Disruption of Mouse Cytochrome P450 4f14 (Cyp4f14 Gene) Causes Severe Perturbations in Vitamin E Metabolism*

Science.gov (United States)

Bardowell, Sabrina A.; Duan, Faping; Manor, Danny; Swanson, Joy E.; Parker, Robert S.

2012-01-01

Vitamin E is a family of naturally occurring and structurally related lipophilic antioxidants, one of which, α-tocopherol (α-TOH), selectively accumulates in vertebrate tissues. The ω-hydroxylase cytochrome P450–4F2 (CYP4F2) is the only human enzyme shown to metabolize vitamin E. Using cDNA cloning, cell culture expression, and activity assays, we identified Cyp4f14 as a functional murine ortholog of CYP4F2. We then investigated the effect of Cyp4f14 deletion on vitamin E metabolism and status in vivo. Cyp4f14-null mice exhibited substrate-specific reductions in liver microsomal vitamin E-ω-hydroxylase activity ranging from 93% (γ-TOH) to 48% (γ-tocotrienol). In vivo data obtained from metabolic cage studies showed whole-body reductions in metabolism of γ-TOH of 90% and of 68% for δ- and α-TOH. This metabolic deficit in Cyp4f14−/− mice was partially offset by increased fecal excretion of nonmetabolized tocopherols and of novel ω-1- and ω-2-hydroxytocopherols. 12′-OH-γ-TOH represented 41% of whole-body production of γ-TOH metabolites in Cyp4f14−/− mice fed a soybean oil diet. Despite these counterbalancing mechanisms, Cyp4f14-null mice fed this diet for 6 weeks hyper-accumulated γ-TOH (2-fold increase over wild-type littermates) in all tissues and appeared normal. We conclude that CYP4F14 is the major but not the only vitamin E-ω-hydroxylase in mice. Its disruption significantly impairs whole-body vitamin E metabolism and alters the widely conserved phenotype of preferential tissue deposition of α-TOH. This model animal and its derivatives will be valuable in determining the biological actions of specific tocopherols and tocotrienols in vivo. PMID:22665481

Intraoperative detection of ¹⁸F-FDG-avid tissue sites using the increased probe counting efficiency of the K-alpha probe design and variance-based statistical analysis with the three-sigma criteria.

Science.gov (United States)

Povoski, Stephen P; Chapman, Gregg J; Murrey, Douglas A; Lee, Robert; Martin, Edward W; Hall, Nathan C

2013-03-04

Intraoperative detection of (18)F-FDG-avid tissue sites during 18F-FDG-directed surgery can be very challenging when utilizing gamma detection probes that rely on a fixed target-to-background (T/B) ratio (ratiometric threshold) for determination of probe positivity. The purpose of our study was to evaluate the counting efficiency and the success rate of in situ intraoperative detection of (18)F-FDG-avid tissue sites (using the three-sigma statistical threshold criteria method and the ratiometric threshold criteria method) for three different gamma detection probe systems. Of 58 patients undergoing (18)F-FDG-directed surgery for known or suspected malignancy using gamma detection probes, we identified nine (18)F-FDG-avid tissue sites (from amongst seven patients) that were seen on same-day preoperative diagnostic PET/CT imaging, and for which each (18)F-FDG-avid tissue site underwent attempted in situ intraoperative detection concurrently using three gamma detection probe systems (K-alpha probe, and two commercially-available PET-probe systems), and then were subsequently surgical excised. The mean relative probe counting efficiency ratio was 6.9 (± 4.4, range 2.2-15.4) for the K-alpha probe, as compared to 1.5 (± 0.3, range 1.0-2.1) and 1.0 (± 0, range 1.0-1.0), respectively, for two commercially-available PET-probe systems (P < 0.001). Successful in situ intraoperative detection of 18F-FDG-avid tissue sites was more frequently accomplished with each of the three gamma detection probes tested by using the three-sigma statistical threshold criteria method than by using the ratiometric threshold criteria method, specifically with the three-sigma statistical threshold criteria method being significantly better than the ratiometric threshold criteria method for determining probe positivity for the K-alpha probe (P = 0.05). Our results suggest that the improved probe counting efficiency of the K-alpha probe design used in conjunction with the three-sigma statistical

Crystal growth and electronic structure of low-temperature phase SrMgF{sub 4}

Energy Technology Data Exchange (ETDEWEB)

Atuchin, Victor V. [Laboratory of Optical Materials and Structures, Institute of Semiconductor Physics, SB RAS, Novosibirsk 630090 (Russian Federation); Functional Electronics Laboratory, Tomsk State University, Tomsk 634050 (Russian Federation); Laboratory of Semiconductor and Dielectric Materials, Novosibirsk State University, Novosibirsk 630090 (Russian Federation); Goloshumova, Alina A. [Laboratory of Crystal Growth, Institute of Geology and Mineralogy, SB RAS, Novosibirsk 630090 (Russian Federation); Isaenko, Ludmila I. [Laboratory of Semiconductor and Dielectric Materials, Novosibirsk State University, Novosibirsk 630090 (Russian Federation); Laboratory of Crystal Growth, Institute of Geology and Mineralogy, SB RAS, Novosibirsk 630090 (Russian Federation); Jiang, Xingxing [BCCRD, Key Laboratory of Functional Crystals and Laser Technology, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Lobanov, Sergey I. [Laboratory of Crystal Growth, Institute of Geology and Mineralogy, SB RAS, Novosibirsk 630090 (Russian Federation); Zhang, Zhaoming [Australian Nuclear Science & Technology Organisation, Lucas Heights, NSW 2234 (Australia); Lin, Zheshuai, E-mail: zslin@mail.ipc.ac.cn [BCCRD, Key Laboratory of Functional Crystals and Laser Technology, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190 (China)

2016-04-15

Using the vertical Bridgman method, the single crystal of low temperature phase SrMgF{sub 4} is obtained. The crystal is in a very good optical quality with the size of 10×7×5 mm{sup 3}. Detailed photoemission spectra of the element core levels are determined by a monochromatic AlKa (1486.6 eV) X-ray source. Moreover, the first-principles calculations are performed to investigate the electronic structure of SrMgF{sub 4}. A good agreement between experimental and calculated results is achieved. It is demonstrated that almost all the electronic orbitals are strongly localized and the hybridization with the others is very small, but the Mg–F bonds covalency is relatively stronger than that of Sr–F bonds. - Graphical abstract: Large size of low-temperature phase SrMgF{sub 4} crystal was obtained (right) and its electronic structure was investigated by X-ray photoelectron spectroscopy and first-principles calculation (left). - Highlights: • Large size single crystal of low-temperature phase SrMgF{sub 4} is obtained. • Electronic structure of SrMgF{sub 4} is measured by X-ray photoelectron spectroscopy. • Partial densities of states are determined by first-principles calculation. • Good agreement between experimental and calculated results is achieved. • Strong ionic characteristics of chemical bonds are exhibited in SrMgF{sub 4}.

Generalized deep-tissue hyperalgesia in patients with chronic low-back pain

DEFF Research Database (Denmark)

O'Neill, Søren; Manniche, Claus; Graven-Nielsen, Thomas

2007-01-01

be demonstrated in a group of patients with chronic low-back pain with intervertebral disc herniation. Twelve patients with MRI confirmed lumbar intervertebral disc herniation and 12 age and sex matched controls were included. Subjects were exposed to quantitative nociceptive stimuli to the infraspinatus...... in the anterior tibialis muscle compared to controls. In conclusion, generalized deep-tissue hyperalgesia was demonstrated in chronic low-back pain patients with radiating pain and MRI confirmed intervertebral disc herniation, suggesting that this central sensitization should also be addressed in the pain......Some chronic painful conditions including e.g. fibromyalgia, whiplash associated disorders, endometriosis, and irritable bowel syndrome are associated with generalized musculoskeletal hyperalgesia. The aim of the present study was to determine whether generalized deep-tissue hyperalgesia could...

HYPERDIRE. HYPERgeometric functions DIfferential REduction. MATHEMATICA based packages for differential reduction of generalized hypergeometric functions pFp-1, F1, F2, F3, F4

International Nuclear Information System (INIS)

Bytev, Vladimir V.; Kalmykov, Mikhail Yu.; Kniehl, Bernd A.

2013-05-01

HYPERDIRE is a project devoted to the creation of a set of Mathematica based programs for the differential reduction of hypergeometric functions. The current version includes two parts: one, pfq, is relevant for manipulations of hypergeometric functions p+1 F p , and the second one, AppellF1F4, for manipulations with Appell hypergeometric functions F 1 , F 2 , F 3 , F 4 of two variables.

Unresolved issues in the analysis of F2-isoprostanes, F4-neuroprostanes, isofurans, neurofurans, and F2-dihomo-isoprostanes in body fluids and tissue using gas chromatography/negative-ion chemical-ionization mass spectrometry.

Science.gov (United States)

Yen, H-C; Wei, H-J; Lin, C-L

2015-01-01

F2-isoprostanes (F2-IsoPs) generated from arachidonic acid (AA) have been recognized as the most reliable marker of nonenzymatic lipid peroxidation in vivo. F2-IsoPs are initially produced in esterified form on phospholipids, and then released into body fluids in free form. The same mechanism can lead to generation of F4-neuroprostanes (F4-NPs) and F2-dihomo-IsoPs from docosahexaenoic acid (DHA) and adrenic acid, respectively. In addition, isofurans (IsoFs) and neurofurans (NFs) may be preferentially produced from AA and DHA, respectively, under high oxygen tension. The detection of F2-IsoPs using gas chromatography/negative-ion chemical-ionization mass spectrometry (GC/NICI-MS) has been widely employed, which is important for human body fluids containing low quantity of free-form F2-IsoPs. F4-NPs have also been detected using GC/NICI-MS, but multiple peaks need to be quantified. In this paper, we summarize the basic workflow of the GC/NICI-MS method for analyzing F2-IsoPs and F4-NPs, and various formats of assays conducted by different groups. We then discuss the feasibility of simultaneous analysis of IsoFs, NFs, and F2-dihomo-IsoPs with F2-IsoPs or F4-NPs. Representative GC chromatograms for analyzing these markers in human body fluids and rat brain tissue are demonstrated. Furthermore, we discuss several factors that may affect the performance of the analysis, such as those related to the sample processing steps, interference from specimens, types of GC liners used, and the addition of electron multiplier voltage in the method setting for the MS detector. Finally, we question the appropriateness of measuring total (free plus esterified) levels of these markers in body fluids.

Electrochemistry of TiF4 in 1-butyl-2,3-dimethylimidazolium tetrafluoroborate

International Nuclear Information System (INIS)

Andriyko, Yuriy; Andriiko, Alexander; Babushkina, Olga B.; Nauer, Gerhard E.

2010-01-01

Electrochemical behaviour of Ti(IV) species in the ionic liquid (IL) 1-butyl-2,3-dimethylimidazolium tetrafluoroborate (BMMImBF 4 ) was studied by means of chronopotentiometry (CP) and cyclic voltammetry (CV) in melts with different concentrations of TiF 4 (2-35 mol%) within a temperature range of 65-180 deg. C. The electrochemical reduction of Ti(IV) was suggested to proceed via the sequence of one-electron steps with the formation of poorly soluble low valence intermediates (LVI). LVIs undergo further solid-state electrochemical reduction to Ti metal. Thin Ti coatings on a Pt substrate were thus obtained and characterized by ESEM method. FTIR spectroscopy was used for identification of the electrochemical active species of Ti(IV). The reaction 2BF 4 - + TiF 4 ↔ TiF 6 2- + 2BF 3 ↑ takes place in the concentrated solutions of TiF 4 at elevated temperatures.

Efficacy, pharmacokinetics, tisssue distribution, and metabolism of the Myc-Max disruptor, 10058-F4 [Z,E]-5-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in mice.

Science.gov (United States)

Guo, Jianxia; Parise, Robert A; Joseph, Erin; Egorin, Merrill J; Lazo, John S; Prochownik, Edward V; Eiseman, Julie L

2009-03-01

c-Myc is commonly activated in many human tumors and is functionally important in cellular proliferation, differentiation, apoptosis and cell cycle progression. The activity of c-Myc requires noncovalent interaction with its client protein Max. In vitro studies indicate the thioxothiazolidinone, 10058-F4, inhibits c-Myc/Max dimerization. In this study, we report the efficacy, pharmacokinetics and metabolism of this novel protein-protein disruptor in mice. SCID mice bearing DU145 or PC-3 human prostate cancer xenografts were treated with either 20 or 30 mg/kg 10058-F4 on a qdx5 schedule for 2 weeks for efficacy studies. For pharmacokinetics and metabolism studies, mice bearing PC-3 or DU145 xenografts were treated with 20 mg/kg of 10058-F4 i.v. Plasma and tissues were collected 5-1440 min after dosing. The concentration of 10058-F4 in plasma and tissues was determined by HPLC, and metabolites were characterized by LC-MS/MS. Following a single iv dose, peak plasma 10058-F4 concentrations of approximately 300 muM were seen at 5 min and declined to below the detection limit at 360 min. Plasma concentration versus time data were best approximated by a two-compartment, open, linear model. The highest tissue concentrations of 10058-F4 were found in fat, lung, liver, and kidney. Peak tumor concentrations of 10058-F4 were at least tenfold lower than peak plasma concentrations. Eight metabolites of 10058-F4 were identified in plasma, liver, and kidney. The terminal half-life of 10058-F4 was approximately 1 h, and the volume of distribution was >200 ml/kg. No significant inhibition of tumor growth was seen after i.v. treatment of mice with either 20 or 30 mg/kg 10058-F4. The lack of significant antitumor activity of 10058-F4 in tumor-bearing mice may have resulted from its rapid metabolism and low concentration in tumors.

Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and outcome following adjuvant chemotherapy in premenopausal lymph node-positive breast cancer patients: A retrospective study

International Nuclear Information System (INIS)

Schrohl, Anne-Sofie; Look, Maxime P; Meijer-van Gelder, Marion E; Foekens, John A; Brünner, Nils

2009-01-01

We have previously demonstrated that high tumor tissue levels of TIMP-1 are associated with no or limited clinical benefit from chemotherapy with CMF and anthracyclines in metastatic breast cancer patients. Here, we extend our investigations to the adjuvant setting studying outcome after adjuvant chemotherapy in premenopausal lymph node-positive patients. We hypothesize that TIMP-1 high tumors are less sensitive to chemotherapy and accordingly that high tumor tissue levels are associated with shorter survival. From our original retrospectively collected tumor samples we selected a group of 525 pre-menopausal lymph node-positive patients (adjuvant treatment: CMF, 324 patients; anthracycline-based, 99 patients; no adjuvant chemotherapy, 102 patients). TIMP-1 levels were measured using ELISA in cytosolic extracts of frozen primary tumors. TIMP-1 was analyzed as a continuous variable and as a dichotomized one using the median TIMP-1 concentration as a cut point between high and low TIMP-1 groups. We analyzed the benefit of adjuvant CMF and anthracyclines in univariate and multivariable survival models; endpoints were disease-free (DFS) and overall survival (OS). In this selected cohort of high-risk patients, and in the subgroup of patients receiving no adjuvant therapy, TIMP-1 was not associated with prognosis. In the subgroup of patients treated with anthracyclines, when analyzed as a continuous variable we observed a tendency for increasing TIMP-1 levels to be associated with shorter DFS (multivariable analysis, HR 1.75, 95% CI 1.00-3.07, P = 0.05) and a significant association between increasing TIMP-1 and shorter OS in both univariate (HR 3.52, 95% CI 1.54-8.06, P = 0.003) and multivariable analyses (HR 4.19, 95% CI 1.67-10.51, P = 0.002). No statistically significant association between TIMP-1 and DFS was observed in the CMF-treated patients although high TIMP-1 was associated with shorter OS when analyzed as a dichotomized variable (HR 1.64, 95% CI 1.02-2.65, P

Ionothermal synthesis of β-NH4AlF4 and the determination by single crystal X-ray diffraction of its room temperature and low temperature phases

International Nuclear Information System (INIS)

Parnham, Emily R.; Slawin, Alex M.Z.; Morris, Russell E.

