Directed and persistent movement arises from mechanochemistry of the ParA/ParB system

NASA Astrophysics Data System (ADS)

Hu, Longhua; Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi; Neuman, Keir C.; Liu, Jian

The segregation of DNA prior to cell division is essential for faithful genetic inheritance. In many bacteria, segregation of the low-copy-number plasmids involves an active partition system composed of ParA ATPase and its stimulator protein ParB. Recent experiments suggest that ParA/ParB system motility is driven by a diffusion-ratchet mechanism in which ParB-coated plasmid both creates and follows a ParA gradient on the nucleoid surface. However, the detailed mechanism of ParA/ParB-mediated directed and persistent movement remains unknown. We develop a theoretical model describing ParA/ParB-mediated motility. We show that the ParA/ParB system can work as a Brownian ratchet, which effectively couples the ATPase-dependent cycling of ParA-nucleoid affinity to the motion of the ParB bound cargo. Paradoxically, the resulting processive motion relies on quenching diffusive plasmid motion through a large number of transient ParA/ParB-mediated tethers to the nucleoid surface. Our work sheds light on a new emergent phenomenon in which non-motor proteins work collectively via mechanochemical coupling to propel cargos -- an ingenious solution shaped by evolution to cope with the lack of processive motor proteins in bacteria.

[Gastrointestinal bleeding from capillary hemangioma of the ileum detected by 99mTc-HSAD scintigraphy].

PubMed

Asano, Y; Ishii, K; Sagiuchi, T; Aoki, Y; Yanaihara, H; Hayakawa, K

2001-05-01

It has been well-known that technetium-99m-human serum albumin-diethylenetriaminepenta-acetic acid (99mTc-HSAD) scintigraphy is useful for diagnosis of the localization of the gastrointestinal arterial or venous bleeding. In this report, we describe a case of venous bleeding from capillary hemangioma of the ileum end detected by 99mTc-HSAD scintigraphy. This patient was a 9-year-old girl with severe anemia. Gastrointestinal bleeding was suspected from her clinical course and laboratory tests. Immediately after melena occurred, 99mTc-HSAD scintigraphy showed the extravasation of RI suggesting gastrointestinal bleeding in the ileum end. Abdominal angiography immediately after 99mTc-HSAD scintigraphy, however, could not show the extravasation of contrast agent. Because the condition of the patient became worse, laparotomy was performed on the basis of 99mTc-HSAD scintigraphy findings. At surgery, venous bleeding from capillary hemangioma in the ileum end was observed. It was suggested that 99mTc-HSAD scintigraphy was very useful for identifying the gastrointestinal venous bleeding.

Somatostatin receptor scintigraphy in patients with cat-scratch disease.

PubMed

Krause, R; Piswanger-Soelkner, C; Lipp, R W; Daxböck, F; Schnedl, W J; Hoier, S; Reisinger, E C

2006-01-01

Somatostatin receptor scintigraphy images various neoplastic, granulomatous, and auto-immune diseases. Cat-scratch disease in an infectious granulomatous disease usually affecting the lymphnodes. It is not known whether cat-scratch disease provides positive somatostatin receptor scintigrams. Twelve patients with lymphadenitis and suspected cat-scratch disease were investigated by immunofluorescence antibody testing and somatostatin receptor scintigraphy. Suppurated lymphnodes were extracted or drained and Bartonella henselae specific PCR was then performed. Eleven of 12 patients showed IgG antibodies against B. henselae. SRS showed positive scintigraphic results in 6 of 11 patients with CSD. B. henselae DNA was detected in tissue of lymphnodes from 4 of 5 patients with lymphnode extraction or lymphnode drainage. SRS demonstrated positive scintigrams in all patients with a positive PCR. In one patient with suspected CSD SRS was negative as well as antibody testing. Somatostatin receptor scintigraphy correlated with positive Bartonella henselae specific PCR tests and positive Bartonella henselae specific antibody tests in patients with CSD.

AIDS-related Kaposi sarcoma: findings on thallium-201 scintigraphy

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

Lee, V.W.; Rosen, M.P.; Baum, A.

1988-12-01

No simple, noninvasive method is available for evaluating extracutaneous Kaposi sarcoma in AIDS patients or for following the tumor's response to treatment. We report our preliminary experience with thallium-201 scintigraphy in nine AIDS patients with proved Kaposi sarcoma. Eight of the nine had abnormal uptake of the radionuclide in skin, lymph nodes, oral cavity, vagina, and lungs. Only four of the nine had cutaneous Kaposi sarcoma at the time of scanning. All cutaneous and mucosal lesions were thallium avid. Two of the six patients with thallium-avid nodes underwent nodal biopsy. Both biopsies confirmed the diagnosis of Kaposi sarcoma. Cutaneous Kaposimore » sarcoma developed later in one of these patients, showing the efficacy of thallium scintigraphy for the early detection of extracutaneous lesions. These preliminary results show thallium avidity in Kaposi sarcoma involving the skin and various extracutaneous sites (lymph nodes, lung, mucosa, and vagina). Thallium scintigraphy is a potentially useful procedure for detecting extracutaneous Kaposi sarcoma in AIDS patients.« less

Quantitative bone and 67Ga scintigraphy in the differentiation of necrotizing external otitis from severe external otitis

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

Uri, N.; Gips, S.; Front, A.

1991-06-01

Qualitative technetium Tc 99m bone scintigraphy using phosphate compounds and gallium 67 scintigraphy were described as a helpful means in diagnosing necrotizing external otitis (NEO). They were, however, claimed to be nonspecific. Quantitative Tc 99m methylene diphosphonate bone scintigraphy and gallium 67 scintigraphy were performed in eight patients with NEO and in 20 patients with severe external otitis, in order to prove usefulness of scintigraphy in the diagnosis of NEO. Ratios of lesion to nonlesion for bone scintigraphy were 1.67 {plus minus} 0.16 in patients with NEO and 1.08 {plus minus} 0.09 in patients with severe external otitis, and formore » gallium 67 scintigraphy they were 1.35 {plus minus} 0.24 in NEO patients and 1.05 {plus minus} 0.03 in patients with severe external otitis. There was no difference in uptake between diabetic patients with severe external otitis and nondiabetic patients. The scintigraphic studies were also evaluated using a qualitative scoring method (scores 0 to +4), according to the intensity of the radiopharmaceutical uptake. This method was found to be inferior in the diagnosis of NEO compared with the quantitative method. We conclude that lesion-to-nonlesion ratios greater than 1.5 and 1.3 on bone and gallium 67 scintigraphy, respectively, are indicative of NEO. Quantitative bone scintigraphy, which is quicker to perform, may be used as a single imaging modality for the diagnosis of NEO.« less

(99m)Tc-HYNIC-TOC scintigraphy in evaluation of active Graves' ophthalmopathy (GO).

PubMed

Sun, Hua; Jiang, Xu-Feng; Wang, Shu; Chen, Hao-Yan; Sun, Jiao; Li, Pei-Yong; Ning, Guang; Zhao, Yong-Ju

2007-06-01

A promising radiopharmaceutical (99m)Tc-HYNIC-TOC ((99m)Tc-HYNIC-Octreotide) can be applied for somatostatin receptor scintigraphy with the potential to replace Indium-111 labeled somatostatin analogus. Here we evaluate whether orbital (99m)Tc-HYNIC-TOC scintigraphy can be used as a Graves' ophthalmopathy (GO) activity parameter to predict the retrobulbar irradiation response. Orbital (99m)Tc-HYNIC-TOC scintigraphy was performed on 14 consecutive patients demonstrating moderated to severe Graves' ophthalmopathy. The patients were treated with retrobulbar irradiation following the octreoscan and the response to this therapy was assessed at 3 months after the start of treatment. The orbital (99m)Tc-HYNIC-TOC uptake was calculated to assess the effects of treatment. Among the 14 GO patients, eight (57.1%) responded to retrobulbar radiotherapy; six (42.9%) showed no change. We compared the eight responders and six non-responders in terms of orbital (99m)Tc-HYNIC-TOC uptake, using the orbital/occipital ratio. On the 4-h (99m)Tc-HYNIC-TOC scintigraphy, responders had a higher orbital/occipital uptake ratio than the no-responders (P = 0.001). A significant correlation was found between the orbital/occipital ratio and the clinical activity score (CAS) (P = 0.034). The Receiving-Operator-Characteristic curve showed the best threshold for discriminating active and inactive disease was 1.40 (sensitivity, 100%; specificity, 83.3%). In the responders group, all these eight patients had positive scintigraphy. While there were five patients who had negative scintigraphy in the non-responders group. Orbital (99m)Tc-HYNIC-TOC scintigraphy can be a useful method for the estimation of disease activity and prediction the response to subsequent radiotherapy in GO patient. And the patients with positive octreoscan were more likely to respond to irradiation.

Technetium-99m stannous pyrophosphate myocardial scintigraphy after cardiopulmonary resuscitation with cardioversion

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

Davison, R.; Spies, S.M.; Przybylek, J.

1979-08-01

Thirty consecutive patients underwent technetium-99m stannous pyrophosphate myocardial scintigraphy 48 to 72 h after successful cardiopulmonary resuscitation and direct current cardioversion. Five patients with transmural myocardial infarctions by ECG and enzyme determinations were correctly identified by scintigraphy. Myocardial scans were positive in five of nine patients with nontransmural infarction. Of 16 patients without evidence of myocardial infarction, only two (13%) had false-positive myocardial scans. The overall accuracy of imaging in this series was 80%. We conclude that false-positive scans after cardiopulmonary resuscitation with electrical cardioversion are infrequent, and do not significantly detract from the value of myocardial scintigraphy in themore » diagnosis of myocardial infarction.« less

Hybrid Vision-Fusion system for whole-body scintigraphy.

PubMed

Barjaktarović, Marko; Janković, Milica M; Jeremić, Marija; Matović, Milovan

2018-05-01

Radioiodine therapy in the treatment of differentiated thyroid carcinoma (DTC) is used in clinical practice for the ablation of thyroid residues and/or destruction of tumour tissue. Whole-body scintigraphy for visualization of the spatial 131I distribution performed by a gamma camera (GC) is a standard procedure in DTC patients after application of radioiodine therapy. A common problem is the precise topographic localization of regions where radioiodine is accumulated even in SPECT imaging. SPECT/CT can provide precise topographic localization of regions where radioiodine is accumulated, but it is often unavailable, especially in developing countries because of the high price of the equipment. In this paper, we present a Vision-Fusion system as an affordable solution for 1) acquiring an optical whole-body image during routine whole-body scintigraphy and 2) fusing gamma and optical images (also available for the auto-contour mode of GC). The estimated prediction error for image registration is 1.84 mm. The validity of fusing was tested by performing simultaneous optical and scintigraphy image acquisition of the bar phantom. The fusion result shows that the fusing process has a slight influence and is lower than the spatial resolution of GC (mean value ± standard deviation: 1.24 ± 0.22 mm). The Vision-Fusion system was used for radioiodine post-therapeutic treatment, and 17 patients were followed (11 women and 6 men, with an average age of 48.18 ± 13.27 years). Visual inspection showed no misregistration. Based on our first clinical experience, we noticed that the Vision-Fusion system could be very useful for improving the diagnostic possibility of whole-body scintigraphy after radioiodine therapy. Additionally, the proposed Vision-Fusion software can be used as an upgrade for any GC to improve localizations of thyroid/tumour tissue. Copyright © 2018 Elsevier Ltd. All rights reserved.

Phosphorylation of Mycobacterium tuberculosis ParB Participates in Regulating the ParABS Chromosome Segregation System

PubMed Central

Baronian, Grégory; Ginda, Katarzyna; Berry, Laurence; Cohen-Gonsaud, Martin; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara; Molle, Virginie

2015-01-01

Here, we present for the first time that Mycobacterium tuberculosis ParB is phosphorylated by several mycobacterial Ser/Thr protein kinases in vitro. ParB and ParA are the key components of bacterial chromosome segregation apparatus. ParB is a cytosolic conserved protein that binds specifically to centromere-like DNA parS sequences and interacts with ParA, a weak ATPase required for its proper localization. Mass spectrometry identified the presence of ten phosphate groups, thus indicating that ParB is phosphorylated on eight threonines, Thr32, Thr41, Thr53, Thr110, Thr195, and Thr254, Thr300, Thr303 as well as on two serines, Ser5 and Ser239. The phosphorylation sites were further substituted either by alanine to prevent phosphorylation or aspartate to mimic constitutive phosphorylation. Electrophoretic mobility shift assays revealed a drastic inhibition of DNA-binding by ParB phosphomimetic mutant compared to wild type. In addition, bacterial two-hybrid experiments showed a loss of ParA-ParB interaction with the phosphomimetic mutant, indicating that phosphorylation is regulating the recruitment of the partitioning complex. Moreover, fluorescence microscopy experiments performed in the surrogate Mycobacterium smegmatis ΔparB strain revealed that in contrast to wild type Mtb ParB, which formed subpolar foci similar to M. smegmatis ParB, phoshomimetic Mtb ParB was delocalized. Thus, our findings highlight a novel regulatory role of the different isoforms of ParB representing a molecular switch in localization and functioning of partitioning protein in Mycobacterium tuberculosis. PMID:25807382

Phosphorylation of Mycobacterium tuberculosis ParB participates in regulating the ParABS chromosome segregation system.

PubMed

Baronian, Grégory; Ginda, Katarzyna; Berry, Laurence; Cohen-Gonsaud, Martin; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara; Molle, Virginie

2015-01-01

Here, we present for the first time that Mycobacterium tuberculosis ParB is phosphorylated by several mycobacterial Ser/Thr protein kinases in vitro. ParB and ParA are the key components of bacterial chromosome segregation apparatus. ParB is a cytosolic conserved protein that binds specifically to centromere-like DNA parS sequences and interacts with ParA, a weak ATPase required for its proper localization. Mass spectrometry identified the presence of ten phosphate groups, thus indicating that ParB is phosphorylated on eight threonines, Thr32, Thr41, Thr53, Thr110, Thr195, and Thr254, Thr300, Thr303 as well as on two serines, Ser5 and Ser239. The phosphorylation sites were further substituted either by alanine to prevent phosphorylation or aspartate to mimic constitutive phosphorylation. Electrophoretic mobility shift assays revealed a drastic inhibition of DNA-binding by ParB phosphomimetic mutant compared to wild type. In addition, bacterial two-hybrid experiments showed a loss of ParA-ParB interaction with the phosphomimetic mutant, indicating that phosphorylation is regulating the recruitment of the partitioning complex. Moreover, fluorescence microscopy experiments performed in the surrogate Mycobacterium smegmatis ΔparB strain revealed that in contrast to wild type Mtb ParB, which formed subpolar foci similar to M. smegmatis ParB, phoshomimetic Mtb ParB was delocalized. Thus, our findings highlight a novel regulatory role of the different isoforms of ParB representing a molecular switch in localization and functioning of partitioning protein in Mycobacterium tuberculosis.

Architecture of the ParF*ParG protein complex involved in prokaryotic DNA segregation.

PubMed

Barillà, Daniela; Hayes, Finbarr

2003-07-01

The mechanism by which low copy number plasmids are segregated at cell division involves the concerted action of two plasmid-encoded proteins that assemble on a centromere-like site. This study explores the topology of the DNA segregation machinery specified by the parFG locus of TP228, a partition system which is phylogenetically distinct from more well-characterized archetypes. A variety of genetic, biochemical and biophysical strategies revealed that the ParG protein is dimeric. ParF, which is more closely related to the cell division regulator MinD than to the prototypical ParA partition protein of plasmid P1, is instead multimeric and its polymeric state appears to be modulated by ATP which correlates with the proposed ATP-binding activity of ParF. ParG interacts in a sequence-specific manner with the DNA region upstream of the parFG locus and this binding is modulated by ParF. Intriguingly, the ParF and ParG proteins form at least two types of discrete complex in the absence of this region suggesting that the assembly dynamics of these proteins onto DNA is intricate.

Limitations and pitfalls of 99mTc-EDDA/HYNIC-TOC (Tektrotyd) scintigraphy.

PubMed

Garai, Ildikó; Barna, Sandor; Nagy, Gabor; Forgacs, Attila

2016-01-01

Tektrotyd kit was developed by Polatom company for 99mTc labeling to make an alternative tracer of somatostatin receptor scintigraphy available. Since 2005, 99mTc-EDDA/HYNIC-Tyr3-Octreotide has been used in clinical imaging and achieved high impact in management of patients with neuroendocrine tumors. Knowing the limitations and pitfalls is essential to provide ac-curate diagnosis. Therefore, the potential pitfalls associated with the use of 99mTc-EDDA/HYNIC-TOC are reviewed on the basis of own experience. Data were analyzed of 310 patients who underwent somatostatin receptor scintigraphy with 99mTc-Tektrotyd. Pitfalls during radiolabeling process or acquisition can worsen the sensitivity of SRS (somatostatin receptor scintigraphy). Recognizing physi-ological and clinical pitfalls, the diagnostic accuracy will improve.

Somatostatin receptor scintigraphy in sarcoidosis: relation to selected clinical and laboratory markers.

PubMed

Piotrowski, Wojciech J; Bieńkiewicz, Małgorzata; Frieske, Izabella; Marczak, Jerzy; Antczak, Adam; Górski, Paweł; Kuśmierek, Jacek; Płachcińska, Anna

2012-01-01

Discriminating between active and inactive sarcoidosis may be problematic in everyday clinical practice. There are numerous biochemical markers used in the diagnosis and monitoring of sarcoidosis. Somatostatin receptor (SR) scintigraphy with the use of 99mTc-octreotide may be used to estimate disease activity. The aim of the paper was to assess the value of traditional biomarkers (serum angiotensin-converting enzyme [SACE], C-reactive protein, markers of calcium metabolism, bronchoalveolar lavage fluid [BALF] lymphocytes) and a novel biomarker, 8-isoprostane (8-IP) in exhaled breath condensate (EBC), in the assessment of sarcoidosis activity in relation to somatostatin receptor scintigraphy. The study included 32 patients with sarcoidosis. Scintigraphy was performed using somatostatin analogue, 99mTc-HYNIC-TOC; planar and SPECT/CT images were recorded. The study group was divided into a subgroup with positive radiotracer uptake (n = 20) and without a visible uptake (n = 12). 8-IP levels were measured in EBC by an immunoenzymatic assay. RESULTS We observed a significantly higher EBC 8-IP levels in the subgroup with positive uptake compared with those with negative uptake (19.1 ± 19.8 vs. 5.4 ± 3.5 pg/ml, P = 0.02). The levels of SACE and the percentage of BALF lymphocytes were also nonsignificantly elevated. In the group of patients with positive scintigraphy results, a positive correlation was observed between the uptake ratio and SACE (r = 0.44, P = 0.041). The results indicate low value of biochemical markers in the assessment of disease activity. SR scintigraphy may have practical usefulness in the monitoring of sarcoidosis.

ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation

PubMed Central

Donczew, Magdalena; Mackiewicz, Paweł; Wróbel, Agnieszka; Flärdh, Klas; Zakrzewska-Czerwińska, Jolanta

2016-01-01

In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces. To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins. PMID:27248800

Evaluation of the utility of 99m Tc-MDP bone scintigraphy versus MIBG scintigraphy and cross-sectional imaging for staging patients with neuroblastoma.

PubMed

Gauguet, Jean-Marc; Pace-Emerson, Tamara; Grant, Frederick D; Shusterman, Suzanne; DuBois, Steven G; Frazier, A Lindsay; Voss, Stephan D

2017-11-01

Accurate staging of neuroblastoma requires multiple imaging examinations. The purpose of this study was to determine the relative contribution of 99m Tc-methylene diphosphonate (MDP) bone scintigraphy (bone scan) versus metaiodobenzylguanidine scintigraphy (MIBG scan) for accurate staging of neuroblastoma. A medical record search by the identified patients with neuroblastoma from 1993 to 2012 who underwent both MIBG and bone scan for disease staging. Cross-sectional imaging was used to corroborate the scintigraphy results. Clinical records were used to correlate imaging findings with clinical staging and patient management. One hundred thirty-two patients underwent both MIBG and bone scan for diagnosis. All stage 1 (n = 12), 2 (n = 8), and 4S (n = 4) patients had a normal bone scan with no skeletal MIBG uptake. Six of 30 stage 3 patients had false (+) bone scans. In the 78 stage 4 patients, 58/78 (74%) were both skeletal MIBG(+)/bone scan (+). In 56 of the 58 cases, skeletal involvement detected with MIBG was equal to or greater than that detected by bone scan. Only 3/78 had (-) skeletal MIBG uptake and (+) bone scans; all 3 had other sites of metastatic disease. Five of 78 had (+) skeletal MIBG with a (-) bone scan, while 12/78 had no skeletal involvement by either MIBG or bone scan. In no case did a positive bone scan alone determine a stage 4 designation. In the staging of neuroblastoma, 99m Tc-MDP bone scintigraphy does not identify unique sites of disease that affect disease stage or clinical management, and in the majority of cases bone scans can be omitted from the routine neuroblastoma staging algorithm. © 2017 Wiley Periodicals, Inc.

Pancreas transplants: Evaluation using perfusion scintigraphy

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

Kuni, C.C.; du Cret, R.P.; Boudreau, R.J.

1989-07-01

To determine the value of scintigraphic perfusion studies in evaluating pancreas transplant patients, we reviewed 56 of these studies in 22 patients who had 27 transplants. Seventeen patients underwent two or more studies. The perfusion studies were performed with 20 mCi (740 MBq) of 99mTc-DTPA injected as a bolus followed by eight to 16 serial 2-sec images and a 500,000-count immediate static image. Images were evaluated for (1) the time and intensity of pancreatic peak radioactivity relative to the time and intensity of the iliac arterial peak; (2) relative pancreatic to iliac arterial intensity on the static image; and (3)more » size, homogeneity, and definition of the pancreas. Clinical diagnoses at the time of scintigraphy of normal function (n = 36), rejection (n = 13), pancreatitis (n = 6), or arterial thrombosis (n = 1) were based on insulin requirement, urine amylase, serum glucose, serum amylase, response to therapy, cultures, CT, MR, sonography, scintigraphy with 67Ga or 111In-WBCs, percutaneous drainage results, angiography, surgery, and pathologic examination of resected transplants. Three 99mTc-DTPA perfusion studies showed no pancreatic perfusion, four showed decreasing perfusion on serial studies, and five showed progressive loss of definition of the pancreas on serial studies. Of the three patients with no detectable perfusion, one had a normally functioning transplant, one had arterial thrombosis with transplant infarction, and one had severe rejection with minimal function. Decreasing perfusion was associated with rejection in three patients and pancreatitis in one. Decreasing definition was seen in four patients with rejection and one with pancreatitis. We conclude that perfusion scintigraphy is useful, primarily when performed serially, although nonspecific for evaluating pancreas transplants.« less

Diagnosis of pyogenic pelvic inflammatory diseases by 99mTc-HMPAO leucocyte scintigraphy.

PubMed

Rachinsky, I; Boguslavsky, L; Goldstein, D; Golan, H; Pak, I; Katz, M; Lantsberg, S

2000-12-01

Pelvic inflammatory disease (PID) is one of the major health problems of women of child-bearing age. Among the most serious complications of PID is the formation of a tubo-ovarian abscess (TOA). Early diagnosis of this condition may prevent serious surgical complications such as peritonitis and sepsis, which may be fatal. The purpose of this study was to investigate the efficacy of technetium-99m hexamethylpropylene amine oxime (HMPAO) leucocyte scintigraphy in the diagnosis of TOA. Twenty women with high clinical suspicion of TOA underwent 99mTc-HMPAO leucocyte scintigraphy. The labelling of leucocytes with 99mTc-HMPAO was performed according to a standard protocol. Scans were obtained at 1, 3 and 24 h following the injection of the labelled leucocytes. In eight cases the early and/or late scan was positive, in 11 cases it was negative, and in one case of ovarian cyst torsion, confirmed by laparoscopy, it showed slight uptake in the capsule of the cyst (false-positive). The sensitivity of 99mTc-HMPAO leucocyte scintigraphy was 100%, specificity 91.6%, positive predictive value 89%, negative predictive value 100% and overall accuracy 95%. It is concluded that leucocyte scintigraphy is a non-invasive, safe, physiological and accurate procedure for the diagnosis of TOA. The 24-h scan is crucial, since in some cases the abscess was not clearly visualized on the early scan. Leucocyte scintigraphy may reduce the need for CT, diagnostic laparoscopy and unnecessary invasive surgical procedures.

Identification of Warthin tumor: magnetic resonance imaging versus salivary scintigraphy with technetium-99m pertechnetate.

PubMed

Motoori, Ken; Ueda, Takuya; Uchida, Yoshitaka; Chazono, Hideaki; Suzuki, Homare; Ito, Hisao

2005-01-01

The aim of this study was to evaluate the accuracy of technetium-99m (Tc-99m) pertechnetate scintigraphy and magnetic resonance (MR) imaging in the diagnosis of Warthin tumor. Sixteen cases of Warthin tumor and 17 cases of non-Warthin tumor were examined by Tc-99m pertechnetate scintigraphy with lemon juice stimulation and MR imaging, including T1-weighted, T2-weighted, short inversion time inversion recovery, diffusion-weighted, and contrast-enhanced dynamic images. We used the receiver operating characteristic (ROC) curve to evaluate diagnostic accuracy. The mean area under the ROC curves of MR imaging in the diagnosis of Warthin tumor (0.97) was higher than that of Tc-99m pertechnetate scintigraphy (0.88). Magnetic resonance imaging is more useful in the evaluation of Warthin tumor than Tc-99m pertechnetate scintigraphy.

[Myocardial perfusion scintigraphy - short form of the German guideline].

PubMed

Lindner, O; Burchert, W; Hacker, M; Schaefer, W; Schmidt, M; Schober, O; Schwaiger, M; vom Dahl, J; Zimmermann, R; Schäfers, M

2013-01-01

This guideline is a short summary of the guideline for myocardial perfusion scintigraphy published by the Association of the Scientific Medical Societies in Ger-many (AWMF). The purpose of this guideline is to provide practical assistance for indication and examination procedures as well as image analysis and to present the state-of-the-art of myocardial-perfusion-scintigraphy. After a short introduction on the fundamentals of imaging, precise and detailed information is given on the indications, patient preparation, stress testing, radiopharmaceuticals, examination protocols and techniques, radiation exposure, data reconstruction as well as information on visual and quantitative image analysis and interpretation. In addition possible pitfalls, artefacts and key elements of reporting are described.

Lack of correlation between extended pH monitoring and scintigraphy in the evaluation of infants with gastroesophageal reflux

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

Tolia, V.; Calhoun, J.A.; Kuhns, L.R.

1990-05-01

Sixty-nine infants younger than 1 year of age, with symptoms of persistent vomiting, recurrent choking, apnea, persistent cough, or stridor, were evaluated for gastroesophageal reflux. All infants underwent extended intraesophageal pH monitoring for 16 to 24 hours as well as gastroesophageal scintigraphy with technetium 99m sulfur colloid to study the correlation between the two tests. Forty-eight infants exhibited reflux with extended pH monitoring whereas 46 infants showed reflux with scintigraphy. However, the diagnosis of reflux in individual patients by extended pH monitoring corresponded poorly with the diagnosis of reflux in the same patients by scintigraphy. Similarly, no correlation was observedmore » between extended pH monitoring and scintigraphy results, whether expressed as percent gastric emptying or as gastroesophageal reflux ratio. We conclude that extended pH monitoring and scintigraphy measure different pathophysiologic phenomena and detect reflux under different conditions. The ability of these tests to detect reflux may be complementary and they may be of greatest value when used together to enhance the sensitivity and specificity of the diagnostic evaluation. Extended pH monitoring and scintigraphy should not be used interchangeably to monitor gastroesophageal reflux.« less

Expression of protease-activated receptor (PAR)-2, but not other PARs, is regulated by inflammatory cytokines in rat astrocytes.

PubMed

Sokolova, Elena; Aleshin, Stepan; Reiser, Georg

2012-02-01

Protease-activated receptors (PARs) are widely expressed in the central nervous system (CNS) and are believed to play an important role in normal brain functioning as well as in development of various inflammatory and neurodegenerative disorders. Pathological conditions cause altered expression of PARs in brain cells and therefore altered responsiveness to PAR activation. The exact mechanisms of regulation of PAR expression are not well studied. Here, we evaluated in rat astrocytes the influence of LPS, pro-inflammatory cytokines TNFα and IL-1β and continuous PAR activation by PAR agonists on the expression levels of PARs. These stimuli are important in inflammatory and neurological disorders, where their levels are increased. We report that LPS as well as cytokines TNFα and IL-1β affected only the PAR-2 level, but their effects were opposite. LPS and TNFα increased the functional expression of PAR-2, whereas IL-1β down-regulated the functional response of PAR-2. Agonists of PAR-1 specifically increased mRNA level of PAR-2, but not protein level. Transcript levels of other PARs were not changed after PAR-1 activation. Stimulation of the cells with PAR-2 or PAR-4 agonists did not alter PAR levels. We found that up-regulation of PAR-2 is dependent on PKC activity, mostly via its Ca²⁺-sensitive isoforms. Two transcription factors, NFκB and AP-1, are involved in up-regulation of PAR-2. These findings provide new information about the regulation of expression of PAR subtypes in brain cells. This is of importance for targeting PARs, especially PAR-2, for the treatment of CNS disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Clinical utility of bone scintigraphy in patients with limb pain of suspected musculoskeletal origin

PubMed Central

Ferrari, Robert

2015-01-01

Objective To determine the clinical utility of bone scintigraphy in patients with limb pain of suspected musculoskeletal origin. Material and Methods All patients aged ≥18 years who were referred for diagnosis and management of limb pain were diagnosed on the basis of history, physical examination, and investigations excluding bone scintigraphy. After the presumptive diagnosis was made (the pre-test diagnosis), all subjects underwent bone scintigraphy, or if they had a previous bone scintigram for their pain condition, the results of that scintigram were reviewed. Then, the pre-test diagnosis was reviewed in light of the bone scintigraphy findings and repeat clinical assessment as needed. The post-test diagnosis was considered either as unchanged diagnosis or changed diagnosis for the region or regions of interest. Results There were 118 females (54.8%) and 97 males (45.2%). The mean age of the entire group was 36±8.1 years (range: 18–87 years). The mean duration of the symptoms was 17.4±11.2 months (range: 1–264 months). Of the 215 subjects, 212 had a bone scintigram. Of these 212 subjects, none had a changed diagnosis. Conclusion In the evaluation of limb pain of suspected musculoskeletal origin, scintigraphy is unlikely to alter the pre-test diagnosis or affect treatment decisions after history, physical examination, and non-scintigraphic investigations. The clinical utility of scinitigraphy in this setting is low. PMID:27708914

Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis

PubMed Central

Hasler, W. L.; May, K. P.; Wilson, L. A.; Van Natta, M.; Parkman, H. P.; Pasricha, P. J.; Koch, K. L.; Abell, T. L.; McCallum, R. W.; Nguyen, L. A.; Snape, W. J.; Sarosiek, I.; Clarke, J. O.; Farrugia, G.; Calles-Escandon, J.; Grover, M.; Tonascia, J.; Lee, L. A.; Miriel, L.; Hamilton, F. A.

2018-01-01

Background Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing. Methods A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms. Key Results Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04). Conclusions & Inferences Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities. PMID:28872760

Bone scintigraphy in children with cat scratch disease.

PubMed

Donoso, Gilda; Paulsen, Cesar; Riquelme, Paulina; Lobo, Gabriel; Gutierrez, Daniela; Perez, Andrés; Jiménez, César

2013-12-01

The objective of this study was to evaluate the degree and incidence of bone involvement in patients with cat scratch disease. Patients admitted between 2004 and 2011 at the pediatric department for cat scratch disease and a positive serology for Bartonella henselae were identified. Only those having undergone a bone scintigraphy (BS) were included in this retrospective study. Sixteen girls and 8 boys with a mean age of 7 years were studied. Bone scintigraphy was positive in 6 (25%), but only 2 had bone pain. Axial involvement was present in all 6 patients, and appendicular lesions in 3 of them. Three patients had a BS control, with improvement or normalization after treatment with antibiotics. Bone involvement occurs infrequently in patients with cat scratch disease and is not always associated with specific signs. Cat scratch disease must be suspected in patients with fever of unknown origin presenting multifocal lesions on BS.

Prognostic significance of normal quantitative planar thallium-201 stress scintigraphy in patients with chest pain

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

Wackers, F.J.; Russo, D.J.; Russo, D.

The prognostic significance of normal quantitative planar thallium-201 stress scintigraphy was evaluated in patients with a chest pain syndrome. The prevalence of cardiac events during follow-up was related to the pretest (that is, before stress scintigraphy) likelihood of coronary artery disease determined on the basis of symptoms, age, sex and stress electrocardiography. In a consecutive series of 344 patients who had adequate thallium-201 stress scintigrams, 95 had unequivocally normal studies by quantitative analysis. The pretest likelihood of coronary artery disease in the 95 patients had a bimodal distribution. During a mean follow-up period of 22 +/- 3 months, no patientmore » died. Three patients (3%) had a cardiac event: two of these patients (pretest likelihood of coronary artery disease 54 and 94%) had a nonfatal myocardial infarction 8 and 22 months, respectively, after stress scintigraphy, and one patient (pretest likelihood 98%) underwent percutaneous transluminal coronary angioplasty 16 months after stress scintigraphy for persisting anginal complaints. Three patients were lost to follow-up; all three had a low pretest likelihood of coronary artery disease. It is concluded that patients with chest pain and normal findings on quantitative thallium-201 scintigraphy have an excellent prognosis. Cardiac events are rare (infarction rate 1% per year) and occur in patients with a moderate to high pretest likelihood of coronary artery disease.« less

Thallium-201 scintigraphy in the diagnosis and management of myocardial sarcoidosis

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

Fields, C.L.; Ossorio, M.A.; Roy, T.M.

1990-03-01

We have described three patients with clinical evidence of myocardial sarcoidosis to illustrate the utility of thallium-201 scintigraphy in demonstrating the myocardial lesions. Both the symptomatic and asymptomatic individuals studied showed the characteristic reverse redistribution phenomenon. No abnormalities were seen during the exercise phase of the thallium study, but myocardial defects were detected in each patient when repeat studies were obtained at rest six hours later. Steroid therapy resolved the defects in each case. We propose thallium-201 scintigraphy of the heart as a safe and useful tool for documenting myocardial involvement in sarcoidosis and following the effects of therapy.

Novel role for proteinase-activated receptor 2 (PAR2) in membrane trafficking of proteinase-activated receptor 4 (PAR4).

PubMed

Cunningham, Margaret R; McIntosh, Kathryn A; Pediani, John D; Robben, Joris; Cooke, Alexandra E; Nilsson, Mary; Gould, Gwyn W; Mundell, Stuart; Milligan, Graeme; Plevin, Robin

2012-05-11

Proteinase-activated receptors 4 (PAR(4)) is a class A G protein-coupled receptor (GPCR) recognized through the ability of serine proteases such as thrombin and trypsin to mediate receptor activation. Due to the irreversible nature of activation, a fresh supply of receptor is required to be mobilized to the cell surface for responsiveness to agonist to be sustained. Unlike other PAR subtypes, the mechanisms regulating receptor trafficking of PAR(4) remain unknown. Here, we report novel features of the intracellular trafficking of PAR(4) to the plasma membrane. PAR(4) was poorly expressed at the plasma membrane and largely retained in the endoplasmic reticulum (ER) in a complex with the COPI protein subunit β-COP1. Analysis of the PAR(4) protein sequence identified an arginine-based (RXR) ER retention sequence located within intracellular loop-2 (R(183)AR → A(183)AA), mutation of which allowed efficient membrane delivery of PAR(4). Interestingly, co-expression with PAR(2) facilitated plasma membrane delivery of PAR(4), an effect produced through disruption of β-COP1 binding and facilitation of interaction with the chaperone protein 14-3-3ζ. Intermolecular FRET studies confirmed heterodimerization between PAR(2) and PAR(4). PAR(2) also enhanced glycosylation of PAR(4) and activation of PAR(4) signaling. Our results identify a novel regulatory role for PAR(2) in the anterograde traffic of PAR(4). PAR(2) was shown to both facilitate and abrogate protein interactions with PAR(4), impacting upon receptor localization and cell signal transduction. This work is likely to impact markedly upon the understanding of the receptor pharmacology of PAR(4) in normal physiology and disease.

A Conserved Mode of Protein Recognition and Binding in a ParD−ParE Toxin−Antitoxin Complex

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

Dalton, Kevin M.; Crosson, Sean

2010-05-06

Toxin-antitoxin (TA) systems form a ubiquitous class of prokaryotic proteins with functional roles in plasmid inheritance, environmental stress response, and cell development. ParDE family TA systems are broadly conserved on plasmids and bacterial chromosomes and have been well characterized as genetic elements that promote stable plasmid inheritance. We present a crystal structure of a chromosomally encoded ParD-ParE complex from Caulobacter crescentus at 2.6 {angstrom} resolution. This TA system forms an {alpha}{sub 2}{beta}{sub 2} heterotetramer in the crystal and in solution. The toxin-antitoxin binding interface reveals extensive polar and hydrophobic contacts of ParD antitoxin helices with a conserved recognition and bindingmore » groove on the ParE toxin. A cross-species comparison of this complex structure with related toxin structures identified an antitoxin recognition and binding subdomain that is conserved between distantly related members of the RelE/ParE toxin superfamily despite a low level of overall primary sequence identity. We further demonstrate that ParD antitoxin is dimeric, stably folded, and largely helical when not bound to ParE toxin. Thus, the paradigmatic model in which antitoxin undergoes a disorder-to-order transition upon toxin binding does not apply to this chromosomal ParD-ParE TA system.« less

ROC analysis of diagnostic performance in liver scintigraphy.

PubMed

Fritz, S L; Preston, D F; Gallagher, J H

1981-02-01

Studies on the accuracy of liver scintigraphy for the detection of metastases were assembled from 38 sources in the medical literature. An ROC curve was fitted to the observed values of sensitivity and specificity using an algorithm developed by Ogilvie and Creelman. This ROC curve fitted the data better than average sensitivity and specificity values in each of four subsets of the data. For the subset dealing with Tc-99m sulfur colloid scintigraphy, performed for detection of suspected metastases and containing data on 2800 scans from 17 independent series, it was not possible to reject the hypothesis that interobserver variation was entirely due to the use of different decision thresholds by the reporting clinicians. Thus the ROC curve obtained is a reasonable baseline estimate of the performance potentially achievable in today's clinical setting. Comparison of new reports with these data is possible, but is limited by the small sample sizes in most reported series.

An Alternate, Egg-Free Radiolabeled Meal Formulation for Gastric-Emptying Scintigraphy.

PubMed

Garrigue, Philippe; Bodin-Hullin, Aurore; Gonzalez, Sandra; Sala, Quentin; Guillet, Benjamin

2017-07-01

Tc-radiolabeled scrambled eggs (SEs) are most often used as the ingested solid phase for gastric-emptying scintigraphy, leading egg-reluctant patients to avoid the examination. We formulated and validated 2 egg-free alternate meals, in the absence of any commercialized formulation: chocolate mug cake (MC) and scrambled tofu (ST). Six healthy volunteers underwent gastric-emptying scintigraphy after ingesting Tc-radiolabeled MC, ST, or SE. Gastric retention indexes did not change significantly between formulations (% of overtime variation to SE: MC 7.75% ± 7.1%, ST 7.17% ± 5.8%; P = 0.6618, not statistically significant), suggesting MC and ST as interesting egg-free alternatives.

[Lung scintigraphy].

PubMed

Schümichen, Carl; Schmidt, Matthias; Krause, Thomas

2018-06-01

The S1 guideline for lung scintigraphy has been updated and extended in order to emphasize the advantages oft the method in detecting acute pulmonary embolism (PE) in the periphery oft the lung (subsegmental PE), in underlying subacute and chronic pulmonary disorders, as well as in detecting chronic LE (CTEPH). Method of choice is ventilation / perfusion (V/P) SPECT or V/P SPECT/CT with even higher specificity. Because of its high sensitivity, a threshold (V/P mismatch in at least one segment or two subsegments) is introduced to avoid overtreatment. In case of a change in the therapeutic approach (observation only instead of anticoaculation) the threshold can be omitted. New data concerning the clinical and therapeutical impact of subsegmental PE are included, the chapters open questions have been extented. Other indications for V/P SPECT (secondary diagnoses, abnormalities in pulmonary perfusion, prediction of postoperative lung function) are presented with new data. Schattauer GmbH.

[Utility of methoxy isobutyl isonitrile (MIBI) scintigraphy, ultrasound and computerized axial tomography in preoperative topographic diagnosis of hiperparathyroidism].

PubMed

Gómez Palacios, Angel; Gómez Zábala, Jesús; Gutiérrez, María Teresa; Expósito, Amaya; Barrios, Borja; Zorraquino, Angel; Taibo, Miguel Angel; Iturburu, Ignacio

2006-12-01

1. To assess the sensitivity of scintigraphy using methoxy isobutyl isonitrile (MIBI). 2. To compare its resolution with that of ultrasound (US) and computerized axial tomography (CAT). 3. To use its diagnostic reliability to determine whether selective approaches can be used to treat hyperparathyroidism (HPT). A study of 76 patients who underwent surgery for HPT between 1996 and 2005 was performed. MIBI scintigraphy and cervical US were used for whole-body scanning in all patients; CAT was used in 47 patients. Intraoperative and postoperative biopsies were used for final evaluation of the tests, after visualization and surgical extirpation. The results of scintigraphy were positive in 65 patients (85.52%). The diagnosis was correct in all of the single images. Multiple images were due to hyperplasia and parathyroid adenomas with thyroid disease (5.2%). Three images, incorrectly classified as negative (3.94%), were positive. The sensitivity of US was 63% and allowed detection of three MIBI-negative adenomas (4%). CAT was less sensitive (55%), but detected a further three MIBI-negative adenomas (4%). 1. The sensitivity of MIBI reached 89.46%. In the absence of thyroid nodules, MIBI diagnosed 100% of single lesions. Pathological thyroid processes produced false-positive results (5.2%) and there were diagnostic errors (4%). 2. MIBI scintigraphy was more sensitive than US and CAT. 3. Positive, single image scintigraphy allows a selective cervical approach. US and CAT may help to save a further 8% of patients (with negative scintigraphy).

Miscellaneous indications in bone scintigraphy: metabolic bone diseases and malignant bone tumors.

PubMed

Cook, Gary J R; Gnanasegaran, Gopinath; Chua, Sue

2010-01-01

The diphosphonate bone scan is ideally suited to assess many global, focal or multifocal metabolic bone disorders and there remains a role for conventional bone scintigraphy in metabolic bone disorders at diagnosis, investigation of complications, and treatment response assessment. In contrast, the role of bone scintigraphy in the evaluation of primary malignant bone tumors has reduced with the improvement of morphologic imaging, such as computed tomography and magnetic resonance imaging. However, an increasing role for (18)F-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography is emerging as a functional assessment at diagnosis, staging, and neoadjuvant treatment response assessment.

[Somatostatin receptor scintigraphy in medullary thyroid carcinomas, GEP and carcinoid tumors].

PubMed

Eising, E G; Farahati, J; Bier, D; Knust, E J; Reiners, C

1995-02-01

For this study, 24 patients with medullary thyroid cancer (MTC) and 10 with carcinoid-/GEP-tumours underwent scintigraphy with 123I-Tyr3-octreotide or 111In-DTPA-D-Phe1-octreotide (Octreoscan) or 99mTc-V-DMSA. Calcitonin and CEA were elevated in MTC patients, the other had tumour lesions on CT. Octreoscan-scintigraphy was positive in 68% of all suspicious cases. On the other hand, 123I-Tyr3-octreotide showed only rarely positive results. 99mTc-V-DMSA-scans in MTC patients were positive in 23%. Liver metastases could be seen only with Octreoscan in the non-MTC-group. These results showed better sensitivity of 111In-labelled octreotide.

Association of hyperfunctioning thyroid adenoma with thyroid cancer presenting as "trapping only" nodule at 99mTcO4- scintigraphy.

PubMed

dell'Erba, L; Gerundini, P; Caputo, M; Bagnasco, M

2003-11-01

Rarely may a non-hyperfunctioning thyroid nodule present as "hot" at Technetium-99m pertechnetate (99mTcO4-) and "cold" at radioiodine scintigraphy at late acquisitions. We report the case of a hyperthyroid female patient whose 99mTcO4- scintigraphy showed two "hot" nodules, whereas Iodide-131 (131I-) revealed a lack of indicator uptake by the larger, and intense uptake by the smaller nodule. The patient underwent surgery: histology demonstrated that the larger nodule, mismatched at pertechnetate vs iodine scintigraphy, was a papillary carcinoma. Our suggestion is to perform thyroid scintigraphy with radioiodine in hyperthyroid patients with more than one nodule concentrating pertechnetate, especially when an ultrasonographic pattern possibly suspect for malignancy is present.

[Screening with angiographic images prior to (99m)Tc-HMPAO labelled leukocyte scintigraphy in the diagnosis of periprosthetic infection].

PubMed

Granados, U; Fuster, D; Soriano, A; García, S; Bori, G; Martínez, J C; Mayoral, M; Perlaza, P; Tomás, X; Pons, F

2015-01-01

To evaluate the impact of the angioscintigrapy of the three phase bone scan as screening method to rule out infection of the hip and knee prosthesis prior to performing the (99m)Tc-HMPAO leukocyte scintigraphy. A total of 120 (70 women, 50 men; mean age 71±11years) with clinical suspicion of hip (n=63) or knee (n=57) infection of the prosthesis and clinical suspicion of infection were evaluated prospectively. All patients underwent three-phase bone scan (angioscintigraphy, vascular and bone phase) and (99m)Tc-HMPAO-labelled white blood cell scintigraphy. Final diagnosis of infection was made by microbiological documentation or clinical follow-up for at least 12months. Eighteen out of 120 patients were diagnosed of infection of hip prosthesis (n=10) or knee prosthesis (n=8). The angioscintigraphy was positive in 15/18 infected cases and in 21/102 of the non-infected cases with a sensitivity of 83%, specificity of 79% and negative predictive value of 97%. Sensitivity and specificity of (99m)Tc-HMPAO leukocyte scintigraphy were 72% and 95%, respectively. If the leukocyte labeled scintigraphies had been used exclusively for patients with positive angioscintigraphy, this would have saved up to 70% of the (99m)Tc-HMPAO leukocyte scintigraphies performed. There were no cases of infection with positive labeled leukocyte scintigraphy and negative angioscintigraphy. Angioscintigraphy (blood flow phase of bone scan) is a useful technique for screening for hip and knee joint prosthesis infection, significantly reducing the need for (99m)Tc-HMPAO leukocyte scintigraphy without affecting the sensitivity of the technique. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Importance of the lung perfusion scintigraphy in single lung transplantation.

PubMed

Rodríguez Mesa, N V; Guerrero Cancio, M C; Cordero Jiménez, M D; Alvarez Velázquez, I K

2012-01-01

Lung perfusion scintigraphy (LPS) with (99m)Tc-MAA gives valuable information about patients who will undergo a single lung transplantation. This technique makes it possible to evaluate and quantify the relative function of both lungs to select the organ to be transplanted. Once the surgery has been performed, the LPS represents a diagnostic method to study the status of the transplanted organ. Two patients who underwent single lung transplantation were studied in our hospital. In both cases, a pre-operative LPS was performed before surgery for selection of the organ to be transplanted and the scintigraphy study was performed a few months after transplantation to establish the perfusion function of the transplanted lung. Copyright © 2011 Elsevier España, S.L. y SEMNIM. All rights reserved.

Par Pond vegetation status 1996

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

Mackey, H.E. Jr.; Riley, R.S.

1996-12-01

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995, and into themore » early spring and late summer of 1996. Communities similar to the pre-drawdown, Par Pond aquatic plant communities continue to become re-established. Emergent beds of maidencane, lotus, waterlily, watershield, and Pontederia are extensive and well developed. Measures of percent cover, width of beds, and estimates of area of coverage with satellite data indicate regrowth within two years of from 40 to 60% of levels prior to the draw down. Cattail occurrence continued to increase during the summer of 1996, especially in the former warm arm of Par Pond, but large beds common to Par Pond prior to the draw down still have not formed. Lotus has invaded and occupies many of the areas formerly dominated by cattail beds. To track the continued development of macrophytes in Par Pond, future surveys through the summer and early fall of 1997, along with the evaluation of satellite data to map the extent of the macrophyte beds of Par Pond, are planned.« less

Matrix metalloproteases and PAR1 activation

PubMed Central

Austin, Karyn M.; Covic, Lidija

2013-01-01

Cardiovascular diseases, including atherothrombosis, are the leading cause of morbidity and mortality in the United States, Europe, and the developed world. Matrix metalloproteases (MMPs) have recently emerged as important mediators of platelet and endothelial function, and atherothrombotic disease. Protease-activated receptor-1 (PAR1) is a G protein-coupled receptor that is classically activated through cleavage of the N-terminal exodomain by the serine protease thrombin. Most recently, 2 MMPs have been discovered to have agonist activity for PAR1. Unexpectedly, MMP-1 and MMP-13 cleave the N-terminal exodomain of PAR1 at noncanonical sites, which result in distinct tethered ligands that activate G-protein signaling pathways. PAR1 exhibits metalloprotease-specific signaling patterns, known as biased agonism, that produce distinct functional outputs by the cell. Here we contrast the mechanisms of canonical (thrombin) and noncanonical (MMP) PAR1 activation, the contribution of MMP-PAR1 signaling to diseases of the vasculature, and the therapeutic potential of inhibiting MMP-PAR1 signaling with MMP inhibitors, including atherothrombotic disease, in-stent restenosis, heart failure, and sepsis. PMID:23086754

Predictive value of bone scintigraphy for the detection of joint involvement in Behçet's disease: Dermatologists' perspectives.

PubMed

Seo, Jimyung; Lee, Minseok; Choi, Min Ju; Zheng, Zhenlong; Cho, Arthur; Bang, Dongsik; Kim, Do Young

2015-01-01

Behçet's disease (BD) is a multisystemic inflammatory disease with articular involvement. Non-specific arthralgia without objective signs of arthritis, such as swelling or effusion, is common in such patients. Thus, an accurate diagnosis of joint involvement may be challenging for dermatologists. To evaluate the validity of (99m)Tc-methylene diphosphonate (Tc-99m-MDP) bone scintigraphy for joint involvement assessment in patients with BD. In 211 patients with BD who had scintigraphic evaluations due to joint symptoms, agreement between bone scintigraphy findings and clinically evaluated joint complaints was retrospectively assessed using Cohen's kappa (κ) statistic. A patient subset (n = 104) showing agreement between joint complaints and scintigraphy results was re-evaluated by a rheumatologist to determine the level of diagnostic specificity attained by combining bone scintigraphy with clinical examinations of dermatologists. The total kappa value (211 patients) was 0.604, indicating fair agreement between joint complaints and scintigraphy results. Individual analysis of eleven joint categories revealed statistically significant correlations for wrist (κ = 0.677), shoulder (κ = 0.661), and foot joints (κ = 0.618). Of the 104 referrals to a rheumatologist, 95 (91.34%) were confirmed as having BD-associated articular involvement. Joint acral areas (e.g., foot, hand, wrist and shoulder) that had the highest kappa value correlations also ranked highest in diagnostic specificity. Bone scintigraphy presents a simple and useful option for dermatologists to assess joint involvement in BD patients, especially for specific anatomic sites.

Comparison of Tc-99m GSA scintigraphy and CT volumetry for evaluation in portal vein embolization.

PubMed

Kono, Yumiko; Kariya, Shuji; Komemushi, Atsushi; Nakatani, Miyuki; Yoshida, Rie Yagi; Suzuki, Satoshi; Ha-Kawa, Sung Kil; Utsunomiya, Keita; Ueno, Yasuhiro; Satoi, Sohei; Kaibori, Masaki; Kon, Masanori; Tanigawa, Noboru

2014-08-01

To determine the correlation of the rate of change of each future remnant liver (FRL) before and after portal vein embolization (PVE), by CT volumetry and Tc-99m galactosyl human serum albumin scintigraphy (GSA scintigraphy). From December 2007 to July 2012, ten patients underwent PVE before hepatic resection. CT volumetry and GSA scintigraphy were performed before and after PVE. The FRL was divided at Cantlie's line for CT volumetry, and volume change rates before and after PVE were calculated. The maximum removal rate (Rmax) was calculated using a radiopharmacokinetic model in GSA scintigraphy. The FRL Rmax change rates before and after PVE were calculated. The correlation between the volume change rates and the Rmax change rates was analyzed. The FRL volume change rate was 1.28 ± 0.26 (mean ± SD); the FRL hypertrophied in all patients significantly (p = 0.005). The FRL Rmax change rate was 1.66 ± 0.75; excluding one patient, there was significant FRL Rmax increase (p = 0.022). Although both increased significantly, no correlation between the volume change rate and the Rmax change rate was observed. No correlation was observed between the FRL volume rate and the Rmax rate.

Functional imaging of SDHx-related head and neck paragangliomas: comparison of 18F-fluorodihydroxyphenylalanine, 18F-fluorodopamine, 18F-fluoro-2-deoxy-D-glucose PET, 123I-metaiodobenzylguanidine scintigraphy, and 111In-pentetreotide scintigraphy.

PubMed

King, Kathryn S; Chen, Clara C; Alexopoulos, Dimitrios K; Whatley, Millie A; Reynolds, James C; Patronas, Nicholas; Ling, Alexander; Adams, Karen T; Xekouki, Paraskevi; Lando, Howard; Stratakis, Constantine A; Pacak, Karel

2011-09-01

Accurate diagnosis of head and neck paragangliomas is often complicated by biochemical silence and lack of catecholamine-associated symptoms, making accurate anatomical and functional imaging techniques essential to the diagnostic process. Ten patients (seven SDHD, three SDHB), with a total of 26 head and neck paragangliomas, were evaluated with anatomical and functional imaging. This study compares five different functional imaging techniques [(18)F-fluorodihydroxyphenylalanine ((18)F-FDOPA) positron emission tomography (PET), (18)F-fluorodopamine ((18)F-FDA) PET/computed tomography (CT), (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/CT, (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy, and (111)In-pentetreotide scintigraphy] in the localization of head and neck paragangliomas. Prospectively (18)F-FDOPA PET localized 26 of 26 lesions in the 10 patients, CT/magnetic resonance imaging localized 21 of 26 lesions, (18)F-FDG PET/CT localized 20 of 26 lesions, (111)In-pentetreotide scintigraphy localized 16 of 25 lesions, (18)F-FDA PET/CT localized 12 of 26 lesions, and (123)I-MIBG scintigraphy localized eight of 26 lesions. Differences in imaging efficacy related to genetic phenotype, even in the present small sample size, included the negativity of (18)F-FDA PET/CT and (123)I-MIBG scintigraphy in patients with SDHB mutations and the accuracy of (18)F-FDG PET/CT in all patients with SDHD mutations, as compared with the accuracy of (18)F-FDG PET/CT in only one patient with an SDHB mutation. Overall, (18)F-FDOPA PET proved to be the most efficacious functional imaging modality in the localization of SDHx-related head and neck paragangliomas and may be a potential first-line functional imaging agent for the localization of these tumors.

Periostitis in secondary syphilis: a place for bone scintigraphy.

PubMed Central

Veerapen, K; Bruckner, F E; Halsey, J P; Davidson, F; Saeed, A

1985-01-01

Two cases of secondary syphilis are reported with periostitis as the main presenting feature. Technetium-99m bone scintigraphy was found to be superior to radiography in both defining the extent of involvement and in picking up early lesions. Images Figure 1. Figure 2. Figure 3. PMID:4045902

Premature extravasation. A bleeding site identified during the dynamic phase of Tc-99m red blood cell bleeding scintigraphy.

PubMed

el-Shirbiny, A; Fernandez, R; Zuckier, L S

1995-08-01

Tc-99m RBC scintigraphy is favored by many investigators because it provides the ability to image the abdomen over a prolonged period of time, thereby allowing identification of delayed bleeding sites that are frequently encountered due to the intermittent nature of gastrointestinal bleeding. The authors describe a case of bleeding scintigraphy with labeled red blood cells in which the bleeding site was identifiable only on the dynamic blood-flow and first static images. On later images, the labeled blood cells had spread throughout the colon, rendering localization of the actual bleeding site impossible. Two previous red blood cell scintigraphies and a subsequent contrast angiogram did not reveal sites of active bleeding. As illustrated by this unusual case, factors governing timing and visualization of abnormal bleeding sites are discussed, as is a differential diagnosis of abnormal foci of activity seen on the dynamic phase of bleeding scintigraphy.

Symptomatic rotator cuff tears show higher radioisotope uptake on bone scintigraphy compared with asymptomatic tears.

PubMed

Koike, Yoichi; Sano, Hirotaka; Kita, Atushi; Itoi, Eiji

2013-09-01

Some patients with rotator cuff tears complain of pain, whereas others are asymptomatic. Previous studies have pointed out the presence of active bone metabolism in the painful shoulder, identified with increased radioisotope uptake during bone scintigraphy. Shoulders with symptomatic rotator cuff tears will demonstrate higher radioisotope uptake than shoulders with asymptomatic tears with bone scintigraphy, reflecting active bone metabolism in symptomatic tears. Cross-sectional study; Level of evidence, 3. The study consisted of 3 groups: patients with symptomatic tears (symptomatic group), patients with asymptomatic tears (asymptomatic group), and controls (no tear group). The symptomatic group consisted of 28 shoulders from 28 patients with symptomatic rotator cuff tears (pain score ≤4 on the University of California, Los Angeles [UCLA] shoulder evaluation form) who underwent bone scintigraphy followed by rotator cuff repair. Of 70 volunteers who had previously undergone bone scintigraphy for diseases unrelated to their shoulder, 34 were selected for the asymptomatic group (pain score ≥8 on the UCLA shoulder form), and 32 were selected for the no tear group. The mean radioisotope uptake in the symptomatic group was significantly higher than that in the asymptomatic group (P = .02) and the no tear group (P = .02). Ten of 28 shoulders (36%) in the symptomatic group showed increased radioisotope uptake exceeding 2 standard deviations from the mean of the no tear group. This percentage was significantly higher when compared with the asymptomatic group (0%) (P < .01). Shoulders with a symptomatic rotator cuff tear showed higher radioisotope uptake on bone scintigraphy than those with an asymptomatic tear. The radioisotope uptake in shoulders with an asymptomatic tear was comparable with that in shoulders without a tear. Positive radioisotope uptake may be associated with pain in a subgroup of patients with rotator cuff tears.

The tail of the ParG DNA segregation protein remodels ParF polymers and enhances ATP hydrolysis via an arginine finger-like motif

PubMed Central

Barillà, Daniela; Carmelo, Emma; Hayes, Finbarr

2007-01-01

The ParF protein of plasmid TP228 belongs to the ubiquitous superfamily of ParA ATPases that drive DNA segregation in bacteria. ATP-bound ParF polymerizes into multistranded filaments. The partner protein ParG is dimeric, consisting of C-termini that interweave into a ribbon–helix–helix domain contacting the centromeric DNA and unstructured N-termini. ParG stimulates ATP hydrolysis by ParF ≈30-fold. Here, we establish that the mobile tails of ParG are crucial for this enhancement and that arginine R19 within the tail is absolutely required for activation of ParF nucleotide hydrolysis. R19 is part of an arginine finger-like loop in ParG that is predicted to intercalate into the ParF nucleotide-binding pocket thereby promoting ATP hydrolysis. Significantly, mutations of R19 abrogated DNA segregation in vivo, proving that intracellular stimulation of ATP hydrolysis by ParG is a key regulatory process for partitioning. Furthermore, ParG bundles ParF-ATP filaments as well as promoting nucleotide-independent polymerization. The N-terminal flexible tail is required for both activities, because N-terminal ΔParG polypeptides are defective in both functions. Strikingly, the critical arginine finger-like residue R19 is dispensable for ParG-mediated remodeling of ParF polymers, revealing that the ParG N-terminal tail possesses two separable activities in the interplay with ParF: a catalytic function during ATP hydrolysis and a mechanical role in modulation of polymerization. We speculate that activation of nucleotide hydrolysis via an arginine finger loop may be a conserved, regulatory mechanism of ParA family members and their partner proteins, including ParA-ParB and Soj-Spo0J that mediate DNA segregation and MinD-MinE that determine septum localization. PMID:17261809

The tail of the ParG DNA segregation protein remodels ParF polymers and enhances ATP hydrolysis via an arginine finger-like motif.

PubMed

Barillà, Daniela; Carmelo, Emma; Hayes, Finbarr

2007-02-06

The ParF protein of plasmid TP228 belongs to the ubiquitous superfamily of ParA ATPases that drive DNA segregation in bacteria. ATP-bound ParF polymerizes into multistranded filaments. The partner protein ParG is dimeric, consisting of C-termini that interweave into a ribbon-helix-helix domain contacting the centromeric DNA and unstructured N-termini. ParG stimulates ATP hydrolysis by ParF approximately 30-fold. Here, we establish that the mobile tails of ParG are crucial for this enhancement and that arginine R19 within the tail is absolutely required for activation of ParF nucleotide hydrolysis. R19 is part of an arginine finger-like loop in ParG that is predicted to intercalate into the ParF nucleotide-binding pocket thereby promoting ATP hydrolysis. Significantly, mutations of R19 abrogated DNA segregation in vivo, proving that intracellular stimulation of ATP hydrolysis by ParG is a key regulatory process for partitioning. Furthermore, ParG bundles ParF-ATP filaments as well as promoting nucleotide-independent polymerization. The N-terminal flexible tail is required for both activities, because N-terminal DeltaParG polypeptides are defective in both functions. Strikingly, the critical arginine finger-like residue R19 is dispensable for ParG-mediated remodeling of ParF polymers, revealing that the ParG N-terminal tail possesses two separable activities in the interplay with ParF: a catalytic function during ATP hydrolysis and a mechanical role in modulation of polymerization. We speculate that activation of nucleotide hydrolysis via an arginine finger loop may be a conserved, regulatory mechanism of ParA family members and their partner proteins, including ParA-ParB and Soj-Spo0J that mediate DNA segregation and MinD-MinE that determine septum localization.

Control of cleavage spindle orientation in Caenorhabditis elegans: The role of the genes par-2 and par-3

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

Cheng, N.N.; Kirby, C.M.; Kemphues, K.J.

1995-02-01

Polarized asymmetric divisions play important roles in the development of plants and animals. The first two embryonic cleavages of Caenorhabditis elegans provide an opportunity to study the mechanisms controlling polarized asymmetric divisions. The first cleavage is unequal, producing daughters with different sizes and fates. The daughter blastomeres divide with different orientations at the second cleavage; the anterior blastomere divides equally across the long axis of the egg, whereas the posterior blastomere divides unequally along the long axis. We report here the results of our analysis of the genes par-2 and par-3 with respect to their contribution to the polarity ofmore » these divisions. Strong loss-of-function mutations in both genes lead to an equal first cleavage and an altered second cleavage. Interestingly, the mutations exhibit striking gene-specific differences at the second cleavage. The par-2 mutations lead to transverse spindle orientations in both blastomeres, whereas par-3 mutations lead to longitudinal spindle orientations in both blastomeres. The spindle orientation defects correlate with defects in centrosome movements during both the first and the second cell cycle. Temperature shift experiments with par-2 (it5ts) indicate that the par-2(+) activity is not required after the two-cell stage. Analysis of double mutants shows that par-3 is epistatic to par-2. We propose a model wherein par-2(+) and par-3(+) act in concert during the first cell cycle to affect asymmetric modification of the cytoskeleton. This polar modification leads to different behaviors of centrosomes in the anterior and posterior and leads ultimately to blastomere-specific spindle orientations at the second cleavage. 44 refs., 5 figs., 5 tabs.« less

123I-MIBG scintigraphy and 18F-FDG-PET imaging for diagnosing neuroblastoma.

PubMed

Bleeker, Gitta; Tytgat, Godelieve A M; Adam, Judit A; Caron, Huib N; Kremer, Leontien C M; Hooft, Lotty; van Dalen, Elvira C

2015-09-29

Neuroblastoma is an embryonic tumour of childhood that originates in the neural crest. It is the second most common extracranial malignant solid tumour of childhood.Neuroblastoma cells have the unique capacity to accumulate Iodine-123-metaiodobenzylguanidine (¹²³I-MIBG), which can be used for imaging the tumour. Moreover, ¹²³I-MIBG scintigraphy is not only important for the diagnosis of neuroblastoma, but also for staging and localization of skeletal lesions. If these are present, MIBG follow-up scans are used to assess the patient's response to therapy. However, the sensitivity and specificity of ¹²³I-MIBG scintigraphy to detect neuroblastoma varies according to the literature.Prognosis, treatment and response to therapy of patients with neuroblastoma are currently based on extension scoring of ¹²³I-MIBG scans. Due to its clinical use and importance, it is necessary to determine the exact diagnostic accuracy of ¹²³I-MIBG scintigraphy. In case the tumour is not MIBG avid, fluorine-18-fluorodeoxy-glucose ((18)F-FDG) positron emission tomography (PET) is often used and the diagnostic accuracy of this test should also be assessed. 1.1 To determine the diagnostic accuracy of ¹²³I-MIBG (single photon emission computed tomography (SPECT), with or without computed tomography (CT)) scintigraphy for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old.1.2 To determine the diagnostic accuracy of negative ¹²³I-MIBG scintigraphy in combination with (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old, i.e. an add-on test. 2.1 To determine the diagnostic accuracy of (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old.2.2 To compare the diagnostic accuracy of ¹²³I-MIBG (SPECT-CT) and (18)F

99m-Technetium phosphate compound joint scintigraphy in the management of juvenile osteochondritis dissecans of the femoral condyles

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

Cahill, B.R.; Berg, B.C.

The known sensitivity of joint scintigraphy in following the course of fracture healing caused the authors to believe that this radiologic technique might be valuable in the management of osteochondritis dissecans (OCD). Accordingly, 99mTc-diphosphonate joint scintigraphy was used on 18 patients with OCD of the knee. The average age was 13 1/2 years. The scintigrams were repeated at 6-week intervals until healing had occurred. When the diagnosis of OCD was established by standard roentgenograms and joint scintigraphy, the patients were placed on an activity restriction program, attempting to reach a symptom-free level. The patients were followed for an average ofmore » 18 months. Ninety-five scans were categorized according to their level of scintigraphic activity. This led to a discrete four-part scintigraphic classification that is indicative of the extent of healing or progression of this condition, and precedes changes seen on standard x-rays by months. Joint scintigraphy also rules out anomalies of ossification in the diagnosis of OCD since an anomaly should have a normal scintigraphic appearance. We have concluded that joint scintigraphy is valuable in the management of OCD because of its superior sensitivity to changes in the activity of the lesion. As experience is gained with this technique, those cases that should be prophylactically surgically stabilized may be indicated.« less

99mTc-HYNIC-TOC scintigraphy is superior to 131I-MIBG imaging in the evaluation of extraadrenal pheochromocytoma.

PubMed

Chen, Libo; Li, Fang; Zhuang, Hongming; Jing, Hongli; Du, Yanrong; Zeng, Zhengpei

2009-03-01

In this investigation, the efficacy of scintigraphy using (99m)Tc-labeled hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) in the evaluation of extraadrenal pheochromocytoma was assessed and compared with (131)I-labeled metaiodobenzylguanidine (MIBG) imaging. Ninety-seven patients who were suspected of having pheochromocytoma but showed no definite adrenal abnormalities on CT were evaluated by both (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging. The results were compared with pathology findings or clinical follow-up. Of 58 patients proven to be without pheochromocytoma, (99m)Tc-HYNIC-TOC and (131)I-MIBG imaging excluded 56 and 58 patients, respectively, rendering a specificity of 96.6% for (99m)Tc-HYNIC-TOC imaging and 100% for (131)I-MIBG imaging. In the evaluation of adrenal pheochromocytoma (14 patients), the sensitivity of (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging was 50% and 85.7%, respectively. However, in the evaluation of extraadrenal pheochromocytomas (25 patients), the sensitivity of (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging was 96.0% and 72.0%, respectively. (99m)Tc-HYNIC-TOC scintigraphy is more sensitive than (131)I-MIBG imaging in the detection of extraadrenal pheochromocytomas.

Can computed tomography volumetry of the renal cortex replace MAG3-scintigraphy in all patients for determining split renal function?

PubMed

Houbois, Christian; Haneder, Stefan; Merkt, Martin; Morelli, John N; Schmidt, Matthias; Hellmich, Martin; Mueller, Roman-Ulrich; Wahba, Roger; Maintz, David; Puesken, Michael

2018-06-01

The current gold standard for determination of split renal function (SRF) is Tc-99m-mercapto-acetyltriglycin (MAG3) scintigraphy. Initial studies comparing MAG3-scintigraphy and CT-based renal cortex volumetry (RCV) for calculation of SRF have shown similar results in highly selected patient collectives with normal renal function (i.e. living kidney donors). This study aims to compare MAG3-scintigraphy and CT-RCV within a large unselected patient collective including patients with impaired renal function. For this assessment, 279 datasets (131 men, 148 women; mean age: 54.2 ± 12.9 years, range: 24-84 years) of patients who underwent MAG3-scintigraphy and contrast-enhanced abdominal CT within two weeks were retrospectively analyzed. Two independent readers assessed the CT-RCV in all CT datasets using a semi-automated volumetry tool. The MAG3-scintigraphy and CT-RCV methods were compared, stratified for the eGFR. Statistical analysis included descriptive statistics as well as inter- observer agreement. The absolute mean difference between the percentage contribution of the left and the right kidneys in total MAG3-clearance was 8.6%. Independent of eGFR, an overall sufficient agreement between both methods was established in all patients. A relatively small, tolerable systemic error resulted in an underestimation (max. 2%) of the left renal contribution to overall RCV. The results demonstrate that CT-RCV is a potential clinical replacement for MAG3-scintigraphy for calculation of SRF: CT-RCV demonstrates clinically tolerable differences with MAG3-scintigraphy, independent of patient eGFR. The relative complexity of the RCV method utilized is a potential limitation and may have contributed to the acceptable but only fair to moderate level of intra-reader reliability. Copyright © 2018 Elsevier B.V. All rights reserved.

Myocardial scintigraphy with 201thallium in pediatric cardiology: A review of 52 cases

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

Bjoerkhem, G.E.; Evander, E.; White, T.

1990-01-01

We report our experience of myocardial scintigraphy with 201thallium (201Tl) in 52 children, aged 4 days to 18 years, in which 80 studies were made primarily to demonstrate or exclude impaired myocardial perfusion. For analysis, the patients were divided into the following eight groups: group I, coronary artery malformations (five patients); group II, Kawasaki's syndrome (six patients); group III, arterial switch operation (seven patients); group IV, dilated cardiomyopathy (18 patients); group V, hypertrophic cardiomyopathy (four patients); group VI, myocardial dysfunction after surgery for congenital heart disease (five patients); group VII, pulmonary atresia (three patients); and group VIII, miscellaneous (four patients).more » Myocardial scintigraphy was performed with a planar or tomographic technique at rest or after exercise (four patients). Isotope-uptake defects, indicating impaired myocardial perfusion, were present in 14 patients, including small infants. Defects were seen in all groups except those with hypertrophic cardiomyopathy and pulmonary atresia. The absence of such defects in several of the patients with Kawasaki's syndrome was particularly valuable as it made coronary angiography unnecessary. In the other groups of patients myocardial scintigraphy was a valuable adjunct to other investigations.« less

Incidence rate of symptomatic painless thyroiditis presenting with thyrotoxicosis in Denmark as evaluated by consecutive thyroid scintigraphies.

PubMed

Schwartz, Frederik; Bergmann, Natasha; Zerahn, Bo; Faber, Jens

2013-04-01

Painless thyroiditis (PT) is a transient kind of thyrotoxicosis, with lack of uptake on a thyroid scintigraphy in a non-tender thyroid gland, elevated anti-TPO antibodies, no fever, no history of increased iodine intake, and a normal sedimentation rate. The prevalence of PT varies hugely in the literature. To establish the incidence rate of PT in Denmark as well as to describe the phenotype of PT in more detail. Tc-99m pertechnetate scintigraphies were performed over a period of 9.75 years on 6022 consecutive patients (2349 had a thyrotoxic episode), and were divided into high or normal (5528), reduced (300) or lack of uptake (194). Patient records were evaluated: 292 with reduced, and 186 with lack of uptake. As a control measure, 230 consecutive thyrotoxic patients were also analyzed. Based on scintigraphies, 12 patients had PT, 10 with lack of uptake and two with reduced, corresponding to an incidence rate of 0.49/100,000 person years. It was predicted, that only one patient among the newly diagnosed consecutive thyrotoxic cohort had PT. This patient was identified. The prevalence of PT among thyrotoxic patients was 0.51% as evaluated by scintigraphy, and 0.43% among the biochemically thyrotoxic patient cohort. Twenty-five percent had more than one thyrotoxic episode, 75% had at least one subsequent hypothyroid episode, and 33% developed permanent hypothyroidism. PT presenting with symptomatic thyrotoxicosis is an extremely rare disease in Denmark. Symptomatic PT presents most often with no uptake on a Tc-99m pertechnetate scintigraphy. Clinical follow-up is essential.

