IFTA development by alteration of the host immune response. PMID:27597148

Serial perfusion in native lungs in patients with idiopathic pulmonary fibrosis and other interstitial lung diseases after single lung transplantation.

PubMed

Sokai, Akihiko; Handa, Tomohiro; Chen, Fengshi; Tanizawa, Kiminobu; Aoyama, Akihiro; Kubo, Takeshi; Ikezoe, Kohei; Nakatsuka, Yoshinari; Oguma, Tsuyoshi; Hirai, Toyohiro; Nagai, Sonoko; Chin, Kazuo; Date, Hiroshi; Mishima, Michiaki

2016-04-01

Lung perfusions after single lung transplantation (SLT) have not been fully clarified in patients with interstitial lung disease (ILD). The present study aimed to investigate temporal changes in native lung perfusion and their associated clinical factors in patients with ILD who have undergone SLT. Eleven patients were enrolled. Perfusion scintigraphy was serially performed up to 12 months after SLT. Correlations between the post-operative perfusion ratio in the native lung and clinical parameters, including pre-operative perfusion ratio and computed tomography (CT) volumetric parameters, were evaluated. On average, the perfusion ratio of the native lung was maintained at approximately 30% until 12 months after SLT. However, the ratio declined more significantly in idiopathic pulmonary fibrosis (IPF) than in other ILDs (p = 0.014). The perfusion ratio before SLT was significantly correlated with that at three months after SLT (ρ = 0.64, p = 0.048). The temporal change of the perfusion ratio in the native lung did not correlate with those of the CT parameters. The pre-operative perfusion ratio may predict the post-operative perfusion ratio of the native lung shortly after SLT in ILD. Perfusion of the native lung may decline faster in IPF compared with other ILDs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chronic Hypersensitivity Pneumonitis With a Usual Interstitial Pneumonia-Like Pattern: Correlation Between Histopathologic and Clinical Findings.

PubMed

Chiba, Sahoko; Tsuchiya, Kimitake; Akashi, Takumi; Ishizuka, Masahiro; Okamoto, Tsukasa; Furusawa, Haruhiko; Tateishi, Tomoya; Kishino, Mitsuhiro; Miyazaki, Yasunari; Tateishi, Ukihide; Takemura, Tamiko; Inase, Naohiko

2016-06-01

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of environmental antigens. The relationship between clinical, radiologic, and histopathologic findings of chronic HP remains unclear. Sixteen patients with proven chronic bird-related HP with a usual interstitial pneumonia-like pattern were analyzed retrospectively. Histopathologic findings were semiquantitatively assessed and compared with clinical and radiologic findings. We also evaluated the histopathologic findings affecting prognosis. The extent of centrilobular fibrosis was negatively correlated with Pao2 (r = -0.55, P = .03). The extent of bridging fibrosis was positively correlated with the ratio of maximal expiratory flow at 50% of forced vital capacity to that at 25% (r = 0.60, P = .02). Patients with a greater extent of fibroblastic foci (FF) had more radiologic reticulation (P = .01), honeycombing (P = .01), and traction bronchiectasis (P = .02), and had significantly shorter survival time (P = .01) than patients with a lesser extent of FF. Multivariate analysis showed that the extent of FF was a significant prognostic factor (hazard ratio, 2.36; 95% confidence interval, 1.02-5.48; P = .04). Our findings demonstrated that the extent of FF was significantly associated with reticulation, honeycombing, and traction bronchiectasis on high-resolution CT scanning. Moreover, the extent of FF could be a useful predictor of mortality in chronic HP with a usual interstitial pneumonia-like pattern. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Predicted occultations by Uranus - 1981-1984

NASA Technical Reports Server (NTRS)

Klemola, A. R.; Mink, D. J.; Elliot, J. L.

1981-01-01

Predictions are presented for 11 occultations by and appulses to Uranus and its ring system for ten stars from 1981 through 1984. The brightest stars are occulted on April 26, 1981 (BD - 19 deg 4222) and on April 22, 1982 (Hyd - 20 deg 51699). The ring system occults the same star twice during March 1983 (Hyd - 21 deg 64352).

Cordyceps sinensis attenuates renal fibrosis and suppresses BAG3 induction in obstructed rat kidney.

PubMed

Du, Feng; Li, Si; Wang, Tian; Zhang, Hai-Yan; Zong, Zhi-Hong; Du, Zhen-Xian; Li, De-Tian; Wang, Hua-Qin; Liu, Bo; Miao, Jia-Ning; Bian, Xiao-Hui

2015-01-01

BAG3 regulates a number of cellular processes, including cell proliferation, apoptosis, adhesion and migration, and epithelial-mesenchymal transition (EMT). However, the role of BAG3 in renal tubular EMT and renal interstitial fibrosis remains elusive. This study aimed to examine the dynamic expression of BAG3 during renal fibrosis, and to investigate the efficacy of Cordyceps sinensis (C. sinensis) on renal fibrosis. A rat model of unilateral ureteral obstruction (UUO) was established, and the expression of BAG3 and α-SMA, and the efficacy of C. sinensis on renal fibrosis induced by UUO were examined. The results showed that UUO led to collagen accumulation, which was significantly suppressed by C. sinensis. UUO increased the expression of BAG3 and α-SMA, a mesenchymal marker, while UUO induced BAG3 and α-SMA expression was significantly inhibited by C. sinensis. In addition, immunohistochemical staining demonstrated that BAG3 immunoreactivity was restricted to tubular epithelium. In conclusion, BAG3 is a potential target for the prevention and/or treatment of renal fibrosis, and C. Sinensis is a promising agent for renal fibrosis.

Radio occultation experiments with INAF-IRA radiotelescopes.

NASA Astrophysics Data System (ADS)

Pluchino, S.; Schillirò, F.; Salerno, E.; Pupillo, G.

The Radio Occultation research program performed at the Medicina and Noto Radioastronomical Stations of the Istituto Nazionale di Astrofisica (INAF) - Istituto di Radioastronomia (IRA) includes observations of spacecraft by satellite and satellite by satellite events. The Lunar Radio Occultation (LRO) part of the program consists in collecting data of the lunar Total Electron Content (TEC), at different limb longitudes and at different time, in order to study long term variation of the Moon's ionosphere. The LRO program started at Medicina in September 2006 with the observation of the European probe SMART-1 during its impact on the lunar soil. It proceeded in 2007 with the observation of the lunar occultations of Saturn and Venus, and with the observation of Mars in 2008. On this occasion the probes Cassini, Venus Express, Mars Express, Mars Reconaissance Orbiter and Mars Odissey were respectively occulted by the moon. On Dec 1st 2008 a Venus lunar occultation occurred. On that occasion we performed the first Italian-VLBI (I-VLBI) tracking experiment by detecting the carrier signals coming from the Venus Express (VEX) spacecraft with both the IRA radiotelescopes together with the Matera antenna of the Italian Space Agency. The second part of the radio occultation program includes the observation of satellite by satellite occultation events, as well as mutual occultations of Jupiter satellites. These events are referred to as mutual phenomena (PHEMU). These observations are aimed to measure the radio flux variation during the occultation and to derive surface spatial characteristics such as Io's hot spots. In this work preliminary results of the Radio Occultation program will be presented.

Radiologically occult medulloblastoma with hydrocephalus: case report.

PubMed

Honma, Hirokuni; Ogiwara, Hideki

2017-09-01

There have been no reports of occult medulloblastoma nor noncommunicating hydrocephalus due to radiologically occult brain tumors. Herein, we report radiologically occult medulloblastoma with noncommunicating hydrocephalus. A 3-year-old boy presented with macrocephaly, visual field constriction, and papilledema. Neuroimagings showed enlargement of the ventricles without any mass lesions. The CT cisternography did not show influx of the contrast into the ventricles, which suggested local cerebrospinal fluid (CSF) circulatory disturbance at the outlet of the fourth ventricle. Due to possible obstructive nature of hydrocephalus, endoscopic third ventriculostomy (ETV) was performed. Three months after the ETV, he presented with repeated vomiting. Neuroimagings showed a 3-cm fourth ventricular mass with progressive hydrocephalus. Surgical resection was performed, which revealed the pathology was medulloblastoma. We report the case of radiologically occult medulloblastoma which was demonstrated radiologically in the follow-up period of ETV for noncommunicating hydrocephalus of uncertain etiology. This is the first description of a radiologically occult medulloblastoma and also the first description of an occult brain tumor with noncommunicating hydrocephalus. The occult brain tumor may be included in the etiology of hydrocephalus.

Isozyme-specific comprehensive characterization of transglutaminase-crosslinked substrates in kidney fibrosis.

PubMed

Tatsukawa, Hideki; Otsu, Risa; Tani, Yuji; Wakita, Ryosuke; Hitomi, Kiyotaka

2018-05-09

Chronic kidney disease is characterized by prolonged decline in renal function, excessive accumulation of ECM, and progressive tissue fibrosis. Transglutaminase (TG) is a crosslinking enzyme that catalyzes the formation of covalent bonds between glutamine and lysine residues, and is involved in the induction of renal fibrosis via the stabilization of ECM and the activation of TGF-β1. Despite the accumulating evidences indicating that TG2 is a key enzyme in fibrosis, genetic knockout of TG2 reduced by only 50% the elevated protein crosslinking and fibrous protein in renal fibrosis model, whereas treatment with TG inhibitor almost completely reduced these levels. Here, we also clarified the distributions of TG isozymes and their in situ activities and identified the isozyme-specific crosslinked substrates for both TG1 and TG2 in fibrotic kidney. We found that TG1 activity was markedly enhanced in renal tubular epithelium and interstitial areas, whereas TG2 activity increased only in the extracellular space. In total, 47 and 67 possible candidates were identified as TG1 and TG2 substrates, respectively, only in fibrotic kidney. Among them, several possible substrates related to renal disease and fibrosis were identified. These findings provide novel insights into the mechanisms of renal fibrosis through the targeting of isozyme-specific TG substrates.

Infection-induced airway fibrosis in two rat strains with differential susceptibility.

PubMed Central

McIntosh, J C; Simecka, J W; Ross, S E; Davis, J K; Miller, E J; Cassell, G H

1992-01-01

Chronic infections play a significant role in the morbidity and mortality of patients with chronic airflow limitation. By stimulating airway inflammation, persistent infection has the potential to cause airway fibrosis. However, in patient this condition is most typically found in lungs damaged by other factors, such as smoking, abnormal secretions, or barotrauma. We report the characterization of Mycoplasma pulmonis infection-induced lung fibrosis in two immunocompetent rat strains with no preexisting lung disease. The fibrosis was predominantly in the airways, as demonstrated by the findings for infected animals of increased airway inflammation, airway fibrosis, and airway wall thickness, which correlated with the collagen content of the lungs. Also, the physiological alterations were the opposite of those found in interstitial fibrosis, with a positive correlation between lung compliance and collagen content. The airway fibrosis was noted earlier and to a greater extent in Lewis rats than in Fisher rats, and this result apparently was related to regulation of the inflammatory response. Airway wall thickness, airway inflammation, and airway fibrosis are commonly reported in tissue specimens from patients with chronic airway diseases and have been shown to correlate with airflow limitation in patients with chronic obstructive pulmonary disease. Thus, this model may be useful in furthering our understanding of the role of chronic infection and airway inflammation in airflow obstruction. Images PMID:1612760

Interstitial Features at Chest CT Enhance the Deleterious Effects of Emphysema in the COPDGene Cohort.

PubMed

Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Rahaghi, Farbod N; Sanchez-Ferrero, Gonzalo Vegas; Putman, Rachel K; Hunninghake, Gary M; Onieva, Jorge Onieva; Martinez, Fernando J; Choi, Augustine M; Bowler, Russell P; Lynch, David A; Hatabu, Hiroto; Bhatt, Surya P; Dransfield, Mark T; Wells, J Michael; Rosas, Ivan O; San Jose Estepar, Raul; Washko, George R

2018-06-05

Purpose To determine if interstitial features at chest CT enhance the effect of emphysema on clinical disease severity in smokers without clinical pulmonary fibrosis. Materials and Methods In this retrospective cohort study, an objective CT analysis tool was used to measure interstitial features (reticular changes, honeycombing, centrilobular nodules, linear scar, nodular changes, subpleural lines, and ground-glass opacities) and emphysema in 8266 participants in a study of chronic obstructive pulmonary disease (COPD) called COPDGene (recruited between October 2006 and January 2011). Additive differences in patients with emphysema with interstitial features and in those without interstitial features were analyzed by using t tests, multivariable linear regression, and Kaplan-Meier analysis. Multivariable linear and Cox regression were used to determine if interstitial features modified the effect of continuously measured emphysema on clinical measures of disease severity and mortality. Results Compared with individuals with emphysema alone, those with emphysema and interstitial features had a higher percentage predicted forced expiratory volume in 1 second (absolute difference, 6.4%; P < .001), a lower percentage predicted diffusing capacity of lung for carbon monoxide (DLCO) (absolute difference, 7.4%; P = .034), a 0.019 higher right ventricular-to-left ventricular (RVLV) volume ratio (P = .029), a 43.2-m shorter 6-minute walk distance (6MWD) (P < .001), a 5.9-point higher St George's Respiratory Questionnaire (SGRQ) score (P < .001), and 82% higher mortality (P < .001). In addition, interstitial features modified the effect of emphysema on percentage predicted DLCO, RVLV volume ratio, 6WMD, SGRQ score, and mortality (P for interaction < .05 for all). Conclusion In smokers, the combined presence of interstitial features and emphysema was associated with worse clinical disease severity and higher mortality than was emphysema alone. In addition, interstitial features

Mineralogic parameters related to amosite asbestos-induced fibrosis in humans

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

Churg, A.; Wright, J.; Wiggs, B.

1990-12-01

We have previously shown that in the lungs of a group of chrysotile miners and millers, grade of interstitial fibrosis (asbestosis) is directly proportional to tremolite fiber or chrysotile fiber concentration but is inversely proportional to mean fiber length and length-related parameters. To compare the effects of the commercial amphibole asbestos amosite on parenchymal fibrosis, we histologically graded fibrosis in four different sites in the lungs of 20 shipyard and insulation workers with heavy amosite exposure and measured by analytic electron microscopy fiber concentration and size in corresponding portions of lung tissue. Fibrosis grade was found to be strongly positivelymore » correlated with amosite concentration and negatively correlated with mean fiber size parameters, including fiber length, width, surface area, and mass. A comparison of our present results with our data on the chrysotile miners and millers showed that the regression lines of fibrosis grade versus concentration for amosite, chrysotile, and tremolite were statistically different. These findings indicate that amosite concentration, like chrysotile and tremolite concentration, is closely and directly related to fibrosis at the local lung level. Furthermore, these observations again raise the possibility that short fibers may be more important than is commonly believed in the genesis of fibrosis in man. Last, the concentration comparison data indicate that, fiber for fiber, amosite is more fibrogenic than is chrysotile or tremolite, and indirectly suggest that tremolite is more fibrogenic than is chrysotile.« less

The role of periostin in lung fibrosis and airway remodeling.

PubMed

O'Dwyer, David N; Moore, Bethany B

2017-12-01

Periostin is a protein that plays a key role in development and repair within the biological matrix of the lung. As a matricellular protein that does not contribute to extracellular matrix structure, periostin interacts with other extracellular matrix proteins to regulate the composition of the matrix in the lung and other organs. In this review, we discuss the studies exploring the role of periostin to date in chronic respiratory diseases, namely asthma and idiopathic pulmonary fibrosis. Asthma is a major health problem globally affecting millions of people worldwide with significant associated morbidity and mortality. Periostin is highly expressed in the lungs of asthmatic patients, contributes to mucus secretion, airway fibrosis and remodeling and is recognized as a biomarker of Th2 high inflammation. Idiopathic pulmonary fibrosis is a fatal interstitial lung disease characterized by progressive aberrant fibrosis of the lung matrix and respiratory failure. It predominantly affects adults over 50 years of age and its incidence is increasing worldwide. Periostin is also highly expressed in the lungs of idiopathic pulmonary fibrosis patients. Serum levels of periostin may predict clinical progression in this disease and periostin promotes myofibroblast differentiation and type 1 collagen production to contribute to aberrant lung fibrosis. Studies to date suggest that periostin is a key player in several pathogenic mechanisms within the lung and may provide us with a useful biomarker of clinical progression in both asthma and idiopathic pulmonary fibrosis.

Genetics and Early Detection in Idiopathic Pulmonary Fibrosis

PubMed Central

Putman, Rachel K.; Rosas, Ivan O.

2014-01-01

Genetic studies hold promise in helping to identify patients with early idiopathic pulmonary fibrosis (IPF). Recent studies using chest computed tomograms (CTs) in smokers and in the general population have demonstrated that imaging abnormalities suggestive of an early stage of pulmonary fibrosis are not uncommon and are associated with respiratory symptoms, physical examination abnormalities, and physiologic decrements expected, but less severe than those noted in patients with IPF. Similarly, recent genetic studies have demonstrated strong and replicable associations between a common promoter polymorphism in the mucin 5B gene (MUC5B) and both IPF and the presence of abnormal imaging findings in the general population. Despite these findings, it is important to note that the definition of early-stage IPF remains unclear, limited data exist to definitively connect abnormal imaging findings to IPF, and genetic studies assessing early-stage pulmonary fibrosis remain in their infancy. In this perspective we provide updated information on interstitial lung abnormalities and their connection to IPF. We summarize information on the genetics of pulmonary fibrosis by focusing on the recent genetic findings of MUC5B. Finally, we discuss the implications of these findings and suggest a roadmap for the use of genetics in the detection of early IPF. PMID:24547893

Exploring Animal Models That Resemble Idiopathic Pulmonary Fibrosis

PubMed Central

Tashiro, Jun; Rubio, Gustavo A.; Limper, Andrew H.; Williams, Kurt; Elliot, Sharon J.; Ninou, Ioanna; Aidinis, Vassilis; Tzouvelekis, Argyrios; Glassberg, Marilyn K.

2017-01-01

Large multicenter clinical trials have led to two recently approved drugs for patients with idiopathic pulmonary fibrosis (IPF); yet, both of these therapies only slow disease progression and do not provide a definitive cure. Traditionally, preclinical trials have utilized mouse models of bleomycin (BLM)-induced pulmonary fibrosis—though several limitations prevent direct translation to human IPF. Spontaneous pulmonary fibrosis occurs in other animal species, including dogs, horses, donkeys, and cats. While the fibrotic lungs of these animals share many characteristics with lungs of patients with IPF, current veterinary classifications of fibrotic lung disease are not entirely equivalent. Additional studies that profile these examples of spontaneous fibroses in animals for similarities to human IPF should prove useful for both human and animal investigators. In the meantime, studies of BLM-induced fibrosis in aged male mice remain the most clinically relevant model for preclinical study for human IPF. Addressing issues such as time course of treatment, animal size and characteristics, clinically irrelevant treatment endpoints, and reproducibility of therapeutic outcomes will improve the current status of preclinical studies. Elucidating the mechanisms responsible for the development of fibrosis and disrepair associated with aging through a collaborative approach between researchers will promote the development of models that more accurately represent the realm of interstitial lung diseases in humans. PMID:28804709

Interstitial nephritis.

PubMed

Papper, S

1980-01-01

There are many causes of interstitial nephritis other than pyelonephritis. The term interstitial nephritis does not connote a single etiologic or pathogenetic mechanism; it rather arbitrarily places together a wider variety of renal diseases that have a predilection for early and major involvement of the renal interstitium. The prototype of acute interstitial nephritis is acute pyelonephritis. In addition, there is a drug-related acute interstitial disease that is probably of immunological nature and usually reverses with discontinuance of the offending drug. Chronic interstitial nephritis includes many diverse illnesses. Nonobstructive pyelonephritis occurs but its prevalence is debated. Analgesic abuse nephropathy is not rare and is potentially reversible. Papillary necrosis has many causes and a wide spectrum of clinical presentations. Heavy metals, such as lead, cause interstitial nephritis. Balkan nephropathy occurs in an endemic area and although not bacterial in origin is of unknown cause.

[Progress in research of occult hepatitis B virus infection].

PubMed

Huang, X Y; Shi, Q F; Huang, T

2017-05-10

Occult hepatitis B virus infection is a worldwide public health problem, which seriously affects the clinical diagnosis of hepatitis B and threatens the safety of blood transfusion. The concept of occult hepatitis B virus infection, the pathogenesis of occult hepatitis B virus infection, the prevalence of occult hepatitis B virus infection in different groups, including healthy population and different patients, and the possibility of transmission were summarized. The prevalence of occult hepatitis B virus infection was found in healthy population and different patients, and there is possibility of occult hepatitis B virus infection to be transmitted through blood transfusion. The paper provides a comprehensive introduction of the pathogenesis and prevalence of occult hepatitis B virus infection. More attention should be paid to occult hepatitis B virus infection.

New perspectives in occult hepatitis C virus infection

PubMed Central

Carreño, Vicente; Bartolomé, Javier; Castillo, Inmaculada; Quiroga, Juan Antonio

2012-01-01

Occult hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in liver and in peripheral blood mononuclear cells (PBMCs) in the absence of detectable viral RNA in serum by standard assays, can be found in anti-HCV positive patients with normal serum levels of liver enzymes and in anti-HCV negative patients with persistently elevated liver enzymes of unknown etiology. Occult HCV infection is distributed worldwide and all HCV genotypes seem to be involved in this infection. Occult hepatitis C has been found not only in anti-HCV positive subjects with normal values of liver enzymes or in chronic hepatitis of unknown origin but also in several groups at risk for HCV infection such as hemodialysis patients or family members of patients with occult HCV. This occult infection has been reported also in healthy populations without evidence of liver disease. Occult HCV infection seems to be less aggressive than chronic hepatitis C although patients affected by occult HCV may develop liver cirrhosis and even hepatocellular carcinoma. Thus, anti-HCV negative patients with occult HCV may benefit from antiviral therapy with pegylated-interferon plus ribavirin. The persistence of very low levels of HCV RNA in serum and in PBMCs, along with the maintenance of specific T-cell responses against HCV-antigens observed during a long-term follow-up of patients with occult hepatitis C, indicate that occult HCV is a persistent infection that is not spontaneously eradicated. This is an updated report on diagnosis, epidemiology and clinical implications of occult HCV with special emphasis on anti-HCV negative cases. PMID:22736911

Stellar occultation studies of the solar system

NASA Technical Reports Server (NTRS)

Elliot, J. L.

1979-01-01

The paper covers the principles, observational procedures, and results relating to occultations of stars by solar system bodies other than the moon. Physical processes involved in occultations are presented including (1) extinction by ring material, (2) differential refraction by a planetary atmosphere, (3) extinction by a planetary atmosphere, and (4) Fresnel diffraction by sharp edges. It is noted that from a sufficient number of immersion and emersion timings of a stellar occultation, the radius and ellipticity of the occulting body can be accurately determined. From an occultation by a planet having an atmosphere, temperature, pressure, and number density profiles can be obtained along with information about the composition of the atmosphere and the extinction.

Method of Modeling and Simulation of Shaped External Occulters

NASA Technical Reports Server (NTRS)

Lyon, Richard G. (Inventor); Clampin, Mark (Inventor); Petrone, Peter, III (Inventor)

2016-01-01

The present invention relates to modeling an external occulter including: providing at least one processor executing program code to implement a simulation system, the program code including: providing an external occulter having a plurality of petals, the occulter being coupled to a telescope; and propagating light from the occulter to a telescope aperture of the telescope by scalar Fresnel propagation, by: obtaining an incident field strength at a predetermined wavelength at an occulter surface; obtaining a field propagation from the occulter to the telescope aperture using a Fresnel integral; modeling a celestial object at differing field angles by shifting a location of a shadow cast by the occulter on the telescope aperture; calculating an intensity of the occulter shadow on the telescope aperture; and applying a telescope aperture mask to a field of the occulter shadow, and propagating the light to a focal plane of the telescope via FFT techniques.

Occult Participation: Its Impact on Adolescent Development.

ERIC Educational Resources Information Center

Tennant-Clark, Cynthia M.; And Others

1989-01-01

Investigated relationship between occult participation, substance abuse, and level of self-esteem among 25 clinical (alcohol or drug treatment) and 25 nonclinical adolescents. Results indicated that adolescent substance abuse and occult participation were significantly related. Found significant differences between high versus low occult groups…

Immunephenotype of glomerular and interstitial infiltrating cells in protocol renal allograft biopsies and histological diagnosis.

PubMed

Moreso, F; Seron, D; O'Valle, F; Ibernon, M; Gomà, M; Hueso, M; Cruzado, J M; Bestard, O; Duarte, V; del Moral, R García; Grinyó, J M

2007-12-01

Patients with a protocol renal allograft biopsy simultaneously displaying interstitial fibrosis/tubular atrophy (IF/TA) and subclinical rejection (SCR) have a shortened graft survival than patients with a normal biopsy, or with a biopsy only displaying IF/TA or SCR. The poor outcome of these patients could be related with a more severe inflammation. We evaluate the immunophenotype of infiltrating cells in these diagnostic categories. Nonexhausted paraffin blocks from protocol biopsies done during the first year were stained with anti-CD45, CD3, CD20, CD68 and CD15 monoclonal antibodies. Glomerular and interstitial positive cells were counted. C4d deposition in peritubular capillaries was evaluated. Histological diagnoses were: normal (n = 80), SCR (n = 17), IF/TA (n = 42) and IF/TA + SCR (n = 17). Only interstitial CD20 positive cells were significantly increased in patients displaying IF/TA + SCR; normal (137 +/- 117), SCR (202 +/- 145), IF/TA (208 +/- 151) and IF/TA + SCR (307 +/- 180 cells/mm(2)), p < 0.01. The proportion of biopsies displaying C4d deposition was not different among groups. The upper tertile of CD20 positive interstitial cells was associated with a decreased death-censored graft survival (relative risk: 3.01, 95% confidence interval: 1.23-7.35; p = 0.015). These data suggest that B-cell interstitial infiltrates are associated with histological damage and outcome, but do not distinguish whether these infiltrates were the cause or the consequence of chronic tubulo-interstitial damage.

The Northrop Grumman External Occulter Testbed: Preliminary Results

NASA Astrophysics Data System (ADS)

Lo, Amy; Glassman, T.; Lillie, C.

2007-05-01

We have built a subscale testbed to demonstrate and validate the performance of the New Worlds Observer (NWO), a terrestrial planet finder external-occulter mission concept. The external occulter concept allows observations of nearby exo-Earths using two spacecraft: one carrying an occulter that is tens of meters in diameter and the other carrying a generic space telescope. The occulter is completely opaque, resembling a flower, with petals having a hypergaussian profile that enable 10-10 intensity suppression of stars that potentially harbor terrestrial planets. The baseline flight NWO system has a 30 meter occulter flying 30,000 km in front of a 4 meter class telescope. Testing the flight configuration on the ground is not feasible, so we have matched the Fresnel number of the flight configuration ( 10) using a subscale occulter. Our testbed consists of an 80 meter length evacuated tube, with a high precision occulter in the center of the tube. The occulter is 4 cm in diameter, manufactured with ¼ micron metrological accuracy and less than 2 micron tip truncation. This mimics a 30 meter occulter with millimeter figure accuracy and less than centimeter tip truncation. Our testbed is an evolving experiment, and we report here the first, preliminary, results using a single wavelength laser (532 nm) as the source.

N-acetylcysteine attenuates the development of cardiac fibrosis and remodeling in a mouse model of heart failure.

PubMed

Giam, Beverly; Chu, Po-Yin; Kuruppu, Sanjaya; Smith, A Ian; Horlock, Duncan; Kiriazis, Helen; Du, Xiao-Jun; Kaye, David M; Rajapakse, Niwanthi W

2016-04-01

Oxidative stress plays a central role in the pathogenesis of heart failure. We aimed to determine whether the antioxidantN-acetylcysteine can attenuate cardiac fibrosis and remodeling in a mouse model of heart failure. Minipumps were implanted subcutaneously in wild-type mice (n = 20) and mice with cardiomyopathy secondary to cardiac specific overexpression of mammalian sterile 20-like kinase 1 (MST-1;n = 18) to administerN-acetylcysteine (40 mg/kg per day) or saline for a period of 8 weeks. At the end of this period, cardiac remodeling and function was assessed via echocardiography. Fibrosis, oxidative stress, and expression of collagen types I andIIIwere quantified in heart tissues. Cardiac perivascular and interstitial fibrosis were greater by 114% and 209%, respectively, inMST-1 compared to wild type (P ≤ 0.001). InMST-1 mice administeredN-acetylcysteine, perivascular and interstitial fibrosis were 40% and 57% less, respectively, compared to those treated with saline (P ≤ 0. 03). Cardiac oxidative stress was 119% greater inMST-1 than in wild type (P < 0.001) andN-acetylcysteine attenuated oxidative stress inMST-1 by 42% (P = 0.005). These data indicate thatN-acetylcysteine can blunt cardiac fibrosis and related remodeling in the setting of heart failure potentially by reducing oxidative stress. This study provides the basis to investigate the role ofN-acetylcysteine in chronic heart failure. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Upper lobe fibrosis: a novel manifestation of chronic allograft dysfunction in lung transplantation.

PubMed

Pakhale, Smita Sakha; Hadjiliadis, Denis; Howell, David N; Palmer, Scott M; Gutierrez, Carlos; Waddell, Thomas K; Chaparro, Cecilia; Davis, R Duane; Keshavjee, Shaf; Hutcheon, Michael A; Singer, Lianne G

2005-09-01

Lung transplantation is an established treatment modality for a number of chronic lung diseases. Long-term survival after lung transplantation is limited by chronic allograft dysfunction, usually manifested by bronchiolitis obliterans syndrome. We describe a case series with upper lobe fibrosis, a novel presentation of chronic allograft dysfunction. We reviewed lung transplants at the Toronto General Hospital and Duke University Hospital from 1990 to 2002 and identified patients with upper lobe fibrosis. Thirteen of 686 patients (6 women) developed upper lobe fibrosis (Toronto, 9; Duke, 4); 12 of 13 had bilateral transplants. The median age at diagnosis was 42 years (range, 19-70). Primary diagnoses were cystic fibrosis, 6; emphysema, 4; sarcoidosis, 1; and pulmonary fibrosis, 2 patients. Radiographic diagnosis was made at a median of 700 days post-transplant (range, 150-2,920). Pulmonary function tests demonstrated predominantly a progressively worsening restrictive pattern. Open lung biopsy specimens revealed dense interstitial fibrosis, with occasional features of obliterative bronchitis, bronchiolitis obliterans obstructive pneumonia, and aspiration. Nine patients died at a median follow-up of 2,310 days (range, 266-3,740), 8 due to respiratory failure. Upper lobe fibrosis is a novel presentation of chronic allograft dysfunction in lung transplant recipients and is differentiated from bronchiolitis obliterans syndrome on the basis of physiologic and radiologic findings.

Triton stellar occultation candidates: 1995-1999

NASA Technical Reports Server (NTRS)

Mcdonald, S. W.; Elliot, J. L.

1995-01-01

We have completed a search for candidates for stellar occultations by Triton over the years 1995-1999. CCd strip scan images provided star positions in the relevant sky area to a depth of about 17.5 R magnitude. Over this time period, we find that Triton passes within 1.0 arcsec of 75 stars. Appulses with geocentric minimum separations of less than 0.35 arcsec will result in stellar occultations, but further astrometry and photometry is necessary to refine individual predictions for identification of actual occultations. Finder charts are included to aid in further studies and prediction refinement. The two most promising potential occultations, Tr176 and Tr180, occur in 1997.

Exploring the Solar System with Stellar Occultations

NASA Technical Reports Server (NTRS)

Elliot, J. L.; Dunham, E. W.

1984-01-01

By recording the light intensity as a function of time when a planet occults a relatively bright star, the thermal structure of the upper atmosphere of the planet can be probed. The main feature of stellar occultation observations is their high spatial resolution, typically several thousand times better than the resolution achievable with ground-based imaging. Five stellar occultations have been observed. The main results of these observations are summarized. Stellar occultations have been observed on Uranus, Mars, Pallas, Neptune and the Jovian Ring.

Leptospira Interrogans Induces Fibrosis in the Mouse Kidney through Inos-Dependent, TLR- and NLR-Independent Signaling Pathways

PubMed Central

Fanton d'Andon, Martine; Quellard, Nathalie; Fernandez, Béatrice; Ratet, Gwenn; Lacroix-Lamandé, Sonia; Vandewalle, Alain; Boneca, Ivo G.; Goujon, Jean-Michel; Werts, Catherine

2014-01-01

Background Leptospira (L.) interrogans are bacteria responsible for a worldwide reemerging zoonosis. Rodents carry L. interrogans asymptomatically in their kidneys and excrete bacteria in the urine, contaminating the environment. Humans get infected through skin contact and develop a mild or severe leptospirosis that may lead to renal failure and fibrosis. L. interrogans provoke an interstitial nephritis, but the induction of fibrosis caused by L. interrogans has not been studied in murine models. Innate immune receptors from the TLR and NLR families have recently been shown to play a role in the development and progression of tissue fibrosis in the lung, liver and kidneys under different pathophysiological situations. We recently showed that TLR2, TLR4, and NLRP3 receptors were crucial in the defense against leptospirosis. Moreover, infection of a human cell line with L. interrogans was shown to induce TLR2-dependent production of fibronectin, a component of the extracellular matrix. Therefore, we thought to assess the presence of renal fibrosis in L. interrogans infected mice and to analyze the contribution of some innate immune pathways in this process. Methodology/principal findings Here, we characterized by immunohistochemical studies and quantitative real-time PCR, a model of Leptospira-infected C57BL/6J mice, with chronic carriage of L. interrogans inducing mild renal fibrosis. Using various strains of transgenic mice, we determined that the renal infiltrates of T cells and, unexpectedly, TLR and NLR receptors, are not required to generate Leptospira-induced renal fibrosis. We also show that the iNOS enzyme, known to play a role in Leptospira-induced interstitial nephritis, also plays a role in the induction of renal fibrosis. Conclusion/significance To our knowledge, this work provides the first experimental murine model of sustained renal fibrosis induced by a chronic bacterial infection that may be peculiar, since it does not rely on TLR or NLR receptors

Occult hemorrhage in children with severe ITP.

PubMed

Flores, Adolfo; Buchanan, George R

2016-03-01

Little is known about the frequency and significance of clinically unapparent or occult hemorrhage in ITP. Therefore, we prospectively explored the sites and frequency of occult bleeding in children with severe ITP at diagnosis or upon symptomatic relapse in a prospective, single-institution cohort study of patients ≤ 18 years of age and a platelet count ≤ 10,000/mm(3) . Data collected included bleeding severity assessment, urinalysis, fecal occult blood testing, and non-contrast brain MRI. Stool and urine samples were tested within 7 days of diagnosis or symptomatic relapse. Three months after diagnosis or relapse a noncontrast brain MRI evaluated hemosiderin deposits resulting from prior localized hemorrhage. Fifty-two ITP patients were enrolled with a mean platelet count of 4,000/mm(3) . A significant occurrence of occult hemorrhage was identified in the urine (27%) compared with clinically overt hematuria (0.91%, P < 0.0005). CNS microbleeding in the superficial cortex of the left frontal lobe was identified in one child with occult bleeding in the urinary tract. There was no relationship between occult hemorrhage and bleeding manifestations on physical examination. Occult hemorrhage was not a harbinger of subsequent bleeding. Our findings suggest that occult hemorrhage occurs with greater frequency than overt bleeding in children with severe ITP. CNS microbleeding is a potential risk in this patient population. Assessment of brain microbleeds and microscopic hematuria in this patient population require additional study. © 2015 Wiley Periodicals, Inc.

Personalized medicine in interstitial lung diseases.

PubMed

Spagnolo, Paolo; Oldham, Justin M; Jones, Mark G; Lee, Joyce S

2017-05-01

A number of recent studies have explored the possibility to apply personalized medicine to interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF), the most common and deadly of the idiopathic interstitial pneumonias. In our review, we summarize and discuss the most recent literature on personalized medicine in IPF as well as hypersensitivity pneumonitis and sarcoidosis, with emphasis on patient subgroups for which a personalized approach to disease prognostication and management may become a reality in the near future. Most of the studies that have explored the applicability of personalized medicine to ILDs have been conducted in patients with IPF. Such studies have suggested the existence of several distinct disease subgroups defined by similar genetic profiles, molecular pathways, exposures and individual lifestyles. Personalized medicine in hypersensitivity pneumonitis is in its infancy. The development and applicability of personalized medicine to sarcoidosis, on the other hand, remains problematic for several reasons, including the lack of a diagnostic gold standard, the highly variable and unpredictable disease course, particularly across patients of different ethnicities, the poor correlation between disease activity and disease severity and the lack of a validated management algorithm. A number of distinct patient subgroups have been identified in ILDs. Although available data need to be validated longitudinally, the possibility to study homogeneous groups of patients may allow prediction of disease behavior and response to treatment with dramatic clinical implications.

Diffusion and interactions of interstitials in hard-sphere interstitial solid solutions

NASA Astrophysics Data System (ADS)

van der Meer, Berend; Lathouwers, Emma; Smallenburg, Frank; Filion, Laura

2017-12-01

Using computer simulations, we study the dynamics and interactions of interstitial particles in hard-sphere interstitial solid solutions. We calculate the free-energy barriers associated with their diffusion for a range of size ratios and densities. By applying classical transition state theory to these free-energy barriers, we predict the diffusion coefficients, which we find to be in good agreement with diffusion coefficients as measured using event-driven molecular dynamics simulations. These results highlight that transition state theory can capture the interstitial dynamics in the hard-sphere model system. Additionally, we quantify the interactions between the interstitials. We find that, apart from excluded volume interactions, the interstitial-interstitial interactions are almost ideal in our system. Lastly, we show that the interstitial diffusivity can be inferred from the large-particle fluctuations alone, thus providing an empirical relationship between the large-particle fluctuations and the interstitial diffusivity.

Changes in Urinary Microbiome Populations Correlate in Kidney Transplants With Interstitial Fibrosis and Tubular Atrophy Documented in Early Surveillance Biopsies.

PubMed

Modena, B D; Milam, R; Harrison, F; Cheeseman, J A; Abecassis, M M; Friedewald, J J; Kirk, A D; Salomon, D R

2017-03-01

An unbalanced microbiome may lead to disease by creating aberrant immune responses. A recent association of cellular rejection with the development of interstitial fibrosis and tubular atrophy (IFTA) suggests the role of immune-mediated tissue injury. We hypothesized that developing IFTA correlates with altered urinary tract microbiomes (UMBs). UMBs at two serial time points, 1 and 6-8 months posttransplant, were assessed by 16S microbial ribosomal gene sequencing in 25 patients developing biopsy-proven IFTA compared to 23 transplant patients with normal biopsies and excellent function (TX) and 20 healthy nontransplant controls (HC). Streptococcus, the dominant genera in HC males, was lower in IFTA and TX males at 1 month compared to HCs. At 6-8 months, Streptococcus was further decreased in IFTA males, but normalized in TX. IFTA males and females had increases in number of genera per sample at 6-8 months. UMB composition varied substantially between individuals in all groups. Despite the wide variation in UMBs between individuals, IFTA was associated with a loss in dominant resident urinary microbes in males, and a parallel increase in nonresident, pathogenic bacteria in males and females. UMB changes may contribute to IFTA development by alteration of the host immune response. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Optical performance of the New Worlds Occulter

NASA Astrophysics Data System (ADS)

Arenberg, Jonathan W.; Lo, Amy S.; Glassman, Tiffany M.; Cash, Webster

2007-04-01

The New Worlds Observer (NWO) is a multiple spacecraft mission that is capable of detecting and characterizing extra-solar planets and planetary systems. NWO consists of an external occulter and a generic space telescope, flying in tandem. The external occulter has specific requirements on its shape and size, while the telescope needs no special modification beyond that required to do high-quality astrophysical observations. The occulter is a petal-shaped, opaque screen that creates a high-suppression shadow large enough to accommodate the telescope. This article reports on the optical performance of the novel New Worlds occulter design. It also introduces two new aspects of its optical performance which enhance the detectability of extra-solar planets. We also include a brief discussion of the buildability and the tolerances of the occulter. It is also shown that an occulter design can be found for any set of science requirements. We show that NWO is a viable mission concept for the study of extra-solar planets. To cite this article: J.W. Arenberg et al., C. R. Physique 8 (2007).

Experiment D005: Star occultation navigation

NASA Technical Reports Server (NTRS)

Silva, R. M.; Jorris, T. R.; Vallerie, E. M., III

1971-01-01

The usefulness of star occultation measurements for space navigation and the determination of a horizon density profile which could be used to update atmospheric models for horizon-based measurement systems were studied. The time of occultation of a known star by a celestial body, as seen by an orbiting observer, determines a cylinder of position, the axis of which is the line through the star and the body center, and the radius of which is equal to the occulting-body radius. The dimming percentage, with respect to the altitude of this grazing ray from the star to the observer, is a percentage altitude for occultation. That is, the star can be assumed to be occulted when it reaches a predetermined percentage of its unattenuated value. The procedure used was to measure this attenuation with respect to time to determine the usefulness of the measurements for autonomous space navigation. In this experiment, the crewmembers had to accomplish star acquisition, identification, calibration, and tracking. Instrumentation was required only for measurement of the relative intensity of the star as it set into the atmosphere.

The lung in rheumatoid arthritis - focus on interstitial lung disease.

PubMed

Spagnolo, Paolo; Lee, Joyce C; Sverzellati, Nicola; Rossi, Giulio; Cottin, Vincent

2018-05-27

Interstitial lung disease (ILD) is an increasingly recognized complication of rheumatoid arthritis (RA) and is associated with significant morbidity and mortality. In addition, approximately one-third of patients have subclinical disease with varying degrees of functional impairment. While risk factors for RA-ILD are well established (e.g., older age, male gender, ever smoking history and seropositivity to rheumatoid factor and anti-cyclic citrullinated peptide antibodies) little is known about optimal disease assessment, treatment and monitoring, particularly in patients with progressive disease. Patients with RA-ILD are also at high risk of infection and drug toxicity, which, along with comorbidities, complicate further treatment decision making. There are distinct histopathologic patterns of RA-ILD with different clinical phenotypes, natural history and prognosis. Of these, the usual interstitial pneumonia (UIP) subtype of RA-ILD shares a number of clinical and histopathologic features with idiopathic pulmonary fibrosis (IPF), the most common and severe of the idiopathic interstitial pneumonias, suggesting the existence of common mechanistic pathways and possibly therapeutic targets. There remain substantial gaps in our knowledge of RA-ILD. Concerted multinational effort of expert centres has the potential to elucidate the basic mechanisms underlying RA-UIP and other subtypes of RA-ILD and facilitate the development of more efficacious and safer drugs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evaluation for Occult Fractures in Injured Children

PubMed Central

French, Benjamin; Song, Lihai; Feudtner, Chris

2015-01-01

OBJECTIVES: To examine variation across US hospitals in evaluation for occult fractures in (1) children <2 years old diagnosed with physical abuse and (2) infants <1 year old with injuries associated with a high likelihood of abuse and to identify factors associated with such variation. METHODS: We performed a retrospective study in children <2 years old with a diagnosis of physical abuse and in infants <1 year old with non-motor vehicle crash–related traumatic brain injury or femur fractures discharged from 366 hospitals in the Premier database from 2009 to 2013. We examined across-hospital variation and identified child- and hospital-level factors associated with evaluation for occult fractures. RESULTS: Evaluations for occult fractures were performed in 48% of the 2502 children with an abuse diagnosis, in 51% of the 1574 infants with traumatic brain injury, and in 53% of the 859 infants with femur fractures. Hospitals varied substantially with regard to their rates of evaluation for occult fractures in all 3 groups. Occult fracture evaluations were more likely to be performed at teaching hospitals than at nonteaching hospitals (all P < .001). The hospital-level annual volume of young, injured children was associated with the probability of occult fracture evaluation, such that hospitals treating more young, injured patients were more likely to evaluate for occult fractures (all P < .001). CONCLUSIONS: Substantial variation in evaluation for occult fractures among young children with a diagnosis of abuse or injuries associated with a high likelihood of abuse highlights opportunities for quality improvement in this vulnerable population. PMID:26169425

Evaluation for Occult Fractures in Injured Children.

PubMed

Wood, Joanne N; French, Benjamin; Song, Lihai; Feudtner, Chris

2015-08-01

To examine variation across US hospitals in evaluation for occult fractures in (1) children <2 years old diagnosed with physical abuse and (2) infants <1 year old with injuries associated with a high likelihood of abuse and to identify factors associated with such variation. We performed a retrospective study in children <2 years old with a diagnosis of physical abuse and in infants <1 year old with non-motor vehicle crash-related traumatic brain injury or femur fractures discharged from 366 hospitals in the Premier database from 2009 to 2013. We examined across-hospital variation and identified child- and hospital-level factors associated with evaluation for occult fractures. Evaluations for occult fractures were performed in 48% of the 2502 children with an abuse diagnosis, in 51% of the 1574 infants with traumatic brain injury, and in 53% of the 859 infants with femur fractures. Hospitals varied substantially with regard to their rates of evaluation for occult fractures in all 3 groups. Occult fracture evaluations were more likely to be performed at teaching hospitals than at nonteaching hospitals (all P < .001). The hospital-level annual volume of young, injured children was associated with the probability of occult fracture evaluation, such that hospitals treating more young, injured patients were more likely to evaluate for occult fractures (all P < .001). Substantial variation in evaluation for occult fractures among young children with a diagnosis of abuse or injuries associated with a high likelihood of abuse highlights opportunities for quality improvement in this vulnerable population. Copyright © 2015 by the American Academy of Pediatrics.

Treatment of idiopathic pulmonary fibrosis with losartan: a pilot project.

PubMed

Couluris, Marisa; Kinder, Brent W; Xu, Ping; Gross-King, Margaret; Krischer, Jeffrey; Panos, Ralph J

2012-10-01

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease with no current effective therapies. Treatment has focused on antifibrotic agents to stop proliferation of fibroblasts and collagen deposition in the lung. We present the first clinical trial data on the use of losartan, an antifibrotic agent, to treat idiopathic pulmonary fibrosis. The primary objective was to evaluate the effect of losartan on progression of idiopathic pulmonary fibrosis measured by the change in percentage of predicted forced vital capacity (%FVC) after 12 months. Secondary outcomes included the change in forced expiratory volume at 1 second, diffusing capacity of carbon monoxide, 6-minute walk test distance, and baseline/transition dyspnea index. Patients with idiopathic pulmonary fibrosis and a baseline %FVC of ≥50 % were treated with losartan 50 mg by mouth daily for 12 months. Pulmonary function testing, 6-minute walk, and breathlessness indices were measured every 3 months. Twenty participants with idiopathic pulmonary fibrosis were enrolled and 17 patients were evaluable for response. Twelve patients had a stable or improved %FVC at study month 12. Similar findings were observed in secondary end-point measures, including 58, 71, and 65 % of patients with stable or improved forced expiratory volume at 1 second, diffusing capacity for carbon monoxide, and 6-minute walk test distance, respectively. No treatment-related adverse events that resulted in early study discontinuation were reported. Losartan stabilized lung function in patients with idiopathic pulmonary fibrosis over 12 months. Losartan is a promising agent for the treatment of idiopathic pulmonary fibrosis and has a low toxicity profile.

Unilateral lung transplantation for pulmonary fibrosis.

PubMed

1986-05-01

Improvements in immunosuppression and surgical techniques have made unilateral lung transplantation feasible in selected patients with end-stage interstitial lung disease. We report two cases of successful unilateral lung transplantation for end-stage respiratory failure due to pulmonary fibrosis. The patients, both oxygen-dependent, had progressive disease refractory to all treatment, with an anticipated life expectancy of less than one year on the basis of the rate of progression of the disease. Both patients were discharged six weeks after transplantation and returned to normal life. They are alive and well at 26 months and 14 months after the procedure. Pulmonary-function studies have shown substantial improvement in their lung volumes and diffusing capacities. For both patients, arterial oxygen tension is now normal and there is no arterial oxygen desaturation with exercise. This experience shows that unilateral lung transplantation, for selected patients with end-stage interstitial lung disease, provides a good functional result. Moreover, it avoids the necessity for cardiac transplantation, as required by the combined heart-lung procedure, and permits the use of the donor heart for another recipient.