2007-01-01

β-NH 4 AlF 4 has been synthesised ionothermally using 1-ethyl-3-methylimidazolium hexafluorophosphate as solvent and template provider. β-NH 4 AlF 4 crystals were produced which were suitable for single crystal X-ray diffraction analysis. A phase transition occurs between room temperature (298 K) and low temperature (93 K) data collections. At 298 K the space group=I4/mcm (no. 140), α=11.642(5), c=12.661(5) A, Z=2 (10NH 4 AlF 4 ), wR(F 2 )=0.1278, R(F)=0.0453. At 93 K the space group=P4 2 /ncm (no. 138), α=11.616(3), c=12.677(3) A, Z=2 (10NH 4 AlF 4 ), wR(F 2 )=0.1387, R(F)=0.0443. The single crystal X-ray diffraction study of β-NH 4 AlF 4 shows the presence of two different polymorphs at low and room temperature, indicative of a phase transition. The [AlF 4/2 F 2 ] - layers are undisturbed except for a small tilting of the AlF 6 octahedra in the c-axis direction. -Ionothermal synthesis, the use of an ionic liquid as the solvent in materials preparation, has been used to prepare β-NH 4 AlF 4 , and structural characterisation indicates that there are two versions of the structure, a low temperature primitive phase at 93 K and a high temperature body-centered phase at 298 K

In vivo evaluation in rats of [18F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine as a potential radiotracer for PET assessment of CNS sigma-1 receptors

International Nuclear Information System (INIS)

Waterhouse, Rikki N.; Chang, Raymond C.; Zhao, Jun; Carambot, Patty E.

2006-01-01

Introduction: Sigma-1 receptors are expressed throughout the mammalian central nervous system (CNS) and are implicated in several psychiatric disorders, including schizophrenia and depression. We have recently evaluated the high-affinity (K D =0.5±0.2 nM, log P=2.9) sigma-1 receptor radiotracer [ 18 F]1-(3-fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine, [ 18 F]FPS, in humans. In contrast to appropriate kinetics exhibited in baboon brain, in the human CNS, [ 18 F]FPS does not reach pseudoequilibrium by 4 h, supporting the development of a lower-affinity tracer [Waterhouse RN, Nobler MS, Chang RC, Zhou Y, Morales O, Kuwabara H, et al. First evaluation of the sigma-1 receptor radioligand [ 18 F]1-3-fluoropropyl-4-((4-cyanophenoxy)-methyl)piperidine ([ 18 F]FPS) in healthy humans. Neuroreceptor Mapping 2004, July 15-18th, Vancouver, BC Canada 2004]. We describe herein the in vivo evaluation in rats of [ 18 F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine ([ 18 F]SFE) (K D =5 nM, log P=2.4), a structurally similar, lower-affinity sigma-1 receptor radioligand. Methods: [ 18 F]SFE was synthesized (n=4) as previously described in good yield (54±6% EOB), high specific activity (2.1±0.6 Ci/μmol EOS) and radiochemical purity (98±1%) and evaluated in awake adult male rats. Results: Similar to [ 18 F]FPS, regional brain radioactivity concentrations [percentage of injected dose per gram of tissue (%ID/g), 15 min] for [ 18 F]SFE were highest in occipital cortex (1.86±0.06 %ID/g) and frontal cortex (1.76±0.38 %ID/g), and lowest in the hippocampus (1.01±0.02%ID/g). Unlike [ 18 F]FPS, [ 18 F]SFE cleared from the brain with ∼40% reduction in peak activity over a 90-min period. Metabolite analysis (1 h) revealed that [ 18 F]SFE was largely intact in the brain. Blocking studies showed a large degree (>80%) of saturable binding for [ 18 F]SFE in discrete brain regions. Conclusions: We conclude that [ 18 F]SFE exhibits excellent characteristics in vivo and may provide

Low-frequency 1/f noise in graphene devices

Science.gov (United States)

Balandin, Alexander A.

2013-08-01

Low-frequency noise with a spectral density that depends inversely on frequency has been observed in a wide variety of systems including current fluctuations in resistors, intensity fluctuations in music and signals in human cognition. In electronics, the phenomenon, which is known as 1/f noise, flicker noise or excess noise, hampers the operation of numerous devices and circuits, and can be a significant impediment to the development of practical applications from new materials. Graphene offers unique opportunities for studying 1/f noise because of its two-dimensional structure and widely tunable two-dimensional carrier concentration. The creation of practical graphene-based devices will also depend on our ability to understand and control the low-frequency noise in this material system. Here, the characteristic features of 1/f noise in graphene and few-layer graphene are reviewed, and the implications of such noise for the development of graphene-based electronics including high-frequency devices and sensors are examined.

High specific radioactivity (1R,2S)-4-[18F]fluorometaraminol: a PET radiotracer for mapping sympathetic nerves of the heart

International Nuclear Information System (INIS)

Langer, Oliver; Valette, Heric; Dolle, Frederic; Halldin, Christer; Loc'h, Christian; Fuseau, Chantal; Coulon, Christine; Ottaviani, Michele; Bottlaender, Michel; Maziere, Bernard; Crouzel, Christian

2000-01-01

The radiolabeled catecholamine analogue (1R,2S)-6-[ 18 F]fluorometaraminol (6-[ 18 F]FMR) is a substrate for the neuronal norepinephrine transporter. It has been used as a positron emission tomography (PET) ligand to map sympathetic nerves in dog heart. 6-[ 18 F]FMR could be only synthesized with low specific radioactivity, which precluded its use in human subjects. We have recently prepared (1R,2S)-4-[ 18 F]fluorometaraminol (4-[ 18 F]FMR), a new fluoro-analogue of metaraminol, with high specific radioactivity (56-106 GBq/μmol). In the present study, we demonstrate in rats that 4-[ 18 F]FMR possesses similar affinity toward myocardial norepinephrine transport mechanisms as 6-[ 18 F]FMR. When compared with control animals, an 80% and 76% reduction in myocardial uptake was observed in animals pretreated with desipramine (an inhibitor of the neuronal norepinephrine transporter) and with reserpine (a blocker of the vesicular storage of monoamines), respectively. The entire radioactivity in rat myocardium represented unmetabolized parent tracer as determined by high performance liquid chromatography analysis of tissue extracts. In dogs, myocardial kinetics of 4-[ 18 F]FMR were assessed using PET. A rapid and high uptake was observed, followed by prolonged cardiac retention. A heart-to-lung ratio of 15 was reached 10 min after injection of the radiotracer. Pretreatment with desipramine reduced the heart half-life of 4-[ 18 F]FMR by 90% compared with control. Moreover, an infusion of tyramine caused a rapid decline of radioactivity in the heart. This demonstrates that 4-[ 18 F]FMR specifically visualizes sympathetic neurons in dog heart. High specific radioactivity 4-[ 18 F]FMR is a promising alternative to 6-[ 18 F]FMR for myocardial neuronal mapping with PET in humans

LatY136F knock-in mouse model for human IgG4-related disease.

Science.gov (United States)

Yamada, Kazunori; Zuka, Masahiko; Ito, Kiyoaki; Mizuguchi, Keishi; Kakuchi, Yasushi; Onoe, Tamehito; Suzuki, Yasunori; Yamagishi, Masakazu; Izui, Shozo; Malissen, Marie; Malissen, Bernard; Kawano, Mitsuhiro

2018-01-01

The adaptor protein Linker for activation of T cell (LAT) is a key signaling hub used by the T cell antigen receptor. Mutant mice expressing loss-of-function mutations affecting LAT and including a mutation in which tyrosine 136 is replaced by a phenylalanine (LatY136F) develop lymphoproliferative disorder involving T helper type 2 effector cells capable of triggering a massive polyclonal B cell activation that leads to hypergammaglobulinemia G1 and E and to non-resolving inflammation and autoimmunity. The purpose of this study was to evaluate whether the phenotypes of LatY136F knock-in mice resemble the immunohistopathological features of immunoglobulin G4-related disease (IgG4-RD). LatY136F knock-in mice were sacrificed at 4-20 weeks of age, and pancreas, kidney, salivary gland and lung were obtained. All organs were stained with hematoxylin-eosin and with Azan for estimation of collagen in fibrosis, and the severity scores of inflammation and fibrosis were evaluated. Immunostainings were performed to analyze the types of infiltrating cells. In addition, the effects of corticosteroid treatment on the development of tissue lesions and serum levels of IgG1 were assessed. Tissue lesions characterized by inflammatory mononuclear cell infiltration and fibrosis were detected in pancreas, kidney, and salivary gland starting from 6 weeks of age. Immunostainings showed pronounced infiltration of plasma cells, CD4-positive T cells, and macrophages. Infiltrating plasma cells predominantly expressed IgG1. The extent of inflammation in pancreas and salivary glands was markedly reduced by corticosteroid treatment. LatY136F knock-in mice displayed increased production of Th2-type IgG1 (a homologue of human IgG4) and developed multiple organ tissue lesions reminiscent of those seen in patients with IgG4-RD. Moreover, the development of these tissue lesions was highly sensitive to corticosteroid treatment like in IgG4-RD. For these reasons we consider the LatY136F knock-in mouse

Prognostic value of {sup 18}F-FDG PET/CT in patients with soft tissue sarcoma: comparisons between metabolic parameters

Energy Technology Data Exchange (ETDEWEB)

Hong, Sun-pyo [Sungkyunkwan University School of Medicine, Department of Nuclear Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Lee, Seung Eun; Choi, Yoon-La [Sungkyunkwan University School of Medicine, Department of Pathology, Samsung Medical Center, Seoul (Korea, Republic of); Seo, Sung Wook; Sung, Ki-Sun [Sungkyunkwan University School of Medicine, Department of Orthopedic Surgery, Samsung Medical Center, Seoul (Korea, Republic of); Koo, Hong Hoe [Sungkyunkwan University School of Medicine, Department of Pediatrics, Samsung Medical Center, Seoul (Korea, Republic of); Choi, Joon Young [Sungkyunkwan University School of Medicine, Department of Nuclear Medicine, Samsung Medical Center, Seoul (Korea, Republic of)

2014-05-15

To investigate the relationship between volume-based PET parameters and prognosis in patients with soft tissue sarcoma (STS). We retrospectively reviewed 55 patients with pathologically proven STS who underwent pretreatment with {sup 18} F-Fluorodeoxyglucose ({sup 18}F-FDG) PET/CT. The maximum standardized uptake value (SUV{sub max}), average SUV (SUV{sub avg}), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary tumors were measured using a threshold SUV as liver activity for determining the boundary of tumors. Univariate and multivariate survival analyses for overall survival were performed according to the metabolic parameters and other clinical variables. Cancer-related death occurred in 19 of 55 patients (35 %) during the follow-up period (29 ± 23 months). On univariate analysis, AJCC stage (stage IV vs. I-III, hazard ratio (HR) = 2.837, p = 0.028), necrosis (G2 vs. G0-G1, HR = 3.890, p = 0.004), SUV{sub max} (1 unit - increase, HR = 1.146, p = 0.008), SUV{sub avg} (1 unit - increase, HR = 1.469, p = 0.032) and treatment modality (non-surgical therapy vs. surgery, HR = 4.467, p = 0.002) were significant predictors for overall survival. On multivariate analyses, SUV{sub max} (HR = 1.274, p = 0.015), treatment modality (HR = 3.353, p = 0.019) and necrosis (HR = 5.985, p = 0.006) were identified as significant independent prognostic factors associated with decreased overall survival. The SUV{sub max} of the primary tumor is a significant independent metabolic prognostic factor for overall survival in patients with STS. Volume-based PET parameters may not add prognostic information outside of the SUV{sub max}. (orig.)

Pattern of tissue deposition, gain and body composition of Nellore, F1 Simmental × Nellore and F1 Angus × Nellore steers fed at maintenance or ad libitum with two levels of concentrate in the diet

Directory of Open Access Journals (Sweden)

Ivanna Moraes de Oliveira

2011-12-01

Full Text Available Sixty 18-month-old steers (20 Nellore, 20 F1 Simmental × Nellore and 20 F1 Angus × Nellore with average body weight of 265.6±6.4 kg; 325.3±4.7 kg and 324.6±6.0 kg, respectively were used. The effects of feeding regime and genetic group on physical carcass composition, empty body composition, composition of the gain, as well as the pattern of tissue deposition were evaluated in this trial. The interaction between genetic group and feeding regime was not significant for any variable evaluated. Animals fed at the maintenance level produced carcass with larger proportions of bones and muscle than the animals fed ad libitum and Nellore animals had larger muscle portion and smaller adipose tissue portion on the carcass than the crossbred animals. Nellore animals and those fed at maintenance had smaller amount of total fat in the carcass than the crossbred animals and those fed ad libitum, respectively. Fat was deposited more pronouncedly in the intermuscular depot, followed by the visceral depot. The rate of deposition of the carcass tissues was smaller in the Nellore animals and in the animals fed the diet with concentrate allowance equivalent to 1% body weight (except for subcutaneous fat tissue, when compared with the crossbred animals and those fed the diet with 2% BW on concentrate, respectively. The rate of fat deposition on the visceral depot was larger in the F1 Angus × Nellore animals and on those fed the 2% of BW of concentrate diet when compared with F1 Simmental × Nellore animals and those fed the diet with the lowest concentrate allowance (1% BW.