Single-photon emission computed tomography enhanced Tc-99m-pertechnetate disodium-labelled red blood cell scintigraphy in the localization of small intestine bleeding: a single-centre twelve-year study.

PubMed

Dolezal, Jiri; Vizda, Jaroslav; Kopacova, Marcela

2011-01-01

To present our experience with the detection of bleeding in the small intestine by means of scintigraphy with in vivo-labelled red blood cells (RBCs) in the period of 1998-2009. A 12-year prospective study was accomplished with 40 patients (23 men, 17 women, aged 12-91, mean 56 years) who had lower gastrointestinal bleeding (obscure-overt bleeding) and underwent scintigraphy with in vivo-labelled RBCs by means of technetium 99m. The scintigraphy was usually performed after other diagnostic tests had failed to locate the bleeding. A total of 26 patients had a positive scintigraphy with in vivo-labelled RBCs and 14 patients had negative scintigraphy. The final diagnosis was confirmed in 20 of 26 patients with a positive scintigraphy by push enteroscopy (6/20), intraoperative enteroscopy (7/20), surgery (4/20), duodenoscopy (1/20), double-balloon enteroscopy (1/20) and X-ray angiography (1/20). The correct location of the bleeding site was identified by RBC scintigraphy in 15 of 20 (75%) patients with the confirmed source. The locations of the bleeding site identified by scintigraphy and enteroscopy (push, intraoperative) and surgical investigations were highly correlated in patients with a positive scintigraphy within the first 3 h. Eleven of the 20 correctly localized studies and none of the incorrectly localized studies were positive in the dynamic phase of imaging. In 5 patients (all erroneously localized), scintigraphy was positive only at a period longer than 18 h. RBC scintigraphy is an effective imaging modality in localizing lower gastrointestinal bleeding in patients for whom other diagnostic tests have failed to locate the bleeding. RBC scintigraphy can be successful in the detection of bleeding sites in the small intestine. Copyright © 2011 S. Karger AG, Basel.

Myopericarditis in acquired immunodeficiency syndrome diagnosed by gallium scintigraphy.

PubMed Central

Cregler, L. L.; Sosa, I.; Ducey, S.; Abbey, L.

1990-01-01

Myocarditis is among the cardiac complications of acquired immunodeficiency syndrome and, yet, is often not discovered until autopsy. Gallium scintigraphy has been employed in diagnosing this entity, but few data are available about its diagnostic accuracy and value. Here, the authors report two cases of myopericarditis as diagnosed by gallium scan. Images Figure 1 Figure 2 PMID:2398508

[Verifying the function of hepaticojejunostomies by scintigraphy of the bile ducts].

PubMed

Champetier, J; Busquet, G; Letoublon, C; Vigneau, B; Yver, R; Rambeaud, J J

1984-01-01

Thirty six hepatobiliary scintigraphies with 99mTc-Dimethyl IDA were performed in thirty patients with an hepaticojejunostomy one month to ten years after surgery. Twenty patients underwent surgery for biliary disease and ten for duodenal or pancreatic disease. In most cases (twenty three), the radionuclide study has been systematically performed to assess the scintigraphic pattern of a normal hepaticojejunostomy. In seven cases this pattern was abnormal. Four times the biliary enteric anastomosis was involved. Three times it showed an abnormal liver morphology. After an hepaticojejunostomy, hepatobiliary scintigraphy seems to be the only examination providing dynamic information for the biliary enteric anastomosis and the intestinal loop. But it sometimes is difficult to analyse in all cases, it must be the screening test in patients when symptoms occur after hepaticojejunostomy; but a percutaneous transhepatic cholangiogram cannot always be avoided.

Gallium 67 scintigraphy in glomerular disease

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

Bakir, A.A.; Lopez-Majano, V.; Levy, P.S.

1988-12-01

To evaluate the diagnostic usefulness of gallium 67 scintigraphy in glomerular disease, 45 patients with various glomerulopathies, excluding lupus nephritis and renal vasculitis, were studied. Persistent renal visualization 48 hours after the gallium injection, a positive scintigram, was graded as + (less than), ++ (equal to), and +++ (greater than) the hepatic uptake. Positive scintigrams were seen in ten of 16 cases of focal segmental glomerulosclerosis, six of 11 cases of proliferative glomerulonephritis, and one case of minimal change, and one of two cases of membranous nephropathy; also in three of six cases of sickle glomerulopathy, two cases of diabeticmore » neuropathy, one of two cases of amyloidosis, and one case of mild chronic allograft rejection. The 25 patients with positive scans were younger than the 20 with negative scans (31 +/- 12 v 42 +/- 17 years; P less than 0.01), and exhibited greater proteinuria (8.19 +/- 7.96 v 2.9 +/- 2.3 S/d; P less than 0.01) and lower serum creatinine values (2 +/- 2 v 4.1 +/- 2.8 mg/dL; P less than 0.01). The amount of proteinuria correlated directly with the intensity grade of the gallium image (P less than 0.02), but there was no correlation between the biopsy diagnosis and the outcome of the gallium scan. It was concluded that gallium scintigraphy is not useful in the differential diagnosis of the glomerular diseases under discussion. Younger patients with good renal function and heavy proteinuria are likely to have a positive renal scintigram regardless of the underlying glomerulopathy.« less

Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma.

PubMed

Czepczyński, Rafał; Parisella, Maria Gemma; Kosowicz, Jerzy; Mikołajczak, Renata; Ziemnicka, Katarzyna; Gryczyńska, Maria; Sowiński, Jerzy; Signore, Alberto

2007-10-01

Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue (99m)Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using (99m)Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-DTPA-octreotide and (18)F-FDG-PET) and compared with (99m)Tc-EDDA/HYNIC-TOC. In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using (99m)Tc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. (99m)Tc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making.

Evaluation of prescription of exercise, for rehabilitation of coronary artery disease patients by myocardial scintigraphy.

PubMed

Meneghelo, Romeu S; Magalhães, Hélio M; Smanio, Paola E P; Fuchs, Angela R C N; Ferraz, Almir S; Buchler, Rica D D; Buglia, Susimeire; Mastrocolla, Luiz E; Thom, Anneliese F

2008-10-01

It is advisable that the intensity of the exercises for rehabilitation of patients with coronary artery disease does not cause myocardial ischemia. Compare the capacity of myocardial tomographic scintigraphy with the electrocardiogram capacity in ischemia detection during rehabilitation session. Twenty six patients with coronary artery disease, undergoing the rehabilitation program and with previous scintigraphy, with transient hypo-uptake have been administered a new injection of MIBI-Tc-99m during a training session when they were also monitored with dynamic electrocardiography. The rest scintigraphies, after ergometric treadmill test and rehabilitation session, were assessed in a semi-quantitative way using scores from 0 to 4 to classify each one of the chosen segments (0 = normal; 1 = discrete hypo-uptake; 2 = moderate; 3 = intense; 4 = lack of uptake). The means of the total scores found were: at rest = 12.9; after treadmill test = 19.3; after rehabilitation session = 15.1. There were statistically significant differences among them. An individual assessment showed that in 14 cases (53.8 %) hypo-uptake to some degree was identified during rehabilitation and in 12 cases (46.6%) it was not. Monitoring with the Holter system didn't show in any of the cases a ST segment depression equal or greater than 1mm. The exercises prescribed for patients with coronary artery disease, according to recommendations found in the literature, may trigger myocardial ischemia, assessed by scintigraphy during a rehabilitation session.

PAR-2 regulates dental pulp inflammation associated with caries.

PubMed

Lundy, F T; About, I; Curtis, T M; McGahon, M K; Linden, G J; Irwin, C R; El Karim, I A

2010-07-01

Protease-activated receptors (PARs) are G-protein-coupled receptors that are activated enzymatically by proteolysis of an N-terminal domain. The cleavage and activation of PARs by serine proteases represent a novel mechanism by which such enzymes could influence the host inflammatory response. The aim of this study was to determine whether PAR-2 expression and activation were increased in dental caries. Using immunohistochemistry, we showed PAR-2 to be localized to pulp cells subjacent to caries lesions, but minimally expressed by healthy pulp tissue. Trypsin and the PAR-2 agonist (PAR2-AP) activated PAR-2 in an in vitro functional assay. Endogenous molecules present in pulp cell lysates from carious teeth specifically activated PAR-2, but those from healthy teeth failed to do so. The activation of PAR-2 in vitro was shown to increase the expression of the pro-inflammatory mediator cyclo-oxygenase-2 (COX-2), providing a mechanism whereby PAR-2 could modulate pulpal inflammation.

Par Pond vegetation status Summer 1995 -- Summary

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

Mackey, H.E. Jr.; Riley, R.S.

1996-01-01

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995. Communities similar tomore » the pre-drawdown, Par Pond aquatic plant communities are becoming re-established. Emergent beds of maidencane, lotus, waterlily, and watershield are extensive and well developed. Cattail occurrence continued to increase during the summer, but large beds common to Par Pond prior to the drawdown have not formed. Estimates from SPOT HRV, remote sensing satellite data indicated that as much as 120 hectares of emergent wetlands vegetation may have been present along the Par Pond shoreline by early October, 1995. To track the continued development of macrophytes in Par Pond, future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.« less

Post-radiosynovectomy imaging of Er-169 using scintigraphy and autoradiography.

PubMed

Farahati, Jamshid; Elliott, Johanna; Höppner, Sabrina; Stein, Linda; Gilman, Elena; Kumm, Dietmar; Grodotzki, Thomas

2017-06-01

Currently, there is no protocol for the detection of intra-articular distribution of Er-169 citrate after radiosynovectomy. We propose post-therapeutic imaging using scintigraphy and cobalt-57 pen-marker autoradiography. This technique evaluates the efficacy of the radiosynovectomy and patient safety and could be utilized for dosimetric protocol.

Increased mast cell expression of PAR-2 in skin inflammatory diseases and release of IL-8 upon PAR-2 activation.

PubMed

Carvalho, Ricardo Filipe da Silva; Nilsson, Gunnar; Harvima, Ilkka Tapani

2010-02-01

Mast cells are increasingly present in the lesional skin of chronic skin inflammatory diseases including psoriasis and basal cell carcinoma (BCC). It has previously been shown that proteinase-activated receptor (PAR)-2 is expressed by mast cells, and tryptase is a potent activator of this receptor. In this study, skin biopsies from both healthy-looking and lesional skin of patients with psoriasis and superficial spreading BCC were collected and the expression of PAR-2 immunoreactivity in tryptase-positive mast cells was analysed. PAR-2 expression was confirmed in vitro in different mast cell populations. Cord-blood derived mast cells (CBMC) were stimulated with a PAR-2 activating peptide, 2-furoyl-LIGRLO-NH(2). Consequently, IL-8 and histamine production was analysed in the supernatants. We observed a significant increase in the percentage of mast cells expressing PAR-2 in the lesional skin of psoriasis and BCC patients compared with the healthy-looking skin. HMC-1.2, LAD-2 and CBMC mast cells all expressed PAR-2 both intracellularly and on the cell surface. CBMC activation with the PAR-2 activating peptide resulted in an increased secretion of IL-8, but no histamine release was observed. Furthermore, both PAR-2 and IL-8 were co-localized to the same tryptase-positive mast cells in the lesional BCC skin. These results show that mast cells express increased levels of PAR-2 in chronic skin inflammation. Also, mast cells can be activated by a PAR-2 agonist to secrete IL-8, a chemokine which can contribute to the progress of inflammation.

Magnetic activity and radial velocity filtering of young Suns: the weak-line T-Tauri stars Par 1379 and Par 2244

NASA Astrophysics Data System (ADS)

Hill, C. A.; Carmona, A.; Donati, J.-F.; Hussain, G. A. J.; Gregory, S. G.; Alencar, S. H. P.; Bouvier, J.; The Matysse Collaboration

2017-12-01

We report the results of our spectropolarimetric monitoring of the weak-line T-Tauri stars (wTTSs) Par 1379 and Par 2244, within the MaTYSSE (Magnetic Topologies of Young Stars and the Survival of close-in giant Exoplanets) programme. Both stars are of a similar mass (1.6 and 1.8 M⊙) and age (1.8 and 1.1 Myr), with Par 1379 hosting an evolved low-mass dusty circumstellar disc, and with Par 2244 showing evidence of a young debris disc. We detect profile distortions and Zeeman signatures in the unpolarized and circularly polarized lines for each star, and have modelled their rotational modulation using tomographic imaging, yielding brightness and magnetic maps. We find that Par 1379 harbours a weak (250 G), mostly poloidal field tilted 65° from the rotation axis. In contrast, Par 2244 hosts a stronger field (860 G) split 3:2 between poloidal and toroidal components, with most of the energy in higher order modes, and with the poloidal component tilted 45° from the rotation axis. Compared to the lower mass wTTSs, V819 Tau and V830 Tau, Par 2244 has a similar field strength, but is much more complex, whereas the much less complex field of Par 1379 is also much weaker than any other mapped wTTS. We find moderate surface differential rotation of 1.4× and 1.8× smaller than Solar, for Par 1379 and Par 2244, respectively. Using our tomographic maps to predict the activity-related radial velocity (RV) jitter, and filter it from the RV curves, we find RV residuals with dispersions of 0.017 and 0.086 km s-1 for Par 1379 and Par 2244, respectively. We find no evidence for close-in giant planets around either star, with 3σ upper limits of 0.56 and 3.54 MJup (at an orbital distance of 0.1 au).

Role of (18)F-DOPA PET/CT and (131)I-MIBG planar scintigraphy in evaluating patients with pheochromocytoma.

PubMed

Bandopadhyaya, G P; Kumar, Abhishek; Kumari, Jyotsana

2015-01-01

The aim of this retrospective study was to evaluate role of (18)F-DOPA PET/CT and (131)I-MIBG planar scintigraphy in patients with pheochromocytoma. The patients with diagnosis of pheochromocytoma based on radiological and biochemical markers were retrospectively selected for the study. These patients had undergone both (131)I-MIBG scintigraphy and (18)F-DOPA PET/CT. The imaging findings were compared to patient histopathology reports, biochemical markers and clinical follow up whenever available to establish the diagnosis. (131)I-MIBG showed a sensitivity of 68% and specificity of 100%. (18)F-DOPA PET/CT showed a sensitivity of 82% and specificity of 100%. (18)F-DOPA was better at localizing and finding more no of lesions as compared to (131)I-MIBG scintigraphy. (18)F-DOPA also is a better study in evaluation of paragangliomas. (18)F-DOPA PET/CT seems to be a better modality in comparison to (131)I-MIBG scintigraphy in the evaluation of pheochromocytoma/paraganglioma. At this point both these tracers seem to have mutually additive role in these patients and essential investigations with diagnosis and follow-up of this disease.

PAR-2 inhibition reverses experimental pulmonary hypertension.

PubMed

Kwapiszewska, Grazyna; Markart, Philipp; Dahal, Bhola Kumar; Kojonazarov, Baktybek; Marsh, Leigh Matthew; Schermuly, Ralph Theo; Taube, Christian; Meinhardt, Andreas; Ghofrani, Hossein Ardeschir; Steinhoff, Martin; Seeger, Werner; Preissner, Klaus Theo; Olschewski, Andrea; Weissmann, Norbert; Wygrecka, Malgorzata

2012-04-27

A hallmark of the vascular remodeling process underlying pulmonary hypertension (PH) is the aberrant proliferation and migration of pulmonary arterial smooth muscle cells (PASMC). Accumulating evidence suggests that mast cell mediators play a role in the pathogenesis of PH. In the present study we investigated the importance of protease-activated receptor (PAR)-2 and its ligand mast cell tryptase in the development of PH. Our results revealed strong increase in PAR-2 and tryptase expression in the lungs of idiopathic pulmonary arterial hypertension (IPAH) patients, hypoxia-exposed mice, and monocrotaline (MCT)-treated rats. Elevated tryptase levels were also detected in plasma samples from IPAH patients. Hypoxia and platelet-derived growth factor (PDGF)-BB upregulated PAR-2 expression in PASMC. This effect was reversed by HIF (hypoxia inducible factor)-1α depletion, PDGF-BB neutralizing antibody, or the PDGF-BB receptor antagonist Imatinib. Attenuation of PAR-2 expression was also observed in smooth muscle cells of pulmonary vessels of mice exposed to hypoxia and rats challenged with MCT in response to Imatinib treatment. Tryptase induced PASMC proliferation and migration as well as enhanced synthesis of fibronectin and matrix metalloproteinase-2 in a PAR-2- and ERK1/2-dependent manner, suggesting that PAR-2-dependent signaling contributes to vascular remodeling by various mechanisms. Furthermore, PAR-2(-/-) mice were protected against hypoxia-induced PH, and PAR-2 antagonist application reversed established PH in the hypoxia mouse model. Our study identified a novel role of PAR-2 in vascular remodeling in the lung. Interference with this pathway may offer novel therapeutic options for the treatment of PH.

Sensitivity and positive predictive value of CT, MRI and 123I-MIBG scintigraphy in localizing pheochromocytomas: a prospective study.

PubMed

Lumachi, Franco; Tregnaghi, Alberto; Zucchetta, Pietro; Cristina Marzola, Maria; Cecchin, Diego; Grassetto, Gaia; Bui, Franco

2006-07-01

To establish a standardized non-invasive imaging protocol for patients with pheochromocytoma undergoing surgery. A series of 32 consecutive patients (16 men, 16 women; median age 43 years, range 15-71 years) with biochemically confirmed pheochromocytoma underwent computed tomography (CT) scanning, magnetic resonance imaging (MRI) and meta-[I]iodobenzylguanidine (MIBG) whole-body scintigraphy prior to adrenalectomy or excision of extra-adrenal tumour (paraganglioma). At final pathology no malignant pheochromocytomas were found. The tumour was right-sided in 16 (50%) patients, left-sided in 13 (41%), extra-adrenal (sympathetic ganglia, upper abdomen) in two (6%) and bilateral in one (3%) patient. Overall, the median greatest diameter (size) of the tumour was 35 mm (range, 15-90 mm). The sensitivity of CT, MRI and MIBG scintigraphy was 90%, 93% and 91%, and the specificity was 93%, 93% and 100%, respectively. The three patients with false negative scintigraphy had an intra-adrenal tumour, ranging from 20 to 50 mm in size. The presence of necrosis within the mass might justify the lack of significant uptake of radiopharmaceutical in two patients, and the small size (15 mm) of the mass in the other. There were two false positive results with both CT and MRI, and no false positive MIBG scintigraphy, which had the highest (100%) positive predictive value. The combination of MRI+MIBG scintigraphy reached 100% sensitivity and positive predictive value. Our data suggest that this imaging protocol should be used in all patients with biochemically confirmed pheochromocytoma.

A case of recurrent cholangitis after bile duct injury during laparoscopic cholecystectomy: value of scintigraphy with Tc-99m GSA and hepatobiliary scintigraphy for indication of lobectomy.

PubMed

Nishiguchi, S; Shiomi, S; Sasaki, N; Iwata, Y; Tanaka, H; Kubo, S; Hirohashi, K; Ochi, H

2000-10-01

A 39-year-old woman with acute cholecystitis and gallstones underwent laparoscopic cholecystectomy. She suffered from recurrent episodes of cholangitis due to injury of the major bile ducts during laparoscopic cholecystectomy. Hepatobiliary scintigraphy with Tc-99m Sn-N-pyridoxyl-5-methyltryptophan was performed. Although normal bile excretion was found from the left hepatic duct to the percutaneous transhepatic biliary drainage (PTBD) tube, excretion from the right hepatic lobe was prolonged. Scintigraphy with Tc-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin demonstrated atrophy of the right hepatic lobe and enlargement of the left hepatic lobe. Cholangiography via the PTBD tube revealed complete obstruction of the left hepatico-jejunal anastomosis and could not enhance the right intrahepatic bile duct. A right hepatic lobectomy was performed because of the atrophy, glissonitis and the absence of an appropriate bile duct for reconstruction. Postoperatively she was active and exhibited no evidence of recurrent cholangitis.

The role of protease-activated receptors PAR-1 and PAR-2 in the repair of 16HBE 14o(-) epithelial cell monolayers in vitro.

PubMed

Ewen, D; Clarke, S L; Smith, J R; Berger, C; Salmon, G; Trevethick, M; Shute, J K

2010-03-01

We recently reported that repair following mechanical wounding of epithelial cell layers in vitro is dependent on fibrin formation and the activity of locally expressed coagulation cascade proteins. Serine proteases of the coagulation cascade are an important group of protease-activated receptor (PAR) activators and PAR-1 to 4 are expressed by the normal bronchial epithelium. We tested the hypothesis that activation of PAR-1 and PAR-2 by coagulation cascade proteases stimulates epithelial repair via effects on fibrin formation. Using mechanically wounded 16HBE 14o(-) epithelial cell layers in culture, we investigated the effect of PAR-1 and PAR-2 agonist peptides, control partially scrambled peptides and PAR-neutralizing antibodies on the rate of repair and fibrin formation. Coagulation factors in culture supernatants were measured by immunoblot. RT-PCR was used to investigate PAR-1, PAR-2 and PGE2 receptor (EP-1 to EP-4) expression in this model and qRT-PCR to quantify responses to wounding. Additionally, we investigated the effect of exogenously added factor Xa (FXa) and neutrophil elastase and the influence of PGE2 and indomethacin on the repair response. PAR-1 and PAR-2 peptide agonists stimulated the rate of repair and enhanced the formation of a fibrin provisional matrix to support the repair process. Conversely, PAR-neutralizing antibodies inhibited repair. Under serum-free culture conditions, 16HBE 14o(-) cells expressed EP-2 and EP-3, but not EP-1 or EP-4, receptors. Wounding induced an increased expression of EP-3 but did not alter EP-2, PAR-1 or PAR-2 expression. In the absence of PAR agonists, there was no evidence for a role for PGE2 in fibrin formation or the repair process. Indomethacin attenuated fibrin formation in wounded cultures only in the presence of the PAR-2 peptide. FXa stimulated epithelial repair while neutrophil elastase reduced the levels of coagulation factors and inhibited repair. Locally expressed serine proteases of the coagulation

Comparative analysis of hepatopulmonary shunt obtained from pretherapy 99mTc MAA scintigraphy and post-therapy 90Y Bremsstrahlung imaging in 90Y microsphere therapy.

PubMed

Jha, Ashish Kumar A; Zade, Anand A; Rangarajan, Venkatesh; Purandare, Nilendu; Shah, Sneha A; Agrawal, Archi; Kulkarni, Suyash S; Shetty, Nitin

2012-05-01

(99m)Tc macroaggregate albumin (MAA) scintigraphy is routinely used to estimate the hepatopulmonary shunt (HPS) of (90)Y microspheres because of their comparable average particle sizes (20-30 µm). However, the MAA particle size can vary from 10 to 90 µm. Therefore, HPS computed from (99m)Tc MAA scintigraphy may not accurately represent the HPS of (90)Y microspheres. In view of this, the present study was undertaken to investigate the accuracy of (99m)Tc MAA scintigraphy in estimating the HPS of (90)Y microspheres. Nineteen sessions of transarterial radioembolization using (90)Y therasphere were carried out in 17 patients for hepatic malignancies (both primary and secondary). For each session of therapy, a pretherapeutic (99m)Tc MAA scintigraphy and post-therapeutic (90)Y Bremsstrahlung scintigraphy were performed. The HPSs obtained from these images were compared. The mean HPS fractions calculated from the pretherapeutic (99m)Tc MAA study and the post-therapeutic (90)Y Bremsstrahlung images were 4.77 ± 2.81 and 4.52 ± 2.5%, respectively. The coefficient of correlation (r) was 0.96. (99m)Tc MAA scintigraphy accurately predicts the HPS of (90)Y microspheres.

Analysis of ParB-centromere interactions by multiplex SPR imaging reveals specific patterns for binding ParB in six centromeres of Burkholderiales chromosomes and plasmids.

PubMed

Pillet, Flavien; Passot, Fanny Marie; Pasta, Franck; Anton Leberre, Véronique; Bouet, Jean-Yves

2017-01-01

Bacterial centromeres-also called parS, are cis-acting DNA sequences which, together with the proteins ParA and ParB, are involved in the segregation of chromosomes and plasmids. The specific binding of ParB to parS nucleates the assembly of a large ParB/DNA complex from which ParA-the motor protein, segregates the sister replicons. Closely related families of partition systems, called Bsr, were identified on the chromosomes and large plasmids of the multi-chromosomal bacterium Burkholderia cenocepacia and other species from the order Burkholeriales. The centromeres of the Bsr partition families are 16 bp palindromes, displaying similar base compositions, notably a central CG dinucleotide. Despite centromeres bind the cognate ParB with a narrow specificity, weak ParB-parS non cognate interactions were nevertheless detected between few Bsr partition systems of replicons not belonging to the same genome. These observations suggested that Bsr partition systems could have a common ancestry but that evolution mostly erased the possibilities of cross-reactions between them, in particular to prevent replicon incompatibility. To detect novel similarities between Bsr partition systems, we have analyzed the binding of six Bsr parS sequences and a wide collection of modified derivatives, to their cognate ParB. The study was carried out by Surface Plasmon Resonance imaging (SPRi) mulitplex analysis enabling a systematic survey of each nucleotide position within the centromere. We found that in each parS some positions could be changed while maintaining binding to ParB. Each centromere displays its own pattern of changes, but some positions are shared more or less widely. In addition from these changes we could speculate evolutionary links between these centromeres.

La pelade par plaques

PubMed Central

Spano, Frank; Donovan, Jeff C.

2015-01-01

Résumé Objectif Présenter aux médecins de famille des renseignements de base pour faire comprendre l’épidémiologie, la pathogenèse, l’histologie et l’approche clinique au diagnostic de la pelade par plaques. Sources des données Une recension a été effectuée dans PubMed pour trouver des articles pertinents concernant la pathogenèse, le diagnostic et le pronostic de la pelade par plaques. Message principal La pelade par plaques est une forme de perte pileuse auto-immune dont la prévalence durant une vie est d’environ 2 %. Des antécédents personnels ou familiaux de troubles auto-immuns concomitants, comme le vitiligo ou une maladie de la thyroïde, peuvent être observés dans un petit sous-groupe de patients. Le diagnostic peut souvent être posé de manière clinique en se fondant sur la perte de cheveux non cicatricielle et circulaire caractéristique, accompagnée de cheveux en « point d’exclamation » en périphérie chez ceux dont le problème en est aux premiers stades. Le diagnostic des cas plus complexes ou des présentations inhabituelles peut être facilité par une biopsie et un examen histologique. Le pronostic varie largement et de mauvais résultats sont associés à une apparition à un âge précoce, une perte importante, la variante ophiasis, des changements aux ongles, des antécédents familiaux ou des troubles auto-immuns concomitants. Conclusion La pelade par plaques est une forme auto-immune de perte de cheveux périodiquement observée en soins primaires. Les médecins de famille sont bien placés pour identifier la pelade par plaques, déterminer la gravité de la maladie et poser le diagnostic différentiel approprié. De plus, ils sont en mesure de renseigner leurs patients à propos de l’évolution clinique de la maladie ainsi que du pronostic général selon le sous-type de patients.

PH motifs in PAR1&2 endow breast cancer growth.

PubMed

Kancharla, A; Maoz, M; Jaber, M; Agranovich, D; Peretz, T; Grisaru-Granovsky, S; Uziely, B; Bar-Shavit, R

2015-11-24

Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.

Breast cancer sentinel node scintigraphy: differences between imaging results 1 and 2 h after injection.

PubMed

Wondergem, Maurits; Hobbelink, Monique G G; Witkamp, Arjen J; van Hillegersberg, Richard; de Keizer, Bart

2012-11-01

Timing of image acquisition in breast cancer sentinel node scintigraphy remains a subject of debate. Therefore, the performance of our protocol in which images are acquired 1 and 2 h after injection was evaluated. The results of sentinel node scintigraphy 1 and 2 h after injection were compared with regard to the sentinel lymph nodes visualized. We studied 132 patients who were consecutively referred for sentinel lymph node biopsy. 99mTc-albumine nanocolloid (120 MBq) was injected peritumourally into patients with palpable tumours and intratumourally into patients with nonpalpable tumours. All scintigraphic images taken for the sentinel node procedure were evaluated. The number of sentinel nodes per anatomic localization and the interpretability of the images were scored. A total of 132 patients underwent sentinel node scintigraphy 1 h after injection. Of these, 117 patients also underwent sentinel node scintigraphy 2 h after injection. An axillary sentinel node was visualized in 79.5 and 95.7% of patients, respectively, 1 and 2 h after injection. In 20.5% of the patients the images acquired 1 h after injection did not show a sentinel node. Furthermore, in all procedures, the images 1 h after injection were of no added value to those acquired 2 h after injection. Scintigraphic imaging 2 h after a single peritumoural or intratumoural administration of about 120 MBq 99mTc-albumine nanocolloid yields an axillary sentinel node in over 95% of cases. Imaging 1 h after injection is of no additional value and can be omitted.

Keratometric alterations following the 25-gauge transconjunctival sutureless pars plana vitrectomy versus the conventional pars plana vitrectomy.

PubMed

Citirik, Mehmet; Batman, Cosar; Bicer, Tolga; Zilelioglu, Orhan

2009-09-01

To assess the alterations in keratometric astigmatism following the 25-gauge transconjunctival sutureless pars plana vitrectomy versus the conventional pars plana vitrectomy. Sixteen consecutive patients were enrolled into the study. Conventional vitrectomy was applied to eight of the cases and 25-gauge transconjunctival sutureless vitrectomy was performed in eight patients. Keratometry was performed before and after the surgery. In the 25-gauge transconjunctival sutureless pars plana vitrectomy group, statistically significant changes were not observed in the corneal curvature in any post-operative follow-up measurement (p > 0.05); whereas in the conventional pars plana vitrectomy group, statistically significant changes were observed in the first postoperative day (p = 0.01) and first postoperative month (p = 0.03). We noted that these changes returned to baseline in three months (p = 0.26). Both 25-gauge transconjunctival sutureless and conventional pars plana vitrectomy are effective surgical modalities for selected diseases of the posterior segment. Surgical procedures are critical for the visual rehabilitation of the patients. The post-operative corneal astigmatism of the vitrectomised eyes can be accurately determined at least two months post-operatively.

Analysis of ParB-centromere interactions by multiplex SPR imaging reveals specific patterns for binding ParB in six centromeres of Burkholderiales chromosomes and plasmids

PubMed Central

Pillet, Flavien; Passot, Fanny Marie

2017-01-01

Bacterial centromeres–also called parS, are cis-acting DNA sequences which, together with the proteins ParA and ParB, are involved in the segregation of chromosomes and plasmids. The specific binding of ParB to parS nucleates the assembly of a large ParB/DNA complex from which ParA—the motor protein, segregates the sister replicons. Closely related families of partition systems, called Bsr, were identified on the chromosomes and large plasmids of the multi-chromosomal bacterium Burkholderia cenocepacia and other species from the order Burkholeriales. The centromeres of the Bsr partition families are 16 bp palindromes, displaying similar base compositions, notably a central CG dinucleotide. Despite centromeres bind the cognate ParB with a narrow specificity, weak ParB-parS non cognate interactions were nevertheless detected between few Bsr partition systems of replicons not belonging to the same genome. These observations suggested that Bsr partition systems could have a common ancestry but that evolution mostly erased the possibilities of cross-reactions between them, in particular to prevent replicon incompatibility. To detect novel similarities between Bsr partition systems, we have analyzed the binding of six Bsr parS sequences and a wide collection of modified derivatives, to their cognate ParB. The study was carried out by Surface Plasmon Resonance imaging (SPRi) mulitplex analysis enabling a systematic survey of each nucleotide position within the centromere. We found that in each parS some positions could be changed while maintaining binding to ParB. Each centromere displays its own pattern of changes, but some positions are shared more or less widely. In addition from these changes we could speculate evolutionary links between these centromeres. PMID:28562673

Perfusion Scintigraphy and Patient Selection for Lung Volume Reduction Surgery

PubMed Central

Chandra, Divay; Lipson, David A.; Hoffman, Eric A.; Hansen-Flaschen, John; Sciurba, Frank C.; DeCamp, Malcolm M.; Reilly, John J.; Washko, George R.

2010-01-01

Rationale: It is unclear if lung perfusion can predict response to lung volume reduction surgery (LVRS). Objectives: To study the role of perfusion scintigraphy in patient selection for LVRS. Methods: We performed an intention-to-treat analysis of 1,045 of 1,218 patients enrolled in the National Emphysema Treatment Trial who were non–high risk for LVRS and had complete perfusion scintigraphy results at baseline. The median follow-up was 6.0 years. Patients were classified as having upper or non–upper lobe–predominant emphysema on visual examination of the chest computed tomography and high or low exercise capacity on cardiopulmonary exercise testing at baseline. Low upper zone perfusion was defined as less than 20% of total lung perfusion distributed to the upper third of both lungs as measured on perfusion scintigraphy. Measurements and Main Results: Among 284 of 1,045 patients with upper lobe–predominant emphysema and low exercise capacity at baseline, the 202 with low upper zone perfusion had lower mortality with LVRS versus medical management (risk ratio [RR], 0.56; P = 0.008) unlike the remaining 82 with high perfusion where mortality was unchanged (RR, 0.97; P = 0.62). Similarly, among 404 of 1,045 patients with upper lobe–predominant emphysema and high exercise capacity, the 278 with low upper zone perfusion had lower mortality with LVRS (RR, 0.70; P = 0.02) unlike the remaining 126 with high perfusion (RR, 1.05; P = 1.00). Among the 357 patients with non–upper lobe–predominant emphysema (75 with low and 282 with high exercise capacity) there was no improvement in survival with LVRS and measurement of upper zone perfusion did not contribute new prognostic information. Conclusions: Compared with optimal medical management, LVRS reduces mortality in patients with upper lobe–predominant emphysema when there is low rather than high perfusion to the upper lung. PMID:20538961

Perfusion scintigraphy and patient selection for lung volume reduction surgery.

PubMed

Chandra, Divay; Lipson, David A; Hoffman, Eric A; Hansen-Flaschen, John; Sciurba, Frank C; Decamp, Malcolm M; Reilly, John J; Washko, George R

2010-10-01

It is unclear if lung perfusion can predict response to lung volume reduction surgery (LVRS). To study the role of perfusion scintigraphy in patient selection for LVRS. We performed an intention-to-treat analysis of 1,045 of 1,218 patients enrolled in the National Emphysema Treatment Trial who were non-high risk for LVRS and had complete perfusion scintigraphy results at baseline. The median follow-up was 6.0 years. Patients were classified as having upper or non-upper lobe-predominant emphysema on visual examination of the chest computed tomography and high or low exercise capacity on cardiopulmonary exercise testing at baseline. Low upper zone perfusion was defined as less than 20% of total lung perfusion distributed to the upper third of both lungs as measured on perfusion scintigraphy. Among 284 of 1,045 patients with upper lobe-predominant emphysema and low exercise capacity at baseline, the 202 with low upper zone perfusion had lower mortality with LVRS versus medical management (risk ratio [RR], 0.56; P = 0.008) unlike the remaining 82 with high perfusion where mortality was unchanged (RR, 0.97; P = 0.62). Similarly, among 404 of 1,045 patients with upper lobe-predominant emphysema and high exercise capacity, the 278 with low upper zone perfusion had lower mortality with LVRS (RR, 0.70; P = 0.02) unlike the remaining 126 with high perfusion (RR, 1.05; P = 1.00). Among the 357 patients with non-upper lobe-predominant emphysema (75 with low and 282 with high exercise capacity) there was no improvement in survival with LVRS and measurement of upper zone perfusion did not contribute new prognostic information. Compared with optimal medical management, LVRS reduces mortality in patients with upper lobe-predominant emphysema when there is low rather than high perfusion to the upper lung.

Tc-99m macro aggregated albumin scintigraphy – indications other than pulmonary embolism: A pictorial essay

PubMed Central

Gandhi, Sunny J; Babu, Sanjay; Subramanyam, Padma; Shanmuga Sundaram, Palaniswamy

2013-01-01

Introduction: Tc-99m macro aggregated albumin (MAA) is synonymous for lung perfusion scintigraphy and is part of the study in the evaluation of pulmonary thromboembolism. We wanted to highlight the utilities of Tc-99m MAA other than pulmonary embolism as a pictorial assay. Materials and Methods: Patients referred for Tc-99m MAA scintigraphy under various indications were included in this pictorial essay. Commercially available TechneScan LyoMAA cold kit from Mallinckrodt Medical B.V., Holland was used. Acquisition protocols for different indications are described in this article. Different clinical indications (e.g., pulmonary artery stenosis, hepatopulmonary syndrome, FEV1 calculation in lung surgery planning, selective internal radiation therapy planning, venography for deep venous thrombosis, left to right cardiac shunts, etc.) where Tc-99m MAA scintigraphy was asked for; how it helped in different clinical scenarios and how it can be used clinically is explained with unique and interesting case examples and images. We also reviewed the literature to look for certain remote indications of MAA imaging for the sake of completion like – (shunt scintigraphy, peritoneopleural communication, etc.) Conclusion: Tc-99m MAA is a very useful radiopharmaceutical, which can be used for many other indications apart from the commonly used indication of lung perfusion scan in pulmonary embolism. It can provide useful clinical information in other indications, which we try to highlight in this article. PMID:24250023

A pilot study evaluating 99mTc-anti-TNF-alpha scintigraphy in graves' ophtalmopathy patients with different clinical activity score.

PubMed

Rebelo Pinto, E dos S; Lopes, F P P L; de Souza, S A L; da Fonseca, L M B; Vaisman, M; Gutfilen, B; dos Santos Teixeira, P de F

2013-09-01

The present study describes the preliminary results of the use of 99mTc-anti-TNF-α scintigraphy as a new diagnostic approach to evaluate patients presenting with Graves' ophthalmopathy (GO). Patients (n=25) presenting at different inflammatory stages of GO and 10 healthy volunteers underwent 99mTc-anti-TNF-α scintigraphy. Images were obtained 15 min after the intravenous injection of 370 MBq (10 mCi) 99mTc-anti-TNF-α. Planar images were obtained in a 256×256 matrix (each lasting 5 min) and single photon emission computed tomography (SPECT) scan lasting 13 min. Regions of interest (ROI) were drawn on the orbit and cerebral hemispheres. The uptake of 99m Tc-anti-TNF-α in these regions was compared and positive scintigraphy established when the ROI was >2.5. In addition, uptake for each positive exam was scored as either slight (2.6-5.1), moderate (5.2-7.6), or high (>7.6). In this pilot study, 69 orbits were evaluated (1 patient had only 1 eye), and 27 had a positive CAS (≥3/7). Scintigraphies were positive in 38 orbits. Comparing the results of the exams with CAS, a high sensitivity and negative predictive values were determined for scintigraphy (96.3% and 96.7%, respectively). However, the specificity and the positive predictive values were 71.4% and 68.4%, respectively, with an accuracy of 81.2%. The exclusion of examinations that were slightly positive from the analysis resulted in an improvement in test accuracy (95.5%). The preliminary results suggest that 99mTc-anti-TNF-α scintigraphy is a promising procedure for the evaluation of active orbital inflammation in GO. © Georg Thieme Verlag KG Stuttgart · New York.

Cat-scratch disease and bone scintigraphy.

PubMed

Ismaili-Alaoui, Nadia; Vuong, Valerie; Marcu-Marin, M; Sergent-Alaoui, Aline; Chevallier, Bertrand; de Labriolle-Vaylet, Claire

2012-08-01

Cat-scratch disease is a bacterial infection caused by Bartonella henselae. Bone involvement is rare. We describe the case of a 7-year-old boy with a systemic form of the disease. He presented with a 15-day history of fever, altered general condition, weight loss and cough, associated with back pain, and right-sided coxalgia. Bone scintigraphy with Tc-99m hydroxymethylene diphosphonate showed spinal involvement, the iliac crest, the right ankle, and the right first metatarsal. Magnetic resonance imaging confirmed these locations. He was positive for anti-Bartonella henselae. The fever regressed before treatment with rifampicin began, and he made a full recovery.

99mTc-DTPA diuretic renal scintigraphy in dogs with nephroureterolithiasis

PubMed Central

Hecht, Silke; Lawson, S. Meg; Lane, India F.; Sharp, Dorothy E.; Daniel, Gregory B.

2010-01-01

This study evaluated the results of diuretic renal scintigraphy in dogs with urolithiasis. Eighty-three kidneys with nephroureterolithiasis +/− renal pelvis/ureteral dilation were included in the study. Sixty-three kidneys showed a non-obstructive pattern, with a steep drop or gradual downward slope of renal time-activity curve (TAC). Excretion half-time of radiopharmaceutical (T1/2) was 3.99 (2.99 to 7.95) min. Three kidneys showed an obstructive pattern, with continuous rise of the TAC and median T1/2 of −10.71 (−5.20 to −17.56) min. Fifteen kidneys had non-diagnostic studies characterized by flat TAC. Individual kidney glomerular filtration rate was < 0.5 mL/min/kg body weight in most non-diagnostic studies. Diuretic renal scintigraphy appears to be a useful adjunct modality to rule out or confirm ureteral obstruction in dogs. Additional diagnostic procedures may be necessary to achieve a definitive diagnosis in cases of severely impaired renal function. PMID:21358928

Evaluation of the preventive effect of dexpanthenol in radiation injury by lung perfusion scintigraphy: a preclinical experimental model of radiation injury.

PubMed

Koç, Zehra P; İn, Erdal; Karslioğlu, İhsan; Üçer, Özlem; Canpolat, Sinan

2015-12-01

The aim of this study was to show the preventative effects of dexpanthenol in radiation injuries caused by radiotherapy (RT) through the use of lung perfusion scintigraphy in the pre-RT and post-RT periods. Six male New Zealand rabbits (5-6 months of age and ∼2.5-3 kg in weight) were the used in this study. The animals were subjected to Tc-macroaggregated albumin lung perfusion scintigraphy in the pre-RT and post-RT (i.e. 2 weeks after treatment) periods. The scintigraphies were performed with the same dose by the same staff and the methodology used the same acquisition parameters. The rabbits were divided into two groups: group I (administered RT only) and group II (also administered intramuscular 500 mg dexpanthenol injections for 14 consecutive days after RT). Quantification was performed to compare the groups and the quantification variables were compared using a paired samples t-test, with P value less than 0.05 considered to be statistically significant. Histopathological analysis was also carried out. The post-RT scintigraphies indicated a decrease in the counts in both lungs, suggesting early post-RT injury. The difference between the counts obtained from both lungs in groups I and II was significantly different and favoured group II. Histopathological results confirmed the scintigraphy results. It is possible to estimate post-RT changes in the early period (in contrast to previous data) by lung perfusion scintigraphy. Dexpanthenol may also reduce the effects of RT to a degree. Although this is the first study to report the preventive effects of dexpanthenol on RT injuries, further studies are warranted in this area.

Role of (123)I-Iobenguane Myocardial Scintigraphy in Predicting Short-term Left Ventricular Functional Recovery: An Interesting Image.

PubMed

Feola, Mauro; Chauvie, Stephane; Biggi, Alberto; Testa, Marzia

2015-01-01

(123)I-iobenguane myocardial scintigraphy (MIBG) has been shown to be a predictor of sudden cardiac mortality in patients with heart failure. One patient with recent anterior myocardial infarction (MI) treated with coronary angioplasty and having left ventricular ejection fraction (LVEF) of 30% underwent early MIBG myocardial scintigraphy/tetrofosmin single-photon emission computed tomography (SPECT) in order to help evaluate his eligibility for implantable cardioverter defibrillator (ICD). The late heart/mediastinum (H/M) ratio was calculated to be 1.32% and the washout rate was 1%. At 40-day follow-up after angioplasty, LVEF proved to be 32%, New York Heart Association (NYHA) class was still II-III, and an ICD was placed in order to reduce mortality from ventricular arrhythmias. MIBG myocardial scintigraphy might be a promising method for evaluating left ventricular recovery in post-MI patients.

Diagnostic value of 99mTc-ethambutol scintigraphy in tuberculosis: compared to microbiological and histopathological tests.

PubMed

Kartamihardja, A H S; Kurniawati, Y; Gunawan, R

2018-01-01

Tuberculosis (TB) still remains the world's endemic infection. TB affects the lungs and any part of the body other than the lung. The diagnosis of TB has not changed much over the decades. Ethambutol is one of the first line treatments for TB. It can be labeled using 99m Tc. 99m Tc-ethambutol will be accumulated in the site of TB lesion and can be imaged using gamma camera. The aim of this study was to evaluate the diagnostic value of 99m Tc-ethambutol scintigraphy in detecting and localizing of TB. Retrospective cross-sectional study was done. Subjects were patients suspected of having TB infection. Whole body and SPECT-CT imaging at the suspected area was done 1 and 4 h after injection of 370-555 MBq 99m Tc-ethambutol. 99m Tc-ethambutol scintigraphy was analyzed visually. The results were compared with that of histopathological or microbiological tests. Statistical analysis was done to determine the sensitivity, specificity, PPV, NPV and accuracy. One hundred and sixty-eight subjects were involved in this study. There were 110 men and 58 women with mean age of 34.52 ± 11.94 years. There were concordance results in 156 (92.86%) and discordant in 12 (7.14%) subjects between 99m Tc-ethambutol scintigraphy and histopathological or microbiological result. The sensitivity, specificity, PPV, NPV and accuracy of 99m Tc-ethambutol scintigraphy in the diagnosis of pulmonary TB were 93.9, 85.7, 93.9, 85.7 and 91.4%, respectively, for extra-pulmonary TB 95.5, 77.8, 97.9, 63.6, and 85.1%, respectively, and for total tuberculosis 94.9, 83.3, 96.3, 78.1 and 92.8%, respectively. There was no side effect observed in this study. 99m Tc-ethambutol scintigraphy is a useful diagnostic imaging technique to detect and localize intra- and extra-pulmonary TB. It is safe to be performed even in pediatric patient. Consuming ethambutol less than 2 weeks did not influence the result.

Techniques for measuring intercepted and absorbed PAR in corn canopies

NASA Technical Reports Server (NTRS)

Gallo, K. P.; Daughtry, C. S. T.

1984-01-01

The quantity of radiation potentially available for photosynthesis that is captured by the crop is best described as absorbed photosynthetically active radiation (PAR). Absorbed PAR (APAR) is the difference between descending and ascending fluxes. The four components of APAR were measured above and within two planting densities of corn (Zea mays L.) and several methods of measuring and estimating APAR were examined. A line quantum sensor that spatially averages the photosynthetic photon flux density provided a rapid and portable method of measuring APAR. PAR reflectance from the soil (Typic Argiaquoll) surface decreased from 10% to less than 1% of the incoming PAR as the canopy cover increased. PAR reflectance from the canopy decreased to less than 3% at maximum vegetative cover. Intercepted PAR (1 - transmitted PAR) generally overestimated absorbed PAR by less than 4% throughout most of the growing season. Thus intercepted PAR appears to be a reasonable estimate of absorbed PAR.

Protease-activated receptor (PAR)2, but not PAR1, is involved in collateral formation and anti-inflammatory monocyte polarization in a mouse hind limb ischemia model.

PubMed

van den Hengel, Lisa G; Hellingman, Alwine A; Nossent, Anne Yael; van Oeveren-Rietdijk, Annemarie M; de Vries, Margreet R; Spek, C Arnold; van Zonneveld, Anton Jan; Reitsma, Pieter H; Hamming, Jaap F; de Boer, Hetty C; Versteeg, Henri H; Quax, Paul H A

2013-01-01

In collateral development (i.e. arteriogenesis), mononuclear cells are important and exist as a heterogeneous population consisting of pro-inflammatory and anti-inflammatory/repair-associated cells. Protease-activated receptor (PAR)1 and PAR2 are G-protein-coupled receptors that are both expressed by mononuclear cells and are involved in pro-inflammatory reactions, while PAR2 also plays a role in repair-associated responses. Here, we investigated the physiological role of PAR1 and PAR2 in arteriogenesis in a murine hind limb ischemia model. PAR1-deficient (PAR1-/-), PAR2-deficient (PAR2-/-) and wild-type (WT) mice underwent femoral artery ligation. Laser Doppler measurements revealed reduced post-ischemic blood flow recovery in PAR2-/- hind limbs when compared to WT, while PAR1-/- mice were not affected. Upon ischemia, reduced numbers of smooth muscle actin (SMA)-positive collaterals and CD31-positive capillaries were found in PAR2-/- mice when compared to WT mice, whereas these parameters in PAR1-/- mice did not differ from WT mice. The pool of circulating repair-associated (Ly6C-low) monocytes and the number of repair-associated (CD206-positive) macrophages surrounding collaterals in the hind limbs were increased in WT and PAR1-/- mice, but unaffected in PAR2-/- mice. The number of repair-associated macrophages in PAR2-/- hind limbs correlated with CD11b- and CD115-expression on the circulating monocytes in these animals, suggesting that monocyte extravasation and M-CSF-dependent differentiation into repair-associated cells are hampered. PAR2, but not PAR1, is involved in arteriogenesis and promotes the repair-associated response in ischemic tissues. Therefore, PAR2 potentially forms a new pro-arteriogenic target in coronary artery disease (CAD) patients.

Diagnosis and follow-up of chronic bacterial prostatitis with recurrent urinary tract infection detected by 67Ga scintigraphy and SPECT/CT.

PubMed

Kim, Jun Ho; Baek, Ji-Hyeon; Lee, Jin Soo; Hyun, In Young

2013-11-01

Half of male populations will have symptoms and signs of prostatitis in their lifetime. There is controversy concerning diagnosis of prostatitis with (67)Ga scintigraphy because the focal midline pelvic uptake is usually considered to be physiologic uptake in colon. The authors describe (67)Ga scintigraphy and SPECT/CT findings of a 58-year-old man with right flank pain and fever. The examination demonstrated abnormal uptake of Ga within the prostate and right kidney upper pole, suggesting prostatitis and acute pyelonephritis (APN) contemporary. After completion of antibiotic treatment, follow-up scintigraphy and SPECT/CT showed complete resolution of APN, but uptake remained within the prostate.

Pulmonary vascular volume ratio measured by cardiac computed tomography in children and young adults with congenital heart disease: comparison with lung perfusion scintigraphy.

PubMed

Goo, Hyun Woo; Park, Sang Hyub

2017-11-01

Lung perfusion scintigraphy is regarded as the gold standard for evaluating differential lung perfusion ratio in congenital heart disease. To compare cardiac CT with lung perfusion scintigraphy for estimated pulmonary vascular volume ratio in patients with congenital heart disease. We included 52 children and young adults (median age 4 years, range 2 months to 28 years; 31 males) with congenital heart disease who underwent cardiac CT and lung perfusion scintigraphy without an interim surgical or transcatheter intervention and within 1 year. We calculated the right and left pulmonary vascular volumes using threshold-based CT volumetry. Then we compared right pulmonary vascular volume percentages at cardiac CT with right lung perfusion percentages at lung perfusion scintigraphy by using paired t-test and Bland-Altman analysis. The right pulmonary vascular volume percentages at cardiac CT (66.3 ± 14.0%) were significantly smaller than the right lung perfusion percentages at lung perfusion scintigraphy (69.1 ± 15.0%; P=0.001). Bland-Altman analysis showed a mean difference of -2.8 ± 5.8% and 95% limits of agreement (-14.1%, 8.5%) between these two variables. Cardiac CT, in a single examination, can offer pulmonary vascular volume ratio in addition to pulmonary artery anatomy essential for evaluating peripheral pulmonary artery stenosis in patients with congenital heart disease. However there is a wide range of agreement between cardiac CT and lung perfusion scintigraphy.

Doxycycline directly targets PAR1 to suppress tumor progression.

PubMed

Zhong, Weilong; Chen, Shuang; Zhang, Qiang; Xiao, Ting; Qin, Yuan; Gu, Ju; Sun, Bo; Liu, Yanrong; Jing, Xiangyan; Hu, Xuejiao; Zhang, Peng; Zhou, Honggang; Sun, Tao; Yang, Cheng

2017-03-07

Doxycycline have been reported to exert anti-cancer activity and have been assessed as anti-cancer agents in clinical trials. However, the direct targets of doxycycline in cancer cells remain unclear. In this study, we used a chemical proteomics approach to identify the Protease-activated receptor 1 (PAR1) as a specific target of inhibition of doxycycline. Binding assays and single-molecule imaging assays were performed to confirm the inhibition of doxycycline to PAR1. The effect of doxycycline on multi-omics and cell functions were assessed based on a PAR1/thrombin model. Molecular docking and molecular dynamic simulations revealed that doxycycline interacts with key amino acids in PAR1. Mutation of PAR1 further confirmed the computation-based results. Moreover, doxycycline provides highly selective inhibition of PAR1 signaling in tumors in vitro and in vivo. Using pathological clinical samples co-stained for doxycycline and PAR1, it was found that doxycycline fluorescence intensity and PAR1 expression shown a clear positive correlation. Thus, doxycycline may be a useful targeted anti-cancer drug that should be further investigated in clinical trials.

PAR -- Interface to the ADAM Parameter System

NASA Astrophysics Data System (ADS)

Currie, Malcolm J.; Chipperfield, Alan J.

PAR is a library of Fortran subroutines that provides convenient mechanisms for applications to exchange information with the outside world, through input-output channels called parameters. Parameters enable a user to control an application's behaviour. PAR supports numeric, character, and logical parameters, and is currently implemented only on top of the ADAM parameter system. The PAR library permits parameter values to be obtained, without or with a variety of constraints. Results may be put into parameters to be passed onto other applications. Other facilities include setting a prompt string, and suggested defaults. This document also introduces a preliminary C interface for the PAR library -- this may be subject to change in the light of experience.

An ELISA method detecting the active form of suPAR.

PubMed

Zhou, Xiaolei; Xu, Mingming; Huang, Hailong; Mazar, Andrew; Iqbal, Zafar; Yuan, Cai; Huang, Mingdong

2016-11-01

Urokinase plasminogen activator receptor (uPAR) exists in a number of formats in human plasma, including soluble uPAR (suPAR) and uPAR fragments. We developed an ELISA method to detect specifically the active form suPAR, which binds to its natural ligand uPA. The intra CV and inter CV of this ELISA assay is 8.5% and 9.6% respectively, and the assay can recover 99.74% of added recombinant suPAR from 10% plasma. This assay is quite sensitive, capable of detecting down to 15pg/ml of suPAR, and can measure suPAR concentrations in the range of 0.031-8ng/ml with high linear relationship. Plasma samples from pregnant women were also measured for the active form of suPAR with this assay, giving an averaged level of 1.39ng/ml, slightly higher than the level of pooled plasma from healthy donors (0.96ng/ml). This study demonstrates the feasibility to measure the active form of suPAR, which will likely have value in clinical applications. Copyright © 2016. Published by Elsevier B.V.

Doxycycline directly targets PAR1 to suppress tumor progression

PubMed Central

Qin, Yuan; Gu, Ju; Sun, Bo; Liu, Yanrong; Jing, Xiangyan; Hu, Xuejiao; Zhang, Peng; Zhou, Honggang; Sun, Tao; Yang, Cheng

2017-01-01

Doxycycline have been reported to exert anti-cancer activity and have been assessed as anti-cancer agents in clinical trials. However, the direct targets of doxycycline in cancer cells remain unclear. In this study, we used a chemical proteomics approach to identify the Protease-activated receptor 1 (PAR1) as a specific target of inhibition of doxycycline. Binding assays and single-molecule imaging assays were performed to confirm the inhibition of doxycycline to PAR1. The effect of doxycycline on multi-omics and cell functions were assessed based on a PAR1/thrombin model. Molecular docking and molecular dynamic simulations revealed that doxycycline interacts with key amino acids in PAR1. Mutation of PAR1 further confirmed the computation-based results. Moreover, doxycycline provides highly selective inhibition of PAR1 signaling in tumors in vitro and in vivo. Using pathological clinical samples co-stained for doxycycline and PAR1, it was found that doxycycline fluorescence intensity and PAR1 expression shown a clear positive correlation. Thus, doxycycline may be a useful targeted anti-cancer drug that should be further investigated in clinical trials. PMID:28187433

Evaluation of gastroesophageal reflux before and after sleeve gastrectomy using symptom scoring, scintigraphy, and endoscopy.

PubMed

Sharma, Aditya; Aggarwal, Sandeep; Ahuja, Vineet; Bal, Chandrashekhar

2014-01-01

The effect of laparoscopic sleeve gastrectomy (SG) on gastroesophageal reflux disease (GERD) has been a controversial issue. There have been limited studies on this aspect and most of the published studies are retrospective. Therefore, a prospective study was designed to objectively assess the problem. The objective of this study was to assess the impact of SG on symptoms of gastroesophageal reflux using questionnaire, endoscopy, and radionuclide scintigraphy. Thirty-two patients undergoing laparoscopic sleeve gastrectomy were assessed for gastroesophageal reflux using Carlsson Dent Questionnaire and GERD questionnaire before and after surgery at three monthly intervals. They were also subjected to upper GI endoscopy (UGIE) and radionuclide scintigraphy both pre- and postoperatively. Mean preoperative weight and body mass index were 126.5 kg and 47.8 kg/m2, respectively. Mean percent excess weight loss at 12 months was 64.3 ± 18.4. Both the Carlsson Dent Score (CDS) and Severity Score (SS) exhibited a decline from 2.88 to 1.63 (p<0.05) and 2.28 to 1.06 (p<0.05), respectively after 12 months. Radionuclide scintigraphy revealed a significant rise of GERD from 6.25% to 78.1% in the postoperative period (p<0.001). UGIE showed a rise in incidence of esophagitis from 18.8% to 25%; however, there was improvement in all patients except one in terms of reduction of severity of esophagitis. Presence of GERD may not be considered as a contra-indication for sleeve gastrectomy. There is improvement of GERD as assessed by symptom questionnaires, as well as improvement in grade of esophagitis. The new onset GERD detected on scintigraphy may not be pathologic as there is a decrease in total acid production postsurgery; however, it still remains an important issue and needs long-term follow-up. Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

The utility of 99mTc-EDDA/HYNIC-TOC scintigraphy for assessment of lung lesions in patients with neuroendocrine tumors.

PubMed

Pavlovic, S; Artiko, V; Sobic-Saranovic, D; Damjanovic, S; Popovic, B; Jakovic, R; Petrasinovic, Z; Jaksic, E; Todorovic-Tirnanic, M; Saranovic, D; Micev, M; Novosel, S; Nikolic, N; Obradovic, V

2010-01-01

Our aim was to assess clinical utility of 99mTc-EDDA/HYNIC-TOC scintigraphy for evaluation of lung lesions in patients with neuroendocrine tumors (NETs). Single photon emission computed tomography (SPECT) of the thorax and whole body scintigraphy were performed in 34 patients using 99mTc-EDDA/HYNIC-TOC. Visual assessment was complemented by semiquantitative evaluation based on tumor to non-tumor (T/NT) ratio. Clinical, laboratory, and histological findings served as the standard for comparison. Enhanced tracer uptake was observed on both SPECT and whole body scintigraphy in 29 of 34 patients (88% sensitivity). T/NT ratios were significantly higher on SPECT than whole body images (2.96+/-1.07 vs.1.70+/-0.43, p 99mTc-EDDA/Hynic-TOC, lung involvement of NETs, T/NT ratio.

Effective visualization of suppressed thyroid tissue by means of baseline 99mTc-methoxy isobutyl isonitrile in comparison with 99mTc-pertechnetate scintigraphy after TSH stimulation.

PubMed

Vattimo, A; Bertelli, P; Burroni, L

1992-01-01

Baseline 99mTc-MIBI thyroid scintigraphy was compared with 99mTc-pertechnetate scintigraphy after TSH stimulation in seven patients with suppressed thyroid tissue due to an autonomously functioning thyroid nodule (AFTN). In all patients the suppressed thyroid tissue was visualized by means of both baseline 99mTc-MIBI and post-TSH 99mTc-pertechnetate scintigraphy, and in some cases the former technique provided better visualization. In one patient presenting a "warm" nodule T3-suppression did not affect the nodular/extranodular uptake ratio of 99mTc-MIBI, whereas the 99mTc-pertechnetate uptake ratio increased significantly. This leads us to hypothesize that the thyroid uptake of 99mTc-MIBI is not related to TSH control, but rather to other mechanisms such as the blood flow. Since exogenous TSH is no longer available, 99mTc-MIBI scintigraphy can be successfully used in the place of repeated 99mTc-pertechnetate scintigraphy after TSH stimulation in the assessment of AFTN.

(99m)Tc-DTPA diuretic renal scintigraphy in cats with nephroureterolithiasis.

PubMed

Hecht, Silke; Lawson, Sarah M; Lane, India F; Sharp, Dorothy E; Daniel, Gregory B

2010-06-01

The purpose of this study was to evaluate results of diuretic renal scintigraphy in 32 feline kidneys with nephroureterolithiasis and variable degrees of renal pelvis/ureteral dilation. Six kidneys showed a non-obstructive scintigraphic pattern, with a downward slope of time-activity curves (TAC) and a median excretion half-time of radiopharmaceutical (T((1/2))) of 6.09 (5.08-8.43) min. Eight kidneys showed an obstructive pattern, with a continuous rise of TAC and median T((1/2)) of -7.91 (-43.13-0.00) min. In one kidney with presumptive partial obstruction scintigraphic results were equivocal. Seventeen kidneys, most of which had an individual kidney glomerular filtration rate below 0.5ml/min/kg, had non-diagnostic studies. Diuretic renal scintigraphy may be a useful adjunct modality in the diagnosis of ureteral obstruction in some cats if renal function is maintained. However, the large number of non-diagnostic studies in animals with decreased renal function represents a clear limitation of the technique. Copyright 2009 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Proteinase-Activated Receptor 1 (PAR1) Regulates Leukemic Stem Cell Functions

PubMed Central

Bäumer, Nicole; Krause, Annika; Köhler, Gabriele; Lettermann, Stephanie; Evers, Georg; Hascher, Antje; Bäumer, Sebastian; Berdel, Wolfgang E.

2014-01-01

External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1−/− hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1−/− leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance. PMID:24740120

Proteinase-Activated Receptor 1 (PAR1) regulates leukemic stem cell functions.

PubMed

Bäumer, Nicole; Krause, Annika; Köhler, Gabriele; Lettermann, Stephanie; Evers, Georg; Hascher, Antje; Bäumer, Sebastian; Berdel, Wolfgang E; Müller-Tidow, Carsten; Tickenbrock, Lara

2014-01-01

External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1-/- hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1-/- leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.

Bone scintigraphy in hypervitaminosis A

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

Miller, J.H.; Hayon, I.I.

1985-04-01

The diagnosis of vitamin A intoxification may be difficult at the time of initial presentation. The radionuclide bone scan in cases of vitamin A toxicity may serve as a more sensitive indicator of the presence of this disease than radiographs in the initial evaluation and follow-up of patients with skeletal involvement. This is achieved at a lower radiation dose to the patient. The authors present a case in which bone scintigraphy played a crucial role in the early identification of this disorder. The radionuclide examination was the first method that indicated the presence of this disorder, significantly before changes demonstrablemore » on conventional radiography. The clinical and scintigraphic appearance of this process should be recognized to allow identification of hypervitaminosis A before the clinical symptoms become severe or permanent skeletal deformities result.« less

Technetium-99m diethylenetriaminepentaacetic acid radioaerosol scintigraphy in organophosphate induced pulmonary toxicity: experimental study.

PubMed

Yavuz, Yucel; Kaya, Eser; Yurumez, Yusuf; Sahin, Onder; Bas, Orhan; Fidan, Huseyin; Sezer, Murat

2008-09-01

The aim of this experimental study was to investigate pathological signs of lung damages caused by acute organophosphate (OP) poisoning by using Tc-99m DTPA radioaerosol scintigraphy and histopathological investigation. Fourteen rabbits were divided into two equal groups (n = 7). Group 1 (control group) received normal saline (same volume of fenthion, 2 ml/kg) via orogastric tube. Group 2 (OP toxicity group) received 150 mg/kg of fenthion (diluted fenthion, 2 ml/kg) via orogastric tube. Six hours later, Tc-99m-DTPA aerosol inhalation lung scintigraphy was performed in both groups. Then all rabbits were anesthetized with ketamine hydrochloride (35 mg/kg, i.p.) and xysilazine (5 mg/kg, i.p.), and sacrificed by intracardiac blood discharge. The lungs were then removed. There was a significant difference in T1/2 values of Tc-99m DTPA clearance between control group and OP toxicity group (p = 0.04). Intraparenchymal vascular congestion and thrombosis, intraparenchymal hemorrhage, respiratory epithelial proliferation, number of macrophages in the alveolar, and bronchial lumen, alveolar destruction, emphysematous changes, and bronchoalveolar hemorrhage scores were significantly higher in the rabbits exposed to OP compared with the control group (p < 0.05). This study showed that OP toxicity caused a decrease in the alveolar clearance. Tc-99m DTPA radioaerosol inhalation lung scintigraphy was found to be a sensitive determination of acute lung damage in OP poisoning.

Evaluation of tumor-induced osteomalacia with 111In-pentetreotide scintigraphy.

PubMed

Palot Manzil, Fathima Fijula; Bhambhvani, Pradeep G; O'Malley, Janis P

2013-12-01

In cases of nonhereditary osteomalacia associated with hypophosphatemia and inadequate response to vitamin D supplementation, one should consider the possibility of tumor-induced osteomalacia, a paraneoplastic syndrome caused by small mesenchymal tumors often found in obscure locations. We present a case of tumor-induced osteomalacia in which (111)In-pentetreotide scintigraphy aided in accurate localization of the culprit brachial plexus tumor and cure after resection.

99mTc Labeled Glucagon-Like Peptide-1-Analogue (99mTc-GLP1) Scintigraphy in the Management of Patients with Occult Insulinoma

PubMed Central

Sowa-Staszczak, Anna; Trofimiuk-Müldner, Małgorzata; Stefańska, Agnieszka; Tomaszuk, Monika; Buziak-Bereza, Monika; Gilis-Januszewska, Aleksandra; Jabrocka-Hybel, Agata; Głowa, Bogusław; Małecki, Maciej; Bednarczuk, Tomasz; Kamiński, Grzegorz; Kowalska, Aldona; Mikołajczak, Renata; Janota, Barbara; Hubalewska-Dydejczyk, Alicja

2016-01-01

Introduction The aim of this study was to assess the utility of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 scintigraphy in the management of patients with hypoglycemia, particularly in the detection of occult insulinoma. Materials and Methods Forty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study. In all patients GLP-1 receptor imaging was performed to localise potential pancreatic lesions. Results Positive results of GLP-1 scintigraphy were observed in 28 patients. In 18 patients postsurgical histopathological examination confirmed diagnosis of insulinoma. Two patients had contraindications to the surgery, one patient did not want to be operated. One patient, who presented with postprandial hypoglycemia, with positive result of GLP-1 imaging was not qualified for surgery and is in the observational group. Eight patients were lost for follow up, among them 6 patients with positive GLP-1 scintigraphy result. One patient with negative scintigraphy was diagnosed with malignant insulinoma. In two patients with negative scintigraphy Munchausen syndrome was diagnosed (patients were taking insulin). Other seven patients with negative results of 99mTcGLP-1 scintigraphy and postprandial hypoglycemia with C-peptide and insulin levels within the limits of normal ranges are in the observational group. We would like to mention that 99mTc-GLP1-SPECT/CT was also performed in 3 pts with nesidioblastosis (revealing diffuse tracer uptake in two and a focal lesion in one case) and in two patients with malignant insulinoma (with the a focal uptake in the localization of a removed pancreatic headin one case and negative GLP-1 1 scintigraphy in the other patient). Conclusions 99mTc-GLP1-SPECT/CT could be helpful examination in the management of patients with hypoglycemia enabling proper localization of the pancreatic lesion and effective

PAR(2) and temporomandibular joint inflammation in the rat.

PubMed

Denadai-Souza, A; Cenac, N; Casatti, C A; Câmara, P R de Souza; Yshii, L M; Costa, S K P; Vergnolle, N; Muscará, M N

2010-10-01

The proteinase-activated receptor 2 (PAR(2)) is a putative therapeutic target for arthritis. We hypothesized that the early pro-inflammatory effects secondary to its activation in the temporomandibular joint (TMJ) are mediated by neurogenic mechanisms. Immunofluorescence analysis revealed a high degree of neurons expressing PAR(2) in retrogradely labeled trigeminal ganglion neurons. Furthermore, PAR(2) immunoreactivity was observed in the lining layer of the TMJ, co-localizing with the neuronal marker PGP9.5 and substance-P-containing peripheral sensory nerve fibers. The intra-articular injection of PAR(2) agonists into the TMJ triggered a dose-dependent increase in plasma extravasation, neutrophil influx, and induction of mechanical allodynia. The pharmacological blockade of natural killer 1 (NK(1)) receptors abolished PAR(2)-induced plasma extravasation and inhibited neutrophil influx and mechanical allodynia. We conclude that PAR(2) activation is pro-inflammatory in the TMJ, through a neurogenic mechanism involving NK(1) receptors. This suggests that PAR(2) is an important component of innate neuro-immune response in the rat TMJ.

PAR proteins regulate maintenance-phase myosin dynamics during Caenorhabditis elegans zygote polarization

PubMed Central

Small, Lawrence E.; Dawes, Adriana T.

2017-01-01

Establishment of anterior–posterior polarity in the Caenorhabditis elegans zygote requires two different processes: mechanical activity of the actin–myosin cortex and biochemical activity of partitioning-defective (PAR) proteins. Here we analyze how PARs regulate the behavior of the cortical motor protein nonmuscle myosin (NMY-2) to complement recent efforts that investigate how PARs regulate the Rho GTPase CDC-42, which in turn regulates the actin-myosin cortex. We find that PAR-3 and PAR-6 concentrate CDC-42–dependent NMY-2 in the anterior cortex, whereas PAR-2 inhibits CDC-42–dependent NMY-2 in the posterior domain by inhibiting PAR-3 and PAR-6. In addition, we find that PAR-1 and PAR-3 are necessary for inhibiting movement of NMY-2 across the cortex. PAR-1 protects NMY-2 from being moved across the cortex by forces likely originating in the cytoplasm. Meanwhile, PAR-3 stabilizes NMY-2 against PAR-2 and PAR-6 dynamics on the cortex. We find that PAR signaling fulfills two roles: localizing NMY-2 to the anterior cortex and preventing displacement of the polarized cortical actin–myosin network. PMID:28615321

Incremental value of 99mTc-HYNIC-TOC SPECT/CT over whole-body planar scintigraphy and SPECT in patients with neuroendocrine tumours.

PubMed

Trogrlic, Mate; Težak, Stanko

2017-06-12

The aim of this study was to evaluate the additional value of 99m Tc-HYNIC-TOC SPECT/CT over planar whole-body (WB) scintigraphy and SPECT alone in the detection and accurate localisation of neuroendocrine tumour (NET) lesions. This study included 65 patients with a definitive histological diagnosis of NET prior to scintigraphy. Planar WB scintigraphy, SPECT, and SPECT/CT images were acquired at 4 h post-administration of 670 MBq 99m Tc-HYNIC-TOC. Additional SPECT images at 10 min after tracer administration were also acquired. Clinical and imaging follow-up findings were considered as the reference standards (minimum follow-up period, 15 months). Patient and lesion-based analyses of the efficacies of the imaging modalities were performed. While 38 patients exhibited metastasis of NETs, 27 presented no evidence of metastasis. Upon patient-based analysis, the sensitivity and specificity of SPECT/CT were found to be 88.9 and 79.3 %, respectively. The diagnostic accuracies of WB scintigraphy, 4h-SPECT, and SPECT/CT were 72.3, 73.8, and 84.6 %, respectively. The area under curve (AUC) value for SPECT/CT (0.84) was the highest, followed by those for 4h-SPECT (0.75) and WB scintigraphy (0.74). The accuracy and AUC values of SPECT/CT were significantly better compared to those of WB scintigraphy (p < 0.001), 10 min-SPECT (p < 0.001), and 4 h-SPECT (p = 0.001). The findings of SPECT/CT led to the change in treatment plan of 11 patients (16.9 %). The sensitivity and diagnostic accuracy of SPECT/CT in the evaluation of NET lesions outperforms planar WB imaging or SPECT alone.