Molecular Mechanisms Underlying Occult Hepatitis B Virus Infection

PubMed Central

Samal, Jasmine; Kandpal, Manish

2012-01-01

Summary: Chronic hepatitis B virus (HBV) infection is a complex clinical entity frequently associated with cirrhosis and hepatocellular carcinoma (HCC). The persistence of HBV genomes in the absence of detectable surface antigenemia is termed occult HBV infection. Mutations in the surface gene rendering HBsAg undetectable by commercial assays and inhibition of HBV by suppression of viral replication and viral proteins represent two fundamentally different mechanisms that lead to occult HBV infections. The molecular mechanisms underlying occult HBV infections, including recently identified mechanisms associated with the suppression of HBV replication and inhibition of HBV proteins, are reviewed in detail. The availability of highly sensitive molecular methods has led to increased detection of occult HBV infections in various clinical settings. The clinical relevance of occult HBV infection and the utility of appropriate diagnostic methods to detect occult HBV infection are discussed. The need for specific guidelines on the diagnosis and management of occult HBV infection is being increasingly recognized; the aspects of mechanistic studies that warrant further investigation are discussed in the final section. PMID:22232374

ASTEROID SIZING BY RADIOGALAXY OCCULTATION AT 5 GHZ

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

Lehtinen, K.; Muinonen, K.; Poutanen, M.

Stellar occultations by asteroids observed at visual wavelengths have been an important tool for studying the size and shape of asteroids and for revising the orbital parameters of asteroids. At radio frequencies, a shadow of an asteroid on the Earth is dominated by diffraction effects. Here, we show, for the first time, that a single observation of an occultation of a compact radio source at a frequency of 5 GHz can be used to derive the effective size of the occulting object and to derive the distance between the observer and the center of the occultation path on the Earth.more » The derived diameter of the occulting object, asteroid (115) Thyra, is 75 ± 6 km. The observed occultation profile shows features that cannot be explained by diffraction of a single asteroid.« less

Role of Magnetic Resonance Elastography as a Noninvasive Measurement Tool of Fibrosis in a Renal Allograft: A Case Report.

PubMed

Kim, J K; Yuen, D A; Leung, G; Jothy, S; Zaltzman, J; Ramesh Prasad, G V; Prabhudesai, V; Mnatzakanian, G; Kirpalani, A

2017-09-01

A major reason for poor long-term kidney transplant outcomes is the development of chronic allograft injury, characterized by interstitial fibrosis and tubular atrophy. Currently, an invasive biopsy that samples only <1% of the kidney is the gold standard for detecting kidney allograft fibrosis. We report the use of magnetic resonance elastography (MRE) to quantify tissue stiffness as a noninvasive and whole-kidney measurement tool of allograft fibrosis in a kidney transplant patient at 2 time points. The MRE whole-kidney stiffness values reflected the changes in fibrosis of the kidney allograft as assessed by histologic examination. To our knowledge, this technique is the first observation of change over time in MRE-derived whole-kidney stiffness in an allograft that is consistent with changes in histology-derived fibrosis scores in a single patient. Copyright © 2017 Elsevier Inc. All rights reserved.

Image Analysis of the 2012 Pluto (Near) Occultation

DTIC Science & Technology

2013-09-01

Image Analysis of the 2012 Pluto (Near) Occultation Keith T. Knox Air Force Research Laboratory ABSTRACT Imagery was gathered at the AMOS...observatory on the 3.6-meter telescope for the expected occultation of a star by the dwarf planet, Pluto , on 29 June 2012. The imagery was taken at...5 Hz for 40 minutes before and after the expected time of occultation. The initial analysis of the photometry indicated that Pluto did not occult

Short-term Automated Quantification of Radiologic Changes in the Characterization of Idiopathic Pulmonary Fibrosis Versus Nonspecific Interstitial Pneumonia and Prediction of Long-term Survival.

PubMed

De Giacomi, Federica; Raghunath, Sushravya; Karwoski, Ronald; Bartholmai, Brian J; Moua, Teng

2018-03-01

Fibrotic interstitial lung diseases presenting with nonspecific and overlapping radiologic findings may be difficult to diagnose without surgical biopsy. We hypothesized that baseline quantifiable radiologic features and their short-term interval change may be predictive of underlying histologic diagnosis as well as long-term survival in idiopathic pulmonary fibrosis (IPF) presenting without honeycombing versus nonspecific interstitial pneumonia (NSIP). Forty biopsy-confirmed IPF and 20 biopsy-confirmed NSIP patients with available high-resolution chest computed tomography 4 to 24 months apart were studied. CALIPER software was used for the automated characterization and quantification of radiologic findings. IPF subjects were older (66 vs. 48; P<0.0001) with lower diffusion capacity for carbon monoxide and higher volumes of baseline reticulation (193 vs. 83 mL; P<0.0001). Over the interval period, compared with NSIP, IPF patients experienced greater functional decline (forced vital capacity, -6.3% vs. -1.7%; P=0.02) and radiologic progression, as noted by greater increase in reticulation volume (24 vs. 1.74 mL; P=0.048), and decrease in normal (-220 vs. -37.7 mL; P=0.045) and total lung volumes (-198 vs. 58.1 mL; P=0.03). Older age, male gender, higher reticulation volumes at baseline, and greater interval decrease in normal lung volumes were predictive of IPF. Both baseline and short-term changes in quantitative radiologic findings were predictive of mortality. Baseline quantitative radiologic findings and assessment of short-term disease progression may help characterize underlying IPF versus NSIP in those with difficult to differentiate clinicoradiologic presentations. Our study supports the possible utility of assessing serial quantifiable high-resolution chest computed tomographic findings for disease differentiation in these 2 entities.

Occult pneumomediastinum in blunt chest trauma: clinical significance.

PubMed

Rezende-Neto, J B; Hoffmann, J; Al Mahroos, M; Tien, H; Hsee, L C; Spencer Netto, F; Speers, V; Rizoli, S B

2010-01-01

Thoracic injuries are potentially responsible for 25% of all trauma deaths. Chest X-ray is commonly used to screen patients with chest injury. However, the use of computed tomography (CT) scan for primary screening is increasing, particularly for blunt trauma. CT scans are more sensitive than chest X-ray in detecting intra-thoracic abnormalities such as pneumothoraces and pneumomediastinums. Pneumomediastinum detected by chest X-ray or "overt pneumomediastinum", raises the concern of possible aerodigestive tract injuries. In contrast, there is scarce information on the clinical significance of pneumomediastinum diagnosed by CT scan only or "occult pneumomediastinum". Therefore we investigated the clinical consequences of occult pneumomediastinum in our blunt trauma population. A 2-year retrospective chart review of all blunt chest trauma patients with initial chest CT scan admitted to a level I trauma centre. Data extracted from the medical records include; demographics, occult, overt, or no pneumomediastinum, the presence of intra-thoracic aerodigestive tract injuries (trachea, bronchus, and/or esophagus), mechanism and severity of injury, endotracheal intubation, chest thoracostomy, operations and radiological reports by an attending radiologist. All patients with intra-thoracic aerodigestive tract injuries from 1994 to 2004 were also investigated. Of 897 patients who met the inclusion criteria 839 (93.5%) had no pneumomediastinum. Five patients (0.6%) had overt pneumomediastinum and 53 patients (5.9%) had occult pneumomediastinum. Patients with occult pneumomediastinum had significantly higher ISS and AIS chest (p<0.0001) than patients with no pneumomediastinum. A chest thoracostomy tube was more common (p<0.0001) in patients with occult pneumomediastinum (47.2%) than patients with no pneumomediastinum (10.4%), as well as occult pneumothorax. None of the patients with occult pneumomediastinum had aerodigestive tract injuries (95%CI 0-0.06). Follow up CT scan of

Morphologically occult systemic mastocytosis in bone marrow: clinicopathologic features and an algorithmic approach to diagnosis.

PubMed

Reichard, Kaaren K; Chen, Dong; Pardanani, Animesh; McClure, Rebecca F; Howard, Matthew T; Kurtin, Paul J; Wood, Adam J; Ketterling, Rhett P; King, Rebecca L; He, Rong; Morice, William G; Hanson, Curtis A

2015-09-01

Bone marrow (BM) biopsy specimens involved by systemic mastocytosis (SM) typically show multifocal, compact, dense aggregates of spindled mast cells (MCs). However, some cases lack aggregate formation and fulfill the World Health Organization 2008 criteria for SM, based on minor criteria. We identified 26 BM cases of KIT D816V-mutated, morphologically occult SM in the BM. All patients had some combination of allergic/MC activating symptoms. Peripheral blood counts were generally normal. BM aspirates showed 5% or less MCs, which were only occasionally spindled. BM biopsy specimens showed no morphologic classic MC lesions. Tryptase immunohistochemistry (IHC) demonstrated interstitial, individually distributed MCs (up to 5%) with prominent spindling, lacking aggregate formation. MCs coexpressed CD25 by IHC and/or flow cytometry. Spindled MCs constituted more than 25% of total MCs in all cases and more than 50% in 20 of 26 cases. Morphologically occult involvement of normal-appearing BM by SM will be missed without appropriate clinical suspicion and pathologic evaluation by tryptase and CD25 IHC and KIT D816V mutation analysis. On the basis of these findings, we propose a cost-effective, data-driven, evidence-based algorithmic approach to the workup of these cases. Copyright© by the American Society for Clinical Pathology.

Interstitial cystitis - resources

MedlinePlus

Resources - interstitial cystitis ... The following organizations are good resources for information on interstitial cystitis : Interstitial Cystitis Association -- www.ichelp.org National Institute of Diabetes and Digestive and Kidney Diseases -- www. ...

An Exome Sequencing Study to Assess the Role of Rare Genetic Variation in Pulmonary Fibrosis.

PubMed

Petrovski, Slavé; Todd, Jamie L; Durheim, Michael T; Wang, Quanli; Chien, Jason W; Kelly, Fran L; Frankel, Courtney; Mebane, Caroline M; Ren, Zhong; Bridgers, Joshua; Urban, Thomas J; Malone, Colin D; Finlen Copeland, Ashley; Brinkley, Christie; Allen, Andrew S; O'Riordan, Thomas; McHutchison, John G; Palmer, Scott M; Goldstein, David B

2017-07-01

Idiopathic pulmonary fibrosis (IPF) is an increasingly recognized, often fatal lung disease of unknown etiology. The aim of this study was to use whole-exome sequencing to improve understanding of the genetic architecture of pulmonary fibrosis. We performed a case-control exome-wide collapsing analysis including 262 unrelated individuals with pulmonary fibrosis clinically classified as IPF according to American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines (81.3%), usual interstitial pneumonia secondary to autoimmune conditions (11.5%), or fibrosing nonspecific interstitial pneumonia (7.2%). The majority (87%) of case subjects reported no family history of pulmonary fibrosis. We searched 18,668 protein-coding genes for an excess of rare deleterious genetic variation using whole-exome sequence data from 262 case subjects with pulmonary fibrosis and 4,141 control subjects drawn from among a set of individuals of European ancestry. Comparing genetic variation across 18,668 protein-coding genes, we found a study-wide significant (P < 4.5 × 10 -7 ) case enrichment of qualifying variants in TERT, RTEL1, and PARN. A model qualifying ultrarare, deleterious, nonsynonymous variants implicated TERT and RTEL1, and a model specifically qualifying loss-of-function variants implicated RTEL1 and PARN. A subanalysis of 186 case subjects with sporadic IPF confirmed TERT, RTEL1, and PARN as study-wide significant contributors to sporadic IPF. Collectively, 11.3% of case subjects with sporadic IPF carried a qualifying variant in one of these three genes compared with the 0.3% carrier rate observed among control subjects (odds ratio, 47.7; 95% confidence interval, 21.5-111.6; P = 5.5 × 10 -22 ). We identified TERT, RTEL1, and PARN-three telomere-related genes previously implicated in familial pulmonary fibrosis-as significant contributors to sporadic IPF. These results support the idea that

Occult urolithiasis in asymptomatic primary hyperparathyroidism.

PubMed

Tay, Yu-Kwang Donovan; Liu, Minghao; Bandeira, Leonardo; Bucovsky, Mariana; Lee, James A; Silverberg, Shonni J; Walker, Marcella D

2018-05-01

Recent international guidelines suggest renal imaging to detect occult urolithiasis in all patients with asymptomatic primary hyperparathyroidism (PHPT), but data regarding their prevalence and associated risk factors are limited. We evaluated the prevalence and risk factors for occult urolithiasis. Cross-sectional analysis of 96 asymptomatic PHPT patients from a university hospital in the United States with and without occult nephrolithiasis. Occult urolithiasis was identified in 21% of patients. Stone formers had 47% higher 24-hour urinary calcium excretion (p = 0.002). Although available in only a subset of patients (n = 28), activated vitamin D [1,25(OH) 2 D] was 29% higher (p = 0.02) in stone formers. There was no difference in demographics, BMI, calcium or vitamin D intake, other biochemistries, renal function, BMD, or fractures. Receiver operating characteristic curves indicated that urinary calcium excretion and 1,25(OH) 2 D had an area under the curve of 0.724 (p = 0.003) and 0.750 (p = 0.04), respectively. A urinary calcium threshold of >211mg/day provided a sensitivity of 84.2% and a specificity of 55.3% while a 1,25(OH) 2 D threshold of >91pg/mL provided a sensitivity and specificity of 62.5% and 90.0% respectively for the presence of stones. Occult urolithiasis is present in about one-fifth of patients with asymptomatic PHPT and is associated with higher urinary calcium and 1,25(OH) 2 D. Given that most patients will not have occult urolithiasis, targeted imaging in those most likely to have occult stones rather than screening all asymptomatic PHPT patients may be useful. The higher sensitivity of urinary calcium versus 1,25(OH) 2 D suggests screening those with higher urinary calcium may be an appropriate approach.

Progress on an external occulter testbed at flight Fresnel numbers

NASA Astrophysics Data System (ADS)

Kim, Yunjong; Sirbu, Dan; Galvin, Michael; Kasdin, N. Jeremy; Vanderbei, Robert J.

2016-01-01

An external occulter is a spacecraft flown along the line-of-sight of a space telescope to suppress starlight and enable high-contrast direct imaging of exoplanets. Laboratory verification of occulter designs is necessary to validate the optical models used to design and predict occulter performance. At Princeton, we have designed and built a testbed that allows verification of scaled occulter designs whose suppressed shadow is mathematically identical to that of space occulters. The occulter testbed uses 78 m optical propagation distance to realize the flight Fresnel numbers. We will use an etched silicon mask as the occulter. The occulter is illuminated by a diverging laser beam to reduce the aberrations from the optics before the occulter. Here, we present first light result of a sample design operating at a flight Fresnel number and the mechanical design of the testbed. We compare the experimental results with simulations that predict the ultimate contrast performance.

Earth rotation derived from occultation records

NASA Astrophysics Data System (ADS)

Sôma, Mitsuru; Tanikawa, Kiyotaka

2016-04-01

We determined the values of the Earth's rotation parameter, ΔT = T T - UT, around AD 500 after confirming that the value of the tidal acceleration, dot{n}, of the lunar motion remained unchanged during the period between ancient times and the present. For determining of ΔT, we used contemporaneous occultations of planets by the Moon. In general, occultation records are not useful. However, there are some records that give us a stringent condition for the range of ΔT. Records of the lunar occultations in AD 503 and AD 513 are such examples. In order to assure the usefulness of this occultation data, we used contemporaneous annular and total solar eclipses, which have not been used in the preceding work. This is the first work in which the lunar occultation data have been used as primary data to determine the value of ΔT together with auxiliary contemporaneous annular and total solar eclipses. Our ΔT value is less than a smoothed value (Stephenson 1997) by at least 450 s. The result is consistent with our earlier results obtained from solar eclipses.

Deletion of H-Ras decreases renal fibrosis and myofibroblast activation following ureteral obstruction in mice.

PubMed

Grande, M Teresa; Fuentes-Calvo, Isabel; Arévalo, Miguel; Heredia, Fabiana; Santos, Eugenio; Martínez-Salgado, Carlos; Rodríguez-Puyol, Diego; Nieto, M Angela; López-Novoa, José M

2010-03-01

Tubulointerstitial fibrosis is characterized by the presence of myofibroblasts that contribute to extracellular matrix accumulation. These cells may originate from resident fibroblasts, bone-marrow-derived cells, or renal epithelial cells converting to a mesenchymal phenotype. Ras GTPases are activated during renal fibrosis and play crucial roles in regulating both cell proliferation and TGF-beta-induced epithelial-mesenchymal transition. Here we set out to assess the contribution of Ras to experimental renal fibrosis using the well-established model of unilateral ureteral obstruction. Fifteen days after obstruction, both fibroblast proliferation and inducers of epithelial-mesenchymal transition were lower in obstructed kidneys of H-ras knockout mice and in fibroblast cell lines derived from these mice. Interestingly, fibronectin, collagen I accumulation, overall interstitial fibrosis, and the myofibroblast population were also lower in the knockout than in the wild-type mice. As expected, we found lower levels of activated Akt in the kidneys and cultured fibroblasts of the knockout. Whether Ras inhibition will turn out to prevent progression of renal fibrosis will require more direct studies.

Association of preS/S Mutations with Occult Hepatitis B Virus (HBV) Infection in South Korea: Transmission Potential of Distinct Occult HBV Variants

PubMed Central

Kim, Hong; Kim, Bum-Joon

2015-01-01

Occult hepatitis B virus infection (HBV) is characterized by HBV DNA positivity but HBV surface antigen (HBsAg) negativity. Occult HBV infection is associated with a risk of HBV transmission through blood transfusion, hemodialysis, and liver transplantation. Furthermore, occult HBV infection contributes to the development of cirrhosis and hepatocellular carcinoma. We recently reported the characteristic molecular features of mutations in the preS/S regions among Korean individuals with occult infections caused by HBV genotype C2; the variants of preS and S related to severe liver diseases among chronically infected patients were also responsible for the majority of HBV occult infections. We also reported that HBsAg variants from occult-infected Korean individuals exhibit lower HBsAg secretion capacity but not reduced HBV DNA levels. In addition, these variants exhibit increased ROS-inducing capacity compared with the wild-type strain, linking HBV occult infections to liver cell damage. Taken together, our previous reports suggest the transmission potential of distinct HBV occult infection-related variants in South Korea. PMID:26084041

Association of preS/S Mutations with Occult Hepatitis B Virus (HBV) Infection in South Korea: Transmission Potential of Distinct Occult HBV Variants.

PubMed

Kim, Hong; Kim, Bum-Joon

2015-06-15

Occult hepatitis B virus infection (HBV) is characterized by HBV DNA positivity but HBV surface antigen (HBsAg) negativity. Occult HBV infection is associated with a risk of HBV transmission through blood transfusion, hemodialysis, and liver transplantation. Furthermore, occult HBV infection contributes to the development of cirrhosis and hepatocellular carcinoma. We recently reported the characteristic molecular features of mutations in the preS/S regions among Korean individuals with occult infections caused by HBV genotype C2; the variants of preS and S related to severe liver diseases among chronically infected patients were also responsible for the majority of HBV occult infections. We also reported that HBsAg variants from occult-infected Korean individuals exhibit lower HBsAg secretion capacity but not reduced HBV DNA levels. In addition, these variants exhibit increased ROS-inducing capacity compared with the wild-type strain, linking HBV occult infections to liver cell damage. Taken together, our previous reports suggest the transmission potential of distinct HBV occult infection-related variants in South Korea.

The diagnosis of idiopathic pulmonary fibrosis: current and future approaches

PubMed Central

Martinez, Fernando J; Chisholm, Alison; Collard, Harold R; Flaherty, Kevin R; Myers, Jeffrey; Raghu, Ganesh; Walsh, Simon LF; White, Eric S; Richeldi, Luca

2017-01-01

With the recent development of two effective treatments for patients with idiopathic pulmonary fibrosis, an accurate diagnosis is crucial. The traditional approach to diagnosis emphasises the importance of thorough clinical and laboratory evaluations to exclude secondary causes of disease. High-resolution CT is a critical initial diagnostic test and acts as a tool to identify patients who should undergo surgical lung biopsy to secure a definitive histological diagnosis of usual interstitial pneumonia pattern. This diagnostic approach faces several challenges. Many patients with suspected idiopathic pulmonary fibrosis present with atypical high-resolution CT characteristics but are unfit for surgical lung biopsy, therefore preventing a confident diagnosis. The state of the art suggests an iterative, multidisciplinary process that incorporates available clinical, laboratory, imaging, and histological features. Recent research has explored genomic techniques to molecularly phenotype patients with interstitial lung disease. In the future, clinicians will probably use blood-specific or lung-specific molecular markers in combination with other clinical, physiological, and imaging features to enhance diagnostic efforts, refine prognostic recommendations, and influence the initial or subsequent treatment options. There is an urgent and increasing need for well designed, large, prospective studies measuring the effect of different diagnostic approaches. Ultimately, this will help to inform the development of guidelines and tailor clinical practice for the benefit of patients. PMID:27932290

Probing Titan's atmosphere with a stellar occultation

NASA Technical Reports Server (NTRS)

Hubbard, W. B.

1991-01-01

The 3 July, 1989 occultation of 28 Sgr by Titan is discussed. The star was readily detectable throughout the occultation, reaching a minimum normalized flux of about 0.05. The occultation probed Titan's atmosphere in a region not studied by the Voyager spacecraft. The region is important for the aerobraking of Titan entry probes, and direct information about its properties is important for the Cassini mission. Occultation data (normalized stellar flux vs universal time) is shown in chart form for NASA supported stations, along with data from a collaborating group at the Wise observatory in Israel. Strong scintillation data of the star is noticeable in the data records, and provides information on waves/turbulence in Titan's high atmosphere.

Further characterization of computed tomographic and clinical features for staging and prognosis of idiopathic pulmonary fibrosis in West Highland white terriers.

PubMed

Thierry, Florence; Handel, Ian; Hammond, Gawain; King, Lesley G; Corcoran, Brendan M; Schwarz, Tobias

2017-07-01

Idiopathic pulmonary fibrosis is an interstitial lung disease of unknown etiology resulting in progressive interstitial fibrosis, with a known predilection in West Highland white terriers. In humans, computed tomography (CT) is a standard method for providing diagnostic and prognostic information, and plays a major role in the idiopathic pulmonary fibrosis staging process. Objectives of this retrospective, analytical, cross-sectional study were to establish descriptive criteria for reporting CT findings and test correlations among CT, clinical findings and survival time in West Highland white terriers with idiopathic pulmonary fibrosis. Inclusion criteria for affected West Highland white terriers were a diagnosis of idiopathic pulmonary fibrosis and available CT, bronchoscopy, bronchoalveolar lavage, echocardiography, and routine blood analysis findings. Clinically normal West Highland white terriers were recruited for the control group. Survival times were recorded for affected dogs. The main CT lung pattern and clinical data were blindly and separately graded as mild, moderate, or severe. Twenty-one West Highland white terriers with idiopathic pulmonary fibrosis and 11 control West Highland white terriers were included. The severity of pulmonary CT findings was positively correlated with severity of clinical signs (ρ = 0.48, P = 0.029) and negatively associated with survival time after diagnosis (ρ = -0.56, P = 0.025). Affected dogs had higher lung attenuation (median: -563 Hounsfield Units (HU)) than control dogs (median: -761 HU), (P < 0.001). The most common CT characteristics were ground-glass pattern (16/21) considered as a mild degree of severity, and focal reticular and mosaic ground-glass patterns (10/21) considered as a moderate degree of severity. Findings supported the use of thoracic CT as a method for characterizing idiopathic pulmonary fibrosis in West Highland white terriers and providing prognostic information for owners. © 2017 The Authors

Experimental induction of pulmonary fibrosis in horses with the gammaherpesvirus equine herpesvirus 5.

PubMed

Williams, Kurt J; Robinson, N Edward; Lim, Ailam; Brandenberger, Christina; Maes, Roger; Behan, Ashley; Bolin, Steven R

2013-01-01

Gammaherpesviruses (γHV) are implicated in the pathogenesis of pulmonary fibrosis in humans and murine models of lung fibrosis, however there is little direct experimental evidence that such viruses induce lung fibrosis in the natural host. The equine γHV EHV 5 is associated with equine multinodular pulmonary fibrosis (EMPF), a progressive fibrosing lung disease in its natural host, the horse. Experimental reproduction of EMPF has not been attempted to date. We hypothesized that inoculation of EHV 5 isolated from cases of EMPF into the lungs of clinically normal horses would induce lung fibrosis similar to EMPF. Neutralizing antibody titers were measured in the horses before and after inoculation with EHV 5. PCR and virus isolation was used to detect EHV 5 in antemortem blood and BAL samples, and in tissues collected postmortem. Nodular pulmonary fibrosis and induction of myofibroblasts occurred in EHV 5 inoculated horses. Mean lung collagen in EHV 5 inoculated horses (80 µg/mg) was significantly increased compared to control horses (26 µg/mg) (p < 0.5), as was interstitial collagen (32.6% ± 1.2% vs 23% ± 1.4%) (mean ± SEM; p < 0.001). Virus was difficult to detect in infected horses throughout the experiment, although EHV 5 antigen was detected in the lung by immunohistochemistry. We conclude that the γHV EHV 5 can induce lung fibrosis in the horse, and hypothesize that induction of fibrosis occurs while the virus is latent within the lung. This is the first example of a γHV inducing lung fibrosis in the natural host.

Experimental Induction of Pulmonary Fibrosis in Horses with the Gammaherpesvirus Equine Herpesvirus 5

PubMed Central

Williams, Kurt J.; Robinson, N. Edward; Lim, Ailam; Brandenberger, Christina; Maes, Roger; Behan, Ashley; Bolin, Steven R.

2013-01-01

Gammaherpesviruses (γHV) are implicated in the pathogenesis of pulmonary fibrosis in humans and murine models of lung fibrosis, however there is little direct experimental evidence that such viruses induce lung fibrosis in the natural host. The equine γHV EHV 5 is associated with equine multinodular pulmonary fibrosis (EMPF), a progressive fibrosing lung disease in its natural host, the horse. Experimental reproduction of EMPF has not been attempted to date. We hypothesized that inoculation of EHV 5 isolated from cases of EMPF into the lungs of clinically normal horses would induce lung fibrosis similar to EMPF. Neutralizing antibody titers were measured in the horses before and after inoculation with EHV 5. PCR and virus isolation was used to detect EHV 5 in antemortem blood and BAL samples, and in tissues collected postmortem. Nodular pulmonary fibrosis and induction of myofibroblasts occurred in EHV 5 inoculated horses. Mean lung collagen in EHV 5 inoculated horses (80 µg/mg) was significantly increased compared to control horses (26 µg/mg) (p < 0.5), as was interstitial collagen (32.6% ± 1.2% vs 23% ± 1.4%) (mean ± SEM; p < 0.001). Virus was difficult to detect in infected horses throughout the experiment, although EHV 5 antigen was detected in the lung by immunohistochemistry. We conclude that the γHV EHV 5 can induce lung fibrosis in the horse, and hypothesize that induction of fibrosis occurs while the virus is latent within the lung. This is the first example of a γHV inducing lung fibrosis in the natural host. PMID:24147074

Io hot spots - Infrared photometry of satellite occultations

NASA Technical Reports Server (NTRS)

Goguen, J. D.; Matson, D. L.; Sinton, W. M.; Howell, R. R.; Dyck, H. M.

1988-01-01

Io's active hot spots, which are presently mapped on the basis of IR photometry of this moon's occultation by other Gallilean satellites, are obtained with greatest spatial resolution near the sub-earth point. A model is developed for the occultation lightcurves, and its fitting to the data defines the apparent path of the occulting satellite relative to Io; the mean error in apparent relative position of occulting satellites is of the order of 178 km. A heretofore unknown, 20-km diameter hot spot is noted on Io's leading hemisphere.

Strong scintillations during atmospheric occultations Theoretical intensity spectra. [radio scattering during spacecraft occultations by planetary atmospheres

NASA Technical Reports Server (NTRS)

Hinson, D. P.

1986-01-01

Each of the two Voyager spacecraft launched in 1977 has completed a reconnaissance of the Jovian and Saturnian systems. In connection with occultation experiments, strong scintillations were observed. Further theoretical work is required before these scintillations can be interpreted. The present study is, therefore, concerned with the derivation of a theory for strong scattering during atmospheric occultation experiments, taking into account as fundamental quantity of interest the spatial spectrum (or spectral density) of intensity fluctuations. Attention is given to a theory for intensity spectra, and numerical calculations. The new formula derived for Phi-i accounts for strong scattering of electromagnetic waves during atmospheric occultations.

OCCULT-ORSER complete conversational user-language translator

NASA Technical Reports Server (NTRS)

Ramapriyan, H. K.; Young, K.

1981-01-01

Translator program (OCCULT) assists non-computer-oriented users in setting up and submitting jobs for complex ORSER system. ORSER is collection of image processing programs for analyzing remotely sensed data. OCCULT is designed for those who would like to use ORSER but cannot justify acquiring and maintaining necessary proficiency in Remote Job Entry Language, Job Control Language, and control-card formats. OCCULT is written in FORTRAN IV and OS Assembler for interactive execution.

Sizes, Shapes, and Satellites of Asteroids from Occultations

NASA Astrophysics Data System (ADS)

Waring Dunham, David; Herald, David Russell; Preston, Steve; Timerson, Bradley; Maley, Paul; Frappa, Eric; Hayamizu, Tsutomu; Talbot, John; Poro, Atila

2015-08-01

For 40 years, the sizes and shapes of dozens of asteroids have been determined from observations of asteroidal occultations. Some of the first evidence for satellites of asteroids was obtained from the early efforts; now, the orbits and sizes of some satellites discovered by other means have been refined from occultation observations. Also, several close binary stars have been discovered, and the angular diameters of some stars have been measured from analysis of these observations. The International Occultation Timing Association (IOTA) coordinates this activity worldwide, from predicting and publicizing the events, to accurately timing the occultations from as many stations as possible, and publishing and archiving the observations.The release of the Hipparcos and Tycho catalogs in 1997, from ESA’s Hipparcos space mission, revolutionized asteroidal occultation work, increasing the routine accuracy of the predictions and the annual number of observations by an order of magnitude. IOTA developed an efficient procedure for predicting the occultations using a combination of new star catalogs, based on Hipparcos and new star catalogs, generated mainly at the U. S. Naval Observatory (USNO), and new observations of asteroids relative to the improved astrometric nets mainly from USNO’s Flagstaff Astrometric Scanning Transit Telescope and JPL’s Table Mountain Observatory. In addition, many IOTA observers now use inexpensive low-light-level video cameras and specially built GPS video time inserters to accurately time the events. This automation has also allowed some observers to deploy multiple remote video stations across occultation paths. Then, one observer can record several “chords” across the asteroid. The cameras are sensitive enough that easily-hidden telescopes, many of which can be packed in standard air travel suitcases, can be used for many of the predicted occultations. IOTA’s network of regional coordinators collect and reduce the observations

[Normal lung volumes in patients with idiopathic pulmonary fibrosis and emphysema].

PubMed

Casas, Juan Pablo; Abbona, Horacio; Robles, Adriana; López, Ana María

2008-01-01

Pulmonary function tests in idiopathic pulmonary fibrosis characteristically show a restrictive pattern, resulting from reduction of pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. Previous reports suggest that when both diseases coexist, pulmonary volumes are compensated and a smaller than expected reduction or even normal lung volumes can be found. We report 4 male patients of 64, 60, 73 and 70 years, all with heavy cigarette smoking history and progressive breathlessness. Three of them had severe limitation in their quality of life. All four showed advanced lung interstitial involvement, at high resolution CT scan, fibrotic changes predominantly in the subpleural areas of lower lung fields and concomitant emphysema in the upper lobes. Emphysema and pulmonary fibrosis was confirmed by open lung biopsy in one patient. The four patients showed normal spirometry and lung volumes with severe compromise of gas exchange and poor exercise tolerance evaluated by 6 minute walk test. Severe pulmonary arterial hypertension was also confirmed in three patients. Normal lung volumes does not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

Chymase: a multifunctional player in pulmonary hypertension associated with lung fibrosis.

PubMed

Kosanovic, Djuro; Luitel, Himal; Dahal, Bhola Kumar; Cornitescu, Teodora; Janssen, Wiebke; Danser, A H Jan; Garrelds, Ingrid M; De Mey, Jo G R; Fazzi, Gregorio; Schiffers, Paul; Iglarz, Marc; Fischli, Walter; Ghofrani, Hossein Ardeschir; Weissmann, Norbert; Grimminger, Friedrich; Seeger, Werner; Reiss, Irwin; Schermuly, Ralph Theo

2015-10-01

Limited literature sources implicate mast-cell mediator chymase in the pathologies of pulmonary hypertension and pulmonary fibrosis. However, there is no evidence on the contribution of chymase to the development of pulmonary hypertension associated with lung fibrosis, which is an important medical condition linked with increased mortality of patients who already suffer from a life-threatening interstitial lung disease.The aim of this study was to investigate the role of chymase in this particular pulmonary hypertension form, by using a bleomycin-induced pulmonary hypertension model.Chymase inhibition resulted in attenuation of pulmonary hypertension and pulmonary fibrosis, as evident from improved haemodynamics, decreased right ventricular remodelling/hypertrophy, pulmonary vascular remodelling and lung fibrosis. These beneficial effects were associated with a strong tendency of reduction in mast cell number and activity, and significantly diminished chymase expression levels. Mechanistically, chymase inhibition led to attenuation of transforming growth factor β1 and matrix-metalloproteinase-2 contents in the lungs. Furthermore, chymase inhibition prevented big endothelin-1-induced vasoconstriction of the pulmonary arteries.Therefore, chymase plays a role in the pathogenesis of pulmonary hypertension associated with pulmonary fibrosis and may represent a promising therapeutic target. In addition, this study may provide valuable insights on the contribution of chymase in the pulmonary hypertension context, in general, regardless of the pulmonary hypertension form. Copyright ©ERS 2015.

The occult submucous cleft palate.

PubMed

Kaplan, E N

1975-10-01

We have studied 41 patients with classic submucous cleft and 32 cases with occult submucous cleft. Both groups have the same anatomic abnormality that leads to velar dysfunction-the insertion of the palate muscles onto the hard palate rather than onto the midline soft palate raphe. However, the occult submucous cleft palate does not have the classic triad of bifid uvula, hard palate bony notch, and furrow in the midline of the soft palate. Characteristic facial features, cephalmetric x-rays, and cine voice studies can help make a presumptive diagnosis of occult submucous cleft palate. Surgical management includes a diagnostic palate exploration to identify muscle configuration followed by levator muscle sling reconstruction, palate pushback, and pharyngeal flap. Excellent speech results are obtained except with patients having palate paresis.

Effect of mixing scanner types and reconstruction kernels on the characterization of lung parenchymal pathologies: emphysema, interstitial pulmonary fibrosis and normal non-smokers

NASA Astrophysics Data System (ADS)

Xu, Ye; van Beek, Edwin J.; McLennan, Geoffrey; Guo, Junfeng; Sonka, Milan; Hoffman, Eric

2006-03-01

In this study we utilize our texture characterization software (3-D AMFM) to characterize interstitial lung diseases (including emphysema) based on MDCT generated volumetric data using 3-dimensional texture features. We have sought to test whether the scanner and reconstruction filter (kernel) type affect the classification of lung diseases using the 3-D AMFM. We collected MDCT images in three subject groups: emphysema (n=9), interstitial pulmonary fibrosis (IPF) (n=10), and normal non-smokers (n=9). In each group, images were scanned either on a Siemens Sensation 16 or 64-slice scanner, (B50f or B30 recon. kernel) or a Philips 4-slice scanner (B recon. kernel). A total of 1516 volumes of interest (VOIs; 21x21 pixels in plane) were marked by two chest imaging experts using the Iowa Pulmonary Analysis Software Suite (PASS). We calculated 24 volumetric features. Bayesian methods were used for classification. Images from different scanners/kernels were combined in all possible combinations to test how robust the tissue classification was relative to the differences in image characteristics. We used 10-fold cross validation for testing the result. Sensitivity, specificity and accuracy were calculated. One-way Analysis of Variances (ANOVA) was used to compare the classification result between the various combinations of scanner and reconstruction kernel types. This study yielded a sensitivity of 94%, 91%, 97%, and 93% for emphysema, ground-glass, honeycombing, and normal non-smoker patterns respectively using a mixture of all three subject groups. The specificity for these characterizations was 97%, 99%, 99%, and 98%, respectively. The F test result of ANOVA shows there is no significant difference (p <0.05) between different combinations of data with respect to scanner and convolution kernel type. Since different MDCT and reconstruction kernel types did not show significant differences in regards to the classification result, this study suggests that the 3-D AMFM can

Mesenchymal Stem Cell Therapy Prevents Interstitial Fibrosis and Tubular Atrophy in a Rat Kidney Allograft Model

PubMed Central

Herrero, Esther; Torras, Joan; Ripoll, Elia; Flaquer, Maria; Gomà, Montse; Lloberas, Nuria; Anegon, Ignacio; Cruzado, Josep M.; Grinyó, Josep M.; Herrero-Fresneda, Immaculada

2012-01-01

In solid organ transplantation, mesenchymal stem cell (MSC) therapy is strongly emerging among other cell therapies due to the positive results obtained in vitro and in vivo as an immunomodulatory agent and their potential regenerative role. We aimed at testing whether a single dose of MSCs, injected at 11 weeks after kidney transplantation for the prevention of chronic mechanisms, enhanced regeneration and provided protection against the inflammatory and fibrotic processes that finally lead to the characteristic features of chronic allograft nephropathy (CAN). Either bone marrow mononuclear cells (BMCs) injection or no-therapy (NT) were used as control treatments. A rat kidney transplantation model of CAN with 2.5 h of cold ischemia was used, and functional, histological, and molecular parameters were assessed at 12 and 24 weeks after transplantation. MSC and BMC cell therapy preserves renal function at 24 weeks and abrogates proteinuria, which is typical of this model (NT24w: 68.9±26.5 mg/24 h, MSC24w: 16.6±2.3 mg/24 h, BMC24w: 24.1±5.3 mg/24 h, P<0.03). Only MSC-treated animals showed a reduction in interstitial fibrosis and tubular atrophy (NT24w: 2.3±0.29, MSC24w: 0.4±0.2, P<0.03), less T cells (NT: 39.6±9.5, MSC: 8.1±0.9, P<0.03) and macrophages (NT: 20.9±4.7, MSC: 5.9±1.7, P<0.05) infiltrating the parenchyma and lowered expression of inflammatory cytokines while increasing the expression of anti-inflammatory factors. MSCs appear to serve as a protection from injury development rather than regenerate the damaged tissue, as no differences were observed in Ki67 expression, and kidney injury molecule-1, Clusterin, NGAL, and hepatocyte growth factor expression were only up-regulated in nontreated animals. Considering the results, a single delayed MSC injection is effective for the long-term protection of kidney allografts. PMID:22494435

Study of the technique of stellar occultation

NASA Technical Reports Server (NTRS)

Hays, P. B.; Graves, M. E.; Roble, R. G.; Shah, A. N.

1973-01-01

The results are reported of a study of the stellar occultation technique for measuring the composition of the atmosphere. The intensity of starlight was monitored during the occultation using the Wisconsin stellar ultraviolet photometers aboard the Orbiting Astronomical Observatory (OAO-A2). A schematic diagram of an occultation is shown where the change in intensity at a given wavelength is illustrated. The vertical projection of the attenuation region is typically 60 km deep for molecular oxygen and 30 km deep for ozone. Intensity profiles obtained during various occultations were analyzed by first determining the tangential columm density of the absorbing gases, and then Abel inverting the column densities to obtain the number density profile. Errors are associated with each step in the inversion scheme and have been considered as an integral part of this study.

Production of Fibronectin by the Human Alveolar Macrophage: Mechanism for the Recruitment of Fibroblasts to Sites of Tissue Injury in Interstitial Lung Diseases

NASA Astrophysics Data System (ADS)

Rennard, Stephen I.; Hunninghake, Gary W.; Bitterman, Peter B.; Crystal, Ronald G.

1981-11-01

Because cells of the mononuclear phagocyte system are known to produce fibronectin and because alveolar macrophages are activated in many interstitial lung diseases, the present study was designed to evaluate a role for the alveolar macrophage as a source of the increased levels of fibronectin found in the lower respiratory tract in interstitial lung diseases and to determine if such fibronectin might contribute to the development of the fibrosis found in these disorders by being a chemoattractant for human lung fibroblasts. Production of fibronectin by human alveolar macrophages obtained by bronchoalveolar lavage and maintained in short-term culture in serum-free conditions was demonstrated; de novo synthesis was confirmed by the incorporation of [14C]proline. This fibronectin had a monomer molecular weight of 220,000 and was antigenically similar to plasma fibronectin. Macrophages from patients with idiopathic pulmonary fibrosis produced fibronectin at a rate 20 times higher than did normal macrophages; macrophages from patients with pulmonary sarcoidosis produced fibronectin at 10 times the normal rate. Macrophages from 6 of 10 patients with various other interstitial disorders produced fibronectin at rates greater than the rate of highest normal control. Human alveolar macrophage fibronectin was chemotactic for human lung fibroblasts, suggesting a functional role for this fibronectin in the derangement of the alveolar structures that is characteristic of these disorders.

Normal expiratory flow rate and lung volumes in patients with combined emphysema and interstitial lung disease: a case series and literature review.

PubMed

Heathcote, Karen L; Cockcroft, Donald W; Fladeland, Derek A; Fenton, Mark E

2011-01-01

Pulmonary function tests in patients with idiopathic pulmonary fibrosis characteristically show a restrictive pattern including small lung volumes and increased expiratory flow rates resulting from a reduction in pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. When the diseases coexist, pulmonary volumes are compensated, and a smaller than expected reduction or even normal lung volumes can be found. The present report describes 10 patients with progressive breathlessness, three of whom experienced severe limitation in their quality of life. All patients showed lung interstitial involvement and emphysema on computed tomography scan of the chest. The 10 patients showed normal spirometry and lung volumes with severe compromise of gas exchange. Normal lung volumes do not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

Biopsy in idiopathic pulmonary fibrosis: back to the future.

PubMed

Rossi, Giulio; Spagnolo, Paolo

2017-09-01

Idiopathic Pulmonary Fibrosis (IPF) is a relentlessly progressive, fibrosing interstitial pneumonia characterized by a radiologic and/or histologic pattern of usual interstitial pneumonia (UIP). The availability of two effective anti-fibrotic drugs in IPF has encouraged the identification and treatment of patients in early stages in order to maximize clinical benefit. The ability of high-resolution computed tomography (HRCT) to identify a 'definite' UIP pattern is suboptimal, particularly in the absence of honeycombing. Therefore, radiologic criteria for UIP are currently being redefined. Histology represents the major source of information to define a UIP pattern. Novel and less invasive approaches (particularly cryobiopsy) to sample interstitial lung diseases have demonstrated high sensitivity and specificity. In parallel, researchers are focusing on molecular mechanisms underlying IPF with the aim to identify more specific druggable targets. Lung tissue is therefore essential for diagnostic, pathogenetic and therapeutic purposes. Areas covered: We identified and critically reviewed the most relevant recent literature related to the limitations of current radiologic criteria, new lung sampling procedures, and molecular pathways in support of the need of lung tissue to better understand IPF. Expert commentary: The development of truly effective treatments for IPF requires the identification of key pathogenetic molecules and pathways. To this end, the availability of lung tissue is vital.

Characteristic patterns in the fibrotic lung. Comparing idiopathic pulmonary fibrosis with chronic lung allograft dysfunction.

PubMed

Fernandez, Isis E; Heinzelmann, Katharina; Verleden, Stijn; Eickelberg, Oliver

2015-03-01

Tissue fibrosis, a major cause of death worldwide, leads to significant organ dysfunction in any organ of the human body. In the lung, fibrosis critically impairs gas exchange, tissue oxygenation, and immune function. Idiopathic pulmonary fibrosis (IPF) is the most detrimental and lethal fibrotic disease of the lung, with an estimated median survival of 50% after 3-5 years. Lung transplantation currently remains the only therapeutic alternative for IPF and other end-stage pulmonary disorders. Posttransplant lung function, however, is compromised by short- and long-term complications, most importantly chronic lung allograft dysfunction (CLAD). CLAD affects up to 50% of all transplanted lungs after 5 years, and is characterized by small airway obstruction with pronounced epithelial injury, aberrant wound healing, and subepithelial and interstitial fibrosis. Intriguingly, the mechanisms leading to the fibrotic processes in the engrafted lung exhibit striking similarities to those in IPF; therefore, antifibrotic therapies may contribute to increased graft function and survival in CLAD. In this review, we focus on these common fibrosis-related mechanisms in IPF and CLAD, comparing and contrasting clinical phenotypes, the mechanisms of fibrogenesis, and biomarkers to monitor, predict, or prognosticate disease status.

Atg5-mediated autophagy deficiency in proximal tubules promotes cell cycle G2/M arrest and renal fibrosis.

PubMed

Li, Huiyan; Peng, Xuan; Wang, Yating; Cao, Shirong; Xiong, Liping; Fan, Jinjin; Wang, Yihan; Zhuang, Shougang; Yu, Xueqing; Mao, Haiping

2016-09-01

Macroautophagy/autophagy protects against cellular stress. Renal sublethal injury-triggered tubular epithelial cell cycle arrest at G2/M is associated with interstitial fibrosis. However, the role of autophagy in renal fibrosis is elusive. Here, we hypothesized that autophagy activity in tubular epithelial cells is pivotal for inhibition of cell cycle G2/M arrest and subsequent fibrogenic response. In both renal epithelial cells stimulated by angiotensin II (AGT II) and the murine kidney after unilateral ureteral obstruction (UUO), we observed that occurrence of autophagy preceded increased production of COL1 (collagen, type I). Pharmacological enhancement of autophagy by rapamycin suppressed COL1 accumulation and renal fibrosis. In contrast, genetic ablation of autophagy by proximal tubular epithelial cell-specific deletion of Atg5, with reduction of the LC3-II protein level and degradation of SQSTM1/p62, showed marked cell cycle arrest at the G2/M phase, robust COL1 deposition, and severe interstitial fibrosis in a UUO model, as compared with wild-type mice. In vitro, AGT II exposure triggered autophagy preferentially in the G1/S phase, and increased COL1 expression in the G2/M phase in renal epithelial cells. Stimulation of Atg5-deficient primary proximal tubular cells with AGT II also resulted in elevated G2/M arrest and COL1 production. Pharmacological or genetic inhibition of autophagy increased AGT II-mediated G2/M arrest. Enhanced expression of ATG5, but not the autophagy-deficient ATG5 mutant K130R, rescued the G2/M arrest, suggesting the regulation of cell cycle progression by ATG5 is autophagy dependent. In conclusion, Atg5-mediated autophagy in proximal epithelial cells is a critical host-defense mechanism that prevents renal fibrosis by blocking G2/M arrest.

Toxic Inhalational Injury-Associated Interstitial Lung Disease in Children

PubMed Central

Lee, Eun; Seo, Ju-Hee; Kim, Hyung Young; Yu, Jinho; Jhang, Won-Kyoung; Park, Seong-Jong; Kwon, Ji-Won; Kim, Byoung-Ju; Do, Kyung-Hyun; Cho, Young Ah; Kim, Sun-A; Jang, Se Jin

2013-01-01

Interstitial lung disease in children (chILD) is a group of disorders characterized by lung inflammation and interstitial fibrosis. In the past recent years, we noted an outbreak of child in Korea, which is possibly associated with inhalation toxicity. Here, we report a series of cases involving toxic inhalational injury-associated chILD with bronchiolitis obliterans pattern in Korean children. This study included 16 pediatric patients confirmed by lung biopsy and chest computed tomography, between February 2006 and May 2011 at Asan Medical Center Children's Hospital. The most common presenting symptoms were cough and dyspnea. The median age at presentation was 26 months (range: 12-47 months), with high mortality (44%). Histopathological analysis showed bronchiolar destruction and centrilobular distribution of alveolar destruction by inflammatory and fibroproliferative process with subpleural sparing. Chest computed tomography showed ground-glass opacities and consolidation in the early phase and diffuse centrilobular nodular opacity in the late phase. Air leak with severe respiratory difficulty was associated with poor prognosis. Although respiratory chemicals such as humidifier disinfectants were strongly considered as a cause of this disease, further studies are needed to understand the etiology and pathophysiology of the disease to improve the prognosis and allow early diagnosis and treatment. PMID:23772158

An integrated approach in the diagnosis of smoking-related interstitial lung diseases.