High specific radioactivity (1R,2S)-4-[{sup 18}F]fluorometaraminol: a PET radiotracer for mapping sympathetic nerves of the heart

Energy Technology Data Exchange (ETDEWEB)

Langer, Oliver; Valette, Heric; Dolle, Frederic E-mail: dolle@dsvidf.cea.fr; Halldin, Christer; Loc' h, Christian; Fuseau, Chantal; Coulon, Christine; Ottaviani, Michele; Bottlaender, Michel; Maziere, Bernard; Crouzel, Christian

2000-04-01

The radiolabeled catecholamine analogue (1R,2S)-6-[{sup 18}F]fluorometaraminol (6-[{sup 18}F]FMR) is a substrate for the neuronal norepinephrine transporter. It has been used as a positron emission tomography (PET) ligand to map sympathetic nerves in dog heart. 6-[{sup 18}F]FMR could be only synthesized with low specific radioactivity, which precluded its use in human subjects. We have recently prepared (1R,2S)-4-[{sup 18}F]fluorometaraminol (4-[{sup 18}F]FMR), a new fluoro-analogue of metaraminol, with high specific radioactivity (56-106 GBq/{mu}mol). In the present study, we demonstrate in rats that 4-[{sup 18}F]FMR possesses similar affinity toward myocardial norepinephrine transport mechanisms as 6-[{sup 18}F]FMR. When compared with control animals, an 80% and 76% reduction in myocardial uptake was observed in animals pretreated with desipramine (an inhibitor of the neuronal norepinephrine transporter) and with reserpine (a blocker of the vesicular storage of monoamines), respectively. The entire radioactivity in rat myocardium represented unmetabolized parent tracer as determined by high performance liquid chromatography analysis of tissue extracts. In dogs, myocardial kinetics of 4-[{sup 18}F]FMR were assessed using PET. A rapid and high uptake was observed, followed by prolonged cardiac retention. A heart-to-lung ratio of 15 was reached 10 min after injection of the radiotracer. Pretreatment with desipramine reduced the heart half-life of 4-[{sup 18}F]FMR by 90% compared with control. Moreover, an infusion of tyramine caused a rapid decline of radioactivity in the heart. This demonstrates that 4-[{sup 18}F]FMR specifically visualizes sympathetic neurons in dog heart. High specific radioactivity 4-[{sup 18}F]FMR is a promising alternative to 6-[{sup 18}F]FMR for myocardial neuronal mapping with PET in humans.

Synthesis and biodistribution of 18F-labeled fluoronitroimidazoles: Potential in vivo markers of hypoxic tissue

International Nuclear Information System (INIS)

Jerabek, P.A.; Kilbourn, M.R.; Dischino, D.D.; Welch, M.J.; Patrick, T.B.; Southern Illinois University, Edwardsville

1986-01-01

Three 18 F labeled fluoronitroimidazoles have been prepared as potential in vivo markers of hypoxic cells in tumors, and ischemic areas of the heart and brain. 1-(2-Nitroimidazolyl)-3-[ 18 F]fluoro-2-hydroxy-propanol ([ 18 F]fluoro-normethoxymisonidazole 4, 1-(2-[ 18 F]fluoroethyl)-2-nitroimidazole 7, and 1-(2-[ 18 F]-fluoroethyl)-2-methyl-5-nitromidazole ([ 18 F]fluoro-norhydroxymetronidazole) 10 were prepared in average radiochemical yields of 18 F labeled fluoronitroimidazoles. At 1 and 3 h after administration, the tissue distribution of each of the 18 F labeled nitroimidazoles was quite uniform and consistent with that of nitroimidazoles previously studied. These results suggest the need for a suitable animal model to evaluate their potential as in vivo markers of hypoxic tissue in the brain. (author)

Dynamic 18F-FET PET in newly diagnosed astrocytic low-grade glioma identifies high-risk patients.

Science.gov (United States)

Jansen, Nathalie L; Suchorska, Bogdana; Wenter, Vera; Eigenbrod, Sabina; Schmid-Tannwald, Christine; Zwergal, Andreas; Niyazi, Maximilian; Drexler, Mark; Bartenstein, Peter; Schnell, Oliver; Tonn, Jörg-Christian; Thon, Niklas; Kreth, Friedrich-Wilhelm; la Fougère, Christian

2014-02-01

Because the clinical course of low-grade gliomas in the individual adult patient varies considerably and is unpredictable, we investigated the prognostic value of dynamic (18)F-fluorethyltyrosine ((18)F-FET) PET in the early diagnosis of astrocytic low-grade glioma (World Health Organization grade II). Fifty-nine patients with newly diagnosed low-grade glioma and dynamic (18)F-FET PET before histopathologic assessment were retrospectively investigated. (18)F-FET PET analysis comprised a qualitative visual classification of lesions; assessment of the semiquantitative parameters maximal, mean, and total standardized uptake value as ratio to background and biologic tumor volume; and dynamic analysis of intratumoral (18)F-FET uptake over time (increasing vs. decreasing time-activity curves). The correlation between PET parameters and progression-free survival, overall survival, and time to malignant transformation was investigated. (18)F-FET uptake greater than the background level was found in 34 of 59 tumors. Dynamic (18)F-FET uptake analysis was available for 30 of these 34 patients. Increasing and decreasing time-activity curves were found in 18 and 12 patients, respectively. Neither the qualitative factor presence or absence of (18)F-FET uptake nor any of the semiquantitative uptake parameters significantly influenced clinical outcome. In contrast, decreasing time-activity curves in the kinetic analysis were highly prognostic for shorter progression-free survival and time to malignant transformation (P dynamic (18)F-FET PET constitute an unfavorable prognostic factor in astrocytic low-grade glioma and, by identifying high-risk patients, may ease treatment decisions.

Biodistribution of the 18F-FPPRGD2 PET radiopharmaceutical in cancer patients: an atlas of SUV measurements

International Nuclear Information System (INIS)

Minamimoto, Ryogo; Jamali, Mehran; Gambhir, Sanjiv Sam; Barkhodari, Amir; Mosci, Camila; Mittra, Erik; Iagaru, Andrei; Shen, Bin; Chin, Frederick

2015-01-01

The aim of this study was to investigate the biodistribution of 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) ( 18 F-FPPRGD 2 ) in cancer patients and to compare its uptake in malignant lesions with 18 F-FDG uptake. A total of 35 patients (11 men, 24 women, mean age 52.1 ± 10.8 years) were enrolled prospectively and had 18 F-FPPRGD 2 PET/CT prior to treatment. Maximum standardized uptake values (SUV max ) and mean SUV (SUV mean ) were measured in 23 normal tissues in each patient, as well as in known or suspected cancer lesions. Differences between 18 F-FPPRGD 2 uptake and 18 F-FDG uptake were also evaluated in 28 of the 35 patients. Areas of high 18 F-FPPRGD 2 accumulation (SUV max range 8.9 - 94.4, SUV mean range 7.1 - 64.4) included the bladder and kidneys. Moderate uptake (SUV max range 2.1 - 6.3, SUV mean range 1.1 - 4.5) was found in the choroid plexus, salivary glands, thyroid, liver, spleen, pancreas, small bowel and skeleton. Compared with 18 F-FDG, 18 F-FPPRGD 2 showed higher tumor-to-background ratio in brain lesions (13.4 ± 8.5 vs. 1.1 ± 0.5, P < 0.001), but no significant difference in body lesions (3.2 ± 1.9 vs. 4.4 ± 4.2, P = 0.10). There was no significant correlation between the uptake values (SUV max and SUV mean ) for 18 F FPPRGD 2 and those for 18 F-FDG. The biodistribution of 18 F-FPPRGD 2 in cancer patients is similar to that of other RGD dimer peptides and it is suitable for clinical use. The lack of significant correlation between 18 F-FPPRGD 2 and 18 F-FDG uptake confirms that the information provided by each PET tracer is different. (orig.)

Electrochemistry of TiF{sub 4} in 1-butyl-2,3-dimethylimidazolium tetrafluoroborate

Energy Technology Data Exchange (ETDEWEB)

Andriyko, Yuriy, E-mail: yuriy.andriyko@cest.a [Centre of Electrochemical Surface Technology (CEST), Viktor Kaplan-Strasse 2, A-2700 Wiener Neustadt (Austria); Andriiko, Alexander [National Technical University of Ukraine ' Kyiv Polytechnic Institute' , Prospect Peremogy 37, 03057 Kyiv (Ukraine); Babushkina, Olga B. [Centre of Electrochemical Surface Technology (CEST), Viktor Kaplan-Strasse 2, A-2700 Wiener Neustadt (Austria); Nauer, Gerhard E. [Centre of Electrochemical Surface Technology (CEST), Viktor Kaplan-Strasse 2, A-2700 Wiener Neustadt (Austria); Vienna University, Faculty of Chemistry, Waehringer Strasse 42, A-1090 Wien (Austria)

2010-01-01

Electrochemical behaviour of Ti(IV) species in the ionic liquid (IL) 1-butyl-2,3-dimethylimidazolium tetrafluoroborate (BMMImBF{sub 4}) was studied by means of chronopotentiometry (CP) and cyclic voltammetry (CV) in melts with different concentrations of TiF{sub 4} (2-35 mol%) within a temperature range of 65-180 deg. C. The electrochemical reduction of Ti(IV) was suggested to proceed via the sequence of one-electron steps with the formation of poorly soluble low valence intermediates (LVI). LVIs undergo further solid-state electrochemical reduction to Ti metal. Thin Ti coatings on a Pt substrate were thus obtained and characterized by ESEM method. FTIR spectroscopy was used for identification of the electrochemical active species of Ti(IV). The reaction 2BF{sub 4}{sup -} + TiF{sub 4} reversible TiF{sub 6}{sup 2-} + 2BF{sub 3}arrow up takes place in the concentrated solutions of TiF{sub 4} at elevated temperatures.

In vivo evaluation in rats of [{sup 18}F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine as a potential radiotracer for PET assessment of CNS sigma-1 receptors

Energy Technology Data Exchange (ETDEWEB)

Waterhouse, Rikki N. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States) and Department of Radiology, Columbia University, New York, NY 10032 (United States) and Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States)]. E-mail: rnw7@columbia.edu; Chang, Raymond C. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States); Zhao, Jun [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States); Carambot, Patty E. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States)

2006-02-15

Introduction: Sigma-1 receptors are expressed throughout the mammalian central nervous system (CNS) and are implicated in several psychiatric disorders, including schizophrenia and depression. We have recently evaluated the high-affinity (K {sub D}=0.5{+-}0.2 nM, log P=2.9) sigma-1 receptor radiotracer [{sup 18}F]1-(3-fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine, [{sup 18}F]FPS, in humans. In contrast to appropriate kinetics exhibited in baboon brain, in the human CNS, [{sup 18}F]FPS does not reach pseudoequilibrium by 4 h, supporting the development of a lower-affinity tracer [Waterhouse RN, Nobler MS, Chang RC, Zhou Y, Morales O, Kuwabara H, et al. First evaluation of the sigma-1 receptor radioligand [{sup 18}F]1-3-fluoropropyl-4-((4-cyanophenoxy)-methyl)piperidine ([{sup 18}F]FPS) in healthy humans. Neuroreceptor Mapping 2004, July 15-18th, Vancouver, BC Canada 2004]. We describe herein the in vivo evaluation in rats of [{sup 18}F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine ([{sup 18}F]SFE) (K {sub D}=5 nM, log P=2.4), a structurally similar, lower-affinity sigma-1 receptor radioligand. Methods: [{sup 18}F]SFE was synthesized (n=4) as previously described in good yield (54{+-}6% EOB), high specific activity (2.1{+-}0.6 Ci/{mu}mol EOS) and radiochemical purity (98{+-}1%) and evaluated in awake adult male rats. Results: Similar to [{sup 18}F]FPS, regional brain radioactivity concentrations [percentage of injected dose per gram of tissue (%ID/g), 15 min] for [{sup 18}F]SFE were highest in occipital cortex (1.86{+-}0.06 %ID/g) and frontal cortex (1.76{+-}0.38 %ID/g), and lowest in the hippocampus (1.01{+-}0.02%ID/g). Unlike [{sup 18}F]FPS, [{sup 18}F]SFE cleared from the brain with {approx}40% reduction in peak activity over a 90-min period. Metabolite analysis (1 h) revealed that [{sup 18}F]SFE was largely intact in the brain. Blocking studies showed a large degree (>80%) of saturable binding for [{sup 18}F]SFE in discrete brain regions. Conclusions

EPR experiments in LiTbF4, LiHoF4, and LiErF4 at submillimeter frequencies

DEFF Research Database (Denmark)

Magariño, J.; Tuchendler, J.; Beauvillain, P.

1980-01-01

Electron-paramagnetic-resonance experiments in LiTbF4, LiHoF4, and LiErF4 have been performed at frequencies between 70 and 600 GHz, in magnetic fields up to 60 kG and in the temperature range 1.4......Electron-paramagnetic-resonance experiments in LiTbF4, LiHoF4, and LiErF4 have been performed at frequencies between 70 and 600 GHz, in magnetic fields up to 60 kG and in the temperature range 1.4...

F4/80 inhibits osteoclast differentiation via downregulation of nuclear factor of activated T cells, cytoplasmic 1.

Science.gov (United States)

Kang, Ju-Hee; Sim, Jung-Sun; Zheng, Ting; Yim, Mijung

2017-04-01

Osteoclastogenesis is an essential process in bone metabolism, which can be induced by RANKL stimulation. The F4/80 glycoprotein is a member of the EGF-transmembrane 7 (TM7) family and has been established as a specific cell-surface marker for murine macrophages. This study aimed to identify the role of F4/80 in osteoclastogenesis. Using mouse bone marrow-derived macrophages (BMMs), we observed that the mRNA level of F4/80 was dramatically reduced as these cells differentiated into osteoclasts. Furthermore, osteoclastogenesis was decreased in F4/80 high BMMs compared to F4/80 -/low BMMs. The inhibitory effect of F4/80 was associated with decreased expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). Ectopic overexpression of a constitutively active form of NFATc1 rescued the anti-osteoclastogenic effect of F4/80 completely, suggesting that the anti-osteoclastogenic effect of F4/80 was mainly due to reduction in NFATc1 expression. As an underlying mechanism, we demonstrated that the presence of F4/80 abrogated the effect of RANKL on the phosphorylation of CREB and activated the expression of IFN-β, which are restored by cyclic AMP. Collectively, our results demonstrate that the presence of F4/80 suppresses RANKL-induced osteoclastogenesis by impairing the expression of NFATc1 via CREB and IFN-β. Therefore, F4/80 may hold therapeutic potential for bone destructive diseases.

Combined use of (18)F-FDG and (18)F-FMISO in unresectable non-small cell lung cancer patients planned for radiotherapy: a dynamic PET/CT study.