[Carcinoid tumor and bone metastases: diagnosis by somatostatin receptor scintigraphy].

PubMed

Banzo, J; Abós, M D; Prats, E; Razola, P; García, S; Alonso, V; Velilla, J; García, F; Ubieto, M A; Tardín, L

2004-01-01

The aim of this study has been to retrospectively assess the usefulness of 111In-DTPAOC scintigraphy in the detection of bone metastases (BM) in patients diagnosed of carcinoid tumour (CaT). Between June 1995 and April 2003 78 111In-DTPAOC studies were consecutively performed in 58 patients, 31 females and 27 males, 28 to 73 years old, with a histological diagnosis of CaT. Moreover, whole body bone scans (BS) using 99mTc-MDP were performed in 13 of these patients. The patients were classified into three groups: Group A: Initial CaT staging (n = 23); Group B: CaT staging after surgery (n = 14); and Group C: Post-treatment CaT re-staging (n = 29). In this last group, 6 patients of group A and 2 patients of group B were included. In only 2 patients the diagnoses of bone metastases were established before the 111In-DTPAOC scan. Twenty six (44.8 %9 of the 58 patients with CaT had metastatic disease: 15 patients with hepatic metastases, associated with BM in 4 of them, 10 patients with hepatic and extra-hepatic metastases, abdominal and/or thoracic, associated with BM in 4 and in one patient, the BMs were the only metastases detected. The global incidence of BM in patients diagnosed with CaT was 15.5 % (9/58), whereas the incidence of BM in patients with metastasic disease was 34.6 % (9/26). Significant differences (p = 0.0035) were found on the incidence of BM in patients with or without hepatic metastases. In 4 patients, BMs were detected during the initial staging (group A), whereas in 5 patients, BMs were detected during the post-treatment re-staging (group C). During diagnosis, 4 of the 9 patients with BM had bone pain. BM were multiples in 8 patients, affecting axial skeleton in 4 and axial and appendicular skeleton in 4. One patient had a diffuse infiltration of bone marrow. BS was positive in 8 of the 9 patients with BM. In these 8 patients with abnormal BS, 111In-DTPAOC scintigraphy provides similar information to the BS in one patient, shows a greater number of

Determination of solid- and liquid-phase gastric emptying half times in cats by use of nuclear scintigraphy.

PubMed

Costello, M; Papasouliotis, K; Barr, F J; Gruffydd-Jones, T J; Caney, S M

1999-10-01

To use nuclear scintigraphy to establish a range of gastric emptying half times (t1/2) following a liquid or solid meal in nonsedated cats. 12 clinically normal 3-year-old domestic shorthair cats. A test meal of 75 g of scrambled eggs labeled with technetium Tc 99m tin colloid was fed to 10 of the cats, and solid-phase gastric emptying t1/2 were determined by use of nuclear scintigraphy. In a separate experiment, 8 of these cats plus an additional 2 cats were fed 18 ml (n = 5) or 36 ml (n = 5) of a nutrient liquid meal labeled with technetium Tc 99m pentetate. Liquid-phase gastric emptying t1/2 then were determined by use of scintigraphy. Solid-phase gastric emptying t1/2 were between 210 and 769 minutes (median, 330 minutes). Median liquid-phase gastric emptying t1/2 after ingestion of 18 or 36 ml of the test meal were 67 minutes (range, 60 to 96 minutes) and 117 minutes (range, 101 to 170 minutes), respectively. The median t1/2 determined for cats receiving 18 ml of the radiolabeled liquid was significantly less than that determined for cats receiving 36 ml of the test meal. The protocol was tolerated by nonsedated cats. Solid-phase gastric emptying t1/2 were prolonged, compared with liquid-phase t1/2, and a major factor governing the emptying rate of liquids was the volume consumed. Nuclear scintigraphy may prove useful in assessing gastric motility disorders in cats.

Kallikrein-related peptidase 4 (KLK4) initiates intracellular signaling via protease-activated receptors (PARs). KLK4 and PAR-2 are co-expressed during prostate cancer progression.

PubMed

Ramsay, Andrew J; Dong, Ying; Hunt, Melanie L; Linn, MayLa; Samaratunga, Hemamali; Clements, Judith A; Hooper, John D

2008-05-02

Kallikrein-related peptidase 4 (KLK4) is one of the 15 members of the human KLK family and a trypsin-like, prostate cancer-associated serine protease. Signaling initiated by trypsin-like serine proteases are transduced across the plasma membrane primarily by members of the protease-activated receptor (PAR) family of G protein-coupled receptors. Here we show, using Ca(2+) flux assays, that KLK4 signals via both PAR-1 and PAR-2 but not via PAR-4. Dose-response analysis over the enzyme concentration range 0.1-1000 nM indicated that KLK4-induced Ca(2+) mobilization via PAR-1 is more potent than via PAR-2, whereas KLK4 displayed greater efficacy via the latter PAR. We confirmed the specificity of KLK4 signaling via PAR-2 using in vitro protease cleavage assays and anti-phospho-ERK1/2/total ERK1/2 Western blot analysis of PAR-2-overexpressing and small interfering RNA-mediated receptor knockdown cell lines. Consistently, confocal microscopy analyses indicated that KLK4 initiates loss of PAR-2 from the cell surface and receptor internalization. Immunohistochemical analysis indicated the co-expression of agonist and PAR-2 in primary prostate cancer and bone metastases, suggesting that KLK4 signaling via this receptor will have pathological relevance. These data provide insight into KLK4-mediated cell signaling and suggest that signals induced by this enzyme via PARs may be important in prostate cancer.

Microtubules induce self-organization of polarized PAR domains in C. elegans zygotes

PubMed Central

Motegi, Fumio; Zonies, Seth; Hao, Yingsong; Cuenca, Adrian A.; Griffin, Erik; Seydoux, Geraldine

2011-01-01

A hallmark of polarized cells is the segregation of the PAR polarity regulators into asymmetric domains at the cell cortex1, 2. Antagonistic interactions involving two conserved kinases, atypical protein kinase C (aPKC) and PAR-1, have been implicated in polarity maintenance1, 2, but the mechanisms that initiate the formation of asymmetric PAR domains are not understood. Here, we describe one pathway used by the sperm-donated centrosome to polarize the PAR proteins in Caenorhabditis elegans zygotes. Before polarization, cortical aPKC excludes PAR-1 kinase and its binding partner PAR-2 by phosphorylation. During symmetry breaking, microtubules nucleated by the centrosome locally protect PAR-2 from phosphorylation by aPKC, allowing PAR-2 and PAR-1 to access the cortex nearest the centrosome. Cortical PAR-1 phosphorylates PAR-3, causing the PAR-3/aPKC complex to leave the cortex. Our findings illustrate how microtubules, independent of actin dynamics, stimulate the self-organization of PAR proteins by providing local protection against a global barrier imposed by aPKC. PMID:21983565

Aspergillus fumigatus Increased PAR-2 Expression and Elevated Proinflammatory Cytokines Expression Through the Pathway of PAR-2/ERK1/2 in Cornea.

PubMed

Niu, Yawen; Zhao, Guiqiu; Li, Cui; Lin, Jing; Jiang, Nan; Che, Chengye; Zhang, Jie; Xu, Qiang

2018-01-01

To determine the role of protease-activated receptor-2 (PAR-2) in cornea infected by Aspergillus fumigatus. PAR-2 was tested in normal and infected corneas of C57BL/6 mice. Mice corneas were infected with A. fumigatus with or without pretreatment of PAR-2 antagonist (FSLLRY-NH2). Polymorphonuclear neutrophilic leukocytes (PMNs) were stimulated with 75% ethanol-killed A. fumigatus with or without pretreatment of FSLLRY-NH2. Disease severity was documented by clinical score and photographs with a slit lamp. PCR, Western blot, and ELISA tested expression of PAR-2, IL-1β, TNF-α, IFN-γ, MIP-2, and p-ERK1/2. PMN infiltration was assessed by myeloperoxidase assay and immunofluorescent staining. PAR-2 expression was significantly elevated by A. fumigatus, whereas the upregulation was significantly inhibited by FSLLRY-NH2 in mice corneas. FSLLRY-NH2 decreased disease response, PMN infiltration, and proinflammatory cytokine expression compared with infected control. In PMNs, PAR-2 expression was also significantly increased by A. fumigatus, which was significantly inhibited by FSLLRY-NH2. FSLLRY-NH2 significantly inhibited proinflammatory cytokine protein expression, as compared with that in infected control cells, which may be modified by p-ERK1/2. These data provide evidence that A. fumigatus increased PAR-2 expression and elevated disease, PMN infiltration, and proinflammatory cytokine expression through PAR-2, which may be modified by p-ERK1/2.

Integrated imaging using MRI and 123I metaiodobenzylguanidine scintigraphy to improve sensitivity and specificity in the diagnosis of pediatric neuroblastoma.

PubMed

Pfluger, Thomas; Schmied, Christoph; Porn, Ute; Leinsinger, Gerda; Vollmar, Christian; Dresel, Stefan; Schmid, Irene; Hahn, Klaus

2003-10-01

The objectives of this study were to compare MRI and iodine-123 ((123)I) metaiodobenzylguanidine (MIBG) scintigraphy in the detection of neuroblastoma lesions in pediatric patients and to assess the additional value of combined imaging. Fifty MRI and 50 (123)I MIBG examinations (mean interval, 6.4 days) were analyzed retrospectively with regard to suspected or proven neuroblastoma lesions (n = 193) in 28 patients. MRI and MIBG scans were reviewed by two independent observers each. Separate and combined analyses of MRI and MIBG scintigraphy were compared with clinical and histologic findings. With regard to the diagnosis of neuroblastoma lesion, MIBG scintigraphy, MRI, and combined analysis showed a sensitivity of 69%, 86%, and 99% and a specificity of 85%, 77%, and 95%, respectively. On MRI, 15 false-positive findings were recorded: posttherapeutic reactive changes (n = 10), benign adrenal tumors (n = 3), and enlarged lymph nodes (n = 2). On MIBG scintigraphy, 10 false-positive findings occurred: ganglioneuromas (n = 2), benign liver tumors (n = 2), and physiologic uptake (n = 6). Thirteen neuroblastoma metastases and two residual masses under treatment with chemotherapy were judged to be false-negative findings on MRI. Two primary or residual neuroblastomas and one orbital metastasis were misinterpreted as Wilms' tumor, reactive changes after surgery, and rhabdomyosarcoma on MRI. Thirty-two bone metastases, six other neuroblastoma metastases, and one adrenal neuroblastoma showed no MIBG uptake. On combined imaging, one false-negative (bone metastasis) and three false-positive (two ganglioneuromas and one pheochromocytoma) findings remained. In the assessment of neuroblastoma lesions in pediatric patients, MRI showed a higher sensitivity and MIBG scintigraphy a higher specificity. However, integrated imaging showed an increase in both sensitivity and specificity.

Assessment of branch pulmonary artery stenosis in children after repair of tetralogy of Fallot using lung perfusion scintigraphy comparison with echocardiography.

PubMed

Chien, Kuang-Jen; Huang, Hurng-Wern; Huang, Ta-Cheng; Lee, Cheng-Liang; Weng, Ken-Pen; Lin, Chu-Chuan; Shieh, Po-Chuen; Wu, Ming-Ting; Hsieh, Kai-Sheng

2016-01-01

The aim of this study was to compare the usefulness of lung perfusion scintigraphy and echocardiogram in the evaluation of the branch pulmonary arteries stenosis in children with tetralogy of Fallot (TOF). From February 2006 to November 2008, 74 children (mean age 7.8 years, range 1–18 years) who underwent repair of TOF at ages from 10 months to 13 years were suspected to have unilateral or bilateral branch pulmonary artery stenosis. In all patients, cardiac angiography was performed to confirm the diagnosis of branch pulmonary artery stenosis. Lung perfusion scintigraphy and two-dimensional transthoracic echocardiography were performed in all patients to compare their abilities to diagnose branch pulmonary artery stenosis. Of the 74 patients, 51 cases were found to have branch pulmonary artery stenosis by cardiac angiography. There was agreement between the scintigraphic and angiographic findings in 44 (86%) patients and there were discrepancies in 11 (15%) patients. The positive predictive value of our lung perfusion scintigraphy in detecting the branch pulmonary artery stenosis was 92 %. The positive and negative likelihood ratios of lung perfusion scintigraphy were 4.96 and 0.17, respectively. There was conformity between the echocardiographic and angiographic findings in 40 (78%) patients with discrepancies in 16 (21%) patients. The positive predictive value of our echocardiography in detecting the branch pulmonary artery stenosis was 89%. The positive and negative likelihood ratios of echocardiography were 3.61 and 0.28, respectively. Lung perfusion scintigraphy is a valuable, non-invasive screening tool in the assessment of branch pulmonary artery stenosis in children after TOF.

Lung scintigraphy in differential diagnosis of peripheral lung cancer and community-acquired pneumonia

NASA Astrophysics Data System (ADS)

Krivonogov, Nikolay G.; Efimova, Nataliya Y.; Zavadovsky, Konstantin W.; Lishmanov, Yuri B.

2016-08-01

Ventilation/perfusion lung scintigraphy was performed in 39 patients with verified diagnosis of community-acquired pneumonia (CAP) and in 14 patients with peripheral lung cancer. Ventilation/perfusion ratio, apical-basal gradients of ventilation (U/L(V)) and lung perfusion (U/L(P)), and alveolar capillary permeability of radionuclide aerosol were determined based on scintigraphy data. The study demonstrated that main signs of CAP were increases in ventilation/perfusion ratio, perfusion and ventilation gradient on a side of the diseased lung, and two-side increase in alveolar capillary permeability rate for radionuclide aerosol. Unlike this, scintigraphic signs of peripheral lung cancer comprise an increase in ventilation/perfusion ratio over 1.0 on a side of the diseased lung with its simultaneous decrease on a contralateral side, normal values of perfusion and ventilation gradients of both lungs, and delayed alveolar capillary clearance in the diseased lung compared with the intact lung.

Relationship between Calcium Score and Myocardial Scintigraphy in the Diagnosis of Coronary Disease

PubMed Central

Siqueira, Fabio Paiva Rossini; Mesquita, Claudio Tinoco; dos Santos, Alair Augusto Sarmet M. Damas; Nacif, Marcelo Souto

2016-01-01

Half the patients with coronary artery disease present with sudden death - or acute infarction as first symptom, making early diagnosis pivotal. Myocardial perfusion scintigraphy is frequently used in the assessment of these patients, but it does not detect the disease without flow restriction, exposes the patient to high levels of radiation and is costly. On the other hand, with less radiological exposure, calcium score is directly correlated to the presence and extension of coronary atherosclerosis, and also to the risk of cardiovascular events. Even though calcium score is a tried-and-true method for stratification of asymptomatic patients, its use is still reduced in this context, since current guidelines are contradictory to its use on symptomatic diseases. The aim of this review is to identify, on patients under investigation for coronary artery disease, the main evidence of the use of calcium score associated with functional evaluation and scintigraphy. PMID:27437867

Dishevelled-induced phosphorylation regulates membrane localization of Par1b

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

Terabayashi, Takeshi; Funato, Yosuke; Miki, Hiroaki, E-mail: hmiki@protein.osaka-u.ac.jp

2008-10-31

Par1b is an evolutionarily conserved kinase that plays crucial roles in cell polarity. Controlling intracellular localization of Par1b is important for its biological activity. We previously reported that Wnt stimulation or expression of Dvl promotes accumulation of Par1b in the membrane (T. Terabayashi, T.J. Itoh, H. Yamaguchi, Y. Yoshimura, Y. Funato, S. Ohno, H. Miki, Polarity-Regulating Kinase Partitioning-Defective 1/Microtubule Affinity-Regulating Kinase 2 Negatively Regulates Development of Dendrites on Hippocampal Neurons, J. Neurosci. 27 (2007) 13098-13107). However, its molecular mechanism remains unclear. Here we show the importance of Par1b phosphorylation in the regulation of membrane localization. We find that Thr-324 ismore » phosphorylated in a Dvl-dependent manner. Interestingly, the conversion of Thr-324 to Glu results in a significant accumulation of Par1b in the membrane, without any effects on the kinase activity. Moreover, the phospho-mimicking Par1b mutant does not antagonistically function against Dvl in microtubule stabilization and neurite extension, although wildtype Par1b does. These results suggest that membrane accumulation of Par1b induced by Dvl is regulated by its phosphorylation status, which is important for Par1b to regulate the microtubule dynamics.« less

PREOPERATIVE PREDICTION OF LUNG FUNCTION IN PNEUMONECTOMY BY SPIROMETRY AND LUNG PERFUSION SCINTIGRAPHY

PubMed Central

Cukic, Vesna

2012-01-01

Introduction: Nowadays an increasing number of lung resections are being done because of the rising prevalence of lung cancer that occurs mainly in patients with limited lung function, what is caused by common etiologic factor - smoking cigarettes. Loss of lung tissue in such patients can worsen much the postoperative pulmonary function. So it is necessary to asses the postoperative pulmonary function especially after maximal resection, i.e. pneumonectomy. Objective: To check over the accuracy of preoperative prognosis of postoperative lung function after pneumonectomy using spirometry and lung perfusion scinigraphy. Material and methods: The study was done on 17 patients operated at the Clinic for thoracic surgery, who were treated previously at the Clinic for Pulmonary Diseases “Podhrastovi” in the period from 01. 12. 2008. to 01. 06. 2011. Postoperative pulmonary function expressed as ppoFEV1 (predicted postoperative forced expiratory volume in one second) was prognosticated preoperatively using spirometry, i.e.. simple calculation according to the number of the pulmonary segments to be removed and perfusion lung scintigraphy. Results: There is no significant deviation of postoperative achieved values of FEV1 from predicted ones obtained by both methods, and there is no significant differences between predicted values (ppoFEV1) obtained by spirometry and perfusion scintigraphy. Conclusion: It is necessary to asses the postoperative pulmonary function before lung resection to avoid postoperative respiratory failure and other cardiopulmonary complications. It is absolutely necessary for pneumonectomy, i.e.. maximal pulmonary resection. It can be done with great possibility using spirometry or perfusion lung scintigraphy. PMID:23378687

Protease-Activated Receptor 4 (PAR4): A Promising Target for Antiplatelet Therapy.

PubMed

Rwibasira Rudinga, Gamariel; Khan, Ghulam Jilany; Kong, Yi

2018-02-14

Cardiovascular diseases (CVDs) are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs), including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR). Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.

Bone scintigraphy for neonatal osteomyelitis: simulation by extravasation of intravenous calcium

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

Balsam, D.; Goldfarb, C.R.; Stringer, B.

Intravenously administered calcium gluconate has become increasingly popular in the treatment of neonatal tetany. Occasionally, extravasation results in cellulitis, leading to a clinical diagnosis of superimposed osteomyelitis. Osseous scintigraphy, as the accepted modality in the early detection of osteomyelitis, would tend to be used in this circumstance. This case illustrates a false-positive result, probably due to soft-tissue calcification.

Reduction of intracerebral hemorrhage by rivaroxaban after tPA thrombolysis is associated with downregulation of PAR-1 and PAR-2.

PubMed

Morihara, Ryuta; Yamashita, Toru; Kono, Syoichiro; Shang, Jingwei; Nakano, Yumiko; Sato, Kota; Hishikawa, Nozomi; Ohta, Yasuyuki; Heitmeier, Stefan; Perzborn, Elisabeth; Abe, Koji

2017-09-01

This study aimed to assess the risk of intracerebral hemorrhage (ICH) after tissue-type plasminogen activator (tPA) treatment in rivaroxaban compared with warfarin-pretreated male Wistar rat brain after ischemia in relation to activation profiles of protease-activated receptor-1, -2, -3, and -4 (PAR-1, -2, -3, and -4). After pretreatment with warfarin (0.2 mg/kg/day), low-dose rivaroxaban (60 mg/kg/day), high-dose rivaroxaban (120 mg/kg/day), or vehicle for 14 days, transient middle cerebral artery occlusion was induced for 90 min, followed by reperfusion with tPA (10 mg/kg/10 ml). Infarct volume, hemorrhagic volume, immunoglobulin G leakage, and blood parameters were examined. Twenty-four hours after reperfusion, immunohistochemistry for PARs was performed in brain sections. ICH volume was increased in the warfarin-pretreated group compared with the rivaroxaban-treated group. PAR-1, -2, -3, and -4 were widely expressed in the normal brain, and their levels were increased in the ischemic brain, especially in the peri-ischemic lesion. Warfarin pretreatment enhanced the expression of PAR-1 and PAR-2 in the peri-ischemic lesion, whereas rivaroxaban pretreatment did not. The present study shows a lower risk of brain hemorrhage in rivaroxaban-pretreated compared with warfarin-pretreated rats following tPA administration to the ischemic brain. It is suggested that the relative downregulation of PAR-1 and PAR-2 by rivaroxaban compared with warfarin pretreatment might be partly involved in the mechanism of reduced hemorrhagic complications in patients receiving rivaroxaban in clinical trials. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Factor X/Xa elicits protective signaling responses in endothelial cells directly via PAR-2 and indirectly via endothelial protein C receptor-dependent recruitment of PAR-1.

PubMed

Bae, Jong-Sup; Yang, Likui; Rezaie, Alireza R

2010-11-05

We recently demonstrated that the Gla domain-dependent interaction of protein C with endothelial protein C receptor (EPCR) leads to dissociation of the receptor from caveolin-1 and recruitment of PAR-1 to a protective signaling pathway. Thus, the activation of PAR-1 by either thrombin or PAR-1 agonist peptide elicited a barrier-protective response if endothelial cells were preincubated with protein C. In this study, we examined whether other vitamin K-dependent coagulation protease zymogens can modulate PAR-dependent signaling responses in endothelial cells. We discovered that the activation of both PAR-1 and PAR-2 in endothelial cells pretreated with factor FX (FX)-S195A, but not other procoagulant protease zymogens, also results in initiation of protective intracellular responses. Interestingly, similar to protein C, FX interaction with endothelial cells leads to dissociation of EPCR from caveolin-1 and recruitment of PAR-1 to a protective pathway. Further studies revealed that, FX activated by factor VIIa on tissue factor bearing endothelial cells also initiates protective signaling responses through the activation of PAR-2 independent of EPCR mobilization. All results could be recapitulated by the receptor agonist peptides to both PAR-1 and PAR-2. These results suggest that a cross-talk between EPCR and an unknown FX/FXa receptor, which does not require interaction with the Gla domain of FX, recruits PAR-1 to protective signaling pathways in endothelial cells.

PAR1 activation affects the neurotrophic properties of Schwann cells.

PubMed

Pompili, Elena; Fabrizi, Cinzia; Somma, Francesca; Correani, Virginia; Maras, Bruno; Schininà, Maria Eugenia; Ciraci, Viviana; Artico, Marco; Fornai, Francesco; Fumagalli, Lorenzo

2017-03-01

Protease-activated receptor-1 (PAR1) is the prototypic member of a family of four G-protein-coupled receptors that signal in response to extracellular proteases. In the peripheral nervous system, the expression and/or the role of PARs are still poorly investigated. High PAR1 mRNA expression was found in the rat dorsal root ganglia and the signal intensity of PAR1 mRNA increased in response to sciatic nerve transection. In the sciatic nerve, functional PAR1 receptor was reported at the level of non-compacted Schwann cell myelin microvilli of the nodes of Ranvier. Schwann cells are the principal population of glial cells of the peripheral nervous system which myelinate axons playing an important role during axonal regeneration and remyelination. The present study was undertaken in order to determine if the activation of PAR1 affects the neurotrophic properties of Schwann cells. Our results suggest that the stimulation of PAR1 could potentiate the Schwann cell ability to favour nerve regeneration. In fact, the conditioned medium obtained from Schwann cell cultures challenged with a specific PAR1 activating peptide (PAR1 AP) displays increased neuroprotective and neurotrophic properties with respect to the culture medium from untreated Schwann cells. The proteomic analysis of secreted proteins in untreated and PAR1 AP-treated Schwann cells allowed the identification of factors differentially expressed in the two samples. Some of them (such as macrophage migration inhibitory factor, matrix metalloproteinase-2, decorin, syndecan 4, complement C1r subcomponent, angiogenic factor with G patch and FHA domains 1) appear to be transcriptionally regulated after PAR1 AP treatment as shown by RT-PCR. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of the value of quantitative thyroid scintigraphy for determination of thyroid function in dogs.

PubMed

Shiel, R E; Pinilla, M; McAllister, H; Mooney, C T

2012-05-01

To assess the value of thyroid scintigraphy to determine thyroid status in dogs with hypothyroidism and various non-thyroidal illnesses. Thyroid hormone concentrations were measured and quantitative thyroid scintigraphy performed in 21 dogs with clinical and/or clinicopathological features consistent with hypothyroidism. In 14 dogs with technetium thyroidal uptake values consistent with euthyroidism, further investigations supported non-thyroidal illness. In five dogs with technetium thyroidal uptake values within the hypothyroid range, primary hypothyroidism was confirmed as the only disease in four. The remaining dog had pituitary-dependent hyperadrenocorticism. Two dogs had technetium thyroidal uptake values in the non-diagnostic range. One dog had iodothyronine concentrations indicative of euthyroidism. In the other, a dog receiving glucocorticoid therapy, all iodothyronine concentrations were decreased. Markedly asymmetric technetium thyroidal uptake was present in two dogs. All iodothyronine concentrations were within reference interval but canine thyroid stimulating hormone concentration was elevated in one. Non-thyroidal illness was identified in both cases. In dogs, technetium thyroidal uptake is a useful test to determine thyroid function. However, values may be non-diagnostic, asymmetric uptake can occur and excess glucocorticoids may variably suppress technetium thyroidal uptake and/or thyroid hormone concentrations. Further studies are necessary to evaluate quantitative thyroid scintigraphy as a gold standard method for determining canine thyroid function. © 2012 British Small Animal Veterinary Association.

[The development of a computer model in the quantitative assessment of thallium-201 myocardial scintigraphy].

PubMed

Raineri, M; Traina, M; Rotolo, A; Candela, B; Lombardo, R M; Raineri, A A

1993-05-01

Thallium-201 scintigraphy is a widely used noninvasive procedure for the detection and prognostic assessment of patients with suspected or proven coronary artery disease. Thallium uptake can be evaluated by a visual analysis or by a quantitative interpretation. Quantitative scintigraphy enhances disease detection in individual coronary arteries, provides a more precise estimate of the amount of ischemic myocardium, distinguishing scar from hypoperfused tissue. Due to the great deal of data, analysis, interpretation and comparison of thallium uptake can be very complex. We designed a computer-based system for the interpretation of quantitative thallium-201 scintigraphy data uptake. We used a database (DataEase 4.2-DataEase Italia). Our software has the following functions: data storage; calculation; conversion of numerical data into different definitions classifying myocardial perfusion; uptake data comparison; automatic conclusion; comparison of different scintigrams for the same patient. Our software is made up by 4 sections: numeric analysis, descriptive analysis, automatic conclusion, clinical remarks. We introduced in the computer system appropriate information, "logical paths", that use the "IF ... THEN" rules. The software executes these rules in order to analyze the myocardial regions in the 3 phases of scintigraphic analysis (stress, redistribution, re-injection), in the 3 projections (LAO 45 degrees, LAT,ANT), considering our uptake cutoff, obtaining, finally, the automatic conclusions. For these reasons, our computer-based system could be considered a real "expert system".

PAR2 (Protease-Activated Receptor 2) Deficiency Attenuates Atherosclerosis in Mice.

PubMed

Jones, Shannon M; Mann, Adrien; Conrad, Kelsey; Saum, Keith; Hall, David E; McKinney, Lisa M; Robbins, Nathan; Thompson, Joel; Peairs, Abigail D; Camerer, Eric; Rayner, Katey J; Tranter, Michael; Mackman, Nigel; Owens, A Phillip

2018-06-01

PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis. PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice (8-12 weeks old) that were Par2 +/+ or Par2 -/- were fed a fat- and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines Ccl2 and Cxcl1 in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced Ccl2 and Cxcl1 mRNA expression and protein release into the supernatant resulting in less monocyte migration. Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting Ccl2 - and Cxcl1 -induced monocyte infiltration. © 2018 American Heart Association, Inc.

Budget impact of applying appropriateness criteria for myocardial perfusion scintigraphy: The perspective of a developing country.

PubMed

Dos Santos, Mauro Augusto; Santos, Marisa Silva; Tura, Bernardo Rangel; Félix, Renata; Brito, Adriana Soares X; De Lorenzo, Andrea

2016-10-01

Myocardial perfusion imaging is widely used for the risk stratification of coronary artery disease. In view of its cost, besides radiation issues, judicious evaluation of the appropriateness of its indications is essential to prevent an unnecessary economic burden on the health system. We evaluated, at a tertiary-care, public Brazilian hospital, the appropriateness of myocardial perfusion scintigraphy indications, and estimated the budget impact of applying appropriateness criteria. An observational, cross-sectional study of 190 patients with suspected or known coronary artery disease referred for myocardial perfusion imaging was conducted. The appropriateness of myocardial perfusion imaging indications was evaluated with the Appropriate Use Criteria for Cardiac Radionuclide Imaging published in 2009. Budget impact analysis was performed with a deterministic model. The prevalence of appropriate requests was 78%; of inappropriate indications, 12%; and of uncertain indications, 10%. Budget impact analysis showed that the use of appropriateness criteria, applied to the population referred to myocardial perfusion scintigraphy within 1 year, could generate savings of $ 64,252.04 dollars. The 12% inappropriate requests for myocardial perfusion scintigraphy at a tertiary-care hospital suggest that a reappraisal of MPI indications is needed. Budget impact analysis estimated resource savings of 18.6% with the establishment of appropriateness criteria for MPI.

Bone scintigraphy in the investigation of occult lameness in the dog.

PubMed

Schwarz, T; Johnson, V S; Voute, L; Sullivan, M

2004-05-01

99mTechnetium methylene diphosphonate (99mTc-MDP) scintigraphy was performed in 14 dogs of different breeds after clinical lameness examination, radiography and synovial fluid analysis failed to localise lameness to a specific area of pain. The scintigraphic protocol included an intravenous injection of 17 MBq 99mTc-MDP/kg bodyweight and vascular, soft tissue and bone phase scans in standardised positions with a low-energy all-purpose collimator. Confirmation of diagnosis was achieved in nine dogs by arthroscopy, repeated lesion-orientated radiography, computed tomography and response to treatment. In seven cases, bone phase scans showed single elbow uptakes, in two cases unilateral limb uptake, and in one case each a single shoulder and tibia uptake; in three cases there was no increased uptake. Vascular and soft tissue phase images did not reveal additional information. Diagnosis of humeral condyle fissures, a fragmented medial coronoid process, panosteitis and arthropathy was possible in nine cases. Skeletal pathology was ruled out in three normal scintigrams. In two dogs with unilateral uptake of multiple joints, no diagnostic benefit was gained from scintigraphy. The highly sensitive and relatively specific uptake allowed localisation and characterisation or exclusion of skeletal lesions in most dogs.

Endocrine radionuclide scintigraphy with fusion single photon emission computed tomography/computed tomography

PubMed Central

Wong, Ka-Kit; Gandhi, Arpit; Viglianti, Benjamin L; Fig, Lorraine M; Rubello, Domenico; Gross, Milton D

2016-01-01

AIM: To review the benefits of single photon emission computed tomography (SPECT)/computed tomography (CT) hybrid imaging for diagnosis of various endocrine disorders. METHODS: We performed MEDLINE and PubMed searches using the terms: “SPECT/CT”; “functional anatomic mapping”; “transmission emission tomography”; “parathyroid adenoma”; “thyroid cancer”; “neuroendocrine tumor”; “adrenal”; “pheochromocytoma”; “paraganglioma”; in order to identify relevant articles published in English during the years 2003 to 2015. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts (case reports, reviews, meta-analyses and abstracts) concerning the application of SPECT/CT to endocrine imaging were analyzed to provide a descriptive synthesis of the utility of this technology. RESULTS: The emergence of hybrid SPECT/CT camera technology now allows simultaneous acquisition of combined multi-modality imaging, with seamless fusion of three-dimensional volume datasets. The usefulness of combining functional information to depict the bio-distribution of radiotracers that map cellular processes of the endocrine system and tumors of endocrine origin, with anatomy derived from CT, has improved the diagnostic capability of scintigraphy for a range of disorders of endocrine gland function. The literature describes benefits of SPECT/CT for 99mTc-sestamibi parathyroid scintigraphy and 99mTc-pertechnetate thyroid scintigraphy, 123I- or 131I-radioiodine for staging of differentiated thyroid carcinoma, 111In- and 99mTc- labeled somatostatin receptor analogues for detection of neuroendocrine tumors, 131I-norcholesterol (NP-59) scans for assessment of adrenal cortical hyperfunction, and 123I- or 131I-metaiodobenzylguanidine imaging for evaluation of pheochromocytoma and paraganglioma. CONCLUSION: SPECT/CT exploits the synergism between the functional information from radiopharmaceutical imaging and anatomy

Protease-activated receptor-2 (PAR(2)) in human periodontitis.

PubMed

Holzhausen, M; Cortelli, J R; da Silva, V Araújo; Franco, G C Nobre; Cortelli, S Cavalca; Vergnolle, N

2010-09-01

No evidence for the role of protease-activated receptor-2 (PAR(2)) in human periodontal disease has been demonstrated so far. Thus, we sought to investigate the expression of PAR(2) mRNA in chronic periodontitis, and to examine whether its expression is related to the presence of PAR(2) potential activators. Microbiological and gingival crevicular fluid samples were collected from individuals with chronic periodontitis and control individuals, and the presence of neutrophil serine proteinase 3 (P3) and Porphyromonas gingivalis was evaluated. PAR(2) mRNA expression was higher (p < 0.001) in those with chronic periodontitis compared with control individuals, and it was statistically decreased (p = 0.0006) after periodontal treatment. Furthermore, those with chronic periodontitis presented higher (p < 0.05) levels of IL-1alpha, IL-6, IL-8, and TNF-alpha, total proteolytic activity, P. gingivalis prevalence, and P3mRNA expression compared with control individuals. We conclude that PAR(2) mRNA expression and its potential activators are elevated in human chronic periodontitis, therefore suggesting that PAR(2) may play a role in periodontal inflammation.

Lung scintigraphy in differential diagnosis of peripheral lung cancer and community-acquired pneumonia

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

Krivonogov, Nikolay G., E-mail: kng@cardio-tomsk.ru; Efimova, Nataliya Y., E-mail: efimova@cardio-tomsk.ru; Zavadovsky, Konstantin W.

Ventilation/perfusion lung scintigraphy was performed in 39 patients with verified diagnosis of community-acquired pneumonia (CAP) and in 14 patients with peripheral lung cancer. Ventilation/perfusion ratio, apical-basal gradients of ventilation (U/L(V)) and lung perfusion (U/L(P)), and alveolar capillary permeability of radionuclide aerosol were determined based on scintigraphy data. The study demonstrated that main signs of CAP were increases in ventilation/perfusion ratio, perfusion and ventilation gradient on a side of the diseased lung, and two-side increase in alveolar capillary permeability rate for radionuclide aerosol. Unlike this, scintigraphic signs of peripheral lung cancer comprise an increase in ventilation/perfusion ratio over 1.0 on amore » side of the diseased lung with its simultaneous decrease on a contralateral side, normal values of perfusion and ventilation gradients of both lungs, and delayed alveolar capillary clearance in the diseased lung compared with the intact lung.« less

Malignant external otitis: The diagnostic value of bone scintigraphy

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

Ostfeld, E.; Aviel, A.; Pelet, D.

1981-06-01

Technetium99m Methylene Diphosphate bone scintigraphy (BS) of the skull was performed in three patients with malignant external otitis (MEO). Pathological uptake of the radioisotope in the mastoid region was found during the early stages of MEO updating radiologic findings. The extent of the radioisotope accumulation during the early stages of MEO indicates that the actual tissue damage exceeds the clinical estimation. The follow-up BS findings correlate well with the clinical course of MEO indicating either healing or extension to the base of skull.

StePar: an automatic code for stellar parameter determination

NASA Astrophysics Data System (ADS)

Tabernero, H. M.; González Hernández, J. I.; Montes, D.

2013-05-01

We introduce a new automatic code (StePar) for determinig stellar atmospheric parameters (T_{eff}, log{g}, ξ and [Fe/H]) in an automated way. StePar employs the 2002 version of the MOOG code (Sneden 1973) and a grid of Kurucz ATLAS9 plane-paralell model atmospheres (Kurucz 1993). The atmospheric parameters are obtained from the EWs of 263 Fe I and 36 Fe II lines (obtained from Sousa et al. 2008, A&A, 487, 373) iterating until the excitation and ionization equilibrium are fullfilled. StePar uses a Downhill Simplex method that minimizes a quadratic form composed by the excitation and ionization equilibrium conditions. Atmospheric parameters determined by StePar are independent of the stellar parameters initial-guess for the problem star, therefore we employ the canonical solar values as initial input. StePar can only deal with FGK stars from F6 to K4, also it can not work with fast rotators, veiled spectra, very metal poor stars or Signal to noise ratio below 30. Optionally StePar can operate with MARCS models (Gustafson et al. 2008, A&A, 486, 951) instead of Kurucz ATLAS9 models, additionally Turbospectrum (Alvarez & Plez 1998, A&A, 330, 1109) can replace the MOOG code and play its role during the parameter determination. StePar has been used to determine stellar parameters for some studies (Tabernero et al. 2012, A&A, 547, A13; Wisniewski et al. 2012, AJ, 143, 107). In addition StePar is being used to obtain parameters for FGK stars from the GAIA-ESO Survey.

Bacterial DNA segregation dynamics mediated by the polymerizing protein ParF.

PubMed

Barillà, Daniela; Rosenberg, Mark F; Nobbmann, Ulf; Hayes, Finbarr

2005-04-06

Prokaryotic DNA segregation most commonly involves members of the Walker-type ParA superfamily. Here we show that the ParF partition protein specified by the TP228 plasmid is a ParA ATPase that assembles into extensive filaments in vitro. Polymerization is potentiated by ATP binding and does not require nucleotide hydrolysis. Analysis of mutations in conserved residues of the Walker A motif established a functional coupling between filament dynamics and DNA partitioning. The partner partition protein ParG plays two separable roles in the ParF polymerization process. ParF is unrelated to prokaryotic polymerizing proteins of the actin or tubulin families, but is a homologue of the MinD cell division protein, which also assembles into filaments. The ultrastructures of the ParF and MinD polymers are remarkably similar. This points to an evolutionary parallel between DNA segregation and cytokinesis in prokaryotic cells, and reveals a potential molecular mechanism for plasmid and chromosome segregation mediated by the ubiquitous ParA-type proteins.

The role of pars flaccida in human middle ear sound transmission.

PubMed

Aritomo, H; Goode, R L; Gonzalez, J

1988-04-01

The role of the pars flaccida in middle ear sound transmission was studied with the use of twelve otoscopically normal, fresh, human temporal bones. Peak-to-peak umbo displacement in response to a constant sound pressure level at the tympanic membrane was measured with a noncontacting video measuring system capable of repeatable measurements down to 0.2 micron. Measurements were made before and after pars flaccida modifications at 18 frequencies between 100 and 4000 Hz. Four pars flaccida modifications were studied: (1) acoustic insulation of the pars flaccida to the ear canal with a silicone rubber baffle, (2) stiffening the pars flaccida with cyanoacrylate cement, (3) decreasing the tension of the pars flaccida with a nonperforating incision, and (4) perforation of the pars flaccida. All of the modifications (except the perforation) had a minimal effect on umbo displacement; this seems to imply that the pars flaccida has a minor acoustic role in human beings.

Sensitivity of scintigraphy for detection of pulmonary capillary albumin leak in canine oleic acid ARDS

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

Sugerman, H.J.; Strash, A.M.; Hirsch, J.I.

1981-07-01

Computerized gamma scintigraphy was shown in this study to be a sensitive technique for the detection and kinetic analysis of a pulmonary capillary protein leak. A rising lung:heart radioactivity of slope of injury was found at each dose of intravenous oleic acid in dogs from 0.01 to 0.20 ml/kg (p less than 0.01). This slope of injury was proportional to the dose of oleic acid (r . +0.97; p less than 0.004) and was more sensitive than changes in arterial oxygen tension, standard chest radiography, bloodless wet:dry lung weight, or alveolar epithelial membrane permeability. Only standard light microscopy and rightmore » lymphatic duct flow were able to document the leakage of protein detected by gamma scintigraphy at 0.01 ml/kg oleic acid.« less

PAR-1 contributes to the innate immune response during viral infection

PubMed Central

Antoniak, Silvio; Owens, A. Phillip; Baunacke, Martin; Williams, Julie C.; Lee, Rebecca D.; Weithäuser, Alice; Sheridan, Patricia A.; Malz, Ronny; Luyendyk, James P.; Esserman, Denise A.; Trejo, JoAnn; Kirchhofer, Daniel; Blaxall, Burns C.; Pawlinski, Rafal; Beck, Melinda A.; Rauch, Ursula; Mackman, Nigel

2013-01-01

Coagulation is a host defense system that limits the spread of pathogens. Coagulation proteases, such as thrombin, also activate cells by cleaving PARs. In this study, we analyzed the role of PAR-1 in coxsackievirus B3–induced (CVB3-induced) myocarditis and influenza A infection. CVB3-infected Par1–/– mice expressed reduced levels of IFN-β and CXCL10 during the early phase of infection compared with Par1+/+ mice that resulted in higher viral loads and cardiac injury at day 8 after infection. Inhibition of either tissue factor or thrombin in WT mice also significantly increased CVB3 levels in the heart and cardiac injury compared with controls. BM transplantation experiments demonstrated that PAR-1 in nonhematopoietic cells protected mice from CVB3 infection. Transgenic mice overexpressing PAR-1 in cardiomyocytes had reduced CVB3-induced myocarditis. We found that cooperative signaling between PAR-1 and TLR3 in mouse cardiac fibroblasts enhanced activation of p38 and induction of IFN-β and CXCL10 expression. Par1–/– mice also had decreased CXCL10 expression and increased viral levels in the lung after influenza A infection compared with Par1+/+ mice. Our results indicate that the tissue factor/thrombin/PAR-1 pathway enhances IFN-β expression and contributes to the innate immune response during single-stranded RNA viral infection. PMID:23391721

The risk of avascular necrosis following chevron osteotomy: a prospective study using bone scintigraphy.

PubMed

Shariff, Raheel; Attar, Fahad; Osarumwene, Donald; Siddique, Rehan; Attar, Gulam Dastagir

2009-04-01

Controversy exists with regard to the effects of chevron osteotomy on blood supply and subsequent development of avascular necrosis (AVN) of the first metatarsal head. The aim of this study was to assess the incidence of avascular necrosis in our centre following chevron osteotomy for hallux valgus, using bone scintigraphy. Thirty nine patients who had a chevron osteotomy for treatment of hallux valgus were prospectively studied. Mean follow-up was 14 months. Bone scintigraphy was used to assess metatarsal head perfusion at an average 8.5 weeks post operatively. Three patients (7.7%) showed abnormal bone scan around the metatarsal head. Further evaluation of these patients did not show any sign of AVN. We conclude there appears to be a risk of circulatory disturbance to the metatarsal head following chevron osteotomy of the first metarsal (7.7% in this study); however this does not translate into clinically significant AVN.

Bacterial DNA segregation dynamics mediated by the polymerizing protein ParF

PubMed Central

Barillà, Daniela; Rosenberg, Mark F; Nobbmann, Ulf; Hayes, Finbarr

2005-01-01

Prokaryotic DNA segregation most commonly involves members of the Walker-type ParA superfamily. Here we show that the ParF partition protein specified by the TP228 plasmid is a ParA ATPase that assembles into extensive filaments in vitro. Polymerization is potentiated by ATP binding and does not require nucleotide hydrolysis. Analysis of mutations in conserved residues of the Walker A motif established a functional coupling between filament dynamics and DNA partitioning. The partner partition protein ParG plays two separable roles in the ParF polymerization process. ParF is unrelated to prokaryotic polymerizing proteins of the actin or tubulin families, but is a homologue of the MinD cell division protein, which also assembles into filaments. The ultrastructures of the ParF and MinD polymers are remarkably similar. This points to an evolutionary parallel between DNA segregation and cytokinesis in prokaryotic cells, and reveals a potential molecular mechanism for plasmid and chromosome segregation mediated by the ubiquitous ParA-type proteins. PMID:15775965

Neo-Positivist Intrusions, Post-Qualitative Challenges, and PAR's Generative Indeterminacies

ERIC Educational Resources Information Center

Miller, Janet L.

2017-01-01

Although committed to PAR's overarching aspirations, many advocates also have noted myriad complexities of engaging in PAR, where ambiguities and disarrays--all kinds of inconclusive evidence--can proliferate. Uncertainties especially can erupt if PAR education-focused projects are positioned, oxymoronically, as expected to produce "high…

Identification of Hürthle cell tumor by single-injection, double-phase scintigraphy with technetium-99m-sestamibi.

PubMed

Vattimo, A; Bertelli, P; Cintorino, M; Burroni, L; Volterrani, D; Vella, A

1995-05-01

Early and late (double-phase) scintigraphy with 99mTc-MIBI was used in a comparative study of the scintigraphic aspects of Hürthle cell tumors and other thyroid tumors. Single-injection, dual-phase (15-30 min and 3-4 hr) thyroid scintigraphy with 99mTc-sestamibi (MIBI) was performed on 41 patients who displayed a cold nodule on previous 99mTc scintigraphy. Visual scoring of nodular uptake was done to compare thyroidal and background tracer uptake. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late images and the washout rate from the nodule (WON) and thyroidal tissue (WOT) were measured. Cytologic results were obtained for all patients; histopathologic results were obtained for the 20 patients who had surgery. In eight patients (Group A), the nodule displayed intense and persistent uptake of MIBI (N/T = 1.77 +/- 0.46 and 3.20 +/- 1.37; WON = 17.2% +/- 6.3%; WOT = 24.6% +/- 7.5%); histopathology revealed Hürthle cell tumors (two carcinomas and three adenomas) in five surgical patients. In 15 patients (Group B), the nodule displayed intense uptake in the early image with fading activity in the late image (N/T = 1.45 +/- 0.54 and 0.84 +/- 0.30; WON = 30.0% +/- 7.3%; WOT = 24.5% +/- 6.8%); histopathology revealed a colloid nodule (n = 1), papillary carcinoma (n = 4) and follicular carcinoma (n = 5) in 10 surgical patients. In the remaining 18 patients (Group C), the nodule was cold and late images were not acquired. Histopathology revealed colloid nodules (n = 2) and follicular adenoma (n = 3) in five surgical patients. Single-injection, dual-phase MIBI scintigraphy of the thyroid can identify Hürthle cell tumors because these tumors have intense, persistent tracer uptake in contrast to other thyroid tumors.

Clinical value of gallium-67 scintigraphy in assessment of disease activity in Wegener's granulomatosis

PubMed Central

Slart, R; Jager, P; Poot, L; Piers, D; Cohen, T; Stegeman, C

2003-01-01

Background: Diagnosis of active pulmonary and paranasal involvement in patients with Wegener's granulomatosis (WG) can be difficult. The diagnostic value of gallium-67 scintigraphy in WG is unclear. Objective: To evaluate the added diagnostic value of gallium-67 scintigraphy in patients with WG with suspected granulomatous inflammation in the paranasal and chest regions. Methods: Retrospectively, the diagnostic contribution of chest and head planar gallium scans in 40 episodes of suspected vasculitis disease activity in 28 patients with WG was evaluated. Scans were grouped into normal or increased uptake for each region. Histological proof or response to treatment was the "gold standard" for the presence of WG activity. Results: WG activity was confirmed in 8 (20%) episodes, with pulmonary locations in three, paranasal in four, and both in one (n=7 patients); all these gallium scans showed increased gallium uptake (sensitivity 100%). Gallium scans were negative for the pulmonary area in 23/36 scans (specificity 64%), and negative for paranasal activity in 13/16 scans (specificity 81%) in episodes without WG activity. Positive predictive value of WG activity for lungs and paranasal region was 24% and 63%, respectively, negative predictive value was 100% for both regions. False positive findings were caused by bacterial or viral infections. Conclusion: Gallium scans are clinically helpful as a negative scan virtually excludes active WG. Gallium scintigraphy of chest and nasal region has a high sensitivity for the detection of disease activity in WG. However, because of positive scans in cases of bacterial or viral infections, specificity was lower. PMID:12810430

Gastric cancer bone metastases together with osteopoikilosis diagnosed using bone scintigraphy and 18F-FDG PET/CT.

PubMed

Prado Wohlwend, S; Sánchez Vaño, R; Sopena Novales, P; Uruburu García, E; Aparisi Rodríguez, F; Martínez Carsí, C

The coexistence of different bone diseases in the same patient involves a complex differential diagnosis. A patient is presented who was studied due to a renal mass that showed many sclerotic lesions in spine and limbs in conventional radiology and CT. These lesions were evaluated with 99m TC-HDP bone scintigraphy and 18 F-FDG PET/CT, which helped to obtain the definitive pathological diagnosis of osteopoikilosis (OP) co-existing with gastric cancer bone metastases. Of the different imaging scans performed, bone scintigraphy was particularly relevant due to its ability to discriminate between benign and metastatic bone disease. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Comparison of glomerular filtration rate determined by use of single-slice dynamic computed tomography and scintigraphy in cats.

PubMed

Schmidt, David M; Scrivani, Peter V; Dykes, Nathan L; Goldstein, Richard M; Erb, Hollis N; Reeves, Anthony P

2012-04-01

To compare estimation of glomerular filtration rate determined via conventional methods (ie, scintigraphy and plasma clearance of technetium Tc 99m pentetate) and dynamic single-slice computed tomography (CT). 8 healthy adult cats. Scintigraphy, plasma clearance testing, and dynamic CT were performed on each cat on the same day; order of examinations was randomized. Separate observers performed GFR calculations for scintigraphy, plasma clearance testing, or dynamic CT. Methods were compared via Bland-Altman plots and considered interchangeable and acceptable when the 95% limits of agreement (mean difference between methods ± 1.96 SD of the differences) were ≤ 0.7 mL/min/kg. Global GFR differed < 0.7 mL/min/kg in 5 of 8 cats when comparing plasma clearance testing and dynamic CT; the limits of agreement were 1.4 and -1.7 mL/min/kg. The mean ± SD difference was -0.2 ± 0.8 mL/min/kg, and the maximum difference was 1.6 mL/min/kg. The mean ± SD difference (absolute value) for percentage filtration by individual kidneys was 2.4 ± 10.5% when comparing scintigraphy and dynamic CT; the maximum difference was 20%, and the limits of agreement were 18% and 23% (absolute value). GFR estimation via dynamic CT exceeded the definition for acceptable clinical use, compared with results for conventional methods, which was likely attributable to sample size and preventable technical complications. Because 5 of 8 cats had comparable values between methods, further investigation of dynamic CT in a larger sample population with a wide range of GFR values should be performed.

Proteases in agricultural dust induce lung inflammation through PAR-1 and PAR-2 activation.

PubMed

Romberger, Debra J; Heires, Art J; Nordgren, Tara M; Souder, Chelsea P; West, William; Liu, Xiang-de; Poole, Jill A; Toews, Myron L; Wyatt, Todd A

2015-08-15

Workers exposed to aerosolized dust present in concentrated animal feeding operations (CAFOs) are susceptible to inflammatory lung diseases, such as chronic obstructive pulmonary disease. Extracts of dust collected from hog CAFOs [hog dust extract (HDE)] are potent stimulators of lung inflammatory responses in several model systems. The observation that HDE contains active proteases prompted the present study, which evaluated the role of CAFO dust proteases in lung inflammatory processes and tested whether protease-activated receptors (PARs) are involved in the signaling pathway for these events. We hypothesized that the damaging proinflammatory effect of HDE is due, in part, to the proteolytic activation of PARs, and inhibiting the proteases in HDE or disrupting PAR activation would attenuate HDE-mediated inflammatory indexes in bronchial epithelial cells (BECs), in mouse lung slices in vitro, and in a murine in vivo exposure model. Human BECs and mouse lung slice cultures stimulated with 5% HDE released significantly more of each of the cytokines measured (IL-6, IL-8, TNF-α, keratinocyte-derived chemokine/CXC chemokine ligand 1, and macrophage inflammatory protein-2/CXC chemokine ligand 2) than controls, and these effects were markedly diminished by protease inhibition. Inhibition of PARs also blunted the HDE-induced cytokine release from BECs. In addition, protease depletion inhibited HDE-induced BEC intracellular PKCα and PKCε activation. C57BL/6J mice administered 12.5% HDE intranasally, either once or daily for 3 wk, exhibited increased total cellular and neutrophil influx, bronchial alveolar fluid inflammatory cytokines, lung histopathology, and inflammatory scores compared with mice receiving protease-depleted HDE. These data suggest that proteases in dust from CAFOs are important mediators of lung inflammation, and these proteases and their receptors may provide novel targets for therapeutic intervention in CAFO dust-induced airways disease.

Indium-111 leukocyte scintigraphy in Wegener's granulomatosis involving the spleen

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

Morayati, S.J.; Fink-Bennett, D.

1986-12-01

Indium-111-labeled leukocyte scintigraphy was performed on a 44-yr-old man to exclude an occult abscess. Four- and twenty-four-hour images of the abdomen revealed splenic photopenia except for a rim of activity medially. A subsequent computed tomography (CT) study demonstrated necrosis or hemorrhage of the spleen except for a medial rim. Exploratory laparotomy demonstrated necrotizing vasculitis with granuloma formation consistent with Wegener's granulomatosis and a rim of viable splenic tissue corresponding to the radionuclide and CT studies.

Potential Role of Lung Ventilation Scintigraphy in the Assessment of COPD

PubMed Central

Cukic, Vesna; Begic, Amela

2014-01-01

Objective: To highlight the importance of the lung ventilation scintigraphy (LVS) to study the regional distribution of lung ventilation and to describe most frequent abnormal patterns of lung ventilation distribution obtained by this technique in COPD and to compare the information obtained by LVS with the that obtained by traditional lung function tests. Material and methods: The research was done in 20 patients with previously diagnosed COPD who were treated in Intensive care unit of Clinic for pulmonary diseases and TB “Podhrastovi” Clinical Center, University of Sarajevo in exacerbation of COPD during first three months of 2014. Each patient was undergone to testing of pulmonary function by body plethysmography and ventilation/perfusion lung scintigraphy with radio pharmaceutics Technegas, 111 MBq Tc -99m-MAA. We compared the results obtained by these two methods. Results: All patients with COPD have a damaged lung function tests examined by body plethysmography implying airflow obstruction, but LVS indicates not only airflow obstruction and reduced ventilation, but also indicates the disorders in distribution in lung ventilation. Conclusion: LVS may add further information to the functional evaluation of COPD to that provided by traditional lung function tests and may contribute to characterizing the different phenotypes of COPD. PMID:25132709

12 CFR 925.19 - Par value and price of stock.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Par value and price of stock. 925.19 Section... ASSOCIATES MEMBERS OF THE BANKS Stock Requirements § 925.19 Par value and price of stock. The capital stock of each Bank shall be sold at par, unless the Board has fixed a higher price. ...

Effect and mechanism of PAR-2 on the proliferation of esophageal cancer cells.

PubMed

Quanjun, D; Qingyu, Z; Qiliang, Z; Liqun, X; Jinmei, C; Ziquan, L; Shike, H

2016-11-01

Esophageal Cancer (EC) is a common malignant tumor occurred in the digestive tract. In this study, we investigated the mechanism of Protease Activated Receptor 2 (PAR-2) on the proliferation of esophageal cancer cell. Transfected esophageal cancer (EC) cell (PAR-2shRNA EC109) was established with low stable PAR-2 expression. EC109 cell was treated with PAR-2 agonist, PAR-2 anti-agonist and MAPK inhibitor respectively; Untreated EC109 cell (blank control) and PAR-2shRNA EC109 cell were used for analysis also. The mRNA expressions of PAR-2, ERK1, Cyclin D1, and c-fos in each group were detected by reverse transcript and polymerase chain reaction. Western blot was used to detect the protein expressions in each group. The cell growth curves were drawn to compare the cell growth. Compared with the blank control, the mRNA and protein expressions of PAR-2, Cyclin D1, and c-fos in PAR-2 agonist group increased significantly (p < 0.05), while decreased significantly in PAR-2shRNA EC109 cell and MAPK inhibitor group (p < 0.05). The mRNA expression of ERK1 and protein expression of p-ERK1 increased in PAR-2 agonist group, decreased in PAR-2shRNA EC109 cell and MAPK inhibitor group when compared with blank control (p < 0.05). The growth of cells was upward in PAR-2 agonist group at cell growth phase when compared with blank control, while decreased in PAR-2 shRNA EC109 cell and MAPK inhibitor group with statistical difference (p < 0.05). PAR-2 regulate cell proliferation through the MAPK pathway in esophageal carcinoma cell, and Cyclin D1, c-fos are involved in this process.

Myocardial contusion in patients with blunt chest trauma as evaluated by thallium 201 myocardial scintigraphy

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

Bodin, L.; Rouby, J.J.; Viars, P.

1988-07-01

Fifty five patients suffering from blunt chest trauma were studied to assess the diagnosis of myocardial contusion using thallium 201 myocardial scintigraphy. Thirty-eight patients had consistent scintigraphic defects and were considered to have a myocardial contusion. All patients with scintigraphic defects had paroxysmal arrhythmias and/or ECG abnormalities. Of 38 patients, 32 had localized ST-T segment abnormalities; 29, ST-T segment abnormalities suggesting involvement of the same cardiac area as scintigraphic defects; 21, echocardiographic abnormalities. Sixteen patients had segmental hypokinesia involving the same cardiac area as the scintigraphic defects. Fifteen patients had clinical signs suggestive of myocardial contusion and scintigraphic defects. Almostmore » 70 percent of patients with blunt chest trauma had scintigraphic defects related to areas of myocardial contusion. When thallium 201 myocardial scintigraphy directly showed myocardial lesion, two-dimensional echocardiography and standard ECG detected related functional consequences of cardiac trauma.« less

Thyroid scintigraphy findings in 2096 cats with hyperthyroidism.

PubMed

Peterson, Mark E; Broome, Michael R

2015-01-01

Thyroid scintigraphy is currently the reference standard for diagnosing and staging cats with hyperthyroidism, but few studies describing the scintigraphic characteristics in a large number of cats have been reported. The objective of this study was to better characterize thyroid scintigraphy findings by evaluating 2096 consecutive cats with hyperthyroidism that were referred over a 3.5-year period. Of these cats, 2068 (98.7%) had a high thyroid-to-salivary ratio (>1.5), whereas 2014 (96.1%) were found to have a high thyroid-to-background ratio (>6.1). When the patterns of the cats' thyroid disease were recorded, 665 (31.7%) had unilateral disease, 1060 (50.6%) had bilateral-asymmetric disease (two thyroid lobes unequal in size), 257 (12.3%) had bilateral-symmetric disease (both lobes similar in size), and 81 (3.9%) had multifocal disease (≥3 areas of increased radionuclide uptake). The number of areas of (99m) TcO(-) 4 uptake in the 2096 cats ranged from 1 to 6 (median, 2), located in the cervical area in 2057 (98.1%), thoracic inlet in 282 (13.5%), and in the thoracic cavity in 115 (5.5%). Ectopic thyroid tissue (e.g. lingual or mediastinal) was diagnosed in 81 (3.9%) cats, whereas thyroid carcinoma was suspected in 35 (1.7%) of the cats. The results of this study support conclusions that most hyperthyroid cats have unilateral or bilateral thyroid nodules, but that multifocal disease will develop in a few cats that have ectopic thyroid disease or thyroid carcinoma. Both ectopic thyroid disease and thyroid carcinoma are relatively uncommon in hyperthyroid cats, with a respective prevalence of ∼4% and ∼2% in this study. © 2014 American College of Veterinary Radiology.

Comparison between computed tomography and (99m)TC- pertechnetate scintigraphy characteristics of the thyroid gland in cats with hyperthyroidism.

PubMed

Lautenschlaeger, Ines E; Hartmann, Antje; Sicken, Julia; Mohrs, Sabrina; Scholz, Volkher B; Neiger, Reto; Kramer, Martin

2013-01-01

Scintigraphy is currently the reference standard for diagnosing feline hyperthyroidism; however, computed tomography (CT) is more widely available in veterinary practice. The purposes of this prospective study were to describe the CT appearance of thyroid glands in cats with hyperthyroidism and compare CT findings with findings from (99m) Tc-pertechnetate scintigraphy. Twenty-five adult hyperthyroid cats were included. Plain CT images were acquired for each cat and the following characteristics recorded for each thyroid lobe: visibility, delineation, position, attenuation, shape, and subjective size. Scintigraphic images were also acquired and the following characteristics recorded: radiopharmaceutical uptake, delineation, ectopic foci, shape, and subjective size. In CT images, thyroid lobes were most commonly found between the second and fourth cervical vertebrae, dorsolateral to the trachea. Affected thyroid lobes (based on scintigraphy reference standard) were most commonly oval and moderately enlarged in CT images. A heterogeneous attenuation pattern (isoattenuating to adjacent soft tissues with hypo- and hyperattenuating foci) was most commonly found in affected thyroid lobes. A positive correlation (P < 0.01) was identified between CT and scintigraphy for left-to-right thyroid lobe size relationship and subjective size of the larger thyroid lobe. The CT estimated mass was significantly higher (median = 148.8; range = [0;357.6]) for the more active thyroid lobe compared to the less active thyroid lobe (median = 84.6; range = [0;312.3]); (W = 154; P < 0.01). Findings indicated that CT may not reliably differentiate unilateral vs. bilateral hyperthyroidism in cats; however, CT may be a reliable alternative test for correctly identifying the more active thyroid lobe. © 2013 Veterinary Radiology & Ultrasound.

99mTc-sestamibi scintigraphy used to evaluate tumor response to neoadjuvant chemotherapy in locally advanced breast cancer: A quantitative analysis

PubMed Central

KOGA, KATIA HIROMOTO; MORIGUCHI, SONIA MARTA; NETO, JORGE NAHÁS; PERES, STELA VERZINHASSE; SILVA, EDUARDO TINÓIS DA; SARRI, ALMIR JOSÉ; MICHELIN, ODAIR CARLITO; MARQUES, MARIANGELA ESTHER ALENCAR; GRIVA, BEATRIZ LOTUFO

2010-01-01

To evaluate the tumor response to neoadjuvant chemotherapy, 99mTc-sestamibi breast scintigraphy was proposed as a quantitative method. Fifty-five patients with ductal carcinoma were studied. They underwent breast scintigraphy before and after neoadjuvant chemotherapy, along with clinical assessment and surgical specimen analysis. The regions of interest on the lesion and contralateral breast were identified, and the pixel counts were used to evaluate lesion uptake in relation to background radiation. The ratio of these counts before to after neoadjuvant chemotherapy was assessed. The decrease in uptake rate due to chemotherapy characterized the scintigraphy tumor response. The Kruskal-Wallis test was used to compare the mean scintigraphic tumor response and histological type. Dunn’s multiple comparison test was used to detect differences between histological types. The Mann-Whitney test was used to compare means between quantitative and qualitative variables: scintigraphic tumor response vs. clinical response and uptake before chemotherapy vs. scintigraphic tumor response. The Spearman’s test was used to correlate the quantitative variables of clinical reduction in tumor size and scintigraphic tumor response. All of the variables compared presented significant differences. The change in 99mTc-sestamibi uptake noted on breast scintigraphy, before to after neoadjuvant chemotherapy, may be used as an effective method for evaluating the response to neoadjuvant chemotherapy, since this quantification reflects the biological behavior of the tumor towards the chemotherapy regimen. Furthermore, additional analysis on the uptake rate before chemotherapy may accurately predict treatment response. PMID:22966312

[Utility of early imaging of myocardial innervation scintigraphy in the diagnosis of Lewy Body Dementia].

PubMed

Camacho, V; Estorch, M; Marquié, M; Domènech, A; Flotats, A; Fernández, A; Duch, J; Geraldo, L L; Deportos, J; Artigas, C; Lleó, A; Carrió, I

2013-03-01

The importance of accurate and early diagnosis of dementia with Lewy bodies (DLB) lies in its pharmacological management. Delayed imaging of cardiac (123)I-MIBG scintigraphy allows differentiation between DLB and other neurodegenerative diseases with cognitive impairment. The aim of this study was to assess the utility of early imaging of cardiac (123)I-MIBG scintigraphy for differentiating DLB from others neurodegenerative disease with cognitive impairment. We assess retrospectively 106 patients (51 men, mean age 78 years) with cognitive impairment that underwent a cardiac (123)I-MIBG study. Planar images were acquired in anterior view of the thorax 15min (early) and 4h (delayed) after tracer administration. The heart-to-mediastinum ratios (HMR) at 15m (HMR15m) and at 4h (HMR4h) were obtained. After four years, 52 patients were diagnosed of DLB.HMR15m and HMR4h were significantly inferior in DLB respect to the others neurodegenerative diseases (1,27±0,15 vs 1,76±0,15,p<0,05) and (1,14±0,13 vs 1,68±0,19,p<0.01), respectively. The ROC analysis showed a HMR15m cut off point of 1.56 to differentiated DLB from the other dementias with a sensitivity and a specificity of 98%. Early imaging of cardiac (123)I-MIBG scintigraphy can help to differentiate DLB from other neurodegenerative diseases with cognitive impairment. Copyright © 2012 Elsevier España, S.L. y SEMNIM. All rights reserved.

The signaling adapter Gab1 regulates cell polarity by acting as a PAR protein scaffold

PubMed Central

Yang, Ziqiang; Xue, Bin; Umitsu, Masataka; Ikura, Mitsuhiko; Muthuswamy, Senthil K.; Neel, Benjamin G.

2012-01-01

Summary Cell polarity plays a key role in development and is disrupted in tumors, yet the molecules and mechanisms that regulate polarity remain poorly defined. We found that the scaffolding adaptor GAB1 interacts with two polarity proteins, PAR1 and PAR3. GAB1 binds PAR1 and enhances its kinase activity. GAB1 brings PAR1 and PAR3 into a transient complex, stimulating PAR3 phosphorylation by PAR1. GAB1 and PAR6 bind the PAR3 PDZ1 domain and thereby compete for PAR3 binding. Consequently, GAB1 depletion causes PAR3 hypo-phosphorylation and increases PAR3/PAR6 complex formation, resulting in accelerated and enhanced tight junction formation, increased trans-epithelial resistance and lateral domain shortening. Conversely, GAB1 over-expression, in a PAR1/PAR3-dependent manner, disrupts epithelial apical-basal polarity, promotes multi-lumen cyst formation, and enhances growth factor-induced epithelial cell scattering. Our results identify GAB1 as a novel negative regulator of epithelial cell polarity that functions as a scaffold for modulating PAR protein complexes on the lateral membrane. PMID:22883624

Accuracy of increased thyroid activity during pertechnetate scintigraphy by subcutaneous injection for diagnosing hyperthyroidism in cats.

PubMed

Page, Richard B; Scrivani, Peter V; Dykes, Nathan L; Erb, Hollis N; Hobbs, Jeff M

2006-01-01

Our purpose was to determine the accuracy of increased thyroid activity for diagnosing hyperthyroidism in cats suspected of having that disease during pertechnetate scintigraphy using subcutaneous rather than intravenous radioisotope administration. Increased thyroid activity was determined by two methods: the thyroid:salivary ratio (T:S) and visual inspection. These assessments were made on the ventral scintigram of the head and neck. Scintigraphy was performed by injecting sodium pertechnetate (111 MBq, SQ) in the right-dorsal-lumbar region; static-acquisition images were obtained 20 min after injection. We used 49 cats; 34 (69%) had hyperthyroidism based on serum-chemistry analysis. Using a Wilcoxon's rank-sum test, a significant difference (P < 0.0001) was detected in the T:S between cats with and without hyperthyroidism. Using a decision criterion of 2.0 for the T:S, the test accurately predicted hyperthyroidism in 32/34 cats (sensitivity, 94%; 95% confidence interval (CI), 85-100%) and correctly predicted that hyperthyroidism was absent in 15/15 cats (specificity, 100%; CI, 97-100%). Using visual inspection, the test accurately predicted hyperthyroidism in 34/34 cats (sensitivity, 100%; CI, 99-100%) and correctly predicted that hyperthyroidism was absent in 12/15 cats (specificity, 80%; CI, 56-100%). The positive and negative predictive values were high for a wide range of prevalence of hyperthyroidism. And, the test had excellent agreement within and between examiners. Therefore, detecting increased thyroid activity during pertechnetate scintigraphy by subcutaneous injection is an accurate and reproducible test for feline hyperthyroidism.

Gastric emptying scintigraphy results in children are affected by age, anthropometric factors, and study duration

USDA-ARS?s Scientific Manuscript database

A standardized 4-hour adult-based gastric emptying scintigraphy (GES) protocol is increasingly being used in children to evaluate for gastroparesis. We sought to determine the effect of age, anthropometrics, and study duration on GES results using this protocol in children. Retrospective review of c...

PAR-2 expression in the gingival crevicular fluid reflects chronic periodontitis severity.

PubMed

Fukushima, Henrique; Alves, Vanessa Tubero Euzebio; Carvalho, Verônica Franco de; Ambrósio, Lucas Macedo Batitucci; Eichler, Rosangela Aparecida Dos Santos; Carvalho, Maria Helena Catelli de; Saraiva, Luciana; Holzhausen, Marinella

2017-01-26

Recent studies investigating protease-activated receptor type 2 (PAR-2) suggest an association between the receptor and periodontal inflammation. It is known that gingipain, a bacterial protease secreted by the important periodontopathogen Porphyromonas gingivalis can activate PAR-2. Previous studies by our group found that PAR-2 is overexpressed in the gingival crevicular fluid (GCF) of patients with moderate chronic periodontitis (MP). The present study aimed at evaluating whether PAR-2 expression is associated with chronic periodontitis severity. GCF samples and clinical parameters, including plaque and bleeding on probing indices, probing pocket depth and clinical attachment level, were collected from the control group (n = 19) at baseline, and from MP patients (n = 19) and severe chronic periodontitis (SP) (n = 19) patients before and 6 weeks after periodontal non-surgical treatment. PAR-2 and gingipain messenger RNA (mRNA) in the GCF of 4 periodontal sites per patient were evaluated by Reverse Transcription Polymerase Chain Reaction (RT-qPCR). PAR-2 and gingipain expressions were greater in periodontitis patients than in control group patients. In addition, the SP group presented increased PAR-2 and gingipain mRNA levels, compared with the MP group. Furthermore, periodontal treatment significantly reduced (p <0.05) PAR-2 expression in patients with periodontitis. In conclusion, PAR-2 is associated with chronic periodontitis severity and with gingipain levels in the periodontal pocket, thus suggesting that PAR-2 expression in the GCF reflects the severity of destruction during periodontal infection.

Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles.

PubMed

Bharat, Tanmay A M; Murshudov, Garib N; Sachse, Carsten; Löwe, Jan

2015-07-02

Active segregation of Escherichia coli low-copy-number plasmid R1 involves formation of a bipolar spindle made of left-handed double-helical actin-like ParM filaments. ParR links the filaments with centromeric parC plasmid DNA, while facilitating the addition of subunits to ParM filaments. Growing ParMRC spindles push sister plasmids to the cell poles. Here, using modern electron cryomicroscopy methods, we investigate the structures and arrangements of ParM filaments in vitro and in cells, revealing at near-atomic resolution how subunits and filaments come together to produce the simplest known mitotic machinery. To understand the mechanism of dynamic instability, we determine structures of ParM filaments in different nucleotide states. The structure of filaments bound to the ATP analogue AMPPNP is determined at 4.3 Å resolution and refined. The ParM filament structure shows strong longitudinal interfaces and weaker lateral interactions. Also using electron cryomicroscopy, we reconstruct ParM doublets forming antiparallel spindles. Finally, with whole-cell electron cryotomography, we show that doublets are abundant in bacterial cells containing low-copy-number plasmids with the ParMRC locus, leading to an asynchronous model of R1 plasmid segregation.

PAR-2 receptor-induced effects on human eccrine sweat gland cells.