PubMed

Caminati, Antonella; Cavazza, Alberto; Sverzellati, Nicola; Harari, Sergio

2012-09-01

Cigarette smoke consists of several chemical compounds with a variety of effects in many organs. In the lung, apart being the main cause of chronic obstructive pulmonary disease, carcinoma and idiopathic spontaneous pneumothorax, tobacco smoke is associated with interstitial lung diseases (ILDs), including respiratory bronchiolitis-associated ILD (RB-ILD), desquamative interstitial pneumonia (DIP), pulmonary Langerhans' cell histiocytosis (PLCH), idiopathic pulmonary fibrosis, acute eosinophilic pneumonia, ILD in rheumatoid arthritis and pulmonary haemorrhage in Goodpasture syndrome. This review will focus on the diseases with a stronger epidemiological association with tobacco smoke, namely RB-ILD, DIP and PLCH. Although the exact pathogenetic evidence linking smoking with these disorders is still not completely understood, there is growing evidence that tobacco smoke targets the terminal or respiratory bronchioles in these diseases, and the differences are reflective of the degree of severity of small airway and parenchymal reaction to the smoke exposure. Despite considerable clinical, radiological and histological overlap between RB-ILD, DIP and PLCH, it is useful to retain the separate classifications for prognostic and therapeutic implications.

A pilot study: a combined therapy using polymyxin-B hemoperfusion and extracorporeal membrane oxygenation for acute exacerbation of interstitial pneumonia.

PubMed

Itai, Junji; Ohshimo, Shinichiro; Kida, Yoshiko; Ota, Kohei; Iwasaki, Yasumasa; Hirohashi, Nobuyuki; Bonella, Francesco; Guzman, Josune; Costabel, Ulrich; Kohno, Nobuoki; Tanigawa, Koichi

2015-01-05

Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) might be beneficial for treating acute exacerbation (AE) of interstitial pneumonia (IP). Venovenous extracorporeal membranous oxygenation (VV-ECMO) is an emerging tool to avoid ventilator-induced lung injury. This is a report presenting the first three patients with AE of IP treated with a combined therapy of PMX-DHP and VV-ECMO. Patient 1 was a 68-year-old male with acute interstitial pneumonia, patient 2 a 67-year-old male with AE of idiopathic pulmonary fibrosis, and patient 3 a 61-year-old female with AE of collagen vascular disease-associated interstitial pneumonia. All patients were severely hypoxemic and required mechanical ventilation. A combined therapy using PMX-DHP and VV-ECMO was initiated with support of intravenous corticosteroids and antibiotics. Radiological findings, oxygenation and laboratory findings markedly improved and all patients survived without severe complications. A combined therapy of PMX-DHP and VV-ECMO might be a therapeutic option for AE of IP.

Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown.

PubMed

Castillo, Inmaculada; Pardo, Margarita; Bartolomé, Javier; Ortiz-Movilla, Nuria; Rodríguez-Iñigo, Elena; de Lucas, Susana; Salas, Clara; Jiménez-Heffernan, Jose A; Pérez-Mota, Arturo; Graus, Javier; López-Alcorocho, Juan Manuel; Carreño, Vicente

2004-01-01

There are patients in whom the etiology of long-standing abnormal results of liver-function tests is unknown (ALF-EU) after exclusion of all known causes of liver diseases. We analyzed the presence of hepatitis C virus (HCV) RNA in liver-biopsy specimens from 100 patients who were negative for anti-HCV antibodies and for serum HCV RNA and who had ALF-EU. HCV RNA status was tested by reverse-transcription polymerase chain reaction (RT-PCR) and by in situ hybridization, in liver and peripheral-blood mononuclear cells (PBMCs). HCV RNA was detected in liver-biopsy specimens from 57 of 100 patients negative for anti-HCV antibodies and for serum HCV RNA (i.e., who had occult HCV infection). HCV RNA of negative polarity was found in the liver of 48 (84.2%) of these 57 patients with occult HCV infection. Nucleotide-sequence analysis confirmed the specificity of detection of HCV RNA and that patients were infected with the HCV 1b genotype. Of these 57 patients with intrahepatic HCV RNA, 40 (70%) had viral RNA in their PBMCs. With regard to liver histology, patients with occult HCV infection were more likely to have necroinflammatory activity (P=.017) and fibrosis (P=.022) than were patients without intrahepatic HCV RNA. Patients with ALF-EU may have intrahepatic HCV RNA in the absence of anti-HCV antibodies and of serum HCV RNA.

Testing for Occult Heartworm Infection

PubMed Central

Stogdale, L.

1984-01-01

Heartworm infection in dogs is endemic in southern Ontario but occurs only sporadically throughout the remainder of Canada. The disease may either be associated with microfilariae in the patient's blood, a patent infection, or it may be occult. This paper describes a case of occult dirofilariasis in a dog, with emphasis on the diagnosis. A patent infection could be missed if the clinician tests an insufficient amount of blood. He should perform multiple concentration tests using either the modified Knott's technique or a filtration method. Occult infections occur in prepatent or unisexual infections, when the worms become sterile following therapy, or when the host produces antibodies that result in the destruction of the microfilariae. The recent release of a kit which detects the presence of antibodies to the adult heartworms now enables veterinarians to make an accurate diagnosis in the vast majority of dogs. PMID:17422386

Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis

PubMed Central

Sharma, Amit; Khan, Md. Abdul Hye; Levick, Scott P.; Lee, Kin Sing Stephen; Hammock, Bruce D.; Imig, John D.

2016-01-01

Cytochrome P450 (CYP) monooxygenases epoxidize the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid into novel epoxydocosapentaenoic acids (EDPs) that have multiple biological actions. The present study determined the ability of the most abundant EDP regioisomer, 19,20-EDP to reduce kidney injury in an experimental unilateral ureteral obstruction (UUO) renal fibrosis mouse model. Mice with UUO developed kidney tubular injury and interstitial fibrosis. UUO mice had elevated kidney hydroxyproline content and five-times greater collagen positive fibrotic area than sham control mice. 19,20-EDP treatment to UUO mice for 10 days reduced renal fibrosis with a 40%–50% reduction in collagen positive area and hydroxyproline content. There was a six-fold increase in kidney α-smooth muscle actin (α-SMA) positive area in UUO mice compared to sham control mice, and 19,20-EDP treatment to UUO mice decreased α-SMA immunopositive area by 60%. UUO mice demonstrated renal epithelial-to-mesenchymal transition (EMT) with reduced expression of the epithelial marker E-cadherin and elevated expression of multiple mesenchymal markers (FSP-1, α-SMA, and desmin). Interestingly, 19,20-EDP treatment reduced renal EMT in UUO by decreasing mesenchymal and increasing epithelial marker expression. Overall, we demonstrate that a novel omega-3 fatty acid metabolite 19,20-EDP, prevents UUO-induced renal fibrosis in mice by reducing renal EMT. PMID:27213332

Fecal Occult Blood Test (FOBT): MedlinePlus Lab Test Information

MedlinePlus

... medlineplus.gov/labtests/fecaloccultbloodtestfobt.html Fecal Occult Blood Test (FOBT) To use the sharing features on this ... enable JavaScript. What is a Fecal Occult Blood Test? A fecal occult blood test (FOBT) looks at ...

A Digital Video System for Observing and Recording Occultations

NASA Astrophysics Data System (ADS)

Barry, M. A. Tony; Gault, Dave; Pavlov, Hristo; Hanna, William; McEwan, Alistair; Filipović, Miroslav D.

2015-09-01

Stellar occultations by asteroids and outer solar system bodies can offer ground based observers with modest telescopes and camera equipment the opportunity to probe the shape, size, atmosphere, and attendant moons or rings of these distant objects. The essential requirements of the camera and recording equipment are: good quantum efficiency and low noise; minimal dead time between images; good horological faithfulness of the image timestamps; robustness of the recording to unexpected failure; and low cost. We describe an occultation observing and recording system which attempts to fulfil these requirements and compare the system with other reported camera and recorder systems. Five systems have been built, deployed, and tested over the past three years, and we report on three representative occultation observations: one being a 9 ± 1.5 s occultation of the trans-Neptunian object 28978 Ixion (m v =15.2) at 3 seconds per frame; one being a 1.51 ± 0.017 s occultation of Deimos, the 12 km diameter satellite of Mars, at 30 frames per second; and one being a 11.04 ± 0.4 s occultation, recorded at 7.5 frames per second, of the main belt asteroid 361 Havnia, representing a low magnitude drop (Δm v = ~0.4) occultation.

A role for MCP-1/CCR2 in interstitial lung disease in children

PubMed Central

Hartl, Dominik; Griese, Matthias; Nicolai, Thomas; Zissel, Gernot; Prell, Christine; Reinhardt, Dietrich; Schendel, Dolores J; Krauss-Etschmann, Susanne

2005-01-01

Background Interstitial lung diseases (ILD) are chronic inflammatory disorders leading to pulmonary fibrosis. Monocyte chemotactic protein 1 (MCP-1) promotes collagen synthesis and deletion of the MCP-1 receptor CCR2 protects from pulmonary fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1 and CCR2+ T cells accumulate in pediatric ILD and are related to disease severity. Methods Bronchoalveolar lavage fluid was obtained from 25 children with ILD and 10 healthy children. Levels of pulmonary MCP-1 and Th1/Th2-associated cytokines were quantified at the protein and the mRNA levels. Pulmonary CCR2+, CCR4+, CCR3+, CCR5+ and CXCR3+ T cells were quantified by flow-cytometry. Results CCR2+ T cells and MCP-1 levels were significantly elevated in children with ILD and correlated with forced vital capacity, total lung capacity and ILD disease severity scores. Children with lung fibrosis had significantly higher MCP-1 levels and CCR2+ T cells in bronchoalveolar lavage fluid compared to non-fibrotic children. Conclusion The results indicate that pulmonary CCR2+ T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies. PMID:16095529

Ultrasound for diagnosing radiographically occult scaphoid fracture.

PubMed

Kwee, Robert M; Kwee, Thomas C

2018-04-04

To systematically review the literature on the performance of ultrasound in diagnosing radiographically occult scaphoid fracture. A systematic search was performed in the MEDLINE and Embase databases. Original studies investigating the performance of ultrasound in diagnosing radiographically occult scaphoid fracture in more than 10 patients were eligible for inclusion. Studies that included both radiographically apparent and occult scaphoid fractures (at initial radiography) were only included if independent data on radiographically occult fractures were reported. Methodological quality of the studies included was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Accuracy data were extracted. Sensitivity and specificity were pooled with a bivariate random-effects model. The inclusion criteria were met by 7 studies; total sample size comprised 314 patients. All studies, except 1, included cortical disruption of the scaphoid in their diagnostic criteria. The sensitivity and specificity of ultrasound in diagnosing radiographically occult scaphoid fracture ranged from 77.8% to 100% and from 71.4% to 100% respectively, with pooled estimates of 85.6% (95% CI: 73.9%, 92.6%) and 83.3% % (95% CI: 72.0%, 90.6%) respectively. Exclusion of two studies with a high risk of bias in any QUADAS-2 domain did not affect the pooled results. Ultrasound can diagnose radiographically occult scaphoid fracture with a fairly high degree of accuracy. Because of its relatively low costs and fairly high sensitivity, ultrasound seems more cost-effective than empiric cast immobilization and may be used when CT and MRI are not readily available.

Chiron stellar occultation candidates: 1993-1996

NASA Technical Reports Server (NTRS)

Bus, S. J.; Wasserman, L. H.; Elliot, J. L.

1994-01-01

A photographic search was conducted for stars that may be occulted by the unusual solar system object (2060) Chiron during the period from fall 1993 through summer 1996. 44 candidates were identified to a limiting V magnitude of 16, and for which the minimum appulse separation with Chiron is predicted to be less than 2.5 arcsec. The successful observation of a stellar occultation by Chiron would give a direct measure of its diameter (currently estimated to be between 60 and 300 km), and would help considerably in constraining Chiron's surface properties and volatile makeup. If at the time of the occultation, Chiron exhibits a significant coma, there is also the potential for measuring the optical-depth profile of the dust in its inner coma.

Nondimensional Representations for Occulter Design and Performance Evaluation

NASA Technical Reports Server (NTRS)

Cady, Eric

2011-01-01

An occulter is a spacecraft with a precisely-shaped optical edges which ies in formation with a telescope, blocking light from a star while leaving light from nearby planets una ected. Using linear optimization, occulters can be designed for use with telescopes over a wide range of telescope aperture sizes, science bands, and starlight suppression levels. It can be shown that this optimization depends primarily on a small number of independent nondimensional parameters, which correspond to Fresnel numbers and physical scales and enter the optimization only as constraints. We show how these can be used to span the parameter space of possible optimized occulters; this data set can then be mined to determine occulter sizes for various mission scenarios and sets of engineering constraints.

Sizes, Shapes, and Satellites of Asteroids from Occultations

NASA Astrophysics Data System (ADS)

Dunham, David W.; Herald, David; Preston, Steve; Timerson, Brad; Maley, Paul; Frappa, Eric; Hayamizu, Tsutomu; Talbot, John; Poro, Atila

2016-01-01

For 40 years, the sizes and shapes of many dozens of asteroids have been determined from observations of asteroidal occultations, and over a thousand high-precision positions of the asteroids relative to stars have been measured. Some of the first evidence for satellites of asteroids was obtained from the early efforts; now, the orbits and sizes of some satellites discovered by other means have been refined from occultation observations. Also, several close binary stars have been discovered, and the angular diameters of some stars have been measured from analysis of these observations. The International Occultation Timing Association (IOTA) coordinates this activity worldwide, from predicting and publicizing the events, to accurately timing the occultations from as many stations as possible, and publishing and archiving the observations.

L-Endoglin Overexpression Increases Renal Fibrosis after Unilateral Ureteral Obstruction

PubMed Central

Arévalo, Miguel; Núñez-Gómez, Elena; Pérez-Roque, Lucía; Pericacho, Miguel; González-Núñez, María; Langa, Carmen; Martínez-Salgado, Carlos; Perez-Barriocanal, Fernando; Bernabeu, Carmelo; Lopez-Novoa, José M.

2014-01-01

Transforming growth factor-β (TGF-β) plays a pivotal role in renal fibrosis. Endoglin, a 180 KDa membrane glycoprotein, is a TGF-β co-receptor overexpressed in several models of chronic kidney disease, but its function in renal fibrosis remains uncertain. Two membrane isoforms generated by alternative splicing have been described, L-Endoglin (long) and S-Endoglin (short) that differ from each other in their cytoplasmic tails, being L-Endoglin the most abundant isoform. The aim of this study was to assess the effect of L-Endoglin overexpression in renal tubulo-interstitial fibrosis. For this purpose, a transgenic mouse which ubiquitously overexpresses human L-Endoglin (L-ENG+) was generated and unilateral ureteral obstruction (UUO) was performed in L-ENG+ mice and their wild type (WT) littermates. Obstructed kidneys from L-ENG+ mice showed higher amounts of type I collagen and fibronectin but similar levels of α-smooth muscle actin (α-SMA) than obstructed kidneys from WT mice. Smad1 and Smad3 phosphorylation were significantly higher in obstructed kidneys from L-ENG+ than in WT mice. Our results suggest that the higher increase of renal fibrosis observed in L-ENG+ mice is not due to a major abundance of myofibroblasts, as similar levels of α-SMA were observed in both L-ENG+ and WT mice, but to the higher collagen and fibronectin synthesis by these fibroblasts. Furthermore, in vivo L-Endoglin overexpression potentiates Smad1 and Smad3 pathways and this effect is associated with higher renal fibrosis development. PMID:25313562

Mutations Associated With Occult Hepatitis B in HIV-Positive South Africans

PubMed Central

Powell, Eleanor A.; Gededzha, Maemu P.; Rentz, Michael; Rakgole, Nare J.; Selabe, Selokela G.; Seleise, Tebogo A.; Mphahlele, M. Jeffrey; Blackard, Jason T.

2015-01-01

Occult hepatitis B is characterized by the absence of hepatitis B surface antigen (HBsAg) but the presence of HBV DNA. Because diagnosis of hepatitis B virus (HBV) typically includes HBsAg detection, occult HBV remains largely undiagnosed. Occult HBV is associated with increased risk of hepatocellular carcinoma, reactivation to chronic HBV during immune suppression, and transmission during blood transfusion and liver transplant. The mechanisms leading to occult HBV infection are unclear, although viral mutations are likely a significant factor. In this study, sera from 394 HIV-positive South Africans were tested for HBV DNA and HBsAg. For patients with detectable HBV DNA, the overlapping surface and polymerase open reading frames (ORFs) were sequenced. Occult-associated mutations—those mutations found exclusively in individuals with occult HBV infection but not in individuals with chronic HBV infection from the same cohort or GenBank references—were identified. Ninety patients (22.8%) had detectable HBV DNA. Of these, 37 had detectable HBsAg, while 53 lacked detectable surface antigen. The surface and polymerase ORFs were cloned successfully for 19 patients with chronic HBV and 30 patients with occult HBV. In total, 235 occult-associated mutations were identified. Ten occult-associated mutations were identified in more than one patient. Additionally, 15 amino acid positions had two distinct occult-associated mutations at the same residue. Occult-associated mutations were common and present in all regions of the surface and polymerase ORFs. Further study is underway to determine the effects of these mutations on viral replication and surface antigen expression in vitro. PMID:25164924

Mutations associated with occult hepatitis B in HIV-positive South Africans.

PubMed

Powell, Eleanor A; Gededzha, Maemu P; Rentz, Michael; Rakgole, Nare J; Selabe, Selokela G; Seleise, Tebogo A; Mphahlele, M Jeffrey; Blackard, Jason T

2015-03-01

Occult hepatitis B is characterized by the absence of hepatitis B surface antigen (HBsAg) but the presence of HBV DNA. Because diagnosis of hepatitis B virus (HBV) typically includes HBsAg detection, occult HBV remains largely undiagnosed. Occult HBV is associated with increased risk of hepatocellular carcinoma, reactivation to chronic HBV during immune suppression, and transmission during blood transfusion and liver transplant. The mechanisms leading to occult HBV infection are unclear, although viral mutations are likely a significant factor. In this study, sera from 394 HIV-positive South Africans were tested for HBV DNA and HBsAg. For patients with detectable HBV DNA, the overlapping surface and polymerase open reading frames (ORFs) were sequenced. Occult-associated mutations-those mutations found exclusively in individuals with occult HBV infection but not in individuals with chronic HBV infection from the same cohort or GenBank references-were identified. Ninety patients (22.8%) had detectable HBV DNA. Of these, 37 had detectable HBsAg, while 53 lacked detectable surface antigen. The surface and polymerase ORFs were cloned successfully for 19 patients with chronic HBV and 30 patients with occult HBV. In total, 235 occult-associated mutations were identified. Ten occult-associated mutations were identified in more than one patient. Additionally, 15 amino acid positions had two distinct occult-associated mutations at the same residue. Occult-associated mutations were common and present in all regions of the surface and polymerase ORFs. Further study is underway to determine the effects of these mutations on viral replication and surface antigen expression in vitro. © 2014 Wiley Periodicals, Inc.

EGF receptor tyrosine kinase inhibitors diminish transforming growth factor-alpha-induced pulmonary fibrosis.

PubMed

Hardie, William D; Davidson, Cynthia; Ikegami, Machiko; Leikauf, George D; Le Cras, Timothy D; Prestridge, Adrienne; Whitsett, Jeffrey A; Korfhagen, Thomas R

2008-06-01

Transforming growth factor-alpha (TGF-alpha) is a ligand for the EGF receptor (EGFR). EGFR activation is associated with fibroproliferative processes in human lung disease and animal models of pulmonary fibrosis. We determined the effects of EGFR tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva) on the development and progression of TGF-alpha-induced pulmonary fibrosis. Using a doxycycline-regulatable transgenic mouse model of lung-specific TGF-alpha expression, we determined effects of treatment with gefitinib and erlotinib on changes in lung histology, total lung collagen, pulmonary mechanics, pulmonary hypertension, and expression of genes associated with synthesis of ECM and vascular remodeling. Induction in the lung of TGF-alpha caused progressive pulmonary fibrosis over an 8-wk period. Daily administration of gefitinib or erlotinib prevented development of fibrosis, reduced accumulation of total lung collagen, prevented weight loss, and prevented changes in pulmonary mechanics. Treatment of mice with gefitinib 4 wk after the induction of TGF-alpha prevented further increases in and partially reversed total collagen levels and changes in pulmonary mechanics and pulmonary hypertension. Increases in expression of genes associated with synthesis of ECM as well as decreases of genes associated with vascular remodeling were also prevented or partially reversed. Administration of gefitinib or erlotinib did not cause interstitial fibrosis or increases in lavage cell counts. Administration of small molecule EGFR tyrosine kinase inhibitors prevented further increases in and partially reversed pulmonary fibrosis induced directly by EGFR activation without inducing inflammatory cell influx or additional lung injury.

Grape seed extract ameliorates bleomycin-induced mouse pulmonary fibrosis.

PubMed

Liu, Qi; Jiang, Jun-Xia; Liu, Ya-Nan; Ge, Ling-Tian; Guan, Yan; Zhao, Wei; Jia, Yong-Liang; Dong, Xin-Wei; Sun, Yun; Xie, Qiang-Min

2017-05-05

Pulmonary fibrosis is common in a variety of inflammatory lung diseases, such as interstitial pneumonia, chronic obstructive pulmonary disease, and silicosis. There is currently no effective clinical drug treatment. It has been reported that grape seed extracts (GSE) has extensive pharmacological effects with minimal toxicity. Although it has been found that GSE can improve the lung collagen deposition and fibrosis pathology induced by bleomycin in rat, its effects on pulmonary function, inflammation, growth factors, matrix metalloproteinases and epithelial-mesenchymal transition remain to be researched. In the present study, we studied whether GSE provided protection against bleomycin (BLM)-induced mouse pulmonary fibrosis. ICR strain mice were treated with BLM in order to establish pulmonary fibrosis models. GSE was given daily via intragastric administration for three weeks starting at one day after intratracheal instillation. GSE at 50 or 100mg/kg significantly reduced BLM-induced inflammatory cells infiltration, proinflammatory factor protein expression, and hydroxyproline in lung tissues, and improved pulmonary function in mice. Additionally, treatment with GSE also significantly impaired BLM-induced increases in lung fibrotic marker expression (collagen type I alpha 1 and fibronectin 1) and decreases in an anti-fibrotic marker (E-cadherin). Further investigation indicated that the possible molecular targets of GSE are matrix metalloproteinases-9 (MMP-9) and TGF-β1, given that treatment with GSE significantly prevented BLM-induced increases in MMP-9 and TGF-β1 expression in the lungs. Together, these results suggest that supplementation with GSE may improve the quality of life of lung fibrosis patients by inhibiting MMP-9 and TGF-β1 expression in the lungs. Copyright © 2017 Elsevier B.V. All rights reserved.

Design of an occulter testbed at flight Fresnel numbers

NASA Astrophysics Data System (ADS)

Sirbu, Dan; Kasdin, N. Jeremy; Kim, Yunjong; Vanderbei, Robert J.

2015-01-01

An external occulter is a spacecraft flown along the line-of-sight of a space telescope to suppress starlight and enable high-contrast direct imaging of exoplanets. Laboratory verification of occulter designs is necessary to validate the optical models used to design and predict occulter performance. At Princeton, we are designing and building a testbed that allows verification of scaled occulter designs whose suppressed shadow is mathematically identical to that of space occulters. Here, we present a sample design operating at a flight Fresnel number and is thus representative of a realistic space mission. We present calculations of experimental limits arising from the finite size and propagation distance available in the testbed, limitations due to manufacturing feature size, and non-ideal input beam. We demonstrate how the testbed is designed to be feature-size limited, and provide an estimation of the expected performance.

Smoking-related emphysema is associated with idiopathic pulmonary fibrosis and rheumatoid lung.

PubMed

Antoniou, Katerina M; Walsh, Simon L; Hansell, David M; Rubens, Michael R; Marten, Katharina; Tennant, Rachel; Hansel, Trevor; Desai, Sujal R; Siafakas, Nikolaos M; du Bois, Roland M; Wells, Athol U

2013-11-01

A combined pulmonary fibrosis/emphysema syndrome has been proposed, but the basis for this syndrome is currently uncertain. The aim was to evaluate the prevalence of emphysema in idiopathic pulmonary fibrosis (IPF) and rheumatoid lung (rheumatoid arthritis-interstitial lung disease (RA-ILD)), and to compare the morphological features of lung fibrosis between smokers and non-smokers. Using high-resolution computed tomography, the prevalence of emphysema and the pack-year smoking histories associated with emphysema were compared between current/ex-smokers with IPF (n = 186) or RA-ILD (n = 46), and non-chronic obstructive pulmonary disease (COPD) controls (n = 103) and COPD controls (n = 34). The coarseness of fibrosis was compared between smokers and non-smokers. Emphysema, present in 66/186 (35%) patients with IPF and 22/46 (48%) smokers with RA-ILD, was associated with lower pack-year smoking histories than in control groups (P < 0.05 for all comparisons). The presence of emphysema in IPF was positively linked to the pack-year smoking history (odds ratio 1.04, 95% confidence interval (CI) 1.02-1.06, P < 0.0005). In IPF, fibrosis was coarser in smokers than in non-smokers on univariate and multivariate analysis (P < 0.01 for all comparisons). In RA-ILD, fibrosis was coarser in patients with emphysema but did not differ significantly between smokers and non-smokers. In IPF and RA-ILD, a high prevalence of concurrent emphysema, in association with low pack-year smoking histories, and an association between coarser pulmonary fibrosis and a history of smoking in IPF together provide support for possible pathogenetic linkage to smoking in both diseases. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Role of pirfenidone in the management of pulmonary fibrosis.

PubMed

Meyer, Keith C; Decker, Catherine A

2017-01-01

Pulmonary fibrosis is associated with a number of specific forms of interstitial lung disease (ILD) and can lead to progressive decline in lung function, poor quality of life, and, ultimately, early death. Idiopathic pulmonary fibrosis (IPF), the most common fibrotic ILD, affects up to 1 in 200 elderly individuals and has a median survival that ranges from 3 to 5 years following initial diagnosis. IPF has not been shown to respond to immunomodulatory therapies, but recent trials with novel antifibrotic agents have demonstrated lessening of lung function decline over time. Pirfenidone has been shown to significantly slow decline in forced vital capacity (FVC) over time and prolong progression-free survival, which led to its licensing by the United States Food and Drug Administration (FDA) in 2014 for the treatment of patients with IPF. However, pirfenidone has been associated with significant side effects, and patients treated with pirfenidone must be carefully monitored. We review recent and ongoing clinical research and experience with pirfenidone as a pharmacologic therapy for patients with IPF, provide a suggested approach to incorporate pirfenidone into a treatment algorithm for patients with IPF, and examine the potential of pirfenidone as a treatment for non-IPF forms of ILD accompanied by progressive pulmonary fibrosis.

Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis

PubMed Central

Wex, Eva; Pautsch, Alexander; Schnapp, Gisela; Hostettler, Katrin E.; Stowasser, Susanne; Kolb, Martin

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease characterised by fibrosis of the lung parenchyma and loss of lung function. Although the pathogenic pathways involved in IPF have not been fully elucidated, IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair, in which there is uncontrolled proliferation of lung fibroblasts and differentiation of fibroblasts into myofibroblasts, which excessively deposit extracellular matrix (ECM) proteins in the interstitial space. A number of profibrotic mediators including platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and transforming growth factor-β are believed to play important roles in the pathogenesis of IPF. Nintedanib is a potent small molecule inhibitor of the receptor tyrosine kinases PDGF receptor, FGF receptor and vascular endothelial growth factor receptor. Data from in vitro studies have shown that nintedanib interferes with processes active in fibrosis such as fibroblast proliferation, migration and differentiation, and the secretion of ECM. In addition, nintedanib has shown consistent anti-fibrotic and anti-inflammatory activity in animal models of lung fibrosis. These data provide a strong rationale for the clinical efficacy of nintedanib in patients with IPF, which has recently been demonstrated in phase III clinical trials. PMID:25745043

Diagnostic strategy for occult hepatitis B virus infection

PubMed Central

Ocana, Sara; Casas, Maria Luisa; Buhigas, Ingrid; Lledo, Jose Luis

2011-01-01

In 2008, the European Association for the study of the liver (EASL) defined occult hepatitis B virus infection (OBI) as the “presence of hepatitis B virus (HBV) DNA in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing hepatitis B surface antigen (HBsAg) negative by currently available assays”. Several aspects of occult HBV infection are still poorly understood, including the definition itself and a standardized approach for laboratory-based detection, which is the purpose of this review. The clinical significance of OBI has not yet been established; however, in terms of public health, the clinical importance arises from the risk of HBV transmission. Consequently, it is important to detect high-risk groups for occult HBV infection to prevent transmission. The main issue is, perhaps, to identify the target population for screening OBI. Viremia is very low or undetectable in occult HBV infection, even when the most sensitive methods are used, and the detection of the viral DNA reservoir in hepatocytes would provide the best evaluation of occult HBV prevalence in a defined set of patients. However, this diagnostic approach is obviously unsuitable: blood detection of occult hepatitis B requires assays of the highest sensitivity and specificity with a lower limit of detection < 10 IU/mL for HBV DNA and < 0.1 ng/mL for HBsAg. PMID:21472120

Portable high speed photometry systems for observing occultations

NASA Astrophysics Data System (ADS)

Elliot, J. L.; Dunham, E. W.

1986-09-01

Ring orbit studies for Uranus have been particularly fruitful because of the ability, through occultations, to obtain data of high spatial resolution at the rate of 1 to 2 times per year. The occultation program at M.I.T. involves: (1) identifying the scientific questions that can be answered by occultation events, (2) predicting the zone of visibility for the useful events, (3) maintaining and improving a set of portable high-speed photometric systems, (4) obtaining the observations, and (5) reducing the data and interpreting the results. Two stellar occultations by Uranus occurred in May 1985, and were observed with a network of large telescopes that encompassed the Northern and Southern Hemispheres. Portable quartz-oscillator time standards were used at all observatories, and were calibrated before and after each event. Observations obtained form Cerro Tololo and McDonald Observatories of the 4 May and 24 May 1985 occultations by the Uranian rings clearly show a companion to the delta ring on both the immersion and emersion traces. The occultation by Ceres that occurred on 12 November 1984 was observed. Preliminary results give a mean diameter of 933 + or - 10 km, which implies a geometric albedo, Pv = 0.07 + or - 0.01 and a density 2.7 + or - 0.3 gm cu/cm. Hence Ceres is likely composed of silicate material throughout.

First results from stellar occultations in the "GAIA era"

NASA Astrophysics Data System (ADS)

Benedetti-Rossi, G.; Vieira-Martins, R.; Sicardy, B.

2017-09-01

Stellar occultation is a powerful technique to study distant solar system bodies. It allows high angular resolution of the occulting body from the analysis of a light curve acquired with high temporal resolution with uncertainties comparable as probes. In the "GAIA era", stellar occultations is now able to obtain even more impressive results such as the presence of atmosphere, rings and topographic features.

Solar Occultation Retrieval Algorithm Development

NASA Technical Reports Server (NTRS)

Lumpe, Jerry D.

2004-01-01

This effort addresses the comparison and validation of currently operational solar occultation retrieval algorithms, and the development of generalized algorithms for future application to multiple platforms. initial development of generalized forward model algorithms capable of simulating transmission data from of the POAM II/III and SAGE II/III instruments. Work in the 2" quarter will focus on: completion of forward model algorithms, including accurate spectral characteristics for all instruments, and comparison of simulated transmission data with actual level 1 instrument data for specific occultation events.

Intragraft expression of the IL-10 gene is up-regulated in renal protocol biopsies with early interstitial fibrosis, tubular atrophy, and subclinical rejection.

PubMed

Hueso, Miguel; Navarro, Estanis; Moreso, Francesc; O'Valle, Francisco; Pérez-Riba, Mercè; Del Moral, Raimundo García; Grinyó, Josep M; Serón, Daniel

2010-04-01

Grafts with subclinical rejection associated with interstitial fibrosis and tubular atrophy (SCR+IF/TA) show poorer survival than grafts with subclinical rejection without IF/TA (SCR). Aiming to detect differences among SCR+IF/TA and SCR, we immunophenotyped the inflammatory infiltrate (CD45, CD3, CD20, CD68) and used a low-density array to determine levels of T(H)1 (interleukin IL-2, IL-3, gamma-interferon, tumor necrosis factor-alpha, lymphotoxin-alpha, lymphotoxin-beta, granulocyte-macrophage colony-stimulating factor) and T(H)2 (IL-4, IL-5, IL-6, IL-10, and IL-13) transcripts as well as of IL-2R (as marker for T-cell activation) in 31 protocol biopsies of renal allografts. Here we show that grafts with early IF/TA and SCR can be distinguished from grafts with SCR on the basis of the activation of IL-10 gene expression and of an increased infiltration by B-lymphocytes in a cellular context in which the degree of T-cell activation is similar in both groups of biopsies, as demonstrated by equivalent levels of IL-2R mRNA. These results suggest that the up-regulation of the IL-10 gene expression, as well as an increased proportion of B-lymphocytes in the inflammatory infiltrates, might be useful as markers of early chronic lesions in grafts with SCR.

Intragraft Expression of the IL-10 Gene Is Up-Regulated in Renal Protocol Biopsies with Early Interstitial Fibrosis, Tubular Atrophy, and Subclinical Rejection

PubMed Central

Hueso, Miguel; Navarro, Estanis; Moreso, Francesc; O'Valle, Francisco; Pérez-Riba, Mercè; del Moral, Raimundo García; Grinyó, Josep M.; Serón, Daniel

2010-01-01

Grafts with subclinical rejection associated with interstitial fibrosis and tubular atrophy (SCR+IF/TA) show poorer survival than grafts with subclinical rejection without IF/TA (SCR). Aiming to detect differences among SCR+IF/TA and SCR, we immunophenotyped the inflammatory infiltrate (CD45, CD3, CD20, CD68) and used a low-density array to determine levels of TH1 (interleukin IL-2, IL-3, γ-interferon, tumor necrosis factor-α, lymphotoxin-α, lymphotoxin-β, granulocyte-macrophage colony-stimulating factor) and TH2 (IL-4, IL-5, IL-6, IL-10, and IL-13) transcripts as well as of IL-2R (as marker for T-cell activation) in 31 protocol biopsies of renal allografts. Here we show that grafts with early IF/TA and SCR can be distinguished from grafts with SCR on the basis of the activation of IL-10 gene expression and of an increased infiltration by B-lymphocytes in a cellular context in which the degree of T-cell activation is similar in both groups of biopsies, as demonstrated by equivalent levels of IL-2R mRNA. These results suggest that the up-regulation of the IL-10 gene expression, as well as an increased proportion of B-lymphocytes in the inflammatory infiltrates, might be useful as markers of early chronic lesions in grafts with SCR. PMID:20150436

Occult Intertrochanteric Fracture Mimicking the Fracture of Greater Trochanter.

PubMed

Chung, Phil Hyun; Kang, Suk; Kim, Jong Pil; Kim, Young Sung; Lee, Ho Min; Back, In Hwa; Eom, Kyeong Soo

2016-06-01

Occult intertrochanteric fractures are misdiagnosed as isolated greater trochanteric fractures in some cases. We investigated the utility of three-dimensional computed tomography (3D-CT) and magnetic resonance imaging (MRI) in the diagnosis and outcome management of occult intertrochanteric fractures. This study involved 23 cases of greater trochanteric fractures as diagnosed using plain radiographs from January 2004 to July 2013. Until January 2008, 9 cases were examined with 3D-CT only, while 14 cases were screened with both 3D-CT and MRI scans. We analyzed diagnostic accuracy and treatment results following 3D-CT and MRI scanning. Nine cases that underwent 3D-CT only were diagnosed with isolated greater trochanteric fractures without occult intertrochanteric fractures. Of these, a patient with displacement received surgical treatment. Of the 14 patients screened using both CT and MRI, 13 were diagnosed with occult intertrochanteric fractures. Of these, 11 were treated with surgical intervention and 2 with conservative management. Three-dimensional CT has very low diagnostic accuracy in diagnosing occult intertrochanteric fractures. For this reason, MRI is recommended to confirm a suspected occult intertrochanteric fracture and to determine the most appropriate mode of treatment.

Human Umbilical Cord-Derived Mesenchymal Stem Cells Conditioned Medium Attenuate Interstitial Fibrosis and Stimulate the Repair of Tubular Epithelial Cells in an Irreversible Model of Unilateral Ureteral Obstruction.

PubMed

Liu, Bo; Ding, Feng-Xia; Liu, Yang; Xiong, Geng; Lin, Tao; He, Da-Wei; Zhang, Yuan-Yuan; Zhang, De-Ying; Wei, Guang-Hui

2017-07-01

The growing number of patients suffering from chronic renal disease (CKD) is a challenge for the development of innovative therapies. Researchers have studied the therapeutic effects of cell therapy in acute kidney injury (AKI). However, the therapeutical effect of conditional medium (CM) in the CKD models have been rarely reported. Here, we examined the effects of umbilical cord derived-mesenchymal stem cells (hUC-MSCs) CM on renal fibrosis in a rat model of unilateral ureteral obstruction (UUO). We randomly divided the animals into three groups: sham-operated, UUO, UUO + CM. CM was administered via the left renal artery after total ligation of the left ureter. Rats were killed after 14 days of obstruction. Histological changes and oxidative stress parameters were assessed. Western blotting and immunohistochemistry analysis were used to measure epithelial-mesenchymal transition (EMT) markers, including epithelial cadherin (E-cadherin), α-smooth muscle actin (α-SMA), tumor necrosis factor-α (TNF-α), Collagen-I, and transforming growth factor β1 (TGF-β1). Proliferation and apoptosis of renal tubular epithelial cells (RTEs) were also measured. HucMSC-CM significantly reduced the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), and increased the activity of glutathione (GSH) induced by UUO. Moreover, CM significantly reduced the expression of TGF-β1, α-SMA, TNF-α and Collagen-I in UUO kidney, promoted the proliferation of RTEs and inhibited its apoptosis. In addition, the increased expression of E-cadherin also reflects the effective improvement of renal interstitial fibrosis. This study shows that CM protects UUO-induced kidney damage and therefore could be a potential tool to prevent CKD progression. This article is protected by copyright. All rights reserved.

Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis.

PubMed

Humphreys, Benjamin D; Xu, Fengfeng; Sabbisetti, Venkata; Grgic, Ivica; Movahedi Naini, Said; Wang, Ningning; Chen, Guochun; Xiao, Sheng; Patel, Dhruti; Henderson, Joel M; Ichimura, Takaharu; Mou, Shan; Soeung, Savuth; McMahon, Andrew P; Kuchroo, Vijay K; Bonventre, Joseph V

2013-09-01

Acute kidney injury predisposes patients to the development of both chronic kidney disease and end-stage renal failure, but the molecular details underlying this important clinical association remain obscure. We report that kidney injury molecule-1 (KIM-1), an epithelial phosphatidylserine receptor expressed transiently after acute injury and chronically in fibrotic renal disease, promotes kidney fibrosis. Conditional expression of KIM-1 in renal epithelial cells (Kim1(RECtg)) in the absence of an injury stimulus resulted in focal epithelial vacuolization at birth, but otherwise normal tubule histology and kidney function. By 4 weeks of age, Kim1(RECtg) mice developed spontaneous and progressive interstitial kidney inflammation with fibrosis, leading to renal failure with anemia, proteinuria, hyperphosphatemia, hypertension, cardiac hypertrophy, and death, analogous to progressive kidney disease in humans. Kim1(RECtg) kidneys had elevated expression of proinflammatory monocyte chemotactic protein-1 (MCP-1) at early time points. Heterologous expression of KIM-1 in an immortalized proximal tubule cell line triggered MCP-1 secretion and increased MCP-1-dependent macrophage chemotaxis. In mice expressing a mutant, truncated KIM-1 polypeptide, experimental kidney fibrosis was ameliorated with reduced levels of MCP-1, consistent with a profibrotic role for native KIM-1. Thus, sustained KIM-1 expression promotes kidney fibrosis and provides a link between acute and recurrent injury with progressive chronic kidney disease.

Pneumocyte injury and ubiquitin-positive pneumocytes in interstitial lung diseases*

PubMed Central

Yamada, Tsutomu; Kawabata, Yoshinori

2015-01-01

Pneumocyte injury is a characteristic of pulmonary interstitial pneumonias (IPs). Histological markers of pneumocyte injury and inflammation include pneumocyte necrosis, erosion, hyaline membrane and fibrin exudation with subsequent intraluminal granulation tissue formation. We found that intracytoplasmic inclusions in pneumocytes are ubiquitin-positive (Ub+) and that the number of Ub+ pneumocytes shows positive correlation with the extent of diffuse alveolar damage (DAD). To determine the role of Ub+ pneumocytes and inclusions in IPs, we studied their relationship with pathological and clinical features of DAD, usual interstitial pneumonia (UIP) and organizing pneumonia (OP), including airspace enlargement with fibrosis (AEF). We analysed Ub+ pneumocytes, inclusions, erosions and intraluminal granulation tissue in relation to pneumocyte injury. The numbers of immunohistochemically identified Ub+ inclusions in each IP were higher than the number of inclusions detected by light microscopy. The inclusions detected by Ub+ immunostaining were identical to the inclusions observed by light microscopy. UIP and DAD had many Ub+ inclusions, while OP and AEF had fewer Ub+ inclusions. These results suggest that the extent of Ub+ inclusions reflects the severity of pneumocyte injury among IPs. Thus, Ub+ inclusions are a histological marker of pneumocyte injury that may be helpful in determining the severity and prognosis of IPs. PMID:25123224

First light of an external occulter testbed at flight Fresnel numbers

NASA Astrophysics Data System (ADS)

Kim, Yunjong; Sirbu, Dan; Hu, Mia; Kasdin, Jeremy; Vanderbei, Robert J.; Harness, Anthony; Shaklan, Stuart

2017-01-01

Many approaches have been suggested over the last couple of decades for imaging Earth-like planets. One of the main candidates for creating high-contrast for future Earth-like planets detection is an external occulter. The external occulter is a spacecraft flown along the line-of-sight of a space telescope to suppress starlight and enable high-contrast direct imaging of exoplanets. The occulter is typically tens of meters in diameter and the separation from the telescope is of the order of tens of thousands of kilometers. Optical testing of a full-scale external occulter on the ground is impossible because of the long separations. Therefore, laboratory verification of occulter designs is necessary to validate the optical models used to design and predict occulter performance. At Princeton, we have designed and built a testbed that allows verification of scaled occulter designs whose suppressed shadow is mathematically identical to that of space occulters. The goal of this experiment is to demonstrate a pupil plane suppression of better than 1e-9 with a corresponding image plane contrast of better than 1e-11. The occulter testbed uses a 77.2 m optical propagation distance to realize the flight Fresnel number of 14.5. The scaled mask is placed at 27.2 m from the artificial source and the camera is located 50.0 m from the scaled mask. We will use an etched silicon mask, manufactured by the Microdevices Lab(MDL) of the Jet Propulsion Laboratory(JPL), as the occulter. Based on conversations with MDL, we expect that 0.5 μm feature size is an achievable resolution in the mask manufacturing process and is therefore likely the indicator of the best possible performance. The occulter is illuminated by a diverging laser beam to reduce the aberrations from the optics before the occulter. Here, we present first light result of a sample design operating at a flight Fresnel number and the experimental setup of the testbed. We compare the experimental results with simulations

Possible occultation by Pluto from US East Coast

NASA Astrophysics Data System (ADS)

Waagen, Elizabeth O.

2012-06-01

We have been asked to help disseminate the news of a possible occultation by Pluto visible to observers on the US East coast. Although the AAVSO does not ordinarily issue announcements of upcoming occultations, in this case the object is Pluto and the NASA New Horizons mission (http://www.nasa.gov/mission_pages/newhorizons/main/index.html) will be visiting Pluto in 2015. The information below has been supplied by Dr. Leslie Young (Southwest Research Institute), who is coordinating this observing campaign on Pluto. Dr. Young is also Deputy Project Scientist for the New Horizons mission. ALERT: Possible Pluto occultation Wednesday night (2012/06/14 03:28 UT) from US East coast. CONTACT: Leslie Young (layoung@boulder.swri.edu; work: 303-546-6057; skype: drpluto). Also see our planning pages in progress at http://wiki.boulder.swri.edu/mediawiki/index.php/2012-06-14_Pluto_occultation. Pluto's thin, nitrogen atmosphere is in vapor-pressure equilibrium with the surface ice, and changes seasonally. We've seen it double since 1988, and now we measure its pressure once or twice a year. The technique we use is stellar occultation, when a star passes behind Pluto's atmosphere. The atmosphere defocuses the starlight. By the timing of the fading of the star, we measure the pressure and temperature in Pluto's atmosphere at ~10 km resolution. MORE INFORMATION: See http://wiki.boulder.swri.edu/mediawiki/index.php/2012-06-14_Pluto_occultation.

Occultation Lightcurves for Selected Pluto Volatile Transport Models

NASA Astrophysics Data System (ADS)

Young, L. A.

2004-11-01

The stellar occultations by Pluto in 1988 and 2002 are demonstrably sensitive to changes in Pluto's atmosphere near one microbar (Elliot and Young 1992, AJ 103, 991; Elliot et al. 2003, Nature 424, 165; Sicardy 2003, Nature 424, 168). However, Pluto volatile-transport models focus on the changes in the atmospheric pressure at the surface (e.g., Hansen and Paige 1996, Icarus 20, 247; Stansberry and Yelle 1999, Icarus 141, 299). What's lacking is a connection between predictions about the surface properties and either temperature and pressure profiles measurable from stellar occultations, or the occultation light curve morphology itself. Radiative-conductive models can illuminate this connection. I will illustrate how Pluto's changing surface pressure, temperature, and heliocentric distance may affect occultation light curves for a selection of existing volatile transport models. Changes in the light curve include the presence or absence of an observable ``kink'' (or departure from an isothermal light curve), the appearance of non-zero minimum flux levels, and the detectability of the solid surface. These light curves can serve as examples of what we may anticipate during the upcoming Pluto occultation season, as Pluto crosses the galactic plane.

Serum metabonomic analysis of protective effects of Curcuma aromatica oil on renal fibrosis rats.

PubMed

Zhao, Liangcai; Zhang, Haiyan; Yang, Yunjun; Zheng, Yongquan; Dong, Minjian; Wang, Yaqiang; Bai, Guanghui; Ye, Xinjian; Yan, Zhihan; Gao, Hongchang

2014-01-01

Curcuma aromatica oil is a traditional herbal medicine demonstrating protective and anti-fibrosis activities in renal fibrosis patients. However, study of its mechanism of action is challenged by its multiple components and multiple targets that its active agent acts on. Nuclear magnetic resonance (NMR)-based metabonomics combined with clinical chemistry and histopathology examination were performed to evaluate intervening effects of Curcuma aromatica oil on renal interstitial fibrosis rats induced by unilateral ureteral obstruction. The metabolite levels were compared based on integral values of serum 1H NMR spectra from rats on 3, 7, 14, and 28 days after the medicine administration. Time trajectory analysis demonstrated that metabolic profiles of the agent-treated rats were restored to control levels after 7 days of dosage. The results confirmed that the agent would be an effective anti-fibrosis medicine in a time-dependent manner, especially in early renal fibrosis stage. Targeted metabolite analysis showed that the medicine could lower levels of lipid, acetoacetate, glucose, phosphorylcholine/choline, trimethylamine oxide and raise levels of pyruvate, glycine in the serum of the rats. Serum clinical chemistry and kidney histopathology examination dovetailed well with the metabonomics data. The results substantiated that Curcuma aromatica oil administration can ameliorate renal fibrosis symptoms by inhibiting some metabolic pathways, including lipids metabolism, glycolysis and methylamine metabolism, which are dominating targets of the agent working in vivo. This study further strengthens the novel analytical approach for evaluating the effect of traditional herbal medicine and elucidating its molecular mechanism.