Science.gov (United States)

Sachpekidis, Christos; Thieke, Christian; Askoxylakis, Vasileios; Nicolay, Nils H; Huber, Peter E; Thomas, Michael; Dimitrakopoulou, Georgia; Debus, Juergen; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2015-01-01

Aim of this study was to evaluate and compare, by means of dynamic and static PET/CT, the distribution patterns and pharmacokinetics of fluorine-18 fluorodeoxyglucose ((18)F-FDG) and of fluorine-18-fluoromisonidazole ((18)F-FMISO) in non-small cell lung cancer (NSCLC) patients scheduled for intensity modulated radiation therapy (IMRT). Thirteen patients suffering from inoperable stage III NSCLC underwent PET/CTs with (18)F-FDG and (18)F-FMISO for tumor metabolism and hypoxia assessment accordingly. Evaluation of PET/CT studies was based on visual analysis, semi-quantitative (SUV) calculations and absolute quantitative estimations, after application of a two-tissue compartment model and a non-compartmental approach. (18)F-FDG PET/CT revealed all thirteen primary lung tumors as sites of increased (18)F-FDG uptake. Six patients demonstrated also in total 43 (18)F-FDG avid metastases; these patients were excluded from radiotherapy. (18)F-MISO PET/CT demonstrated 12/13 primary lung tumors with faint tracer uptake. Only one tumor was clearly (18)F-FMISO avid, (SUVaverage = 3.4, SUVmax = 5.0). Mean values for (18)F-FDG, as derived from dPET/CT data, were SUVaverage = 8.9, SUVmax = 15.1, K1 = 0.23, k2 = 0.53, k3 = 0.17, k4 = 0.02, influx = 0.05 and fractal dimension (FD) = 1.25 for the primary tumors. The respective values for (18)F-FMISO were SUVaverage = 1.4, SUVmax = 2.2, K1 = 0.26, k2 = 0.56, k3 = 0.06, k4 = 0.06, influx = 0.02 and FD = 1.14. No statistically significant correlation was observed between the two tracers. (18)F-FDG PET/CT changed therapy management in six patients, by excluding them from planned IMRT. (18)F-FMISO PET/CT revealed absence of significant tracer uptake in the majority of the (18)F-FDG avid NSCLCs. Lack of correlation between the two tracers' kinetics indicates that they reflect different molecular mechanisms and implies the discordance between increased glycolysis and hypoxia in the malignancy.

Localization of Microfibrillar-Associated Protein 4 (MFAP4) in Human Tissues

DEFF Research Database (Denmark)

Wulf-Johansson, Helle; Lock Johansson, Sofie; Schlosser, Anders

2013-01-01

Microfibrillar-associated protein 4 (MFAP4) is located in the extracellular matrix (ECM). We sought to identify tissues with high levels of MFAP4 mRNA and MFAP4 protein expression. Moreover, we aimed to evaluate the significance of MFAP4 as a marker of cardiovascular disease (CVD) and to correlate...... of MFAP4 protein mainly at sites rich in elastic fibers and within blood vessels in all tissues investigated. The AlphaLISA technique was used to determine serum MFAP4 levels in a clinical cohort of 172 patients consisting of 5 matched groups with varying degrees of CVD: 1: patients with ST elevation...... MFAP4 with other known ECM markers, such as fibulin-1, osteoprotegerin (OPG), and osteopontin (OPN). Quantitative real-time PCR demonstrated that MFAP4 mRNA was more highly expressed in the heart, lung, and intestine than in other elastic tissues. Immunohistochemical studies demonstrated high levels...

HYPERDIRE. HYPERgeometric functions DIfferential REduction. MATHEMATICA based packages for differential reduction of generalized hypergeometric functions {sub p}F{sub p-1}, F{sub 1}, F{sub 2}, F{sub 3}, F{sub 4}

Energy Technology Data Exchange (ETDEWEB)

Bytev, Vladimir V.; Kalmykov, Mikhail Yu. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik; Joint Institute for Nuclear Research, Dubna (Russian Federation); Kniehl, Bernd A. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik

2013-05-15

HYPERDIRE is a project devoted to the creation of a set of Mathematica based programs for the differential reduction of hypergeometric functions. The current version includes two parts: one, pfq, is relevant for manipulations of hypergeometric functions {sub p+1}F{sub p}, and the second one, AppellF1F4, for manipulations with Appell hypergeometric functions F{sub 1}, F{sub 2}, F{sub 3}, F{sub 4} of two variables.

Changes in the F0F1-ATPase activity of irradiated Lactobacillus acidophilus in the presence of ceftazidime at low pH

International Nuclear Information System (INIS)

Kalantaryan, V.P.; Trchounian, A.H.; Soghomonyan, D.R.

2014-01-01

The aim of this study was the investigation of the effects of low intensity electromagnetic irradiation (EMI) at the frequencies of 51.8 and 53 GHz and of antibiotic ceftazidime on the N,N'-dicyclohexylcarbodiimide (DCCD) inhibited ATPase activity of membrane vesicles of lactic acid bacteria Lactobacillus acidophilus grown at low pH (pH 4.0 or 6.5) and assayed at the same pH. It was shown that both frequencies EMI stimulated ATPase activity of L. acidophilus grown at pH 4.0, but EMI combined with ceftazidime and DCCD decreased ATPase activity at pH 4.0 and pH 6.5. It was suggested that the F 0 F 1 -ATPase might be a target for EMI even at low pH

Differentiated embryonic chondrocytes 1 expression of periodontal ligament tissue and gingival tissue in the patients with chronic periodontitis.

Science.gov (United States)

Hu, Shenlin; Shang, Wei; Yue, Haitao; Chen, Ruini; Dong, Zheng; Hu, Jinhua; Mao, Zhao; Yang, Jian

2015-04-01

To evaluate the DEC1 expression of periodontal ligament tissue and gingival tissue in the patients with chronic periodontitis. 20 non-smoking patients with chronic periodontitis and 20 healthy individuals were enrolled. Periodontal ligament tissue and gingival tissue samples from healthy subjects were collected during teeth extraction for orthodontic reason or the third molar extraction. The parallel samples from patients with chronic periodontitis were obtained during periodontal flap operations or teeth extraction as part of periodontal treatment. The DEC1 expression and the alkaline phosphatase (ALP) activity of both the periodontal ligament tissue and gingival tissue were determined by Western blot, Immunohistochemistry and ALP Detection Kit. The DEC1 expression of periodontal ligament tissue in the patients with chronic periodontitis decreased significantly along with the decreased ALP activity. On the contrary, the DEC1 expression of gingival tissue in the patients with chronic periodontitis increased significantly. Further study found that the DEC1 expression of gingival tissue increased mainly in the suprabasal layer of gingival epithelial cells but decreased in the gingival connective tissue of the patients with chronic periodontitis. The DEC1 expression decreases in the periodontal ligament tissue which is related to the osteogenic capacity, whereas the DEC1 expression increases in the suprabasal layer of gingival epithelial cells which are involved in immune inflammatory response in the patients with chronic periodontitis. The findings provide a new target to explore the pathology and the therapy of periodontitis. Copyright © 2014 Elsevier Ltd. All rights reserved.

"1"8F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with "1"8F-FDG and "1"1C-Methionine PET

International Nuclear Information System (INIS)

Watabe, Tadashi; Ikeda, Hayato; Aoki, Masanao; Nagamori, Shushi; Wiriyasermkul, Pattama; Tanaka, Yoko; Hagiwara, Kohei; Kanai, Yoshikatsu; Naka, Sadahiro; Kanai, Yasukazu; Shimosegawa, Eku; Hatazawa, Jun

2017-01-01

The purpose of this study was to evaluate the usefulness of L-4-borono-2-"1"8F-fluoro-phenylalanine ("1"8F-FBPA) as a tumor-specific probe, in comparison to "1"8F-FDG and "1"1C-methionine (Met), focusing on its transport selectivity by L-type amino acid transporter 1 (LAT1), which is highly upregulated in cancers. Cellular analyses of FBPA were performed to evaluate the transportability and K_m value. PET studies were performed in rat xenograft models of C6 glioma (n = 12) and in rat models of turpentine oil-induced subcutaneous inflammation (n = 9). The kinetic parameters and uptake values on static PET images were compared using the one-tissue compartment model (K_1, k_2) and maximum standardized uptake value (SUVmax). The cellular analyses showed that FBPA had a lower affinity to a normal cell-type transporter LAT2 and induced less efflux through LAT2 among FBPA, Met, and BPA, while the efflux through LAT1 induced by FBPA was similar among the three compounds. The K_m value of "1"8F-FBPA for LAT1 (196.8 ± 11.4 μM) was dramatically lower than that for LAT2 (2813.8 ± 574.5 μM), suggesting the higher selectivity of "1"8F-FBPA for LAT1. K_1 and k_2 values were significantly smaller in "1"8F-FBPA PET (K_1 = 0.04 ± 0.01 ml/ccm/min and k_2 = 0.07 ± 0.01 /min) as compared to "1"1C-Met PET (0.22 ± 0.09 and 0.52 ± 0.10, respectively) in inflammatory lesions. Static PET analysis based on the SUVmax showed significantly higher accumulation of "1"8F-FDG in the tumor and inflammatory lesions (7.2 ± 2.1 and 4.6 ± 0.63, respectively) as compared to both "1"8F-FBPA (3.2 ± 0.40 and 1.9 ± 0.19) and "1"1C-Met (3.4 ± 0.43 and 1.6 ± 0.11). No significant difference was observed between "1"8F-FBPA and "1"1C-Met in the static PET images. This study shows the utility of "1"8F-FBPA as a tumor-specific probe of LAT1 with low accumulation in the inflammatory lesions. (orig.)

Gut-Associated Lymphoid Tissue: A Key Tissue Inside the Mucosal Immune System of Hens Immunized with Escherichia coli F4.

Science.gov (United States)

Peralta, Maria F; Magnoli, Alejandra; Alustiza, Fabrisio; Nilson, Armando; Miazzo, Raúl; Vivas, Adriana

2017-01-01

Immunoglobulin Y (IgY) is the predominant antibody found in hen's ( Gallus domesticus ) egg yolk. This antibody, developed against several microorganisms in hen egg yolk, has been successfully used as an alternative to immunoglobulins from mammals for use in immunodiagnostics and immunotherapy. Enteropathogenic Escherichia coli (E.coli) F 4 is the main etiological agent associated with swine neonatal diarrhea, and it causes notable economic losses in swine production. The aim of the present study was to evaluate the relationship between humoral immune response and the activation of gut-associated lymphoid tissue (GALT) in laying hens intramuscularly immunized with E. coli F 4 . Adult laying Shaver hens were immunized with a bacterin based on an inactivated lysate E. coli F 4 strain that was originally isolated from neonatal piglet diarrhea, following a recommended schedule. The percentage of B lymphocytes in blood and spleen homogenates was determined by flow cytometry. Villi histomorphometry and the size of germinal centers (GC) activated in GALT and the spleen were measured in histological samples either stained with hematoxylin/eosin or through immunofluorescence. Antibody and isotype-specific antibodies in serum and egg yolk were measured using indirect enzyme-linked immunosorbent assay (ELISA). Secretory and serum immunoglobulin A (IgA) were measured by ELISA tests. Laying hen with intramuscular immunization with E. coli F 4 lysate, activated both mucosal and systemic protection. Mucosal protection was provided through B lymphocytes, and most of them were activated on Peyer's patches and esophageal tonsils, in GALT. Furthermore, increased B lymphocyte number in the lamina propria of the gut, and increased intraepithelial plasmatic cell number, produced high levels of mucosal IgA. Activated B lymphocytes interacted with absorptive cells, immune cells, and microbiota in the gut, producing signals that were translated into a powerful physical defense by producing

Radiosynthesis of 3-{l_brace}[4-(4-[{sup 18}F]fluorobenzyl)]piperazin-1-yl{r_brace}methyl-1H-pyrrolo[2,3-b]pyridine: A potential dopamine D{sub 4} receptor imaging agent

Energy Technology Data Exchange (ETDEWEB)

Haibin Tian; Duanzhi Yin; Junling Li; Lan Zhang; Cunfu Zhang; Yongxian Wang; Wei Zhou [Radiopharmaceutical Research Center, Shanghai Inst. of Nuclear Research, The Chinese Academy of Sciences, Shanghai, SH (China)

2003-07-01

The dopamine D{sub 4} receptor (D{sub 4}R) is expressed in low density in various extrastriatal brain regions. This receptor subtype is discussed in relation to the pathophysiology and treatment of schizophrenia but to date no selective positron emission tomography (PET) ligand is available to study its distribution in vivo. The 7-azaindole derivative 3-([4-(4-iodophenyl)piperazin-1-yl]-methyl)-1H-pyrrolo [2,3-b]pyridine (L-750,667) is a novel, high-affinity (K{sub i}=0.51nM) and selective D{sub 4}R ligand. L-750,667 analogue 3-[4-(4-[{sup 18}F]fluorobenzyl)]piperazin-1-yl methyl-1H-pyrrolo[2,3-b]-pyridine was prepared by reacting 3-(piperazin-1-yl)-methyl-1H-pyrrolo[2,3-b]pyridine with 4-[ 18F]fluorobenzaldehyde, which was labeled with no carrier added [ 18F]fluoride. The radiochemical yield of 3-[4-(4-[{sup 18}F]fluorobenzyl)]piperazin-1-yl methyl-1H-pyrrolo[2,3-b]pyridine was 12.0% at end of synthesis (EOS), and the synthesis time was 73min. The labeled benzaldehydes may be useful precursors for the radiosyntheses of other complex radiotracers for PET.

Elevated 18F-NaF uptake in cricoid cartilage in a patient with laryngeal carcinoma

Science.gov (United States)

Xia, Yuxiao; Qi, Chi; Zhang, Shumao; Huang, Zhanwen; Chen, Yue

2017-01-01

Abstract Rationale: Laryngeal cancer is aggressive tumor that arises from the tissues of the larynx. Although any bone can be affected, involvement of cricoid cartilage was reported very rarely, and there has been no report of 18F-sodium fluoride positron emission tomography-computed tomography (18F-NaF PET-CT) and 3D PET-CT for the evaluation of cricoid cartilage invasion. Patient concerns: A 54-year-old male discovered a protruding mass in the right anterior neck, which had rapidly increased in size over a period of 2 months. Subsequently, hoarseness, dysphagia, and dyspnea were gradually developed. Diagnoses: 18F-FDG PET-CT demonstrated that the abnormal activity was located in a soft tissue mass, which was about 4.2 cm × 3.8 cm × 3.6 cm in largest dimension in the laryngeal cavity of supraglottic portion (SUVmax: 23.6). A swollen lymph node was revealed in the right submandibular region, which had intense FDG activity with a SUVmax of 18.4. However, there is a high uptake of 18F-FDG in the region near the bone, which is uncertain whether there is any skeletal invasion. NaF PET-CT and 3D PET-CT demonstrated increased uptake in the right side of cricoid cartilage (SUVmax: 13.2). The histopathologic examination confirmed squamous cell carcinoma of larynx. Interventions: The patient underwent tracheotomy and received anti-infective treatment to relieve symptoms of dyspnea and prevent asphyxia. Outcomes: Clinical follow up of the patient revealed that dyspnea was significantly relieved. Lessons: The case report shows the imaging features of cricoid cartilage invasion, including 18F-FDG PET/CT, 18F-sodium fluoride positron emission tomography-computed tomography (18F-NaF PET-CT), and 3D PET-CT. Precise understanding of the invasion scope, accurately staging of laryngeal carcinoma, and choosing of the most suitable surgical scheme are the factors that lead to the optimal treatment of laryngeal neoplasms. PMID:29245332

Insulinoma imaging with glucagon-like peptide-1 receptor targeting probe (18)F-FBEM-Cys (39)-exendin-4.