PubMed

L Bovell, Douglas; Kofler, Barbara; Lang, Roland

2009-01-01

Serine proteases can induce cell signaling by stimulating G-protein-coupled receptors, called proteinase-activated receptors (PAR's) on a variety of epithelial cells. While PAR-2, one such receptor, activates cell signaling in a secretory cell line derived from human sweat glands, there was no information on their presence and effects on intact sweat glands. PAR-2 presence and activation of eccrine sweat glands isolated from human skin samples was investigated using Western blot analysis, immunohistochemistry, electron microscopy (EM) and Ca(2+) imaging. Anti-human PAR-2 antibody demonstrated the presence of these receptors in eccrine sweat glands. EM showed that PAR-2 activation resulted in degranulation of secretory cells. Ca(2+) imaging using PAR-2 activators demonstrated a two phase increase in [Ca(2+)](i) which was dependent on extracellular Ca(2+) for the second phase, and that the response could be blocked by prior incubation with xestospongin, the IP(3) receptor blocker. The results demonstrated that PAR-2 receptors are present in human sweat gland secretory cells and that these receptors are functionally active and can induce changes associated with secretory events in eccrine glands.

99Tcm-labelled polyclonal human immunoglobulin G scintigraphy before and after intra-articular knee injection of triamcinolone hexacetonide in patients with rheumatoid arthritis.

PubMed

de Bois, M H; Arndt, J W; Tak, P P; Kluin, P M; van der Velde, E A; Pauwels, E K; Breedveld, F C

1993-10-01

The ability of 99Tcm-labelled polyclonal human immunoglobulin G (99Tcm-IgG) scintigraphy to monitor intra-individual variation in arthritis activity was studied in seven patients with rheumatoid arthritis (RA). These patients were treated with an intra-articular injection of 20 mg triamcinolone hexacetonide. The results of semiquantitative 99Tcm-IgG scintigraphy were compared with the degree of joint swelling and the histological changes observed in synovial biopsies before and 14 days after the injection. In all seven patients the local treatment resulted in a decreased arthritis activity of the treated knee as measured clinically or histologically. This decrease was parallelled, in all patients except one, by a lower uptake of 99Tcm-IgG after the injection when compared to uptake prior to treatment. This study shows that 99Tcm-IgG scintigraphy is able to reflect intra-individual variations in arthritis activity in patients with RA.

Utility of Drinking Water in Hepatobiliary Scintigraphy When Possible Acute Cholecystitis Was Considered.

PubMed

Bai, Xia; Wang, Xuemei

2018-06-19

A 15-year-old boy underwent hepatobiliary scintigraphy for suspected acute cholecystitis. The initial images revealed an activity in the neighborhood of normal gallbladder fossa, suggestive of possible activity in the gallbladder, which would be inconsistent with a diagnosis of acute cholecystitis. However, after drinking 6 oz of water, the activity was no longer seen. Acute cholecystitis was confirmed pathologically after cholecystectomy.

Brulure par Plaque de Bistouri Electrique: a Propos de Quatre Cas

PubMed Central

Khales, A.; Achbouk, A.; Belmir, R.; Cherkab, L.; Ennouhi, M.A.; Ababou, K.; Ihrai, H.

2010-01-01

Summary La brûlure par plaque de bistouri électrique est un accident rare mais grave par la profondeur de la lésion et par sa localisation, surtout quand qu’elle survient dans un contexte chirurgical dont le vécu reste difficile de la part du malade et du chirurgien. Cette brûlure bien que imprévisible reste grave par la profondeur et la localisation de la brûlure et par sa survenue dans un contexte opératoire, chez des patients malades. La prise en charge de la brûlure doit se faire en milieu spécialisé. La prévention reste le seul moyen d’éviter ce type d’accident. PMID:21991216

Expression of protease-activated-receptor 2 (PAR-2) in human esophageal mucosa.

PubMed

Inci, Kamuran; Edebo, Anders; Olbe, Lars; Casselbrant, Anna

2009-01-01

The role of duodenal reflux in gastroesophageal reflux disease (GERD) containing bile salts and pancreatic enzymes (with special attention to trypsin) is still under discussion. Proteinase-activated receptors (PARs) are a novel family and PAR-2 is a unique member of this family because it is activated by trypsin. The aim of the present study was to examine the presence and the position of the PAR-2 receptor in human esophageal mucosa in different subgroups of GERD. Distal biopsies taken from healthy controls, patients with erosive reflux disease (ERD), patients with specialized intestinal metaplasia (SIM) and adenocarcinoma were analyzed for the PAR-2 receptor with reverse-transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry. Gene transcripts for the PAR-2 receptor were found in all groups, with increased levels in SIM patients compared to controls. However, this visual pattern was not seen for the protein expression of the PAR-2 receptor showing no apparent quantitative differences between the groups. Immunohistochemistry revealed distinct staining for the PAR-2 receptor in the luminal part of the esophageal epithelium. The localization of the PAR-2 receptor indicates that the receptor can be cleaved and activated by trypsin in duodenogastric esophageal refluxate. The data thus suggest that the trypsin-PAR-2 pathway may be involved in the pathogenesis of GERD.

Discovery of potent and selective small-molecule PAR-2 agonists.

PubMed

Seitzberg, Jimmi Gerner; Knapp, Anne Eeg; Lund, Birgitte Winther; Mandrup Bertozzi, Sine; Currier, Erika A; Ma, Jian-Nong; Sherbukhin, Vladimir; Burstein, Ethan S; Olsson, Roger

2008-09-25

Proteinase activated receptor-2 plays a crucial role in a wide variety of conditions with a strong inflammatory component. We present the discovery and characterization of two structurally different, potent, selective, and metabolically stable small-molecule PAR-2 agonists. These ligands may be useful as pharmacological tools for elucidating the complex physiological role of the PAR-2 receptors as well as for the development of PAR-2 antagonists.

[Importance of parathyroid SPECT and 99mTc scintigraphy, and of clinical, laboratorial, ultrasonographic and citologic correlation in the pre-operative localization of the parathyroid adenoma - pictorial assay].

PubMed

Oliveira, Marco Antônio Condé de; Maeda, Sérgio Setsuo; Dreyer, Patrícia; Lobo, Alberto; Andrade, Victor Piana de; Hoff, Ana O; Biscolla, Rosa Paula Mello; Smanio, Paola; Brandão, Cynthia M A; Vieira, José G

2010-06-01

In patients with primary hyperparathyroidism, candidates for surgical intervention, the parathyroid pre-operative localization is of fundamental importance in planning the appropriate surgical approach. The additional acquisition of SPECT and Technetium-99m images, during parathyroid scintigraphy with Sestamibi, is not common practice. Usually, only planar image acquisition, 15 minutes prior and 2 hours after radiopharmaceutical administration, is performed. In our experience, the complete protocol in parathyroid scintigraphy increases the accuracy of pre-operative parathyroid localization. The complete utilization of all available nuclear medicine methods (SPECT e 99mTc) and image interpretation in a multidisciplinary context can improve the accuracy of parathyroid scintigraphy.

Endophthalmitis following pars plana vitrectomy for vitreous floaters

PubMed Central

Henry, Christopher R; Schwartz, Stephen G; Flynn, Harry W

2014-01-01

A case of Staphylococcus caprae endophthalmitis in a young patient following pars plana vitrectomy for symptomatic vitreous floaters is reported here. Recent literature suggests that there is an increasing trend of performing pars plana vitrectomy for symptomatic floaters. Although rare, the potential risk of endophthalmitis should be explicitly discussed with patients considering surgical intervention for vitreous floaters. PMID:25210434

Endophthalmitis following pars plana vitrectomy for vitreous floaters.

PubMed

Henry, Christopher R; Schwartz, Stephen G; Flynn, Harry W

2014-01-01

A case of Staphylococcus caprae endophthalmitis in a young patient following pars plana vitrectomy for symptomatic vitreous floaters is reported here. Recent literature suggests that there is an increasing trend of performing pars plana vitrectomy for symptomatic floaters. Although rare, the potential risk of endophthalmitis should be explicitly discussed with patients considering surgical intervention for vitreous floaters.

Expression of Par3 polarity protein correlates with poor prognosis in ovarian cancer.

PubMed

Nakamura, Hiroe; Nagasaka, Kazunori; Kawana, Kei; Taguchi, Ayumi; Uehara, Yuriko; Yoshida, Mitsuyo; Sato, Masakazu; Nishida, Haruka; Fujimoto, Asaha; Inoue, Tomoko; Adachi, Katsuyuki; Nagamatsu, Takeshi; Arimoto, Takahide; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

2016-11-17

Previous studies have shown that the cell polarity protein partitioning defective 3 (Par3) plays an essential role in the formation of tight junctions and definition of apical-basal polarity. Aberrant function of this protein has been reported to be involved in epithelial-mesenchymal transition (EMT) and cancer invasion. The aim of this study was to examine the functional mechanism of Par3 in ovarian cancer. First, we investigated the association between Par3 expression level and survival of 50 ovarian cancer patients. Next, we conducted an in vitro analysis of ovarian cancer cell lines, focusing on the cell line JHOC5, to investigate Par3 function. To investigate the function of Par3 in invasion, the IL-6/STAT3 pathway was analyzed upon Par3 knockdown with siRNA. The effect of siRNA treatment was assessed by qPCR, ELISA, and western blotting. Invasiveness and cell proliferation following treatment with siRNA against Par3 were investigated using Matrigel chamber, wound healing, and cell proliferation assays. Expression array data for ovarian cancer patient samples revealed low Par3 expression was significantly associated with good prognosis. Univariate analysis of clinicopathological factors revealed significant association between high Par3 levels and peritoneal dissemination at the time of diagnosis. Knockdown of Par3 in JHOC5 cells suppressed cell invasiveness, migration, and cell proliferation with deregulation of IL-6/STAT3 activity. Taken together, these results suggest that Par3 expression is likely involved in ovarian cancer progression, especially in peritoneal metastasis. The underlying mechanism may be that Par3 modulates IL-6 /STAT3 signaling. Here, we propose that the expression of Par3 in ovarian cancer may control disease outcome.

ParABS Systems of the Four Replicons of Burkholderia cenocepacia: New Chromosome Centromeres Confer Partition Specificity†

PubMed Central

Dubarry, Nelly; Pasta, Franck; Lane, David

2006-01-01

Most bacterial chromosomes carry an analogue of the parABS systems that govern plasmid partition, but their role in chromosome partition is ambiguous. parABS systems might be particularly important for orderly segregation of multipartite genomes, where their role may thus be easier to evaluate. We have characterized parABS systems in Burkholderia cenocepacia, whose genome comprises three chromosomes and one low-copy-number plasmid. A single parAB locus and a set of ParB-binding (parS) centromere sites are located near the origin of each replicon. ParA and ParB of the longest chromosome are phylogenetically similar to analogues in other multichromosome and monochromosome bacteria but are distinct from those of smaller chromosomes. The latter form subgroups that correspond to the taxa of their hosts, indicating evolution from plasmids. The parS sites on the smaller chromosomes and the plasmid are similar to the “universal” parS of the main chromosome but with a sequence specific to their replicon. In an Escherichia coli plasmid stabilization test, each parAB exhibits partition activity only with the parS of its own replicon. Hence, parABS function is based on the independent partition of individual chromosomes rather than on a single communal system or network of interacting systems. Stabilization by the smaller chromosome and plasmid systems was enhanced by mutation of parS sites and a promoter internal to their parAB operons, suggesting autoregulatory mechanisms. The small chromosome ParBs were found to silence transcription, a property relevant to autoregulation. PMID:16452432

Symmetry breaking and polarization of the C. elegans zygote by the polarity protein PAR-2.

PubMed

Zonies, Seth; Motegi, Fumio; Hao, Yingsong; Seydoux, Geraldine

2010-05-01

Polarization of the C. elegans zygote is initiated by ECT-2-dependent cortical flows, which mobilize the anterior PAR proteins (PAR-3, PAR-6 and PKC-3) away from the future posterior end of the embryo marked by the sperm centrosome. Here, we demonstrate the existence of a second, parallel and redundant pathway that can polarize the zygote in the absence of ECT-2-dependent cortical flows. This second pathway depends on the polarity protein PAR-2. We show that PAR-2 localizes to the cortex nearest the sperm centrosome even in the absence of cortical flows. Once on the cortex, PAR-2 antagonizes PAR-3-dependent recruitment of myosin, creating myosin flows that transport the anterior PAR complex away from PAR-2 in a positive-feedback loop. We propose that polarity in the C. elegans zygote is initiated by redundant ECT-2- and PAR-2-dependent mechanisms that lower PAR-3 levels locally, triggering a positive-feedback loop that polarizes the entire cortex.

Applicability of 99m Tc-Labeled Human Serum Albumin Scintigraphy in Dogs With Protein-Losing Enteropathy.

PubMed

Engelmann, N; Ondreka, N; von Pückler, K; Mohrs, S; Sicken, J; Neiger, R

2017-03-01

Diagnosis of protein loss into the gastrointestinal tract using noninvasive techniques is challenging. In people, scintigraphy not only is a sensitive tool to confirm protein-losing enteropathy (PLE), but it also allows for localization of protein loss. To investigate the feasibility of 99m Tc-labeled human serum albumin (HSA) scintigraphy in dogs with PLE in comparison with control dogs. A total of 8 clinically healthy control research dogs and 7 client-owned dogs with gastrointestinal clinical signs and hypoalbuminemia (serum albumin concentration <2.0 g/dL). Prospective case-control study. After IV injection of 400 MBq freshly prepared 99m Tc HSA (30 mg/dog), images of the abdomen were obtained 10, 60, 120, and 240 minutes postinjection. Additional images of the salivary and thyroid glands were obtained to rule out free 99m Tc. A scan was considered positive for PLE when radiopharmaceutical exudation was detectable in the intestinal tract. Only 1 control dog showed exudation of the radiopharmaceutical into the intestinal tract. No free 99m Tc was detected in any dog. In dogs with PLE, focal small intestinal and diffuse small intestinal radiopharmaceutical exudation into the bowel was detected in 2 and 3 dogs, respectively, whereas in 2 dogs, there was disagreement about whether radiopharmaceutical exudation was focal or diffuse. 99m Tc-labeled HSA scintigraphy was feasible to diagnose PLE in dogs. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Specific and non-specific interactions of ParB with DNA: implications for chromosome segregation

PubMed Central

Taylor, James A.; Pastrana, Cesar L.; Butterer, Annika; Pernstich, Christian; Gwynn, Emma J.; Sobott, Frank; Moreno-Herrero, Fernando; Dillingham, Mark S.

2015-01-01

The segregation of many bacterial chromosomes is dependent on the interactions of ParB proteins with centromere-like DNA sequences called parS that are located close to the origin of replication. In this work, we have investigated the binding of Bacillus subtilis ParB to DNA in vitro using a variety of biochemical and biophysical techniques. We observe tight and specific binding of a ParB homodimer to the parS sequence. Binding of ParB to non-specific DNA is more complex and displays apparent positive co-operativity that is associated with the formation of larger, poorly defined, nucleoprotein complexes. Experiments with magnetic tweezers demonstrate that non-specific binding leads to DNA condensation that is reversible by protein unbinding or force. The condensed DNA structure is not well ordered and we infer that it is formed by many looping interactions between neighbouring DNA segments. Consistent with this view, ParB is also able to stabilize writhe in single supercoiled DNA molecules and to bridge segments from two different DNA molecules in trans. The experiments provide no evidence for the promotion of non-specific DNA binding and/or condensation events by the presence of parS sequences. The implications of these observations for chromosome segregation are discussed. PMID:25572315

The role of dynamic renal scintigraphy on clinical decision making in hydronephrotic children.

PubMed

Çamlar, Seçil Arslansoyu; Deveci, Nazlı; Soylu, Alper; Türkmen, Mehmet Atilla; Özmen, Derya; Çapakaya, Gamze; Kavukçu, Salih

2017-01-01

Hydronephrosis may be related to an obstructive cause, ureteropelvic/uretero-vesical junction obstruction or nonobstructive [vesicoureteral reflux (VUR)]. When an obstructive pathology is considered, dynamic renal scintigraphy may help to predict whether it is a true obstruction or not. In this study, we aimed to determine the contribution of dynamic renal scintigraphy with [99] mTc-MAG-3 to the clinical decision-making for surgery in hydronephrotic children. Files of the patients evaluated by MAG-3 scintigraphy for antenatal (AH)/postnatal (PH) hydronephrosis between 1992 and 2014 were reviewed. Gender, age, hydronephrosis (HN) grade by ultrasound (US), presence of VUR, MAG-3 result (obstructive vs. nonobstructive), ultimate diagnosis, and need for surgery were assessed. Cases with double collecting system and neurogenic bladder were excluded from the study. All of the patients had normal serum creatinine and eGFR. There were a total of 178 patients with 218 hydronephrotic renal units (mean age 34.7 ± 52.7 months; male/ female = 121/57, AH of 62%). MAG-3 was nonobstructive in 134 and obstructive in 84 hydronephrotic renal units. MAG-3 was obstructive in 47 of 121 (39%) males and 30 of 57 (53%) females (P = 0.058, odds ratio (OR) for obstruction was 1.9 for girls). MAG-3 was obstructive in 47 of 135 (35%) units with AH and 37 of 83 (45%) units with PH (P = 0.137). In 81 units with the society of fetal urology-4 HN by US, MAG-3 was obstructive in 55 (68%), and surgery was required in 52 of 55 (95%). Surgery was required for only two (7%) of the remaining 26 units with nonobstructive dilatation (P <0.001, sensitivity 96%, specificity 89%, OR 208). Antero-posterior diameter >16.5 mm was the best cutoff level for predicting obstruction by MAG-3 (sensitivity 75.2%; specificity 71%; OR 3.8). MAG-3 significantly affects clinical decision for surgery in HN. Hydronephrotic girls have more risk in terms of true obstruction. Combining MAG-3 with US improves the

Development and gamma scintigraphy evaluation of gastro retentive calcium ion-based oral formulation: an innovative approach for the management of gastro-esophageal reflux disease (GERD).

PubMed

Sharma, Braj Gaurav; Khanna, Kushagra; Kumar, Neeraj; Nishad, Dhruv K; Basu, Mitra; Bhatnagar, Aseem

2017-11-01

Calcium chloride is an essential calcium channel agonist which plays an important role in the contraction of muscles by triggering calcium channel. First time hypothesized about its role in the treatment of GER (gastro-esophageal reflux) and vomiting disorder due to its local action. There are two objectives covered in this study as first, the development and optimization of floating formulation of calcium chloride and another objective was to evaluate optimized formulation through gamma scintigraphy in human subjects. Gastro retentive formulation of calcium chloride was prepared by direct compression method. Thirteen tablet formulations were designed with the help of sodium chloride, HPMC-K4M, and carbopol-934 along with effervescing agent sodium bicarbonate and citric acid. Formulation (F8) fitted best for Korsmeyer-Peppas equation with an R 2 value of 0.993. The optimized formulation was radiolabelled with 99m Tc-99 m pertechnetate for its evaluation by gamma scintigraphy. Gastric retention (6 h) was evaluated by gamma scintigraphy in healthy human subjects and efficacy of present formulation confirmed in GER positive human subjects. Gamma scintigraphy results indicated its usefulness in order to manage GERD. Stability studies of the developed formulation were carried out as per ICH guidelines for region IV and found out to be stable for 24 months.

Par Pond vegetation status Summer 1995 -- October survey descriptive summary

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

Mackey, H.E. Jr.; Riley, R.S.

1995-11-01

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the emergent shoreline aquatic plant communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level and continued with this late October survey. Communities similar to the pre-drawdown Par Pond aquatic plant communitiesmore » are becoming re-established; especially, beds of maiden cane, lotus, waterlily, and watershield are now extensive and well established. Cattail occurrence continues to increase, but large beds common to Par Pond prior to the drawdown have not formed. Future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned.« less

View from east to west of PAR site storage building; ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View from east to west of PAR site storage building; formerly PAR dispensary - Stanley R. Mickelsen Safeguard Complex, Storage Building, Across street from Family Housing Units 110 & 111, Nekoma, Cavalier County, ND

Improved Satellite-based Photosysnthetically Active Radiation (PAR) for Air Quality Studies

NASA Astrophysics Data System (ADS)

Pour Biazar, A.; McNider, R. T.; Cohan, D. S.; White, A.; Zhang, R.; Dornblaser, B.; Doty, K.; Wu, Y.; Estes, M. J.

2015-12-01

One of the challenges in understanding the air quality over forested regions has been the uncertainties in estimating the biogenic hydrocarbon emissions. Biogenic volatile organic compounds, BVOCs, play a critical role in atmospheric chemistry, particularly in ozone and particulate matter (PM) formation. In southeastern United States, BVOCs (mostly as isoprene) are the dominant summertime source of reactive hydrocarbon. Despite significant efforts in improving BVOC estimates, the errors in emission inventories remain a concern. Since BVOC emissions are particularly sensitive to the available photosynthetically active radiation (PAR), model errors in PAR result in large errors in emission estimates. Thus, utilization of satellite observations to estimate PAR can help in reducing emission uncertainties. Satellite-based PAR estimates rely on the technique used to derive insolation from satellite visible brightness measurements. In this study we evaluate several insolation products against surface pyranometer observations and offer a bias correction to generate a more accurate PAR product. The improved PAR product is then used in biogenic emission estimates. The improved biogenic emission estimates are compared to the emission inventories over Texas and used in air quality simulation over the period of August-September 2013 (NASA's Discover-AQ field campaign). A series of sensitivity simulations will be performed and evaluated against Discover-AQ observations to test the impact of satellite-derived PAR on air quality simulations.

PAR(2) expression in peripheral blood monocytes of patients with rheumatoid arthritis.

PubMed

Crilly, A; Burns, E; Nickdel, M B; Lockhart, J C; Perry, M E; Ferrell, P W; Baxter, D; Dale, J; Dunning, L; Wilson, H; Nijjar, J S; Gracie, J A; Ferrell, W R; McInnes, I B

2012-06-01

Proteinase-activated receptor 2 (PAR(2)) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. A study was undertaken to investigate the presence and functional significance of PAR(2) expression on rheumatoid arthritis (RA)-derived leucocyte subsets. Venous blood was obtained from patients with RA and osteoarthritis (OA) as well as healthy control subjects. Surface expression of PAR(2) on peripheral blood mononuclear cells (PBMCs) was analysed by flow cytometry and interleukin 6 (IL-6) generation by ELISA. Patients with RA had elevated but variable surface expression of PAR(2) on CD14+ monocytes compared with control subjects (median (1st to 3rd quartiles) 1.76% (0.86-4.10%) vs 0.06% (0.03-0.81%), p<0.0001). CD3+ T cells showed a similar pattern with significantly higher PAR(2) expression in patients with RA compared with controls (3.05% (0.36-11.82%) vs 0.08% (0.02-0.28%), p<0.0001). For both subsets, PAR(2) expression was significantly higher (p<0.00001) in patients with high levels of disease activity: PAR(2) expression for both CD14+ and CD3+ cells correlated to C reactive protein and erythrocyte sedimentation rate. Furthermore, in a cohort of patients with newly diagnosed RA, elevated PAR(2) expression in both CD14+ and CD3+ cells was significantly reduced 3 months after methotrexate or sulfasalazine treatment and this reduction correlated significantly with the reduction in the 28-joint Disease Activity Scale score (p<0.05). PAR(2) expression on cells from patients with OA was low, similar to levels seen in control subjects. Generation of IL-6 by monocytes in response to a selective PAR(2) agonist was significantly greater in patients with RA than in patients with OA and control subjects (p<0.05). These findings are consistent with a pathogenic role for PAR(2) in RA.

PAR2 expression in peripheral blood monocytes of patients with rheumatoid arthritis

PubMed Central

Crilly, A; Burns, E; Nickdel, M B; Lockhart, J C; Perry, M E; Ferrell, P W; Baxter, D; Dale, J; Dunning, L; Wilson, H; Nijjar, J S; Gracie, J A; Ferrell, W R; McInnes, I B

2012-01-01

Objectives Proteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. A study was undertaken to investigate the presence and functional significance of PAR2 expression on rheumatoid arthritis (RA)-derived leucocyte subsets. Methods Venous blood was obtained from patients with RA and osteoarthritis (OA) as well as healthy control subjects. Surface expression of PAR2 on peripheral blood mononuclear cells (PBMCs) was analysed by flow cytometry and interleukin 6 (IL-6) generation by ELISA. Results Patients with RA had elevated but variable surface expression of PAR2 on CD14+ monocytes compared with control subjects (median (1st to 3rd quartiles) 1.76% (0.86–4.10%) vs 0.06% (0.03–0.81%), p<0.0001). CD3+ T cells showed a similar pattern with significantly higher PAR2 expression in patients with RA compared with controls (3.05% (0.36–11.82%) vs 0.08% (0.02–0.28%), p<0.0001). For both subsets, PAR2 expression was significantly higher (p<0.00001) in patients with high levels of disease activity: PAR2 expression for both CD14+ and CD3+ cells correlated to C reactive protein and erythrocyte sedimentation rate. Furthermore, in a cohort of patients with newly diagnosed RA, elevated PAR2 expression in both CD14+ and CD3+ cells was significantly reduced 3 months after methotrexate or sulfasalazine treatment and this reduction correlated significantly with the reduction in the 28-joint Disease Activity Scale score (p<0.05). PAR2 expression on cells from patients with OA was low, similar to levels seen in control subjects. Generation of IL-6 by monocytes in response to a selective PAR2 agonist was significantly greater in patients with RA than in patients with OA and control subjects (p<0.05). Conclusions These findings are consistent with a pathogenic role for PAR2 in RA. PMID:22294633

123I-Mibg scintigraphy and 18F-Fdg-Pet imaging for diagnosing neuroblastoma

PubMed Central

Bleeker, Gitta; Tytgat, Godelieve Am; Adam, Judit A; Caron, Huib N; Kremer, Leontien Cm; Hooft, Lotty; van Dalen, Elvira C

2015-01-01

Background Neuroblastoma is an embryonic tumour of childhood that originates in the neural crest. It is the second most common extracranial malignant solid tumour of childhood. Neuroblastoma cells have the unique capacity to accumulate Iodine-123-metaiodobenzylguanidine (123I-MIBG), which can be used for imaging the tumour. Moreover, 123I-MIBG scintigraphy is not only important for the diagnosis of neuroblastoma, but also for staging and localization of skeletal lesions. If these are present, MIBG follow-up scans are used to assess the patient's response to therapy. However, the sensitivity and specificity of 123I-MIBG scintigraphy to detect neuroblastoma varies according to the literature. Prognosis, treatment and response to therapy of patients with neuroblastoma are currently based on extension scoring of 123I-MIBG scans. Due to its clinical use and importance, it is necessary to determine the exact diagnostic accuracy of 123I-MIBG scintigraphy. In case the tumour is not MIBG avid, fluorine-18-fluorodeoxy-glucose (18F-FDG) positron emission tomography (PET) is often used and the diagnostic accuracy of this test should also be assessed. Objectives Primary objectives: 1.1 To determine the diagnostic accuracy of 123I-MIBG (single photon emission computed tomography (SPECT), with or without computed tomography (CT)) scintigraphy for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. 1.2 To determine the diagnostic accuracy of negative 123I-MIBG scintigraphy in combination with 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old, i.e. an add-on test. Secondary objectives: 2.1 To determine the diagnostic accuracy of 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. 2.2 To compare the diagnostic accuracy of 123I

A three-dimensional ParF meshwork assembles through the nucleoid to mediate plasmid segregation

PubMed Central

McLeod, Brett N.; Allison-Gamble, Gina E.; Barge, Madhuri T.; Tonthat, Nam K.; Schumacher, Maria A.; Hayes, Finbarr

2017-01-01

Abstract Genome segregation is a fundamental step in the life cycle of every cell. Most bacteria rely on dedicated DNA partition proteins to actively segregate chromosomes and low copy-number plasmids. Here, by employing super resolution microscopy, we establish that the ParF DNA partition protein of the ParA family assembles into a three-dimensional meshwork that uses the nucleoid as a scaffold and periodically shuttles between its poles. Whereas ParF specifies the territory for plasmid trafficking, the ParG partner protein dictates the tempo of ParF assembly cycles and plasmid segregation events by stimulating ParF adenosine triphosphate hydrolysis. Mutants in which this ParG temporal regulation is ablated show partition deficient phenotypes as a result of either altered ParF structure or dynamics and indicate that ParF nucleoid localization and dynamic relocation, although necessary, are not sufficient per se to ensure plasmid segregation. We propose a Venus flytrap model that merges the concepts of ParA polymerization and gradient formation and speculate that a transient, dynamic network of intersecting polymers that branches into the nucleoid interior is a widespread mechanism to distribute sizeable cargos within prokaryotic cells. PMID:28034957

Croissance epitaxiale de GaAs sur substrats de Ge par epitaxie par faisceaux chimiques

NASA Astrophysics Data System (ADS)

Belanger, Simon

La situation energetique et les enjeux environnementaux auxquels la societe est confrontee entrainent un interet grandissant pour la production d'electricite a partir de l'energie solaire. Parmi les technologies actuellement disponibles, la filiere du photovoltaique a concentrateur solaire (CPV pour concentrator photovoltaics) possede un rendement superieur et mi potentiel interessant a condition que ses couts de production soient competitifs. La methode d'epitaxie par faisceaux chimiques (CBE pour chemical beam epitaxy) possede plusieurs caracteristiques qui la rendent interessante pour la production a grande echelle de cellules photovoltaiques a jonctions multiples a base de semi-conducteurs III-V. Ce type de cellule possede la meilleure efficacite atteinte a ce jour et est utilise sur les satellites et les systemes photovoltaiques a concentrateur solaire (CPV) les plus efficaces. Une des principales forces de la technique CBE se trouve dans son potentiel d'efficacite d'utilisation des materiaux source qui est superieur a celui de la technique d'epitaxie qui est couramment utilisee pour la production a grande echelle de ces cellules. Ce memoire de maitrise presente les travaux effectues dans le but d'evaluer le potentiel de la technique CBE pour realiser la croissance de couches de GaAs sur des substrats de Ge. Cette croissance constitue la premiere etape de fabrication de nombreux modeles de cellules solaires a haute performance decrites plus haut. La realisation de ce projet a necessite le developpement d'un procede de preparation de surface pour les substrats de germanium, la realisation de nombreuses sceances de croissance epitaxiale et la caracterisation des materiaux obtenus par microscopie optique, microscopie a force atomique (AFM), diffraction des rayons-X a haute resolution (HRXRD), microscopie electronique a transmission (TEM), photoluminescence a basse temperature (LTPL) et spectrometrie de masse des ions secondaires (SIMS). Les experiences ont permis

Effect of Par Frying on Composition and Texture of Breaded and Battered Catfish

PubMed Central

Woods, Kristin; Lea, Jeanne M.; Brashear, Suzanne S.; Boue, Stephen M.; Daigle, Kim W.; Bett-Garber, Karen L.

2018-01-01

Catfish is often consumed as a breaded and battered fried product; however, there is increasing interest in breaded and battered baked products as a healthier alternative. Par frying can improve the texture properties of breaded and battered baked products, but there are concerns about the increase in lipid uptake from par frying. The objective of this study was to examine the effect of different batters (rice, corn, and wheat) and the effect of par frying on the composition and texture properties of baked catfish. Catfish fillets were cut strips and then coated with batters, which had similar viscosities. Half of the strips were par fried in 177 °C vegetable oil for 1 min and the other half were not par fried. Samples were baked at 177 °C for 25 min. Analysis included % batter adhesion, cooking loss, protein, lipid, ash, and moisture, plus hardness and fracture quality measured using a texture analyzer. A trained sensory panel evaluated both breading and flesh texture attributes. Results found the lipid content of par fried treatments were significantly higher for both corn and wheat batters than for non-par fried treatments. Sensory analysis indicated that the texture of the coatings in the par fried treatments were significantly greater for hardness attributes. Fillet flakiness was significantly greater in the par fried treatments and corn-based batters had moister fillet strips compared to the wheat flour batters. Texture analyzer hardness values were higher for the par fried treatments. PMID:29570660

Papillary carcinoma in ectopic thyroid detected by Tl-201 scintigraphy

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

Michigishi, T.; Mizukami, Y.; Mura, T.

1991-05-01

A 37-year-old man with papillary carcinoma in an ectopic thyroid is presented. Excisional biopsy revealed the cervical mass to be a metastasis from thyroid cancer. X-ray, ultrasonography, and computed tomography, however, failed to identify the primary tumor in the thyroid. Incidental TI-201 uptake was noted in the midline of the anterior neck, and a palpable nodule was discovered in this area. Fine needle aspiration cytology demonstrated Class V papillary adenocarcinoma, and subsequent surgery confirmed a papillary carcinoma in the ectopic thyroid. This case suggests the usefulness of TI-201 scintigraphy for the detection of ectopic thyroid malignancy.

Control of Smc Coiled Coil Architecture by the ATPase Heads Facilitates Targeting to Chromosomal ParB/parS and Release onto Flanking DNA

PubMed Central

Minnen, Anita; Bürmann, Frank; Wilhelm, Larissa; Anchimiuk, Anna; Diebold-Durand, Marie-Laure; Gruber, Stephan

2016-01-01

Summary Smc/ScpAB promotes chromosome segregation in prokaryotes, presumably by compacting and resolving nascent sister chromosomes. The underlying mechanisms, however, are poorly understood. Here, we investigate the role of the Smc ATPase activity in the recruitment of Smc/ScpAB to the Bacillus subtilis chromosome. We demonstrate that targeting of Smc/ScpAB to ParB/parS loading sites is strictly dependent on engagement of Smc head domains and relies on an open organization of the Smc coiled coils. We find that dimerization of the Smc hinge domain stabilizes closed Smc rods and hinders head engagement as well as chromosomal targeting. Conversely, the ScpAB sub-complex promotes head engagement and Smc rod opening and thereby facilitates recruitment of Smc to parS sites. Upon ATP hydrolysis, Smc/ScpAB is released from loading sites and relocates within the chromosome—presumably through translocation along DNA double helices. Our findings define an intermediate state in the process of chromosome organization by Smc. PMID:26904953

ParTIES: a toolbox for Paramecium interspersed DNA elimination studies.

PubMed

Denby Wilkes, Cyril; Arnaiz, Olivier; Sperling, Linda

2016-02-15

Developmental DNA elimination occurs in a wide variety of multicellular organisms, but ciliates are the only single-celled eukaryotes in which this phenomenon has been reported. Despite considerable interest in ciliates as models for DNA elimination, no standard methods for identification and characterization of the eliminated sequences are currently available. We present the Paramecium Toolbox for Interspersed DNA Elimination Studies (ParTIES), designed for Paramecium species, that (i) identifies eliminated sequences, (ii) measures their presence in a sequencing sample and (iii) detects rare elimination polymorphisms. ParTIES is multi-threaded Perl software available at https://github.com/oarnaiz/ParTIES. ParTIES is distributed under the GNU General Public Licence v3. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

View from west to east of PAR site resident engineer's ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View from west to east of PAR site resident engineer's office building (REOB) - Stanley R. Mickelsen Safeguard Complex, Resident Engineers Office Building, Southeast of intersection of PAR Access Road & Fourth Avenue, Nekoma, Cavalier County, ND

Estimating Photosynthetically Available Radiation (PAR) at the Earth's surface from satellite observations

NASA Technical Reports Server (NTRS)

Frouin, Robert

1993-01-01

Current satellite algorithms to estimate photosynthetically available radiation (PAR) at the earth' s surface are reviewed. PAR is deduced either from an insolation estimate or obtained directly from top-of-atmosphere solar radiances. The characteristics of both approaches are contrasted and typical results are presented. The inaccuracies reported, about 10 percent and 6 percent on daily and monthly time scales, respectively, are useful to model oceanic and terrestrial primary productivity. At those time scales variability due to clouds in the ratio of PAR and insolation is reduced, making it possible to deduce PAR directly from insolation climatologies (satellite or other) that are currently available or being produced. Improvements, however, are needed in conditions of broken cloudiness and over ice/snow. If not addressed properly, calibration/validation issues may prevent quantitative use of the PAR estimates in studies of climatic change. The prospects are good for an accurate, long-term climatology of PAR over the globe.

ParCAT: A Parallel Climate Analysis Toolkit

NASA Astrophysics Data System (ADS)

Haugen, B.; Smith, B.; Steed, C.; Ricciuto, D. M.; Thornton, P. E.; Shipman, G.

2012-12-01

Climate science has employed increasingly complex models and simulations to analyze the past and predict the future of our climate. The size and dimensionality of climate simulation data has been growing with the complexity of the models. This growth in data is creating a widening gap between the data being produced and the tools necessary to analyze large, high dimensional data sets. With single run data sets increasing into 10's, 100's and even 1000's of gigabytes, parallel computing tools are becoming a necessity in order to analyze and compare climate simulation data. The Parallel Climate Analysis Toolkit (ParCAT) provides basic tools that efficiently use parallel computing techniques to narrow the gap between data set size and analysis tools. ParCAT was created as a collaborative effort between climate scientists and computer scientists in order to provide efficient parallel implementations of the computing tools that are of use to climate scientists. Some of the basic functionalities included in the toolkit are the ability to compute spatio-temporal means and variances, differences between two runs and histograms of the values in a data set. ParCAT is designed to facilitate the "heavy lifting" that is required for large, multidimensional data sets. The toolkit does not focus on performing the final visualizations and presentation of results but rather, reducing large data sets to smaller, more manageable summaries. The output from ParCAT is provided in commonly used file formats (NetCDF, CSV, ASCII) to allow for simple integration with other tools. The toolkit is currently implemented as a command line utility, but will likely also provide a C library for developers interested in tighter software integration. Elements of the toolkit are already being incorporated into projects such as UV-CDAT and CMDX. There is also an effort underway to implement portions of the CCSM Land Model Diagnostics package using ParCAT in conjunction with Python and gnuplot. Par

Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis.

PubMed

Wu, Yu; Zhang, Guojian; Wang, Xiangcheng; Zhao, Zhenfang; Wang, Tao; Wang, Xuemei; Li, Xiao-Feng

2017-01-24

To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management.

A three-dimensional ParF meshwork assembles through the nucleoid to mediate plasmid segregation.

PubMed

McLeod, Brett N; Allison-Gamble, Gina E; Barge, Madhuri T; Tonthat, Nam K; Schumacher, Maria A; Hayes, Finbarr; Barillà, Daniela

2017-04-07

Genome segregation is a fundamental step in the life cycle of every cell. Most bacteria rely on dedicated DNA partition proteins to actively segregate chromosomes and low copy-number plasmids. Here, by employing super resolution microscopy, we establish that the ParF DNA partition protein of the ParA family assembles into a three-dimensional meshwork that uses the nucleoid as a scaffold and periodically shuttles between its poles. Whereas ParF specifies the territory for plasmid trafficking, the ParG partner protein dictates the tempo of ParF assembly cycles and plasmid segregation events by stimulating ParF adenosine triphosphate hydrolysis. Mutants in which this ParG temporal regulation is ablated show partition deficient phenotypes as a result of either altered ParF structure or dynamics and indicate that ParF nucleoid localization and dynamic relocation, although necessary, are not sufficient per se to ensure plasmid segregation. We propose a Venus flytrap model that merges the concepts of ParA polymerization and gradient formation and speculate that a transient, dynamic network of intersecting polymers that branches into the nucleoid interior is a widespread mechanism to distribute sizeable cargos within prokaryotic cells. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Detection of occult infection following total joint arthroplasty using sequential technetium-99m HDP bone scintigraphy and indium-111 WBC imaging

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

Johnson, J.A.; Christie, M.J.; Sandler, M.P.

1988-08-01

Preoperative exclusion or confirmation of periprosthetic infection is essential for correct surgical management of patients with suspected infected joint prostheses. The sensitivity and specificity of (/sup 111/In)WBC imaging in the diagnosis of infected total joint prostheses was examined in 28 patients and compared with sequential (/sup 99m/Tc)HDP/(/sup 111/In)WBC scintigraphy and aspiration arthrography. The sensitivity of preoperative aspiration cultures was 12%, with a specificity of 81% and an accuracy of 58%. The sensitivity of (/sup 111/In)WBC imaging alone was 100%, with a specificity of 50% and an accuracy of 65%. When correlated with the bone scintigraphy and read as sequential (/supmore » 99m/Tc)HDP/(/sup 111/In)WBC imaging, the sensitivity was 88%, specificity 95%, and accuracy 93%. This study demonstrates that (/sup 111/In)WBC imaging is an extremely sensitive imaging modality for the detection of occult infection of joint prostheses. It also demonstrates the necessity of correlating (/sup 111/In)WBC images with (/sup 99m/Tc)HDP skeletal scintigraphy in the detection of occult periprosthetic infection.« less

Effects of silenced PAR-2 on cell proliferation, invasion and metastasis of esophageal cancer.

PubMed

Chen, Jinmei; Xie, Liqun; Zheng, Yanmin; Liu, Caihong

2017-10-01

The present study aimed to investigate the effect of protease-activated receptor 2 (PAR-2) on cell proliferation, invasion and metastasis in the esophageal EC109 cell line. Two short hairpin RNA (shRNA) expression plasmids were constructed based on the PAR-2 mRNA sequence in humans, and they were transfected into the EC109 esophageal cancer cell line, and the stable interference cell line (shRNA-PAR-2 EC109) was obtained by puromycin selection. Following transfection of PAR-2 shRNA-1, PAR-2 expression was significantly downregulated in mRNA level and protein level in EC109 cells (P<0.05). The proliferation of EC109 cells transfected with PAR-2 shRNA was significantly lower than the negative control group (P<0.05). At 24, 48 and 72 h, the ratio of proliferation inhibition was 15.92, 24.89 and 32.28%, respectively. Compared with the control group, S-phase arrest was observed in cells transfected with shRNA-PAR-2. The ratio of cells in the S phase was 32.79±4.06, 26.54±1.37 and 33.45±2.46% at 24, 48 and 72 h, respectively. For invasion, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.05). For metastasis assay, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.01). In the present study, the PAR-2 shRNA plasmid was constructed successfully, which can significantly downregulate PAR-2 expression in EC109 cells. Subsequent to silencing of PAR-2, the proliferation of EC109 cells was inhibited and the capabilities of invasion and migration were reduced. It is indicated that PAR-2 may be a potential target in esophageal cancer.

Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis.

PubMed

Lee, Hyejoo; Malaspina, Dolores; Ahn, Hongshik; Perrin, Mary; Opler, Mark G; Kleinhaus, Karine; Harlap, Susan; Goetz, Raymond; Antonius, Daniel

2011-05-01

Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia. We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers' age at birth ≥ 35 years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale-Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS. Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early. These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

Par Pond vegetation status Summer 1995 -- June survey descriptive summary

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

Mackey, H.E. Jr.; Riley, R.S.

1995-06-01

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the shoreline aquatic plant communities in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level, indicated that much of the original plant communities and the intermediate shoreline communities present on the exposed sediments havemore » been lost. The extensive old-field and emergent marsh communities that were present on the exposed shoreline during the drawdown have been flooded and much of the pre-drawdown Par Pond aquatic plant communities have not had sufficient time for re-establishment. The shoreline does, however, have extensive beds of maidencane which extend from the shoreline margin to areas as deep as 2 and perhaps 3 meters. Scattered individual plants of lotus and watershield are common and may indicate likely directions of future wetland development in Par Pond. In addition, within isolated coves, which apparently received ground water seepage and/or stream surface flows during the period of the Par Pond draw down, extensive beds of waterlilies and spike rush are common. Invasion of willow and red maple occurred along the lake shoreline as well. Although not absent from this survey, evidence of the extensive redevelopment of the large cattail and eel grass beds was not observed in this first survey of Par Pond. Future surveys during the growing seasons of 1995, 1996, and 1997 along with the evaluation of satellite date to map the areal extent of the macrophyte beds of Par Pond are planned.« less

Provenance of the oil in par-fried French fries after finish frying.

PubMed

Al-Khusaibi, Mohammed; Gordon, Michael H; Lovegrove, Julie A; Niranjan, Keshavan

2012-01-01

Frozen par-fried French fries are finish-fried either by using the same type of oil used for par frying, or a different type. The nutritive quality of the final oil contained in the product depends on the relative amounts and the fatty acid (FA) composition of the oils used for par frying and finish frying. With the aim of understanding the provenance of the oil in the final product, par-fried French fries-either purchased ready or prepared in the laboratory-were finish fried in oils different from the ones used for par frying. The moisture content, oil content, and FA compositions of the par-fried and finish-fried products were experimentally determined, and the relative amounts of each of the oils present in the final product were calculated using the FAs as markers and undertaking a mass balance on each component FA. The results demonstrate that 89% to 93% of the total oil in the final product originates from the finish-frying step. The study also shows that a significant proportion of the oil absorbed during par frying is expelled from the product during finish frying. Further, the expulsion of par-frying oil was found to occur in the early stages of the finish-frying step. Experiments involving different combinations of par-frying and finish-frying oils showed that the relative proportions of the 2 oils did not depend on the individual fatty acid profiles. This study concludes that any positive health benefits of using an oil having a favorable FA profile for par frying, can potentially be lost, if the oil used for finish frying has a less favorable composition. This paper estimates the relative amounts of oil in French fries that have been fried in 2 stages-a par-frying step and a finish-frying step-which is commonly practiced in food service establishments as well as homes. The 2 key conclusions are: (1) nearly 90% of the oil content of the final product is the one used for finish frying; that is, a processor may use very good oil for par frying but if the

[Four-port pars plana vitrectomy for severe proliferative diabetic retinopathy].

PubMed

Wei, Wen-bin; Yang, Qiong; Mo, Jing; Zhou, Dan

2008-01-01

To investigate the 4-port pars plana vitrectomy in eyes with severe proliferative diabetic retinopathy (PDR). It was a case-control study. Twenty-eight eyes in 27 patients with extensive fibrovascular proliferation associated with PDR were retrospectively collected, who were undergone 4-port pars plana vitreous surgery with bimanual manipulation techniques, such as membrane dissections and enbloc membranectomy. The control group consisted of 30 eyes in 30 patients with PDR which were undergone 3-port pars plana vitrectomy by the same surgeon. Twenty-eight eyes were undergone membrane dissection and enbloc membranectomy smoothly during 4-port pars plana vitrectomy, 2 iatrogenic holes occurred in 1 eye. During the follow up 7 months to 4.5 years, the retina was fully attached in all eyes, visual acuity had improved except 1 eye which complicated with neovascular glaucoma. In the control group, membranes partially remained in 2 eyes, 4 iatrogenic holes appeared in 3 eyes, neovascular glaucoma occurred in 3 eyes, the retina was reattached during the follow-up time from 12 to 34 months. For severe proliferative diabetic retinopathy, the 4-port pars plana vitrectomy with bimanual manipulations of membrane peeling is safe and efficiency.

Reconstruction d’une Carbonisation du Pouce par Lambeau Chinois

PubMed Central

Khales, A.; Achbouk, J.A.; Moussaoui, A.; Belmir, R.; Tourabi, K.; Oufkir, A.; Ihrai, H.

2010-01-01

Summary La main en tant qu’organe majeur de la préhension peut être le siège de brûlures graves qui compromettent sa fonction. Bien qu’elle ne représente que 2% de la surface corporelle la brûlure de la main est grave et difficile à traiter, vu la vulnérabilité et la complexité de son appareil locomoteur. Nous rapportons dans ce travail le cas d’un patient victime d’une carbonisation de la main. Huit mois après le parage et la couverture par lambeau inguinal, le patient bénéficie d’une reconstruction du pouce par lambeau chinois associé à une greffe osseuse. Le résultat s’est avéré satisfaisant. Le lambeau chinois prouve par son apport vasculaire et par sa facilité technique qu’il est un moyen très intéressant dans la reconstruction du pouce - ou des doigts en général - surtout dans un contexte de brûlure. PMID:21991226

Role of magnetic resonance imaging and scintigraphy in the diagnosis and follow-up of osteomyelitis in cat-scratch disease.

PubMed

Rozmanic, Vojko; Banac, Srdjan; Miletic, Damir; Manestar, Koraljka; Kamber, Silvija; Paparic, Sime

2007-01-01

Cat-scratch disease (CSD) is a self-limiting infectious disease characterised with lymphadenopathy in a patient with a history of cat contact. Cases of bone involvement in patients with CSD are rare. We reported a case of 11-year-old boy with prolonged intermittent fever, inguinal lymphadenopathy and osteomyelitis. He had a history of exposure to kittens. The physical examination revealed a febrile boy without an apparent site of infection except an enlarged inguinal lymph node. Its histopathology demonstrated granulomatous lesion with no presence of acid-fast bacilli. Serum titers for Bartonella henselae were positive. Multiple bone lesions were detected by skeletal scintigraphy. Magnetic resonance imaging (MRI) confirmed and characterised osteolytic masses. The oral combination of azithromycin and rifampicin were given for 6 weeks with a good clinical response. At follow-up, the boy was without symptoms or signs of the disease. Successive MRI controls showed gradual regression of the bone lesions together with significant decrease of acute-phase reactants. In conclusion, CSD should be considered in the differential diagnosis of osteomyelitis. MRI is more reliable for the characterisation, evaluation of soft-tissue extension and follow-up of the bone lesions than scintigraphy. However, the later method permits an overview of the multiple osseous lesions. Therefore, standard MRI equipment may not exclude bone scintigraphy. Both methods are required until whole-body MRI units become routine.

TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia

PubMed Central

Naeser, Margaret A.; Martin, Paula I.; Theoret, Hugo; Kobayashi, Masahito; Fregni, Felipe; Nicholas, Marjorie; Tormos, Jose M.; Steven, Megan S.; Baker, Errol H.; Pascual-Leone, Alvaro

2011-01-01

This study sought to discover if an optimum 1 cm2 area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1 Hz rTMS was applied to suppress different RH ROIs in eight aphasia cases. Picture naming and response time (RT) were examined before, and immediately after rTMS. In aphasia patients, suppression of right pars triangularis (PTr) led to significant increase in pictures named, and significant decrease in RT. Suppression of right pars opercularis (POp), however, led to significant increase in RT, but no change in number of pictures named. Eight normals named all pictures correctly; similar to aphasia patients, RT significantly decreased following rTMS to suppress right PTr, versus right POp. Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions. PMID:21864891

Effects of silenced PAR-2 on cell proliferation, invasion and metastasis of esophageal cancer

PubMed Central

Chen, Jinmei; Xie, Liqun; Zheng, Yanmin; Liu, Caihong

2017-01-01

The present study aimed to investigate the effect of protease-activated receptor 2 (PAR-2) on cell proliferation, invasion and metastasis in the esophageal EC109 cell line. Two short hairpin RNA (shRNA) expression plasmids were constructed based on the PAR-2 mRNA sequence in humans, and they were transfected into the EC109 esophageal cancer cell line, and the stable interference cell line (shRNA-PAR-2 EC109) was obtained by puromycin selection. Following transfection of PAR-2 shRNA-1, PAR-2 expression was significantly downregulated in mRNA level and protein level in EC109 cells (P<0.05). The proliferation of EC109 cells transfected with PAR-2 shRNA was significantly lower than the negative control group (P<0.05). At 24, 48 and 72 h, the ratio of proliferation inhibition was 15.92, 24.89 and 32.28%, respectively. Compared with the control group, S-phase arrest was observed in cells transfected with shRNA-PAR-2. The ratio of cells in the S phase was 32.79±4.06, 26.54±1.37 and 33.45±2.46% at 24, 48 and 72 h, respectively. For invasion, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.05). For metastasis assay, the number of invasive cells was significantly lower in shRNA-PAR2-2 cells compared with the control group (P<0.01). In the present study, the PAR-2 shRNA plasmid was constructed successfully, which can significantly downregulate PAR-2 expression in EC109 cells. Subsequent to silencing of PAR-2, the proliferation of EC109 cells was inhibited and the capabilities of invasion and migration were reduced. It is indicated that PAR-2 may be a potential target in esophageal cancer. PMID:28943918

Identification of a New Epitope in uPAR as a Target for the Cancer Therapeutic Monoclonal Antibody ATN-658, a Structural Homolog of the uPAR Binding Integrin CD11b (αM)

PubMed Central

Wei, Ying; Donate, Fernando; Juarez, Jose; Parry, Graham; Chen, Liqing; Meehan, Edward J.; Ahn, Richard W.; Ugolkov, Andrey; Dubrovskyi, Oleksii; O'Halloran, Thomas V.; Huang, Mingdong; Mazar, Andrew P.

2014-01-01

The urokinase plasminogen activator receptor (uPAR) plays a role in tumor progression and has been proposed as a target for the treatment of cancer. We recently described the development of a novel humanized monoclonal antibody that targets uPAR and has anti-tumor activity in multiple xenograft animal tumor models. This antibody, ATN-658, does not inhibit ligand binding (i.e. uPA and vitronectin) to uPAR and its mechanism of action remains unclear. As a first step in understanding the anti-tumor activity of ATN-658, we set out to identify the epitope on uPAR to which ATN-658 binds. Guided by comparisons between primate and human uPAR, epitope mapping studies were performed using several orthogonal techniques. Systematic site directed and alanine scanning mutagenesis identified the region of aa 268–275 of uPAR as the epitope for ATN-658. No known function has previously been attributed to this epitope Structural insights into epitope recognition were obtained from structural studies of the Fab fragment of ATN-658 bound to uPAR. The structure shows that the ATN-658 binds to the DIII domain of uPAR, close to the C-terminus of the receptor, corroborating the epitope mapping results. Intriguingly, when bound to uPAR, the complementarity determining region (CDR) regions of ATN-658 closely mimic the binding regions of the integrin CD11b (αM), a previously identified uPAR ligand thought to be involved in leukocyte rolling, migration and complement fixation with no known role in tumor progression of solid tumors. These studies reveal a new functional epitope on uPAR involved in tumor progression and demonstrate a previously unrecognized strategy for the therapeutic targeting of uPAR. PMID:24465541

Absent 99mTc-MIBI Uptake in the Thyroid Gland during Early Phase of Parathyroid Scintigraphy in Patients with Primary and Secondary Hyperparathyroidism.

PubMed

Jovanovska, Anamarija; Stoilovska, Bojana; Mileva, Magdalena; Miladinova, Daniela; Majstorov, Venjamin; Ugrinska, Ana

2018-05-20

Thyroid uptake of technetium-99m methoxyisobutylisonitrile ( 99m Tc-MIBI) during parathyroid scintigraphy can be affected by various conditions. To evaluate the frequency of absent 99m Tc-MIBI uptake by the thyroid gland in the early phase of dual-phase parathyroid scintigraphy. The early planar images of dual phase Tc 99m MIBI parathyroid scintigraphy from 217 patients performed between 2014 and 2017 were retrospectively analysed. Patients were divided into two groups. The first group included 147 patients with primary hyperparathyroidism and the second group included 70 patients with chronic renal failure. Patient records, laboratory and ultrasonographic data were analysed in all patients. Descriptive statistic was used for data analysis. Out of all patients in the first group, 18 patients (12.24%) showed absent thyroid uptake. Thyroidectomy was performed in 44.4% of these patients, and the rest of them had some thyroid disease. Only one patient had no thyroid or another chronic disease. In the second group, 8 patients (11.42%) presented with absent thyroid uptake of MIBI. Among them, 5 patients had no history of thyroid disease and had been on hemodialysis programme, and 3 patients had hypothyroidism. Absent 99m Tc-MIBI uptake in the thyroid during the early phase of parathyroid scintigraphy is most frequently related to thyroid disease. A small proportion of patients with chronic renal failure can present with absent 99m Tc-MIBI uptake in the thyroid as well. The mechanism for this alteration is still unclear and needs further investigation.

Plasmid partition system of the P1par family from the pWR100 virulence plasmid of Shigella flexneri.

PubMed

Sergueev, Kirill; Dabrazhynetskaya, Alena; Austin, Stuart

2005-05-01

P1par family members promote the active segregation of a variety of plasmids and plasmid prophages in gram-negative bacteria. Each has genes for ParA and ParB proteins, followed by a parS partition site. The large virulence plasmid pWR100 of Shigella flexneri contains a new P1par family member: pWR100par. Although typical parA and parB genes are present, the putative pWR100parS site is atypical in sequence and organization. However, pWR100parS promoted accurate plasmid partition in Escherichia coli when the pWR100 Par proteins were supplied. Unique BoxB hexamer motifs within parS define species specificities among previously described family members. Although substantially different from P1parS from the P1 plasmid prophage of E. coli, pWR100parS has the same BoxB sequence. As predicted, the species specificity of the two types proved identical. They also shared partition-mediated incompatibility, consistent with the proposed mechanistic link between incompatibility and species specificity. Among several informative sequence differences between pWR100parS and P1parS is the presence of a 21-bp insert at the center of the pWR100parS site. Deletion of this insert left much of the parS activity intact. Tolerance of central inserts with integral numbers of helical DNA turns reflects the critical topology of these sites, which are bent by binding the host IHF protein.

Bone Metabolism of the Patient with a Malignant Melanoma during the Entry Examination and the Check-up of Whole-body Bone Scintigraphy.

PubMed

Weissensteiner, Jaroslav; Babušíková, Eva

Malignant melanoma is a malignancy located predominantly in the skin and the incidence of melanoma increases. We compared the markers of bone metabolism - osteocalcin (OC), beta-carboxyterminal cross-linked telopeptide of type I collagen (β-CrossLaps, β-CTx) and tumour marker - human epididymis protein 4 (HE4) in the serum with finding during the entry examination and the check-up of whole-body bone scintigraphy of the patient with a malignant melanoma. Serum concentrations of OC, β-CTx, HE4 were determined in 1 patient (female, age 64 years) with malignant melanoma and correlated with the presence of equivocal bone metastases detected by whole-body bone scintigraphy (the entry examination and check-up after 6 months). Concentrations of bone metabolism markers decreased during six months and we observed progress in bone metastases. The change of the markers levels during the entry examination and the check-up of the whole-body bone scintigraphy with equivocal finding of bone metastases could be a sign of a possible initiating progression of malignant melanoma despite a clinically negative finding that does not prove the progression of the disease.

Expression of proteinase-activated receptor (PAR)-2 in monocytes from allergic patients and potential molecular mechanism.

PubMed

Ge, Shuqing; Li, Tao; Yao, Qijian; Yan, Hongling; Huiyun, Zhang; Zheng, Yanshan; Zhang, Bin; He, Shaoheng

2016-12-01

Serine proteases play an important role in inflammation via PARs. However, little is known of expression levels of PARs on monocytes of allergic patients, and influence of serine proteases and PARs on TNF-α secretion from monocytes. Using quantitative real-time PCR (qPCR) and flowcytometry techniques, we observed that the expression level of PAR-2 in monocytes of patients with allergic rhinitis and asthma was increased by 42.9 and 38.2 %. It was found that trypsin, thrombin, and tryptase induced up to 200, 320, and 310 % increase in TNF-α release from monocytes at 16 h, respectively. PAR-1 agonist peptide, SFLLR-NH 2 , and PAR-2 agonist peptide tc-LIGRLO-NH 2 provoked up to 210 and 240 % increase in release of TNF-α. Since SCH 79797, a PAR-1 antagonist, and PD98059, an inhibitor of ERK inhibited thrombin- and SFLLR-NH 2 -induced TNF-α release, the action of thrombin is most likely through a PAR-1- and ERK-mediated signaling mechanism. Similarly, because FSLLRN-NH 2 , an inhibitor of PAR-2 diminished tryptase- and tc-LIGRLO-NH 2 -induced TNF-α release, the action of tryptase appears PAR-2 dependent. Moreover, in vivo study showed that both recombinant cockroach major allergens Per a 1 and Per a 7 provoked upregulation of PAR-2 and PAR-1 expression on CD14+ cells in OVA-sensitized mouse peritoneum. In conclusion, increased expression of PAR-2 in monocytes of AR and asthma implicates that PAR-2 likely play a role in allergy. PAR-2- and PAR-1-mediated TNF-α release from monocytes suggests that these unique protease receptors are involved in the pathogenesis of inflammation.

In-house preparation of iodine -131 metaiodo benzyl guanidine for scintigraphy of neuroendocrine tumors. Fourteen years experience in South India.

PubMed

Oommen, Regi; Shanthly, Nylla; Subramani, Narasimhan; Devadhas, Devakumar; Hephzibah, Julie; Theodore, Bernice; Srinivasan, Jayashankar

2007-01-01

Iodine-131 metaiodobenzyl guanidine ((131)I-MIBG) is routinely used for imaging and treatment of neuroendocrine tumors (NET). As the commercially available radiopharmaceutical was very expensive, we developed an in-house method of labeling MIBG with (131)I in 1993. A total of 247 batches of (131)I-MIBG were prepared and used in our hospital between April 1993 and September 2006. We report our experience over these 14 years of preparation of this tracer in our hospital radiopharmacy, for the scintigraphy of NET. The technique of preparation is simple and the labeled product was found to be of acceptable quality. With the routine availability and cost effectiveness, the utilization of this radiopharmaceutical for scintigraphy increased remarkably in our institution.

Regulation of long-term repopulating hematopoietic stem cells by EPCR/PAR1 signaling

PubMed Central

Gur-Cohen, Shiri; Kollet, Orit; Graf, Claudine; Esmon, Charles T.; Ruf, Wolfram; Lapidot, Tsvee

2016-01-01

The common developmental origin of endothelial and hematopoietic cells is manifested by coexpression of several cell surface receptors. Adult murine bone marrow (BM) long-term repopulating hematopoietic stem cells (LT-HSCs), endowed with the highest repopulation and self-renewal potential, express endothelial protein C receptor (EPCR), which is used as a marker to isolate them. EPCR/PAR1 signaling in endothelial cells has anticoagulant and anti-inflammatory roles, while thrombin/PAR1 signaling induces coagulation and inflammation. Recent studies define two new PAR1-mediated signaling cascades that regulate EPCR+ LT-HSC BM retention and egress. EPCR/PAR1 signaling facilitates LT-HSC BM repopulation, retention, survival, and chemotherapy resistance by restricting nitric oxide (NO) production, maintaining NOlow LT-HSC BM retention with increased VLA4 expression, affinity, and adhesion. Conversely, acute stress and clinical mobilization upregulate thrombin generation and activate different PAR1 signaling which overcomes BM EPCR+ LT-HSC retention, inducing their recruitment to the bloodstream. Thrombin/PAR1 signaling induces NO generation, TACE-mediated EPCR shedding, and upregulation of CXCR4 and PAR1, leading to CXCL12-mediated stem and progenitor cell mobilization. This review discusses new roles for factors traditionally viewed as coagulation related, which independently act in the BM to regulate PAR1 signaling in bone- and blood-forming progenitor cells, navigating their fate by controlling NO production. PMID:26928241

Traumatismes Oculaires par Petards: Bilan sur Trois Annees

PubMed Central

Zouaoui-Kesraoui, N.; Derdour, A.

2009-01-01

Summary Les accidents dus aux pétards sont des accidents graves. Leur recrudescence ces dernières années en Algérie, essentiellement durant les fêtes du Mawlid Ennabaoui (fête de la naissance du prophète), mérite à notre sens d'entreprendre des bilans exhaustifs dont celui-ci dans le but d'une sensibilisation de toutes les compétences concernées. Nous avons réuni sur trois années consécutives (2002, 2003, 2004) 60 dossiers de malades ayant subi des accidents oculaires par pétards. Nos patients sont répartis en 42 consultations pour blessures légères et 18 hospitalisations pour blessures graves. Parmi ces derniers, neuf ont présenté des complications et séquelles graves (cinq cas de cécité par atrophie du globe oculaire, trois cas de cécité cornéenne et un cas de cécité par trou maculaire). Dans tous ces cas l'incapacité permanente partielle est au minimum de 30%. Au vu de ces données nous proposons des mesures d'éducation sanitaire et une sensibilisation du grand public aux traumatismes oculaires, par le biais de mé dias appropriés: radio, télévision, affiches. PMID:21991157

PAR-1/MARK: a kinase essential for maintaining the dynamic state of microtubules.

PubMed

Hayashi, Kenji; Suzuki, Atsushi; Ohno, Shigeo

2012-01-01

The serine/threonine kinase, PAR-1, is an essential component of the evolutionary-conserved polarity-regulating system, PAR-aPKC system, which plays indispensable roles in establishing asymmetric protein distributions and cell polarity in various biological contexts (Suzuki, A. and Ohno, S. (2006). J. Cell Sci., 119: 979-987; Matenia, D. and Mandelkow, E.M. (2009). Trends Biochem. Sci., 34: 332-342). PAR-1 is also known as MARK, which phosphorylates classical microtubule-associated proteins (MAPs) and detaches MAPs from microtubules (Matenia, D. and Mandelkow, E.M. (2009). Trends Biochem. Sci., 34: 332-342). This MARK activity of PAR-1 suggests its role in microtubule (MT) dynamics, but surprisingly, only few studies have been carried out to address this issue. Here, we summarize our recent study on live imaging analysis of MT dynamics in PAR-1b-depleted cells, which clearly demonstrated the positive role of PAR-1b in maintaining MT dynamics (Hayashi, K., Suzuki, A., Hirai, S., Kurihara, Y., Hoogenraad, C.C., and Ohno, S. (2011). J. Neurosci., 31: 12094-12103). Importantly, our results further revealed the novel physiological function of PAR-1b in maintaining dendritic spine morphology in mature neurons.

Critical evaluation of lung scintigraphy in cystic fibrosis: study of 113 patients

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

Piepsz, A.; Wetzburger, C.; Spehl, M.

1980-10-01

A long-term study has been performed on 285 lung perfusion scintigrams obtained from 113 patients with cystic fibrosis. Transverse and longitudinal comparisons with clinical and radiological scores, as well as retrospective analysis of the deceased patients, were the methods used in order to evaluate the importance of the scintigraphic images. It appears that lung scintigraphy is the best index of the regional lung impairment, and contributes, as does a chest radiograph, to the early detection of lung lesions, the two methods being complementary.

Proteinase-activated receptors (PARs) – focus on receptor-receptor-interactions and their physiological and pathophysiological impact

PubMed Central

2013-01-01

Proteinase-activated receptors (PARs) are a subfamily of G protein-coupled receptors (GPCRs) with four members, PAR1, PAR2, PAR3 and PAR4, playing critical functions in hemostasis, thrombosis, embryonic development, wound healing, inflammation and cancer progression. PARs are characterized by a unique activation mechanism involving receptor cleavage by different proteinases at specific sites within the extracellular amino-terminus and the exposure of amino-terminal “tethered ligand“ domains that bind to and activate the cleaved receptors. After activation, the PAR family members are able to stimulate complex intracellular signalling networks via classical G protein-mediated pathways and beta-arrestin signalling. In addition, different receptor crosstalk mechanisms critically contribute to a high diversity of PAR signal transduction and receptor-trafficking processes that result in multiple physiological effects. In this review, we summarize current information about PAR-initiated physical and functional receptor interactions and their physiological and pathological roles. We focus especially on PAR homo- and heterodimerization, transactivation of receptor tyrosine kinases (RTKs) and receptor serine/threonine kinases (RSTKs), communication with other GPCRs, toll-like receptors and NOD-like receptors, ion channel receptors, and on PAR association with cargo receptors. In addition, we discuss the suitability of these receptor interaction mechanisms as targets for modulating PAR signalling in disease. PMID:24215724

Par3L enhances colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway

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

Li, Taiyuan; Liu, Dongning; Lei, Xiong

Partitioning defective 3-like protein (Par3L) is a recently identified cell polarity protein that plays an important role in mammary stem cell maintenance. Previously, we showed that high expression of Par3L is associated with poor survival in malignant colorectal cancer (CRC), but the underlying mechanism remained unknown. To this end, we established a Par3L knockout colorectal cancer cell line using the CRISPR/Cas system. Interestingly, reduced proliferation, enhanced cell death and caspase-3 activation were observed in Par3L knockout (KO) cells as compared with wildtype (WT) cells. Consistent with previous studies, we showed that Par3L interacts with a tumor suppressor protein liver kinasemore » B1 (Lkb1). Moreover, Par3L depletion resulted in abnormal activation of Lkb1/AMPK signaling cascade. Knockdown of Lkb1 in these cells could significantly reduce AMPK activity and partially rescue cell death caused by Par3L knockdown. Furthermore, we showed that Par3L KO cells were more sensitive to chemotherapies and irradiation. Together, these results suggest that Par3L is essential for colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway, and is a putative therapeutic target for CRC. - Highlights: • Par3L knockout using the CRISPR/Cas system induces apoptosis in colorectal cancer cells. • Par3L interacts with Lkb1 and regulates the activity of AMPK signaling cascade. • Par3L knockout cells are more sensitive to treatment of different chemotherapy drugs and irradiation.« less

[Reassessment of a combination of cerebrospinal fluid scintigraphy and nasal pledget counts in patients with suspected rhinorrhea].

PubMed

Kosuda, S; Arai, S; Hohshito, Y; Tokumitsu, H; Kusano, S; Ishihara, S; Shima, K

1998-07-01

A combination study of cerebrospinal fluid scintigraphy and nasal pledget counts was performed using 37 MBq of 111In-DTPA in 12 patients with suspected rhinorrhea. A pledget was inserted and dwelled in each nasal cavity for 6 hours, with the patient prone during at least 30 minutes. A total of 18 studies was implemented and nasal pledget counting method successfully diagnosed all of CSF rhinorrhea. Diagnosis was possible when pledget counts were greater than 1 kcpm. In patients with persistent, intermittent and occult/no nasal discharge, rhinorrhea was found in 100% (5/5), 60% (3/5), 25% (2/8), respectively. Two cases only exhibited positive scintigraphy. MRI or CT cisternography should be first performed in patients with persistent discharge, but in patients with intermittent/occult discharge pledget counting method might take priority of other diagnostic modalities. In conclusion, nasal pledget counting method is a simple and useful tool for detecting rhinorrhea.

Effect of PAR-2 Deficiency in Mice on KC Expression after Intratracheal LPS Administration

PubMed Central

Williams, Julie C.; Lee, Rebecca D.; Doerschuk, Claire M.; Mackman, Nigel

2011-01-01

Protease activated receptors (PAR) have been shown to play a role in inflammation. PAR-2 is expressed by numerous cells in the lung and has either proinflammatory, anti-inflammatory, or no effect depending on the model. Here, we examined the role of PAR-2 in a model of LPS-induced lung inflammation. We found that PAR-2-deficient mice had significantly less KC expression in bronchial lavage fluid compared with wild-type mice but there was no difference in MIP-2 or TNF-α expression. We also found that isolated alveolar and resident peritoneal macrophages lacking PAR-2 showed a similar deficit in KC after LPS stimulation without differences in MIP-2 or TNF-α. Infiltration of neutrophils and macrophages into the lung following LPS administration was not affected by an absence of PAR-2. Our results support the notion that PAR-2 plays a role in LPS activation of TLR4 signaling in macrophages. PMID:22175012

Effect of PAR-2 Deficiency in Mice on KC Expression after Intratracheal LPS Administration.

PubMed

Williams, Julie C; Lee, Rebecca D; Doerschuk, Claire M; Mackman, Nigel

2011-01-01

Protease activated receptors (PAR) have been shown to play a role in inflammation. PAR-2 is expressed by numerous cells in the lung and has either proinflammatory, anti-inflammatory, or no effect depending on the model. Here, we examined the role of PAR-2 in a model of LPS-induced lung inflammation. We found that PAR-2-deficient mice had significantly less KC expression in bronchial lavage fluid compared with wild-type mice but there was no difference in MIP-2 or TNF-α expression. We also found that isolated alveolar and resident peritoneal macrophages lacking PAR-2 showed a similar deficit in KC after LPS stimulation without differences in MIP-2 or TNF-α. Infiltration of neutrophils and macrophages into the lung following LPS administration was not affected by an absence of PAR-2. Our results support the notion that PAR-2 plays a role in LPS activation of TLR4 signaling in macrophages.

BOREAS RSS-10 TOMS Circumpolar One-Degree PAR Images

NASA Technical Reports Server (NTRS)

Dye, Dennis G.; Holben, Brent; Nickeson, Jaime (Editor); Hall, Forrest G. (Editor); Smith, David E. (Technical Monitor)

2000-01-01

The Boreal Ecosystem-Atmosphere Study (BOREAS) Remote Sensing Science (RSS)-10 team investigated the magnitude of daily, seasonal, and yearly variations of Photosynthetically Active Radiation (PAR) from ground and satellite observations. This data set contains satellite estimates of surface-incident PAR (400-700 nm, MJ/sq m) at one-degree spatial resolution. The spatial coverage is circumpolar from latitudes of 41 to 66 degrees north. The temporal coverage is from May through September for years 1979 through 1989. Eleven-year statistics are also provided: (1) mean, (2) standard deviation, and (3) coefficient of variation for 1979-89. The PAR estimates were derived from the global gridded ultraviolet reflectivity data product (average of 360, 380 nm) from the Nimbus-7 Total Ozone Mapping Spectrometer (TOMS). Image mask data are provided for identifying the boreal forest zone, and ocean/land and snow/ice-covered areas. The data are available as binary image format data files. The PAR data are available from the Earth Observing System Data and Information System (EOSDIS) Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC). The data files are available on a CD-ROM (see document number 20010000884).