Muscle Weakness and Fibrosis Due to Cell Autonomous and Non-cell Autonomous Events in Collagen VI Deficient Congenital Muscular Dystrophy.

PubMed

Noguchi, Satoru; Ogawa, Megumu; Malicdan, May Christine; Nonaka, Ikuya; Nishino, Ichizo

2017-02-01

Congenital muscular dystrophies with collagen VI deficiency are inherited muscle disorders with a broad spectrum of clinical presentation and are caused by mutations in one of COL6A1-3 genes. Muscle pathology is characterized by fiber size variation and increased interstitial fibrosis and adipogenesis. In this study, we define critical events that contribute to muscle weakness and fibrosis in a mouse model with collagen VI deficiency. The Col6a1 GT/GT mice develop non-progressive weakness from younger age, accompanied by stunted muscle growth due to reduced IGF-1 signaling activity. In addition, the Col6a1 GT/GT mice have high numbers of interstitial skeletal muscle mesenchymal progenitor cells, which dramatically increase with repeated myofiber necrosis/regeneration. Our results suggest that impaired neonatal muscle growth and the activation of the mesenchymal cells in skeletal muscles contribute to the pathology of collagen VI deficient muscular dystrophy, and more importantly, provide the insights on the therapeutic strategies for collagen VI deficiency. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Functional and prognostic effects when emphysema complicates idiopathic pulmonary fibrosis.

PubMed

Jacob, Joseph; Bartholmai, Brian J; Rajagopalan, Srinivasan; Kokosi, Maria; Maher, Toby M; Nair, Arjun; Karwoski, Ronald; Renzoni, Elisabetta; Walsh, Simon L F; Hansell, David M; Wells, Athol U

2017-07-01

This study aimed to investigate whether the combination of fibrosis and emphysema has a greater effect than the sum of its parts on functional indices and outcome in idiopathic pulmonary fibrosis (IPF), using visual and computer-based (CALIPER) computed tomography (CT) analysis.Consecutive patients (n=272) with a multidisciplinary IPF diagnosis had the extent of interstitial lung disease (ILD) scored visually and by CALIPER. Visually scored emphysema was subcategorised as isolated or mixed with fibrotic lung. The CT scores were evaluated against functional indices forced vital capacity (FVC), diffusing capacity of the lungs for carbon monoxide ( D LCO ), transfer coefficient of the lung for carbon monoxide ( K CO ), composite physiologic index (CPI)) and mortality.The presence and extent of emphysema had no impact on survival. Results were maintained following correction for age, gender, smoking status and baseline severity using D LCO , and combined visual emphysema and ILD extent. Visual emphysema quantitation indicated that relative preservation of lung volumes (FVC) resulted from tractionally dilated airways within fibrotic lung, ventilating areas of admixed emphysema (p<0.0001), with no independent effect on FVC from isolated emphysema. Conversely, only isolated emphysema (p<0.0001) reduced gas transfer ( D LCO ).There is no prognostic impact of emphysema in IPF, beyond that explained by the additive extents of both fibrosis and emphysema. With respect to the location of pulmonary fibrosis, emphysema distribution determines the functional effects of emphysema. Copyright ©ERS 2017.

Structure of scintillations in Neptune's occultation shadow

NASA Technical Reports Server (NTRS)

Hubbard, W. B.; Lellouch, Emmanuel; Sicardy, Bruno; Brahic, Andre; Vilas, Faith

1988-01-01

An exceptionally high-quality data set from a Neptune occultation is used here to derive a number of new results about the statistical properties of the fluctuations of the intensity distribution in various parts of Neptune's occultation shadow. An approximate numerical ray-tracing model which successfully accounts for many of the qualitative aspects of the observed intensity fluctuation distribution is introduced. Strong refractive scintillation is simulated by including the effects of 'turbulence' with projected atmospheric properties allowed to vary in both the direction perpendicular and parallel to the limb, and an explicit two-dimensional picture of a typical intensity distribution throughout an occulting planet's shadow is presented. The results confirm the existence of highly anisotropic turbulence.

Revisiting the 1988 Pluto Occultation

NASA Astrophysics Data System (ADS)

Bosh, Amanda S.; Dunham, Edward W.; Young, Leslie A.; Slivan, Steve; Barba née Cordella, Linda L.; Millis, Robert L.; Wasserman, Lawrence H.; Nye, Ralph

2015-11-01

In 1988, Pluto's atmosphere was surmised to exist because of the surface ices that had been detected through spectroscopy, but it had not yet been directly detected in a definitive manner. The key to making such a detection was the stellar occultation method, used so successfully for the discovery of the Uranian rings in 1977 (Elliot et al. 1989; Millis et al. 1993) and before that for studies of the atmospheres of other planets.On 9 June 1988, Pluto occulted a star, with its shadow falling over the South Pacific Ocean region. One team of observers recorded this event from the Kuiper Airborne Observatory, while other teams captured the event from various locations in Australia and New Zealand. Preceding this event, extensive astrometric observations of Pluto and the star were collected in order to refine the prediction.We will recount the investigations that led up to this important Pluto occultation, discuss the unexpected atmospheric results, and compare the 1988 event to the recent 2015 event whose shadow followed a similar track through New Zealand and Australia.

Occult Intertrochanteric Fracture Mimicking the Fracture of Greater Trochanter

PubMed Central

Chung, Phil Hyun; Kang, Suk; Kim, Jong Pil; Kim, Young Sung; Back, In Hwa; Eom, Kyeong Soo

2016-01-01

Purpose Occult intertrochanteric fractures are misdiagnosed as isolated greater trochanteric fractures in some cases. We investigated the utility of three-dimensional computed tomography (3D-CT) and magnetic resonance imaging (MRI) in the diagnosis and outcome management of occult intertrochanteric fractures. Materials and Methods This study involved 23 cases of greater trochanteric fractures as diagnosed using plain radiographs from January 2004 to July 2013. Until January 2008, 9 cases were examined with 3D-CT only, while 14 cases were screened with both 3D-CT and MRI scans. We analyzed diagnostic accuracy and treatment results following 3D-CT and MRI scanning. Results Nine cases that underwent 3D-CT only were diagnosed with isolated greater trochanteric fractures without occult intertrochanteric fractures. Of these, a patient with displacement received surgical treatment. Of the 14 patients screened using both CT and MRI, 13 were diagnosed with occult intertrochanteric fractures. Of these, 11 were treated with surgical intervention and 2 with conservative management. Conclusion Three-dimensional CT has very low diagnostic accuracy in diagnosing occult intertrochanteric fractures. For this reason, MRI is recommended to confirm a suspected occult intertrochanteric fracture and to determine the most appropriate mode of treatment. PMID:27536653

The Treatment of the Occult in General Encyclopedias.

ERIC Educational Resources Information Center

Sonnenfeld, Gary F.

This paper is a content analysis of three general encyclopedias, "Encyclopedia Americana" (EA), "Encyclopaedia Brittanica" (EB), and "World Book Encyclopedia" (WBC), which quantifies the treatment of the occult. Entries are selected from each by starting with the article "Occultism" and tracing all…

Stellar Occultation Probe of Triton's Atmosphere

NASA Technical Reports Server (NTRS)

Elliot, James L.

1998-01-01

The goals of this research were (i) to better characterize Triton's atmospheric structure by probing a region not well investigated by Voyager and (ii) to begin acquiring baseline data for an investigation of the time evolution of the atmosphere which will set limits on the thermal conductivity of the surface and the total mass of N2 in the atmosphere. Our approach was to use observations (with the Kuiper Airborne Observatory) of a stellar occultation by Triton that was predicted to occur on 1993 July 10. As described in the attached reprint, we achieved these objectives through observation of this occultation and a subsequent one with the KAO in 1995. We found new results about Triton's atmospheric structure from the analysis of the two occultations observed with the KAO and ground-based data. These stellar occultation observations made both in the visible and infrared, have good spatial coverage of Triton including the first Triton central-flash observations, and are the first data to probe the 20-100 km altitude level on Triton. The small-planet light curve model of Elliot and Young (AJ 103, 991-1015) was generalized to include stellar flux refracted by the far limb, and then fitted to the data. Values of the pressure, derived from separate immersion and emersion chords, show no significant trends with latitude indicating that Triton's atmosphere is spherically symmetric at approximately 50 km altitude to within the error of the measurements. However, asymmetry observed in the central flash indicates the atmosphere is not homogeneous at the lowest levels probed (approximately 20 km altitude). From the average of the 1995 occultation data, the equivalent-isothermal temperature of the atmosphere is 47 +/- 1 K and the atmospheric pressure at 1400 km radius (approximately 50 km altitude) is 1.4 +/- 0.1 microbar. Both of these are not consistent with a model based on Voyager UVS and RSS observations in 1989 (Strobel et al, Icarus 120, 266-289). The atmospheric

Role of epithelial cells in idiopathic pulmonary fibrosis: from innocent targets to serial killers.

PubMed

Selman, Moisés; Pardo, Annie

2006-06-01

Idiopathic pulmonary fibrosis (IPF), a progressive and relentless lung scarring of unknown etiology, has been recognized as the most lethal interstitial lung disease. Despite the growing interest in IPF, the precise molecular mechanisms underlying the development of fibrosis and leading to the irreversible destruction of the lung are still unknown. Recently, it has been proposed that IPF, instead of being a chronic inflammatory disorder, results from multiple cycles of epithelial cell injury and activation. In turn, active alveolar epithelial cells provoke the migration, proliferation, and activation of mesenchymal cells with the formation of fibroblastic/myofibroblastic foci and the exaggerated accumulation of extracellular matrix, mirroring abnormal wound repair. In this article, some characteristics of the alveolar epithelium are briefly outlined, and the fibrogenic mechanisms specifically operated by active abnormal epithelial cells are examined.

Interstitial Lung Diseases

MedlinePlus

Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and ... is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among coal ...

All about Occultation.

ERIC Educational Resources Information Center

Riddle, Bob

2001-01-01

Describes occultation events involving the moon, when the moon blocks the view of planets or stars. Describes other events such as a partial solar eclipse, a penumbral lunar eclipse, meteor showers, and moon phases. Provides a list of internet resources related to these events. (DLH)

Occult Carbon Monoxide Poisoning

PubMed Central

Kirkpatrick, John N.

1987-01-01

A syndrome of headache, fatigue, dizziness, paresthesias, chest pain, palpitations and visual disturbances was associated with chronic occult carbon monoxide exposure in 26 patients in a primary care setting. A causal association was supported by finding a source of carbon monoxide in a patient's home, workplace or vehicle; results of screening tests that ruled out other illnesses; an abnormally high carboxyhemoglobin level in 11 of 14 patients tested, and abatement or resolution of symptoms when the source of carbon monoxide was removed. Exposed household pets provided an important clue to the diagnosis in some cases. Recurrent occult carbon monoxide poisoning may be a frequently overlooked cause of persistent or recurrent headache, fatigue, dizziness, paresthesias, abdominal pain, diarrhea and unusual spells. PMID:3825110

Occult carbon monoxide poisoning.

PubMed

Kirkpatrick, J N

1987-01-01

A syndrome of headache, fatigue, dizziness, paresthesias, chest pain, palpitations and visual disturbances was associated with chronic occult carbon monoxide exposure in 26 patients in a primary care setting. A causal association was supported by finding a source of carbon monoxide in a patient's home, workplace or vehicle; results of screening tests that ruled out other illnesses; an abnormally high carboxyhemoglobin level in 11 of 14 patients tested, and abatement or resolution of symptoms when the source of carbon monoxide was removed. Exposed household pets provided an important clue to the diagnosis in some cases. Recurrent occult carbon monoxide poisoning may be a frequently overlooked cause of persistent or recurrent headache, fatigue, dizziness, paresthesias, abdominal pain, diarrhea and unusual spells.

Crackle pitch and rate do not vary significantly during a single automated-auscultation session in patients with pneumonia, congestive heart failure, or interstitial pulmonary fibrosis.

PubMed

Vyshedskiy, Andrey; Ishikawa, Sadamu; Murphy, Raymond L H

2011-06-01

To determine the variability of crackle pitch and crackle rate during a single automated-auscultation session with a computerized 16-channel lung-sound analyzer. Forty-nine patients with pneumonia, 52 with congestive heart failure (CHF), and 18 with interstitial pulmonary fibrosis (IPF) performed breathing maneuvers in the following sequence: normal breathing, deep breathing, cough several times; deep breathing, vital-capacity maneuver, and deep breathing. From the auscultation recordings we measured the crackle pitch and crackle rate. Crackle pitch variability, expressed as a percentage of the average crackle pitch, was small in all patients and in all maneuvers: pneumonia 11%, CHF 11%, pulmonary fibrosis 7%. Crackle rate variability was also small: pneumonia 31%, CHF 32%, IPF 24%. Compared to the first deep-breathing maneuver (100%), the average crackle pitch did not significantly change following coughing (pneumonia 100%, CHF 103%, IPF 100%), the vital-capacity maneuver (pneumonia 100%, CHF 92%, IPF 104%), or during quiet breathing (pneumonia 97%, CHF 100%, IPF 104%). Similarly, the average crackle rate did not change significantly following coughing (pneumonia 105%, CHF 110%, IPF 90%) or the vital-capacity maneuver (pneumonia 102%, CHF 101%, IPF 99%). However, during normal breathing the crackle rate was significantly lower in the patients with pneumonia (74%, P < .001) and significantly higher in the patients with IPF (147%, P < .05) than it was during deep breathing. In patients with CHF the average crackle rate during normal breathing was not significantly different from that during the first deep-breathing maneuver (108%). Crackle pitch and rate were surprisingly stable in all 3 conditions. Neither crackle pitch nor crackle rate changed significantly from breath to breath or from one deep-breathing maneuver to another, even when the maneuvers were separated by cough or the vital-capacity maneuver. The observation that crackle rate is a reproducible

Clinical Impact of Emphysema Evaluated by High-Resolution Computed Tomography on Idiopathic Pulmonary Fibrosis Diagnosed by Surgical Lung Biopsy.

PubMed

Kohashi, Yasuo; Arai, Toru; Sugimoto, Chikatoshi; Tachibana, Kazunobu; Akira, Masanori; Kitaichi, Masanori; Hayashi, Seiji; Inoue, Yoshikazu

2016-01-01

The prognosis of combined cases of pulmonary fibrosis and emphysema is unresolved partially because radiological differentiation between usual interstitial pneumonia and nonspecific interstitial pneumonia is difficult in coexisting emphysema cases. The purpose of this study was to clarify the clinical impact of emphysema on the survival of patients with idiopathic pulmonary fibrosis (IPF). One hundred and seven patients with interstitial lung diseases were diagnosed by surgical lung biopsies between 2006 and 2012, and 47 patients were diagnosed with IPF through multidisciplinary discussion. Emphysema on high-resolution computed tomography scans was evaluated semiquantitatively by visual scoring. Eight out of the 47 IPF patients showed a higher emphysema score (>3) and were diagnosed to have IPF-emphysema. The median survival time of patients with IPF-emphysema (1,734 days) from the initial diagnosis was significantly shorter than that of patients with IPF alone (2,229 days) by Kaplan-Meier analysis (p = 0.007, log-rank test). Univariate Cox proportional hazard regression analyses revealed that a higher total emphysema score (>3.0) was a significantly poor prognostic factor in addition to Krebs von den Lungen-6, surfactant protein-D, arterial oxygen tension, percent forced vital capacity, and percent diffusing capacity of carbon monoxide (%DLCO). Multivariate Cox proportional hazard regression analyses with the stepwise method showed that higher total emphysema score (>3) and %DLCO were significantly poor prognostic factors. The prognosis of IPF-emphysema was significantly worse than that of IPF alone. © 2016 S. Karger AG, Basel.

The clinical significance of occult gynecologic primary tumours in metastatic cancer.

PubMed

Hannouf, M B; Winquist, E; Mahmud, S M; Brackstone, M; Sarma, S; Rodrigues, G; Rogan, P K; Hoch, J S; Zaric, G S

2017-10-01

We estimated the frequency of occult gynecologic primary tumours (gpts) in patients with metastatic cancer from an uncertain primary and evaluated the effect on disease management and overall survival (os). We used Manitoba administrative health databases to identify all patients initially diagnosed with metastatic cancer during 2002-2011. We defined patients as having an "occult" primary tumour if the primary was classified at least 6 months after the initial diagnosis. Otherwise, we considered patients to have "obvious" primaries. We then compared clinicopathologic and treatment characteristics and 2-year os for women with occult and with obvious gpts. We used Cox regression adjustment and propensity score methods to assess the effect on os of having an occult gpt. Among the 5953 patients diagnosed with metastatic cancer, occult primary tumours were more common in women ( n = 285 of 2552, 11.2%) than in men ( n = 244 of 3401, 7.2%). In women, gpts were the most frequent occult primary tumours ( n = 55 of 285, 19.3%). Compared with their counterparts having obvious gpts, women with occult gpts ( n = 55) presented with similar histologic and metastatic patterns but received fewer gynecologic diagnostic examinations during diagnostic work-up. Women with occult gpts were less likely to undergo surgery, waited longer for radiotherapy, and received a lesser variety of chemotherapeutic agents. Having an occult compared with an obvious gpt was associated with decreased os (hazard ratio: 1.62; 95% confidence interval: 1.2 to 2.35). Similar results were observed in adjusted analyses. In women with metastatic cancer from an uncertain primary, gpts constitute the largest clinical entity. Accurate diagnosis of occult gpts early in the course of metastatic cancer might lead to more effective treatment decisions and improved survival outcomes.

Occult spondyloarthritis in inflammatory bowel disease.

PubMed

Bandinelli, Francesca; Manetti, Mirko; Ibba-Manneschi, Lidia

2016-02-01

Spondyloarthritis (SpA) is a frequent extra-intestinal manifestation in patients with inflammatory bowel disease (IBD), although its real diffusion is commonly considered underestimated. Abnormalities in the microbioma and genetic predisposition have been implicated in the link between bowel and joint inflammation. Otherwise, up to date, pathogenetic mechanisms are still largely unknown and the exact influence of the bowel activity on rheumatic manifestations is not clearly explained. Due to evidence-based results of clinical studies, the interest on clinically asymptomatic SpA in IBD patients increased in the last few years. Actually, occult enthesitis and sacroiliitis are discovered in high percentages of IBD patients by different imaging techniques, mainly enthesis ultrasound (US) and sacroiliac joint X-ray examinations. Several diagnostic approaches and biomarkers have been proposed in an attempt to correctly classify and diagnose clinically occult joint manifestations and to define clusters of risk for patient screening, although definitive results are still lacking. The correct recognition of occult SpA in IBD requires an integrated multidisciplinary approach in order to identify common diagnostic and therapeutic strategies. The use of inexpensive and rapid imaging techniques, such as US and X-ray, should be routinely included in daily clinical practice and trials to correctly evaluate occult SpA, thus preventing future disability and worsening of quality of life in IBD patients.

Automated quantification of renal fibrosis with Sirius Red and polarization contrast microscopy

PubMed Central

Street, Jonathan M.; Souza, Ana Carolina P.; Alvarez‐Prats, Alejandro; Horino, Taro; Hu, Xuzhen; Yuen, Peter S. T.; Star, Robert A.

2014-01-01

Abstract Interstitial fibrosis is commonly measured by histology. The Masson trichrome stain is widely used, with semiquantitative scores subjectively assigned by trained operators. We have developed an objective technique combining Sirius Red staining, polarization contrast microscopy, and automated analysis. Repeated analysis of the same sections by the same operator (r = 0.99) or by different operators (r = 0.98) was highly consistent for Sirius Red, while Masson trichrome performed less consistently (r = 0.61 and 0.72, respectively). These techniques performed equally well when comparing sections from the left and right kidneys of mice. Poor correlation between Sirius Red and Masson trichrome may reflect different specificities, as enhanced birefringence with Sirius Red staining is specific for collagen type I and III fibrils. Combining whole‐section imaging and automated image analysis with Sirius Red/polarization contrast is a rapid, reproducible, and precise technique that is complementary to Masson trichrome. It also prevents biased selection of fields as fibrosis is measured on the entire kidney section. This new tool shall enhance our search for novel therapeutics and noninvasive biomarkers for fibrosis. To listen to podcast click here PMID:25052492

All-Sky Earth Occultation Observations with the Fermi Gamma-Ray Burst Monitor

NASA Technical Reports Server (NTRS)

Wilson-Hodge, C. A.; Beklen, E.; Bhat, P. N.; Briggs, M.; Camero-Arranz, A.; Case, G.; Jenke, P.; Chaplin, V.; Cherry, M.; Connaughton, V.;

A review of current and novel therapies for idiopathic pulmonary fibrosis

PubMed Central

Rafii, Rokhsara; Juarez, Maya M.; Albertson, Timothy E.

2013-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic interstitial lung disease that is associated with a median survival of 2-3 years from initial diagnosis. To date, there is no treatment approved for IPF in the United States, and only one pharmacological agent has been approved outside of the United States. Nevertheless, research over the past 10 years has provided us with a wealth of information on its histopathology, diagnostic work-up, and a greater understanding of its pathophysiology. Specifically, IPF is no longer thought to be a predominantly pro-inflammatory disorder. Rather, the fibrosis in IPF is increasingly understood to be the result of a fibroproliferative and aberrant wound healing cascade. The development of therapeutic targets has shifted in accord with this paradigm change. This review highlights the current understanding of IPF, and the recent as well as novel therapeutics being explored in clinical trials for the treatment of this devastating disease. PMID:23372951

All-Sky Earth Occultation Observations with the Fermi Gamma Ray Burst Monitor

NASA Technical Reports Server (NTRS)

Wilson-Hodge, C. A.; Beklen, E.; Bhat, P. N.; Briggs, M.; Camero-Arranz, A.; Case, G.; Chaplin, V.; Cherry, M.; Connaughton, V.; Finger, M.;

Lung fibrosis-associated soluble mediators and bronchoalveolar lavage from idiopathic pulmonary fibrosis patients promote the expression of fibrogenic factors in subepithelial lung myofibroblasts.

PubMed

Bouros, Evangelos; Filidou, Eirini; Arvanitidis, Konstantinos; Mikroulis, Dimitrios; Steiropoulos, Paschalis; Bamias, George; Bouros, Demosthenes; Kolios, George

2017-10-01

Idiopathic pulmonary fibrosis (IPF) is characterized by infiltration of inflammatory cells, excessive collagen production and accumulation of myofibroblasts. We explored the possible role of subepithelial lung myofibroblasts (SELMs) in the development of fibrosis in IPF. SELMs, isolated from surgical specimens of healthy lung tissue, were cultured with pro-inflammatory factors or bronchoalveolar lavage fluid (BALF) from patients with IPF or idiopathic non-specific interstitial pneumonia (iNSIP) and their fibrotic activity was assessed. Stimulation of SELMs with pro-inflammatory factors induced a significant increase of Tissue Factor (TF) and Tumor necrosis factor-Like cytokine 1 A (TL1A) expression and collagen production in culture supernatants. Stimulation with BALF from IPF patients with mild to moderate, but not severe disease, and from iNSIP patients induced a significant increase of TF expression. BALF from all IPF patients induced a significant increase of TL1A expression and collagen production, while BALF from iNSIP patients induced a significant increase of TL1A, but not of collagen production. Interestingly, TGF-β1 and BALF from all IPF, but not iNSIP patients, induced a significant increase in SELMs migration. In conclusion, BALF from IPF patients induces fibrotic activity in lung myofibroblasts, similar to mediators associated with lung fibrosis, indicating a key role of SELMs in IPF. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Research and Education Collaborative Occultation Network: A System for Coordinated TNO Occultation Observations

NASA Astrophysics Data System (ADS)

Buie, Marc W.; Keller, John M.

2016-03-01

We describe a new system and method for collecting coordinated occultation observations of trans-Neptunian objects (TNOs). Occultations by objects in the outer solar system are more difficult to predict due to their large distance and limited span of the astrometric data used to determine their orbits and positions. This project brings together the research and educational community into a unique citizen-science partnership to overcome the difficulties of observing these distant objects. The goal of the project is to get sizes and shapes for TNOs with diameters larger than 100 km. As a result of the system design it will also serve as a probe for binary systems with spatial separations as small as contact systems. Traditional occultation efforts strive to get a prediction sufficiently good to place mobile ground stations in the shadow track. Our system takes a new approach of setting up a large number of fixed observing stations and letting the shadows come to the network. The nominal spacing of the stations is 50 km so that we ensure two chords at our limiting size. The spread of the network is roughly 2000 km along a roughly north-south line in the western United States. The network contains 56 stations that are committed to the project and we get additional ad hoc support from International Occultation Timing Association members. At our minimum size, two stations will record an event while the other stations will be probing the inner regions for secondary events. Larger objects will get more chords and will allow determination of shape profiles. The stations are almost exclusively sited and associated with schools, usually at the 9-12 grade level. We present a full description of the system we have developed for the continued exploration of the Kuiper Belt.

The stellar occultation by the dwarf planet Haumea

NASA Astrophysics Data System (ADS)

Santos-Sanz, Pablo; Ortiz, Jose Luis; Sicardy, Bruno; Rossi, Gustavo; Berard, Diane; Morales, Nicolas; Duffard, Rene; Braga-Ribas, Felipe; Hopp, Ulrich; Ries, Christoph; Nascimbeni, Valerio; Marzari, Francesco; Granata, Valentina; Pál, András; Kiss, Csaba; Pribulla, Theodor; Milan Komzík, Richard; Hornoch, Kamil; Pravec, Petr; Bacci, Paolo; Maestripieri, Martina; Nerli, Luca; Mazzei, Leonardo; Bachini, Mauro; Martinelli, Fabio; Succi, Giacomo; Ciabattari, Fabrizio; Mikuz, Herman; Carbognani, Albino; Gaehrken, Bernd; Mottola, Stefano; Hellmich, Stephan; Rommel, Flavia; Fernández-Valenzuela, Estela; Campo Bagatin, Adriano; Haumea occultation international Collaboration: https://cloud.iaa.csic.es/public.php?service=files&t=d9276f8ab1a316cef13bee28bef75add

2017-10-01

The dwarf planet Haumea is a very peculiar Trans-Neptunian Object (TNO) with unique and exotic characteristics. It is currently classified as one of the five dwarf planets of the solar system, and it is the only one for which size, shape, albedo, density and other basic properties were not accurately known. To solve that we predicted an occultation of the star GaiaDR1 1233009038221203584 by Haumea and organized observations within the expected shadow path. Medium/large telescopes were needed to record the occultation with enough signal to noise ratio because the occulted star is of similar brightness as Haumea (R~17.7 mag). We will report results derived from this successful stellar occultation by Haumea on 2017 January 21st. The occultation was positive from 12 telescopes at 10 observing stations in Europe: the Asiago Observatory 1.8m telescope (Italy), the Mount Agliale Observatory 0.5m telescope (Italy), the Lajatico Astronomical Centre 0.5m telescope (Italy), the S.Marcello Pistoiese Observatory 0.6m telescope (Italy), the Crni Vrh Observatory 0.6m telescope (Slovenia), the Ondrejov Observatory 0.65m telescope (Czech Republic), the Bavarian Public Observatory 0.81m telescope (Germany), the Konkoly Observatory 1m and 0.6m telescopes (Hungary), the Skalnate Pleso Observatory 1.3m telescope (Slovakia), and the Wendelstein Observatory 2m and 0.4m telescopes (Germany). This is the occultation by a TNO with the largest number of chords ever recorded.Part of this work has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 687378.

Occult diaphragmatic injuries caused by stab wounds.

PubMed

Leppäniemi, Ari; Haapiainen, Reijo

2003-10-01

Missed diaphragmatic perforation caused by penetrating trauma can lead to subsequent strangulation of a hollow viscus, which has prompted the use of invasive diagnostic procedures to exclude occult diaphragmatic injuries in asymptomatic, high-risk patients. The objective of this study was to determine the incidence of occult diaphragmatic injuries caused by stab wounds of the lower chest and upper abdomen, and to examine the natural history and consequences of missed diaphragmatic injuries. On the basis of patient data from two previous randomized studies from our institution, a retrospective analysis was performed on 97 patients treated for anterior stab wounds located between the nipple line, the umbilical level, and the posterior axillary lines not having indications for immediate surgical exploration. The patients were divided into two groups on the basis of their initial randomized management (open or laparoscopic exploration vs. expectant observation). In the exploration group (n = 47), four diaphragmatic injuries (9%) were detected (three left-sided and one right-sided). Excluding patients with associated injuries requiring surgical repair, the incidence of occult diaphragmatic injuries was 3 of 43 (7%). In the observation group (n = 50), there were two patients (4%) with delayed presentation of missed left-sided diaphragmatic injury 2 and 23 months later, respectively. Both injuries resulted from stab wounds of the left flank and presented with herniation of the stomach or small bowel and colon. The overall incidence of occult diaphragmatic injuries in left-sided thoracoabdominal stab wounds was 4 of 24 (17%), and was much lower after stab wounds of left epigastrium (0%), right lower chest (0%), and right epigastrium (4%). In asymptomatic patients with anterior or flank stab wounds of the lower chest or upper abdominal area, the risk of an occult diaphragmatic injury is approximately 7% which, if undetected, is associated with a high risk of subsequent

Occult Cushing's syndrome in type-2 diabetes.

PubMed

Catargi, Bogdan; Rigalleau, Vincent; Poussin, Agathe; Ronci-Chaix, Nathalie; Bex, Veronique; Vergnot, Vincent; Gin, Henri; Roger, Patrick; Tabarin, Antoine

2003-12-01

Subclinical Cushing's syndrome (SCS) caused by adrenal incidentalomas is frequently associated with overweight and insulin resistance. Metabolic syndrome X may therefore be a clue to the presence of CS. However, the incidence of CS in this situation remains unknown. We have conducted a prospective study to evaluate the prevalence of occult CS in overweight, type-2 diabetic patients devoided of specific clinical symptoms of CS. Two hundred overweight, type-2 diabetic patients, consecutively referred for poor metabolic control (HbA(1C) > 8%), were studied as inpatients. A first screening step was performed with the 1-mg overnight dexamethasone suppression test (DST) using a revised criterion for cortisol suppression (60 nmol/liter) to maximize the sensitivity of the procedure. A second confirmatory step of biochemical investigations (midnight plasma cortisol concentration, plasma cortisol circadian rhythm, morning plasma ACTH concentration, 24-h urinary free cortisol, and 4-mg i.v. DST) was performed in patients with impaired 1-mg DST. A third step of imaging studies was performed according to the results of second-step investigations. Fifty-two patients had impaired 1-mg DST. Among these, 47 were further evaluated. Thirty were considered as false positives of the 1-mg DST, whereas 17 displayed at least one additional biological abnormality of the hypothalamic-pituitary-adrenal axis. Definitive occult CS was identified in four patients (2% of the whole series) with Cushing's disease (n = 3) and surgically proven adrenal adenoma (n = 1). Definitive diagnosis remains to be established in seven additional patients (3.5%) with mild occult CS associated with unsuppressed plasma ACTH concentrations and a unilateral adrenal tumor of 10-29 mm in size showing prevalent uptake at radiocholesterol scintigraphy. In conclusion, a relatively high prevalence of occult CS was found in our study. Further studies are needed to evaluate the impact of the cure of occult CS on obesity

Cassini First Diametric Radio Occultation of Saturn's Rings

NASA Astrophysics Data System (ADS)

Marouf, E.; French, R.; Rappaport, N.; Kliore, A.; Flasar, M.; Nagy, A.; Ambrosini, R.; McGhee, C.; Schinder, P.; Anabtawi, A.; Barbinis, E.; Goltz, G.; Thomson, F.; Wong, K.

2005-05-01

We present preliminary results expected from the first planned Cassini radio occultation observation of Saturn's rings, to be conducted on May 3rd, 2005. The path of Cassini as seen from Earth (the occultation track) has been designed to cross the rings from the west to the east ansa almost diametrically, allowing for occultation of all major ring features at two widely separated longitudes (about 180 deg apart). The duration of the geometric occultation is about 1.5 hours on each side. During the occultation, Cassini transmits through the rings three coherent monochromatic radio signals of wavelength 0.94, 3.6, and 13 cm (Ka-, X-, and S-band respectively), a capability unique to Cassini. The perturbed signals received at the Earth are recorded at the NASA DSN complexes at Goldstone and Canberra. Both direct and forward-scattered components of the signal may be identified in spectrograms of the received signals. The time history of the extinction of the direct signal is expected to yield high-spatial-resolution optical depth and phase shift profiles of ring structure. The timing of the occultation was optimized to allow probing the rings when the ring-opening-angle B (the angle between the line-of-sight and the ring plane) is relatively large (B = 23 deg), hence maximizing chances of measuring for the first time the structure of the relatively optically thick Ring B. In a similar experiment by Voyager in 1980, excessive signal attenuation along the long path within the nearly closed rings (B = 5.9 deg) limited the utility of the observations in relatively thick ring regions, in particular the main Ring B. For the Cassini optimized occultation geometry, a large B, slow radial velocity along the occultation track, and much improved phase stability of the reference ultrastable oscillator (USO) on board Cassini combine to promise achievable radial resolution approaching 100 m over a good fraction of the rings. Measurement of the amplitude and phase of the diffracted

Close Double Stars from Occultation Video Recordings

NASA Astrophysics Data System (ADS)

Waring Dunham, David; George, Anthony; Loader, Brian; Herald, David Russell

2015-08-01

Astronomers around the world, both amateur and professional, have been recording lunar and asteroidal occultations of close double stars during the past several years using inexpensive but quite sensitive video cameras that are now available. Several new double stars have been discovered, and the parameters of many close systems have been determined. Besides rather good measurements of the relative magnitudes of the components, the actual separations and position angles can be measured if observations of the same event are made from two or more separate stations. These observations collected by the International Occultation Timing Association (IOTA) are published in the Journal of Double Star Observations. Recently, IOTA has encouraged the observation of occultations of stars in the Kepler 2 program, which is interested in data about close duplicity that affects their analyses for exoplanet transits.

The development and validation of the King's Brief Interstitial Lung Disease (K-BILD) health status questionnaire.

PubMed

Patel, Amit S; Siegert, Richard J; Brignall, Katherine; Gordon, Patrick; Steer, Sophia; Desai, Sujal R; Maher, Toby M; Renzoni, Elisabetta A; Wells, Athol U; Higginson, Irene J; Birring, Surinder S

2012-09-01

Health status is impaired in patients with interstitial lung disease (ILD). There is a paucity of tools that assess health status in ILD. The objective of this study was to develop and validate the King's Brief Interstitial Lung Disease questionnaire (K-BILD), a new health status measure for patients with ILD. Patients with ILD were recruited from outpatient clinics. The development of the questionnaire consisted of three phases: item generation; item reduction, allocation to domains by factor analysis, Rasch analysis to create unidimensional scales and validation; and repeatability testing. 173 patients with ILD (49 with idiopathic pulmonary fibrosis) completed a preliminary 71-item questionnaire. 56 items were removed due to redundancy, low factor loadings or poor fit to the Rasch model. The final version of the K-BILD questionnaire consisted of 15 items and three domains (breathlessness and activities, chest symptoms and psychological). Internal consistency assessed with Cronbach's α coefficient was 0.94 for the K-BILD total score. Concurrent validity of the K-BILD questionnaire was high compared with St George's Respiratory Questionnaire (r=0.90) and moderate with lung function (vital capacity, r=0.50). The K-BILD questionnaire was repeatable over 2 weeks (n=44), with intraclass correlation coefficients for domains and total score 0.86-0.94. The K-BILD construct validity for patients with idiopathic pulmonary fibrosis was similar to that of other ILDs. The K-BILD questionnaire is a brief, valid, self-completed health status measure for ILD. It could be used in the clinic to assess ILD from the patients' perspective.

Wave optics-based LEO-LEO radio occultation retrieval

NASA Astrophysics Data System (ADS)

Benzon, Hans-Henrik; Høeg, Per

2016-06-01

This paper describes the theory for performing retrieval of radio occultations that use probing frequencies in the XK and KM band. Normally, radio occultations use frequencies in the L band, and GPS satellites are used as the transmitting source, and the occultation signals are received by a GPS receiver on board a Low Earth Orbit (LEO) satellite. The technique is based on the Doppler shift imposed, by the atmosphere, on the signal emitted from the GPS satellite. Two LEO satellites are assumed in the occultations discussed in this paper, and the retrieval is also dependent on the decrease in the signal amplitude caused by atmospheric absorption. The radio wave transmitter is placed on one of these satellites, while the receiver is placed on the other LEO satellite. One of the drawbacks of normal GPS-based radio occultations is that external information is needed to calculate some of the atmospheric products such as the correct water vapor content in the atmosphere. These limitations can be overcome when a proper selected range of high-frequency waves are used to probe the atmosphere. Probing frequencies close to the absorption line of water vapor have been included, thus allowing the retrieval of the water vapor content. Selecting the correct probing frequencies would make it possible to retrieve other information such as the content of ozone. The retrieval is performed through a number of processing steps which are based on the Full Spectrum Inversion (FSI) technique. The retrieval chain is therefore a wave optics-based retrieval chain, and it is therefore possible to process measurements that include multipath. In this paper simulated LEO to LEO radio occultations based on five different frequencies are used. The five frequencies are placed in the XK or KM frequency band. This new wave optics-based retrieval chain is used on a number of examples, and the retrieved atmospheric parameters are compared to the parameters from a global European Centre for Medium

Distribution of the GNSS-LEO occultation events over Egypt

NASA Astrophysics Data System (ADS)

Ghoniem, Ibrahim; Mousa, Ashraf El-Kutb; El-Fiky, Gamal

2017-06-01

The space-based GNSS RO technique is a promising tool for monitoring the Earth's atmosphere and ionosphere (Mousa et al., 2006). The current paper presents the distribution of the occultation events over Egypt using the operating LEO satellites and GNSS by its two operating systems. By the present research, Egypt could raise NWP Models efficiency by improving meteorological data quality. Twenty operating LEO missions (e.g. Argentinean SAC-C, European MetOp-A, German TerraSAR-X, Indian OceanSat-2, etc.) sent by different countries all over the world were used to derive the occultation events position through Egypt borders by receiving signal from the American global positioning system (GPS) and the Russian global navigation satellite system (GLONASS). Approximately 20,000 km Altitude satellites are transmitting enormous number of rays by the day to approximately 800 km satellites passing by the Earth atmosphere. Our mission is to derive all of these rays position (start and end) by calculating satellites position by the time, determine the rays in the occultation case and derive the atmosphere tangent point position for all occultating rays on the Earth surface (Occultation Events).

Radio Occultation Measurements of Pluto's Atmosphere with New Horizons

NASA Astrophysics Data System (ADS)

Hinson, D. P.; Linscott, I.; Tyler, G. L.; Bird, M. K.; Paetzold, M.; Strobel, D. F.; Summers, M. E.; Woods, W. W.; Stern, A.; Weaver, H. A., Jr.; Olkin, C.; Young, L. A.; Ennico Smith, K.; Gladstone, R.; Greathouse, T.; Kammer, J.; Parker, A. H.; Parker, J. W.; Retherford, K. D.; Schindhelm, E.; Singer, K. N.; Steffl, A.; Tsang, C.; Versteeg, M.

2015-12-01

The reconnaissance of the Pluto System by New Horizons included radio occultations at both Pluto and Charon. This talk will present the latest results from the Pluto occultation. The REX instrument onboard New Horizons received and recorded uplink signals from two 70-m antennas and two 34-m antennas of the NASA Deep Space Network - each transmitting 20 kW at 4.2-cm wavelength - during a diametric occultation by Pluto. At the time this was written only a short segment of data at occultation entry (193°E, 17°S) was available for analysis. The REX measurements extend unequivocally to the surface, providing the first direct measure of the surface pressure and the temperature structure in Pluto's lower atmosphere. Preliminary analysis yields a surface pressure of about 10 microbars, smaller than expected. Data from occultation exit (16°E, 15°N) are scheduled to arrive on the ground in late August 2015. Those observations will yield an improved estimate of the surface pressure, a second temperature profile, and a measure of the diameter of Pluto with a precision of a few hundred meters.

Epithelial to mesenchymal transition-related proteins ZEB1, β-catenin, and β-tubulin-III in idiopathic pulmonary fibrosis.

PubMed

Chilosi, Marco; Caliò, Anna; Rossi, Andrea; Gilioli, Eliana; Pedica, Federica; Montagna, Licia; Pedron, Serena; Confalonieri, Marco; Doglioni, Claudio; Ziesche, Rolf; Grubinger, Markus; Mikulits, Wolfgang; Poletti, Venerino

2017-01-01

Epithelial to mesenchymal transition has been suggested as a relevant contributor to pulmonary fibrosis, but how and where this complex process is triggered in idiopathic pulmonary fibrosis is not fully understood. Beta-tubulin-III (Tubβ3), ZEB1, and β-catenin are partially under the negative control of miR-200, a family of micro-RNAs playing a major role in epithelial to mesenchymal transition, that are reduced in experimental lung fibrosis and idiopathic pulmonary fibrosis. We wonder whether in situ expression of these proteins is increased in idiopathic pulmonary fibrosis, to better understand the significance of miR-200 feedback loop and epithelial to mesenchymal transition. We investigated the immunohistochemical and immunofluorescent expression and precise location of ZEB1, Tubβ3, and β-catenin in tissue samples from 34 idiopathic pulmonary fibrosis cases and 21 controls (5 normal lungs and 16 other interstitial lung diseases). In 100% idiopathic pulmonary fibrosis samples, the three proteins were concurrently expressed in fibroblastic foci, as well in damaged epithelial cells overlying these lesions and in pericytes within neo-angiogenesis areas. These results were also confirmed by immunofluorescence assay. In controls the abnormal expression of the three proteins was absent or limited. This is the first study that relates concurrent expression of Tubβ3, ZEB1, and β-catenin to abnormal epithelial and myofibroblast differentiation in idiopathic pulmonary fibrosis, providing indirect but robust evidence of miR-200 deregulation and epithelial to mesenchymal transition activation in idiopathic pulmonary fibrosis. The abnormal expression and localization of these proteins in bronchiolar fibro-proliferative lesions are unique for idiopathic pulmonary fibrosis, and might represent a disease-specific marker in challenging lung biopsies.

Auscultation of Velcro Crackles is Associated With Usual Interstitial Pneumonia

PubMed Central

Sellarés, Jacobo; Hernández-González, Fernanda; Lucena, Carmen Mª; Paradela, Marina; Brito-Zerón, Pilar; Prieto-González, Sergio; Benegas, Mariana; Cuerpo, Sandra; Espinosa, Gerard; Ramírez, José; Sánchez, Marcelo; Xaubet, Antoni

2016-01-01

Abstract Auscultation of Velcro crackles has been proposed as a key finding in physical lung examination in patients with interstitial lung diseases (ILDs), especially in idiopathic pulmonary fibrosis (IPF). However, no studies have been carried out to assess the association of Velcro crackles with other clinical variables. We evaluated a cohort of 132 patients, prospectively and consecutively included in our ILD diagnostic program at a tertiary referral center. All patients were auscultated during the physical examination. The patients were divided into 2 groups: “presence” or “nonpresence” of bilateral Velcro crackles. Of all patients assessed, 83 (63%) presented Velcro crackles in the respiratory auscultation. Patients with Velcro crackles usually had more frequently cough and dyspnea at the moment of diagnosis. Forced vital capacity (P = 0.002) and lung diffusion capacity for carbon monoxide (P = 0.04) was lower in these patients. The ILD-GAP index was higher in the group with Velcro crackles (P = 0.01). All patients with usual interstitial pneumonia (UIP) in high-resolution computed tomography and all patients with final IPF diagnosis presented Velcro crackles. In multivariate analysis, the presence of Velcro crackles was independently associated with an UIP pattern. In patients suspected of having ILD, the auscultation of Velcro crackles was associated with UIP, a possibility which must be taken into consideration in early ILD detection in primary care. PMID:26844464

Auscultation of Velcro Crackles is Associated With Usual Interstitial Pneumonia.

PubMed

Sellarés, Jacobo; Hernández-González, Fernanda; Lucena, Carmen M; Paradela, Marina; Brito-Zerón, Pilar; Prieto-González, Sergio; Benegas, Mariana; Cuerpo, Sandra; Espinosa, Gerard; Ramírez, José; Sánchez, Marcelo; Xaubet, Antoni

2016-02-01

Auscultation of Velcro crackles has been proposed as a key finding in physical lung examination in patients with interstitial lung diseases (ILDs), especially in idiopathic pulmonary fibrosis (IPF). However, no studies have been carried out to assess the association of Velcro crackles with other clinical variables.We evaluated a cohort of 132 patients, prospectively and consecutively included in our ILD diagnostic program at a tertiary referral center. All patients were auscultated during the physical examination. The patients were divided into 2 groups: "presence" or "nonpresence" of bilateral Velcro crackles.Of all patients assessed, 83 (63%) presented Velcro crackles in the respiratory auscultation. Patients with Velcro crackles usually had more frequently cough and dyspnea at the moment of diagnosis. Forced vital capacity (P = 0.002) and lung diffusion capacity for carbon monoxide (P = 0.04) was lower in these patients. The ILD-GAP index was higher in the group with Velcro crackles (P = 0.01). All patients with usual interstitial pneumonia (UIP) in high-resolution computed tomography and all patients with final IPF diagnosis presented Velcro crackles. In multivariate analysis, the presence of Velcro crackles was independently associated with an UIP pattern.In patients suspected of having ILD, the auscultation of Velcro crackles was associated with UIP, a possibility which must be taken into consideration in early ILD detection in primary care.

Cinnamaldehyde impairs high glucose-induced hypertrophy in renal interstitial fibroblasts

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

Chao, Louis Kuoping; Chang, W.-T.; Shih, Y.-W.

2010-04-15

Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. To explore whether cinnamaldehyde was linked to altered high glucose (HG)-mediated renal tubulointerstitial fibrosis in diabetic nephropathy (DN), the molecular mechanisms of cinnamaldehyde responsible for inhibition of HG-induced hypertrophy in renal interstitial fibroblasts were examined. We found that cinnamaldehyde caused inhibition of HG-induced cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, cleaved poly(ADP-ribose) polymerase (PARP) protein expression, and mitochondrial cytochrome c release in HG or cinnamaldehyde treatments in these cells. HG-induced extracellular signal-regulatedmore » kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) (but not the Janus kinase 2/signal transducers and activators of transcription) activation was markedly blocked by cinnamaldehyde. The ability of cinnamaldehyde to inhibit HG-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of collagen IV, fibronectin, and alpha-smooth muscle actin (alpha-SMA). The results obtained in this study suggest that cinnamaldehyde treatment of renal interstitial fibroblasts that have been stimulated by HG reduces their ability to proliferate and hypertrophy through mechanisms that may be dependent on inactivation of the ERK/JNK/p38 MAPK pathway.« less

Tubule-Derived Wnts Are Required for Fibroblast Activation and Kidney Fibrosis.

PubMed

Zhou, Dong; Fu, Haiyan; Zhang, Lu; Zhang, Ke; Min, Yali; Xiao, Liangxiang; Lin, Lin; Bastacky, Sheldon I; Liu, Youhua

2017-08-01

Cell-cell communication via Wnt ligands is necessary in regulating embryonic development and has been implicated in CKD. Because Wnt ligands are ubiquitously expressed, the exact cellular source of the Wnts involved in CKD remains undefined. To address this issue, we generated two conditional knockout mouse lines in which Wntless (Wls), a dedicated cargo receptor that is obligatory for Wnt secretion, was selectively ablated in tubular epithelial cells or interstitial fibroblasts. Blockade of Wnt secretion by genetic deletion of Wls in renal tubules markedly inhibited myofibroblast activation and reduced renal fibrosis after unilateral ureteral obstruction. This effect associated with decreased activation of β -catenin and downstream gene expression and preserved tubular epithelial integrity. In contrast, fibroblast-specific deletion of Wls exhibited little effect on the severity of renal fibrosis after obstructive or ischemia-reperfusion injury. In vitro , incubation of normal rat kidney fibroblasts with tubule-derived Wnts promoted fibroblast proliferation and activation. Furthermore, compared with kidney specimens from patients without CKD, biopsy specimens from patients with CKD also displayed increased expression of multiple Wnt proteins, predominantly in renal tubular epithelium. These results illustrate that tubule-derived Wnts have an essential role in promoting fibroblast activation and kidney fibrosis via epithelial-mesenchymal communication. Copyright © 2017 by the American Society of Nephrology.