Science.gov (United States)

Xu, Yuping; Pan, Donghui; Xu, Qing; Zhu, Chen; Wang, Lizhen; Chen, Fei; Yang, Runlin; Luo, Shineng; Yang, Min

2014-09-01

Glucagon-like peptide-1 receptor (GLP-1R) is a specific target for insulinomas imaging since it is overexpressed in the tumor. Exendin-4 exhibits high affinity for the GLP-1R. In this study, a novel (18)F-labeled exendin-4 analog, (18)F-FBEM-Cys(39)-exendin-4, was synthesized and its potentials for GLP-1R imaging were also evaluated. (18)F-FBEM was synthesized by coupling (18)F-fluorobenzoic acid ((18)F-FBA) with N-(2-aminoethyl) maleimide, and the reaction conditions were optimized. Cys(39)-exendin-4 was then conjugated with (18)F-FBEM to obtain (18)F-FBEM-Cys(39)-exendin-4. The GLP-1R targeting potential and pharmacokinetic profile of the tracer were analyzed in INS-1 insulinoma and MDA-MB-435 breast tumor model, respectively. Under the optimal conditions, the yield of radiolabeled (18)F-FBEM was 49.1 ± 2.0 % (based on (18)F-FBA, non-decay corrected). The yield of (18)F-FBEM-Cys(39)-exendin-4 was 35.1 ± 2.6 % (based on the starting (18)F-FBEM, non-decay corrected). The radiochemical purity of (18)F-FBEM-Cys(39)-exendin-4 is >95 %, and the specific activity was at least 35 GBq/μmol. The GLP-1R-positive INS-1 insulinoma xenograft was clearly visible with good contrast to background, whereas GLP-1R-negative MDA-MB435 breast tumor was barely visible. Low levels of radioactivity were also detected at pancreas and lungs due to few GLP-1R expressions. GLP-1R binding specificity was demonstrated by reduced INS-1 tumor uptake of the tracer after coinjection with an excess of unlabeled Cys(39)-exendin-4 at 1 h postinjection. The thiol-reactive reagent, (18)F-FBEM, was prepared with high yield and successfully conjugated to Cys(39)-exendin-4. Favorable preclinical data showing specific and effective tumor targeting by (18)F-FBEM-Cys(39)-exendin-4 suggest that the tracer may be a potential probe for insulinomas imaging.

The Prenylated Rab GTPase Receptor PRA1.F4 Contributes to Protein Exit from the Golgi Apparatus.

Science.gov (United States)

Lee, Myoung Hui; Yoo, Yun-Joo; Kim, Dae Heon; Hanh, Nguyen Hong; Kwon, Yun; Hwang, Inhwan

2017-07-01

Prenylated Rab acceptor1 (PRA1) functions in the recruitment of prenylated Rab proteins to their cognate organelles. Arabidopsis ( Arabidopsis thaliana ) contains a large number of proteins belonging to the AtPRA1 family. However, their physiological roles remain largely unknown. Here, we investigated the physiological role of AtPRA1.F4, a member of the AtPRA1 family. A T-DNA insertion knockdown mutant of AtPRA1.F4 , atpra1.f4 , was smaller in stature than parent plants and possessed shorter roots, whereas transgenic plants overexpressing HA:AtPRA1.F4 showed enhanced development of secondary roots and root hairs. However, both overexpression and knockdown plants exhibited increased sensitivity to high-salt stress, lower vacuolar Na + /K + -ATPase and plasma membrane ATPase activities, lower and higher pH in the vacuole and apoplast, respectively, and highly vesiculated Golgi apparatus. HA:AtPRA1.F4 localized to the Golgi apparatus and assembled into high-molecular-weight complexes. atpra1.f4 plants displayed a defect in vacuolar trafficking, which was complemented by low but not high levels of HA : AtPRA1.F4 Overexpression of HA:AtPRA1.F4 also inhibited protein trafficking at the Golgi apparatus, albeit differentially depending on the final destination or type of protein: trafficking of vacuolar proteins, plasma membrane proteins, and trans-Golgi network (TGN)-localized SYP61 was strongly inhibited; trafficking of TGN-localized SYP51 was slightly inhibited; and trafficking of secretory proteins and TGN-localized SYP41 was negligibly or not significantly inhibited. Based on these results, we propose that Golgi-localized AtPRA1.F4 is involved in the exit of many but not all types of post-Golgi proteins from the Golgi apparatus. Additionally, an appropriate level of AtPRA1.F4 is crucial for its function at the Golgi apparatus. © 2017 American Society of Plant Biologists. All Rights Reserved.

Oral administration of a select mixture of Bacillus probiotics generates Tr1 cells in weaned F4ab/acR- pigs challenged with an F4+ ETEC/VTEC/EPEC strain.

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Zhou, Dong; Zhu, Yao-Hong; Zhang, Wei; Wang, Meng-Ling; Fan, Wen-Yi; Song, Dan; Yang, Gui-Yan; Jensen, Bent Borg; Wang, Jiu-Feng

2015-09-17

Although breeding of F4 receptor - negative (F4R(-)) pigs may prevent post-weaning diarrhea, the underlying immunity is poorly understood. Here, various doses of a Bacillus licheniformis and Bacillus subtilis mixture (BLS-mix) were orally administered to F4ab/acR(-) pigs for 1 week before F4 (K88) - positive ETEC/VTEC/EPEC challenge. Administration of BLS-mix increased the percentage of Foxp3(-)IL-10(+) T cells but not of Foxp3(+)IL-10(+) regulatory T (Treg) cells among peripheral blood CD4(+) T cells. A low dose of BLS-mix feeding resulted in increased the expression of IL-6, TNF-α, IL-10, and the transcription factors Foxp3 and T-bet mRNAs in the jejunum. Administration of either a low or high dose BLS-mix also led to an increase in the percentage of CD4(+)Foxp3(+) Treg cells among intraepithelial lymphocytes and CD4(+)IL-10(+) T cells in the small intestinal Peyer's patches and the lamina propria of F4ab/acR(-) pigs following F4(+) ETEC/VTEC/EPEC challenge. The increased number of IL-10-producing CD4(+) T cells was attributed to an increase in the proportion of Foxp3(-)IL-10(+) Treg cells rather than Foxp3(+)IL-10(+) Treg cells. Our data indicate that oral administration of BLS-mix to newly weaned F4ab/acR(-) pigs ameliorates enteritis in an F4(+) ETEC/VTEC/EPEC model; however, induction of IL-10-producing Foxp3(-) Treg cells by BLS-mix administration cannot account for the protection of newly weaned F4ab/acR(-) pigs from F4(+) ETEC/VTEC/EPEC infection, and that excessive generation of CD4(+)IL-10(+) T cells following consumption of BLS-mix during episodes of intestinal inflammation that is caused by enteric pathogens might prohibit clearance of the pathogen. Select probiotic mixtures may allow for tailoring strategies to prevent infectious diseases.

4E-BP1 regulates the differentiation of white adipose tissue.

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Tsukiyama-Kohara, Kyoko; Katsume, Asao; Kimura, Kazuhiro; Saito, Masayuki; Kohara, Michinori

2013-07-01

4E Binding protein 1 (4E-BP1) suppresses translation initiation. The absence of 4E-BP1 drastically reduces the amount of adipose tissue in mice. To address the role of 4E-BP1 in adipocyte differentiation, we characterized 4E-BP1(-/-) mice in this study. The lack of 4E-BP1 decreased the amount of white adipose tissue and increased the amount of brown adipose tissue. In 4E-BP1(-/-) MEF cells, PPARγ coactivator 1 alpha (PGC-1α) expression increased and exogenous 4E-BP1 expression suppressed PGC-1α expression. The level of 4E-BP1 expression was higher in white adipocytes than in brown adipocytes and showed significantly greater up-regulation in white adipocytes than in brown adipocytes during preadipocyte differentiation into mature adipocytes. The amount of PGC-1α was consistently higher in HB cells (a brown preadipocyte cell line) than in HW cells (a white preadipocyte cell line) during differentiation. Moreover, the ectopic over-expression of 4E-BP1 suppressed PGC-1α expression in white adipocytes, but not in brown adipocytes. Thus, the results of our study indicate that 4E-BP1 may suppress brown adipocyte differentiation and PGC-1α expression in white adipose tissues. © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Fabp4-Cre-mediated Sirt6 deletion impairs adipose tissue function and metabolic homeostasis in mice.

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Xiong, Xiwen; Zhang, Cuicui; Zhang, Yang; Fan, Rui; Qian, Xinlai; Dong, X Charlie

2017-06-01

SIRT6 is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis and anti-inflammation. However, its function in the adipose tissue is not well understood. To examine the metabolic function of SIRT6 in the adipose tissue, we generated two mouse models that are deficient in Sirt6 using the Cre-lox approach. Two commonly used Cre lines that are driven by either the mouse Fabp4 or Adipoq gene promoter were chosen for this study. The Sirt6- knockout mice generated by the Fabp4-Cre line ( Sirt6 f/f : Fabp4-Cre) had a significant increase in both body weight and fat mass and exhibited glucose intolerance and insulin resistance as compared with the control wild-type mice. At the molecular levels, the Sirt6 f/f :Fabp4-Cre-knockout mice had increased expression of inflammatory genes including F4/80, TNFα, IL-6 and MCP-1 in both white and brown adipose tissues. Moreover, the knockout mice showed decreased expression of the adiponectin gene in the white adipose tissue and UCP1 in the brown adipose tissue, respectively. In contrast, the Sirt6 knockout mice generated by the Adipoq-Cre line ( Sirt6 f/f :Adipoq-Cre) only had modest insulin resistance. In conclusion, our data suggest that the function of SIRT6 in the Fabp4-Cre-expressing cells in addition to mature adipocytes plays a critical role in body weight maintenance and metabolic homeostasis. © 2017 Society for Endocrinology.

Interactive rhythmic auditory stimulation reinstates natural 1/f timing in gait of Parkinson's patients.

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Michael J Hove

Full Text Available Parkinson's disease (PD and basal ganglia dysfunction impair movement timing, which leads to gait instability and falls. Parkinsonian gait consists of random, disconnected stride times--rather than the 1/f structure observed in healthy gait--and this randomness of stride times (low fractal scaling predicts falling. Walking with fixed-tempo Rhythmic Auditory Stimulation (RAS can improve many aspects of gait timing; however, it lowers fractal scaling (away from healthy 1/f structure and requires attention. Here we show that interactive rhythmic auditory stimulation reestablishes healthy gait dynamics in PD patients. In the experiment, PD patients and healthy participants walked with a no auditory stimulation, b fixed-tempo RAS, and c interactive rhythmic auditory stimulation. The interactive system used foot sensors and nonlinear oscillators to track and mutually entrain with the human's step timing. Patients consistently synchronized with the interactive system, their fractal scaling returned to levels of healthy participants, and their gait felt more stable to them. Patients and healthy participants rarely synchronized with fixed-tempo RAS, and when they did synchronize their fractal scaling declined from healthy 1/f levels. Five minutes after removing the interactive rhythmic stimulation, the PD patients' gait retained high fractal scaling, suggesting that the interaction stabilized the internal rhythm generating system and reintegrated timing networks. The experiment demonstrates that complex interaction is important in the (reemergence of 1/f structure in human behavior and that interactive rhythmic auditory stimulation is a promising therapeutic tool for improving gait of PD patients.

Biodistribution of the {sup 18}F-FPPRGD{sub 2} PET radiopharmaceutical in cancer patients: an atlas of SUV measurements

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Minamimoto, Ryogo; Jamali, Mehran; Gambhir, Sanjiv Sam [Stanford University, Stanford, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford, CA (United States); Stanford University, Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford, CA (United States); Barkhodari, Amir; Mosci, Camila; Mittra, Erik; Iagaru, Andrei [Stanford University, Stanford, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford, CA (United States); Shen, Bin; Chin, Frederick [Stanford University, Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford, CA (United States)

2015-11-15

The aim of this study was to investigate the biodistribution of 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) ({sup 18}F-FPPRGD{sub 2}) in cancer patients and to compare its uptake in malignant lesions with {sup 18}F-FDG uptake. A total of 35 patients (11 men, 24 women, mean age 52.1 ± 10.8 years) were enrolled prospectively and had {sup 18}F-FPPRGD{sub 2} PET/CT prior to treatment. Maximum standardized uptake values (SUV{sub max}) and mean SUV (SUV{sub mean}) were measured in 23 normal tissues in each patient, as well as in known or suspected cancer lesions. Differences between {sup 18}F-FPPRGD{sub 2} uptake and {sup 18}F-FDG uptake were also evaluated in 28 of the 35 patients. Areas of high {sup 18}F-FPPRGD{sub 2} accumulation (SUV{sub max} range 8.9 - 94.4, SUV{sub mean} range 7.1 - 64.4) included the bladder and kidneys. Moderate uptake (SUV{sub max} range 2.1 - 6.3, SUV{sub mean} range 1.1 - 4.5) was found in the choroid plexus, salivary glands, thyroid, liver, spleen, pancreas, small bowel and skeleton. Compared with {sup 18}F-FDG, {sup 18}F-FPPRGD{sub 2} showed higher tumor-to-background ratio in brain lesions (13.4 ± 8.5 vs. 1.1 ± 0.5, P < 0.001), but no significant difference in body lesions (3.2 ± 1.9 vs. 4.4 ± 4.2, P = 0.10). There was no significant correlation between the uptake values (SUV{sub max} and SUV{sub mean}) for {sup 18}F FPPRGD{sub 2} and those for {sup 18}F-FDG. The biodistribution of {sup 18}F-FPPRGD{sub 2} in cancer patients is similar to that of other RGD dimer peptides and it is suitable for clinical use. The lack of significant correlation between {sup 18}F-FPPRGD{sub 2} and {sup 18}F-FDG uptake confirms that the information provided by each PET tracer is different. (orig.)