The correlation between effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) with renal scintigraphy 99mTc-DTPA study

NASA Astrophysics Data System (ADS)

Ratnasari, D.; Nazir, F.; Toresano, L. O. H. Z.; Pawiro, S. A.; Soejoko, D. S.

2016-03-01

The prevalence of chronic renal diseases in Indonesia has an increasing annual trend, because it is frequently unrecognized and often co-exists with other disease. GFR and ERPF are parameters currently utilized to estimate renal function at routine renal scintigraphy 99m-Tc DTPA study. This study used 99m-Tc DTPA to measure GFR and ERPF. The purpose of this study was to find the correlation between ERPF and GFR, for ERPF analysis with Schlegel's method, and GFR analysis with Gate's method, as well as to find correction factor between both variables. Analysis of renal scintigraphy has been performed at Department of Nuclear Medicine Pertamina Center Hospital to thirty patient images acquired from 2014 to 2015 which were analyzed retrospectively data, using gamma camera dual head with counting method from renal scintigraphy 99m-Tc DTPA study. The calculation was executed by means of both display and manual calculation. Pearson's statistical analysis resulted on Positive Correlation for all data, with ERPF and GFR (display) showing Strongly Positive Correlation (r = 0.82; p- value < 0.05). Standard deviation was found to be 27.58 and 107.64 for GFR and ERPF (display), respectively. Our result indicated that the use of 99mTc-DTPA measure ERPF was not recommended.

Étude comparative des techniques d'analyse par fluorescence X à dispersion d'énergie (ED-XRF) et à dispersion de longueur d'onde (WD-XRF), et par spectrométrie d'émission atomique à source plasma couplée par induction (ICP-AES)

NASA Astrophysics Data System (ADS)

Rahmani, A.; Benyaïch, F.; Bounakhla, M.; Bilal, E.; Moutte, J.; Gruffat, J. J.; Zahry, F.

2004-11-01

Dans ce travail, nous présentons une étude comparative des techniques d'analyse par fluorescence X à dispersion d'énergie (ED-XRF) et à dispersion de longueur d'onde (WD-XRF), et par spectrométrie d'émission atomique à source plasma couplée par induction (ICP-AES). Les résultats de la calibration des spectromètres à dispersion d'énergie, à excitation par sources radioactives (55Fe, 109Cd et 241Am) et à excitation secondaire (cible secondaire Mo et Cu) du Centre National pour l'Energie, les Sciences et les Techniques Nucléaires (CNESTEN, Rabat, Maroc) sur des échantillons étalons de références de l'Agence International de l'Energie Atomique (AIEA) et du Community Bureau of Référence (BCR) ont été comparés aux résultats d'analyse des mêmes échantillons étalons par la spectrométrie X à dispersion de longueur d'onde (WD-XRF) et par spectrométrie d'émission atomique à source plasma couplé par induction (ICP-AES) au département GENERIC du centre SPIN à l'Ecole des Mines de Saint-Etienne (France). Les trois techniques d'analyse utilisées donnent des résultats comparables pour le dosage des éléments majeurs, alors que pour les traces on note des déviations importantes à cause des effets de matrice qui sont difficiles à corriger dans le cas de la fluorescence X.

PAR-2 triggers placenta-derived protease-induced altered VE-cadherin reorganization at endothelial junctions in preeclampsia.

PubMed

Gu, Y; Groome, L J; Alexander, J S; Wang, Y

2012-10-01

PAR-2 is a G-protein coupled protease receptor whose activation in endothelial cells (ECs) is associated with increased solute permeability. VE-cadherin is an endothelial-specific junction protein, which exhibits a disorganized distribution at cell junction during inflammation and is a useful indicator of endothelial barrier dysfunction. In the present study, we tested the hypothesis that PAR-2 activation mediates placenta-derived chymotrypsin-like protease (CLP)-induced endothelial junction disturbance and permeability in preeclampsia (PE). PAR-2 and VE-cadherin were examined by immunofluorescent staining. Specific CLP induced PAR-2 activation and altered VE-cadherin distribution was assessed following depletion of protease chymotrypsin in the placental conditioned medium and after PAR-2 siRNA. VE-cadherin assembly was determined by treating cells with protease chymotrypsin and/or the specific PAR-2 agonist SLIGKV-NH2. Our results showed: 1) placental conditioned medium not only disturbed VE-cadherin distribution at cell junctions but also activated PAR-2 in ECs; 2) PAR-2 siRNA blocked the placental conditioned medium induced PAR-2 upregulation and disorganization of VE-cadherin at cell junctions; 3) PAR-2 agonist induced PAR-2 activation and VE-cadherin reorganization were dose-dependent; and 4) PAR-2 agonist could stimulate ERK1/2 activation. These results strongly suggest that proteases produced by the placenta elicit endothelial barrier dysfunction via a PAR-2 signaling regulatory mechanism in PE. Copyright © 2012 Elsevier Ltd. All rights reserved.

PAR-2 triggers placenta-derived protease-induced altered VE-cadherin reorganization at endothelial junctions in preeclampsia

PubMed Central

Gu, Yang; Groome, Lynn J.; Alexander, J. Steven; Wang, Yuping

2014-01-01

PAR-2 is a G-protein coupled protease receptor whose activation in endothelial cells (ECs) is associated with increased solute permeability. VE-cadherin is an endothelial specific junction protein, which exhibits a disorganized distribution at cell junction during inflammation and is a useful indicator of endothelial barrier dysfunction. In the present study, we tested the hypothesis that PAR-2 activation mediates placenta-derived chymotrypsin-like protease (CLP)-induced endothelial junction disturbance and permeability in preeclampsia (PE). PAR-2 and VE-cadherin were examined by immunofluorescent staining. Specific CLP-induced PAR-2 activation and altered VE-cadherin distribution was assessed following depletion of protease chymotrypsin in the placental conditioned medium and after PAR-2 siRNA. VE-cadherin assembly was determined by treating cells with protease chymotrypsin and/or the specific PAR-2 agonist SLIGKV-NH2. Our results showed: 1) placental conditioned medium not only disturbed VE-cadherin distribution at cell junctions but also activated PAR-2 in ECs; 2) PAR-2 siRNA blocked the placental conditioned medium induced PAR-2 upregulation and disorganization of VE-cadherin at cell junctions; 3) PAR-2 agonist induced PAR-2 activation and VE-cadherin reorganization were dose-dependent; and 4) PAR-2 agonist could stimulate ERK1/2 activation. These results strongly suggest that proteases produced by the placenta elicit endothelial barrier dysfunction via a PAR-2 signaling regulatory mechanism in PE. PMID:22840244

Is There an "F" in Your PAR? Understanding, Teaching and Doing Action Research

ERIC Educational Resources Information Center

Lorenzetti, Liza; Walsh, Christine Ann

2014-01-01

Participatory Action Research (PAR) is increasingly recognized within academic research and pedagogy. What are the benefits of including feminism within participatory action research and teaching? In responding to this question, we discuss the similarities and salient differences between PAR and feminist informed PAR (FPAR). There are eight themes…

Diffuse Thyroid Metastasis From Lung Cancer Mimicking Thyroiditis on 99mTc-Pertechnetate Scintigraphy.

PubMed

Gao, Rui; Gao, Shan; Feng, Jinteng; Wang, Yuanbo; Zhang, Guangjian

2017-09-01

Possible thyroiditis was suspected in a 56-year-old man who initially presented sore throat because laboratory examinations revealed decreased serum thyroid hormone and the Tc-pertechnetate scintigraphy showed no tracer uptake by the thyroid gland. However, subsequent examination demonstrated that the absence of pertechnetate activity in the thyroid was due to complete replacement of thyroid gland by the metastasis from lung adenocarcinoma, which was unknown at the initial presentation.

An introduction to Na(18)F bone scintigraphy: basic principles, advanced imaging concepts, and case examples.

PubMed

Bridges, Robert L; Wiley, Chris R; Christian, John C; Strohm, Adam P

2007-06-01

Na(18)F, an early bone scintigraphy agent, is poised to reenter mainstream clinical imaging with the present generations of stand-alone PET and PET/CT hybrid scanners. (18)F PET scans promise improved imaging quality for both benign and malignant bone disease, with significantly improved sensitivity and specificity over conventional planar and SPECT bone scans. In this article, basic acquisition information will be presented along with examples of studies related to oncology, sports medicine, and general orthopedics. The use of image fusion of PET bone scans with CT and MRI will be demonstrated. The objectives of this article are to provide the reader with an understanding of the history of early bone scintigraphy in relation to Na(18)F scanning, a familiarity with basic imaging techniques for PET bone scanning, an appreciation of the extent of disease processes that can be imaged with PET bone scanning, an appreciation for the added value of multimodality image fusion with bone disease, and a recognition of the potential role PET bone scanning may play in clinical imaging.

Par-4-mediated recruitment of Amida to the actin cytoskeleton leads to the induction of apoptosis

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

Boosen, Meike; Vetterkind, Susanne; Koplin, Ansgar

Par-4 (prostate apoptosis response-4) sensitizes cells to apoptotic stimuli, but the exact mechanisms are still poorly understood. Using Par-4 as bait in a yeast two-hybrid screen, we identified Amida as a novel interaction partner, a ubiquitously expressed protein which has been suggested to be involved in apoptotic processes. Complex formation of Par-4 and Amida occurs in vitro and in vivo and is mediated via the C-termini of both proteins, involving the leucine zipper of Par-4. Amida resides mainly in the nucleus but displays nucleo-cytoplasmic shuttling in heterokaryons. Upon coexpression with Par-4 in REF52.2 cells, Amida translocates to the cytoplasm andmore » is recruited to actin filaments by Par-4, resulting in enhanced induction of apoptosis. The synergistic effect of Amida/Par-4 complexes on the induction of apoptosis is abrogated when either Amida/Par-4 complex formation or association of these complexes with the actin cytoskeleton is impaired, indicating that the Par-4-mediated relocation of Amida to the actin cytoskeleton is crucial for the pro-apoptotic function of Par-4/Amida complexes in REF52.2 cells. The latter results in enhanced phosphorylation of the regulatory light chain of myosin II (MLC) as has previously been shown for Par-4-mediated recruitment of DAP-like kinase (Dlk), suggesting that the recruitment of nuclear proteins involved in the regulation of apoptotic processes to the actin filament system by Par-4 represents a potent mechanism how Par-4 can trigger apoptosis.« less

Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis

PubMed Central

Wang, Xiangcheng; Zhao, Zhenfang; Wang, Tao; Wang, Xuemei; Li, Xiao-Feng

2017-01-01

Objectives: To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Methods: Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Results: Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Conclusions: Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management. PMID:27992368

Variable uptake feature of focal nodular hyperplasia in Tc-99m phytate hepatic scintigraphy/single-photon emission computed tomography-A parametric analysis.

PubMed

Hsu, Yu-Ling; Chen, Yu-Wen; Lin, Chia-Yang; Lai, Yun-Chang; Chen, Shinn-Cherng; Lin, Zu-Yau

2015-12-01

Tc-99m phytate hepatic scintigraphy remains the standard method for evaluating the functional features of Kupffer cells. In this study, we demonstrate the variable uptake feature of focal nodular hyperplasia (FNH) in Tc-99m phytate scintigraphy. We reviewed all patients who underwent Tc-99m phytate hepatic scintigraphy between 2008 and 2012 in Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Cases with FNH were diagnosed on the basis of pathology or at least one or more prior imaging with a periodic clinical follow-up. All patients received a standard protocol of dynamic flow study and planar and Tc-99m phytate single-photon emission computed tomography (E. CAM; Siemens). The correlation of variable nodular radioactivity with parameters such as tumor size and localization was analyzed. In total, 15 lesions of 14 patients in the clinic were diagnosed as FNH. The tumor size was approximately 2.9-7.4 cm (mean size 4.6 cm). Four lesions were larger than 5 cm. The major anatomic distribution was in the right hepatic lobe (10 lesions), particularly in the superior segments (7 lesions). Tc-99m phytate single-photon emission computed tomography imaging for determining the functional features of Kupffer cells included cool/cold (8 lesions), isoradioactive/warm (6 lesions), and hot (1 lesion) patterns of uptake. We did not observe any statistically significant correlation between variable nodular radioactivity and tumor size (p=0.68) or localization (p=0.04). Herein, we demonstrate the variable uptake feature of FNH in Tc-99m phytate scintigraphy. In small FNH tumors (< 5 cm), increased or equal uptake still provided specificity for the differential diagnosis of hepatic solid tumors. Copyright © 2015. Published by Elsevier Taiwan.

An Experimental Comparison of Two Different Technetium Source Activities Which Can Imitate Thyroid Scintigraphy in Case of Thyroid Toxic Nodule

PubMed Central

Miftari, Ramë; Fejza, Ferki; Bicaj, Xhavit; Nura, Adem; Topciu, Valdete; Bajrami, Ismet

2014-01-01

Purpose: In cases of thyroid toxic autonomous nodule, anterior projection of Tc-99m pertechnetate image shows a hot nodule that occupies most, or the entire thyroid lobe with near-total or total suppression of the contra lateral lobe. In this case is very difficult to distinguish toxic nodule from lobe agenesis. Our interest was to estimate and determinate the rate of radioactivity when the source with high activity can make total suppression of the second source with low activity in same conditions with thyroid scintigraphy procedures. Material and methodology: Thyroid scintigraphy was performed with Technetium 99 meta stable pertechnetate. A parallel high resolution low energy collimator was used as an energy setting of 140 KeV photo peak for T-99m. Images are acquired at 200 Kilo Counts in the anterior projection with the collimator positioned as close as the patient’s extended neck (approximately in distance of 18 cm). The scintigraphy of thyroid gland was performed 15 minutes after intravenous administration of 1.5 mCi Tc-99m pertechnetate. Technetium 99 meta stable radioactive sources with different activity were used for two scintigraphies studies, performed in same thyroid scintigraphy acquisition procedures. In the first study, were compared the standard source with high activity A=11.2 mCi with sources with variable activities B=1.33 mCi; 1.03 mCi; 0.7 mCi; 0.36 mCi; and 0.16mCi) in distance of 1.5cm from each other sources, which is approximately same with distance between two thyroid lobes. In the second study were compared the sources with low activity in proportion 70:1(source A = 1.5 mCi and source B=0.021mCi). As clinical studies we preferred two different patents with different thyroid disorders. There were one patient with thyroid toxic nodule in the right lobe, therefore the second patient was with left thyroid nodule agenesis. Results: During our examination, we accurately determined that two radioactive sources in proportion 70:1 will be

mTORC2 activation is regulated by the urokinase receptor (uPAR) in bladder cancer.

PubMed

Hau, Andrew M; Leivo, Mariah Z; Gilder, Andrew S; Hu, Jing-Jing; Gonias, Steven L; Hansel, Donna E

2017-01-01

Mammalian target of rapamycin complex 2 (mTORC2) has been identified as a major regulator of bladder cancer cell migration and invasion. Upstream pathways that mediate mTORC2 activation remain poorly defined. Urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored membrane protein and known activator of cell-signaling. We identified increased uPAR expression in 94% of invasive human bladder cancers and in 54-71% of non-invasive bladder cancers, depending on grade. Normal urothelium was uPAR-immunonegative. Analysis of publicly available datasets identified uPAR gene amplification or mRNA upregulation in a subset of bladder cancer patients with reduced overall survival. Using biochemical approaches, we showed that uPAR activates mTORC2 in bladder cancer cells. Highly invasive bladder cancer cell lines, including T24, J82 and UM-UC-3 cells, showed increased uPAR mRNA expression and protein levels compared with the less aggressive cell lines, UROtsa and RT4. uPAR gene-silencing significantly reduced phosphorylation of Serine-473 in Akt, an mTORC2 target. uPAR gene-silencing also reduced bladder cancer cell migration and Matrigel invasion. S473 phosphorylation was observed by immunohistochemistry in human bladder cancers only when the tumors expressed high levels of uPAR. S473 phosphorylation was not controlled by uPAR in bladder cancer cell lines that are PTEN-negative; however, this result probably did not reflect altered mTORC2 regulation. Instead, PTEN deficiency de-repressed alternative kinases that phosphorylate S473. Our results suggest that uPAR and mTORC2 are components of a single cell-signaling pathway. Targeting uPAR or mTORC2 may be beneficial in patients with bladder cancer. Copyright © 2016. Published by Elsevier Inc.

Tryptase activates isolated adult cardiac fibroblasts via protease activated receptor-2 (PAR-2).

PubMed

Murray, David B; McLarty-Williams, Jennifer; Nagalla, Krishna T; Janicki, Joseph S

2012-03-01

Protease activated receptor-2 (PAR-2) derived cycloxygenase-2 (COX-2) was recently implicated in a cardiac mast cell and fibroblast cross-talk signaling cascade mediating myocardial remodeling secondary to mechanical stress. We designed this study to investigate in vitro assays of isolated adult cardiac fibroblasts to determine whether binding of tryptase to the PAR-2 receptor on cardiac fibroblasts will lead to increased expression of COX-2 and subsequent formation of the arachodonic acid metabolite 15-d-Prostaglandin J(2) (15-d-PGJ(2)). The effects of tryptase (100 mU) and co-incubation with PAR-2 inhibitor peptide sequence FSLLRY-NH(2) (10(-6)M) on proliferation, hydroxyproline concentration, 15-d-PGJ(2) formation and PAR-2/COX-2 expression were investigated in fibroblasts isolated from 9 week old SD rats. Tryptase induced a significant increase in fibroproliferation, hydroxyproline, 15-d-PGJ(2) formation and PAR-2 expression which were markedly attenuated by FSLLRY. Tryptase-induced changes in cardiac fibroblast function utilize a PAR-2 dependent mechanism.

Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions

PubMed Central

Cunningham, Orla; Andolfo, Annapaola; Santovito, Maria Lisa; Iuzzolino, Lucia; Blasi, Francesco; Sidenius, Nicolai

2003-01-01

The urokinase-type plasminogen activator receptor (uPAR/CD87) is a glycosylphosphatidylinositol-anchored membrane protein with multiple functions in extracellular proteolysis, cell adhesion, cell migration and proliferation. We now report that cell surface uPAR dimerizes and that dimeric uPAR partitions preferentially to detergent-resistant lipid rafts. Dimerization of uPAR did not require raft partitioning as the lowering of membrane cholesterol failed to reduce dimerization and as a transmembrane uPAR chimera, which does not partition to lipid rafts, also dimerized efficiently. While uPA bound to uPAR independently of its membrane localization and dimerization status, uPA-induced uPAR cleavage was strongly accelerated in lipid rafts. In contrast to uPA, the binding of Vn occurred preferentially to raft- associated dimeric uPAR and was completely blocked by cholesterol depletion. PMID:14609946

The Role of PAR2 in TGF-β1-Induced ERK Activation and Cell Motility

PubMed Central

Ungefroren, Hendrik; Witte, David; Fiedler, Christian; Gädeken, Thomas; Kaufmann, Roland; Lehnert, Hendrik

2017-01-01

Background: Recently, the expression of proteinase-activated receptor 2 (PAR2) has been shown to be essential for activin receptor-like kinase 5 (ALK5)/SMAD-mediated signaling and cell migration by transforming growth factor (TGF)-β1. However, it is not known whether activation of non-SMAD TGF-β signaling (e.g., RAS–RAF–MEK–extracellular signal-regulated kinase (ERK) signaling) is required for cell migration and whether it is also dependent on PAR2. Methods: RNA interference was used to deplete cells of PAR2, followed by xCELLigence technology to measure cell migration, phospho-immunoblotting to assess ERK1/2 activation, and co-immunoprecipitation to detect a PAR2–ALK5 physical interaction. Results: Inhibition of ERK signaling with the MEK inhibitor U0126 blunted the ability of TGF-β1 to induce migration in pancreatic cancer Panc1 cells. ERK activation in response to PAR2 agonistic peptide (PAR2–AP) was strong and rapid, while it was moderate and delayed in response to TGF-β1. Basal and TGF-β1-dependent ERK, but not SMAD activation, was blocked by U0126 in Panc1 and other cell types indicating that ERK activation is downstream or independent of SMAD signaling. Moreover, cellular depletion of PAR2 in HaCaT cells strongly inhibited TGF-β1-induced ERK activation, while the biased PAR2 agonist GB88 at 10 and 100 µM potentiated TGF-β1-dependent ERK activation and cell migration. Finally, we provide evidence for a physical interaction between PAR2 and ALK5. Our data show that both PAR2–AP- and TGF-β1-induced cell migration depend on ERK activation, that PAR2 expression is crucial for TGF-β1-induced ERK activation, and that the functional cooperation of PAR2 and TGF-β1 involves a physical interaction between PAR2 and ALK5. PMID:29261154

The intracellular carboxyl tail of the PAR-2 receptor controls intracellular signaling and cell death.

PubMed

Zhu, Zhihui; Stricker, Rolf; Li, Rong yu; Zündorf, Gregor; Reiser, Georg

2015-03-01

The protease-activated receptors are a group of unique G protein-coupled receptors, including PAR-1, PAR-2, PAR-3 and PAR-4. PAR-2 is activated by multiple trypsin-like serine proteases, including trypsin, tryptase and coagulation proteases. The clusters of phosphorylation sites in the PAR-2 carboxyl tail are suggested to be important for the binding of adaptor proteins to initiate intracellular signaling to Ca(2+) and mitogen-activated protein kinases. To explore the functional role of PAR-2 carboxyl tail in controlling intracellular Ca(2+), ERK and AKT signaling, a series of truncated mutants containing different clusters of serines/threonines were generated and expressed in HEK293 cells. Firstly, we observed that lack of the complete C-terminus of PAR-2 in a mutated receptor gave a relatively low level of localization on the cell plasma membrane. Secondly, the shortened carboxyl tail containing 13 amino acids was sufficient for receptor internalization. Thirdly, the cells expressing truncation mutants showed deficits in their capacity to couple to intracellular Ca(2+) and ERK and AKT signaling upon trypsin challenge. In addition, HEK293 cells carrying different PAR-2 truncation mutants displayed decreased levels of cell survival after long-lasting trypsin stimulation. In summary, the PAR-2 carboxyl tail was found to control the receptor localization, internalization, intracellular Ca(2+) responses and signaling to ERK and AKT. The latter can be considered to be important for cell death control.

PAR-2 mediates increased inflammatory cell adhesion and neointima formation following vascular injury in the mouse.

PubMed

Tennant, Gail M; Wadsworth, Roger M; Kennedy, Simon

2008-05-01

Activation of PAR-2 in the vasculature affects vascular tone and adhesion of leukocytes to the endothelium. Since adhesion of leukocytes is increased following vascular injury and is important in determining the extent of neointima formation, we hypothesised that mice lacking PAR-2 may have reduced neointima formation following vascular injury. PAR-2 activating peptides and trypsin induced endothelium-dependent relaxation of mouse carotid artery which was absent in the knockout mouse. Lack of a PAR-2 receptor did not affect lymphocyte adhesion under basal conditions, but reduced the contractile response produced by lymphocytes. Twenty-eight days after denuding injury, vessel contraction to lymphocytes was reduced in both strains while lymphocyte adhesion was significantly greater in PAR-2(+/+) mice compared to the PAR-2 knockout mice. Neointimal area was markedly reduced in the PAR-2 knockout mouse. Our data show that PAR-2 modulates inflammatory cell adhesion when stimulated and in mice lacking the PAR-2 receptor, adhesion to injured vessels is reduced with a consequent reduction in neointima formation.

The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb.

PubMed

Sun, Miao; Asghar, Suwaiba Z; Zhang, Huaye

2016-09-01

The processing of amyloid precursor protein (APP) into β-amyloid peptide (Aβ) is a key step in the pathogenesis of Alzheimer's disease (AD), and trafficking dysregulations of APP and its secretases contribute significantly to altered APP processing. Here we show that the cell polarity protein Par3 plays an important role in APP processing and trafficking. We found that the expression of full length Par3 is significantly decreased in AD patients. Overexpression of Par3 promotes non-amyloidogenic APP processing, while depletion of Par3 induces intracellular accumulation of Aβ. We further show that Par3 functions by regulating APP trafficking. Loss of Par3 decreases surface expression of APP by targeting APP to the late endosome/lysosome pathway. Finally, we show that the effects of Par3 are mediated through the endocytic adaptor protein Numb, and Par3 functions by interfering with the interaction between Numb and APP. Together, our studies show a novel role for Par3 in regulating APP processing and trafficking. Copyright © 2016 Elsevier Inc. All rights reserved.

Proteolytic Activation of the Protease-activated Receptor (PAR)-2 by the Glycosylphosphatidylinositol-anchored Serine Protease Testisin*

PubMed Central

Driesbaugh, Kathryn H.; Buzza, Marguerite S.; Martin, Erik W.; Conway, Gregory D.; Kao, Joseph P. Y.; Antalis, Toni M.

2015-01-01

Protease-activated receptors (PARs) are a family of seven-transmembrane, G-protein-coupled receptors that are activated by multiple serine proteases through specific N-terminal proteolytic cleavage and the unmasking of a tethered ligand. The majority of PAR-activating proteases described to date are soluble proteases that are active during injury, coagulation, and inflammation. Less investigation, however, has focused on the potential for membrane-anchored serine proteases to regulate PAR activation. Testisin is a unique trypsin-like serine protease that is tethered to the extracellular membrane of cells through a glycophosphatidylinositol (GPI) anchor. Here, we show that the N-terminal domain of PAR-2 is a substrate for testisin and that proteolytic cleavage of PAR-2 by recombinant testisin activates downstream signaling pathways, including intracellular Ca2+ mobilization and ERK1/2 phosphorylation. When testisin and PAR-2 are co-expressed in HeLa cells, GPI-anchored testisin specifically releases the PAR-2 tethered ligand. Conversely, knockdown of endogenous testisin in NCI/ADR-Res ovarian tumor cells reduces PAR-2 N-terminal proteolytic cleavage. The cleavage of PAR-2 by testisin induces activation of the intracellular serum-response element and NFκB signaling pathways and the induction of IL-8 and IL-6 cytokine gene expression. Furthermore, the activation of PAR-2 by testisin results in the loss and internalization of PAR-2 from the cell surface. This study reveals a new biological substrate for testisin and is the first demonstration of the activation of a PAR by a serine protease GPI-linked to the cell surface. PMID:25519908

[Ambroise Paré in French literature].

PubMed

Dumaitre, P

1995-01-01

The 16th century by its passionate side has been the favourite one of authors of historical novels in which among the heroes of "cloak and dagger stories" appears sometime Ambroise Paré. Alexandre Dumas (the father) has shown him at the court of Charles IX in La Reine Margot (1845) where he does not however play a great role. On the contrary, Balzac in Le Martyr calviniste (1842) has given him a capital part close to the dying François II, whom he intended to trepanize but had to give up this idea as a consequence of the opposition of the queen-mother Catherine de Médicis. In the present century, Robert Merle in Paris ma bonne ville (Fortune de France, 3, 1980) shows Paré at the time of the Saint Barthélemy.

Comparative evaluation of intragastric bile acids and hepatobiliary scintigraphy in the diagnosis of duodenogastric reflux.

PubMed

Chen, Teng-Fei; Yadav, Praveen K; Wu, Rui-Jin; Yu, Wei-Hua; Liu, Chang-Qin; Lin, Hui; Liu, Zhan-Ju

2013-01-01

To assess the diagnostic value of a combination of intragastric bile acids and hepatobiliary scintigraphy in the detection of duodenogastric reflux (DGR). The study contained 99 patients with DGR and 70 healthy volunteers who made up the control group. The diagnosis was based on the combination of several objective arguments: a long history of gastric symptoms (i.e., nausea, epigastric pain, and/or bilious vomiting) poorly responsive to medical treatment, gastroesophageal reflux symptoms unresponsive to proton-pump inhibitors, gastritis on upper gastrointestinal (GI) endoscopy and/or at histology, presence of a bilious gastric lake at > 1 upper GI endoscopy, pathologic 24-h intragastric bile monitoring with the Bilitec device. Gastric juice was aspirated in the GI endoscopy and total bile acid (TBA), total bilirubin (TBIL) and direct bilirubin (DBIL) were tested in the clinical laboratory. Continuous data of gastric juice were compared between each group using the independent-samples Mann-Whitney U-test and their relationship was analysed by Spearman's rank correlation test and Fisher's linear discriminant analysis. Histopathology of DGR patients and 23 patients with chronic atrophic gastritis was compared by clinical pathologists. Using the Independent-samples Mann-Whitney U-test, DGR index (DGRi) was calculated in 28 patients of DGR group and 19 persons of control group who were subjected to hepatobiliary scintigraphy. Receiver operating characteristic curve was made to determine the sensitivity and specificity of these two methods in the diagnosis of DGR. The group of patients with DGR showed a statistically higher prevalence of epigastric pain in comparison with control group. There was no significant difference between the histology of gastric mucosa with atrophic gastritis and duodenogastric reflux. The bile acid levels of DGR patients were significantly higher than the control values (Z: TBA: -8.916, DBIL: -3.914, TBIL: -6.197, all P < 0.001). Two of three

Comparative evaluation of intragastric bile acids and hepatobiliary scintigraphy in the diagnosis of duodenogastric reflux

PubMed Central

Chen, Teng-Fei; Yadav, Praveen K; Wu, Rui-Jin; Yu, Wei-Hua; Liu, Chang-Qin; Lin, Hui; Liu, Zhan-Ju

2013-01-01

AIM: To assess the diagnostic value of a combination of intragastric bile acids and hepatobiliary scintigraphy in the detection of duodenogastric reflux (DGR). METHODS: The study contained 99 patients with DGR and 70 healthy volunteers who made up the control group. The diagnosis was based on the combination of several objective arguments: a long history of gastric symptoms (i.e., nausea, epigastric pain, and/or bilious vomiting) poorly responsive to medical treatment, gastroesophageal reflux symptoms unresponsive to proton-pump inhibitors, gastritis on upper gastrointestinal (GI) endoscopy and/or at histology, presence of a bilious gastric lake at > 1 upper GI endoscopy, pathologic 24-h intragastric bile monitoring with the Bilitec device. Gastric juice was aspirated in the GI endoscopy and total bile acid (TBA), total bilirubin (TBIL) and direct bilirubin (DBIL) were tested in the clinical laboratory. Continuous data of gastric juice were compared between each group using the independent-samples Mann-Whitney U-test and their relationship was analysed by Spearman’s rank correlation test and Fisher’s linear discriminant analysis. Histopathology of DGR patients and 23 patients with chronic atrophic gastritis was compared by clinical pathologists. Using the Independent-samples Mann-Whitney U-test, DGR index (DGRi) was calculated in 28 patients of DGR group and 19 persons of control group who were subjected to hepatobiliary scintigraphy. Receiver operating characteristic curve was made to determine the sensitivity and specificity of these two methods in the diagnosis of DGR. RESULTS: The group of patients with DGR showed a statistically higher prevalence of epigastric pain in comparison with control group. There was no significant difference between the histology of gastric mucosa with atrophic gastritis and duodenogastric reflux. The bile acid levels of DGR patients were significantly higher than the control values (Z: TBA: -8.916, DBIL: -3.914, TBIL: -6.197, all

Removal of focal segmental glomerulosclerosis (FSGS) factor suPAR using CytoSorb.

PubMed

Schenk, Heiko; Müller-Deile, Janina; Schmitt, Roland; Bräsen, Jan Hinrich; Haller, Hermann; Schiffer, Mario

2017-12-01

Treatment of primary focal segmental glomerulosclerosis (FSGS) and its recurrence after kidney transplantation associated with rapid deterioration of kidney function remains to be challenging despite advances in immunosuppressive therapy. The presence of circulating factors has been postulated to be a pivotal player in the pathogenesis of FSGS, although suPAR and CLCF-1 have been identified as the most promising causative factors. The potential therapeutic effect of suPAR elimination in an FSGS patient using CytoSorb, a hemoadsorption device that gained attention in the cytokine elimination in septic patients, was studied. Efficiency of total plasma exchange to remove suPAR was determined. CytoSorb hemoadsorption caused a 27.33% reduction of the suPAR level in a single treatment, whereas total plasma exchange showed a suPAR level reduction of 25.12% (n = 3; 95% confidence interval, 0.2777-0.8090; P < 0.01), which may indicate therapeutic potential in the treatment of primary FSGS and its recurrence in a kidney transplant. © 2017 Wiley Periodicals, Inc.

Iodine-123 metaiodobenzylguanidine scintigraphy and iodine-123 ioflupane single photon emission computed tomography in Lewy body diseases: complementary or alternative techniques?

PubMed

Treglia, Giorgio; Cason, Ernesto; Cortelli, Pietro; Gabellini, Anna; Liguori, Rocco; Bagnato, Antonio; Giordano, Alessandro; Fagioli, Giorgio

2014-01-01

To compare myocardial sympathetic imaging using (123)I-Metaiodobenzylguanidine (MIBG) scintigraphy and striatal dopaminergic imaging using (123)I-Ioflupane (FP-CIT) single photon emission computed tomography (SPECT) in patients with suspected Lewy body diseases (LBD). Ninety-nine patients who performed both methods within 2 months for differential diagnosis between Parkinson's disease (PD) and other parkinsonism (n = 68) or between dementia with Lewy bodies (DLB) and other dementia (n = 31) were enrolled. Sensitivity, specificity, accuracy, positive and negative predictive values of both methods were calculated. For (123) I-MIBG scintigraphy, the overall sensitivity, specificity, accuracy, positive and negative predictive values in LBD were 83%, 79%, 82%, 86%, and 76%, respectively. For (123)I-FP-CIT SPECT, the overall sensitivity, specificity, accuracy, positive and negative predictive values in LBD were 93%, 41%, 73%, 71%, and 80%, respectively. There was a statistically significant difference between these two methods in patients without LBD, but not in patients with LBD. LBD usually present both myocardial sympathetic and striatal dopaminergic impairments. (123)I-FP-CIT SPECT presents high sensitivity in the diagnosis of LBD; (123)I-MIBG scintigraphy may have a complementary role in differential diagnosis between PD and other parkinsonism. These scintigraphic methods showed similar diagnostic accuracy in differential diagnosis between DLB and other dementia. Copyright © 2012 by the American Society of Neuroimaging.

Tryptase - PAR2 axis in Experimental Autoimmune Prostatitis, a model for Chronic Pelvic Pain Syndrome

PubMed Central

Roman, Kenny; Done, Joseph D.; Schaeffer, Anthony J.; Murphy, Stephen F.; Thumbikat, Praveen

2014-01-01

Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) affects up to 15% of the male population and is characterized by pelvic pain. Mast cells are implicated in the murine experimental autoimmune prostatitis (EAP) model as key to chronic pelvic pain development. The mast cell mediator tryptase-β and its cognate receptor protease-activated receptor 2 (PAR2) are involved in mediating pain in other visceral disease models. Prostatic secretions and urines from CP/CPPS patients were examined for the presence of mast cell degranulation products. Tryptase-β and PAR2 expression were examined in murine experimental autoimmune prostatitis (EAP). Pelvic pain and inflammation were assessed in the presence or absence of PAR2 expression and upon PAR2 neutralization. Tryptase-β and carboxypeptidase A3 were elevated in CP/CPPS compared to healthy volunteers. Tryptase-β was capable of inducing pelvic pain and was increased in EAP along with its receptor PAR2. PAR2 was required for the development of chronic pelvic pain in EAP. PAR2 signaling in dorsal root ganglia lead to ERK1/2 phosphorylation and calcium influx. PAR2 neutralization using antibodies attenuated chronic pelvic pain in EAP. The tryptase-PAR2 axis is an important mediator of pelvic pain in EAP and may play a role in the pathogenesis of CP/CPPS. PMID:24726923

Discovery of potent peptide-mimetic antagonists for the human thrombin receptor, protease-activated receptor-1 (PAR-1).

PubMed

Maryanoff, Bruce E; Zhang, Han-Cheng; Andrade-Gordon, Patricia; Derian, Claudia K

2003-03-01

Protease-activated receptors (PARs) represent a unique family of seven-transmembrane G-protein-coupled receptors, which are enzymatically cleaved to expose a new extracellular N-terminus that acts as a tethered activating ligand. PAR-1 is cleaved and activated by the serine protease alpha-thrombin, is expressed in various tissues (e.g. platelets and vascular cells), and is involved in cellular responses associated with hemostasis, proliferation, and tissue injury. By using a de novo design approach, we have discovered a series of potent heterocycle-based peptide-miimetic antagonists of PAR-1, exemplified by advanced leads RWJ-56110 (22) and RWJ-58259 (32). These compounds are potent, selective PAR-1 antagonists, devoid of PAR-1 agonist and thrombin inhibitory activity: they bind to PAR-1, interfere with calcium mobilization and cellular functions associated with PAR-1, and do not affect PAR-2, PAR-3, or PAR-4. RWJ-56110 was determined to be a direct inhibitor of PAR-1 activation and internalization, without affecting PAR-1 N-terminal cleavage. At high concentrations of alpha-thrombin, RWJ-56110 fully blocked activation responses in human vascular cells, but not in human platelets; whereas, at high concentrations of TRAP-6, RWJ-56110 blocked activation responses in both cell types. This result is consistent with the presence of another thrombin receptor on human platelets, namely PAR-4. RWJ-56110 and RWJ-58259 clearly interrupt the binding of a tethered ligand to its receptor. RWJ-58259 demonstrated antirestenotic activity in a rat balloon angioplasty model and antithrombotic activity in a cynomolgus monkey arterial injury model. Such PAR-1 antagonists should not only serve as useful tools to delineate the physiological and pathophysiological roles of PAR-1, but also may have therapeutic potential for treating thrombosis and restenosis in humans.

Examining relational empowerment for elementary school students in a yPAR program.

PubMed

Langhout, Regina Day; Collins, Charles; Ellison, Erin Rose

2014-06-01

This paper joins relational empowerment, youth empowerment, and Bridging Multiple Worlds frameworks to examine forms of relational empowerment for children in two intermediary institutions-school and a youth participatory action research after-school program (yPAR ASP). Participants were twelve children, most of whom were Latina/o and from im/migrant families, enrolled in a yPAR ASP for 2 years. A mixed-method approach was utilized; we analyzed children's interviews, self-defined goals, and their social networks to examine their experiences of relational empowerment. We conclude that children experienced each of the five relational empowerment factors-collaborative competence, bridging social divisions, facilitating others' empowerment, mobilizing networks, and passing on a legacy-in the yPAR ASP setting, and some factors in school. These experiences, however, were more pronounced in the yPAR ASP setting. Additionally, social network analyses revealed that a small but meaningful percentage of actors bridged worlds, especially home and family, but by year 2, also school and the yPAR ASP. Finally, most helpers for school-based goals came from school, but a sizable number came from family, friends, and home worlds, and by year 2, also came from the yPAR ASP. Implications range from theoretical to methodological development, including the use of social network analysis as a tool to descriptively examine relational power in context.

Role of the parCBA Operon of the Broad-Host-Range Plasmid RK2 in Stable Plasmid Maintenance

PubMed Central

Easter, Carla L.; Schwab, Helmut; Helinski, Donald R.

1998-01-01

The par region of the stably maintained broad-host-range plasmid RK2 is organized as two divergent operons, parCBA and parDE, and a cis-acting site. parDE encodes a postsegregational killing system, and parCBA encodes a resolvase (ParA), a nuclease (ParB), and a protein of unknown function (ParC). The present study was undertaken to further delineate the role of the parCBA region in the stable maintenance of RK2 by first introducing precise deletions in the three genes and then assessing the abilities of the different constructs to stabilize RK2 in three strains of Escherichia coli and two strains of Pseudomonas aeruginosa. The intact parCBA operon was effective in stabilizing a conjugation-defective RK2 derivative in E. coli MC1061K and RR1 but was relatively ineffective in E. coli MV10Δlac. In the two strains in which the parCBA operon was effective, deletions in parB, parC, or both parB and parC caused an approximately twofold reduction in the stabilizing ability of the operon, while a deletion in the parA gene resulted in a much greater loss of parCBA activity. For P. aeruginosa PAO1161Rifr, the parCBA operon provided little if any plasmid stability, but for P. aeruginosa PAC452Rifr, the RK2 plasmid was stabilized to a substantial extent by parCBA. With this latter strain, parA and res alone were sufficient for stabilization. The cer resolvase system of plasmid ColE1 and the loxP/Cre system of plasmid P1 were tested in comparison with the parCBA operon. We found that, not unlike what was previously observed with MC1061K, cer failed to stabilize the RK2 plasmid with par deletions in strain MV10Δlac, but this multimer resolution system was effective in stabilizing the plasmid in strain RR1. The loxP/Cre system, on the other hand, was very effective in stabilizing the plasmid in all three E. coli strains. These observations indicate that the parA gene, along with its res site, exhibits a significant level of plasmid stabilization in the absence of the parC and

PAR-2 agonists induce contraction of murine small intestine through neurokinin receptors.

PubMed

Zhao, Aiping; Shea-Donohue, Terez

2003-10-01

Protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor and is expressed throughout the gut. It is well known that PAR-2 participates in the regulation of gastrointestinal motility; however, the results are inconsistent. The present study investigated the effect and mechanism of PAR-2 activation on murine small intestinal smooth muscle function in vitro. Both trypsin and PAR-2-activating peptide SLIGRL induced a small relaxation followed by a concentration-dependent contraction. The sensitivity to trypsin was greater than that to SLIGRL (EC50 = 0.03 vs. 40 microM), but maximal responses were similar (12.3 +/- 1.6 vs. 13.7 +/- 1.3 N/cm2). Trypsin-evoked contraction (1 microM) exhibited a rapid desensitization, whereas the desensitization of response to SLIGRL was less even at high concentration (50 microM). Atropine had no effect on PAR-2 agonist-induced contractions. In contrast, TTX and capsaicin significantly attenuated those contractions, implicating a neurogenic mechanism that may involve capsaicin-sensitive sensory nerves. Furthermore, contractions induced by trypsin and SLIGRL were reduced by neurokinin receptor NK1 antagonist SR-140333 or NK2 antagonist SR-48968 alone or were further reduced by combined application of SR-140333 and SR-48968, indicating the involvement of neurokinin receptors. In addition, desensitizing neurokinin receptors with substance P and/or neurokinin A decreased the PAR-2 agonist-evoked contraction. We concluded that PAR-2 agonists induced a contraction of murine intestinal smooth muscle that was mediated by nerves. The excitatory effect is also dependent on sensory neural pathways and requires both NK1 and NK2 receptors.

Activation of PAR-2 elicits NO-dependent and CGRP-independent dilation of the dural artery.

PubMed

Bhatt, Deepak K; Ploug, Kenneth B; Ramachandran, Roshni; Olesen, Jes; Gupta, Saurabh

2010-06-01

The goal of this study was to determine the vascular effects of protease-activated receptor-2 (PAR-2) activation in the rat cranial vasculature. The role of PAR-2 in pain and inflammatory conditions has been established but the information available on its effects and receptor distribution in the trigeminal vascular axis is limited. We studied the dilatory function and expression of PAR-2 in the neuro-vascular circuit, critical in migraine pathogenesis. We also investigated the interaction of PAR-2 with calcitonin gene-related peptide (CGRP) and dural mast cells. We used an improved model of intravital microscopy on the closed cranial window in rats to study the vascular effects of PAR-2 activating peptides (PAR-2 APs; SLIGRL-NH(2), 2-Furoyl-LIGRLO-NH(2)) in the dural vasculature. Measurement of immunoreactive CGRP in skull halves and in trigeminal nucleus caudalis was done by using an enzyme-linked immunosorbent assay. We also analyzed the presence of PAR-2 in different migraine relevant tissues by quantitative real-time PCR and Western blot analysis. PAR-2 APs and trypsin induced a dose-dependent increase in dural artery diameter. The topical application of a nonspecific nitric oxide synthase (NOS) inhibitor, L-N(G)-Nitroarginine methyl ester, attenuated SLIGRL-NH(2) responses. Olcegepant, a CGRP receptor antagonist, did not a have significant effect on the SLIGRL-NH(2) responses, though exogenous CGRP responses were completely blocked. There was no significant release of CGRP from skull halves incubated with SLIGRL-NH(2) as compared with those incubated with the corresponding negative peptide. Chronic mast cell degranulation did not change the vascular effects of PAR-2 APs. mRNA and protein expression of PAR-2 were found throughout trigeminovasuclar axis. PAR-2 activation leads to vasodilation of dural arteries and these responses are partially mediated by nitric oxide. As PAR-2 is present throughout trigeminovasuclar axis, it may have a role in migraine

Proteolytic activation of the protease-activated receptor (PAR)-2 by the glycosylphosphatidylinositol-anchored serine protease testisin.

PubMed

Driesbaugh, Kathryn H; Buzza, Marguerite S; Martin, Erik W; Conway, Gregory D; Kao, Joseph P Y; Antalis, Toni M

2015-02-06

Protease-activated receptors (PARs) are a family of seven-transmembrane, G-protein-coupled receptors that are activated by multiple serine proteases through specific N-terminal proteolytic cleavage and the unmasking of a tethered ligand. The majority of PAR-activating proteases described to date are soluble proteases that are active during injury, coagulation, and inflammation. Less investigation, however, has focused on the potential for membrane-anchored serine proteases to regulate PAR activation. Testisin is a unique trypsin-like serine protease that is tethered to the extracellular membrane of cells through a glycophosphatidylinositol (GPI) anchor. Here, we show that the N-terminal domain of PAR-2 is a substrate for testisin and that proteolytic cleavage of PAR-2 by recombinant testisin activates downstream signaling pathways, including intracellular Ca(2+) mobilization and ERK1/2 phosphorylation. When testisin and PAR-2 are co-expressed in HeLa cells, GPI-anchored testisin specifically releases the PAR-2 tethered ligand. Conversely, knockdown of endogenous testisin in NCI/ADR-Res ovarian tumor cells reduces PAR-2 N-terminal proteolytic cleavage. The cleavage of PAR-2 by testisin induces activation of the intracellular serum-response element and NFκB signaling pathways and the induction of IL-8 and IL-6 cytokine gene expression. Furthermore, the activation of PAR-2 by testisin results in the loss and internalization of PAR-2 from the cell surface. This study reveals a new biological substrate for testisin and is the first demonstration of the activation of a PAR by a serine protease GPI-linked to the cell surface. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Accuracy of 99mTc (V)-Dimercaptosuccinic Acid Scintigraphy and Fecal Calprotectin Compared with Colonoscopy in Localizing Active Lesions in Inflammatory Bowel Disease

PubMed Central

Basirat, Vahid; Azizi, Zahra; Javid Anbardan, Sanam; Taghizadeh Asl, Mina; Farbod, Yasaman; Teimouri, Azam; Ebrahimi Daryani, Nasser

2016-01-01

INTRODUCTION Due to limitation of colonoscopy in assessing the entire bowel and patients’ intolerance in inflammatory bowel disease (IBD), in the current study, we aimed to prospectively compare the accuracy of 99mTc(V)-dimercaptosuccinic acid (DMSA) and fecal calprotectin with ileocolonoscopy as new methods for localizing inflammations. METHODS Current prospective study conducted between 2012 and 2014 on 30 patients with IBD attending Gastroenterology Clinic of Tehran University of Medical Sciences. Fecal calprotectin and disease activity were measured for all participants and all of them underwent 99mTc (V)-DMSA scintigraphy and colonoscopy. The accuracy of 99mTc (V)-DMSA scintigraphy and calprotectin in localizing bowel lesions were calculated. RESULTS A total of 22 patients with ulcerative colitis (UC) and 8 patients with Crohn’s disease (CD) were evaluated in our study. Sensitivity, positive likelihood ratio (PLR), and positive predictive value (PPV) of scintigraphy and calprotectin over colonoscopy in localization of UC lesions were 86.36%, 0.86%, 100.00% and 90.91%, 0.91, and 100.00%, respectively. Meanwhile, it showed 66.67% sensitivity and 81.25% specificity with PLR=3.56, negative likelihood ratio (NLR)=0.41, PPV=84.21%, and negative predictive value (NPV)= 61.90% in localizing lesions in patients with CD. The calprotectin level had sensitivity, PLR, and PPV of 90.00%, 0.90, and 100.00% in detecting active disease over colonoscopy, respectively. CONCLUSION The 99mTc (V)-DMSA scintigraphy would be an accurate method for detecting active inflammation in follow-up of patients with IBD and assessing response to treatment as a non-invasive and complementary method beside colonoscopy for more accurate diagnosis of CD or UC. PMID:27698971

Localization and postoperative follow-up of a bronchial carcinoid tumor causing Cushing's syndrome by 111In-DTPA labelled octreotide scintigraphy.

PubMed

Fernandez-Fernandez, F; Halperin, I; Manzanares, J M; Flores, L; Lomeña, F; Vilardell, E

1997-06-01

Bronchial carcinoid tumor is the most frequent occult source of ectopic ACTH-dependent Cushing's syndrome, but its initial localization may be very difficult, as well as its postoperative follow-up. We here present the case of a 21-year-old man with Cushing's syndrome and biochemical findings suggesting an ectopic source of ACTH (lack of inhibition of cortisol after overnight 8-mg dexamethasone suppression test, and lack of response to h-CRH challenge). Chest CT-scan showed a node adjacent to the left lung hilium whose nature was confirmed by uptake of 111Indium-DTPA labelled octreotide scintigraphy. Surgical resection of the tumor consisted in an upper lobectomy of the left lung. Microscopic examination identified a typical carcinoid tumor. After surgery pituitary-adrenal function normalized and a second scintigraphy offered additional data on the absence of tumor remnants.

Actin dynamics regulate immediate PAR-2-dependent responses to acute epidermal permeability barrier abrogation.

PubMed

Roelandt, Truus; Heughebaert, Carol; Verween, Gunther; Giddelo, Christina; Verbeken, Gilbert; Pirnay, Jean-Paul; Devos, Daniel; Crumrine, Debra; Roseeuw, Diane; Elias, Peter M; Hachem, Jean-Pierre

2011-02-01

Lamellar body (LB) secretion and terminal differentiation of stratum granulosum (SG) cells are signaled by both protease activated receptor-2 (PAR-2) and caveolin-1 (cav-1). To address the early dynamics of LB secretion, we examined cytoskeletal remodeling of keratinocytes in 3 mouse models following acute barrier abrogation: hairless mice, PAR-2 knockout (-/-) and cav-1 -/-. Under basal conditions, globular (G)-actin accumulates in SG cells cytosol, while filamentous (F)-actin is restricted to peri-membrane domains. Barrier abrogation induces the apical movement of F-actin and the retreat of the SG-G-actin front, paralleled by upstream cytoskeletal kinases activation. This phenomenon was both enhanced by PAR-2 agonist, and inhibited by cytochalasin-D and in PAR-2 knockout mice. We found that plasma membrane conformational changes causing LB secretion are controlled by PAR-2-dependent cytoskeletal rearrangements. We next addressed the interaction dynamics between cytoskeleton and plasma membrane following PAR-2-induced actin stress fiber formation in both cav-1 -/- and wildtype cells. Actin stress fiber formation is increased in cav-1 -/- cells prior to and following PAR-2 agonist peptide-treatment, while absence of cav-1 inhibits E-cadherin-mediated cell-to-cell adhesion. PAR-2 drives cytoskeletal/plasma membrane dynamics that regulate early LB secretion following barrier abrogation, stress fiber formation and keratinocyte adhesion. Copyright © 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Low-activity 124I-PET/low-dose CT versus 99mTc-pertechnetate planar scintigraphy or 99mTc-pertechnetate single-photon emission computed tomography of the thyroid: a pilot comparison.

PubMed

Darr, Andreas M; Opfermann, Thomas; Niksch, Tobias; Driesch, Dominik; Marlowe, Robert J; Freesmeyer, Martin

2013-10-01

The standard thyroid functional imaging method, 99mTc-pertechnetate (99mTc-PT) planar scintigraphy, has technical drawbacks decreasing its sensitivity in detecting nodules or anatomical pathology. 124I-PET, lacking these disadvantages and allowing simultaneous CT, may have greater sensitivity for these purposes. We performed a blinded pilot comparison of 124I-PET(/CT) versus 99mTc-PT planar scintigraphy or its cross-sectional enhancement, 99mTc-PT single-photon emission CT (SPECT), in characterizing the thyroid gland with benign disease. Twenty-one consecutive adults with goiter underwent low-activity (1 MBq/0.027 mCi) 124I-PET/low-dose (30 mAs) CT, 99mTc-PT planar scintigraphy, and 99mTc-PT-SPECT. Endpoints included the numbers of “hot spots” with/without central photopenia and “cold spots” detected, the proportion of these lesions with morphological correlates, the mean volume and diameter of visualized nodules, and the number of cases of lobus pyramidalis or retrosternal thyroid tissue identified. 124I-PET detected significantly more “hot spots” with/without central photopenia (P < 0.001), significantly more nodules (P < 0.001), and more “cold spots” than did 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT, including all lesions seen on the 99mTc-PT modalities. Ultrasonographic correlates were found for all nodules visualized on all 3 modalities and 92.5% of nodules seen only on 124I-PET. Nodules discernible only on 124I-PET had significantly smaller mean volume or diameter (P < 0.001) than did those visualized on 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT. 124I-PET(/CT) identified significantly more patients with a lobus pyramidalis (P < 0.001) or retrosternal thyroid tissue (P < 0.05). 124I-PET(/CT) may provide superior imaging of benign thyroid disease compared to planar or cross-sectional 99mTc-PT scintigraphy.

Prognosis in adenocarcinomas of lower oesophagus, gastro-oesophageal junction and cardia evaluated by uPAR-immunohistochemistry.

PubMed

Laerum, Ole Didrik; Ovrebo, Kjell; Skarstein, Arne; Christensen, Ib Jarle; Alpízar-Alpízar, Warner; Helgeland, Lars; Danø, Keld; Nielsen, Boye Schnack; Illemann, Martin

2012-08-01

Adenocarcinomas of lower oesophagus, gastro-oesophageal junction and cardia in humans are highly invasive tumours with poor prognosis. The localisation of urokinase-type plasminogen activator receptor (uPAR) was determined in 66 patients; 60 with adenocarcinomas and six cases with Barrett's oesophagus. uPAR was expressed in nearly all cases of invasive adenocarcinomas by populations of cancer cells, macrophages and myofibroblasts at both the invasion front and the tumour core. In areas with high-grade dysplasia or with Barrett's metaplasia adjacent to the tumour tissue, no uPAR-immunoreactivity was found. High local expression of uPAR, therefore, appears to be a characteristic marker for invasive behaviour in this tumour, suggesting that uPAR's contribution to matrix degradation during invasive growth is a late event in carcinogenesis. Using a scoring system for semiquantitative estimation of uPAR-positivity on immmunohistochemically stained specimens, a significant association was found between poor overall survival and high uPAR-score for cancer cells in the tumour core and for macrophages peripherally at the tumour invasion zone. In multivariate analysis, these two uPAR-scores were confirmed as highly significant prognostic parameters independent of Tumour, Node, Metastasis (TNM)-stage and World Health Organization (WHO) classification. The proteolytic action of these malignant and nonmalignant accessory cells thus seemed to follow two main patterns: one dominated by uPAR positive cancer cells and one by uPAR-positive macrophages. Scoring of uPAR-positivity might be a useful parameter for onset of invasion and prognosis in these adenocarcinomas. Copyright © 2011 UICC.

Aspirin inhibition of platelet deposition at angioplasty sites: demonstration by platelet scintigraphy

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

Cuningham, D.A.; Kumar, B.; Siegel, B.A.

In-111 platelet scintigraphy was used to evaluate the effects of prior aspirin administration on the accumulation of In-111-labeled autologous platelets at sites of arterial injury resulting from iliac, femoral, or popliteal transluminal angioplasty in a nonrandomized study of 17 men. The degree of platelet localization at angioplasty sites was significantly less in nine men who had received aspirin in varying doses within the 4 days before angioplasty than in eight men who had not received aspirin for at least two weeks. The results suggest that aspirin treatment before angioplasty limits the early platelet deposition at the angioplasty site in men.

Re-Signifying Participatory Action Research (PAR) in Higher Education: What Does "P" Stand for in PAR?

ERIC Educational Resources Information Center

Santos, Doris

2016-01-01

While carrying out a study aimed at understanding the contribution of participatory action research (PAR) to the political realm in contemporary higher education, a problematic situation was found when doing a literature review in the field of action research. This problem concerns the intermittent appearance of the "participatory"…

Estimation of photosynthetically available radiation (PAR) from OCEANSAT-I OCM using a simple atmospheric radiative transfer model

NASA Astrophysics Data System (ADS)

Tripathy, Madhumita; Raman, Mini; Chauhan, Prakash

2015-10-01

Photosynthetically available radiation (PAR) is an important variable for radiation budget, marine and terrestrial ecosystem models. OCEANSAT-1 Ocean Color Monitor (OCM) PAR was estimated using two different methods under both clear and cloudy sky conditions. In the first approach, aerosol optical depth (AOD) and cloud optical depth (COD) were estimated from OCEANSAT-1 OCM TOA (top-of-atmosphere) radiance data on a pixel by pixel basis and PAR was estimated from extraterrestrial solar flux for fifteen spectral bands using a radiative transfer model. The second approach used TOA radiances measured by OCM in the PAR spectral range to compute PAR. This approach also included surface albedo and cloud albedo as inputs. Comparison between OCEANSAT-1 OCM PAR at noon with in situ measured PAR shows that root mean square difference was 5.82% for the method I and 7.24% for the method II in daily time scales. Results indicate that methodology adopted to estimate PAR from OCEANSAT-1 OCM can produce reasonably accurate PAR estimates over the tropical Indian Ocean region. This approach can be extended to OCEANSAT-2 OCM and future OCEANSAT-3 OCM data for operational estimation of PAR for regional marine ecosystem applications.

Nurse exposure doses resulted from bone scintigraphy patient

NASA Astrophysics Data System (ADS)

Tunçman, Duygu; Kovan, Bilal; Poyraz, Leyla; ćapali, Veli; Demir, Bayram; Türkmen, Cüneyt

2016-03-01

Bone scintigraphy is used for displaying the radiologic undiagnosed bone lesions in nuclear medicine. It's general indications are researching bone metastases, detection of radiographically occult fractures, staging and follow-up in primary bone tumors, diagnosis of paget's disease, investigation of loosening and infection in orthopedic implants. It is applied with using 99mTc labeled radiopharmaceuticals (e.g 99m Tc MDP,99mTc HEDP and 99mTc HMDP). 20 -25 mCi IV radiotracer was injected into vein and radiotracer emits gamma radiation. Patient waits in isolated room for about 3 hours then a gamma camera scans radiation area and creates an image. When some patient's situation is not good, patients are hospitalized until the scanning because of patients' close contact care need. In this study, measurements were taken from ten patients using Geiger Muller counter. After these measurements, we calculated nurse's exposure radiations from patient's routine treatment, examination and emergency station.

MtPAR MYB transcription factor acts as an on switch for proanthocyanidin biosynthesis in Medicago truncatula

PubMed Central

Verdier, Jerome; Zhao, Jian; Torres-Jerez, Ivone; Ge, Shujun; Liu, Chenggang; He, Xianzhi; Mysore, Kirankumar S.; Dixon, Richard A.; Udvardi, Michael K.

2012-01-01

MtPAR (Medicago truncatula proanthocyanidin regulator) is an MYB family transcription factor that functions as a key regulator of proanthocyanidin (PA) biosynthesis in the model legume Medicago truncatula. MtPAR expression is confined to the seed coat, the site of PA accumulation. Loss-of-function par mutants contained substantially less PA in the seed coat than the wild type, whereas levels of anthocyanin and other specialized metabolites were normal in the mutants. In contrast, massive accumulation of PAs occurred when MtPAR was expressed ectopically in transformed hairy roots of Medicago. Transcriptome analysis of par mutants and MtPAR-expressing hairy roots, coupled with yeast one-hybrid analysis, revealed that MtPAR positively regulates genes encoding enzymes of the flavonoid–PA pathway via a probable activation of WD40-1. Expression of MtPAR in the forage legume alfalfa (Medicago sativa) resulted in detectable levels of PA in shoots, highlighting the potential of this gene for biotechnological strategies to increase PAs in forage legumes for reduction of pasture bloat in ruminant animals. PMID:22307644

Astrocytes Secrete Exosomes Enriched with Proapoptotic Ceramide and Prostate Apoptosis Response 4 (PAR-4)

PubMed Central

Wang, Guanghu; Dinkins, Michael; He, Qian; Zhu, Gu; Poirier, Christophe; Campbell, Andrew; Mayer-Proschel, Margot; Bieberich, Erhard

2012-01-01

Amyloid protein is well known to induce neuronal cell death, whereas only little is known about its effect on astrocytes. We found that amyloid peptides activated caspase 3 and induced apoptosis in primary cultured astrocytes, which was prevented by caspase 3 inhibition. Apoptosis was also prevented by shRNA-mediated down-regulation of PAR-4, a protein sensitizing cells to the sphingolipid ceramide. Consistent with a potentially proapoptotic effect of PAR-4 and ceramide, astrocytes surrounding amyloid plaques in brain sections of the 5xFAD mouse (and Alzheimer disease patient brain) showed caspase 3 activation and were apoptotic when co-expressing PAR-4 and ceramide. Apoptosis was not observed in astrocytes with deficient neutral sphingomyelinase 2 (nSMase2), indicating that ceramide generated by nSMase2 is critical for amyloid-induced apoptosis. Antibodies against PAR-4 and ceramide prevented amyloid-induced apoptosis in vitro and in vivo, suggesting that apoptosis was mediated by exogenous PAR-4 and ceramide, potentially associated with secreted lipid vesicles. This was confirmed by the analysis of lipid vesicles from conditioned medium showing that amyloid peptide induced the secretion of PAR-4 and C18 ceramide-enriched exosomes. Exosomes were not secreted by nSMase2-deficient astrocytes, indicating that ceramide generated by nSMase2 is critical for exosome secretion. Consistent with the ceramide composition in amyloid-induced exosomes, exogenously added C18 ceramide restored PAR-4-containing exosome secretion in nSMase2-deficient astrocytes. Moreover, isolated PAR-4/ceramide-enriched exosomes were taken up by astrocytes and induced apoptosis in the absence of amyloid peptide. Taken together, we report a novel mechanism of apoptosis induction by PAR-4/ceramide-enriched exosomes, which may critically contribute to Alzheimer disease. PMID:22532571

Plasma suPAR as a prognostic biological marker for ICU mortality in ARDS patients.

PubMed

Geboers, Diederik G P J; de Beer, Friso M; Tuip-de Boer, Anita M; van der Poll, Tom; Horn, Janneke; Cremer, Olaf L; Bonten, Marc J M; Ong, David S Y; Schultz, Marcus J; Bos, Lieuwe D J

2015-07-01

We investigated the prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) on day 1 in patients with the acute respiratory distress syndrome (ARDS) for intensive care unit (ICU) mortality and compared it with established disease severity scores on day 1. suPAR was determined batchwise in plasma obtained within 24 h after admission. 632 ARDS patients were included. Significantly (P = 0.02) higher median levels of suPAR were found with increasing severity of ARDS: 5.9 ng/ml [IQR 3.1-12.8] in mild ARDS (n = 82), 8.4 ng/ml [IQR 4.1-15.0] in moderate ARDS (n = 333), and 9.0 ng/ml [IQR 4.5-16.0] in severe ARDS (n = 217). Non-survivors had higher median levels of suPAR [12.5 ng/ml (IQR 5.1-19.5) vs. 7.4 ng/ml (3.9-13.6), P < 0.001]. The area under the receiver operator characteristic curve (ROC-AUC) for mortality of suPAR (0.62) was lower than the ROC-AUC of the APACHE IV score (0.72, P = 0.007), higher than that of the ARDS definition classification (0.53, P = 0.005), and did not differ from that of the SOFA score (0.68, P = 0.07) and the oxygenation index (OI) (0.58, P = 0.29). Plasma suPAR did not improve the discrimination of the established disease severity scores, but did improve net reclassification of the APACHE score (29%), SOFA score (23%), OI (38%), and Berlin definition classification (39%). As a single biological marker, the prognostic value for death of plasma suPAR in ARDS patients is low. Plasma suPAR, however, improves the net reclassification, suggesting a potential role for suPAR in ICU mortality prediction models.

IFN-γ, CXCL16, uPAR: potential biomarkers for systemic lupus erythematosus.

PubMed

Wen, Si; He, Fang; Zhu, Xuejing; Yuan, Shuguang; Liu, Hong; Sun, Lin

2018-01-01

IFN-γ, CXCL16 and uPAR have recently been regarded as potential biomarkers in systemic lupus erythematosus (SLE). However, few researches have focused on the comparison of these three markers in SLE. We conducted this study to evaluate their role as biomarkers of disease activity and renal damage. We enrolled 50 SLE patients with or without lupus nephritis (LN) and 15 healthy control subjects. The levels of IFN-γ, CXCL16, uPAR in serum, urine and renal tissues were detected by ELISA or immunohistochemistry. Relevant clinical and laboratory features were recorded. Serum and urine IFN-γ, CXCL16 and suPAR levels in SLE patients were significantly higher than that in healthy controls. Moreover, LN patients had higher levels than non-LN patients. A positive correlation was observed between these markers, and disease activity and suPAR had a stronger association with disease activity. The expression of these biomarkers in renal tissues was significantly higher in LN patients and was also associated with the activity of pathological lesions. IFN-γ, CXCL16 and uPAR are promising as effective biomarkers of disease activity, renal damage, and the activity of pathological lesions in SLE.

Participatory action research (PAR) in middle school: opportunities, constraints, and key processes.

PubMed

Ozer, Emily J; Ritterman, Miranda L; Wanis, Maggie G

2010-09-01

Late childhood and early adolescence represent a critical transition in the developmental and academic trajectory of youth, a time in which there is an upsurge in academic disengagement and psychopathology. PAR projects that can promote youth's sense of meaningful engagement in school and a sense of efficacy and mattering can be particularly powerful given the challenges of this developmental stage. In the present study, we draw on data from our own collaborative implementation of PAR projects in secondary schools to consider two central questions: (1) How do features of middle school settings and the developmental characteristics of the youth promote or inhibit the processes, outcomes, and sustainability of the PAR endeavor? and (2) How can the broad principles and concepts of PAR be effectively translated into specific intervention activities in schools, both within and outside of the classroom? In particular, we discuss a participatory research project conducted with 6th and 7th graders at an urban middle school as a means of highlighting the opportunities, constraints, and lessons learned in our efforts to contribute to the high-quality implementation and evaluation of PAR in diverse urban public schools.

Nanomechanical recognition of prognostic biomarker suPAR with DVD-ROM optical technology.

PubMed

Bache, Michael; Bosco, Filippo G; Brøgger, Anna L; Frøhling, Kasper B; Alstrøm, Tommy Sonne; Hwu, En-Te; Chen, Ching-Hsiu; Eugen-Olsen, Jesper; Hwang, Ing-Shouh; Boisen, Anja

2013-11-08

In this work the use of a high-throughput nanomechanical detection system based on a DVD-ROM optical drive and cantilever sensors is presented for the detection of urokinase plasminogen activator receptor inflammatory biomarker (uPAR). Several large scale studies have linked elevated levels of soluble uPAR (suPAR) to infectious diseases, such as HIV, and certain types of cancer. Using hundreds of cantilevers and a DVD-based platform, cantilever deflection response from antibody-antigen recognition is investigated as a function of suPAR concentration. The goal is to provide a cheap and portable detection platform which can carry valuable prognostic information. In order to optimize the cantilever response the antibody immobilization and unspecific binding are initially characterized using quartz crystal microbalance technology. Also, the choice of antibody is explored in order to generate the largest surface stress on the cantilevers, thus increasing the signal. Using optimized experimental conditions the lowest detectable suPAR concentration is currently around 5 nM. The results reveal promising research strategies for the implementation of specific biochemical assays in a portable and high-throughput microsensor-based detection platform.

TGF-β induced PAR-1 expression promotes tumor progression and osteoclast differentiation in giant cell tumor of bone.

PubMed

Wang, Ting; Jiao, Jian; Zhang, Hao; Zhou, Wang; Li, Zhenxi; Han, Shuai; Wang, Jing; Yang, Xinghai; Huang, Quan; Wu, Zhipeng; Yan, Wangjun; Xiao, Jianru

2017-10-15

Although protease activated receptor-1 (PAR-1) has been confirmed as an oncogene in many cancers, the role of PAR-1 in giant cell tumor (GCT) of bone has been rarely reported. The mechanism of PAR-1 in tumor-induced osteoclastogenesis still remains unclear. In the present study, we detected that PAR-1 was significantly upregulated in GCT of bone compared to normal tissues, while TGF-β was also overexpressed in GCT tissues and could promote the expression of PAR-1 in a dose and time dependent manner. Using the luciferase reporter assay, we found that two downstreams of TGF-β, Smad3 and Smad4, could activate the promoter of PAR-1, which might explain the mechanism of TGF-β induced PAR-1 expression. Meanwhile, PAR-1 was also overexpressed in microvesicles from stromal cells of GCT (GCTSCs), and might be transported from GCTSCs to monocytes through microvesicles. In addition, knockout of PAR-1 by TALENs in GCTSCs inhibited tumor growth, angiogenesis and osteoclastogenesis in GCT in vitro. Using the chick CAM models, we further showed that inhibition of PAR-1 suppressed tumor growth and giant cell formation in vivo. Using microarray assay, we detected a number of genes involved in osteoclastogenesis as the possible downstreams of PAR-1, which may partly explain the mechanism of PAR-1 in GCT. In brief, for the first time, these results reveal an upstream regulatory role of TGF-β in PAR-1 expression, and PAR-1 expression promotes tumor growth, angiogenesis and osteoclast differentiation in GCT of bone. Hence, PAR-1 represents a novel potential therapeutic target for GCT of bone. © 2017 UICC.

The 14-3-3 protein PAR-5 regulates the asymmetric localization of the LET-99 spindle positioning protein.

PubMed

Wu, Jui-Ching; Espiritu, Eugenel B; Rose, Lesilee S

2016-04-15

PAR proteins play important roles in establishing cytoplasmic polarity as well as regulating spindle positioning during asymmetric division. However, the molecular mechanisms by which the PAR proteins generate asymmetry in different cell types are still being elucidated. Previous studies in Caenorhabditis elegans revealed that PAR-3 and PAR-1 regulate the asymmetric localization of LET-99, which in turn controls spindle positioning by affecting the distribution of the conserved force generating complex. In wild-type embryos, LET-99 is localized in a lateral cortical band pattern, via inhibition at the anterior by PAR-3 and at the posterior by PAR-1. In this report, we show that the 14-3-3 protein PAR-5 is also required for cortical LET-99 asymmetry. PAR-5 associated with LET-99 in pull-down assays, and two PAR-5 binding sites were identified in LET-99 using the yeast two-hybrid assay. Mutation of these sites abolished binding in yeast and altered LET-99 localization in vivo: LET-99 was present at the highest levels at the posterior pole of the embryo instead of a band in par-5 embryos. Together the results indicate that PAR-5 acts in a mechanism with PAR-1 to regulate LET-99 cortical localization. Copyright © 2016 Elsevier Inc. All rights reserved.

The 14-3-3 Protein PAR-5 Regulates the Asymmetric localization of the LET-99 Spindle Positioning Protein

PubMed Central

Rose, Lesilee S.

2016-01-01

PAR proteins play important roles in establishing cytoplasmic polarity as well as regulating spindle positioning during asymmetric division. However, the molecular mechanisms by which the PAR proteins generate asymmetry in different cell types are still being elucidated. Previous studies in C. elegans revealed that PAR-3 and PAR-1 regulate the asymmetric localization of LET-99, which in turn controls spindle positioning by affecting the distribution of the conserved force generating complex. In wild-type embryos, LET-99 is localized in a lateral cortical band pattern, via inhibition at the anterior by PAR-3 and at the posterior by PAR-1. In this report, we show that the 14-3-3 protein PAR-5 is also required for cortical LET-99 asymmetry. PAR-5 associated with LET-99 in pull-down assays, and two PAR-5 binding sites were identified in LET-99 using the yeast two-hybrid assay. Mutation of these sites abolished binding in yeast and altered LET-99 localization in vivo: LET-99 was present at the highest levels at the posterior pole of the embryo instead of a band in par-5 embryos. Together the results indicate that PAR-5 acts in a mechanism with PAR-1 to regulate LET-99 cortical localization. PMID:26921457

Postoperative osteomyelitis following implant arthroplasty of the foot: diagnosis with indium-111 white blood cell scintigraphy

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

Bakst, R.H.; Kanat, I.O.