Diagnostic accuracy of oblique chest radiograph for occult pneumothorax: comparison with ultrasonography.

PubMed

Matsumoto, Shokei; Sekine, Kazuhiko; Funabiki, Tomohiro; Orita, Tomohiko; Shimizu, Masayuki; Hayashida, Kei; Kazamaki, Taku; Suzuki, Tatsuya; Kishikawa, Masanobu; Yamazaki, Motoyasu; Kitano, Mitsuhide

2016-01-01

An occult pneumothorax is a pneumothorax that is not seen on a supine chest X-ray but is detected by computed tomography scanning. However, critical patients are difficult to transport to the computed tomography suite. We previously reported a method to detect occult pneumothorax using oblique chest radiography (OXR). Several authors have also reported that ultrasonography is an effective technique for detecting occult pneumothorax. The aim of this study was to evaluate the usefulness of OXR in the diagnosis of the occult pneumothorax and to compare OXR with ultrasonography. All consecutive blunt chest trauma patients with clinically suspected pneumothorax on arrival at the emergency department were prospectively included at our tertiary-care center. The patients underwent OXR and ultrasonography, and underwent computed tomography scans as the gold standard. Occult pneumothorax size on computed tomography was classified as minuscule, anterior, or anterolateral. One hundred and fifty-nine patients were enrolled. Of the 70 occult pneumothoraces found in the 318 thoraces, 19 were minuscule, 32 were anterior, and 19 were anterolateral. The sensitivity and specificity of OXR for detecting occult pneumothorax was 61.4 % and 99.2 %, respectively. The sensitivity and specificity of lung ultrasonography was 62.9 % and 98.8 %, respectively. Among 27 occult pneumothoraces that could not be detected by OXR, 16 were minuscule and 21 could be conservatively managed without thoracostomy. OXR appears to be as good method as lung ultrasonography in the detection of large occult pneumothorax. In trauma patients who are difficult to transfer to computed tomography scan, OXR may be effective at detecting occult pneumothorax with a risk of progression.

The clinical significance of occult gynecologic primary tumours in metastatic cancer

PubMed Central

Hannouf, M.B.; Winquist, E.; Mahmud, S.M.; Brackstone, M.; Sarma, S.; Rodrigues, G.; Rogan, P.K.; Hoch, J.S.; Zaric, G.S.

2017-01-01

Objective We estimated the frequency of occult gynecologic primary tumours (gpts) in patients with metastatic cancer from an uncertain primary and evaluated the effect on disease management and overall survival (os). Methods We used Manitoba administrative health databases to identify all patients initially diagnosed with metastatic cancer during 2002–2011. We defined patients as having an “occult” primary tumour if the primary was classified at least 6 months after the initial diagnosis. Otherwise, we considered patients to have “obvious” primaries. We then compared clinicopathologic and treatment characteristics and 2-year os for women with occult and with obvious gpts. We used Cox regression adjustment and propensity score methods to assess the effect on os of having an occult gpt. Results Among the 5953 patients diagnosed with metastatic cancer, occult primary tumours were more common in women (n = 285 of 2552, 11.2%) than in men (n = 244 of 3401, 7.2%). In women, gpts were the most frequent occult primary tumours (n = 55 of 285, 19.3%). Compared with their counterparts having obvious gpts, women with occult gpts (n = 55) presented with similar histologic and metastatic patterns but received fewer gynecologic diagnostic examinations during diagnostic work-up. Women with occult gpts were less likely to undergo surgery, waited longer for radiotherapy, and received a lesser variety of chemotherapeutic agents. Having an occult compared with an obvious gpt was associated with decreased os (hazard ratio: 1.62; 95% confidence interval: 1.2 to 2.35). Similar results were observed in adjusted analyses. Conclusions In women with metastatic cancer from an uncertain primary, gpts constitute the largest clinical entity. Accurate diagnosis of occult gpts early in the course of metastatic cancer might lead to more effective treatment decisions and improved survival outcomes. PMID:29089807

Overweight female rats selectively breed for low aerobic capacity exhibit increased myocardial fibrosis and diastolic dysfunction

PubMed Central

Johnson, Megan S.; Ma, Lixin; Pulakat, Lakshmi; Mugerfeld, Irina; Hayden, Melvin R.; Garro, Mona; Knight, William; Britton, Steven L.; Koch, Lauren G.; Sowers, James R.

2012-01-01

The statistical association between endurance exercise capacity and cardiovascular disease suggests that impaired aerobic metabolism underlies the cardiovascular disease risk in men and women. To explore this connection, we applied divergent artificial selection in rats to develop low-capacity runner (LCR) and high-capacity runner (HCR) rats and found that disease risks segregated strongly with low running capacity. Here, we tested if inborn low aerobic capacity promotes differential sex-related cardiovascular effects. Compared with HCR males (HCR-M), LCR males (LCR-M) were overweight by 34% and had heavier retroperitoneal, epididymal, and omental fat pads; LCR females (LCR-F) were 20% heavier than HCR females (HCR-F), and their retroperitoneal, but not perireproductive or omental, fat pads were heavier as well. Unlike HCR-M, blood pressure was elevated in LCR-M, and this was accompanied by left ventricular (LV) hypertrophy. Like HCR-F, LCR-F exhibited normal blood pressure and LV weight as well as increased spontaneous cage activity compared with males. Despite normal blood pressures, LCR-F exhibited increased myocardial interstitial fibrosis and diastolic dysfunction, as indicated by increased LV stiffness, a decrease in the initial filling rate, and an increase in diastolic relaxation time. Although females exhibited increased arterial stiffness, ejection fraction was normal. Increased interstitial fibrosis and diastolic dysfunction in LCR-F was accompanied by the lowest protein levels of phosphorylated AMP-actived protein kinase [phospho-AMPK (Thr172)] and silent information regulator 1. Thus, the combination of risk factors, including female sex, intrinsic low aerobic capacity, and overweightness, promote myocardial stiffness/fibrosis sufficient to induce diastolic dysfunction in the absence of hypertension and LV hypertrophy. PMID:22345570

Pluto-Charon Stellar Occultation Candidates: 1990-1995

NASA Technical Reports Server (NTRS)

Dunham, E. W.; McDonald, S. W.; Elliot, J. L.

1991-01-01

We have carried out a search to identify stars that might be occulted by Pluto or Charon during the period 1990-1995 and part of 1996. This search was made with an unfiltered CCD camera operated in the strip scanning mode, and it reaches an R magnitude of approximately 17.5-about 1.5 mag fainter than previous searches. Circumstances for each of the 162 potential occultations are given, including an approximate R magnitude of the star, which allows estimation of the signal-to-noise ratio (S/N) for observation of each occultation. The faintest stars in our list would yield an S/N of about 20 for a 1 S integration when observed with a CCD detector on an 8 m telescope under a dark sky. Our astrometric precision (+/- 0.2 arcsec, with larger systematic errors possible for individual cases) is insufficient to serve as a final prediction for these potential occultations, but is sufficient to identify stars deserving of further, more accurate, astrometric observations. Statistically, we expect about 32 of these events to be observable somewhere on Earth. The number of events actually observed will be substantially smaller because of clouds and the sparse distribution of large telescopes. Finder charts for each of the 91 stars involved are presented.

Pluto-Charon stellar occultation candidates - 1990-1995

NASA Technical Reports Server (NTRS)

Dunham, E. W.; Mcdonald, S. W.; Elliot, J. L.

1991-01-01

A search to identify stars that might be occulted by Pluto or Charon during the period 1990-1995 and part of 1996 is studied. This search was made with an unfiltered CCD camera operated in the strip scanning mode, and it reaches an R magnitude of approximately 17.5 - about 1.5 mag fainter than previous searches. Circumstances for each of the 162 potential occultations are given, including an approximate R magnitude of the star, which allows estimation of the signal-to-noise ratio (S/N) for observation of each occultation. The faintest stars in the list would yield an S/N of about 20 for a 1 s integration when observed with a CCD detector on an 8 m telescope under a dark sky. The astrometric precision (+/- 0.2 arcsec, with larger systematic errors possible for individual cases) is insufficient to serve as a final prediction for these potential occultations, but is sufficient to identify stars deserving of further, more accurate, astrometric observations. Statistically, about 32 of these events to be observable somewhere on earth are expected. The number of events actually observed will be substantially smaller because of clouds and the sparse distribution of large telescopes. Finder charts for each of the 91 stars involved are presented.

Arctigenin suppresses renal interstitial fibrosis in a rat model of obstructive nephropathy.

PubMed

Li, Ao; Zhang, Xiaoxun; Shu, Mao; Wu, Mingjun; Wang, Jun; Zhang, Jingyao; Wang, Rui; Li, Peng; Wang, Yitao

2017-07-01

Renal tubulointerstitial fibrosis (TIF) is commonly the final result of a variety of progressive injuries and leads to end-stage renal disease. There are few therapeutic agents currently available for retarding the development of renal TIF. The aim of the present study is to evaluate the role of arctigenin (ATG), a lignan component derived from dried burdock (Arctium lappa L.) fruits, in protecting the kidney against injury by unilateral ureteral obstruction (UUO) in rats. Rats were subjected to UUO and then administered with vehicle, ATG (1 and 3mg/kg/d), or losartan (20mg/kg/d) for 11 consecutive days. The renoprotective effects of ATG were evaluated by histological examination and multiple biochemical assays. Our results suggest that ATG significantly protected the kidney from injury by reducing tubular dilatation, epithelial atrophy, collagen deposition, and tubulointerstitial compartment expansion. ATG administration dramatically decreased macrophage (CD68-positive cell) infiltration. Meanwhile, ATG down-regulated the mRNA levels of pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) and cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ), in the obstructed kidneys. This was associated with decreased activation of nuclear factor κB (NF-κB). ATG attenuated UUO-induced oxidative stress by increasing the activity of renal manganese superoxide dismutase (SOD2), leading to reduced levels of lipid peroxidation. Furthermore, ATG inhibited the epithelial-mesenchymal transition (EMT) of renal tubules by reducing the abundance of transforming growth factor-β1 (TGF-β1) and its type I receptor, suppressing Smad2/3 phosphorylation and nuclear translocation, and up-regulating Smad7 expression. Notably, the efficacy of ATG in renal protection was comparable or even superior to losartan. ATG could protect the kidney from UUO-induced injury and fibrogenesis by suppressing inflammation, oxidative

CT detection of occult pneumothorax in head trauma

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

Tocino, I.M.; Miller, M.H.; Frederick, P.R.

1984-11-01

A prospective evaluation for occult pneumothorax was performed in 25 consecutive patients with serious head trauma by combining a limited chest CT examination with the emergency head CT examination. Of 21 pneuomothoraces present in 15 patients, 11 (52%) were found only by chest CT and were not identified clinically or by supine chest radiograph. Because of pending therapeutic measures, chest tubes were placed in nine of the 11 occult pneumothoraces, regardless of the volume. Chest CT proved itself as the most sensitive method for detection of occult pneumothorax, permitting early chest tube placement to prevent transition to a tension pneumothoraxmore » during subsequent mechanical ventilation or emergency surgery under general anesthesia.« less

Bone scanning in the detection of occult fractures

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

Batillas, J.; Vasilas, A.; Pizzi, W.F.

1981-07-01

The potential role of bone scanning in the early detection of occult fractures following acute trauma was investigated. Technetium 99m pyrophosphate bone scans were obtained in patients with major clinical findings and negative or equivocal roentgenograms following trauma. Bone scanning facilitated the prompt diagnosis of occult fractures in the hip, knee, wrist, ribs and costochondral junctions, sternum, vertebrae, sacrum, and coccyx. Several illustrative cases are presented. Roentgenographic confirmation occurred following a delay of days to weeks and, in some instances, the roentgenographic findings were subtle and could be easily overlooked. This study demonstrates bone scanning to be invaluable and definitivemore » in the prompt detection of occult fractures.« less

Exploring the Solar System using stellar occultations

NASA Astrophysics Data System (ADS)

Sicardy, Bruno

2018-04-01

Stellar occultations by solar system objects allow kilometric accuracy, permit the detection of tenuous atmospheres (at nbar level), and the discovery of rings. The main limitation was the prediction accuracy, typically 40 mas, corresponding to about 1,000 km projected at the body. This lead to large time dedicated to astrometry, tedious logistical issues, and more often than not, mere miss of the event. The Gaia catalog, with sub-mas accuracy, hugely improves both the star positions, resulting in achievable accuracies of about 1 mas for the shadow track on Earth. This permits much more carefully planned campaigns, with success rate approaching 100%, weather permitting. Scientific perspectives are presented, e.g. central flashes caused by Plutos atmosphere revealing hazes and winds near its surface, grazing occultations showing topographic features, occultations by Chariklos rings unveiling dynamical features such as proper mode ``breathing''.

Review: Occult hepatitis C virus infection: still remains a controversy.

PubMed

Vidimliski, Pavlina Dzekova; Nikolov, Igor; Geshkovska, Nadica Matevska; Dimovski, Aleksandar; Rostaing, Lionel; Sikole, Aleksandar

2014-09-01

Occult hepatitis C virus (HCV) infection is characterized by the presence of HCV RNA in the liver cells or peripheral blood mononuclear cells of the patients whose serum samples test negative for HCV RNA, with or without presence of HCV antibodies. The present study reviews the existing literature on the persistence of occult hepatitis C virus infection, with description of the clinical characteristics and methods for identification of occult hepatitis C. Occult hepatitis C virus infection was detected in patients with abnormal results of liver function tests of unknown origin, with HCV antibodies and HCV RNA negativity in serum, and also in patients with spontaneous or treatment-induced recovery from hepatitis C. The viral replication in the liver cells and/or peripheral blood mononuclear cells was present in all clinical presentations of occult hepatitis C. The peripheral blood mononuclear cells represent an extra-hepatic site of HCV replication. The reason why HCV RNA was not detectable in the serum of patients with occult hepatitis C, could be the low number of circulating viral particles not detectable by the diagnostic tests with low sensitivity. It is uncertain whether occult hepatitis C is a different clinical entity or just a form of chronic hepatitis C virus infection. Data accumulated over the last decade demonstrated that an effective approach to the diagnosis of HCV infection would be the implementation of more sensitive HCV RNA diagnostic assays, and also, examination of the presence of viral particles in the cells of the immune system. © 2014 Wiley Periodicals, Inc.

Cassini Radio Occultation by Enceladus Plume

NASA Astrophysics Data System (ADS)

Kliore, A.; Armstrong, J.; Flasar, F.; French, R.; Marouf, E.; Nagy, A.; Rappaport, N.; McGhee, C.; Schinder, P.; Anabtawi, A.; Asmar, S.; Barbinis, E.; Fleischman, D.; Goltz, G.; Aguilar, R.; Rochblatt, D.

2006-12-01

A fortuitous Cassini radio occultation by Enceladus plume occurs on September 15, 2006. The occultation track (the spacecraft trajectory in the plane of the sky as viewed from the Earth) has been designed to pass behind the plume (to pass above the south polar region of Enceladus) in a roughly symmetrical geometry centered on a minimum altitude above the surface of about 20 km. The minimum altitude was selected primarily to ensure probing much of the plume with good confidence given the uncertainty in the spacecraft trajectory. Three nearly-pure sinusoidal signals of 0.94, 3.6, and 13 cm-wavelength (Ka-, X-, and S-band, respectively) are simultaneously transmitted from Cassini and are monitored at two 34-m Earth receiving stations of the Deep Space Network (DSN) in Madrid, Spain (DSS-55 and DSS-65). The occultation of the visible plume is extremely fast, lasting less than about two minutes. The actual observation time extends over a much longer time interval, however, to provide a good reference baseline for potential detection of signal perturbations introduced by the tenuous neutral and ionized plume environment. Given the likely very small fraction of optical depth due to neutral particles of sizes larger than about 1 mm, detectable changes in signal intensity is perhaps unlikely. Detection of plume plasma along the radio path as perturbations in the signals frequency/phase is more likely and the magnitude will depend on the electron columnar density probed. The occultation time occurs not far from solar conjunction time (Sun-Earth-probe angle of about 33 degrees), causing phase scintillations due to the solar wind to be the primary limiting noise source. We estimate a delectability limit of about 1 to 3E16 electrons per square meter columnar density assuming about 100 seconds integration time. Potential measurement of the profile of electron columnar density along the occultation track is an exciting prospect at this time.

Regulatory polymorphism of CXCL10 rs1439490 in seronegative occult hepatitis C virus infection.

PubMed

Wang, Xu; Wang, Song; Liu, Zhen-Hua; Qi, Wen-Qian; Zhang, Qian; Zhang, Yong-Gui; Sun, De-Rong; Xu, Yan; Wang, Hong-Guang; Li, Zhong-Xie; Cong, Xian-Ling; Zhao, Ping; Zhou, Chang-Yu; Wang, Jiang-Bin

2018-05-28

To examine the relationship between the single nucleotide polymorphism CXCL10 rs1439490 and seronegative occult hepatitis C virus (HCV) infection (OCI). One hundred and three cases of seronegative OCI and 155 cases of seropositive chronic HCV infection (CHC) were diagnosed at five Liver Centers in Northeastern China, from 2012 to 2016. CXCL10 rs1439490, rs1440802, and IL-28B rs12979860 were analyzed by sequencing. Serum CXCL10 was measured by ELISA. Intrahepatic CXCL10 was determined by quantitative PCR and immunohistochemical semi-quantitative scoring. Liver necroinflammation and fibrosis were scored according to the METAVIR system. CXCL10 rs1439490 G/G was more prevalent in OCI patients ( n = 93/103; 90.3%) than in CHC patients ( n = 116/155; 74.8%; P = 0.008). OCI patients had lower serum CXCL10 levels than CHC patients (192.91 ± 46.50 pg/mL vs 354.78 ± 102.91 pg/mL, P < 0.0001). Of IL-28B rs12979860 C/C patients, OCI patients with rs1439490 G/G had lower serum and liver levels of CXCL10 and lower levels of liver necroinflammation and fibrosis than non-G/G patients. OCI patients had higher alanine aminotransferase normalization rates after Peg-interferon treatment than CHC patients (P < 0.05) and serum CXCL10 decreased significantly (P < 0.0001). Liver necroinflammation and fibrosis were alleviated in 8 OCI patients after treatment. Multivariate analysis indicated that rs1439490 G/G significantly influenced the occurrence of OCI in HCV infection (OR = 0.31, 95%CI: 0.15-0.66, P = 0.002). CXCL10 rs1439490 G/G is positively associated with OCI in HCV infection and antiviral outcome.

Predictions of stellar occultations by TNOs/Centaurs using Gaia

NASA Astrophysics Data System (ADS)

Desmars, Josselin; Camargo, Julio; Berard, Diane; Sicardy, Bruno; Leiva, Rodrigo; Vieira-Martins, Roberto; Braga-Ribas, Felipe; Assafin, Marcelo; Rossi, Gustavo; Chariklo occultations Team, Rio Group, Lucky Star Occultation Team, Granada Occultation Team

2017-10-01

Stellar occultations are the unique technique from the ground to access physical parameters of the distant solar system objects, such as the measure of the size and the shape at kilometric level, the detection of tenuous atmospheres (few nanobars), and the investigation of close vicinity (satellites, rings, jets).Predictions of stellar occultations require accurate positions of the star and the object.The Gaia DR1 catalog now allows to get stellar position to the milliarcsecond (mas) level. The main uncertainty in the prediction remains in the position of the object (tens to hundreds of mas).Now, we take advantage of the NIMA method for the orbit determination that uses the most recent observations reduced by the Gaia DR1 catalog and the astrometric positions derived from previous positive occultations.Up to now, we have detected nearly 50 positive occultations for about 20 objects that provide astrometric positions of the object at the time of the occultation. The uncertainty of these positions only depends on the uncertainty on the position of the occulted stars, which is a few mas with the Gaia DR1 catalog. The main limitation is now on the proper motion of the star which is only given for bright stars in the Tycho-Gaia Astrometric Solution. This limitation will be solved with the publicationof the Gaia DR2 expected on April 2018 giving proper motions and parallaxes for the Gaia stars. Until this date, we use hybrid stellar catalogs (UCAC5, HSOY) that provide proper motions derived from Gaia DR1 and another stellar catalog.Recently, the Gaia team presented a release of three preliminary Gaia DR2 stellar positions involved in the occultations by Chariklo (22 June and 23 July 2017) and by Triton (5 October 2017).Taking the case of Chariklo as an illustration, we will present a comparison between the proper motions of DR2 and the other catalogs and we will show how the Gaia DR2 will lead to a mas level precision in the orbit and in the prediction of stellar

Detection of Occult Invasion in Melanoma In Situ.

PubMed

Bax, Michael J; Johnson, Timothy M; Harms, Paul W; Schwartz, Jennifer L; Zhao, Lili; Fullen, Douglas R; Chan, May P

2016-11-01

It is unclear why some patients with in situ melanoma develop metastases. Few reports demonstrate occult invasion with immunohistochemistry staining, which were discordant with reports interpreting such staining as false-positive. To investigate the occurrence of occult invasive disease within in situ melanoma by using methods to circumvent potential limitations in prior study designs. Unequivocal in situ melanoma without associated nevi or regression was identified using a consecutive sample of 33 cases plus 1 index case in an academic medical center. After cutting deeper into the most representative tissue block, 3 sequential slides were stained with hematoxylin-eosin (H-E), melanoma antigen (melan-A), and again with H-E. Melan-A-stained slides showing definitive invasion were double-stained with Sry-related HMg-Box gene 10 (SOX10) to confirm the melanocytic nature of the cells of interest. The study evaluated the possibilities of occult invasion detected by immunohistochemistry, sectioning deeper into the tissue block, or both. Slides were independently scored by 3 dermatopathologists with interrater reliability assessed. The study was conducted from January 1, 2012, to July 31, 2014. Assessment of the occurrence of occult invasion, diagnosis of invasion by immunohistochemistry alone vs cutting deeper into the tissue block, and occurrence of false-positive results using immunohistochemistry alone. Occult invasive melanoma was detected in 11 of 33 consecutive cases (33%) of previously diagnosed unequivocal in situ melanoma. Six of 11 melanomas (55%) were diagnosable only by immunohistochemistry. The remaining 5 tumors (45%) were diagnosable by both melan-A and H-E staining, likely as a result of simply cutting deeper into the tissue block. Four cases (12%) showed a few melan-A-positive cells in the dermis, which was insufficient for a diagnosis of invasive melanoma and most consistent on a cytomorphologic basis with occult nevi. Although rare, in situ melanoma

A search for stellar occultations by Uranus, Neptune, Pluto, and their satellites: 1990-1999

NASA Technical Reports Server (NTRS)

Mink, Douglas J.

1991-01-01

A search for occultations of stars by Uranus, Neptune, and Pluto between 1990 and 1999 was carried out by combining ephemeris information and star positions using very accurate occultation modeling software. Stars from both the Space Telescope Guide Catalog and photographic plates taken by Arnold Klemola at Lick Observatory were compared with planet positions from the JPL DE-130 ephemeris, with local modifications for Pluto and Charon. Some 666 possible occultations by the Uranian ring, 143 possible occultations by Neptune, and 40 possible occultations by Pluto and/or Charon were found among stars with visual magnitudes as faint as 16. Before the star positions could be obtained, the occultation prediction software was used to aid many observers in observing the occultation of 28 Sagitarii by Saturn in July 1989. As a test on other outer solar system objects, 17 possible occultations were found in a search of the Guide Star Catalog for occultations by 2060 Chiron, and interesting object between Saturn and Uranus which shows both cometary and asteroidal properties.

A search for stellar occultations by Uranus, Neptune, Pluto, and their satellites: 1990-1999

NASA Astrophysics Data System (ADS)

Mink, Douglas J.

1991-03-01

A search for occultations of stars by Uranus, Neptune, and Pluto between 1990 and 1999 was carried out by combining ephemeris information and star positions using very accurate occultation modeling software. Stars from both the Space Telescope Guide Catalog and photographic plates taken by Arnold Klemola at Lick Observatory were compared with planet positions from the JPL DE-130 ephemeris, with local modifications for Pluto and Charon. Some 666 possible occultations by the Uranian ring, 143 possible occultations by Neptune, and 40 possible occultations by Pluto and/or Charon were found among stars with visual magnitudes as faint as 16. Before the star positions could be obtained, the occultation prediction software was used to aid many observers in observing the occultation of 28 Sagitarii by Saturn in July 1989. As a test on other outer solar system objects, 17 possible occultations were found in a search of the Guide Star Catalog for occultations by 2060 Chiron, and interesting object between Saturn and Uranus which shows both cometary and asteroidal properties.

Increased megakaryocytic proliferation, pro-platelet deposition and expression of fibrosis-associated factors in children with chronic myeloid leukaemia with bone marrow fibrosis.

PubMed

Hussein, K; Stucki-Koch, A; Göhring, G; Kreipe, H; Suttorp, M

2017-07-01

Paediatric chronic myeloid leukaemia (ped-CML) is rare and ped-CML with fibre accumulation in the bone marrow (MF) is thought to be even rarer. In adults (ad-CML), fibrosis represents an adverse prognostic factor. So far, the pro-fibrotic changes in the bone marrow microenvironment have not been investigated in detail in ped-CML. From a total of 66 ped-CML in chronic phase, biopsies were analysable and 10 had MF1/2 (MF1, n=8/10; MF2, n=2/10). We randomly selected 16 ped-CML and 16 ad-CML cases with and without fibrosis (each n=8) as well as 18 non-neoplastic controls. Bone marrow samples were analysed with a real-time PCR-based assay (including 127 genes for paediatric cases) and by immunohistochemistry. We found increased expression of megakaryocytic genes in ped-CML. The number of megakaryocytes and pro-platelets are increased in CML patients, but the most significant increase was noted for ped-CML-MF1/2. Anti-fibrotic MMP9 expression was lower in children than in adults. Cell mobilisation-related CXCL12 was decreased in young and adult patients with CML but not the corresponding receptor CXCR4. In summary, fibre accumulation in ped-CML-MF1/2 is associated with increased megakaryocytic proliferation and increased interstitial pro-platelet deposition. Deregulated expression of matrix-modulating factors shifts the bone marrow microenvironment towards fibrosis.

Role of Autoantibodies in the Diagnosis of Connective-Tissue Disease ILD (CTD-ILD) and Interstitial Pneumonia with Autoimmune Features (IPAF)

PubMed Central

Jee, Adelle S.; Adelstein, Stephen; Bleasel, Jane; Keir, Gregory J.; Nguyen, MaiAnh; Sahhar, Joanne; Youssef, Peter; Corte, Tamera J.

2017-01-01

The diagnosis of interstitial lung disease (ILD) requires meticulous evaluation for an underlying connective tissue disease (CTD), with major implications for prognosis and management. CTD associated ILD (CTD-ILD) occurs most commonly in the context of an established CTD, but can be the first and/or only manifestation of an occult CTD or occur in patients who have features suggestive of an autoimmune process, but not meeting diagnostic criteria for a defined CTD—recently defined as “interstitial pneumonia with autoimmune features” (IPAF). The detection of specific autoantibodies serves a critical role in the diagnosis of CTD-ILD, but there remains a lack of data to guide clinical practice including which autoantibodies should be tested on initial assessment and when or in whom serial testing should be performed. The implications of detecting autoantibodies in patients with IPAF on disease behaviour and management remain unknown. The evaluation of CTD-ILD is challenging due to the heterogeneity of presentations and types of CTD and ILD that may be encountered, and thus it is imperative that immunologic tests are interpreted in conjunction with a detailed rheumatologic history and examination and multidisciplinary collaboration between respiratory physicians, rheumatologists, immunologists, radiologists and pathologists. PMID:28471413

Exploring small bodies in the outer solar system with stellar occultations

NASA Technical Reports Server (NTRS)

Elliot, Jim L.; Dunham, Edward W.; Olkin, C. B.

1995-01-01

Stellar occultation observations probe the atmospheric structure and extinction of outer solar system bodies with a spatial resolution of a few kilometers, and an airborne platform allows the observation of occultations by small bodies that are not visible from fixed telescopes. Results from occultations by Triton, Pluto, and Chiron observed with KAO are discussed, and future directions for this program are presented.

Diffraction-based analysis of tunnel size for a scaled external occulter testbed

NASA Astrophysics Data System (ADS)

Sirbu, Dan; Kasdin, N. Jeremy; Vanderbei, Robert J.

2016-07-01

For performance verification of an external occulter mask (also called a starshade), scaled testbeds have been developed to measure the suppression of the occulter shadow in the pupil plane and contrast in the image plane. For occulter experiments the scaling is typically performed by maintaining an equivalent Fresnel number. The original Princeton occulter testbed was oversized with respect to both input beam and shadow propagation to limit any diffraction effects due to finite testbed enclosure edges; however, to operate at realistic space-mission equivalent Fresnel numbers an extended testbed is currently under construction. With the longer propagation distances involved, diffraction effects due to the edge of the tunnel must now be considered in the experiment design. Here, we present a diffraction-based model of two separate tunnel effects. First, we consider the effect of tunnel-edge induced diffraction ringing upstream from the occulter mask. Second, we consider the diffraction effect due to clipping of the output shadow by the tunnel downstream from the occulter mask. These calculations are performed for a representative point design relevant to the new Princeton occulter experiment, but we also present an analytical relation that can be used for other propagation distances.

The occultation of Kappa Geminorum by Eros. [stellar occultation observed for asteroid size and shape

NASA Technical Reports Server (NTRS)

Oleary, B.; Marsden, B. G.; Dragon, R.; Hauser, E.; Mcgrath, M.; Backus, P.; Robkoff, H.

1976-01-01

The paper discusses predictions and observations of the occultation of Kappa Gem by (433) Eros on January 24, 1975. Several positive and negative observations made in western New England are described. Local circumstances for the occultation are reconstructed, and the size and shape of Eros are determined analytically as well as graphically. The calculations yield two extremes for the cross section: a circle 23 km in diameter or a somewhat irregular figure 20 km by 6 or 7 km. Arguments based on the expected albedo of the asteroid suggest that the circle should be warped into an ellipse 21 by 13 km or that the irregular figure might be one component of a dumbbell-like profile.

High Resolution Asteroid Profile by Multi Chord Occultation Observations

NASA Astrophysics Data System (ADS)

Degenhardt, Scott

2009-05-01

For millennia man has observed celestial objects occulting other bodies and distant stars. We have used these celestial synchronicities to measure the properties of objects. On January 1, 1801 Italian astronomer Giusappe Piazzi discovered the first asteroid that would soon be named Ceres. To date 190,000 of these objects have been catalogued, but only a fraction of these have accurate measurements of their true size and shape. The International Occultation Timing Association (IOTA) currently facilitates the prediction and reduction of asteroidal occultations. By measuring the shadow cast on the earth by an asteroid during a stellar occultation one can directly measure the physical size, shape, and position in space of this body to accuracies orders of magnitudes better than the best ground based adaptive optics telescope and can provide verification to 3D inverted reflective lightcurve prediction models. Recent novel methods developed by IOTA involving an individual making multiple observations through unattended remote observing stations have made way for numerous chords of occultation measurement through a single body yielding high resolution profiles of asteroid bodies. Methodology of how observing stations are deployed will be demonstrated, results of some of these observations are presented as comparisons to their inverted lightcurve are shown.

Chronic type 1 diabetes in spontaneously hypertensive rats leads to exacerbated cardiac fibrosis.

PubMed

Black, Mary Jane; D'Amore, Angelo; Auden, Alana; Stamp, Laura; Osicka, Tanya; Panagiotopoulos, Sianna; Jerums, George

2010-01-01

Diabetes in human subjects is often associated with hypertension. The aim of this study was to examine the development of cardiac fibrosis following induction of type 1 diabetes in genetically hypertensive rats. Diabetes was induced by streptozotocin (STZ) injection in 8-week-old normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) for a duration of 16 or 24 weeks. Aged-matched, nondiabetic WKY and SHRs were used as controls. At termination of treatment, the rats were anaesthetized, hearts arrested in diastole and perfusion fixed. A comprehensive examination of cardiac fibrosis throughout the right and left ventricles was undertaken in picrosirius red-stained sections, using image analysis and by undertaking collagen type I and type III immunohistochemistry. Induction of diabetes in the SHRs led to a marked increase in the levels of interstitial fibrosis in the left ventricle plus septum (LV+S) at both 16 and 24 weeks duration (59% and 43% increase, respectively) and also in the right ventricle after 24 weeks duration of diabetes (35% increase compared to the nondiabetic SHR). Exacerbated perivascular fibrosis was also observed in the LV+S in the diabetic-hypertensive rats at the later time point. These effects of induction of diabetes were not observed in the normotensive strain. Our findings clearly demonstrate elevations in cardiac fibrosis when type 1 diabetes is combined with hypertension. Our findings thus stress the importance of closely monitoring both blood pressure and glucose levels in type 1 diabetic patients in order to prevent myocardial collagen deposition. Copyright © 2010 Elsevier Inc. All rights reserved.

STAT-3 contributes to pulmonary fibrosis through epithelial injury and fibroblast-myofibroblast differentiation

PubMed Central

Pedroza, Mesias; Le, Thuy T.; Lewis, Katherine; Karmouty-Quintana, Harry; To, Sarah; George, Anuh T.; Blackburn, Michael R.; Tweardy, David J.; Agarwal, Sandeep K.

2016-01-01

Lung fibrosis is the hallmark of the interstitial lung diseases. Alveolar epithelial cell (AEC) injury is a key step that contributes to a profibrotic microenvironment. Fibroblasts and myofibroblasts subsequently accumulate and deposit excessive extracellular matrix. In addition to TGF-β, the IL-6 family of cytokines, which signal through STAT-3, may also contribute to lung fibrosis. In the current manuscript, the extent to which STAT-3 inhibition decreases lung fibrosis is investigated. Phosphorylated STAT-3 was elevated in lung biopsies from patients with idiopathic pulmonary fibrosis and bleomycin (BLM)-induced fibrotic murine lungs. C-188-9, a small molecule STAT-3 inhibitor, decreased pulmonary fibrosis in the intraperitoneal BLM model as assessed by arterial oxygen saturation (control, 84.4 ± 1.3%; C-188-9, 94.4 ± 0.8%), histology (Ashcroft score: untreated, 5.4 ± 0.25; C-188-9, 3.3 ± 0.14), and attenuated fibrotic markers such as diminished α–smooth muscle actin, reduced collagen deposition. In addition, C-188-9 decreased the expression of epithelial injury markers, including hypoxia-inducible factor-1α (HIF-1α) and plasminogen activator inhibitor-1 (PAI-1). In vitro studies show that inhibition of STAT-3 decreased IL-6– and TGF-β–induced expression of multiple genes, including HIF-1α and PAI-1, in AECs. Furthermore, C-188-9 decreased fibroblast-to-myofibroblast differentiation. Finally, TGF-β stimulation of lung fibroblasts resulted in SMAD2/SMAD3-dependent phosphorylation of STAT-3. These findings demonstrate that STAT-3 contributes to the development of lung fibrosis and suggest that STAT-3 may be a therapeutic target in pulmonary fibrosis.—Pedroza, M., Le, T. T., Lewis, K., Karmouty-Quintana, H., To, S., George, A. T., Blackburn, M. R., Tweardy, D. J., Agarwal, S. K. STAT-3 contributes to pulmonary fibrosis through epithelial injury and fibroblast-myofibroblast differentiation. PMID:26324850

Earth Occultation Monitoring with the Fermi Gamma Ray Burst Monitor

NASA Technical Reports Server (NTRS)

Wilson-Hodge, Colleen A.

2014-01-01

Using the Gamma Ray Burst Monitor (GBM) on-board Fermi, we are monitoring the hard X-ray/soft gamma ray sky using the Earth occultation technique (EOT). Each time a source in our catalog is occulted by (or exits occultation by) the Earth, we measure its flux using the change in count rates due to the occultation. Currently we are using CTIME data with 8 energy channels spanning 8 keV to 1 MeV for the GBM NaI detectors for daily monitoring. Light curves, updated daily, are available on our website http://heastro.phys.lsu.edu/gbm. Our software is also capable of performing the Earth occultation monitoring using up to 128 energy bands, or any combination of those bands, using our 128-channel, 4-s CSPEC data. The GBM BGO detectors, sensitive from about 200 keV to 40 keV, can also be used with this technique. In our standard application of the EOT, we use a catalog of sources to drive the measurements. To ensure that our catalog is complete, our team has developed an Earth occultation imaging method. In this talk, I will describe both techniques and the current data products available. I will highlight recent and important results from the GBM EOT, including the current status of our observations of hard X-ray variations in the Crab Nebula.

Analysis of a Triple Star System Occulted By Saturn’s Rings

NASA Astrophysics Data System (ADS)

Bratcher, Allison; Colwell, J. E.; Bolin, B.

2012-10-01

On January 4, 2012, the Ultraviolet Imaging Spectrograph aboard the Cassini Spacecraft observed Saturn’s rings as they occulted the triple star system, Iota Orionis. Remarkably, the brightest star was occulted by the moon Prometheus, and we provide the timing information of first and last contact for navigation purposes and a chord across the moon. The large separation of the individual stars projected in the ring plane makes it possible to measure the profiles of narrow features in the rings as they were occulted by each of the three stars. This occultation thus provides a unique opportunity to measure short-scale longitudinal variations in narrow ringlets with stellar occultation data that usually provide only a single longitudinal sample. Iota Orionis has a low elevation angle (B=1.4 degrees) above the plane of the rings, enhancing the sensitivity of the occultation (by a factor of 1/sin(B)=41) to the optically thin regions of the rings such as the C Ring and the Cassini Division as well as faint ringlets in the Encke gap. We distinguished the three signals by creating a model triple star signal using data from another occultation. We were able to identify several faint, narrow ringlets, including two in the Encke gap, occulted by two of the three stars and more prominent ringlets, such as the Huygens ringlet, in all three stellar light curves. We present the equivalent widths of these ringlets in the data from this triple star system and limits on ring variability over the azimuthal separation of the stars that ranges from 6000 km at the inner C ring to 200 km at the outer A ring.

Observation and Interpretation of Lunar Occultations. Ph.D. Thesis; [Uranus and beta Capricorni

NASA Technical Reports Server (NTRS)

Radick, R. R.

1978-01-01

The importance of timings and high resolution astrometry in occultation observations is discussed as well as the occultation process itself. The design and operation of the telescope, photodetector, and data acquisition systems are described. Methods are presented for data analysis and model fitting. Observations of beta Capricorni and Uranus occultations are examined. General conclusions concerning occultation observations are explored and future activities at Prairie Observatory are discussed.

The Atmosphere of Titan from Cassini Radio Occultations

NASA Astrophysics Data System (ADS)

Schinder, Paul J.; Flasar, F. M.; Marouf, E. A.; French, R. G.; McGhee, C. A.; Kliore, A. J.; Rappaport, N.; Nagy, A. F.; Anabtawi, A.; Asmar, S.; Barbinis, E.; Fleischman, D. U.; Goltz, G. L.

2006-09-01

The first two radio occultations of Cassini by Titan occurred on March 19 and May 20, 2006. On March 19, the ingress occultation occurred at a latitude of 31 S, and egress at 53 S. On May 20, ingress was at 33 S, and egress at 34 S. We present the temperature-pressure profiles for the atmosphere of Titan for these 4 locations.

Occult chemical deposition to a Maritime forest

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

Vong, R.J.; Kowalski, A.S.

1996-12-31

Studies of chemical fluxes from the atmosphere to vegetated surfaces have suggested that, along with conventional wet and dry processes, an additional chemical input occurs when wind-blown cloud droplets are directly intercepted by vegetation. This cloud water deposition process has been sometimes termed {open_quote}occult deposition{close_quote} because the water fluxes cannot ordinarily be observed using rain gauges. Such occult deposition of cloud water has rarely been measured directly, in part because of the complexity of the governing turbulent transfer process. However, reviews by the National Acidic Precipitation Assessment Program (NAPAP SoS/T-2,6) have suggested that the chemical flux to be forest declinemore » in the eastern USA. This paper presents direct field measurements occult chemical fluxes to a silver fir forest located in complex terrain on the Olympic Peninsula near the coast of Washington State, USA.« less

Trace metals in fluids lining the respiratory system of patients with idiopathic pulmonary fibrosis and diffuse lung diseases.

PubMed

Bargagli, Elena; Lavorini, Federico; Pistolesi, Massimo; Rosi, Elisabetta; Prasse, Antje; Rota, Emilia; Voltolini, Luca

2017-07-01

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an undefined etiopathogenesis. Oxidative stress contributes to alveolar injury and fibrosis development and, because transition metals are essential to the functioning of most proteins involved in redox reactions, a better knowledge of metal concentrations and metabolism in the respiratory system of IPF patients may provide a valuable complementary approach to prevent and manage a disease which is often misdiagnosed or diagnosed in later stages. The present review summarizes and discusses literature data on the elemental composition of bronchoalveolar lavage (BAL), induced sputum and exhaled breath condensate (EBC) from patients affected by IPF and healthy subjects. Available data are scanty and the lack of consistent methods for the collection and analysis of lung and airways lining fluids makes it difficult to compare the results of different studies. However, the elemental composition of BAL samples from IPF patients seems to have a specific profile that can be distinguished from that of patients with other interstitial lung diseases (ILD) or control subjects. Suggestions are given towards standard sampling and analytical procedures of BAL samples, in the aim to assess typical element concentration patterns and their potential role as biomarkers of IPF. Copyright © 2017 Elsevier GmbH. All rights reserved.

Altimetry Using GPS-Reflection/Occultation Interferometry

NASA Technical Reports Server (NTRS)

Cardellach, Estel; DeLaTorre, Manuel; Hajj, George A.; Ao, Chi

2008-01-01

A Global Positioning System (GPS)- reflection/occultation interferometry was examined as a means of altimetry of water and ice surfaces in polar regions. In GPS-reflection/occultation interferometry, a GPS receiver aboard a satellite in a low orbit around the Earth is used to determine the temporally varying carrier- phase delay between (1) one component of a signal from a GPS transmitter propagating directly through the atmosphere just as the GPS transmitter falls below the horizon and (2) another component of the same signal, propagating along a slightly different path, reflected at glancing incidence upon the water or ice surface.

Partially Transparent Petaled Mask/Occulter for Visible-Range Spectrum

NASA Technical Reports Server (NTRS)

Shiri, Ron Shahram; Wasylkiwskyj, Wasyl

2013-01-01

The presence of the Poisson Spot, also known as the spot of Arago, has been known since the 18th century. This spot is the consequence of constructive interference of light diffracted by the edge of the obstacle where the central position can be determined by symmetry of the object. More recently, many NASA missions require the suppression of this spot in the visible range. For instance, the exoplanetary missions involving space telescopes require telescopes to image the planetary bodies orbiting central stars. For this purpose, the starlight needs to be suppressed by several orders of magnitude in order to image the reflected light from the orbiting planet. For the Earth-like planets, this suppression needs to be at least ten orders of magnitude. One of the common methods of suppression involves sharp binary petaled occulters envisioned to be placed many thousands of miles away from the telescope blocking the starlight. The suppression of the Poisson Spot by binary sharp petal tips can be problematic when the thickness of the tips becomes smaller than the wavelength of the incident beam. First they are difficult to manufacture and also it invalidates the laws of physical optics. The proposed partially transparent petaled masks/occulters compensate for this sharpness with transparency along the surface of the petals. Depending on the geometry of the problem, this transparency can be customized such that only a small region of the petal is transparent and the remaining of the surface is opaque. This feature allows easy fabrication of this type of occultation device either as a mask or occulter. A partially transparent petaled mask/ occulter has been designed for the visible spectrum range. The mask/occulter can suppress the intensity along the optical axis up to ten orders of magnitude. The design process can tailor the mask shape, number of petals, and transparency level to the near-field and farfield diffraction region. The mask/occulter can be used in space

Immunohistochemical detection of virus through its nuclear cytopathic effect in idiopathic interstitial pneumonia other than acute exacerbation

PubMed Central

dos Santos, G.C.; Parra, E.R.; Stegun, F.W.; Cirqueira, C.S.; Capelozzi, V.L.

2013-01-01

Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures. PMID:24270907

General Information about Metastatic Squamous Neck Cancer with Occult Primary

MedlinePlus

... Occult Primary Treatment (Adult) (PDQ®)–Patient Version General Information About Metastatic Squamous Neck Cancer with Occult Primary ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Nintedanib (OFEV) in the treatment of idiopathic pulmonary fibrosis.

PubMed

Fukihara, Jun; Kondoh, Yasuhiro

2016-12-01

Nintedanib is a new anti-fibrosis agent that is an intracellular tyrosine kinase inhibitor targeting platelet derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor. Although nintedanib is attracting much attention as a new treatment option for patients with idiopathic pulmonary fibrosis (IPF), the clinical evidence is limited mainly to the results from the dose-deciding phase II TOMORROW trial and phase III INPULSIS trials, which evaluated efficacy and safety of nintedanib for patients with IPF, prespecified subgroup analyses, pooled analyses and meta-analyses derived from those trials. Areas covered: In this document, we mainly reviewed reports on working mechanisms of nintedanib, and efficacy and safety of nintedanib for patients with IPF. The literature search was undertaken using Pub Med. Expert commentary: It is unknown whether the efficacy of nintedanib in patients enrolled in the clinical trials will be the same for the entire spectrum of patients, including patients unfit for the clinical trials due to age, severity, timing of IPF diagnosis or diagnosis of interstitial pneumonias other than IPF. Sufficient consideration should be given when selecting candidates for nintedanib in the real world.

[The association of diffuse pulmonary fibrosis and hiatal hernia: a simple coincidence? (author's transl)].

PubMed

Sauret, J; Casán, P

1980-03-25

Gastroesophageal diseases with reflux can cause numerous pulmonary complications (bronchospasm crisis, bronchitis, pneumonias, lung abscesses). These manifestations are very frequent in the hiatal hernias and in some series have reached up to 46 percent of the cases studied. Recently it has been suggested that microaspirations, repeated over a long period of time, may cause an alteration of the pulmonary interstitium and the consecutive development of a clinical and roentgenologic picture similar to pulmonary fibrosis. The aspirations are produced more frequently at night, favoured by the lying down position and because of it the patients present attacks of nocturnal cough. In this paper, two patients who presented the association of pulmonary fibrosis and hiatal hernia with esophageal relux are described. The first case was diagnosed early; he had minimal radiographic anomalies and the disappearance of the respiratory symptomatology was achieved by means of the medical treatment of the esophageal reflux. The second case was in a very advanced stage with severe respiratory insufficiency and gastrointestinal manifestations of many years' evolution. Both patients had been diagnosed as having idiopathic pulmonary fibrosis. Although there is no experimental proof of the "reflux-fibrosis" theory, we think that this possibility should be kept in mind before diagnosing the interstitial pulmonary pattern as idiopathic, especially in the cases of only slight radiographic and functional involvement susceptible to improvement with correction of the esophageal reflux.

Protein kinase C alpha drives fibroblast activation and kidney fibrosis by stimulating autophagic flux.

PubMed

Xue, Xian; Ren, Jiafa; Sun, Xiaoli; Gui, Yuan; Feng, Ye; Shu, Bingyan; Wei, Wei; Lu, Qingmiao; Liang, Yan; He, Weichun; Yang, Junwei; Dai, Chunsun

2018-05-23

Kidney fibrosis is a histological hallmark of chronic kidney disease and arises in large part through excessive extracellular matrix (ECM) deposition by activated fibroblasts. The signaling protein complex mTOR complex 2 (mTORC2) plays a critical role in fibroblast activation and kidney fibrosis. Protein kinase C alpha (PKCα) is one of the major sub-pathways of mTORC2, but its role in fibroblast activation and kidney fibrosis remains to be determined. Here, we found that transforming growth factor beta 1 (TGFβ1) activates PKCα signaling in cultured NRK-49F cells in a time-dependent manner. Blocking PKCα signaling with the chemical inhibitor Go6976 or by transfection with PKCα siRNA largely reduced expression of the autophagy-associated protein lysosomal-associated membrane protein 2 (LAMP2) and also inhibited autophagosome-lysosome fusion and autophagic flux in the cells. Similarly to chloroquine, Go6976 treatment and PKCα siRNA transfection also markedly inhibited TGFβ1-induced fibroblast activation. In murine fibrotic kidneys with unilateral ureteral obstruction (UUO) nephropathy, PKCα signaling is activated in the interstitial myofibroblasts. Go6976 administration largely blocked autophagic flux in fibroblasts in the fibrotic kidneys and attenuated the UUO nephropathy. Together, our findings suggest that blocking PKCα activity may retard autophagic flux and thereby prevent fibroblast activation and kidney fibrosis. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Influences of innate immunity, autophagy, and fibroblast activation in the pathogenesis of lung fibrosis

PubMed Central

O'Dwyer, David N.; Ashley, Shanna L.