Increased PADI4 expression in blood and tissues of patients with malignant tumors

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Zhao Yan

2009-01-01

Full Text Available Abstract Background Peptidylarginine deiminase type 4 (PAD4/PADI4 post-translationally converts peptidylarginine to citrulline. Recent studies suggest that PADI4 represses expression of p53-regulated genes via citrullination of histones at gene promoters. Methods Expression of PADI4 was investigated in various tumors and non-tumor tissues (n = 1673 as well as in A549, SKOV3 and U937 tumor cell lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4 and citrullinated antithrombin (cAT were investigated in the blood of patients with various tumors by ELISA (n = 1121. Results Immunohistochemistry detected significant PADI4 expression in various malignancies including breast carcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas, endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas, as well as other metastatic carcinomas. However, PADI4 expression was not observed in benign leiomyomas of stomach, uterine myomas, endometrial hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas, neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally, PADI4 expression was not detected in non-tumor tissues including cholecystitis, cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed tissues such as in gastritis and appendicitis. Quantitative PCR and western blot analysis showed higher PADI4 expression in gastric adenocarcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and breast cancers (n = 5 for each disease than in the surrounding healthy tissues. Furthermore, western blot analysis detected PADI4 expression in cultured tumor cell lines. ELISA detected increased PADI4 and cAT levels in the blood of patients with

Increased PADI4 expression in blood and tissues of patients with malignant tumors

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Chang, Xiaotian; Han, Jinxiang; Pang, Li; Zhao, Yan; Yang, Yi; Shen, Zhonglin

2009-01-01

Peptidylarginine deiminase type 4 (PAD4/PADI4) post-translationally converts peptidylarginine to citrulline. Recent studies suggest that PADI4 represses expression of p53-regulated genes via citrullination of histones at gene promoters. Expression of PADI4 was investigated in various tumors and non-tumor tissues (n = 1673) as well as in A549, SKOV3 and U937 tumor cell lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4 and citrullinated antithrombin (cAT) were investigated in the blood of patients with various tumors by ELISA (n = 1121). Immunohistochemistry detected significant PADI4 expression in various malignancies including breast carcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas, endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas, as well as other metastatic carcinomas. However, PADI4 expression was not observed in benign leiomyomas of stomach, uterine myomas, endometrial hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas, neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally, PADI4 expression was not detected in non-tumor tissues including cholecystitis, cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed tissues such as in gastritis and appendicitis. Quantitative PCR and western blot analysis showed higher PADI4 expression in gastric adenocarcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and breast cancers (n = 5 for each disease) than in the surrounding healthy tissues. Furthermore, western blot analysis detected PADI4 expression in cultured tumor cell lines. ELISA detected increased PADI4 and cAT levels in the blood of patients with various malignant tumors compared to those in patients

Value of 18F-3,4-dihydroxyphenylalanine PET/MR image fusion in pediatric supratentorial infiltrative astrocytomas: a prospective pilot study.

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Morana, Giovanni; Piccardo, Arnoldo; Milanaccio, Claudia; Puntoni, Matteo; Nozza, Paolo; Cama, Armando; Zefiro, Daniele; Cabria, Massimo; Rossi, Andrea; Garrè, Maria Luisa

2014-05-01

Infiltrative astrocytomas (IAs) represent a group of astrocytic gliomas ranging from low-grade to highly malignant, characterized by diffuse invasion of the brain parenchyma. When compared with their adult counterpart, pediatric IAs may be considered biologically distinct entities; nevertheless, similarly to those in adults they represent a complex oncologic challenge. The aim of this study was to investigate the diagnostic role, clinical contribution, and prognostic value of fused (18)F-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET/MR images in pediatric supratentorial IAs. Pediatric patients with supratentorial IAs involving at least 2 cerebral lobes, either newly diagnosed or with suspected disease progression, prospectively underwent (18)F-DOPA PET and conventional MR imaging, performed within 10 d of each other. (18)F-DOPA PET data were interpreted qualitatively and semiquantitatively, fusing images with MR images. PET scans were classified as positive if tumors identified on MR imaging exhibited tracer uptake above the level of the corresponding contralateral normal brain. Maximum standardized uptake values, tumor-to-normal contralateral tissue ratios, and tumor-to-normal striatum ratios were calculated for all tumors. Correlations between the degree and extent of (18)F-DOPA uptake, MR imaging tumor characteristics, and histologic results were investigated. The contribution of (18)F-DOPA PET/MR image fusion was considered relevant if it enabled one to select the most appropriate biopsy site, discriminate between disease progression and treatment-related changes, or influence treatment strategy. The patient's outcome was finally correlated with (18)F-DOPA uptake. Thirteen patients (8 boys and 5 girls) were included (5 diffuse astrocytomas, 2 anaplastic astrocytomas, 5 gliomatosis cerebri, and 1 glioblastoma multiforme). The (18)F-DOPA uptake pattern was heterogeneous in all positive scans (9/13), revealing metabolic heterogeneities within each tumor. Significant

Pattern of leukemia induction in BC3F1 mice transplanted with irradiated lymphohemopoietic tissues

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Covelli, V.; Di Majo, V.; Bassani, B.; Metalli, P.; Silini, G.

1982-01-01

(C57BL/Cne X C3H/Cne)F 1 male mice spontaneously develop reticulum cell sarcoma (RCS) with an average final incidence of 56%; neither myeloid leukemia (ML) nor thymic lymphoma (TL) has been observed in intact animals. X rays (4Gy, 250 kV) induce a few cases of ML but no TL. In increasing the dose to 6 Gy, we observed a few cases of TL, no ML, and a drastic reduction (8%) of RCS. The same dose of 6 Gy fractionated into four weekly doses of 1.5 Gy induced 24% of TL. By transplanting cells into appropriately preirradiated (4 Gy) syngeneic recipients we found evidence that four weekly doses of 1.5 Gy to donor animals caused an excess of ML and drastic changes of both TL and RCS incidences and rates in recipients as a function of time postirradiation at which the lymphohemopoietic tissues are transplanted. Furthermore, the same transplanted animals showed an evident acceleration of time of appearance of RCS and an enhanced incidence of NL; the latter effect is significant 10 days after the last X-ray fraction, but not thereafter. These data are in line with the hypothesis that committed cells for these two types of systemic tumors may be present among the irradiated transplanted tissues

26 CFR 1.860F-4 - REMIC reporting requirements and other administrative rules.

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2010-04-01

... 26 Internal Revenue 9 2010-04-01 2010-04-01 false REMIC reporting requirements and other administrative rules. 1.860F-4 Section 1.860F-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Real Estate Investment Trusts § 1.860F-4 REMIC...

Treatment response evaluation with 18F-FDG PET/CT and 18F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation.

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Sachpekidis, Christos; Hillengass, J; Goldschmidt, H; Wagner, B; Haberkorn, U; Kopka, K; Dimitrakopoulou-Strauss, A

2017-01-01

The aim of this study was to assess the combined use of the radiotracers 18 F-FDG and 18 F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with 18 F-FDG and 18 F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, 18 F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, 18 F-FDG PET/CT-based treatment response revealed CR in 14 patients ( 18 F-FDG PET/CT CR), PR in 11 patients ( 18 F-FDG PET/CT PR) and progressive disease in four patients ( 18 F-FDG PET/CT PD). In terms of 18 F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, 18 F-NaF PET/CT depicted 56 of the 129 18 F-FDG positive lesions (43 %). Follow-up 18 F-NaF PET/CT showed persistence of 81.5 % of the baseline 18 F-NaF positive MM lesions after treatment, despite the fact that 64

Analytical variables affecting analysis of F2-isoprostanes and F4-neuroprostanes in human cerebrospinal fluid by gas chromatography/mass spectrometry.

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Yen, Hsiu-Chuan; Wei, Hsing-Ju; Chen, Ting-Wei

2013-01-01

F2-isoprostanes (F2-IsoPs) are a gold marker of lipid peroxidation in vivo, whereas F4-neuroprostanes (F4-NPs) measured in cerebrospinal fluid (CSF) or brain tissue selectively indicate neuronal oxidative damage. Gas chromatography/negative-ion chemical-ionization mass spectrometry (GC/NICI-MS) is the most sensitive and robust method for quantifying these compounds, which is essential for CSF samples because abundance of these compounds in CSF is very low. The present study revealed potential interferences on the analysis of F2-IsoPs and F4-NPs in CSF by GC/NICI-MS due to the use of improper analytical methods that have been employed in the literature. First, simultaneous quantification of F2-IsoPs and F4-NPs in CSF samples processed for F4-NPs analysis could cause poor chromatographic separation and falsely higher F2-IsoPs values for CSF samples with high levels of F2-IsoPs and F4-NPs. Second, retention of unknown substances in GC columns from CSF samples during F4-NPs analysis and from plasma samples during F2-IsoPs analysis might interfere with F4-NPs analysis of subsequent runs, which could be solved by holding columns at a high temperature for a period of time after data acquisition. Therefore, these special issues should be taken into consideration when performing analysis of F2-IsoPs and F4-NPs in CSF to avoid misleading results.

SU-G-IeP4-07: Feasibility of Low Dose 18FDG PET in Pediatric Oncology Patients

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Zhang, J; Binzel, K; Hall, NC; Natwa, M; Knopp, MI; Knopp, MV [The Ohio State University, Columbus, OH (United States)

2016-06-15

Purpose: To evaluate and demonstrate the feasibility of low dose FDG PET in pediatric oncology patients using virtual dose reduction as well as true patients PET/CT scans. Methods: Wholebody 18F-FDG PET/CT of 39 clinical pediatric patients (0.16±0.06MBq/kg) were scanned on a Gemini TF 64 system at 75±5 min post FDG injection using 3min/bed. Based on the 180s/bed listmode PET data, subsets of total counts in 120s, 90s, 60s, 30s and 15s per bed position were extracted for PET reconstruction to simulate lower dose PET at 2/3th, 1/2th, 1/3th, 1/6th and 1/12th dose levels. PET/CT scans of Jaszczak PET phantom with 6 hot hollow spheres varying with sizes and contrast ratios were performed (real PET versus simulated PET) to validate the methodology of virtual dose PET simulation. Region of interests (ROIs) were placed on lesions and normal anatomical tissues with quantitative and qualitative assessment performed. Significant lower FDG dose PET/CT of 5 research adolescents were scanned to validate the proposal and low dose PET feasibility. Results: Although all lesions are visible on the 1/12th dose PET, overall PET image quality appears to be influenced in a multi-factorial way. 30%–60% dose reduction from current standard of care FDG PET is recommended to maintain equivalent quality and PET quantification. An optimized BMI-based FDG administration is recommended (from 1.1±0.5 mCi for BMI < 18.5 to 4.8±1.5 mCi for BMI > 30). A linear lowest “Dose-BMI” relationship is given. SUVs from 1/12th to full dose PETs were identified as consistent (R2 = 1.08, 0.99, 1.01, 1.00 and 0.98). No significant variances of count density, SUV and SNR were found across certain dose ranges (p<0.01). Conclusion: Pediatric PET/CT can be performed using current time-of-flight systems at substantially lower PET doses (30–60%) than the standard of care PET/CT without compromising qualitative and quantitative image quality in clinical.

Mtb-specific CD27low CD4 T cells as markers of lung tissue destruction during pulmonary tuberculosis in humans.

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Nikitina, Irina Yu; Kondratuk, Natalya A; Kosmiadi, George A; Amansahedov, Rasul B; Vasilyeva, Irina A; Ganusov, Vitaly V; Lyadova, Irina V

2012-01-01

Effector CD4 T cells represent a key component of the host's anti-tuberculosis immune defense. Successful differentiation and functioning of effector lymphocytes protects the host against severe M. tuberculosis (Mtb) infection. On the other hand, effector T cell differentiation depends on disease severity/activity, as T cell responses are driven by antigenic and inflammatory stimuli released during infection. Thus, tuberculosis (TB) progression and the degree of effector CD4 T cell differentiation are interrelated, but the relationships are complex and not well understood. We have analyzed an association between the degree of Mtb-specific CD4 T cell differentiation and severity/activity of pulmonary TB infection. The degree of CD4 T cell differentiation was assessed by measuring the percentages of highly differentiated CD27(low) cells within a population of Mtb- specific CD4 T lymphocytes ("CD27(low)IFN-γ(+)" cells). The percentages of CD27(low)IFN-γ+ cells were low in healthy donors (median, 33.1%) and TB contacts (21.8%) but increased in TB patients (47.3%, p76%), but varied in blood (12-92%). The major correlate for the accumulation of CD27(low)IFN-γ(+) cells in blood was lung destruction (r = 0.65, p = 2.7 × 10(-7)). A cutoff of 47% of CD27(low)IFN-γ(+) cells discriminated patients with high and low degree of lung destruction (sensitivity 89%, specificity 74%); a decline in CD27(low)IFN-γ(+)cells following TB therapy correlated with repair and/or reduction of lung destruction (ppulmonary TB. Accumulation of CD27(low)IFN-γ(+) cells in the blood is associated with lung destruction. The findings indicate that there is no deficiency in CD4 T cell differentiation during TB; evaluation of CD27(low)IFN-γ(+) cells provides a valuable means to assess TB activity, lung destruction, and tissue repair following TB therapy.

Urea, Uric Acid, Prolactin and fT4 Concentrations in Aqueous Humor of Keratoconus Patients.

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Stachon, Tanja; Stachon, Axel; Hartmann, Ulrike; Seitz, Berthold; Langenbucher, Achim; Szentmáry, Nóra

2017-06-01

Keratoconus is a noninflammatory disease of the cornea associated with progressive thinning and conical shape. Metabolic alterations in the urea cycle, with changes in collagen fibril stability, oxidative stress, thyroid hormones and prolactin with regulatory effect on biosynthesis and biomechanical stability of corneal stroma, may all play a role in keratoconus etiology. Our purpose was to determine urea, uric acid, prolactin and free thyroxin (fT4) concentrations in human aqueous humor (hAH) of keratoconus and cataract patients. hAH was collected from 100 keratoconus (penetrating keratoplasty) (41.9 ± 14.9 years, 69 males) and 100 cataract patients (cataract surgery) (71.2 ± 12.4 years, 58 males). Urea, uric acid, prolactin and fT4 concentrations were measured by Siemens clinical chemistry or immunoassay system. For statistical analysis, a generalized linear model (GLM) was used. Urea concentration was 11.88 ± 3.03 mg/dl in keratoconus and 16.44 ± 6.40 mg/dl in cataract patients, uric acid 2.04 ± 0.59 mg/dl in keratoconus and 2.18 ± 0.73 mg/dl in cataract groups. Prolactin concentration was 3.18 ± 0.34 ng/ml in keratoconus and 3.33 ± 0.32 ng/ml in cataract patients, fT4 20.57 ± 4.76 pmol/l in KC and 19.06 ± 3.86 pmol/l in cataract group. Urea concentration was effected through gender (p = 0.039), age (p = 0.001) and diagnosis (p = 0.025). Uric acid concentration was not effected through any of the analyzed parameters (p > 0.056). Prolactin and fT4 concentration were effected only through diagnosis (p = 0.009 and p = 0.006). Urea and prolactin concentrations are decreased, fT4 concentration is increased in aqueous humor of keratoconus patients, and uric acid concentration remains unchanged. Urea concentration in aqueous humor is also increased in older and male patients. Therefore, metabolic disorder and hormonal balance may both have an impact on keratoconus development. Further studies are necessary to assess the specific impact.

CLEC4F is an inducible C-type lectin in F4/80-positive cells and is involved in alpha-galactosylceramide presentation in liver.