1987-11-01

Many complications can occur following insertion of silicone elastomer implants into the foot. Postoperative infection may be difficult to distinguish from other conditions such as dislodgment, fracture, ectopic and heterotopic new bone formation, synovitis, and bursitis. White blood cell scintigraphy, in conjunction with the clinical scenario, may prove to be an invaluable tool in the diagnosis of postoperative osteomyelitis, subsequent to implant arthroplasties. 32 references.

Simulating Carbon Flux Dynamics with the Product of PAR Absorbed by Chlorophyll (fAPARchl)

NASA Astrophysics Data System (ADS)

Yao, T.; Zhang, Q.

2016-12-01

A common way to estimate the gross primary production (GPP) is to use the fraction of photosynthetically radiation (PAR) absorbed by vegetation (FPAR). However, only the PAR absorbed by chlorophyll of the canopy, not the PAR absorbed by the foliage or by the entire canopy, is used for photosynthesis. MODIS fAPARchl product, which refers to the fraction of PAR absorbed by chlorophyll of the canopy, is derived from Moderate Resolution Imaging Spectroradiometer (MODIS) surface reflectance by using an advanced leaf-canopy-soil-water-snow coupled radiative transfer model PROSAIL4. PROSAIL4 can retrieve surface water cover fraction, snow cover fraction, and physiologically active canopy chemistry components (chlorophyll concentration and water content), fraction of photosynthetically active radiation (PAR) absorbed by a canopy (fAPARcanopy), fraction of PAR absorbed by photosynthetic vegetation (PV) component (mainly chlorophyll) throughout the canopy (fAPARPV, i.e., fAPARchl) and fraction of PAR absorbed by non-photosynthetic vegetation (NPV) component of the canopy (fAPARNPV). We have successfully retrieved these vegetation parameters for selected areas with PROSAIL4 and the MODIS images, or simulated spectrally MODIS-like images. In this study, the product of PAR absorbed by chlorophyll (fAPARchl) has been used to simulate carbon flux over different kinds of vegetation types. The results show that MODIS fAPARchl product has the ability to better characterize phenology than current phenology model in the Community Land Model and it also will likely be able to increase the accuracy of carbon fluxes simulations.

uPA/uPAR system activation drives a glycolytic phenotype in melanoma cells.

PubMed

Laurenzana, Anna; Chillà, Anastasia; Luciani, Cristina; Peppicelli, Silvia; Biagioni, Alessio; Bianchini, Francesca; Tenedini, Elena; Torre, Eugenio; Mocali, Alessandra; Calorini, Lido; Margheri, Francesca; Fibbi, Gabriella; Del Rosso, Mario

2017-09-15

In this manuscript, we show the involvement of the uPA/uPAR system in the regulation of aerobic glycolysis of melanoma cells. uPAR over-expression in human melanoma cells controls an invasive and glycolytic phenotype in normoxic conditions. uPAR down-regulation by siRNA or its uncoupling from integrins, and hence from integrin-linked tyrosine kinase receptors (IL-TKRs), by an antagonist peptide induced a striking inhibition of the PI3K/AKT/mTOR/HIF1α pathway, resulting into impairment of glucose uptake, decrease of several glycolytic enzymes and of PKM2, a checkpoint that controls metabolism of cancer cells. Further, binding of uPA to uPAR regulates expression of molecules that govern cell invasion, including extracellular matrix metallo-proteinases inducer (EMPPRIN) and enolase, a glycolytyc enzyme that also serves as a plasminogen receptor, thus providing a common denominator between tumor metabolism and phenotypic invasive features. Such effects depend on the α5β1-integrin-mediated uPAR connection with EGFR in melanoma cells with engagement of the PI3K-mTOR-HIFα pathway. HIF-1α trans-activates genes whose products mediate tumor invasion and glycolysis, thus providing the common denominator between melanoma metabolism and its invasive features. These findings unveil a unrecognized interaction between the invasion-related uPAR and IL-TKRs in the control of glycolysis and disclose a new pharmacological target (i.e., uPAR/IL-TKRs axis) for the therapy of melanoma. © 2017 UICC.

Blockade of protease-activated receptor-4 (PAR4) provides robust antithrombotic activity with low bleeding.

PubMed

Wong, Pancras C; Seiffert, Dietmar; Bird, J Eileen; Watson, Carol A; Bostwick, Jeffrey S; Giancarli, Mary; Allegretto, Nick; Hua, Ji; Harden, David; Guay, Jocelyne; Callejo, Mario; Miller, Michael M; Lawrence, R Michael; Banville, Jacques; Guy, Julia; Maxwell, Brad D; Priestley, E Scott; Marinier, Anne; Wexler, Ruth R; Bouvier, Michel; Gordon, David A; Schumacher, William A; Yang, Jing

2017-01-04

Antiplatelet agents are proven efficacious treatments for cardiovascular and cerebrovascular diseases. However, the existing drugs are compromised by unwanted and sometimes life-threatening bleeding that limits drug usage or dosage. There is a substantial unmet medical need for an antiplatelet drug with strong efficacy and low bleeding risk. Thrombin is a potent platelet agonist that directly induces platelet activation via the G protein (heterotrimeric guanine nucleotide-binding protein)-coupled protease-activated receptors PAR1 and PAR4. A PAR1 antagonist is approved for clinical use, but its use is limited by a substantial bleeding risk. Conversely, the potential of PAR4 as an antiplatelet target has not been well characterized. Using anti-PAR4 antibodies, we demonstrated a low bleeding risk and an effective antithrombotic profile with PAR4 inhibition in guinea pigs. Subsequently, high-throughput screening and an extensive medicinal chemistry effort resulted in the discovery of BMS-986120, an orally active, selective, and reversible PAR4 antagonist. In a cynomolgus monkey arterial thrombosis model, BMS-986120 demonstrated potent and highly efficacious antithrombotic activity. BMS-986120 also exhibited a low bleeding liability and a markedly wider therapeutic window compared to the standard antiplatelet agent clopidogrel tested in the same nonhuman primate model. These preclinical findings define the biological role of PAR4 in mediating platelet aggregation. In addition, they indicate that targeting PAR4 is an attractive antiplatelet strategy with the potential to treat patients at a high risk of atherothrombosis with superior safety compared with the current standard of care. Copyright © 2017, American Association for the Advancement of Science.

Proteinase-Activated Receptor-1 and Immunomodulatory Effects of a PAR1-Activating Peptide in a Mouse Model of Prostatitis

PubMed Central

Stanton, M. Mark; Nelson, Lisa K.; Benediktsson, Hallgrimur; Hollenberg, Morley D.; Buret, Andre G.; Ceri, Howard

2013-01-01

Background. Nonbacterial prostatitis has no established etiology. We hypothesized that proteinase-activated receptor-1 (PAR1) can play a role in prostatitis. We therefore investigated the effects of PAR1 stimulation in the context of a new model of murine nonbacterial prostatitis. Methods. Using a hapten (ethanol-dinitrobenzene sulfonic acid- (DNBS-)) induced prostatitis model with both wild-type and PAR1-null mice, we examined (1) the location of PAR1 in the mouse prostate and (2) the impact of a PAR1-activating peptide (TFLLR-NH2: PAR1-TF) on ethanol-DNBS-induced inflammation. Results. Ethanol-DNBS-induced inflammation was maximal at 2 days. In the tissue, PAR1 was expressed predominantly along the apical acini of prostatic epithelium. Although PAR1-TF on its own did not cause inflammation, its coadministration with ethanol-DNBS reduced all indices of acute prostatitis. Further, PAR1-TF administration doubled the prostatic production of interleukin-10 (IL-10) compared with ethanol-DNBS treatment alone. This enhanced IL-10 was not observed in PAR1-null mice and was not caused by the reverse-sequence receptor-inactive peptide, RLLFT-NH2. Surprisingly, PAR1-TF, also diminished ethanol-DNBS-induced inflammation in PAR1-null mice. Conclusions. PAR1 is expressed in the mouse prostate and its activation by PAR1-TF elicits immunomodulatory effects during ethanol-DNBS-induced prostatitis. However, PAR1-TF also diminishes ethanol-DNBS-induced inflammation via a non-PAR1 mechanism by activating an as-yet unknown receptor. PMID:24459330

Cortical PAR polarity proteins promote robust cytokinesis during asymmetric cell division

PubMed Central

Jordan, Shawn N.; Davies, Tim; Zhuravlev, Yelena; Dumont, Julien; Shirasu-Hiza, Mimi

2016-01-01

Cytokinesis, the physical division of one cell into two, is thought to be fundamentally similar in most animal cell divisions and driven by the constriction of a contractile ring positioned and controlled solely by the mitotic spindle. During asymmetric cell divisions, the core polarity machinery (partitioning defective [PAR] proteins) controls the unequal inheritance of key cell fate determinants. Here, we show that in asymmetrically dividing Caenorhabditis elegans embryos, the cortical PAR proteins (including the small guanosine triphosphatase CDC-42) have an active role in regulating recruitment of a critical component of the contractile ring, filamentous actin (F-actin). We found that the cortical PAR proteins are required for the retention of anillin and septin in the anterior pole, which are cytokinesis proteins that our genetic data suggest act as inhibitors of F-actin at the contractile ring. Collectively, our results suggest that the cortical PAR proteins coordinate the establishment of cell polarity with the physical process of cytokinesis during asymmetric cell division to ensure the fidelity of daughter cell formation. PMID:26728855

The pars intermedia: an anatomic basis for a coordinated vascular response to female genital arousal.

PubMed

Shih, Cheryl; Cold, Christopher J; Yang, Claire C

2013-06-01

The pars intermedia is an area of the vulva that has been inconsistently described in the literature. We conducted anatomic studies to better describe the tissues and vascular structures of the pars intermedia and proposed a functional rationale of the pars intermedia in the female sexual response. Nine cadaveric vulvectomy specimens were used. Each was serially sectioned and stained with hematoxylin and eosin and Masson's trichrome. Histologic ultrastructural description of the pars intermedia. The pars intermedia contains veins traveling longitudinally in the angle of the clitoris, supported by collagen-rich stromal tissues. These veins drain the different vascular compartments of the vulva, including the clitoris, the bulbs, and labia minora; also, the interconnecting veins link the different vascular compartments. The pars intermedia is not composed of erectile tissue, distinguishing it from the erectile tissues of the corpora cavernosa of the clitoris as well as the corpus spongiosum of the clitoral (vestibular) bulbs. The venous communications of the pars intermedia, linking the erectile tissues with the other vascular compartments of the vulva, appear to provide the anatomic basis for a coordinated vascular response during female sexual arousal. © 2012 International Society for Sexual Medicine.

PAR-1 and thrombin: the ties that bind the microenvironment to melanoma metastasis.

PubMed

Zigler, Maya; Kamiya, Takafumi; Brantley, Emily C; Villares, Gabriel J; Bar-Eli, Menashe

2011-11-01

Progression of melanoma is dependent on cross-talk between tumor cells and the adjacent microenvironment. The thrombin receptor, protease-activated receptor-1 (PAR-1), plays a key role in exerting this function during melanoma progression. PAR-1 and its activating factors, which are expressed on tumor cells and the surrounding stroma, induce not only coagulation but also cell signaling, which promotes the metastatic phenotype. Several adhesion molecules, cytokines, growth factors, and proteases have recently been identified as downstream targets of PAR-1 and have been shown to modulate interactions between tumor cells and the microenvironment in the process of melanoma growth and metastasis. Inhibiting such interactions by targeting PAR-1 could potentially be a useful therapeutic modality for melanoma patients. ©2011 AACR.

Project Plan 7930 Cell G PaR Remote Handling System Replacement

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

Kinney, Kathryn A

2009-10-01

For over 40 years the US Department of Energy (DOE) and its predecessors have made Californium-252 ({sup 252}Cf) available for a wide range of industries including medical, nuclear fuels, mining, military and national security. The Radiochemical Engineering Development Center (REDC) located within the Oak Ridge National Laboratory (ORNL) processes irradiated production targets from the High Flux Isotope Reactor (HFIR). Operations in Building 7930, Cell G provide over 70% of the world's demand for {sup 252}Cf. Building 7930 was constructed and equipped in the mid-1960s. Current operations for {sup 252}Cf processing in Building 7930, Cell G require use of through-the-wall manipulatorsmore » and the PaR Remote Handling System. Maintenance and repairs for the manipulators is readily accomplished by removal of the manipulator and relocation to a repair shop where hands-on work can be performed in glove boxes. Contamination inside cell G does not currently allow manned entry and no provisions were created for a maintenance area inside the cell. There has been no maintenance of the PaR system or upgrades, leaving operations vulnerable should the system have a catastrophic failure. The Cell G PaR system is currently being operated in a run to failure mode. As the manipulator is now 40+ years old there is significant risk in this method of operation. In 2006 an assessment was completed that resulted in recommendations for replacing the manipulator operator control and power centers which are used to control and power the PaR manipulator in Cell G. In mid-2008 the chain for the bridge drive failed and subsequent examinations indicated several damaged links (see Figure 1). To continue operations the PaR manipulator arm is being used to push and pull the bridge as a workaround. A retrieval tool was fabricated, tested and staged inside Cell G that will allow positioning of the bridge and manipulator arm for removal from the cell should the PaR system completely fail. A fully

Serologically Defined Variations in Malaria Endemicity in Pará State, Brazil

PubMed Central

Cunha, Maristela G.; Silva, Eliane S.; Sepúlveda, Nuno; Costa, Sheyla P. T.; Saboia, Tiago C.; Guerreiro, João F.; Póvoa, Marinete M.; Corran, Patrick H.; Riley, Eleanor; Drakeley, Chris J.

2014-01-01

Background Measurement of malaria endemicity is typically based on vector or parasite measures. A complementary approach is the detection of parasite specific IgG antibodies. We determined the antibody levels and seroconversion rates to both P. vivax and P. falciparum merozoite antigens in individuals living in areas of varying P. vivax endemicity in Pará state, Brazilian Amazon region. Methodology/Principal Findings The prevalence of antibodies to recombinant antigens from P. vivax and P. falciparum was determined in 1,330 individuals. Cross sectional surveys were conducted in the north of Brazil in Anajás, Belém, Goianésia do Pará, Jacareacanga, Itaituba, Trairão, all in the Pará state, and Sucuriju, a free-malaria site in the neighboring state Amapá. Seroprevalence to any P. vivax antigens (MSP1 or AMA-1) was 52.5%, whereas 24.7% of the individuals were seropositive to any P. falciparum antigens (MSP1 or AMA-1). For P. vivax antigens, the seroconversion rates (SCR) ranged from 0.005 (Sucuriju) to 0.201 (Goianésia do Pará), and are strongly correlated to the corresponding Annual Parasite Index (API). We detected two sites with distinct characteristics: Goianésia do Pará where seroprevalence curve does not change with age, and Sucuriju where seroprevalence curve is better described by a model with two SCRs compatible with a decrease in force of infection occurred 14 years ago (from 0.069 to 0.005). For P. falciparum antigens, current SCR estimates varied from 0.002 (Belém) to 0.018 (Goianésia do Pará). We also detected a putative decrease in disease transmission occurred ∼29 years ago in Anajás, Goianésia do Pará, Itaituba, Jacareacanga, and Trairão. Conclusions We observed heterogeneity of serological indices across study sites with different endemicity levels and temporal changes in the force of infection in some of the sites. Our study provides further evidence that serology can be used to measure and monitor transmission of both major

Molecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex.

PubMed

Roll, Patrice; Vernes, Sonja C; Bruneau, Nadine; Cillario, Jennifer; Ponsole-Lenfant, Magali; Massacrier, Annick; Rudolf, Gabrielle; Khalife, Manal; Hirsch, Edouard; Fisher, Simon E; Szepetowski, Pierre

2010-12-15

It is a challenge to identify the molecular networks contributing to the neural basis of human speech. Mutations in transcription factor FOXP2 cause difficulties mastering fluent speech (developmental verbal dyspraxia, DVD), whereas mutations of sushi-repeat protein SRPX2 lead to epilepsy of the rolandic (sylvian) speech areas, with DVD or with bilateral perisylvian polymicrogyria. Pathophysiological mechanisms driven by SRPX2 involve modified interaction with the plasminogen activator receptor (uPAR). Independent chromatin-immunoprecipitation microarray screening has identified the uPAR gene promoter as a potential target site bound by FOXP2. Here, we directly tested for the existence of a transcriptional regulatory network between human FOXP2 and the SRPX2/uPAR complex. In silico searches followed by gel retardation assays identified specific efficient FOXP2-binding sites in each of the promoter regions of SRPX2 and uPAR. In FOXP2-transfected cells, significant decreases were observed in the amounts of both SRPX2 (43.6%) and uPAR (38.6%) native transcripts. Luciferase reporter assays demonstrated that FOXP2 expression yielded a marked inhibition of SRPX2 (80.2%) and uPAR (77.5%) promoter activity. A mutant FOXP2 that causes DVD (p.R553H) failed to bind to SRPX2 and uPAR target sites and showed impaired down-regulation of SRPX2 and uPAR promoter activity. In a patient with polymicrogyria of the left rolandic operculum, a novel FOXP2 mutation (p.M406T) was found in the leucine-zipper (dimerization) domain. p.M406T partially impaired the FOXP2 regulation of SRPX2 promoter activity, whereas that of the uPAR promoter remained unchanged. Together with recently described FOXP2-CNTNAP2 and SRPX2/uPAR links, the FOXP2-SRPX2/uPAR network provides exciting insights into molecular pathways underlying speech-related disorders.

Protease activated receptor-2 (PAR2): possible target of phytochemicals.

PubMed

Kakarala, Kavita Kumari; Jamil, Kaiser

2015-09-01

The use of phytochemicals either singly or in combination with other anticancer drugs comes with an advantage of less toxicity and minimal side effects. Signaling pathways play central role in cell cycle, cell growth, metabolism, etc. Thus, the identification of phytochemicals with promising antagonistic effect on the receptor/s playing key role in single transduction may have better therapeutic application. With this background, phytochemicals were screened against protease-activated receptor 2 (PAR2). PAR2 belongs to the superfamily of GPCRs and is an important target for breast cancer. Using in silico methods, this study was able to identify the phytochemicals with promising binding affinity suggesting their therapeutic potential in the treatment of breast cancer. The findings from this study acquires importance as the information on the possible agonists and antagonists of PAR2 is limited due its unique mechanism of activation.

Traumatisme de la main par injection a haute pression

PubMed Central

Mabchoure, K.; Diouri, M.; Bahechar, N.; Chlihi, A.

2016-01-01

Summary Les traumatismes de la main par injection à haute pression sont des accidents relativement rares et souvent mal connus par le praticien. Les lésions qui dépendent du produit injecté et du site d’injection sont pourvoyeuses de séquelles esthétiques et fonctionnelles lourdes. Le traitement repose sur la chirurgie, l’antibiothérapie et la rééducation précoce et spécifique. Nous rapportons notre expérience ainsi qu’une revue de la littérature. PMID:27857654

PAR-1 mediated apoptosis of breast cancer cells by V. cholerae hemagglutinin protease.

PubMed

Ray, Tanusree; Pal, Amit

2016-05-01

Bacterial toxins have emerged as promising agents in cancer treatment strategy. Hemagglutinin (HAP) protease secreted by Vibrio cholerae induced apoptosis in breast cancer cells and regresses tumor growth in mice model. The success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity for normal tissues. Increased expression of Protease Activated Receptor-1 (PAR-1) has been reported in different malignant cells. In this study we report that HAP induced activation and over expression of PAR-1 in breast cancer cells (EAC). Immunoprecipitation studies have shown that HAP specifically binds with PAR-1. HAP mediated activation of PAR-1 caused nuclear translocation of p50-p65 and the phosphorylation of p38 which triggered the activation of NFκB and MAP kinase signaling pathways. These signaling pathways enhanced the cellular ROS level in malignant cells that induced the intrinsic pathway of cell apoptosis. PAR-1 mediated apoptosis by HAP of malignant breast cells without effecting normal healthy cells in the same environment makes it a good therapeutic agent for treatment of cancer.

A visual grading study for different administered activity levels in bone scintigraphy.

PubMed

Gustafsson, Agnetha; Karlsson, Henrik; Nilsson, Kerstin A; Geijer, Håkan; Olsson, Anna

2015-05-01

The aim of the study is to assess the administered activity levels versus visual-based image quality using visual grading regression (VGR) including an assessment of the newly stated image criteria for whole-body bone scintigraphy. A total of 90 patients was included and grouped in three levels of administered activity: 400, 500 and 600 MBq. Six clinical image criteria regarding image quality was formulated by experienced nuclear medicine physicians. Visual grading was performed in all images, where three physicians rated the fulfilment of the image criteria on a four-step ordinal scale. The results were analysed using VGR. A count analysis was also made where the total number of counts in both views was registered. The administered activity of 600 MBq gives significantly better image quality than 400 MBq in five of six criteria (P<0·05). Comparing the administered activity of 600 MBq to 500 MBq, four criteria of six show significantly better image quality (P<0·05). The administered activity of 500 MBq gives no significantly better image quality than 400 Mbq (P<0·05). The count analysis shows that none of the three levels of administrated activity fulfil the recommendations by the EANM. There was a significant improvement in perceived image quality using an activity level of 600 MBq compared to lower activity levels in whole-body bone scintigraphy for the gamma camera equipment end set-up used in this study. This type of visual-based grading study seems to be a valuable tool and easy to implement in the clinical environment. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Allergic sensitization enhances anion current responsiveness of murine trachea to PAR-2 activation.

PubMed

Rievaj, Juraj; Davidson, Courtney; Nadeem, Ahmed; Hollenberg, Morley; Duszyk, Marek; Vliagoftis, Harissios

2012-03-01

Protease-activated receptor 2 (PAR-2) is a G protein-coupled receptor possibly involved in the pathogenesis of asthma. PAR-2 also modulates ion transport in cultured epithelial cells, but these effects in native airways are controversial. The influence of allergic inflammation on PAR-2-induced changes in ion transport has received little attention. Here, we studied immediate changes in transepithelial short circuit current (I (sc)) induced by PAR-2 activation in the tracheas of naive and allergic mice. Activation of PAR-2 with an apically added activation peptide (AP) induced a small increase in I (sc), while a much larger increase was observed following basolateral AP addition. In ovalbumin-sensitized and -challenged animals used as a model of allergic airway inflammation, the effect of basolateral AP addition was enhanced. Responses to basolateral AP in both naive and allergic mice were not decreased by blocking sodium absorption with amiloride or CFTR function with CFTR(inh)172 but were reduced by the cyclooxygenase inhibitor indomethacin and largely blocked (>80%) by niflumic acid, a calcium-activated chloride channels' (CaCC) blocker. Allergic mice also showed an enhanced response to ATP and thapsigargin. There was no change in mRNA expression of Par-2 or of the chloride channels Ano1 (Tmem16a) and Bestrophin 2 in tracheas from allergic mice, while mRNA levels of Bestrophin 1 were increased. In conclusion, basolateral PAR-2 activation in the mouse airways led to increased anion secretion through apical CaCC, which was more pronounced in allergic animals. This could be a protective mechanism aimed at clearing allergens and defending against mucus plugging.

ParFit: A Python-Based Object-Oriented Program for Fitting Molecular Mechanics Parameters to ab Initio Data.

PubMed

Zahariev, Federico; De Silva, Nuwan; Gordon, Mark S; Windus, Theresa L; Dick-Perez, Marilu

2017-03-27

A newly created object-oriented program for automating the process of fitting molecular-mechanics parameters to ab initio data, termed ParFit, is presented. ParFit uses a hybrid of deterministic and stochastic genetic algorithms. ParFit can simultaneously handle several molecular-mechanics parameters in multiple molecules and can also apply symmetric and antisymmetric constraints on the optimized parameters. The simultaneous handling of several molecules enhances the transferability of the fitted parameters. ParFit is written in Python, uses a rich set of standard and nonstandard Python libraries, and can be run in parallel on multicore computer systems. As an example, a series of phosphine oxides, important for metal extraction chemistry, are parametrized using ParFit. ParFit is in an open source program available for free on GitHub ( https://github.com/fzahari/ParFit ).

Comparison of the use of scapular ultrasonography, physical examination, and measurement of serum biomarkers of bone turnover versus scintigraphy for detection of bone fragility syndrome in horses.

PubMed

Arens, Amanda M; Puchalski, Sarah M; Whitcomb, Mary Beth; Bell, Robin; Gardner, Ian A; Stover, Susan M

2013-01-01

To define scintigraphic, physical examination, and scapular ultrasonographic findings consistent with bone fragility syndrome (BFS) in horses; develop indices of BFS severity; and assess accuracy of physical examination, scapular ultrasonography, and serum biomarkers for BFS diagnosis. Prospective case-control study. 48 horses (20 horses with BFS and 28 control horses). Horses underwent forelimb scintigraphic evaluation, physical examination, scapular ultrasonography, and serum collection. Scintigraphy was used as a reference standard to which physical examination, scapular ultrasonography, and concentrations of serum biomarkers (carboxy-terminal telopeptide of collagen crosslinks and bone-specific alkaline phosphatase activity) were compared for assessing accuracy in BFS diagnosis. A diagnosis of BFS was strongly supported on scintigraphy by ≥ 2 regions of increased radiopharmaceutical uptake, including 1 region in the scapular spine and 1 region in the scapular body or ribs; on physical examination by lateral bowing of the scapulae; and on ultrasonography by widening of the scapular spine. None of the tests evaluated were accurate enough to replace scintigraphy for mild disease; however, physical examination and scapular ultrasonography were accurate in horses with moderate to severe BFS. Serum biomarkers were not accurate for BFS diagnosis. Scintigraphy remained the most informative diagnostic modality for BFS, providing insight into disease severity and distribution; however, physical examination and scapular ultrasonographic abnormalities were diagnostic in horses with moderate to severe disease. Proposed severity indices classified the spectrum of disease manifestations. Clearly defined criteria for interpretation of diagnostic tests aid in the detection of BFS. Severity indices may be useful for assessing disease progression and response to treatment.

Pars plana Ahmed valve and vitrectomy in patients with glaucoma associated with posterior segment disease.

PubMed

Wallsh, Josh O; Gallemore, Ron P; Taban, Mehran; Hu, Charles; Sharareh, Behnam

2013-01-01

To assess the safety and efficacy of a modified technique for pars plana placement of the Ahmed valve in combination with pars plana vitrectomy in the treatment of glaucoma associated with posterior segment disease. Thirty-nine eyes with glaucoma associated with posterior segment disease underwent pars plana vitrectomy combined with Ahmed valve placement. All valves were placed in the pars plana using a modified technique, without the pars plana clip, and using a scleral patch graft. The 24 eyes diagnosed with neovascular glaucoma had an improvement in intraocular pressure from 37.6 mmHg to 13.8 mmHg and best-corrected visual acuity from 2.13 logarithm of minimum angle of resolution to 1.40 logarithm of minimum angle of resolution. Fifteen eyes diagnosed with steroid-induced glaucoma had an improvement in intraocular pressure from 27.9 mmHg to 14.1 mmHg and best-corrected visual acuity from 1.38 logarithm of minimum angle of resolution to 1.13 logarithm of minimum angle of resolution. Complications included four cases of cystic bleb formation and one case of choroidal detachment and explantation for hypotony. Ahmed valve placement through the pars plana during vitrectomy is an effective option for managing complex cases of glaucoma without the use of the pars plana clip.

A family of ParA-like ATPases promotes cell pole maturation by facilitating polar localization of chemotaxis proteins

PubMed Central

Ringgaard, Simon; Schirner, Kathrin; Davis, Brigid M.; Waldor, Matthew K.

2011-01-01

Stochastic processes are thought to mediate localization of membrane-associated chemotaxis signaling clusters in peritrichous bacteria. Here, we identified a new family of ParA-like ATPases (designated ParC [for partitioning chemotaxis]) encoded within chemotaxis operons of many polar-flagellated γ-proteobacteria that actively promote polar localization of chemotaxis proteins. In Vibrio cholerae, a single ParC focus is found at the flagellated old pole in newborn cells, and later bipolar ParC foci develop as the cell matures. The cell cycle-dependent redistribution of ParC occurs by its release from the old pole and subsequent relocalization at the new pole, consistent with a “diffusion and capture” model for ParC dynamics. Chemotaxis proteins encoded in the same cluster as ParC have a similar unipolar-to-bipolar transition; however, they reach the new pole after the arrival of ParC. Cells lacking ParC exhibit aberrantly localized foci of chemotaxis proteins, reduced chemotaxis, and altered motility, which likely accounts for their enhanced colonization of the proximal small intestine in an animal model of cholera. Collectively, our findings indicate that ParC promotes the efficiency of chemotactic signaling processes. In particular, ParC-facilitated development of a functional chemotaxis apparatus at the new pole readies this site for its development into a functional old pole after cell division. PMID:21764856

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation

PubMed Central

2012-01-01

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors. PMID:22731117

Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

PubMed

Chen, Chen-Wen; Chen, Qian-Bo; Ouyang, Qing; Sun, Ji-Hu; Liu, Fang-Ting; Song, Dian-Wen; Yuan, Hong-Bin

2012-06-25

Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

Modeles numeriques de la stimulation optique de neurones assistee par nanoparticules plasmoniques

NASA Astrophysics Data System (ADS)

Le Hir, Nicolas

La stimulation de neurones par laser emerge depuis plusieurs annees comme une alternative aux techniques plus traditionnelles de stimulation artificielle. Contrairement a celles-ci, la stimulation lumineuse ne necessite pas d'interagir directement avec le tissu organique, comme c'est le cas pour une stimulation par electrodes, et ne necessite pas de manipulation genetique comme c'est le cas pour les methodes optogenetiques. Plus recemment, la stimulation lumineuse de neurones assistee par nanoparticules a emerge comme un complement a la stimulation simplement lumineuse. L'utilisation de nanoparticules complementaires permet d'augmenter la precision spatiale du procede et de diminuer la fluence necessaire pour observer le phenomene. Ceci vient des proprietes d'interaction entre les nanoparticules et le faisceau laser, comme par exemple les proprietes d'absorption des nanoparticules. Deux phenomenes princpaux sont observes. Dans certains cas, il s'agit d'une depolarisation de la membrane, ou d'un potentiel d'action. Dans d'autres experiences, un influx de calcium vers l'interieur du neurone est detecte par une augmentation de la fluorescence d'une proteine sensible a la concentration calcique. Certaines stimulations sont globales, c'est a dire qu'une perturbation se propage a l'ensemble du neurone : c'est le cas d'un potentiel d'action. D'autres sont, au contraire, locales et ne se propagent pas a l'ensemble de la cellule. Si une stimulation lumineuse globale est rendue possible par des techniques relativement bien maitrisees a l'heure actuelle, comme l'optogenetique, une stimulation uniquement locale est plus difficile a realiser. Or, il semblerait que les methodes de stimulation lumineuse assistees par nanoparticules puissent, dans certaines conditions, offrir cette possibilite. Cela serait d'une grande aide pour conduire de nouvelles etudes sur le fonctionnement des neurones, en offrant de nouvelles possibilites experimentales en complement des possibilites

Brulures par Diluant

PubMed Central

Benbrahim, A.; Jerrah, H.; Diouri, M.; Bahechar, N.; Boukind, E.H.

2009-01-01

Summary La flamme de diluant est une cause non rare de brûlure dans le contexte marocain. Nous avons jugé intéressant de faire une étude épidémiologique sur la brûlure par flamme de diluant (BFD) au centre national des brûlés (CNB) du CHU Ibn-Rochd de Casablanca. Ce travail a été réalisé sur une période de 10 mois (septembre 2007/juin 2008). Le but du travail est de montrer les caractéristiques de ce type de brûlures pour les prévenir et ce par l'information sur le diluant, produit causant ces brûlures, et ses différents dangers, la brûlure notamment. Durant cette période, nous avons colligé 17 cas de BFD sur un total de 356 patients admis au CNB pour brûlures aiguës toute étiologie confondue. La moyenne d'age des patients concernés est de 32 ans. Ils sont presque tous de sexe masculin (16 hommes/1 femme) et ont des antécédents de toxicomanie et/ou de délinquance. Tous nos patients sont de bas niveau socio-économique et habitent dans des bidonvilles pour la plupart. La brûlure est souvent secondaire à une agression dans la rue (92% des cas). Concernant les caractéristiques de la brûlure, la surface cutanée brûlée moyenne est de 23%; elle est souvent profonde et siège surtout au niveau des membres supérieurs et du tronc. PMID:21991179

L'analyse par activation de neutrons de réacteur

NASA Astrophysics Data System (ADS)

Meyer, G.

2003-02-01

Quand les neutrons traversent la matière, certains sont transmis sans interaction, les autres interagissent avec le milieu traversé par diffusion et par absorption. Ce phénomène d'absorption est utilisé pour se protéger des neutrons, mais aussi pour les détecter; il peut également être utilisé pour identifier les noyaux “absorbants" et ainsi analyser le milieu traversé. En effet par différentes réactions nucléaires (n,γ), (n,p), (n,α), (n,fission), on obtient des noyaux résiduels qui sont souvent radioactifs; on dit que l'échantillon est “activé". Si l'on connaît le rendement d'activation et donc le pourcentage de noyaux ainsi “transmutés", les mesures de radioactivité induite vont permettre de déterminer la composition de l'échantillon irradié. Cette méthode dite d'analyse par activation neutronique est pratiquée depuis la découverte du neutron. Elle a permis grâce à sa sélectivité et à sa sensibilité d'avoir accès au domaine des traces et des ultra-traces dans des champs d'application très divers comme la métallurgie, l'archéologie, la biologie, la géochimie etc...

Bacterial actin homolog ParM: arguments for an apolar, antiparallel double helix.

PubMed

Erickson, Harold P

2012-09-28

The bacterial actin homolog ParM has always been modeled as a polar filament, comprising two parallel helical strands, like actin itself. I present arguments here that ParM may be an apolar filament, in which the two helical strands are antiparallel. Copyright © 2012 Elsevier Ltd. All rights reserved.

Proteinase-activated receptor (PAR)-2 activation impacts bone resorptive properties of human osteoarthritic subchondral bone osteoblasts.

PubMed

Amiable, Nathalie; Tat, Steeve Kwan; Lajeunesse, Daniel; Duval, Nicolas; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Boileau, Christelle

2009-06-01

In osteoarthritis (OA), the subchondral bone undergoes a remodelling process involving several factors synthesized by osteoblasts. In this study, we investigated the expression, production, modulation, and role of PAR-2 in human OA subchondral bone osteoblasts. PAR-2 expression and production were determined by real-time PCR and flow cytometry, respectively. PAR-2 modulation was investigated in OA subchondral bone osteoblasts treated with IL-1 beta (100 pg/ml), TNF-alpha (5 ng/ml), TGF-beta1 (10 ng/ml), PGE(2) (500 nM), IL-6 (10 ng/ml) and IL-17 (10 ng/ml). Membranous RANKL protein was assessed by flow cytometry, and OPG, MMP-1, MMP-9, MMP-13, IL-6 and intracellular signalling pathways by specific ELISAs. Bone resorptive activity was measured by using a co-culture model of human PBMC and OA subchondral bone osteoblasts. PAR-2 expression and production (p<0.05) were markedly increased when human OA subchondral bone osteoblasts were compared to normal. On OA osteoblasts, PAR-2 production was significantly increased by IL-1 beta, TNF-alpha and PGE(2). Activation of PAR-2 with a specific agonist, SLIGKV-NH(2), induced a significant up-regulation of MMP-1, MMP-9, IL-6, and membranous RANKL, but had no effect on MMP-13 or OPG production. Interestingly, bone resorptive activity was also significantly enhanced following PAR-2 activation. The PAR-2 effect was mediated by activation of the MAP kinases Erk1/2 and JNK. This study is the first to demonstrate that PAR-2 activation plays a role in OA subchondral bone resorption via an up-regulation of major bone remodelling factors. These results shed new light on the potential of PAR-2 as a therapeutic target in OA.

Prevalence and pattern of abnormal myocardial perfusion in patients with isolated coronary artery ectasia: study by 99mTc-sestamibi radionuclide scintigraphy.

PubMed

Ismail, Ahmed M; Rayan, Mona; Adel, Amr; Demerdash, Salah; Atef, Mohamed; Abdallah, Mohamed; Nammas, Wail

2014-02-01

We explored the prevalence and pattern of abnormal myocardial perfusion in patients with isolated coronary artery ectasia (CAE), as demonstrated by (99m)Tc-sestamibi scintigraphy. Prospectively, we enrolled 35 patients with angiographically documented CAE and no significant coronary obstruction, who underwent elective coronary angiography. Patients underwent Stress-rest (99m)Tc-sestamibi scintigraphy within 4 days of coronary angiography. They were divided into 2 groups: group I: with normal perfusion scan; and group II: with reversible perfusion defects. The mean age was 49.6 ± 6.9 years; 34 (97.1 %) were males. Seventy-nine (75.2 %) arteries were affected by CAE. Among 79 arteries affected by CAE, affection was diffuse in 37 (46.8 %). Thirteen (37.1 %) patients had normal perfusion scan (group I), whereas 22 (62.9 %) had reversible perfusion defects (group II). Among 22 patients with reversible perfusion defects, 20 (90.9 %) had mild and 2 (9.1 %) had moderate ischemia. Among 49 myocardial segments with reversible perfusion defects, 22 (44.9 %) were basal, 18 (36.7 %) mid-, and 9 (18.4 %) apical segments. Diffuse CAE was significantly more prevalent in group II versus group I, in all 3 major coronary arteries (p < 0.05 for all). In patients with isolated CAE who underwent elective coronary angiography, reversible perfusion defects demonstrated by (99m)Tc-sestamibi scintigraphy were rather prevalent, mostly mild, more likely to affect the basal and mid-segments of the myocardium, and more frequently associated with diffuse ectasia.

Towards an improved LAI collection protocol via simulated field-based PAR sensing

DOE PAGES

Yao, Wei; Van Leeuwen, Martin; Romanczyk, Paul; ...

2016-07-14

In support of NASA’s next-generation spectrometer—the Hyperspectral Infrared Imager (HyspIRI)—we are working towards assessing sub-pixel vegetation structure from imaging spectroscopy data. Of particular interest is Leaf Area Index (LAI), which is an informative, yet notoriously challenging parameter to efficiently measure in situ. While photosynthetically-active radiation (PAR) sensors have been validated for measuring crop LAI, there is limited literature on the efficacy of PAR-based LAI measurement in the forest environment. This study (i) validates PAR-based LAI measurement in forest environments, and (ii) proposes a suitable collection protocol, which balances efficiency with measurement variation, e.g., due to sun flecks and various-sized canopymore » gaps. A synthetic PAR sensor model was developed in the Digital Imaging and Remote Sensing Image Generation (DIRSIG) model and used to validate LAI measurement based on first-principles and explicitly-known leaf geometry. Simulated collection parameters were adjusted to empirically identify optimal collection protocols. Furthermore, these collection protocols were then validated in the field by correlating PAR-based LAI measurement to the normalized difference vegetation index (NDVI) extracted from the “classic” Airborne Visible Infrared Imaging Spectrometer (AVIRIS-C) data (R 2 was 0.61). The results indicate that our proposed collecting protocol is suitable for measuring the LAI of sparse forest (LAI < 3–5 ( m 2/m 2)).« less

Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration

PubMed Central

Wang, Shujie; Watanabe, Takashi; Matsuzawa, Kenji; Katsumi, Akira; Kakeno, Mai; Matsui, Toshinori; Ye, Feng; Sato, Kazuhide; Murase, Kiyoko; Sugiyama, Ikuko; Kimura, Kazushi; Mizoguchi, Akira; Ginsberg, Mark H.; Collard, John G.

2012-01-01

Migrating cells acquire front-rear polarity with a leading edge and a trailing tail for directional movement. The Rac exchange factor Tiam1 participates in polarized cell migration with the PAR complex of PAR3, PAR6, and atypical protein kinase C. However, it remains largely unknown how Tiam1 is regulated and contributes to the establishment of polarity in migrating cells. We show here that Tiam1 interacts directly with talin, which binds and activates integrins to mediate their signaling. Tiam1 accumulated at adhesions in a manner dependent on talin and the PAR complex. The interactions of talin with Tiam1 and the PAR complex were required for adhesion-induced Rac1 activation, cell spreading, and migration toward integrin substrates. Furthermore, Tiam1 acted with talin to regulate adhesion turnover. Thus, we propose that Tiam1, with the PAR complex, binds to integrins through talin and, together with the PAR complex, thereby regulates Rac1 activity and adhesion turnover for polarized migration. PMID:23071154

Characterization of a point mutation in the parC gene of Mycoplasma bovirhinis associated with fluoroquinolone resistance.

PubMed

Hirose, K; Kawasaki, Y; Kotani, K; Abiko, K; Sato, H

2004-05-01

Quinolone-resistant (QR) mutants of Mycoplasma bovirhinis strain PG43 (type strain) were generated by stepwise selection in increasing concentrations of enrofloxacin (ENR). An alteration was found in the quinolone resistance-determining region (QRDR) of the parC gene coding for the ParC subunit of topoisomerase IV from these mutants, but not in the gyrA, gyrB, and parE gene coding for the GyrA and GyrB subunits of DNA gyrase and the ParE subunit of topoisomerase IV. Similarly, such an alteration in QRDR of parC was found in the field isolates of M. bovirhinis, which possessed various levels of QR. The substitution of leucine (Leu) by serine (Ser) at position 80 of QRDR of ParC was observed in both QR-mutants and QR-isolates. This is the first report of QR based on a point mutation of the parC gene in M. bovirhinis.

A method for estimating the diffuse attenuation coefficient (KdPAR)from paired temperature sensors

USGS Publications Warehouse

Read, Jordan S.; Rose, Kevin C.; Winslow, Luke A.; Read, Emily K.

2015-01-01

A new method for estimating the diffuse attenuation coefficient for photosynthetically active radiation (KdPAR) from paired temperature sensors was derived. We show that during cases where the attenuation of penetrating shortwave solar radiation is the dominant source of temperature changes, time series measurements of water temperatures at multiple depths (z1 and z2) are related to one another by a linear scaling factor (a). KdPAR can then be estimated by the simple equation KdPAR ln(a)/(z2/z1). A suggested workflow is presented that outlines procedures for calculating KdPAR according to this paired temperature sensor (PTS) method. This method is best suited for conditions when radiative temperature gains are large relative to physical noise. These conditions occur frequently on water bodies with low wind and/or high KdPARs but can be used for other types of lakes during time periods of low wind and/or where spatially redundant measurements of temperatures are available. The optimal vertical placement of temperature sensors according to a priori knowledge of KdPAR is also described. This information can be used to inform the design of future sensor deployments using the PTS method or for campaigns where characterizing sub-daily changes in temperatures is important. The PTS method provides a novel method to characterize light attenuation in aquatic ecosystems without expensive radiometric equipment or the user subjectivity inherent in Secchi depth measurements. This method also can enable the estimation of KdPAR at higher frequencies than many manual monitoring programs allow.

Pectus excavatum in children: pulmonary scintigraphy before and after corrective surgery

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

Blickman, J.G.; Rosen, P.R.; Welch, K.J.

1985-09-01

Regional distribution of pulmonary function was evaluated preoperatively and postoperatively with xenon-133 perfusion and ventilation scintigraphy in 17 patients with pectus excavatum. Ventilatory preoperative studies were abnormal in 12 of 17 patients, resolving in seven of 12 postoperatively. Perfusion scans were abnormal in ten of 17 patients preoperatively; six of ten showed improvement postoperatively. Ventilation-perfusion ratios were abnormal in ten of 17 patients, normalizing postoperatively in six of ten. Symmetry of ventilation-perfusion ratio images improved in six out of nine in the latter group. The distribution of regional lung function in pectus excavatum can be evaluated preoperatively to support indicationsmore » for surgery. Postoperative improvement can be documented by physiological changes produced by the surgical correction.« less

Prospective Comparison of 99mTc-MDP Scintigraphy, Combined 18F-NaF and 18F-FDG PET/CT, and Whole-Body MRI in Patients with Breast and Prostate Cancer.

PubMed

Minamimoto, Ryogo; Loening, Andreas; Jamali, Mehran; Barkhodari, Amir; Mosci, Camila; Jackson, Tatianie; Obara, Piotr; Taviani, Valentina; Gambhir, Sanjiv Sam; Vasanawala, Shreyas; Iagaru, Andrei

2015-12-01

We prospectively evaluated the use of combined (18)F-NaF/(18)F-FDG PET/CT in patients with breast and prostate cancer and compared the results with those for (99m)Tc-MDP bone scintigraphy and whole-body MRI. Thirty patients (15 women with breast cancer and 15 men with prostate cancer) referred for standard-of-care bone scintigraphy were prospectively enrolled in this study. (18)F-NaF/(18)F-FDG PET/CT and whole-body MRI were performed after bone scintigraphy. The whole-body MRI protocol consisted of both unenhanced and contrast-enhanced sequences. Lesions detected with each test were tabulated, and the results were compared. For extraskeletal lesions, (18)F-NaF/(18)F-FDG PET/CT and whole-body MRI had no statistically significant differences in sensitivity (92.9% vs. 92.9%, P = 1.00), positive predictive value (81.3% vs. 86.7%, P = 0.68), or accuracy (76.5% vs. 82.4%, P = 0.56). However, (18)F-NaF/(18)F-FDG PET/CT showed significantly higher sensitivity and accuracy than whole-body MRI (96.2% vs. 81.4%, P < 0.001, 89.8% vs. 74.7%, P = 0.01) and bone scintigraphy (96.2% vs. 64.6%, P < 0.001, 89.8% vs. 65.9%, P < 0.001) for the detection of skeletal lesions. Overall, (18)F-NaF/(18)F-FDG PET/CT showed higher sensitivity and accuracy than whole-body MRI (95.7% vs. 83.3%, P < 0.002, 87.6% vs. 76.0%, P < 0.02) but not statistically significantly so when compared with a combination of whole-body MRI and bone scintigraphy (95.7% vs. 91.6%, P = 0.17, 87.6% vs. 83.0%, P = 0.53). (18)F-NaF/(18)F-FDG PET/CT showed no significant difference from a combination of (18)F-NaF/(18)F-FDG PET/CT and whole-body MRI. No statistically significant differences in positive predictive value were noted among the 3 examinations. (18)F-NaF/(18)F-FDG PET/CT is superior to whole-body MRI and (99m)Tc-MDP scintigraphy for evaluation of skeletal disease extent. Further, (18)F-NaF/(18)F-FDG PET/CT and whole-body MRI detected extraskeletal disease that may change the management of these patients. (18)F

Nurse exposure doses resulted from bone scintigraphy patient

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

Tunçman, Duygu, E-mail: duygutuncman@gmail.com; Demir, Bayram; Kovan, Bilal

Bone scintigraphy is used for displaying the radiologic undiagnosed bone lesions in nuclear medicine. It’s general indications are researching bone metastases, detection of radiographically occult fractures, staging and follow-up in primary bone tumors, diagnosis of paget’s disease, investigation of loosening and infection in orthopedic implants. It is applied with using {sup 99m}Tc labeled radiopharmaceuticals (e.g {sup 99m} Tc MDP,{sup 99m}Tc HEDP and {sup 99m}Tc HMDP). 20 -25 mCi IV radiotracer was injected into vein and radiotracer emits gamma radiation. Patient waits in isolated room for about 3 hours then a gamma camera scans radiation area and creates an image. Whenmore » some patient’s situation is not good, patients are hospitalized until the scanning because of patients’ close contact care need. In this study, measurements were taken from ten patients using Geiger Muller counter. After these measurements, we calculated nurse’s exposure radiations from patient’s routine treatment, examination and emergency station.« less

Historic macrophyte development in Par Pond

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

Grace, J.B.

1985-08-01

Aerial photographs from 1975, 1980, and 1983 were examined to evaluate the changes that have occurred in the wetland vegetation of Par Pond, a reactor-cooling reservoir. Evaluation of the aerial photographs was based on comparisons with ground-level vegetation maps made during July 1984. Comparisons of photographs from August and December of 1983 revealed the main seasonal change in the aerial coverage of wetland vegetation to be the wintertime loss of non-persistent emergent species such as Nelumbo lutea and Nymphaea odorata. Comparisons between September 1980 and August 1983 revealed that the lakeward extent of non-persistent macrophytes has increased by an averagemore » of 8.2 m, though not all sites have changed equally. For persistent macrophytes (principally Typha), the average increase in lakeward extent between December 1975 and August 1983 was 3.48 m. The extensive development of wetland vegetation in Par Pond as well as the substantial spread of vegetation over only a few years time indicates the high suitability of this habitat for the growth of wetland plants.« less

Three-phase bone scintigraphy for diagnosis of Charcot neuropathic osteoarthropathy in the diabetic foot - does quantitative data improve diagnostic value?

PubMed

Fosbøl, M; Reving, S; Petersen, E H; Rossing, P; Lajer, M; Zerahn, B

2017-01-01

To investigate whether inclusion of quantitative data on blood flow distribution compared with visual qualitative evaluation improve the reliability and diagnostic performance of 99 m Tc-hydroxymethylene diphosphate three-phase bone scintigraphy (TPBS) in patients suspected for charcot neuropathic osteoarthropathy (CNO) of the foot. A retrospective cohort study of TPBS performed on 148 patients with suspected acute CNO referred from a single specialized diabetes care centre. The quantitative blood flow distribution was calculated based on the method described by Deutsch et al. All scintigraphies were re-evaluated by independent, blinded observers twice with and without quantitative data on blood flow distribution at ankle and focus level, respectively. The diagnostic validity of TPBS was determined by subsequent review of clinical data and radiological examinations. A total of 90 patients (61%) had confirmed diagnosis of CNO. The sensitivity, specificity and accuracy of three-phase bone scintigraphy without/with quantitative data were 89%/88%, 58%/62% and 77%/78%, respectively. The intra-observer agreement improved significantly by adding quantitative data in the evaluation (Kappa value 0·79/0·94). The interobserver agreement was not significantly improved. Adding quantitative data on blood flow distribution in the interpretation of TBPS improves intra-observer variation, whereas no difference in interobserver variation was observed. The sensitivity of TPBS in the diagnosis of CNO is high, but holds limited specificity. Diagnostic performance does not improve using quantitative data in the evaluation. This may be due to the reference intervals applied in the study or the absence of a proper gold standard diagnostic procedure for comparison. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Hürthle cell tumor dwelling in hot thyroid nodules: preoperative detection with technetium-99m-MIBI dual-phase scintigraphy.

PubMed

Vattimo, A; Bertelli, P; Cintorino, M; Burroni, L; Volterrani, D; Vella, A; Lazzi, S

1998-05-01

Single injection dual-phase scintigraphy (early and late acquisitions) with 99mTc-MIBI was used to differentiate benign and malignant hot thyroid nodules. Thirteen euthyroid and two hyperthyroid patients displaying a hot thyroid nodule on the 99mTc scan due to an autonomously functioning thyroid nodule (AFTN) underwent early (15-30 min) and late (3-4 hr) thyroid scintigraphy after the administration of 740-1000 MBq 99mTc-MIBI. Visual scoring was done to assess nodular tracer uptake and retention. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late image and the washout rates (WO) from the nodule and thyroidal tissue were measured. All patients underwent thyroid surgery. Histopathology revealed a Hürthle cell tumor in three nodules, a benign adenoma with oxyphilic metaplasia in two nodules and a benign adenoma without oxyphilic cells in the remaining 10 nodules. The Hürthle cell tumor nodules displayed intense and persistent uptake of 99mTc-MIBI (N/T was 2.81 +/- 0.52 and 5.53 +/- 1.06 in early and late images, respectively; WO from the nodule was 12.33 +/- 0.47, WO from the thyroidal tissue was 22.00 +/- 3.56). The benign nodules showed intense uptake in the early image and intense uptake to absent retention in the late image (N/T was 2.94 +/- 1.31 and 1.62 +/- 0.50 in the early and late images, respectively; WO from the nodule was 20.25 +/- 2.92, WO from the thyroidal tissue was 20.33 +/- 2.92). Single injection dual-phase 99mTc-MIBI scintigraphy of the thyroid with AFTN can identify nodules as a result of the activity of a Hürthle cell tumor, since these tumors cause intense and persistent tracer uptake in contrast with a benign AFTN.

A Single-Cell Biochemistry Approach Reveals PAR Complex Dynamics during Cell Polarization.

PubMed

Dickinson, Daniel J; Schwager, Francoise; Pintard, Lionel; Gotta, Monica; Goldstein, Bob

2017-08-21

Regulated protein-protein interactions are critical for cell signaling, differentiation, and development. For the study of dynamic regulation of protein interactions in vivo, there is a need for techniques that can yield time-resolved information and probe multiple protein binding partners simultaneously, using small amounts of starting material. Here we describe a single-cell protein interaction assay. Single-cell lysates are generated at defined time points and analyzed using single-molecule pull-down, yielding information about dynamic protein complex regulation in vivo. We established the utility of this approach by studying PAR polarity proteins, which mediate polarization of many animal cell types. We uncovered striking regulation of PAR complex composition and stoichiometry during Caenorhabditis elegans zygote polarization, which takes place in less than 20 min. PAR complex dynamics are linked to the cell cycle by Polo-like kinase 1 and govern the movement of PAR proteins to establish polarity. Our results demonstrate an approach to study dynamic biochemical events in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of normality and reproducibility parameters of scintigraphy with (99m)Tc-MAA in the diagnosis of intrapulmonary vascular dilatations.

PubMed

de Queirós, Andréa Simone Siqueira; Brandão, Simone Cristina Soares; Macedo, Liana Gonçalves; Ourem, Maira Souto; Mota, Vitor Gomes; Leite, Luiz Arthur Calheiros; Lopes, Edmundo Pessoa Almeida; Domingues, Ana Lúcia Coutinho

2015-01-01

The formation of intrapulmonary vascular dilations (IPVD) is the key event for the onset of hepatopulmonary syndrome, vascular changes secondary to portal hypertension that leads to hypoxemia. The diagnosis of IPVD can be made by contrasted transthoracic echocardiography or scintigraphy with technetium-macroaggregated albumin-((99m)Tc-MAA)-that is a sensitive and specific diagnostic method and quantifies the IPVD magnitude. However, its procedure and diagnostic indices are not yet standardized and well defined in health services. The aims of this study were to define normality values and evaluate the inter- and intra-observer reproducibility degree of diagnostic indexes of IPVD through (99m)Tc-MAA scintigraphy. Cross-sectional study was conducted at the Clinical Hospital, Federal University of Pernambuco (HC-UFPE) between July and December 2012. Fifteen patients with hepatosplenic schistosomiasis and nine patients without liver or heart disease (control group) were assessed. After clinical assessment, ultrasound and echocardiography, patients underwent (99m)Tc-MAA scintigraphy, and a relative brain uptake value exceeding 6 % or systemic uptake value exceeding 11 % was considered diagnostic of IPVD. Each assessment was performed by two independent observers. To analyze the results of the normal group, the nonparametric Bootsptrap method simulation model combined with the Monte Carlo method was used and to analyze inter- and intra-observer reproducibility indexes, the kappa and intra-class correlation coefficient were used. In normal subjects, the average brain uptake of (99m)Tc-MAA was 7.9 ± 0.01 % and systemic uptake was 12.4 ± 0.03 %, with low dispersal rates for both measures. The intra-observer agreement was 100 %, with kappa index of 1.0 (p < 0.0001), suggesting a perfect agreement. The inter-observer agreement was also 100 % (kappa = 1.0, p < 0.0001) for brain uptake; however, systemic uptake showed kappa = 0.25 (p = 0.07), which features

The DNA binding parvulin Par17 is targeted to the mitochondrial matrix by a recently evolved prepeptide uniquely present in Hominidae

PubMed Central

Kessler, Daniel; Papatheodorou, Panagiotis; Stratmann, Tina; Dian, Elke Andrea; Hartmann-Fatu, Cristina; Rassow, Joachim; Bayer, Peter; Mueller, Jonathan Wolf

2007-01-01

Background The parvulin-type peptidyl prolyl cis/trans isomerase Par14 is highly conserved in all metazoans. The recently identified parvulin Par17 contains an additional N-terminal domain whose occurrence and function was the focus of the present study. Results Based on the observation that the human genome encodes Par17, but bovine and rodent genomes do not, Par17 exon sequences from 10 different primate species were cloned and sequenced. Par17 is encoded in the genomes of Hominidae species including humans, but is absent from other mammalian species. In contrast to Par14, endogenous Par17 was found in mitochondrial and membrane fractions of human cell lysates. Fluorescence of EGFP fusions of Par17, but not Par14, co-localized with mitochondrial staining. Par14 and Par17 associated with isolated human, rat and yeast mitochondria at low salt concentrations, but only the Par17 mitochondrial association was resistant to higher salt concentrations. Par17 was imported into mitochondria in a time and membrane potential-dependent manner, where it reached the mitochondrial matrix. Moreover, Par17 was shown to bind to double-stranded DNA under physiological salt conditions. Conclusion Taken together, the DNA binding parvulin Par17 is targeted to the mitochondrial matrix by the most recently evolved mitochondrial prepeptide known to date, thus adding a novel protein constituent to the mitochondrial proteome of Hominidae. PMID:17875217

Exercise thallium-201 perfusion scintigraphy in the assessment of coronary artery disease

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

Mahmarian, J.J.; Verani, M.S.

1991-05-21

Exercise thallium-201 perfusion scintigraphy has been used extensively over the last decade for the detection and localization of coronary artery disease. Single-photon emission computed tomography (SPECT) is a refinement of presently available techniques, offering improved identification over planar imaging of individual vessel stenosis and quantification of the extent of abnormally perfused myocardium. In this review, the planar and SPECT techniques are discussed in light of the most recently published large patient series, and with regard to the many factors that affect the sensitivity and specificity of perfusion imaging in identifying coronary artery disease. The clinical implications of exercise perfusion scintigraphymore » and its future applications in cardiology practice are discussed.67 references.« less

Vps26B-retromer negatively regulates plasma membrane resensitization of PAR-2.

PubMed

Bugarcic, Andrea; Vetter, Irina; Chalmers, Silke; Kinna, Genevieve; Collins, Brett M; Teasdale, Rohan D

2015-11-01

Retromer is a trimeric complex composed of Vps26, Vps29, and Vps35 and has been shown to be involved in trafficking and sorting of transmembrane proteins within the endosome. The Vps26 paralog, Vps26B, defines a distinct retromer complex (Vps26B-retromer) in vivo and in vitro. Although endosomally associated, Vps26B-retromer does not bind the established retromer transmembrane cargo protein, cation-independent mannose 6-phosphate receptor (CI-M6PR), indicating it has a distinct role to retromer containing the Vps26A paralog. In the present study we use the previously established Vps26B-expressing HEK293 cell model to address the role of Vps26B-retromer in trafficking of the protease activated G-protein coupled receptor PAR-2 to the plasma membrane. In these cells there is no apparent defect in the initial activation of the receptor, as evidenced by release of intracellular calcium, ERK1/2 signaling and endocytosis of activated receptor PAR-2 into degradative organelles. However, we observe a significant delay in plasma membrane repopulation of the protease activated G protein-coupled receptor PAR-2 following stimulation, resulting in a defect in PAR-2 activation after resensitization. Here we propose that PAR-2 plasma membrane repopulation is regulated by Vps26B-retromer, describing a potential novel role for this complex. © 2015 International Federation for Cell Biology.

Localization of amylin-like immunoreactivity in melanocyte-stimulating hormone-containing cells of the pars intermedia but not those of the pars distalis in the axolotl (Ambystoma mexicanum) pituitary.

PubMed

Suzuki, Hirohumi; Yamamoto, Toshiharu

2016-04-01

Immunohistochemical techniques were employed to investigate the distribution of amylin-like immunoreactivity in the axolotl (Ambystoma mexicanum) pituitary. Amylin-immunoreactive cells were observed in the pars intermedia, and these cells were found to be immunoreactive for α-melanocyte-stimulating hormone (αMSH) as well. In contrast, αMSH-immunoreactive cells in the pars distalis were immuno-negaitive for amylin. These light microscopic findings were confirmed by immunoelectron microscopy. Amylin-immunoreactive signals were located on the haloes of presumable secretory granules in association with αMSH-immunoreactive signals in the amylin-positive cells. However, in the pars distalis, the αMSH-positive cells did not contain amylin-immunoreactive secretory granules. Western blot analysis of axolotl pituitary extracts revealed the labeling of a protein band at approximately 10.5-kDa by the anti-rat amylin serum, which was not labeled by the anti-αMSH antibody. These findings indicate that amylin secreted from MSH-producing cells in the pars intermedia may modulate MSH secretion in an autocrine fashion and may participate in MSH functions such as fatty homeostasis together with MSH. Copyright © 2016 Elsevier GmbH. All rights reserved.

In Vitro Activity of Five Quinolones and Analysis of the Quinolone Resistance-Determining Regions of gyrA, gyrB, parC, and parE in Ureaplasma parvum and Ureaplasma urealyticum Clinical Isolates from Perinatal Patients in Japan

PubMed Central

Kawai, Yasuhiro; Nakura, Yukiko; Wakimoto, Tetsu; Nomiyama, Makoto; Tokuda, Tsugumichi; Takayanagi, Toshimitsu; Shiraishi, Jun; Wasada, Kenshi; Kitajima, Hiroyuki; Fujita, Tomio; Nakayama, Masahiro; Mitsuda, Nobuaki; Nakanishi, Isao; Takeuchi, Makoto

2015-01-01

Ureaplasma spp. cause several disorders, such as nongonococcal urethritis, miscarriage, and preterm delivery with lung infections in neonates, characterized by pathological chorioamnionitis in the placenta. Although reports on antibiotic resistance in Ureaplasma are on the rise, reports on quinolone-resistant Ureaplasma infections in Japan are limited. The purpose of this study was to determine susceptibilities to five quinolones of Ureaplasma urealyticum and Ureaplasma parvum isolated from perinatal samples in Japan and to characterize the quinolone resistance-determining regions in the gyrA, gyrB, parC, and parE genes. Out of 28 clinical Ureaplasma strains, we isolated 9 with high MICs of quinolones and found a single parC gene mutation, resulting in the change S83L. Among 158 samples, the ParC S83L mutation was found in 37 samples (23.4%), including 1 sample harboring a ParC S83L–GyrB P462S double mutant. Novel mutations of ureaplasmal ParC (S83W and S84P) were independently found in one of the samples. Homology modeling of the ParC S83W mutant suggested steric hindrance of the quinolone-binding pocket (QBP), and de novo prediction of peptide structures revealed that the ParC S84P may break/kink the formation of the α4 helix in the QBP. Further investigations are required to unravel the extent and mechanism of antibiotic resistance of Ureaplasma spp. in Japan. PMID:25645833

Par-4, a Gene Required for Cytoplasmic Localization and Determination of Specific Cell Types in Caenorhabditis Elegans Embryogenesis

PubMed Central

Morton, D. G.; Roos, J. M.; Kemphues, K. J.

1992-01-01

Specification of some cell fates in the early Caenorhabditis elegans embryo is mediated by cytoplasmic localization under control of the maternal genome. Using nine newly isolated mutations, and two existing mutations, we have analyzed the role of the maternally expressed gene par-4 in cytoplasmic localization. We recovered seven new par-4 alleles in screens for maternal effect lethal mutations that result in failure to differentiate intestinal cells. Two additional par-4 mutations were identified in noncomplementation screens using strains with a high frequency of transposon mobility. All 11 mutations cause defects early in development of embryos produced by homozygous mutant mothers. Analysis with a deficiency in the region indicates that it33 is a strong loss-of-function mutation. par-4(it33) terminal stage embryos contain many cells, but show no morphogenesis, and are lacking intestinal cells. Temperature shifts with the it57ts allele suggest that the critical period for both intestinal differentiation and embryo viability begins during oogenesis, about 1.5 hr before fertilization, and ends before the four-cell stage. We propose that the primary function of the par-4 gene is to act as part of a maternally encoded system for cytoplasmic localization in the first cell cycle, with par-4 playing a particularly important role in the determination of intestine. Analysis of a par-4;par-2 double mutant suggests that par-4 and par-2 gene products interact in this system. PMID:1582558

The cost-effectiveness of iodine 131 scintigraphy, ultrasonography, and fine-needle aspiration biopsy in the initial diagnosis of solitary thyroid nodules.

PubMed

Khalid, Ayesha N; Hollenbeak, Christopher S; Quraishi, Sadeq A; Fan, Chris Y; Stack, Brendan C

2006-03-01

To compare the cost-effectiveness of fine-needle aspiration biopsy, iodine 131 scintigraphy, and ultrasonography for the initial diagnostic workup of a solitary palpable thyroid nodule. A deterministic cost-effectiveness analysis was conducted using a decision tree to model the diagnostic strategies. A single, mid-Atlantic academic medical center. Expected costs, expected number of cases correctly diagnosed, and incremental cost per additional case correctly diagnosed. Relative to the routine use of fine-needle aspiration biopsy, the incremental cost per case correctly diagnosed is 24,554 dollars for the iodine 131 scintigraphy strategy and 1212 dollars for the ultrasound strategy. A diagnostic strategy using initial fine-needle aspiration biopsy for palpable thyroid nodules was found to be cost-effective compared with the other approaches as long as a payor's willingness to pay for an additional correct diagnosis is less than 1212 dollars. Prospective studies are needed to validate these finding in clinical practice.

Comparison of oral iodine-131-cellulose and indium-111-DTPA as tracers for colon transit scintigraphy: Analysis by colon activity profiles

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

Smart, R.C.; McLean, R.G.; Gaston-Parry, D.

1991-09-01

In 11 normal subjects and 11 patients with a clinical diagnosis of constipation, oral 131I-cellulose and 111In-DTPA were compared simultaneously as tracers for radionuclide colon transit scintigraphy. Visual assessment of the images revealed no differences between tracers. Quantitation was performed using total and segmental percent retention and the derived value of clearance half-time. In addition, profiles of the activity distribution along the length of the colon were generated and the mean position of the activity in the colon calculated. For all indices, the results were similar in both normal subjects and constipated patients when comparing tracers, although marked differences weremore » present between normal subjects and constipated patients for each tracer. Indium-111-DTPA was easy to administer and dosimetry was more acceptable than for 131I-cellulose, especially in constipated patients. It is concluded that 111In-DTPA is the preferred tracer for oral colon transit scintigraphy.« less

u-PAR expression in cancer associated fibroblast: new acquisitions in multiple myeloma progression.

PubMed

Ciavarella, S; Laurenzana, A; De Summa, S; Pilato, B; Chillà, A; Lacalamita, R; Minoia, C; Margheri, F; Iacobazzi, A; Rana, A; Merchionne, F; Fibbi, G; Del Rosso, M; Guarini, A; Tommasi, S; Serratì, S

2017-03-24

Multiple Myeloma (MM) is a B-cell malignancy in which clonal plasma cells progressively expand within the bone marrow (BM) as effect of complex interactions with extracellular matrix and a number of microenvironmental cells. Among these, cancer-associated fibroblasts (CAF) mediate crucial reciprocal signals with MM cells and are associated to aggressive disease and poor prognosis. A large body of evidence emphasizes the role of the urokinase plasminogen activator (u-PA) and its receptor u-PAR in potentiating the invasion capacity of tumor plasma cells, but little is known about their role in the biology of MM CAF. In this study, we investigated the u-PA/u-PAR axis in MM-associated fibroblasts and explore additional mechanisms of tumor/stroma interplay in MM progression. CAF were purified from total BM stromal fraction of 64 patients including monoclonal gammopathy of undetermined significance, asymptomatic and symptomatic MM, as well as MM in post-treatment remission. Flow cytometry, Real Time PCR and immunofluorescence were performed to investigate the u-PA/u-PAR system in relation to the level of activation of CAF at different stages of the disease. Moreover, proliferation and invasion assays coupled with silencing experiments were used to prove, at functional level, the function of u-PAR in CAF. We found higher activation level, along with increased expression of pro-invasive molecules, including u-PA, u-PAR and metalloproteinases, in CAF from patients with symptomatic MM compared to the others stages of the disease. Consistently, CAF from active MM as well as U266 cell line under the influence of medium conditioned by active MM CAF, display higher proliferative rate and invasion potential, which were significantly restrained by u-PAR gene expression inhibition. Our data suggest that the stimulation of u-PA/u-PAR system contributes to the activated phenotype and function of CAF during MM progression, providing a biological rationale for future targeted therapies

Proteinase-activated receptor 2 (PAR(2)) in cholangiocarcinoma (CCA) cells: effects on signaling and cellular level.

PubMed

Kaufmann, Roland; Hascher, Alexander; Mussbach, Franziska; Henklein, Petra; Katenkamp, Kathrin; Westermann, Martin; Settmacher, Utz

2012-12-01

In this study, we demonstrate functional expression of the proteinase-activated receptor 2 (PAR(2)), a member of a G-protein receptor subfamily in primary cholangiocarcinoma (PCCA) cell cultures. Treatment of PCCA cells with the serine proteinase trypsin and the PAR(2)-selective activating peptide, furoyl-LIGRLO-NH(2), increased migration across a collagen membrane barrier. This effect was inhibited by a PAR(2)-selective pepducin antagonist peptide (P2pal-18S) and it was also blocked with the Met receptor tyrosine kinase (Met) inhibitors SU 11274 and PHA 665752, the MAPKinase inhibitors PD 98059 and SL 327, and the Stat3 inhibitor Stattic. The involvement of Met, p42/p44 MAPKinases and Stat3 in PAR(2)-mediated PCCA cell signaling was further supported by the findings that trypsin and the PAR(2)-selective agonist peptide, 2-furoyl-LIGRLO-NH(2), stimulated activating phosphorylation of these signaling molecules in cholangiocarcinoma cells. With our results, we provide a novel signal transduction module in cholangiocarcinoma cell migration involving PAR(2)-driven activation of Met, p42/p44 MAPKinases and Stat3.

Detection of Sentinel Lymph Nodes in Gynecologic Tumours by Planar Scintigraphy and SPECT/CT

PubMed Central

Kraft, Otakar; Havel, Martin

2012-01-01

Objective: Assess the role of planar lymphoscintigraphy and fusion imaging of SPECT/CT in sentinel lymph node (SLN) detection in patients with gynecologic tumours. Material and Methods: Planar scintigraphy and hybrid modality SPECT/CT were performed in 64 consecutive women with gynecologic tumours (mean age 53.6 with range 30-77 years): 36 pts with cervical cancer (Group A), 21 pts with endometrial cancer (Group B), 7 pts with vulvar carcinoma (Group C). Planar and SPECT/CT images were interpreted separately by two nuclear medicine physicians. Efficacy of these two techniques to image SLN were compared. Results: Planar scintigraphy did not image SLN in 7 patients (10.9%), SPECT/CT was negative in 4 patients (6.3%). In 35 (54.7%) patients the number of SLNs captured on SPECT/CT was higher than on planar imaging. Differences in detection of SLN between planar and SPECT/CT imaging in the group of all 64 patients are statistically significant (p<0.05). Three foci of uptake (1.7% from totally visible 177 foci on planar images) in 2 patients interpreted on planar images as hot LNs were found to be false positive non-nodal sites of uptake when further assessed on SPECT/CT. SPECT/CT showed the exact anatomical location of all visualised sentinel nodes. Conclusion: In some patients with gynecologic cancers SPECT/CT improves detection of sentinel lymph nodes. It can image nodes not visible on planar scintigrams, exclude false positive uptake and exactly localise pelvic and paraaortal SLNs. It improves anatomic localization of SLNs. Conflict of interest:None declared. PMID:23486989

Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

NASA Astrophysics Data System (ADS)

Hansen, Line; Unmack Larsen, Esben Kjær; Nielsen, Erik Holm; Iversen, Frank; Liu, Zhuo; Thomsen, Karen; Pedersen, Michael; Skrydstrup, Troels; Nielsen, Niels Chr.; Ploug, Michael; Kjems, Jørgen

2013-08-01

Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific

Paraplégie compliquant une plaie abdominale antérieure par arme blanche

PubMed Central

Elahmadi, Brahim; Awab, Almahdi; El Moussaoui, Rachid; El Hijri, Ahmed; Azzouzi, Abderrahim; Alilou, Mustapha

2015-01-01

Les traumatismes médullaires sont des complications rares des plaies abdominales antérieures par arme blanche. Son diagnostic est difficile parfois retardé. L'imagerie par résonance magnétique reste l'examen de choix. Le traitement dépend du tableau clinique et de la gravité de la souffrance médullaire. Le pronostic est corrélé à l’étendue et à la nature de la lésion médullaire. Nous rapportons un cas exceptionnel d'un traumatisme médullaire chez une patiente victime d'une plaie abdominale antérieure par arme blanche. PMID:25995808

In vitro activity of five quinolones and analysis of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE in Ureaplasma parvum and Ureaplasma urealyticum clinical isolates from perinatal patients in Japan.