2016-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by accumulation of extracellular matrix (ECM) and impaired gas exchange. The pathobiological mechanisms that account for disease progression are poorly understood but likely involve alterations in innate inflammatory cells, epithelial cells, and fibroblasts. Thus we seek to review the most recent literature highlighting the complex roles of neutrophils and macrophages as both promoters of fibrosis and defenders against infection. With respect to epithelial cells and fibroblasts, we review the data suggesting that defective autophagy promotes the fibrogenic potential of both cell types and discuss new evidence related to matrix metalloproteinases, growth factors, and cellular metabolism in the form of lactic acid generation that may have consequences for promoting fibrogenesis. We discuss potential cross talk between innate and structural cell types and also highlight literature that may help explain the limitations of current IPF therapies. PMID:27474089

Muc1 deficiency exacerbates pulmonary fibrosis in a mouse model of silicosis.

PubMed

Kato, Kosuke; Zemskova, Marina A; Hanss, Alec D; Kim, Marianne M; Summer, Ross; Kim, Kwang Chul

2017-11-25

MUC1 (MUC in human and Muc in animals) is a membrane-tethered mucin expressed on the apical surface of lung epithelial cells. However, in the lungs of patients with interstitial lung disease, MUC1 is aberrantly expressed in hyperplastic alveolar type II epithelial (ATII) cells and alveolar macrophages (AM), and elevated levels of extracellular MUC1 are found in bronchoalveolar lavage (BAL) fluid and the serum of these patients. While pro-fibrotic effects of extracellular MUC1 have recently been described in cultured fibroblasts, the contribution of MUC1 to the pathobiology of pulmonary fibrosis is unknown. In this study, we hypothesized that MUC1 deficiency would reduce susceptibility to pulmonary fibrosis in a mouse model of silicosis. We employed human MUC1 transgenic mice, Muc1 deficient mice and wild-type mice on C57BL/6 background in these studies. Some mice received a one-time dose of crystalline silica instilled into their oropharynx in order to induce pulmonary fibrosis and assess the effects of Muc1 deficiency on fibrotic and inflammatory responses in the lung. As previously described in other mouse models of pulmonary fibrosis, we found that extracellular MUC1 levels were markedly increased in whole lung tissues, BALF and serum of human MUC1 transgenic mice after silica. We also detected an increase in total MUC1 levels in the lungs of these mice, indicating that production as well as release contributed to elevated levels after lung injury. Immunohistochemical staining revealed that increased MUC1 expression was mostly confined to ATII cells and AMs in areas of fibrotic remodeling, illustrating a pattern similar to the expression of MUC1 in human fibrotic lung tissues. However, contrary to our hypothesis, we found that Muc1 deficiency resulted in a worsening of fibrotic remodeling in the mouse lung as judged by an increase in number of silicotic nodules, an increase in lung collagen deposition and an increase in the severity of pulmonary inflammation

Computed tomography imaging of a leopard tortoise (Geochelone pardalis pardalis) with confirmed pulmonary fibrosis: a case report

PubMed Central

2013-01-01

An approximately 20-year-old, female Leopard tortoise (Geochelone pardalis pardalis) was presented with dypsnea, wheezing, anorexia and depression. Whole body radiographs revealed generalized diffuse unstructured ‘interstitial lung pattern’ with thickened pulmonary septae while computed tomography (CT) showed emphysematous lung parenchyma and thickened pulmonary septae bordered by irregular ground-glass opacity with smaller areas of ‘honeycombing’. These imaging findings together with histopathologic findings were compatible with chronic, extensive ‘interstitial’ pulmonary fibrosis. PMID:23618386

Radio Occultation Measurements of Pluto’s Atmosphere with New Horizons

NASA Astrophysics Data System (ADS)

Hinson, David P.; Linscott, Ivan; Tyler, Len; Bird, Mike; Paetzold, Martin; Strobel, Darrell; Summers, Mike; Woods, Will; Stern, Alan; Weaver, Hal; Olkin, Cathy; Young, Leslie; Ennico, Kimberly; Gladstone, Randy; Greathouse, Tommy; Kammer, Josh; Parker, Alex; Parker, Joel; Retherford, Kurt; Schindhelm, Eric; Singer, Kelsi; Steffl, Andrew; Tsang, Con; Versteeg, Maarten

2015-11-01

The reconnaissance of the Pluto System by New Horizons included radio occultations at both Pluto and Charon. This talk will present the latest results from the Pluto occultation. The REX instrument onboard New Horizons received and recorded uplink signals from two 70-m antennas and two 34-m antennas of the NASA Deep Space Network - each transmitting 20 kW at 4.2-cm wavelength - during a diametric occultation by Pluto. At the time this was written only a short segment of data at occultation entry (193°E, 17°S) was available for analysis. The REX measurements extend unequivocally to the surface, providing the first direct measure of the surface pressure and the temperature structure in Pluto’s lower atmosphere. Data from occultation exit (16°E, 15°N) are scheduled to arrive on the ground in late August 2015. Those observations will yield an improved estimate of the surface pressure, a second temperature profile, and a measure of the diameter of Pluto with a precision of a few hundred meters. This work is supported by the NASA New Horizons Mission.

Recent progress on external occulter technology for imaging exosolar planets

NASA Astrophysics Data System (ADS)

Kasdin, N. J.; Vanderbei, R. J.; Sirbu, D.; Samuels, J.; Shaklan, S.; Lisman, D.; Thomson, M.; Cady, E.; Martin, S.

Imaging planets orbiting nearby stars requires a system for suppressing the host starlight by at least ten orders of magnitude. One such approach uses an external occulter, a satellite flying far from the telescope and employing a large screen, or starshade, to suppress the incoming starlight. This trades the added complexity of building the precisely shaped starshade and flying it in formation against simplifications in the telescope since extremely precise wavefront control is no longer necessary. Much progress has been made recently in designing, testing and manufacturing starshade technology. In this paper we describe the design of starshades and report on recent accomplishments in manufacturing and measuring a prototype occulter petal as part of NASA's first Technology Development for Exoplanet Missions (TDEM) program. We demonstrate that the as-built petal is consistent with a full-size occulter achieving better than 10-10 contrast. We also discuss laboratory testing at the Princeton Occulter Testbed. These experiments use sub-scale, long-distance beam propagation to verify the diffraction analysis associated with occulter starlight suppression. We demonstrate roughly 10-10 suppression in the laboratory and discuss the important challenges and limitations.

Stellar occultation spikes as probes of atmospheric structure and composition. [for Jupiter

NASA Technical Reports Server (NTRS)

Elliot, J. L.; Veverka, J.

1976-01-01

The characteristics of spikes observed in occultation light curves of Beta Scorpii by Jupiter are discussed in terms of the gravity-gradient model. The occultation of Beta Sco by Jupiter on May 13, 1971, is reviewed, and the gravity-gradient model is defined as an isothermal atmosphere of constant composition in which the refractivity is a function only of the radial coordinate from the center of refraction, which is assumed to lie parallel to the local gravity gradient. The derivation of the occultation light curve in terms of the atmosphere, the angular diameter of the occulted star, and the occultation geometry is outlined. It is shown that analysis of the light-curve spikes can yield the He/H2 concentration ratio in a well-mixed atmosphere, information on fine-scale atmospheric structure, high-resolution images of the occulted star, and information on ray crossing. Observational limits are placed on the magnitude of horizontal refractivity gradients, and it is concluded that the spikes are the result of local atmospheric density variations: atmospheric layers, density waves, or turbulence.

Prevalence and incidence of interstitial lung diseases in a multi-ethnic county of Greater Paris.

PubMed

Duchemann, Boris; Annesi-Maesano, Isabella; Jacobe de Naurois, Camille; Sanyal, Shreosi; Brillet, Pierre-Yves; Brauner, Michel; Kambouchner, Marianne; Huynh, Sophie; Naccache, Jean Marc; Borie, Raphael; Piquet, Jacques; Mekinian, Arsène; Virally, Jerôme; Uzunhan, Yurdagul; Cadranel, Jacques; Crestani, Bruno; Fain, Olivier; Lhote, Francois; Dhote, Robin; Saidenberg-Kermanac'h, Nathalie; Rosental, Paul-André; Valeyre, Dominique; Nunes, Hilario

2017-08-01

The objective of the study was to estimate the prevalence and incidence of interstitial lung diseases (ILDs) in Seine-Saint-Denis, a multi-ethnic county of Greater Paris, France.Patients with ILDs were identified between January and December 2012 by using several sources; all potentially involved medical specialists from public and private hospitals, community-based pulmonologists and general practitioners, and the Social Security system. Diagnoses were validated centrally by an expert multidisciplinary discussion.1170 ILD cases were reported (crude overall prevalence: 97.9/10 5 and incidence: 19.4/10 5 /year). In the 848 reviewed cases, the most prevalent diagnoses were sarcoidosis (42.6%), connective tissue diseases associated ILDs (CTDs-ILDs) (16%), idiopathic pulmonary fibrosis (IPF) (11.6%), and occupational ILDs (5.0%), which corresponded to a crude prevalence of 30.2/10 5 for sarcoidosis, 12.1/10 5 for CTDs-ILDs and 8.2/10 5 for IPF. The prevalence of fibrotic idiopathic interstitial pneumonias, merging IPF, nonspecific interstitial pneumonia and cases registered with code J84.1 was 16.34/10 5 An adjusted multinomial model demonstrated an increased risk of sarcoidosis in North Africans and Afro-Caribbeans and of CTDs-ILDs in Afro-Caribbeans, compared to that in Europeans.This study, with a comprehensive recruitment and stringent diagnostic criteria, emphasises the importance of secondary ILDs, particularly CTDs-ILDs and the relatively low prevalence of IPF, and confirms that sarcoidosis is a rare disease in France. Copyright ©ERS 2017.

Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).

PubMed

Mukhopadhyay, Sanjay; Parambil, Joseph G

2012-10-01

Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Preliminary evaluation of the diffraction behind the PROBA 3/ASPIICS optimized occulter

NASA Astrophysics Data System (ADS)

Baccani, Cristian; Landini, Federico; Romoli, Marco; Taccola, Matteo; Schweitzer, Hagen; Fineschi, Silvano; Bemporad, Alessandro; Loreggia, Davide; Capobianco, Gerardo; Pancrazzi, Maurizio; Focardi, Mauro; Noce, Vladimiro; Thizy, Cédric; Servaye, Jean-Sébastien; Renotte, Etienne

2016-07-01

PROBA-3 is a technological mission of the European Space Agency (ESA), devoted to the in-orbit demon- stration of formation flying (FF) techniques and technologies. ASPIICS is an externally occulted coronagraph approved by ESA as payload in the framework of the PROBA-3 mission and is currently in its C/D phase. FF offers a solution to investigate the solar corona close the solar limb using a two-component space system: the external occulter on one spacecraft and the optical instrument on the other, separated by a large distance and kept in strict alignment. ASPIICS is characterized by an inter-satellite distance of ˜144 m and an external occulter diameter of 1.42 m. The stray light due to the diffraction by the external occulter edge is always the most critical offender to a coronagraph performance: the designer work is focused on reducing the stray light and carefully evaluating the residuals. In order to match this goal, external occulters are usually characterized by an optimized shape along the optical axis. Part of the stray light evaluation process is based on the diffraction calculation with the optimized occulter and with the whole solar disk as a source. We used the field tracing software VirtualLabTM Fusion by Wyrowski Photonics [1] to simulate the diffraction. As a first approach and in order to evaluate the software, we simulated linear occulters, through as portions of the flight occulter, in order to make a direct comparison with the Phase-A measurements [2].

Using GPS radio occultation data in the study of tropical cyclogenesis

NASA Astrophysics Data System (ADS)

Didlake, A. C., Jr.; Kuo, Y. B.; Metcalfe, T.

2005-12-01

Numerous studies have examined atmospheric conditions and patterns in tropical cyclogenesis. Although much has been accomplished, a complete understanding of tropical cyclogenesis is hindered by the lack of data in the regions where formation occurs. The GPS (Global Positioning System) radio occultation technique can provide valuable data in key areas. In GPS radio occultation, GPS satellites emit radio signals through the atmosphere that are received by another satellite in a low Earth orbit. Various atmospheric properties are calculated based on the alteration of the signal. This study assessed the value of GPS radio occultation data in the study of tropical cyclogenesis by examining storms of the 2002 Western North Pacific typhoon season. The signature of precursor disturbances to tropical cyclogenesis was determined by analyzing composites of data from the NCEP Aviation (AVN) analysis over four days. Similar composites of GPS radio occultation data were produced. The AVN analysis showed strong signals of precursor disturbances in the low-level wind fields and atmospheric refractivity. The GPS radio occultation data detected similarly increased refractivity values in corresponding regions, but had sizeable measurement differences with the AVN analysis. These differences were attributed to AVN analysis error due to the lack of input observational data and the high accuracy of GPS radio occultation measurements. Further comparisons showed that with the limited quantity of data currently available, GPS radio occultation by itself was not sufficient to detect precursor disturbances. It can best be used in data assimilation to improve the analysis and forecasts of tropical storms.

Constraints on Pluto's Hazes from 2-Color Occultation Lightcurves

NASA Astrophysics Data System (ADS)

Hartig, Kara; Barry, T.; Carriazo, C. Y.; Cole, A.; Gault, D.; Giles, B.; Giles, D.; Hill, K. M.; Howell, R. R.; Hudson, G.; Loader, B.; Mackie, J. A.; Olkin, C. B.; Rannou, P.; Regester, J.; Resnick, A.; Rodgers, T.; Sicardy, B.; Skrutskie, M. F.; Verbiscer, A. J.; Wasserman, L. H.; Watson, C. R.; Young, E. F.; Young, L. A.; Buie, M. W.; Nelson, M.

2015-11-01

The controversial question of aerosols in Pluto's atmosphere first arose in 1988, when features in a Pluto occultation lightcurve were alternately attributed to haze opacity (Elliot et al. 1989) or a thermal inversion (Eshleman 1989). A stellar occultation by Pluto in 2002 was observed from several telescopes on Mauna Kea in wavelengths ranging from R- to K-bands (Elliot et al. 2003). This event provided compelling evidence for haze on Pluto, since the mid-event baseline levels were systematically higher at longer wavelengths (as expected if there were an opacity source that scattered more effectively at shorter wavelengths). However, subsequent occultations in 2007 and 2011 showed no significant differences between visible and IR lightcurves (Young et al. 2011).The question of haze on Pluto was definitively answered by direct imaging of forward-scattering aerosols by the New Horizons spacecraft on 14-JUL-2015. We report on results of a bright stellar occultation which we observed on 29-JUN-2015 in B- and H-bands from both grazing and central sites. As in 2007 and 2011, we see no evidence for wavelength-dependent extinction. We will present an analysis of haze parameters (particle sizes, number density profiles, and fractal aggregations), constraining models of haze distribution to those consistent with and to those ruled out by the occultation lightcurves and the New Horizons imaging.References:Elliot, J.L., et al., "Pluto's Atmosphere." Icarus 77, 148-170 (1989)Eshleman, V.R., "Pluto's Atmosphere: Models based on refraction, inversion, and vapor pressure equilibrium." Icarus 80 439-443 (1989)Elliot, J.L., et al., "The recent expansion of Pluto's atmosphere." Nature 424 165-168 (2003)Young, E.F., et al., "Search for Pluto's aerosols: simultaneous IR and visible stellar occultation observations." EPSC-DPS Joint Meeting 2011, held 2-7 October 2011 in Nantes, France (2011)

Stellar Occultation Studies of Pluto, Triton, Charon, and Chiron

NASA Technical Reports Server (NTRS)

Elliot, James L.

2002-01-01

Bodies inhabiting the outer solar system are of interest because, due to the colder conditions, they exhibit unique physical processes. Also, some of the lessons learned from them can be applied to understanding what occurred in the outer solar system during its formation and early evolution. The thin atmospheres of Pluto and Triton have structure that is not yet understood, and they have been predicted to undergo cataclysmic seasonal changes. Charon may have an atmosphere - we don't know. Chiron exhibits cometary activity so far from the sun (much further than most comets), so that H2O sublimation cannot be the driving mechanism. Probing these bodies from Earth with a spatial resolution of a few kilometers can be accomplished only with the stellar occultation technique. In this program we find and predict stellar occultation events by small outer-solar system bodies and then attempt observations of the ones that can potentially answer interesting questions. We also develop new methods of data analysis for occultations and secure other observations that are necessary for interpretation of the occultation data.

[A retrospective analysis on occult neck lymphatic metastasis in early tongue cancer].

PubMed

Gong, Q L; Bian, C; Liu, H

2016-10-07

Objective: To investigate the number and level of occult neck lymphatic metastasis for squamous cell carcinoma of tongue in clinical stage Ⅰ/Ⅱ, and the relationship between cell differentiation and occult neck lymphatic metastasis. Methods: A total of 101 cases diagnosed preoperatively as having squamous cell carcinoma of tongue in clinical stage Ⅰ/Ⅱ (cT1/T2N0M0) between January 2005 and April 2015 were analysed retrospectively. Whether presence of occult neck lymphatic metastasis in these cases was studied. Results: Occult neck lymphatic metastases were found in 22 (21.78%) of 101 cases, 10 men and 12 women, with an age range of 22 to 83 years. There was not statistically significant association between tumor size or cell differentiation and occult neck lymphatic metastasis ( P >0.05). The metastasis occurred most commonly in level Ⅱ, followed by levelsⅠ, Ⅲ and Ⅳ. There was no lymph node metastasis in Level Ⅴ. There were total 20 cases with occult neck lymphatic metastasis in at least one of levelⅠ, Ⅱ, Ⅲ(90.9%), One of these case was skipping metastasis in level Ⅲ(4.6%). Conclusion: The early tongue cancer has a high rate of occult lymph metastasis, which occurs commonly in levels Ⅱ, Ⅰ and Ⅲ, but there is not significant association between the metastasis and tumor size or cell differentiation.

Wave optics of the central spot in planetary occultations

NASA Technical Reports Server (NTRS)

Hubbard, W. B.

1977-01-01

The detection of a bright central spot during the occultation of epsilon Geminorum by Mars demonstrates that an exponentially-stratified planetary atmosphere can act as a lens providing very high resolution of distant objects (e.g., quasars, white dwarfs, and pulsars). The diffraction nature of the central occultation spot is investigated, with special reference to Mars and Venus. In practice, however, central occultations by these planets are seldom observable from the earth's surface, and spacecraft would have to be used to obtain a suitable orientation for observers. Further difficulties may be encountered in image deconvolution needed for extended objects, in location of the image of a true point source, and in compensation for peculiarities of planets and their atmospheres.

An occultation satellite system for determining pressure levels in the atmosphere

NASA Technical Reports Server (NTRS)

Ungar, S. G.; Lusignan, B. B.

1972-01-01

An operational two-satellite microwave occultation system will establish a pressure reference level to be used in fixing the temperature-pressure profile generated by the SIRS infrared sensor as a function of altitude. In the final error analysis, simulated data for the SIRS sensor were used to test the performance of the occultation system. The results of this analysis indicate that the occultation system is capable of measuring the altitude of the 300-mb level to within 24 mrms, given a maximum error of 2 K in the input temperature profile. The effects of water vapor can be corrected by suitable climatological profiles, and improvements in the accuracy of the SIRS instrument should yield additional improvements in the performance of the occultation system.

The Occult: Diabolica to Alchemists

ERIC Educational Resources Information Center

Delaney, Oliver J.

1971-01-01

The 91 items in this bibliography deal with works of occult science. The material is subdivided into biographies, dictionaries, encyclopedias, handbooks, noteworthy histories, indices, annuals, and a few miscellany works with treatises. (95 references) (Author)

Tenascin-C Is a Major Component of the Fibrogenic Niche in Kidney Fibrosis

PubMed Central

Fu, Haiyan; Tian, Yuan; Zhou, Lili; Zhou, Dong; Tan, Roderick J.; Stolz, Donna B.

2017-01-01

Kidney fibrosis initiates at certain focal sites in which the fibrogenic niche provides a specialized microenvironment that facilitates fibroblast activation and proliferation. However, the molecular identity of these fibrogenic niches is poorly characterized. Here, we determined whether tenascin-C (TNC), an extracellular matrix glycoprotein, is a component of the fibrogenic niche in kidney fibrosis. In vivo, TNC expression increased rapidly in kidneys subjected to unilateral ureteral obstruction or ischemia/reperfusion injury and predominantly localized at the foci rich in fibroblasts in renal interstitium. In vitro, TNC selectively promoted renal interstitial fibroblast proliferation, bromodeoxyuridine incorporation, and the expression of proliferation-related genes. The mitogenic activity of TNC required the integrin/focal adhesion kinase/mitogen-activated protein kinase signaling cascade. Using decellularized extracellular matrix scaffolds, we found that TNC-enriched scaffolds facilitated fibroblast proliferation, whereas TNC-deprived scaffolds inhibited proliferation. Matrix scaffold prepared from fibrotic kidney also promoted greater ex vivo fibroblast proliferation than did scaffolds prepared from healthy kidney. Conversely, small interfering RNA-mediated knockdown of TNC in vivo repressed injury-induced fibroblast expansion and renal fibrosis. These studies identify TNC as a major constituent of the fibrogenic niche that promotes fibroblast proliferation, and illustrate a pivotal role for the TNC-enriched microenvironment in kidney fibrogenesis. PMID:27612995

Seroprevalence of occult hepatitis B among Egyptian paediatric hepatitis C cancer patients.

PubMed

Raouf, H E; Yassin, A S; Megahed, S A; Ashour, M S; Mansour, T M

2015-02-01

Occult hepatitis B infection is characterized by the presence of hepatitis B virus (HBV) DNA in the serum in the absence of hepatitis B surface antigen (HBsAg). Prevalence of hepatitis C virus (HCV) infections in Egypt is among the highest in the world. In this study, we aim at analysing the rates of occult HBV infections among HCV paediatric cancer patients in Egypt. The prevalence of occult HBV was assessed in two groups of paediatric cancer patients (HCV positive and HCV negative), in addition to a third group of paediatric noncancer patients, which was used as a general control. All groups were negative for HBsAg and positive for HCV antibody. HBV DNA was detected by nested PCR and real-time PCR. HCV was detected by real-time PCR. Sequencing was carried out in order to determine HBV genotypes to all HBV patients as well as to detect any mutation that might be responsible for the occult phenotype. Occult hepatitis B infection was observed in neither the non-HCV paediatric cancer patients nor the paediatric noncancer patients but was found in 31% of the HCV-positive paediatric cancer patients. All the detected HBV patients belonged to HBV genotype D, and mutations were found in the surface genome of HBV leading to occult HBV. Occult HBV infection seems to be relatively frequent in HCV-positive paediatric cancer patients, indicating that HBsAg negativity is not sufficient to completely exclude HBV infection. These findings emphasize the importance of considering occult HBV infection in HCV-positive paediatric cancer patients especially in endemic areas as Egypt. © 2014 John Wiley & Sons Ltd.

Occult Hepatitis B Virus Infection in a Previously Vaccinated Injection Drug User.

PubMed

Powell, Eleanor A; Razeghi, Sanam; Zucker, Stephen; Blackard, Jason T

2016-02-01

Occult hepatitis B virus (HBV) is defined by the presence of HBV DNA in patient sera in the absence of HBsAg. Occult HBV has been associated with hepatocellular carcinoma, reactivation during immune suppression, and transmission to others. While the hepatitis B vaccine is very effective at preventing chronic HBV infection, recent studies indicate it is less effective at preventing occult HBV following infant vaccination. No studies, however, have examined the efficacy of adult HBV vaccination at preventing occult HBV. Here, we present the first report of occult HBV following adult vaccination. A 21-year old Caucasian female presented with tricuspid valve endocarditis secondary to methicillin-susceptible Staphylococcus aureus with non-ischemic cardiomyopathy. She reported active use of intravenous drugs. Her liver enzymes were elevated (ALT = 1873 IU/mL; AST = 4518 IU/mL), and she was found to have HCV and occult HBV. HBV viral loads ranged from 4608 - 8364 copies IU/mL during hospitalization. The patient's HBV was sequenced and found to be genotype D3 without any known diagnostic escape mutations. Immune complexes that may have prevented HBsAg detection were not observed. HBV vaccination in infancy is effective at preventing chronic HBV infection but is less effective at preventing occult HBV infection. Similar studies examining the efficacy of adult HBV vaccination in preventing occult HBV have not been performed. This case highlights the importance of carefully determining the HBV status of high-risk individuals, as vaccination history and the presence of anti-HBs may not be adequate to rule out HBV infection, even in the absence of HBsAg.

Periprosthetic Occult Fractures of the Acetabulum Occur Frequently During Primary THA.

PubMed

Hasegawa, Kazuhiro; Kabata, Tamon; Kajino, Yoshitomo; Inoue, Daisuke; Tsuchiya, Hiroyuki

2017-02-01

Periprosthetic fractures of the acetabulum occurring during primary THA are rare. Periprosthetic occult fractures are defined as those not identified by the surgeon during the procedure which might be missed on a routine postoperative radiograph. However, it is unclear how frequently these fractures occur and whether their presence affects functional recovery. In this study, using routine CT scans that were obtained as part of another primary hip arthroplasty study protocol, we retrospectively assessed (1) the prevalence of occult fractures of the acetabulum occurring during primary THA, (2) the location of occult fractures of the acetabulum during THA, and (3) risk factors contributing to such occult fractures. Between 2004 and 2013, our institute performed 585 primary THAs (cementless or hybrid) in 494 patients with DICOM pre- and postoperative CT; during the period in question, all patients undergoing THA underwent CT before and after surgery. Preoperative CT images were taken as part of a CT-based three-dimensional templating software and navigation system. Postoperative CT images were taken an average of 1 week after surgery as part of a different protocol to evaluate cup position, restoration of leg length and offset, volume of postoperative hematoma to assess anticoagulation effects after THA, and fractures that were not found on routine postoperative radiographs (which we defined as occult fractures). Patients with a history of prior pelvic osteotomy, trauma, and infection were excluded (88 patients/99 hips); 406 patients (102 males and 304 females; 486 hips) form the basis of this report. The mean age of the patients was 60 ± 11 years, with a mean BMI of 23 ± 4 kg/m 2 . The mean followup of the patients with periprosthetic fracture of the acetabulum was 58 ± 28 months (range, 12-131 months). Potential risk factors for occult acetabular fracture including age, sex, BMI, preoperative diagnosis, additional dome screw fixation, composition and size of each

Occult cancer detection in patients with hemostatic disorder and venous thromboembolism.

PubMed

Husseinzadeh, Holleh; Carrier, Marc

2018-03-01

There are physiologic ties between Von Willebrand Factor (VWF) and circulating tumor cells. VWF appears to play a role in tumor biology, but it is unclear whether cancer behavior differs in Von Willebrand Disease. In patients presenting with venous thromboembolism (VTE), occult cancer is frequently considered as an underlying cause. The prevalence of occult cancer after provoked VTE is low (3%); therefore, cancer screening in these patients is not routinely recommended. In those with unprovoked VTE, occult cancer is more prevalent, estimated between 4 and 10%. Due to this elevated risk, occult cancer screening is recommended in this population. Multiple studies have investigated whether a "limited" approach (including history and physical exam, basic labs, and chest X-ray) versus "extensive" approach (addition of advanced imaging, such as computer tomography) is more effective. Current data fails to demonstrate extensive screening strategies diagnose more occult cancer, miss fewer cancers during follow up, or improve cancer-related mortality. Furthermore, many patients may be needlessly exposed to unnecessary diagnostic procedures with their associated complications and costs, as well as significant anxiety. Therefore, the decision to perform additional testing should be made on a case-by-case basis. Additional studies are needed to identify subgroups of patients with unprovoked VTE at highest risk for occult cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Astrometry of Single-Chord Occultations: Application to the 1993 Triton Event

NASA Technical Reports Server (NTRS)

Olkin, Catherine B.; Elliot, J. L.; Bus, Schelte J.; McDonald, Stephen W.; Dahn, Conrad C.

1996-01-01

This paper outlines a method for reducing astrometric data to derive the closest approach time and distance to the center of an occultation shadow for a single observer. The method applies to CCD frames, strip scans or photographic plates and uses a set of field stars of unknown positions to define a common coordinate system for all frames. The motion of the occulting body is used to establish the transformation between this common coordinate system and the celestial coordinate system of the body's ephemeris. This method is demonstrated by application to the Tr6O occultation by Triton on 1993 July 10 UT. Over an interval of four nights that included the occultation time, 80 frames of Triton and Tr6O were taken near the meridian with the U.S. Naval Observatory (USNO) 61-inch astrometric reflector. Application of the method presented here to these data yields a closest approach distance of 359 +/- 133 km (corresponding to 0.017 +/- 0.006 arcsec) for the occultation chord obtained with the Kuiper Airborne Observatory (KAO). Comparison of the astrometric closest approach time with the KAO light-curve midtime shows a difference of 2.2 +/- 4.1 s. Relative photometry of Triton and Tr6O, needed for photometric calibration of the occultation light curve, is also presented.

[Occultism, parapsychology and the esoteric from the perspective of psychopathology].

PubMed

Scharfetter, C

1998-10-01

The concepts and main themes of occultism, parapsychology and esoterics are set in comparison to religion, spirituality, mysticism. The cultural relativity of these concepts is emphasised. Occultism means dealing with phenomena, processes, and/or powers which are not accessible to "normal perception". The manipulation of such powers is effected via (white, black, grey) magic. Parapsychology, in its popular sense, deals with occult phenomena, whereas scientific parapsychology investigates them empirically. Esoterics is a complex of beliefs within a hermetic tradition about occult processes and about desting after death. Transpersonal psychology deals with these issues while calling them "spiritual". Effects of paranormal experiences and actions on the side of the actor as well as the adept are discussed: personality types, interpersonal effects, crises and psychoses (mediumistic psychoses). The concept of dissociation of subpersonalities (subselves) appears to be a viable perspective to explain these phenomena. In mediumistic psychoses, the splitting of non-ego parts of the psyche leads to a manifestation of schizophrenic symptoms. Dangers for mental health are an ego inflation by self-attribution of "superhuman" power. A personality disposition for parapsychological perception and/or action may be seen in schizotypia and similar near-psychotic "personalities up the border". Adepts of occultism may present with a "false self" in the sense of Winnicott.

Effects of vitamin E on mercuric chloride-induced renal interstitial fibrosis in rats and the antioxidative mechanism.

PubMed

Tao, Yan-yan; Wang, Qing-lan; Yuan, Ji-li; Shen, Li; Liu, Cheng-hai

2011-02-01

To observe the effects of vitamin E (Vit E) on mercuric chloride (HgCl2)-induced renal interstitial fibrosis (RIF) in rats and discuss its antioxidative mechanism. A total of 32 Sprague-Dawley rats were randomly assigned to three groups: normal group, model group and Vit E group. RIF was induced by oral administration of HgCl(2) at a dose of 8 mg/kg body weight once a day for 9 weeks. Rats in Vit E group were administered with Vit E capsule at 100 mg/kg body weight, and rats in normal and model groups were treated with normal saline. At the end of the 9th week, rats were sacrificed and renal hydroxyproline (Hyp)'s trichrome and periodic acid-silver methenamine (PASM) staining. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and contents of glutathione (GSH) and malondialdehyde (MDA) in kidney tissue were tested with commercial kits. The expressions of nuclear factor-κB (NF-κB), inhibitor-κB (IκB), phospho-IκB (p-IκB) and tumor necrosis factor-α (TNF-α) were determined by Western blot. The expression of α-smooth muscle actin (α-SMA) was assayed by Western blot and immunofluorescent staining. Renal Hyp content, HE, Masson's trichrome and PASM staining results and α-SMA expression confirmed development of HgCl2-induced RIF in rats. Oxidative stress markers GSH, GSH-Px and MDA confirmed oxidative stress in RIF rats. Compared with model rats, rats in Vit E group had lower kidney Hyp content (P<0.01). GSH and MDA contents decreased significantly in Vit E group compared with model group (P<0.01). The expressions of NF-κB and IκB had no significant difference among all groups (P>0.05). In Vit E group, the expressions of p-IκB and TNF-α decreased significantly compared with model group (P<0.01). The expression of α-SMA in Vit E group was also decreased significantly compared with model group (P<0.01). Vit E has a protective effect on experimental RIF induced by HgCl(2) in rats and it is related to inhibition of lipid

A loss of telocytes accompanies fibrosis of multiple organs in systemic sclerosis

PubMed Central

Manetti, Mirko; Rosa, Irene; Messerini, Luca; Guiducci, Serena; Matucci-Cerinic, Marco; Ibba-Manneschi, Lidia

2014-01-01

Systemic sclerosis (SSc) is a complex connective tissue disease characterized by fibrosis of the skin and various internal organs. In SSc, telocytes, a peculiar type of stromal (interstitial) cells, display severe ultrastructural damages and are progressively lost from the clinically affected skin. The aim of the present work was to investigate the presence and distribution of telocytes in the internal organs of SSc patients. Archival paraffin-embedded samples of gastric wall, myocardium and lung from SSc patients and controls were collected. Tissue sections were stained with Masson's trichrome to detect fibrosis. Telocytes were studied on tissue sections subjected to CD34 immunostaining. CD34/CD31 double immunofluorescence was performed to unequivocally differentiate telocytes (CD34-positive/CD31-negative) from vascular endothelial cells (CD34-positive/CD31-positive). Few telocytes entrapped in the fibrotic extracellular matrix were found in the muscularis mucosae and submucosa of SSc gastric wall. In the muscle layers and myenteric plexus, the network of telocytes was discontinuous or even completely absent around smooth muscle cells and ganglia. Telocytes were almost completely absent in fibrotic areas of SSc myocardium. In SSc fibrotic lung, few or no telocytes were observed in the thickened alveolar septa, around blood vessels and in the interstitial space surrounding terminal and respiratory bronchioles. In SSc, the loss of telocytes is not restricted to the skin, but it is a widespread process affecting multiple organs targeted by the fibrotic process. As telocytes are believed to be key players in the regulation of tissue/organ homoeostasis, our data suggest that telocyte loss might have important pathophysiological implications in SSc. PMID:24467430

McDonald's and the Occult.

ERIC Educational Resources Information Center

Singer, Barry

1979-01-01

Discusses "occult" and "paranormal" literature which is often mistaken for nonfiction. Suggests that most publishers are unwilling to publish scientific perspectives on the paranormal because such writings would be unmarketable. Journal availability: see SO 507 190. (KC)

The Smad3/Smad4/CDK9 complex promotes renal fibrosis in mice with unilateral ureteral obstruction.

PubMed

Qu, Xinli; Jiang, Mengjie; Sun, Yu Bo Yang; Jiang, Xiaoyun; Fu, Ping; Ren, Yi; Wang, Die; Dai, Lie; Caruana, Georgina; Bertram, John F; Nikolic-Paterson, David J; Li, Jinhua

2015-12-01

Transforming growth factor-β1 (TGF-β1)/Smad signaling has a central role in the pathogenesis of renal fibrosis. Smad3 and Smad4 are pro-fibrotic, while Smad2 is anti-fibrotic. However, these Smads form heterogeneous complexes, the functions of which are poorly understood. Here we studied Smad complex function in renal fibrosis using the mouse model of unilateral ureteric obstruction. Mice heterozygous for Smad3/4 (Smad3/4 +/- ) exhibited substantial protection from renal fibrosis through day 7 of obstruction, whereas Smad2/3 +/- and Smad2/4 +/- mice showed only modest protection. Formation of Smad3/Smad4/CDK9 complexes was an early event following obstruction in wild-type mice, which involved nuclear phosphorylation of the linker regions of Smad3. Significantly, Smad3 or Smad4 deficiency decreased the formation of Smad4/CDK9 or Smad3/CDK9 complex, Smad3 linker phosphorylation, and fibrosis but at different degrees. In vitro, TGF-β1 stimulation of collagen I promoter activity involved formation of Smad3/Smad4/CDK9 complexes, and overexpression of each component gave additive increases in collagen promoter activity. Co-administration of a CDK9 inhibitor and Smad3-specific inhibition achieved better protection from TGF-β1-induced fibrotic response in vitro and renal interstitial fibrosis in vivo. Thus formation of Smad3/Smad4/CDK9 complex drives renal fibrosis during ureteral obstruction. Formation of this complex represents a novel target for antifibrotic therapies.

Idiopathic Interstitial Pneumonia Associated With Autoantibodies: A Large Case Series Followed Over 1 Year.

PubMed

Collins, Bridget F; Spiekerman, Charles F; Shaw, Megan A; Ho, Lawrence A; Hayes, Jennifer; Spada, Carolyn A; Stamato, Caroline M; Raghu, Ganesh

2017-07-01

Some patients with autoimmune characteristics and idiopathic interstitial pneumonia, particularly usual interstitial pneumonia (UIP), do not fit neatly into the category of connective tissue disease-associated interstitial lung disease (CTD-ILD), idiopathic pulmonary fibrosis (IPF), or recently proposed yet to be validated criteria for interstitial pneumonia with autoimmune features (IPAF). Outcomes of these patients are unknown. This was a retrospective single-center study. Analyses of variance compared differences in mean change in FVC and diffusion capacity (Dlco) over 1 year among 124 well-defined patients (20 patients with positive autoantibodies with or without symptoms of connective tissue disease [AI-ILD], 15 patients with IPAF, 36 patients with CTD-ILD, and 53 patients with IPF with negative CTD serologies [Lone-IPF]). Of the patients, 75% with AI-ILD, 33% with IPAF, and 33% with CTD-ILD had UIP. Initial FVC and Dlco were similarly moderately reduced across groups. Mean change in FVC over 12 months was as follows: -60 mL (IPAF), -110 mL (AI-ILD), -10 mL (CTD-ILD), and -90 mL (Lone-IPF) (P = .52). Mean change in Dlco was as follows: 2.39 mL/mm Hg/min (IPAF), -1.15 mL/mm Hg/min (AI-ILD), -0.27 mL/mm Hg/min (CTD-ILD), and -1.05 mL/mm Hg/min (Lone-IPF) (P < .001). By pattern of disease, the mean change in FVC was as follows: -140 mL (UIP), 10 mL (nonspecific interstitial pneumonia), and 12 mL (unclassifiable/other) (P = .001). No clinically significant differences in pulmonary function to distinguish between patients with AI-ILD, IPAF, CTD-ILD, and Lone-IPF were observed after 1 year. Longer periods of follow-up are needed to understand the outcomes of these patients. It is not yet clear whether AI-ILD is a distinct phenotype or a variant of the newly proposed entity IPAF. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Influences of innate immunity, autophagy, and fibroblast activation in the pathogenesis of lung fibrosis.

PubMed

O'Dwyer, David N; Ashley, Shanna L; Moore, Bethany B

2016-09-01

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by accumulation of extracellular matrix (ECM) and impaired gas exchange. The pathobiological mechanisms that account for disease progression are poorly understood but likely involve alterations in innate inflammatory cells, epithelial cells, and fibroblasts. Thus we seek to review the most recent literature highlighting the complex roles of neutrophils and macrophages as both promoters of fibrosis and defenders against infection. With respect to epithelial cells and fibroblasts, we review the data suggesting that defective autophagy promotes the fibrogenic potential of both cell types and discuss new evidence related to matrix metalloproteinases, growth factors, and cellular metabolism in the form of lactic acid generation that may have consequences for promoting fibrogenesis. We discuss potential cross talk between innate and structural cell types and also highlight literature that may help explain the limitations of current IPF therapies. Copyright © 2016 the American Physiological Society.

Changes in Pluto's Atmosphere Revealed by Occultations

NASA Astrophysics Data System (ADS)

Sicardy, Bruno; Widemann, Thomas; Lellouch, Emmanuel; Veillet, Christian; Colas, Francois; Roques, Francoise; Beisker, Wolfgang; Kretlow, Mike; Cuillandre, Jean-Charles; Hainaut, Olivier

After the discovery and study of Pluto's tenuous atmosphere in 1985 and 1988 with stellar occultations 14 years were necessary before two other occultations by the planet could be observed on 20 July 2002 and 21 August 2002 from Northern Chile with a portable telescope and from CFHT in Hawaii respectively. These occultations reveal drastric changes in Pluto's nitrogen atmosphere whose pressure increased by a factor two or more since 1988. In spite of an increasing distance to the Sun (and a correlated decrease of solar energy input at Pluto) this increase can be explained by the fact that Pluto's south pole went from permanent darkness to permanent illumination between 1988 and 2002. This might cause the sublimation of the south polar cap and the increase of pressure which could go on till 2015 according to current nitrogen cycle models. Furthermore we detect temperature contrasts between the polar and the equatorial regions probed on Pluto possibly caused by different diurnally averaged insolations at those locations. Finally spikes observed in the light curves reveal a dynamical activity in Pluto's atmosphere.

High spatial resolution multi-color observations of Neptune during occultation by the moon

NASA Technical Reports Server (NTRS)

Veverka, J.

1976-01-01

Preparations for the observation of Mars occultation using the 36 inch telescope on a C-141 airborne observatory were described, including technical improvements made to existing equipment. The abstracts of the following four publications supported by the grant were presented: (1) atmosphere composition from refractivity measurements made during occultations, (2) how big is lapetus?, (3) the diameter of Titan, (4) design and operating characteristics of voltage to frequency converters suited for occultation work. The planned observation of the April 8, 1976 occultation of the epsilon Gem star from the C-141 airborne observatory was described.

Prevalence of occult inflammatory bowel disease in ankylosing spondylitis.

PubMed Central

Costello, P B; Alea, J A; Kennedy, A C; McCluskey, R T; Green, F A

1980-01-01

Fifty-five patients with ankylosing spondylitis and 16 control patients matched for sex and age were examined for evidence of occult inflammatory bowel disease. In all patients evaluation included history and physical examination, barium enema, sigmoidoscopy, and rectal biopsy. The results of this study suggest that there is no increased prevalence of occult inflammatory bowel disease in patients with ankylosing spondylitis. PMID:7436576

Prevalence of occult inflammatory bowel disease in ankylosing spondylitis.

PubMed

Costello, P B; Alea, J A; Kennedy, A C; McCluskey, R T; Green, F A

1980-10-01

Fifty-five patients with ankylosing spondylitis and 16 control patients matched for sex and age were examined for evidence of occult inflammatory bowel disease. In all patients evaluation included history and physical examination, barium enema, sigmoidoscopy, and rectal biopsy. The results of this study suggest that there is no increased prevalence of occult inflammatory bowel disease in patients with ankylosing spondylitis.

Probing Pluto's Atmosphere Using Ground-Based Stellar Occultations

NASA Astrophysics Data System (ADS)

Sicardy, Bruno; Rio de Janeiro Occultation Team, Granada Team, International Occultation and Timing Association, Royal Astronomical Society New Zealand Occultation Section, Lucky Star associated Teams

2016-10-01

Over the last three decades, some twenty stellar occultations by Pluto have been monitored from Earth. They occur when the dwarf planet blocks the light from a star for a few minutes as it moves on the sky. Such events led to the hint of a Pluto's atmosphere in 1985, that was fully confirmed during another occultation in 1988, but it was only in 2002 that a new occultation could be recorded. From then on, the dwarf planet started to move in front of the galactic center, which amplified by a large factor the number of events observable per year.Pluto occultations are essentially refractive events during which the stellar rays are bent by the tenuous atmosphere, causing a gradual dimming of the star. This provides the density, pressure and temperature profiles of the atmosphere from a few kilometers above the surface up to about 250 km altitude, corresponding respectively to pressure levels of about 10 and 0.1 μbar. Moreover, the extremely fine spatial resolution (a few km) obtained through this technique allows the detection of atmospheric gravity waves, and permits in principle the detection of hazes, if present.Several aspects make Pluto stellar occultations quite special: first, they are the only way to probe Pluto's atmosphere in detail, as the dwarf planet is far too small on the sky and the atmosphere is far too tenuous to be directly imaged from Earth. Second, they are an excellent example of participative science, as many amateurs have been able to record those events worldwide with valuable scientific returns, in collaboration with professional astronomers. Third, they reveal Pluto's climatic changes on decade-scales and constrain the various seasonal models currently explored.Finally, those observations are fully complementary to space exploration, in particular with the New Horizons (NH) mission. I will show how ground-based occultations helped to better calibrate some NH profiles, and conversely, how NH results provide some key boundary conditions

Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

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

Van Beneden, Katrien, E-mail: kvbenede@vub.ac.be; Geers, Caroline; Pauwels, Marina

Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as didmore » the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.« less

Associations of electrocardiographic P-wave characteristics with left atrial function, and diffuse left ventricular fibrosis defined by cardiac magnetic resonance: The PRIMERI Study.

PubMed

Tiffany Win, Theingi; Ambale Venkatesh, Bharath; Volpe, Gustavo J; Mewton, Nathan; Rizzi, Patricia; Sharma, Ravi K; Strauss, David G; Lima, Joao A; Tereshchenko, Larisa G

2015-01-01

Abnormal P-terminal force in lead V1 (PTFV1) is associated with an increased risk of heart failure, stroke, atrial fibrillation, and death. Our goal was to explore associations of left ventricular (LV) diffuse fibrosis with left atrial (LA) function and electrocardiographic (ECG) measures of LA electrical activity. Patients without atrial fibrillation (n = 91; mean age 59.5 years; 61.5% men; 65.9% white) with structural heart disease (spatial QRS-T angle ≥105° and/or Selvester QRS score ≥5 on ECG) but LV ejection fraction >35% underwent clinical evaluation, cardiac magnetic resonance, and resting ECG. LA function indices were obtained by multimodality tissue tracking using 2- and 4-chamber long-axis images. T1 mapping and late gadolinium enhancement were used to assess diffuse LV fibrosis and presence of scar. P-prime in V1 amplitude (PPaV1) and duration (PPdV1), averaged P-wave-duration, PR interval, and P-wave axis were automatically measured using 12 SLTM algorithm. PTFV1 was calculated as a product of PPaV1 and PPdV1. In linear regression after adjustment for demographic characteristics, body mass index, maximum LA volume index, presence of scar, and LV mass index, each decile increase in LV interstitial fibrosis was associated with 0.76 mV*ms increase in negative abnormal PTFV1 (95% confidence interval [CI] -1.42 to -0.09; P = .025), 15.3 ms prolongation of PPdV1 (95% CI 6.9 to 23.8; P = .001) and 5.4 ms prolongation of averaged P-duration (95% CI 0.9-10.0; P = .020). LV fibrosis did not affect LA function. PPaV1 and PTFV1 were associated with an increase in LA volumes and decrease in LA emptying fraction and LA reservoir function. LV interstitial fibrosis is associated with abnormal PTFV1, prolonged PPdV1, and P-duration, but does not affect LA function. Copyright © 2015 Heart Rhythm Society. All rights reserved.

Dysregulation of Galectin-3. Implications for Hermansky-Pudlak Syndrome Pulmonary Fibrosis

PubMed Central

Cullinane, Andrew R.; Yeager, Caroline; Dorward, Heidi; Carmona-Rivera, Carmelo; Wu, Hai Ping; Moss, Joel; O’Brien, Kevin J.; Nathan, Steven D.; Meyer, Keith C.; Rosas, Ivan O.; Helip-Wooley, Amanda; Huizing, Marjan; Gahl, William A.