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Chih-Ya Yang

Full Text Available CLEC4F, a member of C-type lectin, was first purified from rat liver extract with high binding affinity to fucose, galactose (Gal, N-acetylgalactosamine (GalNAc, and un-sialylated glucosphingolipids with GalNAc or Gal terminus. However, the biological functions of CLEC4F have not been elucidated. To address this question, we examined the expression and distribution of murine CLEC4F, determined its binding specificity by glycan array, and investigated its function using CLEC4F knockout (Clec4f-/- mice. We found that CLEC4F is a heavily glycosylated membrane protein co-expressed with F4/80 on Kupffer cells. In contrast to F4/80, CLEC4F is detectable in fetal livers at embryonic day 11.5 (E11.5 but not in yolk sac, suggesting the expression of CLEC4F is induced as cells migrate from yolk cells to the liver. Even though CLEC4F is not detectable in tissues outside liver, both residential Kupffer cells and infiltrating mononuclear cells surrounding liver abscesses are CLEC4F-positive upon Listeria monocytogenes (L. monocytogenes infection. While CLEC4F has strong binding to Gal and GalNAc, terminal fucosylation inhibits CLEC4F recognition to several glycans such as Fucosyl GM1, Globo H, Bb3∼4 and other fucosyl-glycans. Moreover, CLEC4F interacts with alpha-galactosylceramide (α-GalCer in a calcium-dependent manner and participates in the presentation of α-GalCer to natural killer T (NKT cells. This suggests that CLEC4F is a C-type lectin with diverse binding specificity expressed on residential Kupffer cells and infiltrating monocytes in the liver, and may play an important role to modulate glycolipids presentation on Kupffer cells.

High proportion of PD-1-expressing CD4+ T cells in adipose tissue constitutes an immunomodulatory microenvironment that may support HIV persistence.

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Damouche, Abderaouf; Pourcher, Guillaume; Pourcher, Valérie; Benoist, Stéphane; Busson, Elodie; Lataillade, Jean-Jacques; Le Van, Mélanie; Lazure, Thierry; Adam, Julien; Favier, Benoit; Vaslin, Bruno; Müller-Trutwin, Michaela; Lambotte, Olivier; Bourgeois, Christine

2017-12-01

We and others have demonstrated that adipose tissue is a reservoir for HIV. Evaluation of the mechanisms responsible for viral persistence may lead to ways of reducing these reservoirs. Here, we evaluated the immune characteristics of adipose tissue in HIV-infected patients receiving antiretroviral therapy (ART) and in non-HIV-infected patients. We notably sought to determine whether adipose tissue's intrinsic properties and/or HIV induced alteration of the tissue environment may favour viral persistence. ART-controlled HIV infection was associated with a difference in the CD4/CD8 T-cell ratio and an elevated proportion of Treg cells in subcutaneous adipose tissue. No changes in Th1, Th2 and Th17 cell proportions or activation markers expression on T cell (Ki-67, HLA-DR) could be detected, and the percentage of CD69-expressing resident memory CD4 + T cells was not affected. Overall, our results indicate that adipose-tissue-resident CD4 + T cells are not extensively activated during HIV infection. PD-1 was expressed by a high proportion of tissue-resident memory CD4 + T cells in both HIV-infected patients and non-HIV-infected patients. Our findings suggest that adipose tissue's intrinsic immunomodulatory properties may limit immune activation and thus may strongly contribute to viral persistence. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Treatment response evaluation with {sup 18}F-FDG PET/CT and {sup 18}F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation

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Sachpekidis, Christos [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Bern, Department of Nuclear Medicine, Inselspital, Bern University Hospital, Bern (Switzerland); Hillengass, J.; Wagner, B. [University Hospital Heidelberg, Department of Internal Medicine V, Heidelberg (Germany); Goldschmidt, H. [University Hospital Heidelberg, Department of Internal Medicine V, Heidelberg (Germany); National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg (Germany); Haberkorn, U. [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Kopka, K. [German Cancer Research Center (DKFZ), Department of Radiopharmaceutical Chemistry, Heidelberg (Germany); Dimitrakopoulou-Strauss, A. [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany)

2017-01-15

The aim of this study was to assess the combined use of the radiotracers {sup 18}F-FDG and {sup 18}F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with {sup 18}F-FDG and {sup 18}F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, {sup 18}F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, {sup 18}F-FDG PET/CT-based treatment response revealed CR in 14 patients ({sup 18}F-FDG PET/CT CR), PR in 11 patients ({sup 18}F-FDG PET/CT PR) and progressive disease in four patients ({sup 18}F-FDG PET/CT PD). In terms of {sup 18}F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, {sup 18}F-NaF PET/CT depicted 56 of the 129 {sup 18}F-FDG positive lesions (43 %). Follow-up {sup 18}F-NaF PET/CT showed persistence of 81.5 % of the baseline {sup 18}F-NaF

F4+ ETEC infection and oral immunization with F4 fimbriae elicits an IL-17-dominated immune response.

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Luo, Yu; Van Nguyen, Ut; de la Fe Rodriguez, Pedro Y; Devriendt, Bert; Cox, Eric

2015-10-21

Enterotoxigenic Escherichia coli (ETEC) are an important cause of post-weaning diarrhea (PWD) in piglets. Porcine-specific ETEC strains possess different fimbrial subtypes of which F4 fimbriae are the most frequently associated with ETEC-induced diarrhea in piglets. These F4 fimbriae are potent oral immunogens that induce protective F4-specific IgA antibody secreting cells at intestinal tissues. Recently, T-helper 17 (Th17) cells have been implicated in the protection of the host against extracellular pathogens. However, it remains unknown if Th17 effector responses are needed to clear ETEC infections. In the present study, we aimed to elucidate if ETEC elicits a Th17 response in piglets and if F4 fimbriae trigger a similar response. F4(+) ETEC infection upregulated IL-17A, IL-17F, IL-21 and IL-23p19, but not IL-12 and IFN-γ mRNA expression in the systemic and mucosal immune system. Similarly, oral immunization with F4 fimbriae triggered a Th17 signature evidenced by an upregulated mRNA expression of IL-17F, RORγt, IL-23p19 and IL-21 in the peripheral blood mononuclear cells (PBMCs). Intriguingly, IL-17A mRNA levels were unaltered. To further evaluate this difference between systemic and mucosal immune responses, we assayed the cytokine mRNA profile of F4 fimbriae stimulated PBMCs. F4 fimbriae induced IL-17A, IL-17F, IL-22 and IL-23p19, but downregulated IL-17B mRNA expression. Altogether, these data indicate a Th17 dominated response upon oral immunization with F4 fimbriae and F4(+) ETEC infection. Our work also highlights that IL-17B and IL-17F participate in the immune response to protect the host against F4(+) ETEC infection and could aid in the design of future ETEC vaccines.

Low Expression of TBX4 Predicts Poor Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma

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Meijuan Zong

2011-08-01

Full Text Available This study was designed to investigate the expression of the T-box transcription factor 4 (TBX4, a tumor biomarker that was previously identified by proteomics, in pancreatic ductal adenocarcinoma (PDAC and evaluate its clinical utility as a potential prognostic biomarkers for PDAC. The expression of TBX4 was detected in 77 stage II PDAC tumors by immunohistochemistry, and the results were analyzed with regard to clinicopathological characteristics and overall survival. Moreover, Tbx4 promoter methylation status in primary PDAC tumors and normal adjacent pancreas tissues was measured by bisulfite sequencing. Among 77 stage II PDAC tumors, 48 cases (62.3% expressed TBX4 at a high level. No significant correlation between TBX4 expression and other clinicopathological parameters, except tumor grade and liver metastasis recurrence, was found. The survival of patients with TBX4-high expression was significantly longer than those with TBX4-low expression (P = 0.010. In multivariate analysis, low TBX4 expression was an independent prognostic factor for overall survival in patients with stage II PDAC. TBX4 promoter methylation status was frequently observed in both PDAC and normal adjacent pancreas. We conclude that a low level of TBX4 expression suggests a worse prognosis for patients with stage II PDAC. Down-regulation of the TBX4 gene in pancreas is less likely to be regulated by DNA methylation.

In vitro reduction of dental erosion by low-concentration TiF4 solutions

NARCIS (Netherlands)

Vieira, A.M.; Ruben, J.L.; Bronkhorst, E.M.; Huysmans, M.C.D.N.J.M.

2011-01-01

The aims of this study were to compare daily versus single applications of low-concentration TiF(4) solutions for reduction of enamel erosion and to evaluate the enamel surface loss due to application of these solutions. Sixty bovine enamel samples were randomly divided into 2 groups: single versus

In vitro Reduction of Dental Erosion by Low-Concentration TiF4 Solutions

NARCIS (Netherlands)

Vieira, A. M.; Ruben, J. L.; Bronkhorst, E. M.; Huysmans, M. C. D. N. J. M.

2011-01-01

The aims of this study were to compare daily versus single applications of low-concentration TiF4 solutions for reduction of enamel erosion and to evaluate the enamel surface loss due to application of these solutions. Sixty bovine enamel samples were randomly divided into 2 groups: single versus

Thermoluminescent characteristics of LiF:Mg, Cu, P and CaSO_4:Dy for low dose measurement

International Nuclear Information System (INIS)

Del Sol Fernández, S.; García-Salcedo, R.; Mendoza, J. Guzmán; Sánchez-Guzmán, D.; Rodríguez, G. Ramírez; Gaona, E.; Montalvo, T. Rivera

2016-01-01

Thermoluminescence (TL) characteristics for LiF:Mg, Cu, P, and CaSO_4:Dy under the homogeneous field of X-ray beams of diagnostic irradiation and its verification using thermoluminescence dosimetry are presented. The irradiation were performed utilizing a conventional X-ray equipment installed at the Hospital Juárez Norte of México. Different thermoluminescence characteristics of two material were studied, such as batch homogeneity, glow curve, linearity, detection threshold, reproducibility, relative sensitivity and fading. Materials were calibrated in terms of absorbed dose to the standard calibration distance and they were positioned in a generic phantom. The dose analysis, verification and comparison with the measurements obtained by the TLD-100 were performed. Results indicate that the dosimetric peak appears at 202 °C and 277.5 °C for LiF:Mg, Cu, P and CaSO_4:Dy, respectively. TL response as a function of X-ray dose showed a linearity behavior in the very low dose range for all materials. However, the TLD-100 is not accurate for measurements below 4 mGy. CaSO_4:Dy is 80% more sensitive than TLD-100 and it show the lowest detection threshold, whereas LiF:Mg, Cu, P is 60% more sensitive than TLD-100. All materials showed very good repeatability. Fading for a period of one month at room temperature showed low fading LiF:Mg, Cu, P, medium and high for TLD-100 and CaSO_4:Dy. The results suggest that CaSO_4:Dy and LiF:Mg, Cu, P are suitable for measurements at low doses used in radiodiagnostic. - Highlights: • Several dosimetric characteristics were evaluated. • TL dose response to very low dose X-rays was studied. • The applications proposed for each material may be useful for diagnostic radiology dosimetry.

A green process for the preparation of 11-{4-[2-(2-hydroxyethoxyethyl]-1-piperazinyl}dibenzo[b,f][1,4]thiazepine

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GANESH D. MAHALE

2008-04-01

Full Text Available A green process for the synthesis of 11-{4-[2-(2-hydroxyethoxyethyl]-1-piperazinyl}dibenzo[b,f][1,4]thiazepine by the reaction of 11-(1-piperazinyldibenzo[b,f][1,4]thiazepine or its dihydrochloride salt with 2-(2-chloroethoxyethanol in the presence of an inorganic base and water is reported (conversion 99.9 % in a short time and without any impurities. The metal halides and phase transfer catalyst increase the rate of reaction, especially in water as the solvent.

[Expression of high mobility group box-1 in the lung tissue and serum of patients with pulmonary tuberculosis].

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Yang, Xiao-min; Yang, Hua

2013-07-01

To explore the expression of high mobility group box-1 (HMGB1) in the lung tissue and serum of patients with pulmonary tuberculosis and to explore its relationship with tumor necrosis factor (TNF)-α and interleukin(IL)-1β. Sixty samples of lung tissues were obtained from patients with pulmonary tuberculosis who had underwent pneumonectomy in Department of Chest Surgery, First Affiliated Hospital of Zunyi Medical College from June 2010 to December 2011. At the same period, 40 normal lung samples were also obtained from patients with pulmonary contusion and lung cancer by surgical resections as the control group. The mRNA expressions of HMGB1 was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the protein level of HMGB1 was measured by immunohistochemical staining of tissue microarrays in lung tissue. Blood samples were taken from 89 patients with active pulmonary tuberculosis (pulmonary tuberculosis group), including hematogenous disseminated pulmonary tuberculosis (type II) in 35 cases and secondary pulmonary tuberculosis (type III) in 54 cases, and 50 healthy volunteers (control group). Furthermore, the 54 patients with secondary pulmonary tuberculosis were divided into different subgroups according to cavity formation and the lung fields involved: patients without lung cavity (35 cases) vs those with lung cavity (19 cases), patients with involvement of pulmonary tuberculosis (69 ± 29) was significantly higher than that in normal lung tissue (22 ± 12) (t = 2.389, P pulmonary tuberculosis (786 ± 86) was significantly higher than that in normal lung tissue (202 ± 60) (t = 3.872, P pulmonary tuberculosis group were (5.0 ± 3.2) µg/L, (118 ± 77) ng/L and (33 ± 20) ng/L, respectively, which were significantly higher than those in the control group [(1.7 ± 1.0) µg/L, (40 ± 11) ng/L and (18 ± 12) ng/L, respectively], the respective t values being -0.928, 4.268 and 11.064, all P pulmonary tuberculosis, the serum concentration of HMGB

Macrophage entry mediated by HIV Envs from brain and lymphoid tissues is determined by the capacity to use low CD4 levels and overall efficiency of fusion

International Nuclear Information System (INIS)

Thomas, Elaine R.; Dunfee, Rebecca L.; Stanton, Jennifer; Bogdan, Derek; Taylor, Joann; Kunstman, Kevin; Bell, Jeanne E.; Wolinsky, Steven M.; Gabuzda, Dana

2007-01-01

HIV infects macrophages and microglia in the central nervous system (CNS), which express lower levels of CD4 than CD4+ T cells in peripheral blood. To investigate mechanisms of HIV neurotropism, full-length env genes were cloned from autopsy brain and lymphoid tissues from 4 AIDS patients with HIV-associated dementia (HAD). Characterization of 55 functional Env clones demonstrated that Envs with reduced dependence on CD4 for fusion and viral entry are more frequent in brain compared to lymphoid tissue. Envs that mediated efficient entry into macrophages were frequent in brain but were also present in lymphoid tissue. For most Envs, entry into macrophages correlated with overall fusion activity at all levels of CD4 and CCR5. gp160 nucleotide sequences were compartmentalized in brain versus lymphoid tissue within each patient. Proline at position 308 in the V3 loop of gp120 was associated with brain compartmentalization in 3 patients, but mutagenesis studies suggested that P308 alone does not contribute to reduced CD4 dependence or macrophage-tropism. These results suggest that HIV adaptation to replicate in the CNS selects for Envs with reduced CD4 dependence and increased fusion activity. Macrophage-tropic Envs are frequent in brain but are also present in lymphoid tissues of AIDS patients with HAD, and entry into macrophages in the CNS and other tissues is dependent on the ability to use low receptor levels and overall efficiency of fusion

18F-DOPA PET/CT Physiological Distribution and Pitfalls: Experience in 215 Patients.