PubMed

Kawai, Yasuhiro; Nakura, Yukiko; Wakimoto, Tetsu; Nomiyama, Makoto; Tokuda, Tsugumichi; Takayanagi, Toshimitsu; Shiraishi, Jun; Wasada, Kenshi; Kitajima, Hiroyuki; Fujita, Tomio; Nakayama, Masahiro; Mitsuda, Nobuaki; Nakanishi, Isao; Takeuchi, Makoto; Yanagihara, Itaru

2015-04-01

Ureaplasma spp. cause several disorders, such as nongonococcal urethritis, miscarriage, and preterm delivery with lung infections in neonates, characterized by pathological chorioamnionitis in the placenta. Although reports on antibiotic resistance in Ureaplasma are on the rise, reports on quinolone-resistant Ureaplasma infections in Japan are limited. The purpose of this study was to determine susceptibilities to five quinolones of Ureaplasma urealyticum and Ureaplasma parvum isolated from perinatal samples in Japan and to characterize the quinolone resistance-determining regions in the gyrA, gyrB, parC, and parE genes. Out of 28 clinical Ureaplasma strains, we isolated 9 with high MICs of quinolones and found a single parC gene mutation, resulting in the change S83L. Among 158 samples, the ParC S83L mutation was found in 37 samples (23.4%), including 1 sample harboring a ParC S83L-GyrB P462S double mutant. Novel mutations of ureaplasmal ParC (S83W and S84P) were independently found in one of the samples. Homology modeling of the ParC S83W mutant suggested steric hindrance of the quinolone-binding pocket (QBP), and de novo prediction of peptide structures revealed that the ParC S84P may break/kink the formation of the α4 helix in the QBP. Further investigations are required to unravel the extent and mechanism of antibiotic resistance of Ureaplasma spp. in Japan. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Monomer–dimer dynamics and distribution of GPI-anchored uPAR are determined by cell surface protein assemblies

PubMed Central

Caiolfa, Valeria R.; Zamai, Moreno; Malengo, Gabriele; Andolfo, Annapaola; Madsen, Chris D.; Sutin, Jason; Digman, Michelle A.; Gratton, Enrico; Blasi, Francesco; Sidenius, Nicolai

2007-01-01

To search for functional links between glycosylphosphatidylinositol (GPI) protein monomer–oligomer exchange and membrane dynamics and confinement, we studied urokinase plasminogen activator (uPA) receptor (uPAR), a GPI receptor involved in the regulation of cell adhesion, migration, and proliferation. Using a functionally active fluorescent protein–uPAR in live cells, we analyzed the effect that extracellular matrix proteins and uPAR ligands have on uPAR dynamics and dimerization at the cell membrane. Vitronectin directs the recruitment of dimers and slows down the diffusion of the receptors at the basal membrane. The commitment to uPA–plasminogen activator inhibitor type 1–mediated endocytosis and recycling modifies uPAR diffusion and induces an exchange between uPAR monomers and dimers. This exchange is fully reversible. The data demonstrate that cell surface protein assemblies are important in regulating the dynamics and localization of uPAR at the cell membrane and the exchange of monomers and dimers. These results also provide a strong rationale for dynamic studies of GPI-anchored molecules in live cells at steady state and in the absence of cross-linker/clustering agents. PMID:18056417

Optical heterogeneous bioassay for the detection of the inflammatory biomarker suPAR

NASA Astrophysics Data System (ADS)

Tombelli, S.; Trono, C.; Adinolfi, B.; Chiavaioli, F.; Giannetti, A.; Eugen-Olsen, J.; Bernini, R.; Grimaldi, I. A.; Persichetti, G.; Testa, G.; Baldini, F.

2015-03-01

Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory protein present in blood and a marker of disease presence, severity and prognosis. A heterogeneous sandwich assay is proposed for quantifying suPAR by employing a capture antibody from rat and a biotinylated detection antibody from mouse. Optical detection was achieved by a successive exposure of the biotinylated sandwich to streptavidin labelled with ATTO647N. The heterogeneous assay was implemented on a multichannel polymethylmetacrylate (PMMA) optical biochip, potentially capable of the simultaneous detection of more than one analyte. Capture antibody was immobilized on the PMMA surface of the microfluidic channel and the assay was performed with the following protocol: i) surface blocking with BSA, ii) incubation with suPAR or PBS, iii) incubation with biotinylated suPAR detection Ab and iv) incubation with streptavidin-ATTO647N. Promising preliminary results were obtained with this protocol. Moreover, an improved optical setup is proposed which avoids the mechanical scanning of the chip and consequently the in-series fluorescence excitation and read out, allowing the simultaneous measurement of the fluorescence on all the channels of the microfluidic chip.

Effect of Par Frying on Composition and Texture of Breaded and Battered Catfish

USDA-ARS?s Scientific Manuscript database

Catfish is often consumed as a breaded and battered fried product; however, baking is considered a healthier alternative to frying. One method of improving the texture properties of baked products is to par fried prior to baking. The objective of this study was to examine the effect of par frying ...

Lambeaux autofermants pour le traitement des brulures electriques du scalp par haut voltage

PubMed Central

Hafidi, J.; El Mazouz, S.; El Mejatti, H.; Fejjal, N.; Gharib, N.E.; Abbassi, A.; Belmahi, A.M.

2011-01-01

Summary Les brûlures électriques par haut voltage sont responsables de gros dégâts tissulaires en immédiat et dans les jours suivant l’accident du fait de la chaleur importante dégagée par effet joule et de la thrombose microvasculaire évolutive. Les pertes de substances du scalp secondaires à ces brûlures nécessitent une couverture par lambeaux vu la destruction du périoste et du calvarium en regard. De juin 1997 à juin 2008, 15 patients ont été traités pour des pertes de substance du scalp secondaires à des brûlures électriques par haut voltage de diamètre allant de 8 à 11 cm et siégeant dans la région tonsurale. Ces patients ont été opérés dans la première semaine suivant l’accident. Les pertes de substance du scalp de taille moyenne secondaires à ces brûlures peuvent être couvertes per primam de façon fiable par des lambeaux locaux axialisés et multiples. Nous relatons l’expérience du Service de Chirurgie Plastique du Centre Hospitalier Universitaire Ibn-Sina, Rabat, Maroc, dans la gestion et la prise en charge de ces brûlures. PMID:22262963

Planar Cell Polarity Breaks the Symmetry of PAR Protein Distribution prior to Mitosis in Drosophila Sensory Organ Precursor Cells.

PubMed

Besson, Charlotte; Bernard, Fred; Corson, Francis; Rouault, Hervé; Reynaud, Elodie; Keder, Alyona; Mazouni, Khalil; Schweisguth, François

2015-04-20

During development, cell-fate diversity can result from the unequal segregation of fate determinants at mitosis. Polarization of the mother cell is essential for asymmetric cell division (ACD). It often involves the formation of a cortical domain containing the PAR complex proteins Par3, Par6, and atypical protein kinase C (aPKC). In the fly notum, sensory organ precursor cells (SOPs) divide asymmetrically within the plane of the epithelium and along the body axis to generate two distinct cells. Fate asymmetry depends on the asymmetric localization of the PAR complex. In the absence of planar cell polarity (PCP), SOPs divide with a random planar orientation but still asymmetrically, showing that PCP is dispensable for PAR asymmetry at mitosis. To study when and how the PAR complex localizes asymmetrically, we have used a quantitative imaging approach to measure the planar polarization of the proteins Bazooka (Baz, fly Par3), Par6, and aPKC in living pupae. By using imaging of functional GFP-tagged proteins with image processing and computational modeling, we find that Baz, Par6, and aPKC become planar polarized prior to mitosis in a manner independent of the AuroraA kinase and that PCP is required for the planar polarization of Baz, Par6, and aPKC during interphase. This indicates that a "mitosis rescue" mechanism establishes asymmetry at mitosis in PCP mutants. This study therefore identifies PCP as the initial symmetry-breaking signal for the planar polarization of PAR proteins in asymmetrically dividing SOPs. Copyright © 2015 Elsevier Ltd. All rights reserved.

In vitro and in vivo inhibition of proangiogenic retinal phenotype by an antisense oligonucleotide downregulating uPAR expression.

PubMed

Lulli, Matteo; Cammalleri, Maurizio; Granucci, Irene; Witort, Ewa; Bono, Silvia; Di Gesualdo, Federico; Lupia, Antonella; Loffredo, Rosa; Casini, Giovanni; Dal Monte, Massimo; Capaccioli, Sergio

2017-08-26

Neoangiogenesis is the main pathogenic event involved in a variety of retinal diseases. It has been recently demonstrated that inhibiting the urokinase-type plasminogen activator receptor (uPAR) results in reduced angiogenesis in a mouse model of oxygen-induced retinopathy (OIR), establishing uPAR as a therapeutic target in proliferative retinopathies. Here, we evaluated in cultured human retinal endothelial cells (HRECs) and in OIR mice the potential of a specific antisense oligodeoxyribonucleotide (ASO) in blocking the synthesis of uPAR and in providing antiangiogenic effects. uPAR expression in HRECs was inhibited by lipofection with the phosphorotioated 5'-CGGCGGGTGACCCATGTG-3' ASO-uPAR, complementary to the initial translation site of uPAR mRNA. Inhibition of uPAR expression via ASO-uPAR was evaluated in HRECs by analyzing VEGF-induced tube formation and migration. In addition, the well-established and reproducible murine OIR model was used to induce retinal neovascularization in vivo. OIR mice were injected intraperitoneally with ASO-uPAR and retinopathy was evaluated considering the extent of the avascular area in the central retina and neovascular tuft formation. The ASO-uPAR specifically decreased uPAR mRNA and protein levels in HRECs and mitigated VEGF-induced tube formation and cell migration. Noteworthy, in OIR mice ASO-uPAR administration reduced both the avascular area and the formation of neovascular tufts. In conclusion, although the extrapolation of these experimental findings to the clinic is not straightforward, ASO-uPAR may be considered a potential therapeutic tool for treatment of proliferative retinal diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

ParFit: A Python-Based Object-Oriented Program for Fitting Molecular Mechanics Parameters to ab Initio Data

DOE PAGES

Zahariev, Federico; De Silva, Nuwan; Gordon, Mark S.; ...

2017-02-23

Here, a newly created object-oriented program for automating the process of fitting molecular-mechanics parameters to ab initio data, termed ParFit, is presented. ParFit uses a hybrid of deterministic and stochastic genetic algorithms. ParFit can simultaneously handle several molecular-mechanics parameters in multiple molecules and can also apply symmetric and antisymmetric constraints on the optimized parameters. The simultaneous handling of several molecules enhances the transferability of the fitted parameters. ParFit is written in Python, uses a rich set of standard and nonstandard Python libraries, and can be run in parallel on multicore computer systems. As an example, a series of phosphine oxides,more » important for metal extraction chemistry, are parametrized using ParFit.« less

ParFit: A Python-Based Object-Oriented Program for Fitting Molecular Mechanics Parameters to ab Initio Data

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

Zahariev, Federico; De Silva, Nuwan; Gordon, Mark S.

Here, a newly created object-oriented program for automating the process of fitting molecular-mechanics parameters to ab initio data, termed ParFit, is presented. ParFit uses a hybrid of deterministic and stochastic genetic algorithms. ParFit can simultaneously handle several molecular-mechanics parameters in multiple molecules and can also apply symmetric and antisymmetric constraints on the optimized parameters. The simultaneous handling of several molecules enhances the transferability of the fitted parameters. ParFit is written in Python, uses a rich set of standard and nonstandard Python libraries, and can be run in parallel on multicore computer systems. As an example, a series of phosphine oxides,more » important for metal extraction chemistry, are parametrized using ParFit.« less

Décontamination nucléaire par laser UV

NASA Astrophysics Data System (ADS)

Delaporte, Ph.; Gastaud, M.; Marine, W.; Sentis, M.; Uteza, O.; Thouvenot, P.; Alcaraz, J. L.; Le Samedy, J. M.; Blin, D.

2003-06-01

Le développement et l'utilisation de procédés propres pour le nettoyage ou la préparation de surfaces est l'une des priorités du milieu industriel. Cet intérêt est d'autant plus grand dans le domaine du nucléaire pour lequel la réduction des déchets est un axe de recherche important. Un dispositif de décontamination nucléaire par laser UV impulsionnel a été développé et testé. Il est composé. d'un laser à excimères de 1kW, d'un faisceau de fibres optiques et d'un dispositif de récupération des particules. Les essais réalisés en milieu actif ont démontré sa capacité à nettoyer des surfaces métalliques polluées par différents radioéléments avec des facteurs de décontamination généralement supérieurs à 10. Ce dispositif permet de décontaminer de grandes surfaces de géométrie simple en réduisant fortement la génération de déchets secondaires. Il est, à ce jour et dans ces conditions d'utilisations, le procédé de décontamination par voie sèche le plus efficace.

Identification of exosite residues of factor Xa involved in recognition of PAR-2 on endothelial cells.

PubMed

Manithody, Chandrashekhara; Yang, Likui; Rezaie, Alireza R

2012-03-27

Recent results have indicated that factor Xa (FXa) cleaves protease-activated receptor 2 (PAR-2) to elicit protective intracellular signaling responses in endothelial cells. In this study, we investigated the molecular determinants of the specificity of FXa interaction with PAR-2 by monitoring the cleavage of PAR-2 by FXa in endothelial cells transiently transfected with a PAR-2 cleavage reporter construct in which the extracellular domain of the receptor was fused to cDNA encoding for alkaline phosphatase. Comparison of the cleavage efficiency of PAR-2 by a series of FXa mutants containing mutations in different surface loops indicated that the acidic residues of 39-loop (Glu-36, Glu-37, and Glu-39) and the basic residues of 60-loop (Lys-62 and Arg-63), 148-loop (Arg-143, Arg-150, and Arg-154), and 162-helix (Arg-165 and Lys-169) contribute to the specificity of receptor recognition by FXa on endothelial cells. This was evidenced by significantly reduced activity of mutants toward PAR-2 expressed on transfected cells. The extent of loss in the PAR-2 cleavage activity of FXa mutants correlated with the extent of loss in their PAR-2-dependent intracellular signaling activity. Further characterization of FXa mutants indicated that, with the exception of basic residues of 162-helix, which play a role in the recognition specificity of the prothrombinase complex, none of the surface loop residues under study makes a significant contribution to the activity of FXa in the prothrombinase complex. These results provide new insight into mechanisms through which FXa specifically interacts with its macromolecular substrates in the clotting and signaling pathways.

Enhanced proliferation of human hepatoma cells by PAR-2 agonists via the ERK/AP-1 pathway.

PubMed

Xie, Liqun; Zheng, Yanmin; Li, Xuan; Zhao, Junyan; Chen, Xiaoyi; Chen, Li; Zhou, Jing; Hai, Ou; Li, Fei

2012-11-01

To investigate the expression and role of PAR-2 in the proliferation of the human hepatoma cell line HepG2, PAR-2 protein and mRNA expression were evaluated by immuno-histochemistry, immunofluorescence and RT-PCR analysis. The signaling pathways downstream of PAR-2 activation that lead to hepatoma cell proliferation were analyzed. The results showed that PAR-2 is expressed in human hepatoma cells and PAR-2 mRNA expression was found to be upregulated in cells treated with trypsin or SLIGKV-NH2 (P<0.001). The proliferation rate of HepG2 cells treated with trypsin or SLIGKV-NH2 was significantly increased (P<0.001). The percentage of S phase, G2/M phase and the proliferation index (PI) of HepG2 cells treated with trypsin or SLIGKV-NH2 were significantly elevated (P<0.001). The proliferative responses of HepG2 to trypsin and SLIGKV-NH2 were associated with the upregulation of c-fos and PCNA, which were significantly blocked by PD98059 pretreatment. In conclusion, our results indicate that PAR-2 enhances proliferation of human hepatoma cells possibly via the ERK/AP-1 pathway.

Effects of dietary milk thistle on blood parameters, liver pathology, and hepatobiliary scintigraphy in white carneaux pigeons (Columba livia) challenged with B1 aflatoxin.

PubMed

Grizzle, Judith; Hadley, Tarah L; Rotstein, David S; Perrin, Shannon L; Gerhardt, Lillian E; Beam, James D; Saxton, Arnold M; Jones, Michael P; Daniel, Gregory B

2009-06-01

Milk thistle (Silybum marianum) has been used in humans for the treatment of liver disease because of its antioxidant properties and its ability to stabilize cell membranes and regulate cell permeability. To investigate possible hepatoprotective effects in birds, standardized extracts (80%) of silymarin from milk thistle were tested in white Carneaux pigeons (Columba livia). Pigeons were separated into 3 groups and fed diets formulated to provide milk thistle at a level of 0, 10, or 100 mg/kg body weight per day. After acclimation, the birds were challenged with B1 aflatoxin (3 mg/kg body weight for 2 consecutive days) by oral gavage. Liver function then was assessed by hematologic testing and plasma biochemical analysis, liver histopathology, and hepatobiliary scintigraphy. Results of histopathology and hepatobiliary scintigraphy showed no protective effects from milk-thistle administration. Aflatoxin challenge resulted in hepatic inflammation and necrosis, biliary-duct hyperplasia, and lymphocyte infiltration. All hepatobiliary scintigraphy elements increased significantly after aflatoxin challenge. Bile acid levels and plasma enzyme concentrations of aspartate aminotransferase, lactate dehydrogenase, alanine aminotransferase, and creatine phosphokinase all increased after aflatoxin exposure and were mostly unchanged with consumption of milk thistle. Only birds fed 10 mg/kg body weight milk thistle showed significant reductions in lactate dehydrogenase, alanine aminotransferase, and creatine phosphokinase concentrations after aflatoxin exposure. Our results show that consumption of milk thistle is not associated with hepatoprotective effects against acute B1 aflatoxin exposure in pigeons.

Questioning Our Questions: Assessing Question Asking Practices to Evaluate a yPAR Program

ERIC Educational Resources Information Center

Grace, Sarah; Langhout, Regina Day

2014-01-01

The purpose of this research was to examine question asking practices in a youth participatory action research (yPAR) after school program housed at an elementary school. The research question was: In which ways did the adult question asking practices in a yPAR setting challenge and/or reproduce conventional models of power in educational…

[Effect of ERK/AP-1 signaling pathway on proliferation of hepatoma cells induced by PAR-2 agonists].

PubMed

Zheng, Yan-min; Xie, Li-qun; Li, Xuan; Zhao, Jun-yan; Chen, Xiao-yi; Chen, Li; Zhou, Jing; Li, Fei

2009-12-01

To investigate the expression of protease activated receptor-2 (PAR-2) in human HepG2 hepatoma cells and elucidate the effects of trypsin and PAR-2 agonist peptide SLIGKV-NH(2) upon the proliferation of hepatoma cells and its intracellular signaling mechanism. PAR-2 protein and mRNA expression were detected by immunofluorescence and RT-PCR. The cells were treated with SLIGKV-NH(2), trypsin, reverse PAR-2 agonist peptide VKGILS-NH(2) or PD98059. The changes of cell cycle distribution were evaluated by flow cytometry. The proliferative potential of HepG2 cells was estimated by MTT. The changes of PAR-2, c-fos and PCNA mRNA expression were detected by RT-PCR. The changes of c-fos and PCNA protein expression were detected by Western blotting. PAR-2 protein and mRNA were expressed in HepG2 cells. PAR-2 mRNA expression (PAR-2/beta-actin) were 0.70 +/- 0.04 and 0.99 +/- 0.05 respectively in cells treated with trypsin and SLIGKV-NH(2). They were both significantly higher than that in the control group (0.35 +/- 0.05, F = 135.534, P < 0.01). Percent G(0)/G(1) phase of HepG2 cells treated with trypsin or SLIGKV-NH(2) were significantly lower than those in the control group [(56.11 +/- 0.85)%, (57.85 +/- 0.46)% vs (79.12 +/- 0.67)%, both P < 0.01] Percent S phase, G(2)/M phase and proliferation index (PI) of HepG2 cells treated with trypsin or SLIGKV-NH(2) were significantly elevated (P < 0.01). The proliferation-enhancing effects and the up-regulation of mRNA and protein of c-fos and PCNA induced by trypsin or SLIGKV-NH(2) were significantly blocked by pretreatment with PD98059 (P < 0.01). There was no statistical significance in proliferation of HepG2 cells between the reverse PAR-2 agonist peptide VKGILS-NH(2) and control group (P > 0.05). PAR-2 is expressed in HepG2 hepatoma cells. PAR-2 activation induced by trypsin or SLIGKV-NH(2) promotes the proliferation of HepG2 cells partially via the ERK/AP-1 pathway.

Combination with CK19 Might Increase the Prognostic Power of Hep Par 1 in Hepatocellular Carcinoma after Curative Resection.

PubMed

Jin, Ye; Liang, Zhi-Yong; Zhou, Wei-Xun; Zhou, Li

2017-07-31

Hepatocyte Paraffin 1 (Hep Par 1) and cytokeratin 19 (CK19) were shown to be associated with post-surgical prognosis of hepatocellular carcinoma (HCC). However, further validation might be needed. Besides, their combined evaluation has not been reported. The present study was designed to address the issues. Expressions of Hep Par 1 and CK19 were detected using tissue microarray-based immunohistochemical staining in 79 patients with HCC underwent curative hepatectomy. Their associations with cliniopathologic variables, overall and recurrence-free survival were analyzed. Hep Par 1 was highly expressed in 61 patients (77.2%), whereas CK19 was positive in 8 patients (10.1%). Moreover, expressions of these two proteins were all associated with tumor-node-metastasis (TNM) stage and vascular invasion. It was found that high Hep Par 1 expression was univariately associated with good overall and recurrence-free survival, while CK19 was marginally prognostic. Also in univariate analyses, combination of the two markers more effectively predicted for long-term prognosis in HCC than Hep Par 1 did. However, neither Hep Par 1 nor Hep Par 1/CK19 was multivariately significant. Finally, Hep Par 1/CK19 combined with TNM stage might obtain more satisfactory outcome prediction, especially for overall survival. Combination of CK19 with Hep Par 1 might have higher prognostic power, which might be further improved by adding TNM stage, than Hep Par 1 alone, in resected HCC. Of course, subsequent confirmation is necessary.

Fully human antibodies against the Protease-Activated Receptor-2 (PAR-2) with anti-inflammatory activity.

PubMed

Giblin, Patricia; Boxhammer, Rainer; Desai, Sudha; Kroe-Barrett, Rachel; Hansen, Gale; Ksiazek, John; Panzenbeck, Maret; Ralph, Kerry; Schwartz, Racheline; Zimmitti, Clare; Pracht, Catrin; Miller, Sandra; Magram, Jeanne; Litzenburger, Tobias

2011-01-01

PAR-2 belongs to a family of G-protein coupled Protease-Activated Receptors (PAR) which are activated by specific proteolytic cleavage in the extracellular N-terminal region. PAR-2 is activated by proteases such as trypsin, tryptase, proteinase 3, factor VIIa, factor Xa and is thought to be a mediator of inflammation and tissue injury, where elevated levels of proteases are found. Utilizing the HuCAL GOLD® phage display library we generated fully human antibodies specifically blocking the protease cleavage site in the N-terminal domain. In vitro affinity optimization resulted in antibodies with up to 1000-fold improved affinities relative to the original parental antibodies with dissociation constants as low as 100 pM. Corresponding increases in potency were observed in a mechanistic protease cleavage assay. The antibodies effectively inhibited PAR-2 mediated intracellular calcium release and cytokine secretion in various cell types stimulated with trypsin. In addition, the antibodies demonstrated potent inhibition of trypsin induced relaxation of isolated rat aortic rings ex vivo. In a short term mouse model of inflammation, the trans vivo DTH model, anti-PAR-2 antibodies showed inhibition of the inflammatory swelling response. In summary, potent inhibitors of PAR-2 were generated which allow further assessment of the role of this receptor in inflammation and evaluation of their potential as therapeutic agents.

Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers

PubMed Central

Miotto, D; Hollenberg, M; Bunnett, N; Papi, A; Braccioni, F; Boschetto, P; Rea, F; Zuin, A; Geppetti, P; Saetta, M; Maestrelli, P; Fabbri, L; Mapp, C

2002-01-01

Background: Protease activated receptor-2 (PAR-2) is a transmembrane G protein coupled receptor preferentially activated by trypsin and tryptase. The protease activated receptors play an important role in most components of injury responses including cell proliferation, migration, matrix remodelling, and inflammation. Cigarette smoking causes an inflammatory process in the central airways, peripheral airways, lung parenchyma, and adventitia of pulmonary arteries. Methods: To quantify the expression of PAR-2 in the central airways of smokers and non-smokers, surgical specimens obtained from 30 subjects undergoing lung resection for localised pulmonary lesions (24 with a history of cigarette smoking and six non-smoking control subjects) were examined. Central airways were immunostained with an antiserum specific for PAR-2 and PAR-2 expression was quantified using light microscopy and image analysis. Results: PAR-2 expression was found in bronchial smooth muscle, epithelium, glands, and in the endothelium and smooth muscle of bronchial vessels. PAR-2 expression was similar in the central airways of smokers and non-smokers. When smokers were divided according to the presence of symptoms of chronic bronchitis and chronic airflow limitation, PAR-2 expression was increased in smooth muscle (median 3.8 (interquartile range 2.9–5.8) and 1.4 (1.07–3.4) respectively); glands (33.3 (18.2–43.8) and 16.2 (11.5–22.2), respectively); and bronchial vessels (54.2 (48.7–56.8) and 40.0 (36–40.4), respectively) of smokers with symptoms of chronic bronchitis with normal lung function compared with smokers with chronic airflow limitation (COPD), but the increase was statistically significant (p<0.005) only for bronchial vessels. Conclusions: PAR-2 is present in bronchial smooth muscle, glands, and bronchial vessels of both smokers and non-smokers. An increased expression of PAR-2 was found in bronchial vessels of patients with bronchitis compared with those with COPD. PMID

Diffraction de rayons X sur les plaquettes de fer durcies par cyanuration

NASA Astrophysics Data System (ADS)

Popescu, M.; Hoyer, W.; Stegarescu, M.; Cornet, A.; Broll, N.

2004-11-01

Une méthode de cyanuration a été developpée pour les surfaces des plaquettes de fer, basée sur une réaction thermochimique qui conduit à la formation des couches dures sur le métal. Les échantillons ont été analysés, pour de temps différents de traitement, par diffraction de rayons X et par mesures de dureté.

PAR1 participates in the ability of multidrug resistance and tumorigenesis by controlling Hippo-YAP pathway.

PubMed

Fujimoto, Daisuke; Ueda, Yuki; Hirono, Yasuo; Goi, Takanori; Yamaguchi, Akio

2015-10-27

The Hippo pathway significantly correlates with organ size control and tumorigenesis. The activity of YAP/TAZ, a transducer of the Hippo pathway, is required to sustain self-renewal and tumor-initiation capacities in cancer stem cells (CSCs). But, upstream signals that control the mammalian Hippo pathway have not been well understood. Here, we reveal a connection between the Protease-activated receptor 1 (PAR1) signaling pathway and the Hippo-YAP pathway in gastric cancer stem-like cells. The selective PAR1 agonist TFLLR-NH2 induces an increase in the fraction of side population cells which is enriched in CSCs, and promotes tumorigenesis, multi cancer drug resistance, cell morphological change, and cell invasion which are characteristics of CSCs. In addition, PAR1 activation inhibits the Hippo-YAP pathway kinase Lats via Rho GTPase. Lats kinase inhibition in turn results in increased nuclear localization of dephosphorylated YAP. Furthermore, PAR1 activation confers CSCs related traits via the Hippo-YAP pathway, and the Hippo-YAP pathway correlates with epithelial mesenchymal transition which is induced by PAR1 activation. Our research suggests that the PAR1 signaling deeply participates in the ability of multi drug resistance and tumorigenesis through interactions with the Hippo-YAP pathway signaling in gastric cancer stem-like cells. We presume that inhibited YAP is a new therapeutic target in the treatment human gastric cancer invasion and metastasis by dysregulated PAR1 or its agonists.

Loss of Par-1a/MARK3/C-TAK1 kinase leads to reduced adiposity, resistance to hepatic steatosis, and defective gluconeogenesis.

PubMed

Lennerz, Jochen K; Hurov, Jonathan B; White, Lynn S; Lewandowski, Katherine T; Prior, Julie L; Planer, G James; Gereau, Robert W; Piwnica-Worms, David; Schmidt, Robert E; Piwnica-Worms, Helen

2010-11-01

Par-1 is an evolutionarily conserved protein kinase required for polarity in worms, flies, frogs, and mammals. The mammalian Par-1 family consists of four members. Knockout studies of mice implicate Par-1b/MARK2/EMK in regulating fertility, immune homeostasis, learning, and memory as well as adiposity, insulin hypersensitivity, and glucose metabolism. Here, we report phenotypes of mice null for a second family member (Par-1a/MARK3/C-TAK1) that exhibit increased energy expenditure, reduced adiposity with unaltered glucose handling, and normal insulin sensitivity. Knockout mice were protected against high-fat diet-induced obesity and displayed attenuated weight gain, complete resistance to hepatic steatosis, and improved glucose handling with decreased insulin secretion. Overnight starvation led to complete hepatic glycogen depletion, associated hypoketotic hypoglycemia, increased hepatocellular autophagy, and increased glycogen synthase levels in Par-1a(-/-) but not in control or Par-1b(-/-) mice. The intercrossing of Par-1a(-/-) with Par-1b(-/-) mice revealed that at least one of the four alleles is necessary for embryonic survival. The severity of phenotypes followed a rank order, whereby the loss of one Par-1b allele in Par-1a(-/-) mice conveyed milder phenotypes than the loss of one Par-1a allele in Par-1b(-/-) mice. Thus, although Par-1a and Par-1b can compensate for one another during embryogenesis, their individual disruption gives rise to distinct metabolic phenotypes in adult mice.

Nd:YAG vitreolysis and pars plana vitrectomy: surgical treatment for vitreous floaters.

PubMed

Delaney, Y M; Oyinloye, A; Benjamin, L

2002-01-01

To determine the efficacy of Nd:YAG vitreolysis and pars plana vitrectomy in the treatment of vitreous floaters. This is a single centre retrospective study of 31 patients (42 eyes) who underwent 54 procedures, Nd:YAG vitreolysis or pars plana vitrectomy, for the treatment of vitreous floaters between January 1992 and December 2000. Main outcome measures were percentage symptomatic improvement following treatment and incidence of post-operative complications. Statistical analysis was performed using the Fisher exact test. Posterior vitreous detachment was the primary cause of floaters in all 42 eyes with co-existing vitreous veils in three eyes and asteroid hyalosis in two eyes. Thirty-nine of 42 eyes received Nd:YAG vitreolysis. Thirty-eight percent found Nd:YAG vitreolysis moderately improved their symptoms while 61.5% found no improvement. After an average of 14.7 months follow-up no post-operative complications were recorded. Fifteen eyes underwent a pars plana vitrectomy, one with combined phacoemulsification and posterior chamber implantation and 11 following unsuccessful laser vitreolysis. Pars plana vitrectomy resulted in full resolution of symptoms in 93.3% of eyes. One patient developed a post-operative retinal detachment which was successfully treated leaving the patient with 6/5 VA. Patients' symptoms from vitreous floaters are often underestimated resulting in no intervention. This paper shows Nd:YAG vitreolysis to be a safe but only moderately effective primary treatment conferring clinical benefit in one third of patients. Pars plana vitrectomy, while offering superior results, should be reserved for patients who remain markedly symptomatic following vitreolysis, until future studies further clarify its role in the treatment of patients with floaters and posterior vitreous detachment.

[Tryptase inhibits cell apoptosis through upregulating PAR-2 and Rho kinase in rheumatoid arthritis synovial fibroblasts].

PubMed

Zheng, Qianqian; Li, Shigang; Jia, Yunli; Liu, Wei; Yu, Lingling; Chen, Xianyong; Wang, Jinling

2016-12-01

Objective To investigate the regulatory effects of tryptase on protease-activated receptors 2 (PAR-2), Rho signal pathway and apoptosis of MH7A rheumatoid arthritis synovial fibroblasts. Methods In MH7A cells, the expression of PAR-2 was measured by flow cytometry; cell apoptosis was examined by annexin V- FITC/PI staining combined with flow cytometry; the expression of Rho kinase was detected by Pull-down assay and Western botting. Results Tryptase upregulated the expression of PAR-2 in MH7A cells, and suppressed Fas-mediated apoptosis of MH7A cells in a dose-dependent manner. Meanwhile, PAR-2 inhibitor, FSLLRY-NH2 significantly reduced anti-apoptotic effects of tryptase in MH7A cells, which was related with the increase of activated Rho kinase expression. Conclusion Tryptase plays a role in resistance to the apoptosis of MH7A cells through raising PAR-2 and activating Rho kinase.

TGF-beta inhibits IL-1beta-activated PAR-2 expression through multiple pathways in human primary synovial cells.

PubMed

Tsai, Shin-Han; Sheu, Ming-Thau; Liang, Yu-Chih; Cheng, Hsiu-Tan; Fang, Sheng-Shiung; Chen, Chien-Ho

2009-10-23

To investigate the mechanism how Transforming growth factor-beta(TGF-beta) represses Interleukin-1beta (IL-1beta)-induced Proteinase-Activated Receptor-2 (PAR-2) expression in human primary synovial cells (hPSCs). Human chondrocytes and hPSCs isolated from cartilages and synovium of Osteoarthritis (OA) patients were cultured with 10% fetal bovine serum media or serum free media before treatment with IL-1beta, TGF-beta1, or Connective tissue growth factor (CTGF). The expression of PAR-2 was detected using reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. Collagen zymography was performed to assess the activity of Matrix metalloproteinases-13 (MMP-13). It was demonstrated that IL-1beta induces PAR-2 expression via p38 pathway in hPSCs. This induction can be repressed by TGF-beta and was observed to persist for at least 48 hrs, suggesting that TGF-beta inhibits PAR-2 expression through multiple pathways. First of all, TGF-beta was able to inhibit PAR-2 activity by inhibiting IL-1beta-induced p38 signal transduction and secondly the inhibition was also indirectly due to MMP-13 inactivation. Finally, TGF-beta was able to induce CTGF, and in turn CTGF represses PAR-2 expression by inhibiting IL-1beta-induced phospho-p38 level. TGF-beta could prevent OA from progression with the anabolic ability to induce CTGF production to maintain extracellular matrix (ECM) integrity and to down regulate PAR-2 expression, and the anti-catabolic ability to induce Tissue inhibitors of metalloproteinase-3 (TIMP-3) production to inhibit MMPs leading to avoid PAR-2 over-expression. Because IL-1beta-induced PAR-2 expressed in hPSCs might play a significantly important role in early phase of OA, PAR-2 repression by exogenous TGF-beta or other agents might be an ideal therapeutic target to prevent OA from progression.

Modelisation par elements finis du muscle strie

NASA Astrophysics Data System (ADS)

Leonard, Mathieu

Ce present projet de recherche a permis. de creer un modele par elements finis du muscle strie humain dans le but d'etudier les mecanismes engendrant les lesions musculaires traumatiques. Ce modele constitue une plate-forme numerique capable de discerner l'influence des proprietes mecaniques des fascias et de la cellule musculaire sur le comportement dynamique du muscle lors d'une contraction excentrique, notamment le module de Young et le module de cisaillement de la couche de tissu conjonctif, l'orientation des fibres de collagene de cette membrane et le coefficient de poisson du muscle. La caracterisation experimentale in vitro de ces parametres pour des vitesses de deformation elevees a partir de muscles stries humains actifs est essentielle pour l'etude de lesions musculaires traumatiques. Le modele numerique developpe est capable de modeliser la contraction musculaire comme une transition de phase de la cellule musculaire par un changement de raideur et de volume a l'aide des lois de comportement de materiau predefinies dans le logiciel LS-DYNA (v971, Livermore Software Technology Corporation, Livermore, CA, USA). Le present projet de recherche introduit donc un phenomene physiologique qui pourrait expliquer des blessures musculaires courantes (crampes, courbatures, claquages, etc.), mais aussi des maladies ou desordres touchant le tissu conjonctif comme les collagenoses et la dystrophie musculaire. La predominance de blessures musculaires lors de contractions excentriques est egalement exposee. Le modele developpe dans ce projet de recherche met ainsi a l'avant-scene le concept de transition de phase ouvrant la porte au developpement de nouvelles technologies pour l'activation musculaire chez les personnes atteintes de paraplegie ou de muscles artificiels compacts pour l'elaboration de protheses ou d'exosquelettes. Mots-cles Muscle strie, lesion musculaire, fascia, contraction excentrique, modele par elements finis, transition de phase

Effects of tissue factor, PAR-2 and MMP-9 expression on human breast cancer cell line MCF-7 invasion.

PubMed

Lin, Zeng-Mao; Zhao, Jian-Xin; Duan, Xue-Ning; Zhang, Lan-Bo; Ye, Jing-Ming; Xu, Ling; Liu, Yin-Hua

2014-01-01

This study aimed to explore the expression of tissue factor (TF), protease activated receptor-2 (PAR-2), and matrix metalloproteinase-9 (MMP-9) in the MCF-7 breast cancer cell line and influence on invasiveness. Stable MCF-7 cells transfected with TF cDNA and with TF ShRNA were established. TF, PAR-2, and MMP-9 protein expression was analyzed using indirect immunofluorescence and invasiveness was evaluated using a cell invasion test. Effects of an exogenous PAR-2 agonist were also examined. TF protein expression significantly differed between the TF cDNA and TF ShRNA groups. MMP-9 protein expression was significantly correlated with TF protein expression, but PAR-2 protein expression was unaffected. The PAR- 2 agonist significantly enhanced MMP-9 expression and slightly increased TF and PAR-2 expression in the TF ShRNA group, but did not significantly affect protein expression in MCF-7 cells transfected with TF cDNA. TF and MMP-9 expression was positively correlated with the invasiveness of tumor cells. TF, PAR-2, and MMP-9 affect invasiveness of MCF-7 cells. TF may increase MMP-9 expression by activating PAR-2.

Diabetes-Induced Superoxide Anion and Breakdown of the Blood-Retinal Barrier: Role of the VEGF/uPAR Pathway

PubMed Central

El-Remessy, Azza B.; Franklin, Telina; Ghaley, Nagla; Yang, Jinling; Brands, Michael W.; Caldwell, Ruth B.; Behzadian, Mohamed Ali

2013-01-01

Diabetes-induced breakdown of the blood-retinal barrier (BRB) has been linked to hyperglycemia-induced expression of vascular endothelial growth factor (VEGF) and is likely mediated by an increase in oxidative stress. We have shown that VEGF increases permeability of retinal endothelial cells (REC) by inducing expression of urokinase plasminogen activator receptor (uPAR). The purpose of this study was to define the role of superoxide anion in VEGF/uPAR expression and BRB breakdown in diabetes. Studies were performed in streptozotocin diabetic rats and mice and high glucose (HG) treated REC. The superoxide dismutase (SOD) mimetic tempol blocked diabetes-induced permeability and uPAR expression in rats and the cell permeable SOD inhibited HG-induced expression of uPAR and VEGF in REC. Inhibiting VEGFR blocked HG-induced expression of VEGF and uPAR and GSK-3β phosphorylation in REC. HG caused β-catenin translocation from the plasma membrane into the cytosol and nucleus. Treatment with HG-conditioned media increased REC paracellular permeability that was blocked by anti-uPA or anti-uPAR antibodies. Moreover, deletion of uPAR blocked diabetes-induced BRB breakdown and activation of MMP-9 in mice. Together, these data indicate that diabetes-induced oxidative stress triggers BRB breakdown by a mechanism involving uPAR expression through VEGF-induced activation of the GSK3β/β-catenin signaling pathway. PMID:23951261

PAR-2, IL-4R, TGF-β and TNF-α in bronchoalveolar lavage distinguishes extrinsic allergic alveolitis from sarcoidosis.

PubMed

Matěj, Radoslav; Smětáková, Magdalena; Vašáková, Martina; Nováková, Jana; Sterclová, Martina; Kukal, Jaromír; Olejár, Tomáš

2014-08-01

Sarcoidosis (SARC) and extrinsic allergic alveolitis (EAA) share certain markers, making a differential diagnosis difficult even with histopathological investigation. In lung tissue, proteinase-activated receptor-2 (PAR-2) is primarily investigated with regard to epithelial and inflammatory perspectives. Varying levels of certain chemokines can be a useful tool for distinguishing EAA and SARC. Thus, in the present study, differences in the levels of transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, interleukin-4 receptor (IL-4R) and PAR-2 in bronchoalveolar lavage fluid (BALF) were compared, using an ELISA method, between 14 patients with EAA and six patients with SARC. Statistically significant higher levels of IL-4R, PAR-2 and the PAR-2/TGF-β1 and PAR-2/TNF-α ratios were observed in EAA patients as compared with SARC patients. Furthermore, the ratios of TNF-α/total protein, TGF-β1/PAR-2 and TNF-α/PAR-2 were significantly lower in EAA patients than in SARC patients. The results indicated a higher detection of PAR-2 in EAA samples in association with TNF-α and TGF-β levels. As EAA and PAR-2 in parallel belong to the Th2-mediated pathway, the results significantly indicated an association between this receptor and etiology. In addition, the results indicated that SARC is predominantly a granulomatous inflammatory disease, thus, higher levels of TNF-α are observed. Therefore, the detection of PAR-2 and investigated chemokines in BALF may serve as a useful tool in the differential diagnosis between EAA and SARC.

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR(2) ) is involved in vascular function.

PubMed

Bucci, M; Vellecco, V; Harrington, L; Brancaleone, V; Roviezzo, F; Mattace Raso, G; Ianaro, A; Lungarella, G; De Palma, R; Meli, R; Cirino, G

2013-01-01

Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR(2) and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models. Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR(2) activating peptide (AP) was used as a PAR(2) agonist. Aortas harvested from TLR4(-/-) mice were also used to characterize the PAR(2) response. PAR(2) , but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR(2) AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR(2) AP-induced vasorelaxation and PAR(2) AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4(-/-) mice, the expression of PAR(2) was reduced and the PAR(2) AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective. Cross-talk between PAR(2) and TLR4 contributes to vascular homeostasis. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Cross-talk between toll-like receptor 4 (TLR4) and proteinase-activated receptor 2 (PAR2) is involved in vascular function

PubMed Central

Bucci, M; Vellecco, V; Harrington, L; Brancaleone, V; Roviezzo, F; Mattace Raso, G; Ianaro, A; Lungarella, G; De Palma, R; Meli, R; Cirino, G

2013-01-01

Background and Purpose Proteinase-activated receptors (PARs) and toll-like receptors (TLRs) are involved in innate immune responses. The aim of this study was to evaluate the possible cross-talk between PAR2 and TLR4 in vessels in physiological condition and how it varies following stimulation of TLR4 by using in vivo and ex vivo models. Experimental Approach Thoracic aortas were harvested from both naïve and endotoxaemic rats for in vitro studies. Arterial blood pressure was monitored in anaesthetized rats in vivo. LPS was used as a TLR4 agonist while PAR2 activating peptide (AP) was used as a PAR2 agonist. Aortas harvested from TLR4–/– mice were also used to characterize the PAR2 response. Key Results PAR2, but not TLR4, expression was enhanced in aortas of endotoxaemic rats. PAR2AP-induced vasorelaxation was increased in aortic rings of LPS-treated rats. TLR4 inhibitors, curcumine and resveratrol, reduced PAR2AP-induced vasorelaxation and PAR2AP-induced hypotension in both naïve and endotoxaemic rats. Finally, in aortic rings from TLR4–/– mice, the expression of PAR2 was reduced and the PAR2AP-induced vasodilatation impaired compared with those from wild-type mice and both resveratrol and curcumine were ineffective. Conclusions and Implications Cross-talk between PAR2 and TLR4 contributes to vascular homeostasis. PMID:22957757

Efficacy of (99m)Tc-EDDA/HYNIC-TOC SPECT/CT scintigraphy in Graves' ophthalmopathy.

PubMed

Zhao, Rong; Wang, Jiang; Deng, Jinglan; Yang, Weidong; Wang, Jing

2012-01-01

The aim of this study was to investigate the predictive role of the orbital somatostatin receptor scintigraphy with (99m)Tc-EDDA/HYNIC-TOC ((99m)Tc-TOC) to detect clinical stage of Graves' ophthalmopathy and the response to corticosteroid therapy. The subjects of the experiment were 46 patients with Graves' ophthalmopathy (GO) and four volunteers without eye disease or GO as the normal group (NG). Single photon emission computed tomography (SPECT), computed tomography (CT) and the left and right lateral position planar imaging of the heads of the all subjects were obtained 4 h after the intravenous injection of 555 MBq of (99m)Tc-TOC. The (99m)Tc-TOC SPECT/CT was repeated 3 months later. 35 (35/46) patients were received corticosteroid therapy (prednisolone, 10 mg po tid ) for 3 months, however, the other 11 patients as control groups did not receive any treatment. The treatment effect was evaluated both by the orbital (99m)Tc-TOC uptake and NOSPECS. A significant decrease in the O/OC ratio was observed in 22 GO patients between pre- and post-treatment (1.64 ± 0.13 vs. 1.21 ± 0.09, P < 0.05). There were neither significant difference of the O/OC ratio in 13 GO patients between pre- and post-treatment periods, nor significant difference in the 9 (9/11) patients before and after three months. Orbital (99m)Tc-TOC scintigraphy is a feasible technique to estimate the Graves' ophthalmopathy activity and predict the response to subsequent corticosteroid therapy in GO patients. The technique could be a useful tool for physicians not familiar with CAS determination.

Efficacy of 99mTc-EDDA/HYNIC-TOC SPECT/CT scintigraphy in Graves’ ophthalmopathy

PubMed Central

Zhao, Rong; Wang, Jiang; Deng, Jinglan; Yang, Weidong; Wang, Jing

2012-01-01

The aim of this study was to investigate the predictive role of the orbital somatostatin receptor scintigraphy with 99mTc-EDDA/HYNIC-TOC (99mTc-TOC) to detect clinical stage of Graves’ ophthalmopathy and the response to corticosteroid therapy. The subjects of the experiment were 46 patients with Graves’ ophthalmopathy (GO) and four volunteers without eye disease or GO as the normal group (NG). Single photon emission computed tomography (SPECT), computed tomography (CT) and the left and right lateral position planar imaging of the heads of the all subjects were obtained 4 h after the intravenous injection of 555 MBq of 99mTc-TOC. The 99mTc-TOC SPECT/CT was repeated 3 months later. 35 (35/46) patients were received corticosteroid therapy (prednisolone, 10 mg po tid ) for 3 months, however, the other 11 patients as control groups did not receive any treatment. The treatment effect was evaluated both by the orbital 99mTc-TOC uptake and NOSPECS. A significant decrease in the O/OC ratio was observed in 22 GO patients between pre- and post-treatment (1.64 ± 0.13 vs. 1.21 ± 0.09, P < 0.05). There were neither significant difference of the O/OC ratio in 13 GO patients between pre- and post-treatment periods, nor significant difference in the 9 (9/11) patients before and after three months. Orbital 99mTc-TOC scintigraphy is a feasible technique to estimate the Graves’ ophthalmopathy activity and predict the response to subsequent corticosteroid therapy in GO patients. The technique could be a useful tool for physicians not familiar with CAS determination. PMID:23133815

Effects of the frame acquisition rate on the sensitivity of gastro-oesophageal reflux scintigraphy

PubMed Central

Codreanu, I; Chamroonrat, W; Edwards, K

2013-01-01

Objective: To compare the sensitivity of gastro-oesophageal reflux (GOR) scintigraphy at 5-s and 60-s frame acquisition rates. Methods: GOR scintigraphy of 50 subjects (1 month–20 years old, mean 42 months) were analysed concurrently using 5-s and 60-s acquisition frames. Reflux episodes were graded as low if activity was detected in the distal half of the oesophagus and high if activity was detected in its upper half or in the oral cavity. For comparison purposes, detected GOR in any number of 5-s frames corresponding to one 60-s frame was counted as one episode. Results: A total of 679 episodes of GOR to the upper oesophagus were counted using a 5-s acquisition technique. Only 183 of such episodes were detected on 60-s acquisition images. To the lower oesophagus, a total of 1749 GOR episodes were detected using a 5-s acquisition technique and only 1045 episodes using 60-s acquisition frames (these also included the high-level GOR on 5-s frames counted as low level on 60-s acquisition frames). 10 patients had high-level GOR episodes that were detected only using a 5-s acquisition technique, leading to a different diagnosis in these patients. No correlation between the number of reflux episodes and the gastric emptying rates was noted. Conclusion: The 5-s frame acquisition technique is more sensitive than the 60-s frame acquisition technique for detecting both high- and low-level GOR. Advances in knowledge: Brief GOR episodes with a relatively low number of radioactive counts are frequently indistinguishable from intense background activity on 60-s acquisition frames. PMID:23520226

Evaluation of the effects of toluene inhalation on alveolar epithelial permeability by 99mTc-DTPA inhalation scintigraphy in automobile painters.

PubMed

Cerci, Sevim Sureyya; Ozturk, Onder; Sutcu, Recep; Ozbek, Feride Meltem; Baydar, Cetin Lutfi; Yildiz, Mustafa; Akkaya, Ahmet; Delibas, Namk

2008-01-01

The main component of paint thinner used in industry is toluene diisocyanate (TDI) which can cause occupational asthma in 5-10% of exposed workers. To investigate the effect of TDI on 99mTc clearance rate of alveolar epithelium and on pulmonary function tests (PFT) in automobile painters, and to determine the relationship between 99mTc-DTPA radioaerosol lung scintigraphy and serum levels of antioxidant enzymes and metalloproteinases (MMPs) of automobile painters. Twenty-eight automobile painters and 13 control subjects were included in the study. 99mTc-DTPA aerosol inhalation scintigraphy and PFT were administered to all subjects. Clearance half-time (T1/2) and penetration index (PI) on the first-minute image after 99mTc-DTPA scintigraphy were calculated. Blood levels of MDA, antioxidant enzymes and metalloproteinases were measured. The mean T1/2 values of automobile painters were longer in both smoker and non-smoker subjects, but the difference was not significant (P>0.05). Although the PFT values decreased in automobile painters, there was no significant difference between each group. Any correlation between spirometric measurements and T1/2 or PI values in non-smoking automobile painters was not detected. Negative correlation among mean T1/2 value and FVC% and FEV1% in smoking automobile painters, and positive correlation between mean T1/2 value and MMP-9, GSH-Px levels in non-smoking automobile painters were detected. Our results suggested that the clearance of 99mTc-DTPA from the lungs of automobile painters was slower than in the control group, but the difference is not statistically significant. This data also supports the observation that TDI occasionally stimulates bronchial changes rather than alveolar changes in automobile painters.

Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells.

PubMed

Tripathi, Trivendra; Abdi, Mahshid; Alizadeh, Hassan

2014-05-29

Acanthamoeba plasminogen activator (aPA) is a serine protease elaborated by Acanthamoeba trophozoites that facilitates the invasion of trophozoites to the host and contributes to the pathogenesis of Acanthamoeba keratitis (AK). The aim of this study was to explore if aPA stimulates proinflammatory cytokine in human corneal epithelial (HCE) cells via the protease-activated receptors (PARs) pathway. Acanthamoeba castellanii trophozoites were grown in peptone-yeast extract glucose for 7 days, and the supernatants were collected and centrifuged. The aPA was purified using the fast protein liquid chromatography system, and aPA activity was determined by zymography assays. Human corneal epithelial cells were incubated with or without aPA (100 μg/mL), PAR1 agonists (thrombin, 10 μM; TRAP-6, 10 μM), and PAR2 agonists (SLIGRL-NH2, 100 μM; AC 55541, 10 μM) for 24 and 48 hours. Inhibition of PAR1 and PAR2 involved preincubating the HCE cells for 1 hour with the antagonist of PAR1 (SCH 79797, 60 μM) and PAR2 (FSLLRY-NH2, 100 μM) with or without aPA. Human corneal epithelial cells also were preincubated with PAR1 and PAR2 antagonists and then incubated with or without PAR1 agonists (thrombin and TRAP-6) and PAR2 agonists (SLIGRL-NH2 and AC 55541). Expression of PAR1 and PAR2 was examined by quantitative RT-PCR (qRT-PCR), flow cytometry, and immunocytochemistry. Interleukin-8 expression was quantified by qRT-PCR and ELISA. Human corneal epithelial cells constitutively expressed PAR1 and PAR2 mRNA. Acanthamoeba plasminogen activator and PAR2 agonists significantly upregulated PAR2 mRNA expression (1- and 2-fold, respectively) (P < 0.05). Protease-activated receptor 2 antagonist significantly inhibited aPA, and PAR2 agonists induced PAR2 mRNA expression in HCE cells (P < 0.05). Protease-activated receptor 1 agonists, but not aPA, significantly upregulated PAR1 mRNA expression, which was significantly inhibited by PAR1 antagonist in HCE cells. Acanthamoeba plasminogen

Evaluation of lung epithelial permeability in the volatile substance abuse using Tc-99m DTPA aerosol scintigraphy.

PubMed

Cayir, Derya; Demirel, Koray; Korkmaz, Meliha; Koca, Gokhan

2011-10-01

Chronic inhalant use is associated with significant toxic effects, including neurological, renal, hepatic, and pulmonary damage. However, there is a paucity of reports regarding respiratory complications in inhalant abusers. The aim of this study was to evaluate pulmonary epithelial permeability in the volatile substance abuse (VSA) using Tc-99m DTPA aerosol scintigraphy. This study included 18 patients with volatile substance abuse and 18 volunteer controls. All of patients and controls were smokers. Tc-99m DTPA aerosol scintigraphy was performed in all cases. Time-activity curves from each lung were generated and clearance half-time (T(1/2)) of Tc-99m DTPA were calculated. T(1/2) of whole lung was calculated as a mean of the T(1/2) of left and right lung. The T(1/2) values of Tc-99m DTPA clearance in the substance abusers were significantly decreased as compared to the control group with respective mean values of 28.86 ± 8.44, and 62.14 ± 26.12 min (p = 0.001). It was seen Tc-99m DTPA clearance from lung was faster as the duration of substance abuse was increased. Tc-99m DTPA pulmonary clearance is markedly accelerated in the volatile substance abuse. This suggests that inhalant abuse of substance may produce abnormalities in pulmonary alveolo-capillary membrane function.

A Pilot Comparison of 18F-fluorocholine PET/CT, Ultrasonography and 123I/99mTc-sestaMIBI Dual-Phase Dual-Isotope Scintigraphy in the Preoperative Localization of Hyperfunctioning Parathyroid Glands in Primary or Secondary Hyperparathyroidism

PubMed Central

Michaud, Laure; Balogova, Sona; Burgess, Alice; Ohnona, Jessica; Huchet, Virginie; Kerrou, Khaldoun; Lefèvre, Marine; Tassart, Marc; Montravers, Françoise; Périé, Sophie; Talbot, Jean-Noël

2015-01-01

Abstract We compared 18F-fluorocholine hybrid positron emission tomography/X-ray computed tomography (FCH-PET/CT) with ultrasonography (US) and scintigraphy in patients with hyperparathyroidism and discordant, or equivocal results of US and 123I/99mTc-sesta-methoxyisobutylisonitrile (sestaMIBI) dual-phase parathyroid scintigraphy. FCH-PET/CT was performed in 17 patients with primary (n = 11) lithium induced (n = 1) or secondary hyperparathyroidism (1 dialyzed, 4 renal-transplanted). The reference standard was based on results of surgical exploration and histopathological examination. The results of imaging modalities were evaluated, on site and by masked reading, on per-patient and per-lesion bases. In a first approach, equivocal images/foci were considered as negative. On a per-patient level, the sensitivity was for US 38%, for scintigraphy 69% by open and 94% by masked reading, and for FCH-PET/CT 88% by open and 94% by masked reading. On a per-lesion level, sensitivity was for US 42%, for scintigraphy 58% by open and 83% by masked reading, and for FCH-PET/CT 88% by open and 96% by masked reading. One ectopic adenoma was missed by the 3 imaging modalities. Considering equivocal images/foci as positive increased the accuracy of the open reading of scintigraphy or of FCH-PET/CT, but not of US. FCH-PET/CT was significantly superior to US in all approaches, whereas it was more sensitive than scintigraphy only for open reading considering equivocal images/foci as negative (P = 0.04). FCH uptake was more intense in adenomas than in hyperplastic parathyroid glands. Thyroid lesions were suspected in 9 patients. They may induce false-positive results as in one case of oncocytic thyroid adenoma, or false-negative results as in one case of intrathyroidal parathyroid adenoma. Thyroid cancer (4 cases) can be visualized with FCH as with 99mTc-sestaMIBI, but the intensity of uptake was moderate, similar to that of parathyroid hyperplasia. This pilot study confirmed

Treatment of endophthalmitis by pars plana vitrectomy.

PubMed

Verbraeken, H; Geeroms, B; Karemera, A

1988-01-01

Between 1976 and 1985 81 cases of endophthalmitis have been treated by pars plana vitrectomy and intravitreous injection of antibiotics or antimycotics. The functional results and the etiology of the endophthalmitis are discussed, as well as the reasons to perform a vitrectomy in endophthalmitis, and a possible explanation for the relatively high incidence of pseudophakic endophthalmitis is given.

[Pars plana vitrectomy with the vitreous stripper].

PubMed

Klöti, R

1975-01-01

We report on the construction and the function of a new microsurgical instrument for vitrectomy. The instrument is introduced into the vitreous cavity through a small scleral incision in the pars plana area. Microscope observation with slit-lamp illumination and a specially designed contact lens are used for this surgical procedure. Our clinical experiences and the indications are discussed.

Role of Stress Myocardial Scintigraphy in the Evaluation of Incompletely Revascularized Post-PCI Patients

PubMed Central

Galassi, Alfredo R.; Marzá, Francesco; Azzarelli, Salvatore; Tomasello, Salvatore D.

2011-01-01

Percutaneous coronary intervention (PCI) is actually the most used method of revascularization. Although complete revascularization remains a desirable goal, it may not be possible or not easy to plan in many patients. Thus, incomplete revascularization might be a preferred treatment strategy in selected patient categories. Stress myocardial scintigraphy, because of its high diagnostic accuracy and prognostic value and its ability to assess location and extent of myocardial ischemia regardless of symptoms as well as to evaluate patients who are unable to exercise or who have uninterpretable electrocardiogram, is of paramount importance for clinical decision making in patients with multivessel disease and incomplete revascularization. PMID:21941646

Monoradiculopathy and secondary segmental instability caused by postoperative pars interarticularis fracture: a case report.

PubMed

Kaner, Tuncay; Tutkan, Ibrahim

2009-04-01

Instability can develop after lumbar spinal surgery. What is also known as secondary segmental instability is one of the important causes of failed back syndrome. In this paper, we described a 45-year-old female patient who was diagnosed with secondary segmental instability caused by left L3 pars interarticularis fracture after a high lumbar disc surgery and was subsequently treated with re-operation. We evaluated the clinical course, diagnosis, and treatment methods for secondary segmental instability caused by postoperative pars interarticularis fracture. Furthermore, we emphasized the importance of preserving the pars interarticularis during upper lumbar disc surgeries in order to avoid a potential stress fracture.

Small molecule antagonists of the urokinase (uPA): urokinase receptor (uPAR) interaction with high reported potencies show only weak effects in cell-based competition assays employing the native uPAR ligand.

PubMed

De Souza, Melissa; Matthews, Hayden; Lee, Jodi A; Ranson, Marie; Kelso, Michael J

2011-04-15

Binding of the urokinase-type plasminogen activator (uPA) to its cell-surface-bound receptor uPAR and upregulation of the plasminogen activation system (PAS) correlates with increased metastasis and poor prognosis in several tumour types. Disruptors of the uPA:uPAR interaction represent promising anti-tumour/metastasis agents and several approaches have been explored for this purpose, including the use of small molecule antagonists. Two highly potent non-peptidic antagonists 1 and 2 (IC(50)1=0.8 nM, IC(50)2=33 nM) from the patent literature were reportedly identified using competition assays employing radiolabelled uPAR-binding uPA fragments and appeared as useful pharmacological tools for studying the PAS. Before proceeding to such studies, confirmation was sought that 1 and 2 retained their potencies in physiologically relevant cell-based competition assays employing uPAR's native binding partner high molecular weight uPA (HMW-uPA). This study describes a new solution phase synthesis of 1, a mixed solid/solution phase synthesis of 2 and reports the activities of 1 and 2 in semi-quantitative competition flow cytometry assays and quantitative cell-based uPA activity assays that employed HMW-uPA as the competing ligand. The flow cytometry experiments revealed that high concentrations of 2 (10-100 μM) are required to compete with HMW-uPA for uPAR binding and that 1 shows no antagonist effects at 100 μM. The cell-based enzyme activity assays similarly revealed that 1 and 2 are poor inhibitors of cell surface-bound HMW-uPA activity (IC(50) >100 μM for 1 and 2). The report highlights the dangers of identifying false-positive lead uPAR antagonists from competition assays employing labelled competing ligands other than the native HMW-uPA. Copyright © 2011 Elsevier Ltd. All rights reserved.

PAR and UV effects on vertical migration and photosynthesis in Euglena gracilis.

PubMed

Richter, Peter; Helbling, Walter; Streb, Christine; Häder, Donat-P

2007-01-01

Recently it was shown that the unicellular flagellate Euglena gracilis changes the sign of gravitaxis from negative to positive upon excessive radiation. This sign change persists in a cell culture for hours even if subsequently transferred to dim light. To test the ecological relevance of this behavior, a vertical column experiment was performed (max. depth 65 cm) to test distribution, photosynthetic efficiency and motility in different horizons of the column (surface, 20, 40 and 65 cm). One column was covered with a UV cut-off filter, which transmits photosynthetically active radiation (PAR) only, the other with a filter which transmits PAR and UV. The columns were irradiated with a solar simulator (PAR 162 W m(-2), UV-A 32.6 W m(-2), UV-B 1.9 W m(-2)). The experiment was conducted for 10 days, normally with a light/dim light cycle of 12 h:12 h, but in some cases the light regime was changed (dim light instead of full radiation). Under irradiation the largest fraction of cells was found at the bottom of the column. The cell density decreased toward the surface. Photosynthetic efficiency, determined with a pulse amplitude modulated fluorometer, was negligible at the surface and increased toward the bottom. While the cell suspension showed a positive gravitaxis at the bottom, the cells in the 40 cm horizon were bimodally oriented (about the same percentage of cells swimming upward and downward, respectively). At 20 cm and at the surface the cells showed negative gravitaxis. Positive gravitaxis was more pronounced in the UV + PAR samples. At the surface and in the 20 and 40 cm horizons photosynthetic efficiency was better in the PAR-only samples than in the PAR + UV samples. At the bottom photosynthetic efficiency was similar in both light treatments. The data suggest that high light reverses gravitaxis of the cells, so that they move downward in the water column. At the bottom the light intensity is lower (attenuation of the water column and self shading of the

PET imaging of urokinase-type plasminogen activator receptor (uPAR) in prostate cancer: current status and future perspectives.

PubMed

Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

2016-01-01

Overexpression of urokinase-type plasminogen activator receptors (uPAR) represents an important biomarker for aggressiveness in most common malignant diseases, including prostate cancer (PC). Accordingly, uPAR expression either assessed directly in malignant PC tissue or assessed directly in plasma (intact/cleaved forms)-provides independent additional clinical information to that contributed by PSA, Gleason score, and other relevant pathological and clinical parameters. In this respect, non-invasive molecular imaging by positron emission tomography (PET) offers a very attractive technology platform, which can provide the required quantitative information on the uPAR expression profile, without the need for invasive procedures and the risk of missing the target due to tumor heterogeneity. These observations support non-invasive PET imaging of uPAR in PC as a clinically relevant diagnostic and prognostic imaging method. In this review, we will focus on the recent development of uPAR PET and the relevance within prostate cancer imaging. Novel antibody and small-molecule radiotracers-targeting uPAR, including a series of uPAR-targeting PET ligands, based on the high affinity peptide ligand AE105, have been synthesized and tested in vitro and in vivo in preclinical murine xenograft models and, recently, in a first-ever clinical uPAR PET study in cancer patients, including patients with PC. In this phase I study, a high and specific uptake of the tracer 64 Cu-DOTA-AE105 was found in both primary tumors and lymph node metastases. The results are encouraging and support large-scale clinical trials to determine the utility of uPAR PET in the management of patients with PC with the goal of improving outcome.

Crystal Structure of Thrombin Bound to the Uncleaved Extracellular Fragment of PAR1

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

Gandhi, Prafull S.; Chen, Zhiwei; Di Cera, Enrico

2010-05-11

Abundant structural information exists on how thrombin recognizes ligands at the active site or at exosites separate from the active site region, but remarkably little is known about how thrombin recognizes substrates that bridge both the active site and exosite I. The case of the protease-activated receptor PAR1 is particularly relevant in view of the plethora of biological effects associated with its activation by thrombin. Here, we present the 1.8 {angstrom} resolution structure of thrombin S195A in complex with a 30-residue long uncleaved extracellular fragment of PAR1 that documents for the first time a productive binding mode bridging the activemore » site and exosite I. The structure reveals two unexpected features of the thrombin-PAR1 interaction. The acidic P3 residue of PAR1, Asp{sup 39}, does not hinder binding to the active site and actually makes favorable interactions with Gly{sup 219} of thrombin. The tethered ligand domain shows a considerable degree of disorder even when bound to thrombin. The results fill a significant gap in our understanding of the molecular mechanisms of recognition by thrombin in ways that are relevant to other physiological substrates.« less

Impacts of Light Use Efficiency and fPAR Parameterization on Gross Primary Production Modeling

NASA Technical Reports Server (NTRS)

Cheng, Yen-Ben; Zhang, Qingyuan; Lyapustin, Alexei I.; Wang, Yujie; Middleton, Elizabeth M.

2014-01-01

This study examines the impact of parameterization of two variables, light use efficiency (LUE) and the fraction of absorbed photosynthetically active radiation (fPAR or fAPAR), on gross primary production(GPP) modeling. Carbon sequestration by terrestrial plants is a key factor to a comprehensive under-standing of the carbon budget at global scale. In this context, accurate measurements and estimates of GPP will allow us to achieve improved carbon monitoring and to quantitatively assess impacts from cli-mate changes and human activities. Spaceborne remote sensing observations can provide a variety of land surface parameterizations for modeling photosynthetic activities at various spatial and temporal scales. This study utilizes a simple GPP model based on LUE concept and different land surface parameterizations to evaluate the model and monitor GPP. Two maize-soybean rotation fields in Nebraska, USA and the Bartlett Experimental Forest in New Hampshire, USA were selected for study. Tower-based eddy-covariance carbon exchange and PAR measurements were collected from the FLUXNET Synthesis Dataset. For the model parameterization, we utilized different values of LUE and the fPAR derived from various algorithms. We adapted the approach and parameters from the MODIS MOD17 Biome Properties Look-Up Table (BPLUT) to derive LUE. We also used a site-specific analytic approach with tower-based Net Ecosystem Exchange (NEE) and PAR to estimate maximum potential LUE (LUEmax) to derive LUE. For the fPAR parameter, the MODIS MOD15A2 fPAR product was used. We also utilized fAPAR chl, a parameter accounting for the fAPAR linked to the chlorophyll-containing canopy fraction. fAPAR chl was obtained by inversion of a radiative transfer model, which used the MODIS-based reflectances in bands 1-7 produced by Multi-Angle Implementation of Atmospheric Correction (MAIAC) algorithm. fAPAR chl exhibited seasonal dynamics more similar with the flux tower based GPP than MOD15A2 fPAR, especially

Partitioning-defective Protein 6 (Par-6) Activates Atypical Protein Kinase C (aPKC) by Pseudosubstrate Displacement*

PubMed Central

Graybill, Chiharu; Wee, Brett; Atwood, Scott X.; Prehoda, Kenneth E.

2012-01-01

Atypical protein kinase C (aPKC) controls cell polarity by modulating substrate cortical localization. Aberrant aPKC activity disrupts polarity, yet the mechanisms that control aPKC remain poorly understood. We used a reconstituted system with purified components and a cultured cell cortical displacement assay to investigate aPKC regulation. We find that aPKC is autoinhibited by two domains within its NH2-terminal regulatory half, a pseudosubstrate motif that occupies the kinase active site, and a C1 domain that assists in this process. The Par complex member Par-6, previously thought to inhibit aPKC, is a potent activator of aPKC in our assays. Par-6 and aPKC interact via PB1 domain heterodimerization, and this interaction activates aPKC by displacing the pseudosubstrate, although full activity requires the Par-6 CRIB-PDZ domains. We propose that, along with its previously described roles in controlling aPKC localization, Par-6 allosterically activates aPKC to allow for high spatial and temporal control of substrate phosphorylation and polarization. PMID:22544755

1,25-Dihydroxyvitamin D(3) Inhibits Podocyte uPAR Expression and Reduces Proteinuria

PubMed Central

Liu, Shuangxin; Xie, Shaoting; Yang, Yun; Ma, Juan; Deng, Yujun; Wang, Wenjian; Xu, Lixia; Li, Ruizhao; Zhang, Li; Yu, Chunping; Shi, Wei

2013-01-01

Background Accumulating studies have demonstrated that 1,25-Dihydroxyvitamin D(3) (1,25(OH)2D3) reduces proteinuria and protects podocytes from injury. Recently, urokinase receptor (uPAR) and its soluble form have been shown to cause podocyte injury and focal segmental glomerulosclerosis (FSGS). Here, our findings showed that 1,25(OH)2D3 did inhibit podocyte uPAR expression and attenuate proteinuria and podocyte injury. Methodology/Principal Findings In this study, the antiproteinuric effect of 1,25(OH)2D3 was examined in the lipopolysaccharide mice model of transient proteinuria (LPS mice) and in the 5/6 nephrectomy rat FSGS model(NTX rats). uPAR protein expression were tested by flow cytometry, immune cytochemistry and western blot analysis, and uPAR mRNA expression by real-time quantitative PCR in cultured podocytes and kidney glomeruli isolated from mice and rats. Podocyte motility was observed by transwell migration assay and wound healing assay. Podocyte foot processes effacement was identified by transmission electron microscopy. We found that 1,25(OH)2D3 inhibited podocyte uPAR mRNA and protein synthesis in LPS-treated podocytes, LPS mice and NTX rats, along with 1,25(OH)2D3 reducing proteinuria in NTX rats and LPS mice.1,25(OH)2D3 reduced glomerulosclerosis in NTX rats and alleviated podocyte foot processes effacement in LPS mice. Transwell migration assay and wound healing assay showed that LPS-induced podocyte motility, irrespective of random or directed motility, were substantially reduced by 1,25(OH)2D3. Conclusions/Significance Our results demonstrated that 1,25(OH)2D3 inhibited podocyte uPAR expression in vitro and in vivo, which may be an unanticipated off target effect of 1,25(OH)2D3 and explain its antiproteinuric effect in the 5/6 nephrectomy rat FSGS model and the LPS mouse model of transient proteinuria. PMID:23741418

The acetabulum: A prospective study of three-phase bone and indium white blood cell scintigraphy following porous-coated hip arthroplasty

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

Oswald, S.G.; Van Nostrand, D.; Savory, C.G.