2014-01-01

The etiology of Hermansky-Pudlak syndrome (HPS) pulmonary fibrosis (HPSPF), a progressive interstitial lung disease with high mortality, is unknown. Galectin-3 is a β-galactoside–binding lectin with profibrotic effects. The objective of this study was to investigate the involvement of galectin-3 in HPSPF. Galectin-3 was measured by ELISA, immunohistochemistry, and immunoblotting in human specimens from subjects with HPS and control subjects. Mechanisms of galectin-3 accumulation were studied by quantitative RT-PCR, Northern blot analysis, membrane biotinylation assays, and rescue of HPS1-deficient cells by transfection. Bronchoalveolar lavage galectin-3 concentrations were significantly higher in HPSPF compared with idiopathic pulmonary fibrosis or that from normal volunteers, and correlated with disease severity. Galectin-3 immunostaining was increased in HPSPF compared with idiopathic pulmonary fibrosis or normal lung tissue. Fibroblasts from subjects with HPS subtypes associated with pulmonary fibrosis had increased galectin-3 protein expression compared with cells from nonfibrotic HPS subtypes. Galectin-3 protein accumulation was associated with reduced Galectin-3 mRNA, normal Mucin 1 levels, and up-regulated microRNA-322 in HPSPF cells. Membrane biotinylation assays showed reduced galectin-3 and normal Mucin 1 expression at the plasma membrane in HPSPF cells compared with control cells, which suggests that galectin-3 is mistrafficked in these cells. Reconstitution of HPS1 cDNA into HPS1-deficient cells normalized galectin-3 protein and mRNA levels, as well as corrected galectin-3 trafficking to the membrane. Intracellular galectin-3 levels are regulated by HPS1 protein. Abnormal accumulation of galectin-3 may contribute to the pathogenesis of HPSPF. PMID:24134621

Serine proteases, inhibitors and receptors in renal fibrosis

PubMed Central

Eddy, Allison A.

2011-01-01

Summary Chronic kidney disease (CKD) is estimated to affect one in eight adults. Their kidney function progressively deteriorates as inflammatory and fibrotic processes damage nephrons. New therapies to prevent renal functional decline must build on basic research studies that identify critical cellular and molecular mediators. Plasminogen activator inhibitor-1 (PAI-1), a potent fibrosis-promoting glycoprotein, is one promising candidate. Absent from normal kidneys, PAI-1 is frequently expressed in injured kidneys. Studies in genetically engineered mice have demonstrated its potency as a pro-fibrotic molecule. Somewhat surprising, its ability to inhibit serine protease activity does not appear to be its primary pro-fibrotic effect in CKD. Both tissue-type plasminogen activator and plasminogen deficiency significantly reduced renal fibrosis severity after ureteral obstruction, while genetic urokinase (uPA) deficiency had no effect. PAI-1 expression is associated with enhanced recruitment of key cellular effectors of renal fibrosis – interstitial macrophages and myofibroblasts. The ability of PAI-1 to promote cell migration involves interactions with the low-density lipoprotein receptor-associate protein-1 and also complex interactions with uPA bound to its receptor (uPAR) and several leukocyte and matrix integrins that associate with uPAR as co-receptors. uPAR is expressed by several cell types in damaged kidneys, and studies in uPAR-deficient mice have shown that its serves a protective role. uPAR mediates additional anti-fibrotic effects - it interacts with specific co-receptors to degrade PAI-1 and extracellular collagens, and soluble uPAR has leukocyte chemoattractant properties. Molecular pathways activated by serine proteases and their inhibitor, PAI-1, are promising targets for future anti-fibrotic therapeutic agents. PMID:19350108

Interstitial laser prostatectomy

NASA Astrophysics Data System (ADS)

Johnson, Douglas E.; Cromeens, Douglas M.; Price, Roger E.

1994-05-01

Interstitial laser coagulation of the canine prostate using the Sharplan interstitial thermal therapy fiber (Model 25432) was performed in 9 adult dogs and the subsequent gross and histopathologic changes occurring in the prostate were studied at intervals ranging from 1 hour to 5 weeks. A large well-demarcated area of acute coagulative necrosis developed around each fiber tract which in turn was surrounded by a prominent narrow zone of marked tissue disruption and an outer zone of hemorrhage. Liquefaction developed within the coagulative areas within 24 hours and by 4 days, each prostatic lobe contained an irregular cavity which became lined by normal-appearing transitional epithelium and that by 5 weeks, communicated with the prostatic urethra. These changes, similar to those reported following transurethral visual laser ablation of the prostate, suggest that interstitial laser thermal therapy may provide an alternative means for treating selected patients suffering from prostatic enlargement.

Lunar occultation of Saturn. IV - Astrometric results from observations of the satellites

NASA Technical Reports Server (NTRS)

Dunham, D. W.; Elliot, J. L.

1978-01-01

The method of determining local lunar limb slopes, and the consequent time scale needed for diameter studies, from accurate occultation timings at two nearby telescopes is described. Results for photoelectric observations made at Mauna Kea Observatory during the occultation of Saturn's satellites on March 30, 1974, are discussed. Analysis of all observations of occultations of Saturn's satellites during 1974 indicates possible errors in the ephemerides of Saturn and its satellites.

Occult HBV Infection: A Faceless Enemy in Liver Cancer Development

PubMed Central

Morales-Romero, Jaime; Vargas, Gustavo; García-Román, Rebeca

2014-01-01

The hepatitis B virus (HBV) represents a worldwide public health problem; the virus is present in one third of the global population. However, this rate may in fact be higher due to occult hepatitis B virus infection (OBI). This condition is characterized by the presence of the viral genome in the liver of individuals sero-negative for the virus surface antigen (HBsAg). The causes of the absence of HBsAg in serum are unknown, however, mutations have been identified that produce variants not recognized by current immunoassays. Epigenetic and immunological host mechanisms also appear to be involved in HBsAg suppression. Current evidence suggests that OBI maintains its carcinogenic potential, favoring the progression of fibrosis and cirrhosis of the liver. In common with open HBV infection, OBI can contribute to the establishment of hepatocellular carcinoma. Epidemiological data regarding the global prevalence of OBI vary due to the use of detection methods of different sensitivity and specificity. In Latin America, which is considered an area of low prevalence for HBV, diagnostic screening methods using gene amplification tests for confirmation of OBI are not conducted. This prevents determination of the actual prevalence of OBI, highlighting the need for the implementation of cutting edge technology in epidemiological surveillance systems. PMID:24717680

Pluto's Atmospheric Figure from the P131.1 Stellar Occultation

NASA Astrophysics Data System (ADS)

Person, M. J.; Elliot, J. L.; Clancy, K. B.; Kern, S. D.; Salyk, C. V.; Tholen, D. J.; Pasachoff, J. M.; Babcock, B. A.; Souza, S. P.; Ticehurst, D. R.; Hall, D.; Roberts, L. C., Jr.; Bosh, A. S.; Buie, M. W.; Dunham, E. W.; Olkin, C. B.; Taylor, B.; Levine, S. E.; Eikenberry, S. S.; Moon, D.-S.; Osip, D. J.

2003-05-01

The stellar occultation by Pluto of the 15th magnitude star designated P131.1 (McDonald and Elliot, AJ, 119, 1999) on 2002 August 21 (UT) provided the first significant chance to compare Pluto's atmospheric structure to that determined from the 1988 occultation of P8 (Millis, et al., Icarus, 105, 282). The P131.1 occultation was observed from several stations in Hawaii and the western United States (Elliot et al., Nature, in press, 2003). Numerous occultation chords were obtained enabling us to examine Pluto's atmospheric figure. The light curves from the observations were analyzed together in the occultation coordinate system of Elliot et al., (AJ, 106, 2544). The Mauna Kea and Lick datasets straddle the center of Pluto's figure, providing strong constraints on model fits to cross sections of the atmospheric shape. In 1988, Millis (et al., Icarus, 105, 282) did not report any deviation from sphericity in Pluto's atmospheric figure. From the 2002 data, Pluto;s isobars at the radii probed by the occultation ( 1250 km) appear to be distorted from a circular cross-section. Least-squares fits to this cross-section by elliptical models reveal ellipticities in the range 0.05-0.08 although the shape may be more complex than ellipsoidal. The orientation of the distortion appears uncorrelated with Pluto;s rotational axis. Taken at face value, this ellipticity could imply wind speeds of up to twice the sonic speed ( 200 m/s), which would be difficult to explain. Similar distortions have been reported for Triton's atmosphere (Elliot, J. L., et al., Icarus 148, 347). This work has been supported in part by Research Corporation, the Air Force Research Laboratory, NSF, and NASA.

Detection of occult endocervical glandular dysplasia in cervical conization specimens for squamous lesions.

PubMed

Sopracordevole, F; Clemente, N; Alessandrini, L; Di Giuseppe, J; Cigolot, F; Buttignol, M; Ciavattini, A; Canzonieri, V

2017-03-01

The aim of this work was to evaluate the incidence of occult cervical glandular intraepithelial neoplasia (CGIN) and adenocarcinoma of the cervix (AC) in women treated with CO2-laser conization for cervical intraepithelial neoplasia (CIN) or squamocellular cervical cancer (SCC). The medical records of all women with a histological diagnosis of squamous lesions of the uterine cervix (persistent CIN1, CIN2, CIN3 and SCC) who were subsequently treated with CO2-laser conization at our institution, during the period from January 1991 to December 2014, were analyzed in a retrospective case series. Among the 1004 women fulfilling the study inclusion/exclusion criteria, 77 cases (7.7%) of occult glandular lesions (CGIN and AC) were detected on the final cone specimen (48 cases of occult low-grade cervical glandular intraepithelial neoplasia (LCGIN), 25 cases of occult high-grade cervical glandular intraepithelial neoplasia (HCGIN), and four cases of occult "usual-type" AC). No difference in the mean age between women diagnosed with occult glandular lesions and women without occult glandular lesions on the final specimen emerged (39.1±9.3 vs 38.4±9.4, p=0.5). In women with occult LCGIN on cone specimen, mean follow-up of 48 months was reported (range 7-206 months) and no cases of progression to HCGIN or AC were observed. In conclusion, a relatively high rate of occult glandular lesions was found in women treated for squamous lesions. The natural history of CGIN is still uncertain and, in particular, there are some controversies as to whether LCGIN is a precursor lesion of HCGIN or AC. In this context the role of pathologists become very important since the appropriate diagnosis of these lesions could have potential implications in the clinical management of these patients. Copyright © 2017 Elsevier GmbH. All rights reserved.

Hyperleptinemia Exacerbates High-Fat Diet-Mediated Atrial Fibrosis and Fibrillation.

PubMed

Fukui, Akira; Ikebe-Ebata, Yuki; Kondo, Hidekazu; Saito, Shotaro; Aoki, Kohei; Fukunaga, Naoya; Shinohara, Tetsuji; Masaki, Takayuki; Teshima, Yasushi; Takahashi, Naohiko

2017-06-01

Obesity including metabolic syndrome is an independent risk factor of atrial fibrillation (AF). Although hyperleptinemia is usually a characteristic of obese subjects, the relationship with atrial fibrosis and AF is unknown. We tested the hypothesis that high-fat diet (HFD)-induced hyperleptinemia exacerbates atrial fibrosis and AF. Eight-week-old male C57BL/6 (WT) and leptin-deficient ob/ob (Ob) mice were treated with a normal-fat diet (NFD) or 60% HFD. After 8 weeks, transesophageal burst pacing and electrophysiological study using isolated perfused hearts were performed and left atrial (LA) tissues were collected for histological analysis, hydroxyproline assay, and reverse transcription-polymerase chain reaction. HFD treatment increased body weight in both WT and Ob mice compared with NFD (both P < 0.01). In WT-HFD mice, hyperleptinemia was observed as expected. While transesophageal burst pacing invariably induced AF (8/8, 100%) in WT-HFD mice, AF was induced less frequently (1/8, 12.5%) in Ob-HFD mice (P < 0.01). In isolated perfused hearts, the interatrial conduction time was prolonged in WT-HFD mice, but not in Ob-HFD mice (P < 0.05). Masson's trichrome staining and the hydroxyproline assay revealed interstitial LA fibrosis in WT-HFD mice, which was not observed in Ob-HFD mice (P < 0.05). Upregulation of collagen1, collagen3, α-smooth muscle actin, tumor necrosis factor-α, and monocyte chemoattractant protein-1 mRNA levels was noted in WT-HFD mice LA, but attenuated in Ob-HFD mice LA. Our findings suggest that hyperleptinemia exacerbates HFD-mediated atrial fibrosis and AF. Inhibition of leptin signaling may become a novel therapeutic target to prevent obesity-related AF. © 2017 Wiley Periodicals, Inc.

Elucidation of the therapeutic role of mitochondrial biogenesis transducers NRF-1 in the regulation of renal fibrosis

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

Hsieh, Pei-Fang; Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan; Liu, Shu-Fen

Background: Mitochondrial dysfunction is a newly established risk factor for the development of renal fibrosis. Cell survival and injury repair is facilitated by mitochondrial biogenesis. Nuclear respiratory factor 1 (NRF-1) is a transcriptional regulation factor that plays a central role in the regulation of mitochondrial biogenesis. However, the transcription factor of this process in renal fibrosis is unknown. Thus, we hereby discussed the correlations of NRF-1 and renal interstitial fibrosis. Materials and methods: In vitro fibrosis model was established by treatment with transforming growth factor-β1 (TGF-β1) in NRK-49F (Normal Rat kidney fibroblast). We investigated the ROS production, mitochondrial biogenesis andmore » fibrogenic marker (e.q. fibronectin) during the progression of renal fibrosis by kit and Western blotting assay. Here, we used that two distinct mechanisms regulate NRF-1 activation and degradation of NRF-1. NRF-1 was transfect by pcDNA-NRF-1 overexpression gene to evaluate the NRF-1 activity of the therapeutic effect in renal fibrosis. In addition, NRF-1 was silenced by shRNA-NRF-1 to evaluate the significance of NRF-1. ELISA was used to evaluate the secreted fibronectin. Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin, NRF-1). Results: Under renal fibrosis conditions, TGF-β1 (5 ng/ml) increased ROS. Simultaneously, TGF-β1-induced extracellular fibronectin by ELISA assay. In addition, TGF-β1 decreased expression of mitochondrial biogenesis. This is the first time to demonstrate that expression of NRF-1 is significantly decreased in renal fibrosis. However, NRK49F was a transfection with pcDNA-NRF-1 (2 μg/ml) expression vector dramatically reverse TGF-β1-induced cellular fibrosis concomitantly with the suppression of fibronectin (both intracellular and extracellular fibronectin). More importantly, transfection with shRNA-NRF-1 (2 μg/ml) significantly increased the expression of

Elucidation of the therapeutic role of mitochondrial biogenesis transducers NRF-1 in the regulation of renal fibrosis.

PubMed

Hsieh, Pei-Fang; Liu, Shu-Fen; Hung, Tsung-Jen; Hung, Chien-Ya; Liu, Guo-Zheng; Chuang, Lea-Yea; Chen, Mei-Fen; Wang, Jue-Long; Shi, Ming-Der; Hsu, Chen Hung; Shiue, Yow-Ling; Yang, Yu-Lin

2016-11-15

Mitochondrial dysfunction is a newly established risk factor for the development of renal fibrosis. Cell survival and injury repair is facilitated by mitochondrial biogenesis. Nuclear respiratory factor 1 (NRF-1) is a transcriptional regulation factor that plays a central role in the regulation of mitochondrial biogenesis. However, the transcription factor of this process in renal fibrosis is unknown. Thus, we hereby discussed the correlations of NRF-1 and renal interstitial fibrosis. In vitro fibrosis model was established by treatment with transforming growth factor-β1 (TGF-β1) in NRK-49F (Normal Rat kidney fibroblast). We investigated the ROS production, mitochondrial biogenesis and fibrogenic marker (e.q. fibronectin) during the progression of renal fibrosis by kit and Western blotting assay. Here, we used that two distinct mechanisms regulate NRF-1 activation and degradation of NRF-1. NRF-1 was transfect by pcDNA-NRF-1 overexpression gene to evaluate the NRF-1 activity of the therapeutic effect in renal fibrosis. In addition, NRF-1 was silenced by shRNA-NRF-1 to evaluate the significance of NRF-1. ELISA was used to evaluate the secreted fibronectin. Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin, NRF-1). Under renal fibrosis conditions, TGF-β1 (5ng/ml) increased ROS. Simultaneously, TGF-β1-induced extracellular fibronectin by ELISA assay. In addition, TGF-β1 decreased expression of mitochondrial biogenesis. This is the first time to demonstrate that expression of NRF-1 is significantly decreased in renal fibrosis. However, NRK49F was a transfection with pcDNA-NRF-1 (2μg/ml) expression vector dramatically reverse TGF-β1-induced cellular fibrosis concomitantly with the suppression of fibronectin (both intracellular and extracellular fibronectin). More importantly, transfection with shRNA-NRF-1 (2μg/ml) significantly increased the expression of fibronectin of both intercellular and extracellular origins

The diameter of Juno from its occultation of AG + 0 deg 1022

NASA Technical Reports Server (NTRS)

Millis, R. L.; Wasserman, L. H.; Bowell, E.; Franz, O. G.; White, N. M.; Lockwood, G. W.; Nye, R.; Bertram, R.; Klemola, A.; Dunham, E.;

Identification of the first New Zealand case of equine multinodular pulmonary fibrosis.

PubMed

Dunowska, M; Hardcastle, M R; Tonkin, F B

2014-07-01

A 10-year-old polo mare presented with a history of weight loss, poor condition and inappetance. The mare was tachycardic, tachypnoeic and febrile. Harsh lung sounds were auscultated over all lung fields. The mare initially responded to treatment with antibiotics, anti-inflammatory drugs and bronchodilators. Throughout the course of treatment, there was a variable lymphocytosis, monocytosis and fluctuation in concentrations of fibrinogen. The mare also developed a mild anaemia, most likely due to chronic disease. Despite treatment, the mare's condition deteriorated over the following 2 months, and she was subject to euthanasia. On post mortem examination, white to pale tan, large coalescing fibrous nodules up to 5 cm in diameter were found distributed throughout the lungs. Histopathology revealed a multifocally severe interstitial pneumonia with superimposed bronchiolar or alveolar inflammation, fibrosis, Type II pneumocyte hyperplasia and histiocytic intranuclear inclusion bodies, consistent with the findings previously reported for cases of equine multinodular pulmonary fibrosis (EMPF). Equine multinodular pulmonary fibrosis based on characteristic gross and histopathological findings. The diagnosis was strengthened by detection of DNA for equine herpesvirus 5 in the lung tissue. This report describes the first recognised case of EMPF in New Zealand. The affected horse did not respond to treatment and was subject to euthanasia. The prognosis for horses with EMPF, based on a limited number of cases worldwide, is currently considered poor.

Ground Support Network for Operational Radio Occultation Missions

NASA Astrophysics Data System (ADS)

Zandbergen, R.; Enderle, W.; Marquardt, C.; Wollenweber, F.

2012-04-01

The EUMETSAT/ESA Metop/EPS GRAS radio occultation mission stands out for its operational nature. From the beginning, EUMETSAT has decided to rely on an operational system for provision of the auxiliary GPS products that are needed in the occultation processing. This system is the GRAS Ground Support Network (GSN), operated in the Navigation Facility of ESOC in Darmstadt, which was first presented at EGU in 2008. The GRAS GSN is driven primarily by timeliness, availability and accuracy requirements. The performance of the GSN, measured on a monthly basis, has not only consistently met these requirements since the start of its operations, but has also been improved through several system enhancements. Currently, an additional service is being delivered on an experimental basis, consisting of a near-real time Navigation Bit Stream product, which will allow the processing of open-loop data, further increasing the scientific return of the GRAS instrument, or any other radio occultation mission using this data. This paper will present the GRAS GSN in its current configuration, and demonstrate its excellent performance in terms of accuracy, availability and timeliness. The application of the bit stream data will be shown. Some future evolution perspectives of the GRAS GSN will also be addressed. It will be demonstrated that the GRAS GSN has the potential of serving also other present and future radio occultation missions.

Impact of fecal occult blood on obscure gastrointestinal bleeding: Observational study

PubMed Central

Kobayashi, Yuka; Watabe, Hirotsugu; Yamada, Atsuo; Suzuki, Hirobumi; Hirata, Yoshihiro; Yamaji, Yutaka; Yoshida, Haruhiko; Koike, Kazuhiko

2015-01-01

AIM: To elucidate the association between small bowel diseases (SBDs) and positive fecal occult blood test (FOBT) in patients with obscure gastrointestinal bleeding (OGIB). METHODS: Between February 2008 and August 2013, 202 patients with OGIB who performed both capsule endoscopy (CE) and FOBT were enrolled (mean age; 63.6 ± 14.0 years, 118 males, 96 previous overt bleeding, 106 with occult bleeding). All patients underwent immunochemical FOBTs twice prior to CE. Three experienced endoscopists independently reviewed CE videos. All reviews and consensus meeting were conducted without any information on FOBT results. The prevalence of SBDs was compared between patients with positive and negative FOBT. RESULTS: CE revealed SBDs in 72 patients (36%). FOBT was positive in 100 patients (50%) and negative in 102 (50%). The prevalence of SBDs was significantly higher in patients with positive FOBT than those with negative FOBT (46% vs 25%, P = 0.002). In particular, among patients with occult OGIB, the prevalence of SBDs was higher in positive FOBT group than negative FOBT group (45% vs 18%, P = 0.002). On the other hand, among patients with previous overt OGIB, there was no significant difference in the prevalence of SBDs between positive and negative FOBT group (47% vs 33%, P = 0.18). In disease specific analysis among patients with occult OGIB, the prevalence of ulcer and tumor were higher in positive FOBT group than negative FOBT group. In multivariate analysis, only positive FOBT was a predictive factors of SBDs in patients with OGIB (OR = 2.5, 95%CI: 1.4-4.6, P = 0.003). Furthermore, the trend was evident among patients with occult OGIB who underwent FOBT on the same day or a day before CE. The prevalence of SBDs in positive vs negative FOBT group were 54% vs 13% in patients with occult OGIB who underwent FOBT on the same day or the day before CE (P = 0.001), while there was no significant difference between positive and negative FOBT group in those who underwent

Impact of fecal occult blood on obscure gastrointestinal bleeding: observational study.

PubMed

Kobayashi, Yuka; Watabe, Hirotsugu; Yamada, Atsuo; Suzuki, Hirobumi; Hirata, Yoshihiro; Yamaji, Yutaka; Yoshida, Haruhiko; Koike, Kazuhiko

2015-01-07

To elucidate the association between small bowel diseases (SBDs) and positive fecal occult blood test (FOBT) in patients with obscure gastrointestinal bleeding (OGIB). Between February 2008 and August 2013, 202 patients with OGIB who performed both capsule endoscopy (CE) and FOBT were enrolled (mean age; 63.6 ± 14.0 years, 118 males, 96 previous overt bleeding, 106 with occult bleeding). All patients underwent immunochemical FOBTs twice prior to CE. Three experienced endoscopists independently reviewed CE videos. All reviews and consensus meeting were conducted without any information on FOBT results. The prevalence of SBDs was compared between patients with positive and negative FOBT. CE revealed SBDs in 72 patients (36%). FOBT was positive in 100 patients (50%) and negative in 102 (50%). The prevalence of SBDs was significantly higher in patients with positive FOBT than those with negative FOBT (46% vs 25%, P = 0.002). In particular, among patients with occult OGIB, the prevalence of SBDs was higher in positive FOBT group than negative FOBT group (45% vs 18%, P = 0.002). On the other hand, among patients with previous overt OGIB, there was no significant difference in the prevalence of SBDs between positive and negative FOBT group (47% vs 33%, P = 0.18). In disease specific analysis among patients with occult OGIB, the prevalence of ulcer and tumor were higher in positive FOBT group than negative FOBT group. In multivariate analysis, only positive FOBT was a predictive factors of SBDs in patients with OGIB (OR = 2.5, 95%CI: 1.4-4.6, P = 0.003). Furthermore, the trend was evident among patients with occult OGIB who underwent FOBT on the same day or a day before CE. The prevalence of SBDs in positive vs negative FOBT group were 54% vs 13% in patients with occult OGIB who underwent FOBT on the same day or the day before CE (P = 0.001), while there was no significant difference between positive and negative FOBT group in those who underwent FOBT two or more days

Risk Factors Associated with Quantitative Evidence of Lung Emphysema and Fibrosis in an HIV-infected Cohort

PubMed Central

Leader, Joseph K.; Crothers, Kristina; Huang, Laurence; King, Mark A.; Morris, Alison; Thompson, Bruce W.; Flores, Sonia C.; Drummond, M. Bradley; Rom, William N.; Diaz, Philip T.

2015-01-01

Introduction The disease spectrum for HIV-infected individuals has shifted towards co-morbid non-AIDS conditions including chronic lung disease, but quantitative image analysis of lung disease has not been performed. Objectives To quantify the prevalence of structural changes of the lung indicating emphysema or fibrosis on radiographic examination. Methods A cross-sectional analysis of 510 HIV-infected participants in the multi-center Lung-HIV study was performed. Data collected included: demographics, biological markers of HIV, pulmonary function testing, and chest CT examinations. Emphysema and fibrosis-like changes were quantified on CT images based on threshold approaches. Results In our cohort: 69% was on antiretroviral therapy, 13% had a current CD4 cell count less than 200 cells/μL, 39% had an HIV viral load greater than 500 copies/mL, 25% had at least a trace level of emphysema (defined as >2.5% of voxels <-950HU). Trace emphysema was significantly correlated with age, smoking, and pulmonary function. Neither current CD4 cell count nor HIV viral load was significantly correlated with emphysema. Fibrosis-like changes were detected in 29% of the participants and were significantly correlated with HIV viral load (Pearson correlation coefficient = 0.210, p<0.05); current CD4 cell count was not associated with fibrosis. In multivariable analyses including age, race, and smoking status, HIV viral load remained significantly correlated with fibrosis-like changes (coefficient = 0.107, P = 0.03). Conclusion A higher HIV viral load was significantly associated with fibrosis-like changes possibly indicating early interstitial lung disease, but emphysematous changes were not related to current CD4 cell count or HIV viral load. PMID:26914911

Immunophenotypic Alterations in Resident Immune Cells and Myocardial Fibrosis in the Aging Rhesus Macaque (Macaca mulatta) Heart

PubMed Central

Macri, Sheila C.; Bailey, Charles C.; de Oca, Nicole Monts; Silva, Nilsa A.; Rosene, Douglas L.; Mansfield, Keith G.; Miller, Andrew D.

2012-01-01

The rhesus macaque (Macaca mulatta) is used extensively in translational biomedical research and drug development studies and is an important model of aging. Macaques often develop myocardial fibrosis with age which can result in the loss of normal cardiac architecture with the expansion of the extracellular matrix and deposition of collagen. The etiology and pathogenesis of this pernicious process is poorly understood. Cardiac fibrosis was assessed using histologic and immunohistochemical techniques in cardiac tissue sections from 34 rhesus macaques. Overall left ventricular and left ventricular mid-myocardial interstitial/perivascular fibrosis were positively correlated with age (r=0.6522, p<0.0001 and r=0.4704, p=0.005, respectively). When divided into young (mean=2.8 years), middle-aged (mean=17.5 years), and advanced age (mean=29.2 years) groups, immunophenotypic characterization of antigen presenting cells revealed differential expression of CD163 and DC-SIGN between the young and middle-aged groups compared to the advanced age group (p<0.0001). HAM-56 expression decreased significantly in the advanced age cohort (p=0.0021). The expression of CD8, CD163, and DCSIGN correlated positively with age (r=0.3999, p= 0.0191; r=0.5676, p=0.0005; r=0.5245, p=0.0014 respectively). These results show the importance of myocardial fibrosis as a common age-related pathology and additionally, alterations in T cell, macrophage, and dendritic cell phenotype in rhesus macaque myocardium are associated with age but unassociated with the fibrosis. PMID:22328408

Scaled model guidelines for solar coronagraphs' external occulters with an optimized shape.

PubMed

Landini, Federico; Baccani, Cristian; Schweitzer, Hagen; Asoubar, Daniel; Romoli, Marco; Taccola, Matteo; Focardi, Mauro; Pancrazzi, Maurizio; Fineschi, Silvano

2017-12-01

One of the major challenges faced by externally occulted solar coronagraphs is the suppression of the light diffracted by the occulter edge. It is a contribution to the stray light that overwhelms the coronal signal on the focal plane and must be reduced by modifying the geometrical shape of the occulter. There is a rich literature, mostly experimental, on the appropriate choice of the most suitable shape. The problem arises when huge coronagraphs, such as those in formation flight, shall be tested in a laboratory. A recent contribution [Opt. Lett.41, 757 (2016)OPLEDP0146-959210.1364/OL.41.000757] provides the guidelines for scaling the geometry and replicate in the laboratory the flight diffraction pattern as produced by the whole solar disk and a flight occulter but leaves the conclusion on the occulter scale law somehow unjustified. This paper provides the numerical support for validating that conclusion and presents the first-ever simulation of the diffraction behind an occulter with an optimized shape along the optical axis with the solar disk as a source. This paper, together with Opt. Lett.41, 757 (2016)OPLEDP0146-959210.1364/OL.41.000757, aims at constituting a complete guide for scaling the coronagraphs' geometry.

Characterization of the occult nature of injury for frequently occurring motor vehicle crash injuries.

PubMed

Schoell, Samantha L; Doud, Andrea N; Weaver, Ashley A; Talton, Jennifer W; Barnard, Ryan T; Winslow, James E; Stitzel, Joel D

2017-01-01

Occult injuries are not easily detected and can be potentially life-threatening. The purpose of this study was to quantify the perceived occultness of the most frequent motor vehicle crash injuries according to emergency medical services (EMS) professionals. An electronic survey was distributed to 1,125 EMS professionals who were asked to quantify the likelihood that first responders would miss symptoms related to a particular injury on a 5-point Likert scale. The Occult Score for each injury was computed from the average of all the survey responses and normalized to be a continuous metric ranging from 0 to 1 where 0 is a non-occult (highly apparent on initial presentation) injury and 1 is an occult (unapparent on initial presentation) injury. Overall, 110,671 survey responses were collected. The Occult Score ranged from 0 to 1 with a mean, median, and standard deviation of 0.443, 0.450, and 0.233, respectively. When comparing the Occult Score of an injury to its corresponding AIS severity, there was no relationship between the metrics. When stratifying by body region, injury type, and AIS severity, it was evident that AIS 2-4 abdominal injuries with lacerations, hemorrhage, or contusions were perceived as the most occult injuries. Timely triage is key to reduce the morbidity and mortality associated with occult injuries. The Occult Score developed in this study to describe the predictability of an injury in a motor vehicle crash will be used as part of a larger effort, including incorporation into an advanced automatic crash notification (AACN) algorithm to detect crash conditions associated with a patient's need for prompt treatment at a trauma center. Copyright © 2016 Elsevier Ltd. All rights reserved.

Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

PubMed

Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

2017-02-01

Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

Enabling Narrow(est) IWA Coronagraphy with STIS BAR5 and BAR10 Occulters

NASA Astrophysics Data System (ADS)

Schneider, Glenn; Gaspar, Andras; Debes, John; Gull, Theodore; Hines, Dean; Apai, Daniel; Rieke, George

2017-09-01

The Space Telescope Imaging Spectrograph's (STIS) BAR5 coronagraphic occulter was designed to provide high-contrast, visible-light, imaging in close (> 0.15") angular proximity to bright point-sources. We explored and verified the functionality and utility of the BAR5 occulter. We also investigated, and herein report on, the use of the BAR10 rounded corners as narrow-angle occulters and compare IWA vs. contrast performance for the BAR5, BAR10, and Wedge occulters. With that, we provide recommendations for the most efficacious BAR5 and BAR10 use on-orbit in support of GO science.

Rare Variants in RTEL1 Are Associated with Familial Interstitial Pneumonia

PubMed Central

Cogan, Joy D.; Zhao, Min; Mitchell, Daphne B.; Rives, Lynette; Markin, Cheryl; Garnett, Errine T.; Montgomery, Keri H.; Mason, Wendi R.; McKean, David F.; Powers, Julia; Murphy, Elissa; Olson, Lana M.; Choi, Leena; Cheng, Dong-Sheng; Blue, Elizabeth Marchani; Young, Lisa R.; Lancaster, Lisa H.; Steele, Mark P.; Brown, Kevin K.; Schwarz, Marvin I.; Fingerlin, Tasha E.; Schwartz, David A.; Lawson, William E.; Loyd, James E.; Zhao, Zhongming; Phillips, John A.; Blackwell, Timothy S.

2015-01-01

Rationale: Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families. Objectives: To determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of affected members from FIP families, providing additional insights into disease pathogenesis. Methods: Affected subjects from 25 kindreds were selected from an ongoing FIP registry for whole-exome sequencing from genomic DNA. Candidate rare variants were confirmed by Sanger sequencing, and cosegregation analysis was performed in families, followed by additional sequencing of affected individuals from another 163 kindreds. Measurements and Main Results: We identified a potentially damaging rare variant in the gene encoding for regulator of telomere elongation helicase 1 (RTEL1) that segregated with disease and was associated with very short telomeres in peripheral blood mononuclear cells in 1 of 25 families in our original whole-exome sequencing cohort. Evaluation of affected individuals in 163 additional kindreds revealed another eight families (4.7%) with heterozygous rare variants in RTEL1 that segregated with clinical FIP. Probands and unaffected carriers of these rare variants had short telomeres (<10% for age) in peripheral blood mononuclear cells and increased T-circle formation, suggesting impaired RTEL1 function. Conclusions: Rare loss-of-function variants in RTEL1 represent a newly defined genetic predisposition for FIP, supporting the importance of telomere-related pathways in pulmonary fibrosis. PMID:25607374

Rare variants in RTEL1 are associated with familial interstitial pneumonia.

PubMed

Cogan, Joy D; Kropski, Jonathan A; Zhao, Min; Mitchell, Daphne B; Rives, Lynette; Markin, Cheryl; Garnett, Errine T; Montgomery, Keri H; Mason, Wendi R; McKean, David F; Powers, Julia; Murphy, Elissa; Olson, Lana M; Choi, Leena; Cheng, Dong-Sheng; Blue, Elizabeth Marchani; Young, Lisa R; Lancaster, Lisa H; Steele, Mark P; Brown, Kevin K; Schwarz, Marvin I; Fingerlin, Tasha E; Schwartz, David A; Lawson, William E; Loyd, James E; Zhao, Zhongming; Phillips, John A; Blackwell, Timothy S

2015-03-15

Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families. To determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of affected members from FIP families, providing additional insights into disease pathogenesis. Affected subjects from 25 kindreds were selected from an ongoing FIP registry for whole-exome sequencing from genomic DNA. Candidate rare variants were confirmed by Sanger sequencing, and cosegregation analysis was performed in families, followed by additional sequencing of affected individuals from another 163 kindreds. We identified a potentially damaging rare variant in the gene encoding for regulator of telomere elongation helicase 1 (RTEL1) that segregated with disease and was associated with very short telomeres in peripheral blood mononuclear cells in 1 of 25 families in our original whole-exome sequencing cohort. Evaluation of affected individuals in 163 additional kindreds revealed another eight families (4.7%) with heterozygous rare variants in RTEL1 that segregated with clinical FIP. Probands and unaffected carriers of these rare variants had short telomeres (<10% for age) in peripheral blood mononuclear cells and increased T-circle formation, suggesting impaired RTEL1 function. Rare loss-of-function variants in RTEL1 represent a newly defined genetic predisposition for FIP, supporting the importance of telomere-related pathways in pulmonary fibrosis.

Occult Klebsiella pneumoniae bacteremia at emergency department: A single center experience.

PubMed

Chang, Eileen Kevyn; Kao, Kai-Liang; Tsai, Mao-Song; Yang, Chia-Jui; Huang, Yu-Tsung; Liu, Chia-Ying; Liao, Chun-Hsing

2015-12-01

Patients with undetected bacteremia when discharged from a hospital are considered to have occult bacteremia. Klebsiella pneumoniae bacteremia (KPB) is endemic to Taiwan. Our purpose was to study the impact of occult KPB. We retrospectively reviewed the records of patients who were discharged from our emergency department (ED) and subsequently diagnosed with KPB (occult bacteremia), from January 2008 to March 2014. All patients are followed for at least 3 months after the index ED visit. The study group was compared to KPB patients who were directly hospitalized (DH) from ED in 2008. Thirty-day mortality was the primary endpoint. A total of 913 patients were admitted to our ED with KPB, and 88 of these patients (9.6%) had occult KPB. Among them, 43 had second ED visit and 41 were admitted. The overall 30-day mortality was 2.3%. Relative to patients with occult KPB, DH patients had more respiratory tract infections (p < 0.001) but fewer other intra-abdominal infections (p = 0.015). Liver abscess was the major diagnosis for the second ED visit (37.2%). DH patients had significantly greater 30-day mortality than that of overall patients with KPB (19.2% vs.2.3%, p < 0.001). Most patients with occult KPB had favorable outcomes, but about half of them required a second ED visit. Clinicians should aggressively follow patients with occult KPB and should seek to identify the focus of infection in this endemic area. Copyright © 2015. Published by Elsevier B.V.

Occult HBV infection in HIV-infected adults and evaluation of pooled NAT for HBV.

PubMed

Dinesha, T R; Boobalan, J; Sivamalar, S; Subashini, D; Solomon, S S; Murugavel, K G; Balakrishnan, P; Smith, D M; Saravanan, S

2018-06-01

The study aimed to determine the prevalence of occult hepatitis B virus infection among HIV-infected persons and to evaluate the use of a pooling strategy to detect occult HBV infection in the setting of HIV infection. Five hundred and two HIV-positive individuals were tested for HBV, occult HBV and hepatitis C and D with serologic and nucleic acid testing (NAT). We also evaluated a pooled NAT strategy for screening occult HBV infection among the HIV-positive individuals. The prevalence of HBV infection among HIV-positive individuals was 32 (6.4%), and occult HBV prevalence was 10%. The pooling HBV NAT had a sensitivity of 66.7% and specificity of 100%, compared to HBV DNA NAT of individual samples. In conclusion, this study found a high prevalence of occult HBV infection among our HIV-infected population. We also demonstrated that pooled HBV NAT is highly specific, moderately sensitive and cost-effective. As conventional HBV viral load assays are expensive in resource-limited settings such as India, pooled HBV DNA NAT might be a good way for detecting occult HBV infection and will reduce HBV-associated complications. © 2018 John Wiley & Sons Ltd.

David Levy's Guide to Eclipses, Transits, and Occultations

NASA Astrophysics Data System (ADS)

Levy, David H.

2010-08-01

Introduction; Part I. The Magic and History of Eclipses: 1. Shakespeare, King Lear, and the Great Eclipse of 1605; 2. Three centuries later: Einstein, relativity, and the solar eclipse of 1919; 3. What causes solar and lunar eclipses; Part II. Observing Solar Eclipses: 4. Safety considerations; 5. What to expect during a partial eclipse; 6. Annular eclipses and what to see in them; 7. Total eclipse of the Sun: introduction to the magic; 8. The onset: temperature drop, Baily's Beads, Diamond Ring; 9. Totality: Corona, Prominences, Chromosphere, and surrounding area; 10. Photographing and imaging a solar eclipse; Part III. Observing Lunar Eclipses: 11. Don't forget the penumbral eclipses!; 12. Partial lunar eclipses; 13. Total lunar eclipses; 14. Photographing and imaging lunar eclipses; Part IV. Occultations: 15. When the Moon occults a star; Part V. Transits: 16. When planets cross the Sun; Part VI. My Favorite Eclipses: 17. A personal canon of eclipses, occultations, and transits I have seen; Appendices; Index.

Occult traumatic hemothorax: when can sleeping dogs lie?

PubMed

Bilello, John F; Davis, James W; Lemaster, Deborah M

2005-12-01

Size of traumatic occult hemothorax on admission requiring drainage has not been defined. Computed axial tomography (CAT) may guide drainage criteria. A retrospective review of patients with hemothoraces on CAT was performed. Extrapolating previously described methods of pleural fluid measurement, hemothoraces were quantified using the fluid stripe in the dependent pleural "gutter." Data included patient age, injury severity, and intervention (thoracentesis or tube thoracostomy). Seventy-eight patients with 99 occult hemothoraces met the criteria for study inclusion: 52 hemothoraces qualified as "minimal" and 47 as "moderate/large." Eight patients (15%) in the minimal group and 31 patients (66%) in the moderate/large group underwent intervention (P < .001). There was no difference in patient age, injury severity, ventilator requirement, or presence of pulmonary contusion. CAT in stable blunt-trauma patients can predict which patients with occult hemothorax are likely to undergo intervention. Patients with hemothorax > or = 1.5 cm on CAT were 4 times more likely to undergo drainage intervention compared with those having hemothorax < 1.5 cm.

Consensus document for the diagnosis and treatment of idiopathic pulmonary fibrosis: Joint Consensus of Sociedade Portuguesa de Pneumologia, Sociedade Portuguesa de Radiologia e Medicina Nuclear e Sociedade Portuguesa de Anatomia Patológica.

PubMed

Robalo Cordeiro, C; Campos, P; Carvalho, L; Campainha, S; Clemente, S; Figueiredo, L; Jesus, J M; Marques, A; Souto-Moura, C; Pinto Basto, R; Ribeiro, A; Serrado, M; Morais, A

2016-01-01

Idiopathic pulmonary fibrosis is a rare interstitial lung disease included in the Idiopathic Interstitial Pneumonias group. Although several potential risk factors have been described, it is a progressive fibrosing disease of unknown cause affecting mainly adults over 50 years and associated with a poor prognosis, reflected in a median survival of 2-3 years after diagnosis. The concept of a multidisciplinary working group for the diagnosis of idiopathic pulmonary fibrosis is based on the need to have experienced pulmonologists, radiologists and pathologists in the evaluation and correct treatment of the disease, and requires the use of all available data about individual patients, standardized (largely through High Resolution Computed Tomography and pathology when needed) as well as non-standardized data (laboratory, serology and biomarkers). This approach helps to increase diagnostic accuracy and is an internationally accepted recommendation. In regard to therapy, the situation has changed radically since the publication of the ATS/ERS/JRS/ALAT 2011 guidelines on the diagnosis and management of idiopathic pulmonary fibrosis where it was stressed that no proven therapy exists for this disease. Currently besides non-pharmacological treatment, therapy of complications and comorbidities and palliative care, nintedanib and pirfenidone, two compounds with pleiotropic mechanisms of action, are to date, the two drugs with confirmed efficacy in slowing functional decline and disease progression in idiopathic pulmonary fibrosis patients. Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

Idiopathic pulmonary fibrosis in a Christmas Island nuclear test veteran

PubMed Central

Parfrey, H; Babar, J; Fiddler, CA; Chilvers, ER

2010-01-01

We describe the case of a 71-year-old man with idiopathic pulmonary fibrosis (usual interstitial pneumonia (UIP) pattern) diagnosed on clinical, radiological and lung function criteria, in accordance with the American Thoracic Society/European Respiratory Society consensus criteria (2000), who had been in close proximity to three atmospheric nuclear bomb blasts during military service in 1957. He does not have clubbing and clinically and radiologically his lung disease is stable. He also has bladder carcinoma and carotid arteriosclerosis, both recognised consequences of radiation injury. This is the first reported case of UIP in a nuclear test veteran. Awareness of this potential association is important given the current attempts of the British Nuclear Test Veterans Association to gain compensation for claimed injuries. PMID:22797205

αvβ6 Integrin Regulates Renal Fibrosis and Inflammation in Alport Mouse

PubMed Central

Hahm, Kyungmin; Lukashev, Matvey E.; Luo, Yi; Yang, William J.; Dolinski, Brian M.; Weinreb, Paul H.; Simon, Kenneth J.; Chun Wang, Li; Leone, Diane R.; Lobb, Roy R.; McCrann, Donald J.; Allaire, Normand E.; Horan, Gerald S.; Fogo, Agnes; Kalluri, Raghu; Shield, Charles F.; Sheppard, Dean; Gardner, Humphrey A.; Violette, Shelia M.

2007-01-01

The transforming growth factor (TGF)-β-inducible integrin αvβ6 is preferentially expressed at sites of epithelial remodeling and has been shown to bind and activate latent precursor TGF-β. Herein, we show that αvβ6 is overexpressed in human kidney epithelium in membranous glomerulonephritis, diabetes mellitus, IgA nephropathy, Goodpasture’s syndrome, and Alport syndrome renal epithelium. To assess the potential regulatory role of αvβ6 in renal disease, we studied the effects of function-blocking αvβ6 monoclonal antibodies (mAbs) and genetic ablation of the β6 subunit on kidney fibrosis in Col4A3−/− mice, a mouse model of Alport syndrome. Expression of αvβ6 in Alport mouse kidneys was observed primarily in cortical tubular epithelial cells and in correlation with the progression of fibrosis. Treatment with αvβ6-blocking mAbs inhibited accumulation of activated fibroblasts and deposition of interstitial collagen matrix. Similar inhibition of renal fibrosis was observed in β6-deficient Alport mice. Transcript profiling of kidney tissues showed that αvβ6-blocking mAbs significantly inhibited disease-associated changes in expression of fibrotic and inflammatory mediators. Similar patterns of transcript modulation were produced with recombinant soluble TGF-β RII treatment, suggesting shared regulatory functions of αvβ6 and TGF-β. These findings demonstrate that αvβ6 can contribute to the regulation of renal fibrosis and suggest this integrin as a potential therapeutic target. PMID:17200187

Sensing Water Vapon via Spacecraft Radio Occultation Observations

NASA Technical Reports Server (NTRS)

Kursinski, E. Robert; Hajj, George A.

2000-01-01

The radio occultation technique has been used to characterize planetary atmospheres since the 1960's spanning atmospheric pressures from 16 microbars to several bars. In 1988, the use of GPS signals to make occultation observations of Earth's atmosphere was realized by Tom Yunck and Gunnar Lindal at JPL. In the GPS to low-Earth-orbiter limb- viewing occultation geometry, Fresnel diffraction yield a unique combination of high vertical resolution of 100 m to 1 km at long wavelengths (approx. 20 cm) insensitive to particulate scattering which allows routine limb sounding from the lower mesosphere through the troposphere. A single orbiting GPS/GLONASS receiver can observe - 1000 to 1400 daily occultations providing as many daily, high vertical resolution soundings as the present global radiosonde network, but with far more evenly distributed, global coverage. The occultations yield profiles of refractivity as a function of height. In the cold, dry conditions of the upper troposphere and above (T less than 240 K), profiles of density, pressure (geopotential), and temperature can be derived. Given additional temperature information, water vapor can be derived in the midddle and lower troposphere with a unique combination of vertical resolution, global distribution and insensitivity to clouds and precipitation to an accuracy of approx. 0.2 g/kg. At low latitudes, moisture profiles will be accurate to 1-5% within the convective boundary layer and better than 20% below 6 to 7 km. Accuracies of climatological averages should be approx. 0. 1 g/kg limited by the biases in the temperature estimates. To use refractivity to constrain water vapor, knowledge of temperature is required. The simplest approach is to use the temperature field from an analysis such as the 6 hour ECMWF global analysis interpolated to the locations of each occultation. A better approach is to combine the temperature and moisture fields from such an analysis with the occultation refractivity in a weighting

Recovery from manual metal arc-stainless steel welding-fume exposure induced lung fibrosis in Sprague-Dawley rats.

PubMed

Yu, Il Je; Song, Kyung Seuk; Chang, Hee Kyung; Han, Jeong Hee; Chung, Yong Hyun; Han, Kuy Tae; Chung, Kyu Hyuck; Chung, Ho Keun

2003-08-28

Welders with radiographic pneumoconiosis abnormalities have exhibited a gradual clearing of the X-ray identified effects following removal from exposure. In some cases, the pulmonary fibrosis associated with welding fumes appears in a more severe form in welders. Accordingly, to investigate the disease and recovery process of pneumoconiosis induced by welding-fume exposure, rats were exposed to welding fumes with concentrations of 63.6+/-4.1 mg/m(3) (low dose) and 107.1+/-6.3 mg/m(3) (high dose) of total suspended particulate for 2 h per day in an inhalation chamber for a total of 2 h or 15, 30, 60 or 90 days. Thereafter, the rats were no longer exposed and allowed to recover from the welding fume-induced lung fibrosis for 90 days. When compared to the unexposed control group, the lung weights significantly increased in both the low- and high-dose rats from day 15 to 90. A histopathological examination combined with fibrosis-specific staining revealed that the lungs from the low-dose rats did not exhibit any significant progressive fibrotic changes. Whereas, the lungs from the high-dose rats exhibited early delicate fibrosis from day 15, which progressed into the perivascular and peribronchiolar regions by day 30. Interstitial fibrosis appeared at day 60 and became prominent by day 90, along with the additional appearance of pleural fibrosis. Recovery, evaluated based on the body and lung weights and a histopathological examination, was observed in both the high and low-dose rats that were exposed up to 30 days. The rats exposed for 60-90 days at the low dose also recovered from the fibrosis, yet the rats exposed for 60-90 days at the high dose did not fully recover. Consequently, recovery from pneumoconiosis induced by welding-fume exposure was observed when the degree of exposure was short-term and moderate.