1990-03-01

Although few studies address the use of three-phase bone scanning (TPBS) and indium-111-labeled white blood cell scintigraphy ({sup 111}In-WBC) in hip arthroplasty utilizing a porous-coated prosthesis, the literature suggests that scintigraphic patterns in the uncomplicated patient may differ from that seen with the cemented prosthesis. In an attempt to determine the scintigraphic natural history, 25 uncomplicated porous-coated hip arthroplasties in 21 patients were prospectively studied with serial TPBS and {sup 111I}n-WBC at approximately 7 days, and 3, 6, 12, 18, and 24 mo postoperatively. This report deals with findings related to the acetabulum. All 25 prostheses (144 of 144 scans)more » demonstrated increased uptake on the bone-phase images. Although this activity decreased with time, 76% had persistent uptake at 24 mo. Twenty-three of 25 prostheses (126 of 140 scans) showed increased uptake on {sup 111}In-WBC scintigraphy, invariably decreasing with time, but with 37% having significant uptake at 24 mo. Scintigraphic patterns in the uncomplicated porous-coated hip arthroplasty patient appear to differ from patterns described in cemented prostheses.« less

Analysis of clinical features and visual outcomes of pars planitis.

PubMed

Berker, Nilufer; Sen, Emine; Elgin, Ufuk; Atilgan, Cemile Ucgul; Dursun, Erdem; Yilmazbas, Pelin

2018-04-01

To evaluate the demographic characteristics, clinical features, treatment and outcomes of patients with pars planitis in a tertiary referral center in Turkey. Medical records of patients with pars planitis were retrospectively reviewed. The data including demographic and ocular features and treatment outcomes were recorded. The distribution of clinical findings and complications were evaluated according to age and gender groups. The changes in final BCVA compared to the initial BCVA were noted. Statistical analysis was performed using SPSS software (Version 18.0, SPSS Inc., Chicago, USA). Twenty-seven patients (54 eyes) were included in this study. 16 patients were male (59.3%), and 11 were female (40.7%). Mean age at diagnosis was 12.84 ± 8.26 (range 4-36) years. Mean follow-up period was 61.3 ± 52.15 (range 9-172) months. Mean BCVA was 0.58 ± 0.36 (range 0.03-1.00) (0.40 ± 0.45 logMAR) at presentation, and 0.81 ± 0.28 (range 0.10-1.00) (0.14 ± 0.27 logMAR) at final visit (P = 0.001). Vitreous inflammation (100%), vitreous haze (92.6%), snowballs (74.1%), snowbanks (66.7%), anterior chamber cells (66.7%) and peripheral retinal vascular sheathing (48.1%) were the most common presentations. Ocular complications included vitreous condensation (51.9%), cystoid macular edema (22.2%), cataract (18.5%), inferior peripheral retinal detachment (11.1%), glaucoma (5.6%) and vitreous hemorrhage (3.7%). Treatments included topical, periocular, intravitreal and systemic corticosteroids, immunosuppressives, peripheral laser photocoagulation and pars plana vitrectomy when needed. Pars planitis is an idiopathic chronic intermediate uveitis mostly affecting children and adolescents. In spite of its chronic nature with high potential of causing ocular complications, adequate treatment and close follow-up lead to favorable visual outcomes.

Bone scintigraphy of the aged patient. 1. /sup 99m/Tc-polyphosphate bone scintigraphy (in Japanese)

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

Yamamoto, M.; Chiba, K.; Tanno, M.

Application and evaluation of a new bone-seeking radiopharmaceuticai, / sup 99m/Tc-polyphosphate are reported. Analysis of the image by digital color display data analyzer (Phosdac) was performed. The subjects of the study were cases at Tokyo Metropolitan Geriatric Hospital ranging from 63 to 85 years old with several kinds of bone diseases. Polyphosphate kits (Diagnostic Isotopes, Inc.) were used to prepare /sup 99m/Tc, and a Rho/gamma HP gamma-camera was used for scintigraphy. The images obtained were analyzed by Phosdac to obtain clear image of the bone system. In the final preparation, presence of approximately 30% of free /sup 99m/Tc was noticedmore » by paper chromatography. /sup 99m/Tc- polyphosphate was cleared from the blood with a half time of about 60 min. Urinary excretion proved to be 40 to 60% within 24 hrs. The bone system was visualized rather clearly with high accumulation of the label in the diseased region in spite of the fact that geriatric cases had marked general osteoporotic tendencies. In some cases, ribs were clearly visualized, and different information from that of x-ray was obtained by scanning images. Data processing by Phosdac increased diagnostic accuracy by enhancing the difference of the density of the image as well as eliminating the background caused by free /sup 99m/TcO/sub 4/. In conclusion, /sup 99m/Tc-polyphosphate was proved to be useful for bone scanning in geriatric cases. A digital color display data analyzer was successfully applied for the processing of the original data. (auth)« less

Could soluble urokinase plasminogen receptor (suPAR) be used as a diagnostic biomarker for ventilator-associated pneumonia?

PubMed

Sunnetcioglu, Aysel; Sunnetcioglu, Mahmut; Adıyaman, Fırat; Binici, Irfan; Soyoral, Lokman

2017-11-01

Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker that is increasingly used for evaluation of systemic inflammation. This study was performed to investigate whether suPAR may possess a diagnostic value in patients with ventilator-associated pneumonia (VAP). This clinical study was performed in the anesthesia intensive care units (ICUs) of our university. In addition to descriptive data, WBC, serum levels of C-reactive protein (CRP) and suPAR prior to and after development of VAP were noted and compared in 31 patients (22 men, 9 women) diagnosed with VAP (Study Group) and 19 patients without VAP (Control Group) in ICU (14 men, 5 women). The suPAR (P = 0.023), CRP (P = 0.037), WBCs (P = 0.024) in patients with VAP were significantly higher than patients without VAP. There was no remarkable difference in terms of WBCs (P = 0.052) and suPAR levels (P = 0.616) between groups on the first day of connection to mechanical ventilator. The suPAR and CRP levels in patients with VAP were significantly higher than prior to development of VAP (P = 0.001 for both). Area under curve value after diagnosis of pneumonia was found 0.248 (P = 0.002). To conclude, our results suggest that suPAR can be a useful diagnostic biomarker in patients with VAP. However, clinical trials on larger series are warranted to explore the clinical significance more accurately. © 2016 John Wiley & Sons Ltd.

Endophthalmitis following 27-Gauge Pars Plana Vitrectomy for Vitreous Floaters

PubMed Central

Lin, Zhong; Wu, Rong Han; Moonasar, Nived

2016-01-01

Purpose To report a case of Staphylococcus epidermidis endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters. Methods The clinical course and imaging findings, including fundus optomap, and spectral domain optical coherence tomography of a 24-year-old male patient were documented. Results The patient, with a preoperative best-corrected visual acuity (BCVA) of 1.0, developed endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters. After a series of treatments, including emergent vitreous tap and silicone oil injection, antibiotic treatment, and silicone oil removal, the patient regained a BCVA of 0.6. Conclusion Although rare, the potential risk of endophthalmitis should be explicitly discussed with patients considering surgical intervention for vitreous floaters. PMID:28101041

Endophthalmitis following 27-Gauge Pars Plana Vitrectomy for Vitreous Floaters.

PubMed

Lin, Zhong; Wu, Rong Han; Moonasar, Nived

2016-01-01

To report a case of Staphylococcus epidermidis endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters. The clinical course and imaging findings, including fundus optomap, and spectral domain optical coherence tomography of a 24-year-old male patient were documented. The patient, with a preoperative best-corrected visual acuity (BCVA) of 1.0, developed endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters. After a series of treatments, including emergent vitreous tap and silicone oil injection, antibiotic treatment, and silicone oil removal, the patient regained a BCVA of 0.6. Although rare, the potential risk of endophthalmitis should be explicitly discussed with patients considering surgical intervention for vitreous floaters.

Cortical Polarity of the RING Protein PAR-2 Is Maintained by Exchange Rate Kinetics at the Cortical-Cytoplasmic Boundary.

PubMed

Arata, Yukinobu; Hiroshima, Michio; Pack, Chan-Gi; Ramanujam, Ravikrishna; Motegi, Fumio; Nakazato, Kenichi; Shindo, Yuki; Wiseman, Paul W; Sawa, Hitoshi; Kobayashi, Tetsuya J; Brandão, Hugo B; Shibata, Tatsuo; Sako, Yasushi

2016-08-23

Cell polarity arises through the spatial segregation of polarity regulators. PAR proteins are polarity regulators that localize asymmetrically to two opposing cortical domains. However, it is unclear how the spatially segregated PAR proteins interact to maintain their mutually exclusive partitioning. Here, single-molecule detection analysis in Caenorhabditis elegans embryos reveals that cortical PAR-2 diffuses only short distances, and, as a result, most PAR-2 molecules associate and dissociate from the cortex without crossing into the opposing domain. Our results show that cortical PAR-2 asymmetry is maintained by the local exchange reactions that occur at the cortical-cytoplasmic boundary. Additionally, we demonstrate that local exchange reactions are sufficient to maintain cortical asymmetry in a parameter-free mathematical model. These findings suggest that anterior and posterior PAR proteins primarily interact through the cytoplasmic pool and not via cortical diffusion. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Appearance of acute gouty arthritis on indium-111-labeled leukocyte scintigraphy

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

Palestro, C.J.; Vega, A.; Kim, C.K.

1990-05-01

Indium-111-labeled leukocyte scintigraphy was performed on a 66-yr-old male with polyarticular acute gouty arthritis. Images revealed intense labeled leukocyte accumulation in a pattern indistinguishable from septic arthritis, in both knees and ankles, and the metatarsophalangeal joint of both great toes, all of which were involved in the acute gouty attack. Joint aspirate as well as blood cultures were reported as no growth; the patient was treated with intravenous colchicine and ACTH for 10 days with dramatic improvement noted. Labeled leukocyte imaging, repeated 12 days after the initial study, revealed near total resolution of joint abnormalities, concordant with the patient's clinicalmore » improvement. This case demonstrates that while acute gouty arthritis is a potential pitfall in labeled leukocyte imaging, in the presence of known gout, it may provide a simple, objective, noninvasive method of evaluating patient response to therapy.« less

Par-4 dependent modulation of cellular β-catenin by medicinal plant natural product derivative 3-azido Withaferin A.

PubMed

Amin, Hina; Nayak, Debasis; Ur Rasool, Reyaz; Chakraborty, Souneek; Kumar, Anmol; Yousuf, Khalid; Sharma, Parduman Raj; Ahmed, Zabeer; Sharma, Neelam; Magotra, Asmita; Mukherjee, Debaraj; Kumar, Lekha Dinesh; Goswami, Anindya

2016-05-01

Here, we provide evidences that natural product derivative 3-azido Withaferin A (3-AWA) abrogated EMT and invasion by modulating β-catenin localization and its transcriptional activity in the prostate as well as in breast cancer cells. This study, for the first time, reveals 3-AWA treatment consistently sequestered nuclear β-catenin and augmented its cytoplasmic pool as evidenced by reducing β-catenin transcriptional activity in these cells. Moreover, 3-AWA treatment triggered robust induction of pro-apoptotic intracellular Par-4, attenuated Akt activity and rescued Phospho-GSK3β (by Akt) to promote β-catenin destabilization. Further, our in vitro studies demonstrate that 3-AWA treatment amplified E-cadherin expression along with sharp downregulation of c-Myc and cyclin D1 proteins. Strikingly, endogenous Par-4 knock down by siRNA underscored 3-AWA mediated inhibition of nuclear β-catenin was Par-4 dependent and suppression of Par-4 activity, either by Bcl-2 or by Ras transfection, restored the nuclear β-catenin level suggesting Par-4 mediated β-catenin regulation was not promiscuous. In vivo results further demonstrated that 3-AWA was effective inhibitor of tumor growth and immunohistochemical studies indicated that increased expression of total β-catenin and decreased expression of phospho-β-catenin and Par-4 in breast cancer tissues as compared to normal breast tissue suggesting Par-4 and β-catenin proteins are mutually regulated and inversely co-related in normal as well as cancer condition. Thus, strategic regulation of intracellular Par-4 by 3-AWA in diverse cancers could be an effective tool to control cancer cell metastasis. Conclusively, this report puts forward a novel approach of controlling deregulated β-catenin signaling by 3-AWA induced Par-4 protein. © 2015 Wiley Periodicals, Inc.

Activation of PAR(2) receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint.

PubMed

Russell, F A; Schuelert, N; Veldhoen, V E; Hollenberg, M D; McDougall, J J

2012-12-01

The PAR(2) receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR(2) activation in the rat knee joint. PAR(2) in rat knee joint dorsal root ganglia (DRG) cells at L3-L5, retrogradely labelled with Fluoro-gold (FG) were demonstrated immunohistochemically. Electrophysiological recordings from knee joint nerve fibres in urethane anaesthetized Wistar rats assessed the effects of stimulating joint PAR(2) with its activating peptide, 2-furoyl-LIGRLO-NH(2) (1-100 nmol·100 μL(-1) , via close intra-arterial injection). Fibre firing rate was recorded during joint rotations before and 15 min after administration of PAR(2) activating peptide or control peptide. Leukocyte kinetics in the synovial vasculature upon PAR(2) activation were followed by intravital microscopy for 60 min after perfusion of 2-furoyl-LIGRLO-NH(2) or control peptide. Roles for transient receptor potential vanilloid-1 (TRPV1) or neurokinin-1 (NK(1) ) receptors in the PAR(2) responses were assessed using the selective antagonists, SB366791 and RP67580 respectively. PAR(2) were expressed in 59 ± 5% of FG-positive DRG cells; 100 nmol 2-furoyl-LIGRLO-NH(2) increased joint fibre firing rate during normal and noxious rotation, maximal at 3 min (normal; 110 ± 43%, noxious; 90 ± 31%). 2-Furoyl-LIGRLO-NH(2) also significantly increased leukocyte rolling and adhesion over 60 min. All these effects were blocked by pre-treatment with SB366791 and RP67580 (P < 0.05 compared with 2-furoyl-LIGRLO-NH(2) alone). PAR(2) receptors play an acute inflammatory role in the knee joint via TRPV1- and NK(1) -dependent mechanisms involving both PAR(2) -mediated neuronal sensitization and leukocyte trafficking. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Deriving the Intrahepatic Arteriovenous Shunt Rate from CT Images and Biochemical Data Instead of from Arterial Perfusion Scintigraphy in Hepatic Arterial Infusion Chemotherapy

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

Ozaki, Toshiro, E-mail: ganronbun@amail.plala.or.jp; Seki, Hiroshi; Shiina, Makoto

2009-09-15

The purpose of the present study was to elucidate a method for predicting the intrahepatic arteriovenous shunt rate from computed tomography (CT) images and biochemical data, instead of from arterial perfusion scintigraphy, because adverse exacerbated systemic effects may be induced in cases where a high shunt rate exists. CT and arterial perfusion scintigraphy were performed in patients with liver metastases from gastric or colorectal cancer. Biochemical data and tumor marker levels of 33 enrolled patients were measured. The results were statistically verified by multiple regression analysis. The total metastatic hepatic tumor volume (V{sub metastasized}), residual hepatic parenchyma volume (V{sub residual};more » calculated from CT images), and biochemical data were treated as independent variables; the intrahepatic arteriovenous (IHAV) shunt rate (calculated from scintigraphy) was treated as a dependent variable. The IHAV shunt rate was 15.1 {+-} 11.9%. Based on the correlation matrixes, the best correlation coefficient of 0.84 was established between the IHAV shunt rate and V{sub metastasized} (p < 0.01). In the multiple regression analysis with the IHAV shunt rate as the dependent variable, the coefficient of determination (R{sup 2}) was 0.75, which was significant at the 0.1% level with two significant independent variables (V{sub metastasized} and V{sub residual}). The standardized regression coefficients ({beta}) of V{sub metastasized} and V{sub residual} were significant at the 0.1 and 5% levels, respectively. Based on this result, we can obtain a predicted value of IHAV shunt rate (p < 0.001) using CT images. When a high shunt rate was predicted, beneficial and consistent clinical monitoring can be initiated in, for example, hepatic arterial infusion chemotherapy.« less

Par Pond vegetation status summer 1995 - July survey descriptive summary

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

Mackey, H.E. Jr.; Riley, R.S.

1995-07-01

A survey of the emergent shoreline aquatic plant, communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet (61 meters) above mean sea level, and continued with this July survey. Aquatic plant communities, similar to the pre-drawdown Par Pond communities, are becoming reestablished. Beds of maidencane (Panicum hemitomon), lotus (Nelumbo lutea), water lily (Nymphaea odorata), and watershield (Brasenia schreberi) are now extensive and well established. In addition, within isolated coves, extensive beds of water lilies and spike-rush (Eleocharis sp.) are common. Cattail occurrence has increased since refill, but large beds common to Parmore » Pond prior to the drawdown have not formed. Invasion of willow (Salix sp.) and red maple (Acer rubrum) occurred along the lake shoreline during drawdown. The red maples along the present shoreline are beginning to show evidence of stress and mortality from flooding over the past four months. Some of the willows appear to be stressed as well. The loblolly pines (Pinus taeda), which were flooded in all but the shallow shoreline areas, are now dead. Future surveys are planned for the growing seasons of 1995, 1996, and 1997, along with the evaluation of satellite data for mapping the areal extent of the macrophyte beds of Par Pond.« less

Loss of Par-1a/MARK3/C-TAK1 Kinase Leads to Reduced Adiposity, Resistance to Hepatic Steatosis, and Defective Gluconeogenesis ▿

PubMed Central

Lennerz, Jochen K.; Hurov, Jonathan B.; White, Lynn S.; Lewandowski, Katherine T.; Prior, Julie L.; Planer, G. James; Gereau, Robert W.; Piwnica-Worms, David; Schmidt, Robert E.; Piwnica-Worms, Helen

2010-01-01

Par-1 is an evolutionarily conserved protein kinase required for polarity in worms, flies, frogs, and mammals. The mammalian Par-1 family consists of four members. Knockout studies of mice implicate Par-1b/MARK2/EMK in regulating fertility, immune homeostasis, learning, and memory as well as adiposity, insulin hypersensitivity, and glucose metabolism. Here, we report phenotypes of mice null for a second family member (Par-1a/MARK3/C-TAK1) that exhibit increased energy expenditure, reduced adiposity with unaltered glucose handling, and normal insulin sensitivity. Knockout mice were protected against high-fat diet-induced obesity and displayed attenuated weight gain, complete resistance to hepatic steatosis, and improved glucose handling with decreased insulin secretion. Overnight starvation led to complete hepatic glycogen depletion, associated hypoketotic hypoglycemia, increased hepatocellular autophagy, and increased glycogen synthase levels in Par-1a−/− but not in control or Par-1b−/− mice. The intercrossing of Par-1a−/− with Par-1b−/− mice revealed that at least one of the four alleles is necessary for embryonic survival. The severity of phenotypes followed a rank order, whereby the loss of one Par-1b allele in Par-1a−/− mice conveyed milder phenotypes than the loss of one Par-1a allele in Par-1b−/− mice. Thus, although Par-1a and Par-1b can compensate for one another during embryogenesis, their individual disruption gives rise to distinct metabolic phenotypes in adult mice. PMID:20733003

[Postoperative uptake of Ga-67 in planar scintigraphy and SPECT after median sternotomy].

PubMed

Montero, A; Carril, J; Quirce, R; Gutiérrez Mendiguchía, C; Uriarte, I; Rabasa, J; Vallina, N K

1998-01-01

Surgical alterations after median sternotomy can difficult the interpretation of scintigraphic images with Ga67. To analize the use of Ga67 scintigraphy in this patology, we wanted to know the Ga67 distribution in patients who had suffered median sternotomy. We studied 8 patients in the first month after median sternotomy without infection complication and performed planar images and SPECT. Ga67 showed uptake in liver, spleen and bone. Sternal uptake was greater or lesser than liver uptake but always showed an homogeneous distribution. No mediastinum uptake was observed. Surgical wound showed Ga67 uptake during the first week after sternotomy. To know the distribution of Ga67 in patients after median sternotomy allows the scan interpretation when we suspect infectous complications.

2. HI PAR (ACQUISITION RADAR) TOWER AND ENLISTED MEN (EM) ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. HI PAR (ACQUISITION RADAR) TOWER AND ENLISTED MEN (EM) BARRACKS WITH RADAR ATTACHED. - Nike Hercules Missile Battery Summit Site, Battery Control Administration & Barracks Building, Anchorage, Anchorage, AK

Application of the newly developed Japanese adenosine normal database for adenosine stress myocardial scintigraphy.

PubMed

Harata, Shingo; Isobe, Satoshi; Morishima, Itsuro; Suzuki, Susumu; Tsuboi, Hideyuki; Sone, Takahito; Ishii, Hideki; Murohara, Toyoaki

2015-10-01

The currently available Japanese normal database (NDB) in stress myocardial perfusion scintigraphy recommended by the Japanese Society of Nuclear Medicine (JSNM-NDB) is created based on the data from exercise tests. The newly developed adenosine normal database (ADS-NDB) remains to be validated for patients undergoing adenosine stress test. We tested whether the diagnostic accuracy of adenosine stress test is improved by the use of ADS-NDB (Kanazawa University). Of 233 consecutive patients undergoing (99m)Tc-MIBI adenosine stress test, 112 patients were tested. The stress/rest myocardial (99m)Tc-MIBI single-photon emission computed tomography (SPECT) images were analyzed by AutoQUANT 7.2 with both ADS-NDB and JSNM-NDB. The summed stress score (SSS) and summed difference score (SDS) were calculated. The agreements of the post-stress defect severity between ADS-NDB and JSNM-NDB were assessed using a weighted kappa statistic. In all patients, mean SSSs of all, right coronary artery (RCA), left anterior descending (LAD), and left circumflex (LCx) territories were significantly lower with ADS-NDB than those with JSNM-NDB. Mean SDSs in all, RCA, and LAD territories were significantly lower with ADS-NDB than those with JSNM-NDB. In 28 patients with significant coronary stenosis, the mean SSS in the RCA territory was significantly lower with ADS-NDB than that with JSNM-NDB. In 84 patients without ischemia, both mean SSSs and SDSs in all, RCA, LAD, and LCx territories were significantly lower with ADS-NDB than those with JSNM-NDB. Weighted kappa values of all patients, patients with significant stenosis, and patients without ischemia were 0.89, 0.83, and 0.92, respectively. Differences were observed between results from ADS-NDB and JSNM-NDB. The diagnostic accuracy of adenosine stress myocardial perfusion scintigraphy may be improved by reducing false-positive results.

Proteinase-activated receptor 2 (PAR-2) in gastrointestinal and pancreatic pathophysiology, inflammation and neoplasia.

PubMed

Søreide, Kjetil

2008-08-01

Of all the body systems, the gastrointestinal (GI) tract is the most exposed to proteinases. Proteolytic activity must thus be tightly regulated in the face of diverse environmental challenges, because unrestrained or excessive proteolysis leads to pathological GI conditions. The protease-activated receptor-2 (PAR-2) is expressed in numerous cell types within the GI tract, suggesting both multiple functions and numerous modes of receptor activation. Although best known as a pancreatic digestive enzyme, trypsin has also been found in other tissues and various cancers. Of interest, trypsin and PAR-2 act together in an autocrine loop that promotes proliferation, invasion and metastasis in neoplasia through various mechanisms. Trypsin and PAR-2 seem to act both directly and indirectly through activation of other proteinase cascades, including metalloproteinases. PAR-2 activation can participate in inflammatory reactions, be protective to mucosal surfaces, send or inhibit nociceptive messages, modify gut motility or secretory functions, and stimulate cell proliferation and motility. Several studies point to a role for the PARs in disease processes of the GI tract and pancreas ranging from inflammatory bowel disease, symptoms associated with irritable bowel syndrome, pain in pancreatitis, development of colon and other GI cancers, and even infectious colitis. Proteinases should not only be considered from the traditional view as digestive or degradative enzymes in the gut, but additionally as signalling molecules that actively participate in the spectrum of physiology and diseased states of the GI tract.

The utility of radioiodine uptake and thyroid scintigraphy in the diagnosis and management of hyperthyroidism.

PubMed

Okosieme, O E; Chan, D; Price, S A; Lazarus, J H; Premawardhana, L D K E

2010-01-01

The value and practice of thyroid radionuclide imaging in the diagnosis and management of hyperthyroidism is unsettled. Our objectives were to determine the influence of thyroid uptake and scintigraphy on the diagnosis of hyperthyroidism and the prediction of outcome following radioiodine therapy. We reviewed records and scintigraphic studies on 881 hyperthyroid patients carried out between 2000 and 2007. The agreement between the clinical and scintigraphic diagnosis was evaluated by kappa statistics. We determined the relationship between 4-h (123)I uptake and the outcome of (131)I treatment in 626 patients. A multiple logistic regression model was used to determine variables influencing treatment outcome in 1 year. The diagnostic categories were Graves' disease (GD, n = 383), toxic multinodular goitre (n = 253), solitary toxic nodule (n = 164) and Graves' disease coexisting with nodules (n = 81). The mean age of the patients was 58 +/- 17, (M:F 160:721). There was good agreement between clinical and scintigraph diagnosis (K = 0.60, 95% CI 0.57-0.64, P < 0.001); and they were correctly matched in 74%; mismatched in 6% and indeterminate in 20% of patients. Treatment outcome was not associated with scintigraph diagnosis (P = 0.98) or radioiodine uptake at 4 h (P = 0.2). The use of antithyroid medications before treatment predicted treatment failure (odds ratio 2.0, 95% CI 1.2-3.6, P = 0.01). Thyroid scintigraphy and uptake studies did not influence diagnosis or treatment outcomes in most cases of hyperthyroidism. Our findings in this retrospective study do not justify their routine use. Selective scanning will reduce cost and exposure to radioisotopes without compromising diagnostic accuracy or treatment outcomes.

Gastroretentive behavior of orally administered radiolabeled tamarind seed formulations in rabbits validated by gamma scintigraphy.

PubMed

Razavi, Mahboubeh; Karimian, Hamed; Yeong, Chai Hong; Fadaeinasab, Mehran; Khaing, Si Lay; Chung, Lip Yong; Mohamad Haron, Didi Erwandi B; Noordin, Mohamed Ibrahim

2017-01-01

This study aimed to formulate floating gastroretentive tablets containing metformin hydrochloric acid (HCl), using various grades of hydrogel such as tamarind powders and xanthan to overcome short gastric residence time of the conventional dosage forms. Different concentrations of the hydrogels were tested to determine the formulation that could provide a sustained release of 12 h. Eleven formulations with different ratios of tamarind seed powder/tamarind kernel powder (TKP):xanthan were prepared. The physical parameters were observed, and in vitro drug-release studies of the prepared formulations were carried out. Optimal formulation was assessed for physicochemical properties, thermal stability, and chemical interaction followed by in vivo gamma scintigraphy study. MKP3 formulation with a TKP:xanthan ratio of 3:2 was found to have 99.87% release over 12 h. Furthermore, in vivo gamma scintigraphy study was carried out for the optimized formulation in healthy New Zealand White rabbits, and the pharmacokinetic parameters of developed formulations were obtained. 153 Sm 2 O 3 was used to trace the profile of release in the gastrointestinal tract of the rabbits, and the drug release was analyzed. The time ( T max ) at which the maximum concentration of metformin HCl in the blood ( C max ) was observed, and it was extended four times for the gastroretentive formulation in comparison with the formulation without polymers. C max and the half-life were found to be within an acceptable range. It is therefore concluded that MKP3 is the optimal formulation for sustained release of metformin HCl over a period of 12 h as a result of its floating properties in the gastric region.

Gastroretentive behavior of orally administered radiolabeled tamarind seed formulations in rabbits validated by gamma scintigraphy

PubMed Central

Razavi, Mahboubeh; Karimian, Hamed; Yeong, Chai Hong; Fadaeinasab, Mehran; Khaing, Si Lay; Chung, Lip Yong; Mohamad Haron, Didi Erwandi B; Noordin, Mohamed Ibrahim

2017-01-01

This study aimed to formulate floating gastroretentive tablets containing metformin hydrochloric acid (HCl), using various grades of hydrogel such as tamarind powders and xanthan to overcome short gastric residence time of the conventional dosage forms. Different concentrations of the hydrogels were tested to determine the formulation that could provide a sustained release of 12 h. Eleven formulations with different ratios of tamarind seed powder/tamarind kernel powder (TKP):xanthan were prepared. The physical parameters were observed, and in vitro drug-release studies of the prepared formulations were carried out. Optimal formulation was assessed for physicochemical properties, thermal stability, and chemical interaction followed by in vivo gamma scintigraphy study. MKP3 formulation with a TKP:xanthan ratio of 3:2 was found to have 99.87% release over 12 h. Furthermore, in vivo gamma scintigraphy study was carried out for the optimized formulation in healthy New Zealand White rabbits, and the pharmacokinetic parameters of developed formulations were obtained. 153Sm2O3 was used to trace the profile of release in the gastrointestinal tract of the rabbits, and the drug release was analyzed. The time (Tmax) at which the maximum concentration of metformin HCl in the blood (Cmax) was observed, and it was extended four times for the gastroretentive formulation in comparison with the formulation without polymers. Cmax and the half-life were found to be within an acceptable range. It is therefore concluded that MKP3 is the optimal formulation for sustained release of metformin HCl over a period of 12 h as a result of its floating properties in the gastric region. PMID:28031701

PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo

PubMed Central

Beatty, Alexander; Morton, Diane G.; Kemphues, Kenneth

2013-01-01

In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The mechanisms by which these proteins interact to maintain polarity are incompletely understood. In this study, we investigate the interplay among PAR-2, LGL-1, myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect cortical myosin accumulation by different mechanisms. LGL-1 does not directly antagonize the accumulation of cortical myosin and instead plays a role in regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in regulating cortical myosin accumulation and preventing the expansion of the anterior cortical domain. We also provide evidence that asymmetry of active CDC-42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary role in regulating the size of the anterior cortical domain via its binding to PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not dependent on PAR-6. PMID:23536568

PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo.

PubMed

Beatty, Alexander; Morton, Diane G; Kemphues, Kenneth

2013-05-01

In the one-cell C. elegans embryo, polarity is maintained by mutual antagonism between the anterior cortical proteins PAR-3, PKC-3, PAR-6 and CDC-42, and the posterior cortical proteins PAR-2 and LGL-1 on the posterior cortex. The mechanisms by which these proteins interact to maintain polarity are incompletely understood. In this study, we investigate the interplay among PAR-2, LGL-1, myosin, the anterior PAR proteins and CDC-42. We find that PAR-2 and LGL-1 affect cortical myosin accumulation by different mechanisms. LGL-1 does not directly antagonize the accumulation of cortical myosin and instead plays a role in regulating PAR-6 levels. By contrast, PAR-2 likely has separate roles in regulating cortical myosin accumulation and preventing the expansion of the anterior cortical domain. We also provide evidence that asymmetry of active CDC-42 can be maintained independently of LGL-1 and PAR-2 by a redundant pathway that includes the CDC-42 GAP CHIN-1. Finally, we show that, in addition to its primary role in regulating the size of the anterior cortical domain via its binding to PAR-6, CDC-42 has a secondary role in regulating cortical myosin that is not dependent on PAR-6.

The rate of endophthalmitis after pars plana vitrectomy and its risk factors.

PubMed

Tabatabaei, Seyed Ali; Soleimani, Mohammad; Vakili, Hadi; Naderan, Morteza; Lashay, Alireza; Faghihi, Houshang; Yaseri, Mehdi

2018-05-11

To study the incidence of endophthalmitis after pars plana vitrectomy, its causative organisms, and visual acuity outcomes. In this retrospective, comparative study, the medical records of patients with acute-onset postoperative endophthalmitis after pars plana vitrectomy at Farabi Eye Hospital, Tehran, Iran, during a 12-year period between January 2004 and November 2015 were reviewed. To compare the endophthalmitis patients with other cases who underwent pars plana vitrectomy at the same day and also the same operating room, a control group was developed by gathering the data from surgical records. In the present study, the incidence rate of pos- vitrectomy endophthalmitis was 0.04% (16/39783). The organisms identified in aqueous or vitreous cultures (culture positive 44%) included Streptococcus pneumoniae (two patients, 12.5%), Pseudomonas aeruginosa (two patients, 12.5%), fungi (two patients, 12.5%), and Streptococcus viridans (one patient, 6.25%). Visual acuity after treatment for endophthalmitis ranged from light perception (7 eyes) to hand motion (1 eye), and evisceration was performed in 8 eyes (50%). When comparing the cases (patients developing endophthalmitis) and controls (patients with no complications operated in the same day and place of operation with the case group), only not using tamponade showed a statistically significant relation with the occurrence of endophthalmitis (p = 0.034). Our results indicated low incidence of endophthalmitis after pars plana vitrectomy comparable to previous studies which resulted in poor visual acuity. It seems that not using tamponade might increase the risk of endophthalmitis among these patients.

[Slaves in purgatory: the Tucunduba Leprosarium (Pará, nineteenth century)].

PubMed

Henrique, Márcio Couto

2012-12-01

The article analyzes the experience of the slaves interned at the Tucunduba Leprosarium in Belém, state of Pará during the nineteenth century. The slaves were freed once they showed the marks of their leprosy, and expectations were that they would submit to the segregation policy meant to keep them from contact with the rest of the population. The documentation produced by Santa Casa de Misericórdia hospital in Pará and by the province's political authorities reveals the strategies the slaves devised in response to this policy; they used their numerical predominance at the leprosarium to create a network of solidarity that allowed them to recreate their lives and stand in opposition to the type of nation that the era's hygienist theories envisioned.

Participatory Action Research (PAR) cum Action Research (AR) in Teacher Professional Development: A Literature Review

ERIC Educational Resources Information Center

Morales, Marie Paz E.

2016-01-01

This paper reviews Participatory Action Research as an approach to teacher professional development. It maps the origins of Participatory Action Research (PAR) and discusses the benefits and challenges that have been identified by other researchers in utilizing PAR approaches in conducting research. It draws ideas of combining the features of…

PAR-2-mediated control of barrier function and motility differs between early and late phases of postinfectious gut dysfunction in the rat.

PubMed

Fernández-Blanco, Joan Antoni; Fernández-Blanco, Juan A; Hollenberg, Morley D; Martínez, Vicente; Vergara, Patri

2013-02-15

Proteinase-activated receptor-2 (PAR-2) and mast cell (MC) mediators contribute to inflammatory and functional gastrointestinal disorders. We aimed to characterize jejunal PAR-2-mediated responses and the potential MC involvement in the early and late phases of a rat model of postinfectious gut dysfunction. Jejunal tissues of control and Trichinella spiralis-infected (14 and 30 days postinfection) rats, treated or not with the MC stabilizer, ketotifen, were used. Histopathology and immunostaining were used to characterize inflammation, PAR-2 expression, and mucosal and connective tissue MCs. Epithelial barrier function (hydroelectrolytic transport and permeability) and motility were assessed in vitro in basal conditions and after PAR-2 activation. Intestinal inflammation on day 14 postinfection (early phase) was significantly resolved by day 30 (late phase) although MC counts and epithelial permeability remained increased. PAR-2-mediated ion transport (Ussing chambers, in vitro) and epithelial surface PAR-2 expression were reduced in the early phase, with a trend toward normalization during the late phase. In control conditions, PAR-2 activation (organ bath) induced biphasic motor responses (relaxation followed by excitation). At 14 days postinfection, spontaneous contractility and PAR-2-mediated relaxations were enhanced; motor responses were normalized on day 30. Postinfectious changes in PAR-2 functions were not affected by ketotifen treatment. We concluded that, in the rat model of Trichinella spiralis infection, alterations of intestinal PAR-2 function and expression depend on the inflammatory phase considered. A lack of a ketotifen effect suggests no interplay between MCs and PAR-2-mediated motility and ion transport alterations. These observations question the role of MC mediators in PAR-2-modulating postinfectious gut dysfunction.

Whole-body scintigraphy with radioiodine-131. A comprehensive list of false-positives with some examples.

PubMed

McDougall, I R

1995-10-01

Whole-body scintigraphy with radioiodine-131 is an important diagnostic test in the management of patients with differentiated thyroid cancer who have undergone surgical treatment. The scan can demonstrate the presence of residual thyroid or functioning metastases in lymph nodes or distant sites. However, there are a number of potential pitfalls in the interpretation of this scan that could lead to a false-positive diagnosis of cancer. The scintiscans are presented for five patients in whom uptake outside of the thyroid was not due to functioning metastases. Some of these abnormalities are physiologic, such as uptake of iodine in the gastrointestinal tract. A comprehensive list of false-positive results are tabulated.

"It was like reading a detective novel": Using PAR to work together for culture change.

PubMed

Fortune, Darla; McKeown, Janet; Dupuis, Sherry; de Witt, Lorna

2015-08-01

Participatory action research (PAR), with its focus on engagement and collaboration, is uniquely suited to enhancing culture change initiatives in dementia care. Yet, there is limited literature of its application to culture change approaches in care settings, and even less in dementia specific care contexts. To address these gaps in the literature, the purpose of this paper is to examine the complexities of a PAR project aimed at changing the culture of dementia care in two diverse dementia care settings, including a long term care (LTC) and community care setting. Drawing from data gathered throughout the PAR process, we unpack the challenges experienced by participants working together to guide culture change within their respective care settings. These challenges include: overextending selves through culture change participation; fluctuating group membership; feeling uncertainty, confusion and apprehension about the process; frustratingly slow process; and seeking diverse group representation in decision making. We also highlight the potential for appreciative inquiry (AI) to be integrated with PAR to guide a process whereby participants involved in culture change initiatives can develop strategies to mitigate challenges they experience. We view the challenges and strategies shared here as being constructive to would-be culture change agents and hope this paper will move others to consider the use of PAR when engaging in culture change initiatives. Copyright © 2015 Elsevier Inc. All rights reserved.

Evidence that compatibility of closely related replicons in Clostridium perfringens depends on linkage to parMRC-like partitioning systems of different subfamilies.

PubMed

Watts, Thomas D; Johanesen, Priscilla A; Lyras, Dena; Rood, Julian I; Adams, Vicki

2017-05-01

Clostridium perfringens produces an extensive repertoire of toxins and extracellular enzymes, many of which are intimately involved in the progression of disease and are encoded by genes on conjugative plasmids. In addition, many C. perfringens strains can carry up to five of these conjugative toxin or antimicrobial resistance plasmids, each of which has a similar 35kb backbone. This conserved backbone includes the tcp conjugation locus and the central control region (CCR), which encodes genes involved in plasmid regulation, replication and partitioning, including a parMRC partitioning locus. Most conjugative plasmids in C. perfringens have a conserved replication protein, raising questions as to how multiple, closely related plasmids are maintained within a single strain. Bioinformatics analysis has highlighted the presence of at least 10 different parMRC partitioning system families (parMRC A-J ) in these plasmids, with differences in amino acid sequence identity between each ParM family ranging from 15% to 54%. No two plasmids that encode genes belonging to the same partitioning family have been observed in a single strain, suggesting that these families represent the basis for plasmid incompatibility. In an attempt to validate the proposed parMRC incompatibility groups, genetically marked C. perfringens plasmids encoding identical parMRC C or parMRC D homologues or different combinations of parMRC A , parMRC C and parMRC D family homologues were introduced into a single strain via conjugation. The stability of each plasmid was determined using an incompatibility assay in which the plasmid profile of each strain was monitored over the course of two days in the absence of direct selection. The results showed that plasmids with identical parMRC C or parMRC D homologues were incompatible and could not coexist in the absence of external selection. By contrast, plasmids that encoded different parMRC homologues were compatible and could coexist in the same cell in the

Kis antitoxin couples plasmid R1 replication and parD (kis,kid) maintenance modules.

PubMed

López-Villarejo, Juan; Diago-Navarro, Elizabeth; Hernández-Arriaga, Ana María; Díaz-Orejas, Ramón

2012-03-01

The coupling between the replication and parD (kis, kid) maintenance modules of R1 has been revisited here by the isolation of a significant collection of conditional replication mutants in the pKN1562 mini-R1 plasmid, and in its derivative, pJLV01, specifically affected in the RNase activity of the Kid toxin. This new analysis aims to identify key factors in this coupling. For this purpose we have quantified and characterized the restriction introduced by parD to isolate conditional replication mutants of this plasmid, a signature of the modular coupling. This restriction depends on the RNase activity of the Kid toxin and it is relieved by either over-expression of the Kis antitoxin or by preventing its degradation by Lon and ClpAP proteases. Based on these data and on the correlation between copy numbers and parD transcriptional levels obtained in the different mutants, it is proposed that a reduction of Kis antitoxin levels in response to inefficient plasmid replication is the key factor for coupling plasmid replication and parD modules. Copyright © 2012 Elsevier Inc. All rights reserved.

The Polarity Protein Partitioning-defective 1 (PAR-1) Regulates Dendritic Spine Morphogenesis through Phosphorylating Postsynaptic Density Protein 95 (PSD-95)*

PubMed Central

Wu, Qian; DiBona, Victoria L.; Bernard, Laura P.; Zhang, Huaye

2012-01-01

The polarity protein PAR-1 plays an essential role in many cellular contexts, including embryogenesis, asymmetric cell division, directional migration, and epithelial morphogenesis. Despite its known importance in different cellular processes, the role of PAR-1 in neuronal morphogenesis is less well understood. In particular, its role in the morphogenesis of dendritic spines, which are sites of excitatory synaptic inputs, has been unclear. Here, we show that PAR-1 is required for normal spine morphogenesis in hippocampal neurons. We further show that PAR-1 functions through phosphorylating the synaptic scaffolding protein PSD-95 in this process. Phosphorylation at a conserved serine residue in the KXGS motif in PSD-95 regulates spine morphogenesis, and a phosphomimetic mutant of this site can rescue the defects of kinase-dead PAR-1. Together, our findings uncover a role of PAR-1 in spine morphogenesis in hippocampal neurons through phosphorylating PSD-95. PMID:22807451

The polarity protein partitioning-defective 1 (PAR-1) regulates dendritic spine morphogenesis through phosphorylating postsynaptic density protein 95 (PSD-95).

PubMed

Wu, Qian; DiBona, Victoria L; Bernard, Laura P; Zhang, Huaye

2012-08-31

The polarity protein PAR-1 plays an essential role in many cellular contexts, including embryogenesis, asymmetric cell division, directional migration, and epithelial morphogenesis. Despite its known importance in different cellular processes, the role of PAR-1 in neuronal morphogenesis is less well understood. In particular, its role in the morphogenesis of dendritic spines, which are sites of excitatory synaptic inputs, has been unclear. Here, we show that PAR-1 is required for normal spine morphogenesis in hippocampal neurons. We further show that PAR-1 functions through phosphorylating the synaptic scaffolding protein PSD-95 in this process. Phosphorylation at a conserved serine residue in the KXGS motif in PSD-95 regulates spine morphogenesis, and a phosphomimetic mutant of this site can rescue the defects of kinase-dead PAR-1. Together, our findings uncover a role of PAR-1 in spine morphogenesis in hippocampal neurons through phosphorylating PSD-95.

Foxo-dependent Par-4 Upregulation Prevents Long-term Survival of Residual Cells Following PI3K-Akt Inhibition.

PubMed

Damrauer, Jeffrey S; Phelps, Stephanie N; Amuchastegui, Katie; Lupo, Ryan; Mabe, Nathaniel W; Walens, Andrea; Kroger, Benjamin R; Alvarez, James V

2018-04-01

Tumor recurrence is a leading cause of death and is thought to arise from a population of residual cells that survive treatment. These residual cancer cells can persist, locally or at distant sites, for years or decades. Therefore, understanding the pathways that regulate residual cancer cell survival may suggest opportunities for targeting these cells to prevent recurrence. Previously, it was observed that the proapoptotic protein (PAWR/Par-4) negatively regulates residual cell survival and recurrence in mice and humans. However, the mechanistic underpinnings on how Par-4 expression is regulated are unclear. Here, it is demonstrated that Par-4 is transcriptionally upregulated following treatment with multiple drugs targeting the PI3K-Akt-mTOR signaling pathway, and identify the Forkhead family of transcription factors as mediators of this upregulation. Mechanistically, Foxo3a directly binds to the Par-4 promoter and activates its transcription following inhibition of the PI3K-Akt pathway. This Foxo-dependent Par-4 upregulation limits the long-term survival of residual cells following treatment with therapeutics that target the PI3K-Akt pathway. Taken together, these results indicate that residual breast cancer tumor cell survival and recurrence requires circumventing Foxo-driven Par-4 upregulation and suggest that approaches to enforce Par-4 expression may prevent residual cell survival and recurrence. Mol Cancer Res; 16(4); 599-609. ©2018 AACR . ©2018 American Association for Cancer Research.

Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma

PubMed Central

Shrestha Palikhe, Nami; Nahirney, Drew; Laratta, Cheryl; Gandhi, Vivek Dipak; Vethanayagam, Dilini; Bhutani, Mohit; Mayers, Irvin

2015-01-01

Background Protease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied. Methods We recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry. Results Subjects with severe asthma had higher PAR-2 expression on CD14++CD16+ monocytes (intermediate monocytes) and also higher percentage of CD14++CD16+PAR-2+ monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14++CD16+PAR-2+ in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14++CD16+ PAR-2+ cells in peripheral blood compared to subjects without exacerbations. Conclusions PAR-2 expression is increased on CD14++CD16+ monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14++CD16+ monocytes may play a role in the pathogenesis of severe asthma. PMID:26658828

Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma.

PubMed

Shrestha Palikhe, Nami; Nahirney, Drew; Laratta, Cheryl; Gandhi, Vivek Dipak; Vethanayagam, Dilini; Bhutani, Mohit; Mayers, Irvin; Cameron, Lisa; Vliagoftis, Harissios

2015-01-01

Protease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied. We recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry. Subjects with severe asthma had higher PAR-2 expression on CD14++CD16+ monocytes (intermediate monocytes) and also higher percentage of CD14++CD16+PAR-2+ monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14++CD16+PAR-2+ in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14++CD16+ PAR-2+ cells in peripheral blood compared to subjects without exacerbations. PAR-2 expression is increased on CD14++CD16+ monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14++CD16+ monocytes may play a role in the pathogenesis of severe asthma.

Astragaloside Alleviates Hepatic Fibrosis Function via PAR2 Signaling Pathway in Diabetic Rats.

PubMed

Wang, Zhenchang; Li, Quanqiang; Xiang, Mingpeng; Zhang, Fengying; Wei, Dongyu; Wen, Zhixi; Zhou, Ying

2017-01-01

Astragaloside (AGS) extracted from radix astragalin (Huangqi) has been considered to be beneficial to liver diseases. In this study, we examined the role played by AGS in alleviating hepatic fibrosis function via protease-activated receptor-2 (PAR2) mechanisms. We hypothesized that AGS affects PAR2 signaling pathway thereby improving hepatic function in rats with hepatic fibrosis induced by carbon tetrachloride (CCl4). We further hypothesized that AGS attenuates impaired hepatic function evoked by CCl4 to a greater degree in diabetic animals. ELISA and Western Blot analysis were used to examine PAR2 signaling pathway in diabetic CCl4-rats and non-diabetic CCl4-rats. AGS inhibited the protein expression of PAR2 and its downstream pathway PKA and PKCɛ in CCl4-rats. Notably, the effects of AGS were greater in CCl4-rats with diabetes. AGS also significantly attenuated the CCl4-induced upregulations of pro-inflammatory cytokines, namely interleukin-1β, interleukin-6 and tumor necrosis factor-α accompanied with decreases of collagenic parameters such as hexadecenoic acid, laminin and hydroxyproline. Additionally, AGS improved the CCl4-induced exaggerations of liver index and functions including alanine aminotransferase, aspartate aminotransferase. Moreover, TGF-β1, a marker of hepatic fibrosis, was increased in CCl4-rats and AGS inhibited increases in TGF-β1 induced by CCl4. AGS alleviates hepatic fibrosis by inhibiting PAR2 signaling expression and its effects are largely enhanced in diabetic animals. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of hepatic fibrosis; and results of our study are likely to shed light on strategies for application of AGS because it has potentially greater therapeutic effectiveness for hepatic fibrosis in diabetes. © 2017 The Author(s)Published by S. Karger AG, Basel.

The Role of Salivary Gland Scintigraphy in the Evaluation of Salivary Gland Dysfunction in Uncontrolled Type II Diabetic Patients.

PubMed

Senthilkumar, B; Sathasivasubramanian, S

2013-09-01

The aim of the present study was to evaluate the salivary gland dysfunction in patients with uncontrolled type II diabetes using salivary gland scintigraphy and then to compare these ratios with quantitative whole salivary secretion rates. Using a gamma camera (siemens-diacam) equipped with a low energy all-purpose collimator, 32 uncontrolled type II diabetic patients and 30 normal healthy patients were studied by injecting a radio isotope (technetium 99m pertechnetate) about 5 mCi was injected intravenously in to anticubital vein and the activity was measured for the 1(st), 20(th) and 40(th) min. At 20 min after injection, vitamin C chewable tablet was given to stimulate the secretion and continued until the end of the study period (40 min). Before scintigraphy, salivary sampling was carried out in both diabetic and normal individuals in a quiet room, saliva was allowed to accumulate and was expectorated into the collecting vessel approximately once a minute for 15 min and the volume was recorded as Unstimulated salivary flow rate and after 5 min break vitamin C chewable tablet was given to stimulate the secretion and the patient was asked to expectorate the saliva in the collecting vessel for 5 min. The expectorated volume was recorded as stimulated salivary flow rate. The mean of the measurements of scintigraphic ratio and salivary secretion rates were compared using the paired Student's t-test. The scintigraphic mean uptake and excretory ratio (ER) and the salivary flow rates were correlated. The result shows that there was a significant correlation between salivary flow rate and scintigraphic uptake and ER. However, statistically significant result could not be derived as it may be due to smaller sample size and marginal difference in the scintigraphic values between the groups. Salivary gland scintigraphy plays a significant role in the evaluation of salivary gland dysfunction. However, its role as an independent investigative procedure in the evaluation of

Ketorolac reduces spinal astrocytic activation and PAR1 expression associated with attenuation of pain after facet joint injury.

PubMed

Dong, Ling; Smith, Jenell R; Winkelstein, Beth A

2013-05-15

Chronic neck pain affects up to 70% of persons, with the facet joint being the most common source. Intra-articular injection of the non-steroidal anti-inflammatory drug ketorolac reduces post-operative joint-mediated pain; however, the mechanism of its attenuation of facet-mediated pain has not been evaluated. Protease-activated receptor-1 (PAR1) has differential roles in pain maintenance depending on the type and location of painful injury. This study investigated if the timing of intra-articular ketorolac injection after painful cervical facet injury affects behavioral hypersensitivity by modulating spinal astrocyte activation and/or PAR1 expression. Rats underwent a painful joint distraction and received an injection of ketorolac either immediately or 1 day later. Separate control groups included injured rats with a vehicle injection at day 1 and sham operated rats. Forepaw mechanical allodynia was measured for 7 days, and spinal cord tissue was immunolabeled for glial fibrillary acidic protein (GFAP) and PAR1 expression in the dorsal horn on day 7. Ketorolac administered on day 1 after injury significantly reduced allodynia (p=0.0006) to sham levels, whereas injection immediately after the injury had no effect compared with vehicle. Spinal astrocytic activation followed behavioral responses and was significantly decreased (p=0.009) only for ketorolac given at day 1. Spinal PAR1 (p=0.0025) and astrocytic PAR1 (p=0.012) were significantly increased after injury. Paralleling behavioral data, astrocytic PAR1 was returned to levels in sham only when ketorolac was administered on day 1. Yet, spinal PAR1 was significantly reduced (p<0.0001) by ketorolac independent of timing. Spinal astrocyte expression of PAR1 appears to be associated with the maintenance of facet-mediated pain.

Ketorolac Reduces Spinal Astrocytic Activation and PAR1 Expression Associated with Attenuation of Pain after Facet Joint Injury

PubMed Central

Dong, Ling; Smith, Jenell R.

2013-01-01

Abstract Chronic neck pain affects up to 70% of persons, with the facet joint being the most common source. Intra-articular injection of the non-steroidal anti-inflammatory drug ketorolac reduces post-operative joint-mediated pain; however, the mechanism of its attenuation of facet-mediated pain has not been evaluated. Protease-activated receptor-1 (PAR1) has differential roles in pain maintenance depending on the type and location of painful injury. This study investigated if the timing of intra-articular ketorolac injection after painful cervical facet injury affects behavioral hypersensitivity by modulating spinal astrocyte activation and/or PAR1 expression. Rats underwent a painful joint distraction and received an injection of ketorolac either immediately or 1 day later. Separate control groups included injured rats with a vehicle injection at day 1 and sham operated rats. Forepaw mechanical allodynia was measured for 7 days, and spinal cord tissue was immunolabeled for glial fibrillary acidic protein (GFAP) and PAR1 expression in the dorsal horn on day 7. Ketorolac administered on day 1 after injury significantly reduced allodynia (p=0.0006) to sham levels, whereas injection immediately after the injury had no effect compared with vehicle. Spinal astrocytic activation followed behavioral responses and was significantly decreased (p=0.009) only for ketorolac given at day 1. Spinal PAR1 (p=0.0025) and astrocytic PAR1 (p=0.012) were significantly increased after injury. Paralleling behavioral data, astrocytic PAR1 was returned to levels in sham only when ketorolac was administered on day 1. Yet, spinal PAR1 was significantly reduced (p<0.0001) by ketorolac independent of timing. Spinal astrocyte expression of PAR1 appears to be associated with the maintenance of facet-mediated pain. PMID:23126437

uPAR and Cathepsin B Downregulation Induces Apoptosis by Targeting Calcineurin A to BAD via Bcl-2 in Glioma

PubMed Central

Malla, Rama Rao; Gopinath, Sreelatha; Gondi, Christopher S.; Alapati, Kiranmai; Dinh, Dzung H.; Tsung, Andrew J.; Rao, Jasti S.

2011-01-01

Cathepsin B and urokinase plasminogen activator receptor (uPAR) are postulated to play key roles in glioma invasion. Calcineurin is one of the key regulators of mitochondrial-dependent apoptosis, but its mechanism is poorly understood. Hence, we studied subcellular localization of calcineurin after transcriptional downregulation of uPAR and cathepsin B in glioma. In the present study, efficient downregulation of uPAR and cathepsin B increased the translocation of calcineurin A from the mitochondria to the cytosol, decreased pBAD (S136) expression and its interaction with 14-3-3ζ, and increased the interaction of BAD with Bcl-Xl. Co-depletion of uPAR and cathepsin B induced mitochondrial translocation of BAD and caspase 3 as well as PARP activation, cytochrome c and SMAC release. These effects were inhibited by FK506 (10 μM), a specific inhibitor of calcineurin. Calcineurin A was co-localized and also co-immunoprecipitated with Bcl-2. This interaction decreased with co-depletion of uPAR and cathepsin B and also with Bcl-2 inhibitor, HA 14-1 (20 μg/mL). Altered localization and interaction of calcineurin A with Bcl-2 was also observed in vivo when uPAR and cathepsin B were downregulated. In conclusion, downregulation of uPAR and cathepsin B induced apoptosis by targeting calcineurin A to BAD via Bcl-2 in glioma. PMID:21964739

Measurement of gastric emptying by intragastric gamma scintigraphy.

PubMed

Malbert, C H; Mathis, C; Bobillier, E; Laplace, J P; Horowitz, M

1997-09-01

Gastric emptying is usually measured in animals and humans by dilution/sampling or external scintigraphy. These methods are either time consuming or require expensive equipment. The capacity of a miniature gamma counter positioned in the stomach to measure emptying of liquid and solid meals was evaluated. In eight conscious pigs fitted with gastric and duodenal cannulae, gastric emptying of saline (500 mL), dextrose (20%, 500 mL), porridge (300 g) and scrambled eggs (300 g), all labelled with 3.5 MBq 99mTC, was evaluated. When positioned in the antrum the probe was unable to quantify gastric emptying. In contrast, measurements of the fractional emptying of saline over 4-min periods by the probe positioned in the corpus and quantification of radioactivity in the duodenal effluent correlated closely (r = 0.88, P < 0.05). Gastric emptying (50% emptying time) of saline and both solid meals measured by the probe was not significantly different from quantification of the duodenal effluent volume. No difference was observed also for the dextrose meal but only while gastric acid secretion was suppressed by omeprazole. We conclude that an intragastric gamma counter permits measurement of gastric emptying of homogeneous meals provided meal stimulation of gastric secretion was not extensive. This was possible probably by monitoring emptying from the proximal stomach.

Soluble urokinase-type plasminogen activator receptor (suPAR) and interleukin-6 levels in hyperemesis gravidarum.

PubMed

Desdicioglu, Raziye; Yildirim, Melahat; Kocaoglu, Gulcan; Demir Cendek, Busra; Avcioglu, Gamze; Tas, Emre Erdem; Sengul, Ozlem; Erel, Ozcan; Yavuz, Ayse Filiz

2017-10-09

The aim was to compare serum soluble urokinase-type plasminogen activator receptor (suPAR) levels as well as interleukin-6 levels (IL-6) in pregnant women with hyperemesis gravidarum (HG) and asymptomatic pregnant women. Our study population consists of voluntary first trimester-pregnant women who applied to the outpatient clinic of the department of obstetrics and gynecology of Ankara Ataturk Training and Research Hospital. Between February and May 2016, 60 pregnant women were included in our prospective study. Serum suPAR and IL-6 levels were evaluated with the ELISA method. Twenty-nine pregnant women with HG and 31 asymptomatic pregnant women were included in the study. Serum suPAR level in the HG group was measured as 0.36 ± 0.56 ng/ml, whereas this level in the healthy pregnant control group was measured as 0.15 ± 0.15 ng/ml (p < 0.05). The interleukin-6 level in the HG group was 5.69 ± 2.16 pg/ml, whereas in the control group it was measured as 3.88 ± 0.28 pg/ml (p < 0.05). Serum suPAR and IL-6 levels proved to be high in the HG group. It is likely that suPAR could play a role in the etiopathogenesis of hyperemesis gravidarum. Copyright © 2017. Published by Elsevier Taiwan LLC.

Per a 10 activates human derived epithelial cell line in a protease dependent manner via PAR-2.

PubMed

Kale, Sagar L; Arora, Naveen

2015-04-01

Protease activity of Per a 10 has been shown to modulate dendritic cells toward Th-2 polarization and to induce airway inflammation. To elucidate the role of serine protease activity of Per a 10 in inducing biochemical responses in epithelial cells. Per a 10 was inactivated by heat treatment (ΔPer a 10) or AEBSF (iPer a 10). A549 cells were exposed to either enzymatically active/inactive Per a 10. The supernatant was analyzed for the secretion of proinflammatory cytokines by ELISA. Ca(2+) mobilization was analyzed by flow cytometry. A PAR-2 derived synthetic peptide 28GTNRSSKGRSLIGKVDGTSHVTGKGVTC54 was incubated with Per a 10 and the resultant cleaved products were analyzed by LC-MS. PAR-2 activation was inhibited by PAR-2 cleavage inhibiting antibody. ΔPer a 10 was completely inactivated whereas iPer a 10 showed some residual activity. nPer a 10 having protease activity increased the secretion of IL-6, IL-8 and GMCSF from A549 in a dose and time dependent manner whereas iPer a 10 has reduced cytokine secretion. ΔPer a 10 and rPer a 10 were unable to activate the cells. nPer a 10 mobilized intracellular Ca(2+). nPer a 10 cleaved the PAR-2 derived peptide between arginine and serine residues (36R-S37) to expose PAR-2 ligand SLIGKV, as determined by LC-MS. Incubating with anti-PAR-2 cleavage antibody showed diminished cytokine secretion when treated with nPer a 10. Serine protease activity of Per a 10 activates A549 cells to secrete proinflammatory cytokines by PAR-2 activation and Ca(2+)mobilization and can be exploited therapeutically. Copyright © 2014 Elsevier GmbH. All rights reserved.

The human airway trypsin-like protease modulates the urokinase receptor (uPAR, CD87) structure and functions.

PubMed

Beaufort, Nathalie; Leduc, Dominique; Eguchi, Hiroshi; Mengele, Karin; Hellmann, Daniela; Masegi, Tsukio; Kamimura, Takashi; Yasuoka, Susumu; Fend, Falko; Chignard, Michel; Pidard, Dominique

2007-05-01

The human airway trypsin-like protease (HAT) is a respiratory epithelium-associated, type II transmembrane serine protease, which is also detected as an extracellular enzyme in lung fluids during airway inflammatory disorders. We have evaluated its capacity to affect the urokinase-type plasminogen activator receptor (uPAR), a membrane glycolipid-anchored, three-domain (D1D2D3) glycoprotein that plays a crucial role in innate immunity and inflammation by supporting cell migration and matrix degradation, with structure and biological properties that can be regulated via limited endoproteolysis. With the use of immunoblotting, flow immunocytometry, and ELISA analyses applied to a recombinant uPAR protein and to uPAR-expressing monocytic and human bronchial epithelial cells, it was shown that exposure of uPAR to soluble HAT in the range of 10-500 nM resulted in the proteolytic processing of the full-length (D1D2D3) into the truncated (D2D3) species, with cleavage occurring in the D1 to D2 linker sequence after arginine residues at position 83 and 89. Using immunohistochemistry, we found that both HAT and uPAR were expressed in the human bronchial epithelium. Moreover, transient cotransfection in epithelial cells showed that membrane coexpression of the two partners produced a constitutive and extensive shedding of the D1 domain, occurring for membrane-associated HAT concentrations in the nanomolar range. Because the truncated receptor was found to be unable to bind two of the major uPAR ligands, the adhesive matrix protein vitronectin and the serine protease urokinase, it thus appears that proteolytic regulation of uPAR by HAT is likely to modulate cell adherence and motility, as well as tissue remodeling during the inflammatory response in the airways.

Actinic cheilitis: epithelial expression of COX-2 and its association with mast cell tryptase and PAR-2.

PubMed

Rojas, I Gina; Martínez, Alejandra; Brethauer, Ursula; Grez, Patricia; Yefi, Roger; Luza, Sandra; Marchesani, Francisco J

2009-03-01

Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies, including oral cancers. Recent studies have shown that mast cell-derived protease tryptase can induce COX-2 expression by the cleavage of proteinase-activated receptor-2 (PAR-2). Actinic cheilitis (AC) is a premalignant form of lip cancer characterized by an increased density of tryptase-positive mast cells. To investigate the possible contribution of tryptase to COX-2 overexpression during early lip carcinogenesis, normal lip (n=24) and AC (n=45) biopsies were processed for COX-2, PAR-2 and tryptase detection, using RT-PCR and immunohistochemistry. Expression scores were obtained for each marker and tested for statistical significance using Mann-Whitney and Spearmann's correlation tests as well as multivariate logistic regression analysis. Increased epithelial co-expression of COX-2 and PAR-2, as well as, elevated subepithelial density of tryptase-positive mast cells were found in AC as compared to normal lip (P<0.001). COX-2 overexpression was found to be a significant predictor of AC (P<0.034, forward stepwise, Wald), and to be correlated with both tryptase-positive mast cells and PAR-2 expression (P<0.01). The results suggest that epithelial COX-2 overexpression is a key event in AC, which is associated with increased tryptase-positive mast cells and PAR-2. Therefore, tryptase may contribute to COX-2 up-regulation by epithelial PAR-2 activation during early lip carcinogenesis.

Spondylolysis in young tennis players

PubMed Central

Ruiz‐Cotorro, A; Balius‐Matas, R; Estruch‐Massana, A; Angulo, J Vilaró

2006-01-01

The general aetiology, diagnosis, and treatment of spondylolysis, a bone defect in the pars interarticularis of the vertebra, are reviewed. A retrospective study of young tennis players diagnosed between 2000 and 2004 with spondylolysis with or without spondylolisthesis, assessed by radiography and planar bone scintigraphy, is described. If the radiographic results were negative, computed tomography was performed. Sixty six cases were evaluated: 53 L5 lesions, eight L4 lesions, two L3 lesions, and one bilateral lesion at the L2 level. Two more lesions at two levels were found (bilateral L5 and unilateral L4 and L3 on the right side). Classification, treatment, and outcome of the cases are reported. A combination of radiography, planar bone scintigraphy, and SPECT is useful for evaluating spondylolysis in tennis players and recommending treatment. Use of a brace did not appear to achieve significant results. PMID:16632576

Usefulness of rCBF analysis in diagnosing Parkinson's disease: supplemental role with MIBG myocardial scintigraphy.

PubMed

Nagamachi, Shigeki; Wakamatsu, Hideyuki; Kiyohara, Shogo; Fujita, Seigo; Futami, Shigemi; Tamura, Shozo; Nakazato, Masamitsu; Yamashita, Syuichi; Arita, Hideo; Nishii, Ryuichi; Kawai, Keiichi

2008-08-01

(123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is a useful tool for differentiating idiopathic Parkinson's disease (PD) from parkinsonism (PS) caused by other disorders. However, cardiac MIBG uptake is affected by various causes. Alternatively, hypoperfusion in the occipital lobe of PD is reported recently. The objective is to clarify the correlation between regional cerebral blood flow (rCBF) alteration and cardiac MIBG uptake in PD. In addition, we examined whether additional brain perfusion analysis improved the differential diagnostic ability for PD from PS when compared with MIBG scintigraphy alone. Forty-nine patients with PD (27 mild groups: Hoehn and Yahr stages I, II; 22 severe groups: Hoehn and Yahr stages III, IV) and 28 patients with PS participated. We compared absolute rCBF values between PD and PS. In addition, we determined correlation between MIBG parameters and each rCBF value. Finally, we compared the diagnostic ability for the differentiation of PD from PS between two diagnostic criteria, each MIBG index abnormality alone [heart-to-mediastinum ratio, H/M (E) < 1.9, H/E (D) < 1.7, washout rate > 40%] and each MIBG index abnormality or occipital lobe hypoperfusion (<36 ml/100 g per min). Absolute rCBF value of occipital lobe was significantly lower in severe PD as compared with PS or mild PD. In the correlation analysis, rCBF of occipital lobe correlated positively with MIBG parameters (H/M). Regarding the diagnostic ability, sensitivity improved by accounting for occipital hypoperfusion as compared with MIBG indices alone. In contrast, neither specificity nor accuracy improved by adding occipital lobe analysis. MIBG parameters (H/M) correlated positively with occipital hypoperfusion in PD. In the differential diagnosis between PD and PS, although its usefulness might be limited, analysis of rCBF in the occipital lobe added to (123)I-MIBG myocardial imaging can be recommended.

Validation of Ultrasonography for Assessment of Gastric Emptying Time in Healthy Cats by Radionuclide Scintigraphy.

PubMed

Husnik, R; Fletcher, J M; Gaschen, L; Gaschen, F P

2017-03-01

The prevalence of gastric emptying (GE) disorders in cats is unknown due to lack of clinically applicable diagnostic tests. The principal aim of this study was to assess correlation between scintigraphic and ultrasonographic measurements of GE time (GET) in healthy cats. Additionally, variability of ultrasonographic GET, and correlation between scintigraphy and ultrasonographic parameters of gastric motility were evaluated. Eight healthy domestic shorthair cats. Prospective study. Scintigraphic GET was determined using a solid test meal containing 4 mCi 99m Tc-mebrofenin. Each cat had 3 separate ultrasonographic assessments of GE, performed independent of scintigraphic assessment, after solid test meal consumption. The motility index (MI) of antral contractions was plotted against time and time for each fraction of the area under the MI curve determined. Ultrasonographic GET and MI were correlated to scintigraphic GET. Scintigraphic GET (mean ± SD) for 25, 50, and 75% GE was 103 ± 32 minutes, 196 ± 45 minutes, and 288 ± 62 minutes, whereas sonographic GET for 25, 50, and 75% GE was 106 ± 13 minutes, 203 ± 19 minutes, and 305 ± 27 minutes. There was good correlation between scintigraphic and sonographic GET (r = 0.72-0.82) at 45-90% fractional GE and between scintigraphic GET and time of corresponding MI curve fraction (r = 0.78-0.86) at 40-90% fraction of the MI curve. There was moderate intraindividual variability for sonographic GET and MI curve fraction times as well as significant variation among individuals. Ultrasonography is a valid alternative to scintigraphy for assessment of solid-phase GE and allows assessment of postprandial gastric motility in healthy cats. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Recuit thermique rapide de semi-conducteur par énergie micro-onde

NASA Astrophysics Data System (ADS)

Covas, M.; Gay, H. C.

1993-05-01

This paper proposes a new technique for rapid thermal annealing of semi-conductors. This technique is based on microwave energy, and offers the same advantages as the rapid thermal annealing by incoherent light, in terms of rapidity, and contamination. However, our technique reduces considerably the required energy for the annealing process. This technique has been compared to the rapid thermal by incoherent light: lab experiments, carried out on boron implanted silicon samples, showed that a power gain ratio of about 10 can be achieved. Nous proposons une méthode de recuit thermique rapide du silicium par énergie micro-onde. Cette technique offre les mêmes avantages que les traitements thermiques rapides par lumière incohérente, c'est-à-dire des durées de chauffage très brèves, limitant ainsi la diffusion des dopants, et un traitement plaquette par plaquette : les risques de contamination de tout un lot sont ainsi éliminés. De plus notre méthode requiert une faible énergie : pour parvenir à des recuits de qualité similaire à celle obtenue dans des fours de recuit rapide à lampes il faut un flux de puissance 10 fois plus faible.

Non-hematopoietic PAR-2 is essential for matriptase-driven pre-malignant progression and potentiation of ras-mediated squamous cell carcinogenesis

PubMed Central

Sales, Katiuchia Uzzun; Friis, Stine; Konkel, Joanne E.; Godiksen, Sine; Hatakeyama, Marcia; Hansen, Karina K.; Rogatto, Silvia Regina; Szabo, Roman; Vogel, Lotte K.; Chen, Wanjun; Gutkind, J. Silvio; Bugge, Thomas H.

2014-01-01

The membrane-anchored serine protease, matriptase, is consistently dysregulated in a range of human carcinomas, and high matriptase activity correlates with poor prognosis. Furthermore, matriptase is unique among tumor-associated proteases in that epithelial stem cell expression of the protease suffices to induce malignant transformation. Here, we use genetic epistasis analysis to identify proteinase-activated receptor (PAR)-2-dependent inflammatory signaling as an essential component of matriptase-mediated oncogenesis. In cell-based assays, matriptase was a potent activator of PAR-2, and PAR-2 activation by matriptase caused robust induction of NFκB through Gαi. Importantly, genetic elimination of PAR-2 from mice completely prevented matriptase-induced pre-malignant progression, including inflammatory cytokine production, inflammatory cell recruitment, epidermal hyperplasia, and dermal fibrosis. Selective ablation of PAR-2 from bone marrow-derived cells did not prevent matriptase-driven pre-malignant progression, indicating that matriptase activates keratinocyte stem cell PAR-2 to elicit its pro-inflammatory and pro-tumorigenic effects. When combined with previous studies, our data suggest that dual induction of PAR-2-NFκB inflammatory signaling and PI3K-Akt-mTor survival/proliferative signaling underlies the transforming potential of matriptase and may contribute to pro-tumorigenic signaling in human epithelial carcinogenesis. PMID:24469043

Non-hematopoietic PAR-2 is essential for matriptase-driven pre-malignant progression and potentiation of ras-mediated squamous cell carcinogenesis.

PubMed

Sales, K U; Friis, S; Konkel, J E; Godiksen, S; Hatakeyama, M; Hansen, K K; Rogatto, S R; Szabo, R; Vogel, L K; Chen, W; Gutkind, J S; Bugge, T H

2015-01-15

The membrane-anchored serine protease, matriptase, is consistently dysregulated in a range of human carcinomas, and high matriptase activity correlates with poor prognosis. Furthermore, matriptase is unique among tumor-associated proteases in that epithelial stem cell expression of the protease suffices to induce malignant transformation. Here, we use genetic epistasis analysis to identify proteinase-activated receptor (PAR)-2-dependent inflammatory signaling as an essential component of matriptase-mediated oncogenesis. In cell-based assays, matriptase was a potent activator of PAR-2, and PAR-2 activation by matriptase caused robust induction of nuclear factor (NF)κB through Gαi. Importantly, genetic elimination of PAR-2 from mice completely prevented matriptase-induced pre-malignant progression, including inflammatory cytokine production, inflammatory cell recruitment, epidermal hyperplasia and dermal fibrosis. Selective ablation of PAR-2 from bone marrow-derived cells did not prevent matriptase-driven pre-malignant progression, indicating that matriptase activates keratinocyte stem cell PAR-2 to elicit its pro-inflammatory and pro-tumorigenic effects. When combined with previous studies, our data suggest that dual induction of PAR-2-NFκB inflammatory signaling and PI3K-Akt-mTor survival/proliferative signaling underlies the transforming potential of matriptase and may contribute to pro-tumorigenic signaling in human epithelial carcinogenesis.

Activated PAR-2 regulates pancreatic cancer progression through ILK/HIF-α-induced TGF-α expression and MEK/VEGF-A-mediated angiogenesis.