Idiopathic Pulmonary Fibrosis and Myasthenia Gravis: An Unusual Association

PubMed Central

Chogtu, Bharti; Malik, Daliparty Vasudev

2016-01-01

Idiopathic Pulmonary Fibrosis (IPF) is a chronic fibrosing lung condition with high morbidity and mortality, accounting for about 25% of the cases of interstitial lung diseases. It usually has a progressive course resulting in death due to respiratory failure. Myasthenia Gravis (MG) is an autoimmune neuromuscular disease, caused by antibody mediated activity against acetylcholine receptor at the neuromuscular junction. It is characterized by fluctuating muscle weakness and fatigue. Extensive literature search did not reveal any case report of an association between these two conditions. Here we present a case of a patient with IPF who also developed MG. The diagnosis of IPF was based on High Resolution Computed Tomography (HRCT) of the lung and that of MG was based on clinical criteria and electrophysiological testing. The case was successfully managed. PMID:27190866

Occult Nodal Disease Prevalence and Distribution in Recurrent Laryngeal Cancer Requiring Salvage Laryngectomy.

PubMed

Birkeland, Andrew C; Rosko, Andrew J; Issa, Mohamad R; Shuman, Andrew G; Prince, Mark E; Wolf, Gregory T; Bradford, Carol R; McHugh, Jonathan B; Brenner, J Chad; Spector, Matthew E

2016-03-01

The indications for neck dissection concurrent with salvage laryngectomy in the clinically N0 setting remain unclear. Our goals were to determine the prevalence of occult nodal disease, analyze nodal disease distribution patterns, and identify predictors of occult nodal disease in a salvage laryngectomy cohort. Case series with planned data collection. Tertiary academic center. Patients with persistent or recurrent laryngeal squamous cell carcinoma (LSCC) after radiation/chemoradiation failure undergoing salvage laryngectomy with neck dissection. We analyzed a single-institution retrospective case series of patients between 1997 and 2014 and identified those who had clinically N0 (cN0) necks (n = 203). Clinical and pathologic data, including nodal prevalence and distribution, were collected and statistical analyses performed. Overall, cN0 necks had histologically positive occult nodes in 17% (n = 35) of cases. Univariate predictors of occult nodal positivity included recurrent T4 stage (34% T4 vs 12% non-T4; P = .0003) and supraglottic subsite (28% supraglottic vs 10% nonsupraglottic; P = .0006). Histologically positive nodes associated with supraglottic primaries were most frequently positive in ipsilateral levels II and III (17% and 16%). Positive nodes for glottic LSCC were most frequently positive in the ipsilateral and contralateral paratracheal nodes (11% and 9%). Histologically positive occult nodes are identified in 17% of cN0 patients undergoing salvage laryngectomy with neck dissection. Occult nodal disease varies in frequency and distribution based on tumor subsite. Predictors of high (>20%) occult nodal positivity include T4 tumors and supraglottic subsite. In glottic LSCC, the most frequent sites of occult nodal disease are the paratracheal nodal basins. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Biopsy of CT-Occult Bone Lesions Using Anatomic Landmarks for CT Guidance.

PubMed

Hillen, Travis J; Talbert, Robert J; Friedman, Michael V; Long, Jeremiah R; Jennings, Jack W; Wessell, Daniel E; Baker, Jonathan C

2017-07-01

The purpose of this study is to evaluate the histopathologic diagnostic yield, sample size, procedural time, and dose-length product (DLP) for the biopsy of CT-occult lesions found at MRI or PET or both. A retrospective review of our radiology information system for biopsies of CT-occult lesions using CT guidance from January 1, 2010, through December 31, 2014, was performed and compared with a selection of CT-guided biopsies of CT-evident bone lesions during the same period. The data were then evaluated for diagnostic yield of histopathologic diagnosis, procedural time, use of sedation medication, DLP, and size of specimens obtained. A total of 30 CT-occult biopsies met the inclusion criteria. Twenty-seven of those biopsies had results that were concordant with the patient's primary histopathologic diagnosis, imaging findings, and clinical course. In the CT-evident lesion group, concordant histopathologic abnormalities were identified in 27 of 30 patients. There was a statistically significant increase in number of samples obtained for the CT-evident lesions compared with CT-occult lesions. There was no statistically significant difference in total specimen length, DLP, number of CT scans, procedural time, or use of sedation medication between the CT-occult and CT-evident biopsy groups. Biopsy of CT-occult lesions using anatomic landmarks achieves diagnostic yields similar to those for CT-guided biopsy of CT-evident lesions.

Laboratory Verification of Occulter Contrast Performance and Formation Flight

NASA Astrophysics Data System (ADS)

Sirbu, Dan

2014-01-01

Direct imaging of an exo-Earth is a difficult technical challenge. First, the intensity ratio between the parent star and its dim, rocky planetary companion is expected to be ten billion times. Additionally, for a planetary companion in the habitable zone the angular separation to the star is very small, such that only nearby stars are feasible targets. An external occulter is a spacecraft that is flown in formation with the observing space telescope and blocks starlight prior to the entrance pupil. Its shape must be specially designed to control for diffraction and be tolerant of errors such as misalignment, manufacturing, and deformations. In this dissertation, we present laboratory results pertaining to the optical verification of the contrast performance of a scaled occulter and implementation of an algorithm for the alignment of the telescope in the shadow of the occulter. The experimental testbed is scaled from space dimensions to the laboratory by maintaining constant Fresnel numbers while preserving an identical diffraction integral. We present monochromatic results in the image plane showing contrast better than 10 orders of magnitude, consistent with the level required for imaging an Exo-earth, and obtained using an optimized occulter shape. We compare these results to a baseline case using a circular occulter and to the theoretical predictions. Additionally, we address the principal technical challenge in the formation flight problem through demonstration of an alignment algorithm that is based on out-of-band leaked light. Such leaked light can be used a map to estimate the location of the telescope in the shadow and perform fine alignment during science observations.

Cystic fibrosis - resources

MedlinePlus

Resources - cystic fibrosis ... The following organizations are good resources for information on cystic fibrosis : Cystic Fibrosis Foundation -- www.cff.org March of Dimes -- www.marchofdimes.org/baby/cystic-fibrosis-and- ...

Occurrence of occult CSF leaks during standard FESS procedures.

PubMed

Bucher, S; Kugler, A; Probst, E; Epprecht, L; Stadler, R S; Holzmann, D; Soyka, M B

2018-03-18

To determine the incidence of occult cerebrospinal fluid leaks (CSF) after functional endoscopic sinus surgery (FESS) and to evaluate the diagnostic performance of beta2-transferrin in blood-contaminated conditions. Prospective cohort study. An analysis of 57 intraoperative samples using hydrogel 6 beta2-transferrin assay after FESS was undertaken. In case of CSF positive samples and continuing rhinorrhea, reanalysis after more than 1 year was conducted. In-vivo analysis of a primary spontaneous CSF leak sample took place to verify difficulties in detecting beta2-transferrin in blood-contaminated settings. Own titrations were performed to evaluate detection limits of CSF by beta2-transferrin and beta-trace protein assays in these settings. An incidence of 13% for occult CSF leaks after FESS was found. In blood-contaminated conditions, routine beta2-transferrin assays showed low sensitivity. In over 1 year follow-up, all samples were negative for CSF and none of them developed clinical relevant CSF leaks or meningitis. Occult and clinically irrelevant CSF leaks do occur in a significant proportion of patients during and shortly after FESS. Intra- and postoperatively, routine beta2-transferrin assays show low sensitivity. They should not be used in these settings. The clinical course of patients with occult CSF leaks indicated possibility of an uneventful follow-up.

Occupational risks for idiopathic pulmonary fibrosis mortality in the United States.

PubMed

Pinheiro, Germania A; Antao, Vinicius C; Wood, John M; Wassell, James T

2008-01-01

Metal and wood dust exposures have been identified as possible occupational risk factors for idiopathic pulmonary fibrosis (IPF). We analyzed mortality data using ICD-10 code J84.1--"Other interstitial pulmonary diseases with fibrosis," derived age-adjusted mortality rates for 1999-2003, and assessed occupational risks for 1999, by calculating proportionate mortality ratios (PMRs) and mortality odds ratios (MORs) using a matched case-control approach. We identified 84,010 IPF deaths, with an age-adjusted mortality rate of 75.7 deaths/million. Mortality rates were highest among males, whites, and those aged 85 and older. Three industry categories with potential occupational exposures recognized as risk factors for IPF were identified: "Wood buildings and mobile homes" (PMR = 4.5, 95% confidence interval (CI) 1.2-11.6 and MOR = 5.3, 95% CI 1.2-23.8), "Metal mining" (PMR = 2.4, 95% CI 1.3-4.0 and MOR = 2.2, 95% CI 1.1-4.4), and "Fabricated structural metal products" (PMR = 1.9, 95% CI 1.1-3.1 and MOR = 1.7, 95% CI 1.0-3.1). Workers in these industry categories may benefit from toxicological studies and improved surveillance for this disease.

Calculated occultation profiles of Io and the hot spots

NASA Technical Reports Server (NTRS)

Mcewen, A. S.; Soderblom, L. A.; Matson, D. L.; Johnson, T. V.; Lunine, J. I.

1986-01-01

Occultations of Io by other Galilean satellites in 1985 provide a means to locate volcanic hot spots and to model their temperatures. The expected time variations in the integral reflected and emitted radiation of the occultations are computed as a function of wavelength (visual to 8.7 microns). The best current ephemerides were used to calculate the geometry of each event as viewed from earth. Visual reflectances were modeled from global mosaics of Io. Thermal emission from the hot spots was calculated from Voyager 1 IRIS observations and, for regions unobserved by IRIS, from a model based on the distribution of low-albedo features. The occultations may help determine (1) the location and temperature distribution of Loki; (2) the source(s) of excess emission in the region from long 50 deg to 200 deg and (3) the distribution of small, high-temperature sources.

Deep Proteome Profiling Reveals Common Prevalence of MZB1-Positive Plasma B Cells in Human Lung and Skin Fibrosis.

PubMed

Schiller, Herbert B; Mayr, Christoph H; Leuschner, Gabriela; Strunz, Maximilian; Staab-Weijnitz, Claudia; Preisendörfer, Stefan; Eckes, Beate; Moinzadeh, Pia; Krieg, Thomas; Schwartz, David A; Hatz, Rudolf A; Behr, Jürgen; Mann, Matthias; Eickelberg, Oliver

2017-11-15

Analyzing the molecular heterogeneity of different forms of organ fibrosis may reveal common and specific factors and thus identify potential future therapeutic targets. We sought to use proteome-wide profiling of human tissue fibrosis to (1) identify common and specific signatures across end-stage interstitial lung disease (ILD) cases, (2) characterize ILD subgroups in an unbiased fashion, and (3) identify common and specific features of lung and skin fibrosis. We collected samples of ILD tissue (n = 45) and healthy donor control samples (n = 10), as well as fibrotic skin lesions from localized scleroderma and uninvolved skin (n = 6). Samples were profiled by quantitative label-free mass spectrometry, Western blotting, or confocal imaging. We determined the abundance of more than 7,900 proteins and stratified these proteins according to their detergent solubility profiles. Common protein regulations across all ILD cases, as well as distinct ILD subsets, were observed. Proteomic comparison of lung and skin fibrosis identified a common upregulation of marginal zone B- and B1-cell-specific protein (MZB1), the expression of which identified MZB1 + /CD38 + /CD138 + /CD27 + /CD45 - /CD20 - plasma B cells in fibrotic lung and skin tissue. MZB1 levels correlated positively with tissue IgG and negatively with diffusing capacity of the lung for carbon monoxide. Despite the presumably high molecular and cellular heterogeneity of ILD, common protein regulations are observed, even across organ boundaries. The surprisingly high prevalence of MZB1-positive plasma B cells in tissue fibrosis warrants future investigations regarding the causative role of antibody-mediated autoimmunity in idiopathic cases of organ fibrosis, such as idiopathic pulmonary fibrosis.

Optimization of the occulter for the Solar Orbiter/METIS coronagraph

NASA Astrophysics Data System (ADS)

Landini, Federico; Vivès, Sébastien; Romoli, Marco; Guillon, Christophe; Pancrazzi, Maurizio; Escolle, Clement; Focardi, Mauro; Antonucci, Ester; Fineschi, Silvano; Naletto, Giampiero; Nicolini, Gianalfredo; Nicolosi, Piergiorgio; Spadaro, Daniele

2012-09-01

METIS (Multi Element Telescope for Imaging and Spectroscopy investigation), selected to fly aboard the Solar Orbiter ESA/NASA mission, is conceived to perform imaging (in visible, UV and EUV) and spectroscopy (in EUV) of the solar corona, by means of an integrated instrument suite located on a single optical bench and sharing the same aperture on the satellite heat shield. As every coronagraph, METIS is highly demanding in terms of stray light suppression. Coronagraphs history teaches that a particular attention must be dedicated to the occulter optimization. The METIS occulting system is of particular interest due to its innovative concept. In order to meet the strict thermal requirements of Solar Orbiter, METIS optical design has been optimized by moving the entrance pupil at the level of the external occulter on the S/C thermal shield, thus reducing the size of the external aperture. The scheme is based on an inverted external-occulter (IEO). The IEO consists of a circular aperture on the Solar Orbiter thermal shield. A spherical mirror rejects back the disk-light through the IEO. A breadboard of the occulting assembly (BOA) has been manufactured in order to perform stray light tests in front of two solar simulators (in Marseille, France and in Torino, Italy). A first measurement campaign has been carried on at the Laboratoire d'Astrophysique de Marseille. In this paper we describe the BOA design, the laboratory set-up and the preliminary results.

Chylothorax in dermatomyositis complicated with interstitial pneumonia.

PubMed

Isoda, Kentaro; Kiboshi, Takao; Shoda, Takeshi

2017-04-01

Chylothorax is a disease in which chyle leaks and accumulates in the thoracic cavity. Interstitial pneumonia and pneumomediastinum are common thoracic manifestations of dermatomyositis, but chylothorax complicated with dermatomyositis is not reported. We report a case of dermatomyositis with interstitial pneumonia complicated by chylothorax. A 77-year-old woman was diagnosed as dermatomyositis with Gottron's papules, skin ulcers, anti-MDA5 antibody and rapid progressive interstitial pneumonia. Treatment with betamethasone, tacrolimus and intravenous high-dose cyclophosphamide was initiated, and her skin symptoms and interstitial pneumonia improved once. However, right-sided chylothorax began to accumulate and gradually increase, and at the same time, her interstitial pneumonia began to exacerbate, and skin ulcers began to reappear on her fingers and auricles. Although her chylothorax improved by fasting and parenteral nutrition, she died due to further exacerbations of dermatomyositis and interstitial pneumonia in spite of steroid pulse therapy, increase in the betamethasone dosage, additional intravenous high-dose cyclophosphamide and plasma pheresis. An autopsy showed no lesions such as malignant tumors in the thoracic cavity. This is the first report of chylothorax complicated by dermatomyositis with interstitial pneumonia.

Interstitial lung disease in an adult with Fanconi anemia: Clues to the pathogenesis

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

Rubinstein, W.S.; Wenger, S.L.; Hoffman, R.M.

1997-03-31

We have studied a 38-year-old man with a prior diagnosis of Holt-Oram syndrome, who presented with diabetes mellitus. He had recently taken prednisone for idiopathic interstitial lung disease and trimethoprim-sulfamethoxazole for sinusitis. Thrombocytopenia progressed to pancytopenia. The patient had skeletal, cardiac, renal, cutaneous, endocrine, hepatic, neurologic, and hematologic manifestations of Fanconi anemia (FA). Chest radiographs showed increased interstitial markings at age 25, dyspnea began in his late 20s, and he stopped smoking at age 32. At age 38, computerized tomography showed bilateral upper lobe fibrosis, lower lobe honeycombing, and bronchiectasis. Pulmonary function tests, compromised at age 29, showed a moderatelymore » severe obstructive and restrictive pattern by age 38. Serum alpha-1 antitrypsin level was 224 (normal 85-213) mg/dL and PI phenotype was M1. Karyotype was 46,X-Y with a marked increase in chromosome aberrations induced in vitro by diepoxybutane. The early onset and degree of pulmonary disease in this patient cannot be fully explained by environmental or known genetic causes. The International Fanconi Anemia Registry (IFAR) contains no example of a similar pulmonary presentation. Gene-environment (ecogenetic) interactions in FA seem evident in the final phenotype. The pathogenic mechanism of lung involvement in FA may relate to oxidative injury and cytokine anomalies. 49 refs., 2 figs., 1 tab.« less

Interstitial pneumonitis and the risk of chronic allograft rejection in lung transplant recipients.

PubMed

Mihalek, Andrew D; Rosas, Ivan O; Padera, Robert F; Fuhlbrigge, Anne L; Hunninghake, Gary M; DeMeo, Dawn L; Camp, Phillip C; Goldberg, Hilary J

2013-05-01

The presence of interstitial pneumonitis (IP) on surveillance lung biopsy specimens in lung transplant recipients is poorly described, and its impact on posttransplant outcomes is not established. The following study assessed the association of posttransplant IP with the development of bronchiolitis obliterans syndrome (BOS). We examined all recipients of primary cadaveric lung transplants at our institution between January 1, 2000, and December 31, 2007 (N = 145). Patients had bronchoscopies with BAL, and transbronchial biopsies performed for surveillance during posttransplant months 1, 3, 6, and 12 as well as when clinically indicated. Patients were given a diagnosis of IP if, in the absence of active infection and organizing pneumonia, they showed evidence of interstitial inflammation and fibrosis on two or more biopsy specimens. IP was a significant predictor of BOS (OR, 7.84; 95% CI, 2.84-21.67; P < .0001) and was significantly associated with time to development of BOS (hazard ratio, 3.8; 95% CI, 1.93-7.39; P = .0001) within the first 6 years posttransplant. The presence of IP did not correlate with a significantly higher risk of mortality or time to death. There was no association between the presence of IP and the development of or time to acute rejection. The presence of IP on lung transplant biopsy specimens suggests an increased risk for BOS, which is independent of the presence of acute cellular rejection.

Forthcoming Occultations of Astrometric Radio Sources by Planets

NASA Technical Reports Server (NTRS)

L'vov, Victor; Malkin, Zinovy; Tsekmeister, Svetlana

2010-01-01

Astrometric observations of radio source occultations by solar system bodies may be of large interest for testing gravity theories, dynamical astronomy, and planetary physics. In this paper, we present an updated list of the occultations of astrometric radio sources by planets expected in the coming years. Such events, like solar eclipses, generally speaking can only be observed in a limited region. A map of the shadow path is provided for the events that will occurr in regions with several VLBI stations and hence will be the most interesting for radio astronomy experiments.

Radioimmune localization of occult carcinoma

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

Duda, R.B.; Zimmer, A.M.; Rosen, S.T.

1990-07-01

Patients with a rising serum carcinoembryonic antigen level and no clinical or roentgenographic evidence of recurrent or metastatic cancer present a treatment dilemma. Eleven such patients, 10 with a previously treated colorectal carcinoma and 1 with a previously treated breast carcinoma, received an injection of the anticarcinoembryonic antigen monoclonal antibody ZCE-025 labeled with the radioisotope indium 111. Nuclear scintigraphy was performed on days 3 and 5 through 7 to detect potential sites of tumor recurrence. The monoclonal antibody scan accurately predicted the presence or absence of occult malignancy in 7 (64%) patients. Second-look laparotomy confirmed the monoclonal antibody scan resultsmore » in the patients with colorectal cancer, and magnetic resonance imaging confirmed metastatic breast cancer. This study demonstrates that In-ZCE-025 can localize occult carcinoma and may assist the surgeon in facilitating the operative exploration. In-ZCE-025 assisted in the initiation of adjuvant therapy for the patient with breast cancer.« less

Intra-tubular hydrodynamic forces influence tubulo-interstitial fibrosis in the kidney

PubMed Central

Rohatgi, Rajeev; Flores, Daniel

2010-01-01

Purpose of review Renal epithelial cells respond to mechanical stimuli with immediate transduction events (e.g., activation of ion channels), intermediate biological responses (e.g., changes in gene expression), and long term cellular adaptation (e.g., protein expression). Progressive renal disease is characterized by disturbed glomerular hydrodynamics that contributes to glomerulosclerosis, but, how intra-tubular biomechanical forces contribute to tubulo-interstital inflammation and fibrosis is poorly understood. Recent findings In vivo and in vitro models of obstructive uropathy demonstrate that tubular stretch induces robust expression of transforming growth factor β-1 (TGFβ-1), activation of tubular apoptosis, and induction of NF-κB signaling which contribute to the inflammatory and fibrotic milieu. Non-obstructive structural kidney diseases associated with nephron loss follow a course characterized by compensatory increases of single nephron glomerular filtration rate and tubular flow rate. Resulting increases in tubular fluid shear stress (FSS) reduce tissue-plasminogen activator and urokinase enzymatic activity which diminishes breakdown of extracellular matrix. In models of high dietary Na intake, which increase tubular flow, urinary TGFβ-1 concentrations and renal mitogen activated protein kinase activity are increased. Summary In conclusion, intra-tubular biomechanical forces, stretch and FSS, generate changes in intracellular signaling and gene expression that contribute to the pathobiology of obstructive, and non-obstructive kidney disease. PMID:19851105

Stray light rejection in giant externally-occulted solar coronagraphs: experimental developments

NASA Astrophysics Data System (ADS)

Venet, M.; Bazin, C.; Koutchmy, S.; Lamy, P.

2017-11-01

The advent of giant, formation-flight, externally-occulted solar coronagraphs such as ASPIICS (Association de Satellites Pour l'Imagerie et l'Interférométrie de la Couronne Solaire [1,2,3,4]) selected by the European Space Agency (ESA) for its third PROBA (Project for On-Board Autonomy) mission of formation flying demonstration (presently in phase B) and Hi-RISE proposed in the framework of ESA Cosmic Vision program, presents formidable challenges for the study and calibration of instrumental stray light. With distances between the external occulter (EO) and the optical pupil (OP) exceeding hundred meters and occulter sizes larger than a meter, it becomes impossible to perform tests at the real scale. The requirement to limit the over-occultation to less than 1.05 Rsun, orders of magnitude to what has been achieved so far in past coronagraphs, further adds to the challenge. We are approaching the problem experimentally using reduced scale simulators and present below a progress report of our work.

Characterization of the occult nature of frequently occurring pediatric motor vehicle crash injuries.

PubMed

Doud, Andrea N; Schoell, Samantha L; Talton, Jennifer W; Barnard, Ryan T; Petty, John K; Stitzel, Joel D; Weaver, Ashley A

2018-04-01

Occult injuries are those likely to be missed on initial assessment by first responders and, though initially asymptomatic, they may present suddenly and lead to rapid patient decompensation. No scoring systems to quantify the occultness of pediatric injuries have been established. Such a scoring system will be useful in the creation of an Advanced Automotive Crash Notification (AACN) system that assists first responders in making triage decisions following a motor vehicle crash (MVC). The most frequent MVC injuries were determined for 0-4, 5-9, 10-14 and 15-18 year olds. For each age-specific injury, experts with pediatric trauma expertise were asked to rate the likelihood that the injury may be missed by first responders. An occult score (ranging from 0-1) was calculated by averaging and normalizing the responses of the experts polled. Evaluation of all injuries across all age groups demonstrated greater occult scores for the younger age groups compared to older age groups (mean occult score 0-4yo: 0.61 ± 0.23, 5-9yo: 0.53 ± 0.25, 10-14yo: 0.48 ± 0.23, and 15-18yo: 0.42 ± 0.22, p < 0.01). Body-region specific occult scores revealed that experts judged abdominal, spine and thoracic injuries to be more occult than injuries to other body regions. The occult scores suggested that injuries are more difficult to detect in younger age groups, likely given their inability to express symptoms. An AACN algorithm that can predict the presence of clinically undetectable injuries at the scene can improve triage of children with these injuries to higher levels of care. Copyright © 2018 Elsevier Ltd. All rights reserved.

Idiopathic pulmonary fibrosis in BRIC countries: the cases of Brazil, Russia, India, and China.

PubMed

Richeldi, Luca; Rubin, Adalberto Sperb; Avdeev, Sergey; Udwadia, Zarir F; Xu, Zuo Jun

2015-09-24

Idiopathic pulmonary fibrosis (IPF), the prototype of interstitial lung diseases, has the worst prognosis and is the only interstitial lung disease for which approved pharmacological treatments are available. Despite being considered a rare disease, IPF patients pose major challenges to both physicians and healthcare systems. It is estimated that a large number of IPF patients reside in BRIC countries (Brazil, Russia, India, and China) given their overall total population of approximately 3 billion inhabitants. Nevertheless, the limited availability of chest imaging in BRIC countries is considered a chief obstacle to diagnosis, since high-resolution computed tomography of the chest is the key diagnostic test for IPF. Further, obtaining reliable lung function tests and providing treatment access is difficult in the more rural areas of these countries. However, IPF might represent an opportunity for BRIC countries: the exponentially increasing demand for the enrollment of IPF patients in clinical trials of new drugs is predicted to face a shortage of patients - BRIC countries may thus play a crucial role in advancing towards a cure for IPF.

[Occult hepatitis B virus infection in normal population, Xiamen].

PubMed

He, Shuizhen; Su, Chenghao; Shen, Litong; Niu, Jianjun

2015-02-01

To investigate the prevalence of occult HBV infection in the normal population in Xiamen. 4 437 registered permanent residents, aged 1-59 years old, were selected in Xiamen using stratified random sampling method from September to October in 2006. Serum samples were obtained, the basic characteristics, inoculation of HBV vaccine, and liver disease were surveyed. The serum samples were tested five HBV seroimmunological markers. The HBsAg-negative specimens were subjected to HBV-DNA detection by nested PCR targeting for multiple gene segments. The amplified products were sequenced and the sequence was used for determination of HBV genotype and mutation analysis of amino acids located in HBsAg "a" epitope. Subjects with serum detectable HBV-DNA and negative result of HBsAg were considered as occult HBV infection. Among the 4 437 subjects, 482 individuals were observed HBsAg positive and 3 944 were observed negative. Of the 3 955 HBsAg- negative specimens, 27 occult HBV infections were determined with the positive rate of 0.68% (27/3 955). There were 16 samples with genotype B and 11 with genotype C. 3 types of amino acid (AA) mutation (M133T, T140I, G145R) that influence "a" epitope conformation were observed in 9 subjects with occult HBV infection. S region was successfully sequenced in 312 of the 482 HBsAg positive samples. In subjects with occult HBV infection, the infection rate of genotype C HBV (40.74%, 11/27), inoculation rate of HBV vaccine (62.96%, 17/27), positive rate of HBsAb (51.85%, 14/27), and mutation rate of critical amino acid of "a" epitope (33.33%, 9/27) were higher than HBsAg positive individuals (22.76% (71/312), 13.78% (43/312),0.32% (1/312),0.99% (31/312), respectively), and all the difference were significant (χ(2) = 4.29, 41.26, 156.00, 13.07, respectively, and P value = 0.038, <0.001, <0.001, <0.001, respectively). While the average age in subjects with occult HBV infection (18.3 ± 16.2) were lower than that in HBsAg positive infection (34

Pharmacologic inhibition of the enzymatic effects of tissue transglutaminase reduces cardiac fibrosis and attenuates cardiomyocyte hypertrophy following pressure overload.

PubMed

Shinde, Arti V; Su, Ya; Palanski, Brad A; Fujikura, Kana; Garcia, Mario J; Frangogiannis, Nikolaos G

2018-04-01

Tissue transglutaminase (tTG) is a multifunctional protein with a wide range of enzymatic and non-enzymatic functions. We have recently demonstrated that tTG expression is upregulated in the pressure-overloaded myocardium and exerts fibrogenic actions promoting diastolic dysfunction, while preventing chamber dilation. Our current investigation dissects the in vivo and in vitro roles of the enzymatic effects of tTG on fibrotic remodeling in pressure-overloaded myocardium. Using a mouse model of transverse aortic constriction, we demonstrated perivascular and interstitial tTG activation in the remodeling pressure-overloaded heart. tTG inhibition through administration of the selective small molecule tTG inhibitor ERW1041E attenuated left ventricular diastolic dysfunction and reduced cardiomyocyte hypertrophy and interstitial fibrosis in the pressure-overloaded heart, without affecting chamber dimensions and ejection fraction. In vivo, tTG inhibition markedly reduced myocardial collagen mRNA and protein levels and attenuated transcription of fibrosis-associated genes. In contrast, addition of exogenous recombinant tTG to fibroblast-populated collagen pads had no significant effects on collagen transcription, and instead increased synthesis of matrix metalloproteinase (MMP)3 and tissue inhibitor of metalloproteinases (TIMP)1 through transamidase-independent actions. However, enzymatic effects of matrix-bound tTG increased the thickness of pericellular collagen in fibroblast-populated pads. tTG exerts distinct enzymatic and non-enzymatic functions in the remodeling pressure-overloaded heart. The enzymatic effects of tTG are fibrogenic and promote diastolic dysfunction, but do not directly modulate the pro-fibrotic transcriptional program of fibroblasts. Targeting transamidase-dependent actions of tTG may be a promising therapeutic strategy in patients with heart failure and fibrosis-associated diastolic dysfunction. Copyright © 2018 Elsevier Ltd. All rights reserved.

Stellar occultation candidates from the guide star catalog. I - Saturn, 1991-1999

NASA Technical Reports Server (NTRS)

Bosh, A. S.; Mcdonald, S. W.

1992-01-01

A list of 203 potential occultations by Saturn and its ring of stars from the HST Guide Star Catalog (GSC) during the years 1991-1999 is presented. This list features many fainter candidates than do current occultation candidate lists for Saturn; these fainter stars can also provide a high signal-to-noise ratio if observed with a large telescope or in the IR where Saturn and its rings have absorption bands. The occultation circumstances are listed, as well as star information found in the GSC.

Chronic hypersensitivity pneumonitis in patients diagnosed with idiopathic pulmonary fibrosis: a prospective case-cohort study.

PubMed

Morell, Ferran; Villar, Ana; Montero, María-Ángeles; Muñoz, Xavier; Colby, Thomas V; Pipvath, Sudhakar; Cruz, María-Jesús; Raghu, Ganesh

2013-11-01

The clinical features of idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis can be indistinguishable; the need to eliminate occult environmental factors known to cause pulmonary fibrosis in patients suspected to have IPF during diagnostic evaluation is evident. We aimed to investigate occult, putative causes in the environments of patients diagnosed with IPF using tests beyond those conventionally used. In this case-cohort study, 60 consecutive patients diagnosed with IPF on the basis of the 2000 American Thoracic Society (ATS) and the European Respiratory Society (ERS) criteria were prospectively followed up every 4 months for 6 years between Jan 1, 2004, and Dec 31, 2009. At each visit a uniformly applied questionnaire was administered to these 60 patients to identify occult antigen exposure known to cause hypersensitivity pneumonitis. Patients underwent specific IgG determination, bronchoalveolar lavage, bronchial challenge testing with suspected antigens, and re-review of histopathological features in existing and subsequently obtained surgical lung biopsy samples and from lung explants. Specimens obtained from suspected sources from the patient's environment were subjected to cultures in microbiology laboratory. These clinical data and discussions among pulmonologists and radiologists familiar with IPF were used to confirm the diagnosis in accordance with 2011 ATS, ERS, Japanese Respiratory Society, and Latin American Thoracic Association guidelines; 46 of the 60 patients had IPF according to the 2011 guidelines, and our analyses in this study were focused on these 46 patients. 20 of the 46 (43%, 95% CI 29-58) patients with IPF according to 2011 guidelines had a subsequent diagnosis of chronic hypersensitivity pneumonitis: nine patients had positive bronchial challenge testing (eight of whom were also IgG positive and six of these patients also had surgical lung biopsy showing a pattern consistent with chronic hypersensitivity

Interstitial granulomatous dermatitis with arthritis.

PubMed

Long, D; Thiboutot, D M; Majeski, J T; Vasily, D B; Helm, K F

1996-06-01

Interstitial granulomatous dermatitis with arthritis is an uncommon systemic disorder involving the cutaneous and musculoskeletal systems. The eruption may mimic other dermatoses including granuloma annulare, erythema chronicum migrans, and the inflammatory stage of morphea. Key histopathologic characteristics, along with clinical correlation, allow accurate diagnosis. We describe the clinical, serologic, and histologic features in three patients with interstitial granulomatous dermatitis with arthritis. Skin biopsy specimens were examined and correlated with the clinical and laboratory findings. Erythematous, annular, indurated plaques on the extremities were present in two women. An erythematous, papular eruption on the head and neck was present in a third patient. All patients had myalgia and migratory polyarthralgias of the extremities along with various serologic abnormalities. Histologic examination revealed a dense lymphohistiocytic interstitial infiltrate involving primarily the reticular dermis. Foci of necrobiotic collagen were present. Vasculitis was absent. Interstitial granulomatous dermatitis with arthritis is unique multisystem disease with variable cutaneous expression. Abnormal serologic findings indicate a possible connection to collagen vascular disease.

Advanced Electrocardiography Can Identify Occult Cardiomyopathy in Doberman Pinschers

NASA Technical Reports Server (NTRS)

Spiljak, M.; Petric, A. Domanjko; Wilberg, M.; Olsen, L. H.; Stepancic, A.; Schlegel, T. T.; Starc, V.

2011-01-01

Recently, multiple advanced resting electrocardiographic (A-ECG) techniques have improved the diagnostic value of short-duration ECG in detection of dilated cardiomyopathy (DCM) in humans. This study investigated whether 12-lead A-ECG recordings could accurately identify the occult phase of DCM in dogs. Short-duration (3-5 min) high-fidelity 12-lead ECG recordings were obtained from 31 privately-owned, clinically healthy Doberman Pinschers (5.4 +/- 1.7 years, 11/20 males/females). Dogs were divided into 2 groups: 1) 19 healthy dogs with normal echocardiographic M-mode measurements: left ventricular internal diameter in diastole (LVIDd . 47mm) and in systole (LVIDs . 38mm) and normal 24-hour ECG recordings (<50 ventricular premature complexes, VPCs); and 2) 12 dogs with occult DCM: 11/12 dogs had increased M-mode measurements (LVIDd . 49mm and/or LVIDs . 40mm) and 5/11 dogs had also >100 VPCs/24h; 1/12 dogs had only abnormal 24-hour ECG recordings (>100 VPCs/24h). ECG recordings were evaluated via custom software programs to calculate multiple parameters of high-frequency (HF) QRS ECG, heart rate variability, QT variability, waveform complexity and 3-D ECG. Student's t-tests determined 19 ECG parameters that were significantly different (P < 0.05) between groups. Principal component factor analysis identified a 5-factor model with 81.4% explained variance. QRS dipolar and non-dipolar voltages, Cornell voltage criteria and QRS waveform residuum were increased significantly (P < 0.05), whereas mean HF QRS amplitude was decreased significantly (P < 0.05) in dogs with occult DCM. For the 5 selected parameters the prediction of occult DCM was performed using a binary logistic regression model with Chi-square tested significance (P < 0.01). ROC analyses showed that the five selected ECG parameters could identify occult ECG with sensitivity 89% and specificity 83%. Results suggest that 12-lead A-ECG might improve diagnostic value of short-duration ECG in earlier detection

Risk factors of occult malignancy in patients with unprovoked venous thromboembolism.

PubMed

Robin, Philippe; Le Roux, Pierre-Yves; Tromeur, Cécile; Planquette, Benjamin; Prévot-Bitot, Nathalie; Lavigne, Christian; Pastre, Jean; Merah, Adel; Couturaud, Francis; Le Gal, Grégoire; Salaun, Pierre-Yves

2017-11-01

Venous thromboembolism (VTE) can occur as the first manifestation of an underlying occult malignancy. It remains unclear whether or not a better selection of high risk patients might lead to more efficient occult cancer screening strategies. Our aim was to assess the predictors of occult malignancy diagnosis in patients with unprovoked VTE. Univariate analyses were performed to assess the effect of candidate predictors on occult cancer detection in patients enrolled in a prospective, multicenter, randomized, controlled study (MVTEP study) whose primary aim was to compare a limited screening strategy with a strategy combining limited screening and FDG PET/CT in patients with unprovoked VTE. This trial is completed and registered with ClinicalTrials.gov, number NCT00964275. Between March 3, 2009, and August 18, 2012, 399 patients were included. Five patients withdrew consent and refused the use of their data, and no VTE was confirmed in 2 patients who were excluded from this analysis. A total of 25 (6.4%) out of the 392 analysed patients received a new diagnosis of malignancyduring the 2-years follow-up. Age≥50years (p=0.01), male gender (p=0.04), leukocytes count (p=0.01), and platelets count (p=0.03) were associated with occult cancer detection. Patients with leukocytosis or thrombocytosis had a risk of cancer way above 10%. Previous VTE and smoker status (combining previous and current smokers) were not associated with occult cancer diagnosis (p>0.05). Demographic characteristics (age and sex), and laboratory tests (high platelets and leukocytes counts) may be associated with cancer detection in patients withunprovoked VTE. Copyright © 2017 Elsevier Ltd. All rights reserved.

Magnitudes of selected stellar occultation candidates for Pluto and other planets, with new predictions for Mars and Jupiter

NASA Technical Reports Server (NTRS)

Sybert, C. B.; Bosh, A. S.; Sauter, L. M.; Elliot, J. L.; Wasserman, L. H.

1992-01-01

Occultation predictions for the planets Mars and Jupiter are presented along with BVRI magnitudes of 45 occultation candidates for Mars, Jupiter, Saturn, Uranus, and Pluto. Observers can use these magnitudes to plan observations of occultation events. The optical depth of the Jovian ring can be probed by a nearly central occultation on 1992 July 8. Mars occults an unusually red star in early 1993, and the occultations for Pluto involving the brightest candidates would possibly occur in the spring of 1992 and the fall of 1993.

Evaluation and Improved Use of Fecal Occult Blood Test in the Constipated Child.

PubMed

Kilway, Denise M

2016-01-01

This quality improvement project examined the use of fecal occult blood test in the constipated child in a pediatric gastroenterology outpatient clinic. A retrospective chart review was completed on 100 children seen for an initial visit with the gastroenterology provider. The number of fecal occult blood tests performed and the child's coinciding symptoms were tallied and compared with the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition recommendations. An educational intervention was held with the pediatric gastroenterology providers consisting of a PowerPoint presentation summarizing aims of the quality improvement project and reviewing recommendations for use of fecal occult blood test in the constipated child. Pre- and post-intervention chart review data sets were compared. Results showed a 19.6% decrease in the use of fecal occult blood tests performed during the post-intervention timeframe. However, when used in conjunction with North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition recommendations, the appropriateness of fecal occult blood test use increased by 71.4% in the post-intervention patients. Reviewing the recommendations with gastroenterology providers assisted in optimizing the meaningful use of fecal occult blood test, improving quality and safety of care for children seen in the pediatric gastroenterology outpatient clinic.

Occultation Predictions Using CCD Strip-Scanning Astrometry

NASA Technical Reports Server (NTRS)

Dunham, Edward W.; Ford, C. H.; Stone, R. P. S.; McDonald, S. W.; Olkin, C. B.; Elliot, J. L.; Witteborn, Fred C. (Technical Monitor)

1994-01-01

We are developing the method of CCD strip-scanning astrometry for the purpose of deriving reliable advance predictions for occultations involving small objects in the outer solar system. We are using a camera system based on a Ford/Loral 2Kx2K CCD with the Crossley telescope at Lick Observatory for this work. The columns of die CCD are aligned East-West, the telescope drive is stopped, and the CCD is clocked at the same rate that the stars drift across it. In this way we obtain arbitrary length strip images 20 arcmin wide with 0.58" pixels. Since planets move mainly in RA, it is possible to obtain images of the planet and star to be occulted on the same strip well before the occultation occurs. The strip-to-strip precision (i.e. reproducibility) of positions is limited by atmospheric image motion to about 0.1" rms per strip. However, for objects that are nearby in R.A., the image motion is highly correlated and their relative positions are good to 0.02" rms per strip. We will show that the effects of atmospheric image motion on a given strip can be removed if a sufficient number of strips of a given area have been obtained. Thus, it is possible to reach an rms precision of 0.02" per strip, corresponding to about 0.3 of Pluto or Triton's angular radius. The ultimate accuracy of a prediction based on strip-scanning astrometry is currently limited by the accuracy of the positions of the stars in the astrometric network used and by systematic errors most likely due to the optical system. We will show the results of . the prediction of some recent occultations as examples of the current capabilities and limitations of this technique.

Turbulence in planetary occultations. IV - Power spectra of phase and intensity fluctuations

NASA Technical Reports Server (NTRS)

Haugstad, B. S.

1979-01-01

Power spectra of phase and intensity scintillations during occultation by turbulent planetary atmospheres are significantly affected by the inhomogeneous background upon which the turbulence is superimposed. Such coupling is particularly pronounced in the intensity, where there is also a marked difference in spectral shape between a central and grazing occultation. While the former has its structural features smoothed by coupling to the inhomogeneous background, such features are enhanced in the latter. Indeed, the latter power spectrum peaks around the characteristic frequency that is determined by the size of the free-space Fresnel zone and the ray velocity in the atmosphere; at higher frequencies strong fringes develop in the power spectrum. A confrontation between the theoretical scintillation spectra computed here and those calculated from the Mariner 5 Venus mission by Woo et al. (1974) is inconclusive, mainly because of insufficient statistical resolution. Phase and/or intensity power spectra computed from occultation data may be used to deduce characteristics of the turbulence and to distinguish turbulence from other perturbations in the refractive index. Such determinations are facilitated if observations are made at two or more frequencies (radio occultation) or in two or more colors (stellar occultation).

Density Waves in Saturn's Rings from Cassini Radio Occultations

NASA Astrophysics Data System (ADS)

French, R. G.; Rappaport, N. J.; Marouf, E. A.; McGhee, C. A.

2005-12-01

The Cassini Radio Science Team conducted a set of optimized diametric occultations by Saturn and its rings from May to September 2005, providing 11 separate probes of Saturn's ionosphere and atmosphere, and 12 optical depth profiles of the complete ring system. Each event was observed by the stations of the Deep Space Net (DSN) at three radio frequencies (S, X, Ka bands, with corresponding wavelengths of ? = 13, 3.6, and 0.9 cm). Very accurate pointing by the spacecraft and ground antennas resulted in stable baseline signal levels, and the relatively large ring opening angle (B=19-25°) permitted us to probe even quite dense ring regions with excellent SNR. The RSS occultation technique enables us to recover very fine detailed radial structure by correcting for diffraction effects. Multiple occultation chords, covering a variety of ring longitudes and ring opening angles, reveal the structure of the rings in remarkable detail, including density and bending waves, satellite wakes, and subtle variations at the 100-m radius scale. Janus and Epimetheus are responsible for a particularly rich set of density waves, and their coorbital interactions result in a complex interplay of time-variable ring structure over the 8-year libration period of the two satellites. We compare the first-order 2:1, 4:3, 5:4, and 6:5 coorbital density waves from multiple occultation chords to linear density wave models based on a dynamical model of the orbital exchange between the moons. From the observed dispersion relation of the wave crests, we infer the surface mass density and eccentricity gradient of particle streamlines, and match the detailed shapes of the wave crests using a non-linear analysis. Second-order coorbital features are also evident, and there are even hints of third-order density waves in the high SNR radio occultation data.

On Combining Thermal-Infrared and Radio-Occultation Data of Saturn's Atmosphere

NASA Technical Reports Server (NTRS)

Flasar, F. M.; Schinder, P. J.; Conrath, B. J.

2008-01-01

Radio-occultation and thermal-infrared measurements are complementary investigations for sounding planetary atmospheres. The vertical resolution afforded by radio occultations is typically approximately 1 km or better, whereas that from infrared sounding is often comparable to a scale height. On the other hand, an instrument like CIRS can easily generate global maps of temperature and composition, whereas occultation soundings are usually distributed more sparsely. The starting point for radio-occultation inversions is determining the residual Doppler-shifted frequency, that is the shift in frequency from what it would be in the absence of the atmosphere. Hence the positions and relative velocities of the spacecraft, target atmosphere, and DSN receiving station must be known to high accuracy. It is not surprising that the inversions can be susceptible to sources of systematic errors. Stratospheric temperature profiles on Titan retrieved from Cassini radio occultations were found to be very susceptible to errors in the reconstructed spacecraft velocities (approximately equal to 1 mm/s). Here the ability to adjust the spacecraft ephemeris so that the profiles matched those retrieved from CIRS limb sounding proved to be critical in mitigating this error. A similar procedure can be used for Saturn, although the sensitivity of its retrieved profiles to this type of error seems to be smaller. One issue that has appeared in inverting the Cassini occultations by Saturn is the uncertainty in its equatorial bulge, that is, the shape in its iso-density surfaces at low latitudes. Typically one approximates that surface as a geopotential surface by assuming a barotropic atmosphere. However, the recent controversy in the equatorial winds, i.e., whether they changed between the Voyager (1981) era and later (after 1996) epochs of Cassini and some Hubble observations, has made it difficult to know the exact shape of the surface, and it leads to uncertainties in the retrieved

James Webb Space Telescope Observations of Stellar Occultations by Solar System Bodies and Rings

NASA Technical Reports Server (NTRS)

Santos-Sanz, P.; French, R. G.; Pinilla-Alonso, N.; Stansberry, J.; Lin, Z-Y.; Zhang, Z-W.; Vilenius, E.; Mueller, Th.; Ortiz, J. L.; Braga-Ribas, F.;

Occult cancer-related first venous thromboembolism is associated with an increased risk of recurrent venous thromboembolism.

PubMed

Gran, O V; Braekkan, S K; Paulsen, B; Skille, H; Rosendaal, F R; Hansen, J-B

2017-07-01

Essentials Recurrence risk after an occult cancer-related incident venous thromboembolism (VTE) is unknown. We compared the risk of VTE recurrence in occult-, overt- and non-cancer related first VTE. Patients with occult-cancer related first VTE had the highest risk of VTE recurrence. The high recurrence risk in occult cancer is likely due to the advanced cancers. Background Although venous thromboembolism (VTE) is associated with a high recurrence rate, the absolute recurrence rates for cancer-related VTE, particularly occult cancer, are not well known. Objectives To investigate the risk of VTE recurrence in patients with occult and overt cancer-related VTE. Methods Incident VTE events among participants of the first to sixth Tromsø surveys occurring in the period 1994-2012 were included. Occult cancer was defined as cancer diagnosed within a year following a VTE, and overt cancer was defined as cancer diagnosed within the 2 years before a VTE. Results Among 733 patients with incident VTE, 110 had overt cancer and 40 had occult cancer. There were 95 recurrent VTE events during a median of 3.2 years of follow-up. The 1-year cumulative incidence of VTE recurrence was 38.6% in subjects with occult cancer, 15.5% in subjects with overt cancer, and 3.8% in non-cancer subjects. The 1-year risk of recurrence was 12-fold (hazard ratio [HR] 12.4, 95% confidence interval [CI] 5.9-26.3) higher in subjects with occult cancer and four-fold (HR 4.3, 95% CI 2.0-9.2) higher in subjects with overt cancer than in non-cancer subjects. The occult cancers associated with VTE recurrence were typically located at prothrombotic sites (i.e. lung and gastrointestinal) and presented at advanced stages. The majority (69%) of recurrences in subjects with occult cancer occurred before or shortly after cancer diagnosis, and were therefore not treatment-related. Conclusion Our findings suggest that the increased risk of recurrence in patients with occult cancer is mainly attributable to the