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Calabria, Ferdinando F; Chiaravalloti, Agostino; Jaffrain-Rea, Marielise L; Zinzi, Maddalena; Sannino, Pasqualina; Minniti, Giuseppe; Rubello, Domenico; Schillaci, Orazio

2016-10-01

F-DOPA PET/CT is potentially helpful in the management of patients with low-grade brain tumors, movement disorders, and somatic neuroendocrine tumors. We describe the whole-body physiological distribution of F-DOPA uptake. We examined 215 patients with F-DOPA PET/CT. Among these, 161 had brain scans and 54 had whole-body scans. Physiological distribution was negligible in the brain, with the exception of basal ganglia, whereas greatest activity was noted in the liver, pancreas, other exocrine glands, and the urinary system. Incidental tracer uptake sites were identified in 5.5% of patients. Some of these findings were due to inflammation, whereas in most cases, uptake was seen in benign tumors of the brain or in the endocrine or exocrine glands. F-DOPA uptake may be seen in inflammatory tissue or benign tumors. Correlations with history, physical examination, laboratory examination, CT, MRI, and histology are necessary for optimal diagnosis.

Low carbohydrate diet before 18F-FDG tumor imaging contributes to reduce myocardial 18F-FDG uptake

International Nuclear Information System (INIS)

Miao Weibing; Chen Shaoming; Zheng Shan; Wu Jing; Peng Jiequan; Jiang Zhihong

2014-01-01

Objective: To evaluate whether low carbohydrate diet before 18 F-FDG tumor imaging could reduce myocardial 18 F-FDG uptake. Methods: From April 2011 to January 2012, 70 patients were enrolled in this study.They were randomly divided into control group (34 cases) and test group (36 cases). Patients in control group were on regular diet, while those in test group had low carbohydrate diet in the evening before imaging. Blood samples were taken before injection of 18 F-FDG for the measurement of serum glucose, free fatty acid,insulin and ketone body. Whole body 18 F-FDG tomography was performed with dual-head coincidence SPECT. The myocardial uptake of FDG was assessed visually and scored as 0 for no uptake, 1 for uptake lower than liver, 2 for uptake similar to liver, 3 for uptake higher than liver, and 4 for remarkable uptake.The ratio of myocardium to liver (H/L) was calculated. Two-sample t test, Wilcoxon rank sum test and linear correlation analysis were performed. Results: The myocardial uptake in test group was significantly lower than that in control group with H/L ratios of 0.94±0.57 and 1.50±1.04, respectively (t=-2.75, P<0.05). The concentrations of serum free fatty acid and ketone body in test group were significantly higher than those in control group: (0.671±0.229) mmol/L vs (0.547±0.207) mmol/L and (0.88±0.60) mmol/L vs (0.57±0.32) mmol/L, t=2.38 and 2.67, both P<0.05. The concentrations of glucose and insulin were (5.28±1.06) mmol/L and (35.16±33.70) pmol/L in test group, which showed no significant difference with those in control group ((5.19±0.78) mmol/L and (41.64±35.13) pmol/L, t=0.39 and-0.79, both P>0.05). A negative correlation was found between the myocardial uptake of 18 F-FDG and serum free fatty acid/ketone body concentration (r=-0.40, -0.33, both P<0.01), respectively. There was no correlation between the myocardial uptake of 18 F-FDG and glucose/insulin (r=-0.02, 0.13, both P>0.05), respectively. Conclusion: Low carbohydrate

[18F]FDG PET/MRI of patients with chronic pain alters management: early experience

International Nuclear Information System (INIS)

Biswal, Sandip; Behera, Deepak; Yoon, Dae Hyun; Holley, Dawn; Ith, Ma Agnes Martinez; Carroll, Ian; Smuck, Matthew; Hargreaves, Brian

2015-01-01

The chronic pain sufferer is currently faced with a lack of objective tools to identify the source of their pain. The overarching goal is to develop clinical [18F]FDG PET/MRI methods to more accurately localize sites of increased neuronal and muscular metabolism or inflammation as it relates to neurogenic sources of pain and to ultimately improve outcomes of chronic pain sufferers. The aims are to 1) correlate imaging findings with location of pain symptomology, 2) predict location of symptoms based on imaging findings alone and 3) to determine whether the imaging results affect current management decisions. Six patients suffering from chronic lower extremity neuropathic pain (4 complex regional pain syndrome, 1 chronic sciatica and 1 neuropathic pain) have been imaged with a PET/MRI system (time-of-flight PET; 3.0T bore) from mid thorax through the feet. All patients underwent PET/MR imaging one hour after a injection of 10mCi [18F]FDG. Two radiologists evaluated PET/MR images (one blinded and the other unblinded to patient exam/history). ROI analysis showed focal increased [18F]FDG uptake in affected nerves and muscle (approx 2-4 times more) over background tissue in various regions of the body in 5 of 6 patients at the site of greatest pain symptoms and other areas of the body (SUVmax of Target 0.9-4.2 vs. Background 0.2-1.2). The radiologist blind to the patient history/exam was able to correctly identify side/location of the symptoms in 5 out of 6 patients. Imaging results were reviewed with the referring physician, who then determined whether a modification in the management plan was needed: 1/6 no change, 2/6 mild modification (e.g., additional diagnostic test ordered) and 3/6 significant modification.

[18F]FDG PET/MRI of patients with chronic pain alters management: early experience

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Biswal, Sandip; Behera, Deepak; Yoon, Dae Hyun; Holley, Dawn; Ith, Ma Agnes Martinez; Carroll, Ian; Smuck, Matthew; Hargreaves, Brian [Stanford University School of Medicine, California (United States)

2015-05-18

The chronic pain sufferer is currently faced with a lack of objective tools to identify the source of their pain. The overarching goal is to develop clinical [18F]FDG PET/MRI methods to more accurately localize sites of increased neuronal and muscular metabolism or inflammation as it relates to neurogenic sources of pain and to ultimately improve outcomes of chronic pain sufferers. The aims are to 1) correlate imaging findings with location of pain symptomology, 2) predict location of symptoms based on imaging findings alone and 3) to determine whether the imaging results affect current management decisions. Six patients suffering from chronic lower extremity neuropathic pain (4 complex regional pain syndrome, 1 chronic sciatica and 1 neuropathic pain) have been imaged with a PET/MRI system (time-of-flight PET; 3.0T bore) from mid thorax through the feet. All patients underwent PET/MR imaging one hour after a injection of 10mCi [18F]FDG. Two radiologists evaluated PET/MR images (one blinded and the other unblinded to patient exam/history). ROI analysis showed focal increased [18F]FDG uptake in affected nerves and muscle (approx 2-4 times more) over background tissue in various regions of the body in 5 of 6 patients at the site of greatest pain symptoms and other areas of the body (SUVmax of Target 0.9-4.2 vs. Background 0.2-1.2). The radiologist blind to the patient history/exam was able to correctly identify side/location of the symptoms in 5 out of 6 patients. Imaging results were reviewed with the referring physician, who then determined whether a modification in the management plan was needed: 1/6 no change, 2/6 mild modification (e.g., additional diagnostic test ordered) and 3/6 significant modification.

The 4s- and 4p- XPS spectra of Xe, XeF2 and XeF4

International Nuclear Information System (INIS)

Ohno, Masahide

2003-01-01

The 4s- and 4p- XPS spectra of Xe gas, XeF 2 molecule and XeF 4 molecule are calculated by an ab-initio atomic many-body theory. The 4s-peak and the prominent '4p'-peak are predicted well by the present theory. In XeF 2 and XeF 4 the spectral lines observed below the 4d-double ionization threshold are the 4d -2 4f multiplet states strongly perturbed by the interaction with the initial 4p 1/2 -hole state. They are very similar to the spectral lines which emerge with an increase in atomic number (e.g. Ba)

Intraindividual comparison of F-18-FLT PET and F-18 FET PET in brain tumor patients

International Nuclear Information System (INIS)

Kim, Sung Eun; Cheon, G. J.; Cho, Y. S.; Kwak, H. S.; Lee, C. H.; Choi, C. W.; Lim, S. M.

2003-01-01

To compare findings on FLT PET with FET PET, we prospectively undertaken FLT, FET and FDG PET in same patient with suspected primary/metastatic and recurrent brain tumors. Seventeen studies in 16 patients (47 8.3 years, M: F 10: 6) with brain tumor (3 for initial diagnosis, 6 for therapeutic response, 6 for detecting recurrence, 1 for diagnosis and recurrence both) were included. Brain tumors were 14 gliomas (6 high- grade 9 low-grade by the WHO classification), 2 metastatic brain tumors and 1 CNS lymphoma. 18F-FDG, FLT and FET PET were performed within two weeks. Attenuation-corrected brain images were acquired 30 minutes after injection of 370-555 MBq FDG, FLT and FET with a dedicated PET scanner (ECAT HR scanner, Siemens-CTI). Maximum SUV (max SUV) and relative uptake defined by FLT and FET accumulation within the tumor in relation to a contralateral control region (max SUV for tumor/ mean SUV for contralateral normal gray matter) were calculated. 26 tumor foci were analyzed. Relative FLT uptake (4.17 2.4, 0.58 to 7.45) was grater than than FET uptake (2.03 1.17, 0.92 to 4.53 (p<0.0006)) and FDG uptake (1.16 0.34, 0.76 to 2.08). Among FLT, FET and FDG uptakes in 20 tumor foci, correlation were poor. the relative FLT uptake of high-grade glioma was higher than low-glioma (6.070.76 vs 3.11 2.15, p=0.002), however, relative FET uptake was not different significantly (2.68 1.51, high-grade vs 1.970.78, low-grade). The correlation between tumor grade (high vs low grade) and relative uptake (FLT and FET) was shown only with relative FLT uptake (r=0.62, p=0.002). The best cut off value of relative FLT uptake between high-grade and low-grade glioma was 4.54 (AUC: 0.89 sensitivity: 100 specificity: 86.7%). Compared with FET uptake, FLT uptake showed much higher contrast and associated with tumor grade. Further study, evaluation of proliferative index of Ki-67 and its relationship with FLT and FET uptake, are ongoing

Over-expression of thymosin β4 in granulomatous lung tissue with active pulmonary tuberculosis.

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Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun; Yoo, Young-Bin; Chun, Bong-Kwon; Oak, Chul-Ho; Cha, Hee-Jae

2014-05-01

Recent studies have shown that thymosin β4 (Tβ4) stimulates angiogenesis by inducing vascular endothelial growth factor (VEGF) expression and stabilizing hypoxia inducible factor-1α (HIF-1α) protein. Pulmonary tuberculosis (TB), a type of granulomatous disease, is accompanied by intense angiogenesis and VEGF levels have been reported to be elevated in serum or tissue inflamed by pulmonary tuberculosis. We investigated the expression of Tβ4 in granulomatous lung tissues at various stages of active pulmonary tuberculosis, and we also examined the expression patterns of VEGF and HIF-1α to compare their Tβ4 expression patterns in patients' tissues and in the tissue microarray of TB patients. Tβ4 was highly expressed in both granulomas and surrounding lymphocytes in nascent granulomatous lung tissue, but was expressed only surrounding tissues of necrotic or caseous necrotic regions. The expression pattern of HIF-1α was similar to that of Tβ4. VEGF was expressed in both granulomas and blood vessels surrounding granulomas. The expression pattern of VEGF co-localized with CD31 (platelet endothelial cell adhesion molecule, PECAM-1), a blood endothelial cell marker, and partially co-localized with Tβ4. However, the expression of Tβ4 did not co-localize with alveolar macrophages. Stained alveolar macrophages were present surrounding regions of granuloma highly expressing Tβ4. We also analyzed mRNA expression in the sputum of 10 normal and 19 pulmonary TB patients. Expression of Tβ4 was significantly higher in patients with pulmonary tuberculosis than in normal controls. These data suggest that Tβ4 is highly expressed in granulomatous lung tissue with active pulmonary TB and is associated with HIF-1α- and VEGF-mediated inflammation and angiogenesis. Furthermore, the expression of Tβ4 in the sputum of pulmonary tuberculosis patients can be used as a potential marker for diagnosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular cloning and characterization of the porcine prostaglandin transporter (SLCO2A1: evaluation of its role in F4 mediated neonatal diarrhoea

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Cox Eric

2009-10-01

Full Text Available Abstract Background Because prostaglandins are involved in many (pathophysiological processes, SLCO2A1 was already characterized in several species in an attempt to unravel specific processes/deficiencies. Here, we describe the molecular cloning and characterization of the porcine ortholog in order to evaluate its possible involvement in F4 enterotoxigenic E. coli mediated neonatal diarrhoea, based on a positional candidate gene approach study. Results Porcine SLCO2A1 is organized in 14 exons, containing an open reading frame of 1935 bp, encoding a 12-transmembrane organic anion cell surface transporter of 644 aa. The -388 to -5 upstream region comprises a (CpG48 island containing a number of conserved promoter elements, including a TATA box. A potential alternative promoter region was found in the conserved -973 to -700 upstream region. No consensus polyadenylation signal was discovered in the 3' UTR. Repeat sequences were found in 15% of all the non coding sequences. As expected for a multifunctional protein, a wide tissue distribution was observed. mRNA expression was found in the adrenal gland, bladder, caecum, colon (centripetal coil/centrifugal coil, diaphragm, duodenum, gallbladder, heart, ileum, jejunum, kidney, liver, longissimus dorsi muscle, lung, lymph node, mesenterium, rectum, spleen, stomach, tongue and ureter, but not in the aorta, oesophagus and pancreas. The promoter region and the exons (including the splice sites of SLCO2A1 were resequenced in 5 F4ab/ac receptor positive and 5 F4ab/ac receptor negative pigs. Two silent and 2 missense (both S → L at position 360 and 633 mutations were found, but none was associated with the F4ab/ac receptor phenotype. In addition, no phenotype associated differential mRNA expression or alternative/abberant splicing/polyadenylation was found in the jejunum. Conclusion The molecular cloning and characterization of porcine SLCO2A1 not only contributes to the already existing knowledge about the

Heterologous prime-boost regimens with a recombinant chimpanzee adenoviral vector and adjuvanted F4 protein elicit polyfunctional HIV-1-specific T-Cell responses in macaques.

Science.gov (United States)

Lorin, Clarisse; Vanloubbeeck, Yannick; Baudart, Sébastien; Ska, Michaël; Bayat, Babak; Brauers, Geoffroy; Clarinval, Géraldine; Donner, Marie-Noëlle; Marchand, Martine; Koutsoukos, Marguerite; Mettens, Pascal; Cohen, Joe; Voss, Gerald

2015-01-01

, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4+ T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.

A phase I study of vaccination with NY-ESO-1f peptide mixed with Picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen.

Science.gov (United States)

Kakimi, Kazuhiro; Isobe, Midori; Uenaka, Akiko; Wada, Hisashi; Sato, Eiichi; Doki, Yuichiro; Nakajima, Jun; Seto, Yasuyuki; Yamatsuji, Tomoki; Naomoto, Yoshio; Shiraishi, Kenshiro; Takigawa, Nagio; Kiura, Katsuyuki; Tsuji, Kazuhide; Iwatsuki, Keiji; Oka, Mikio; Pan, Linda; Hoffman, Eric W; Old, Lloyd J; Nakayama, Eiichi

2011-12-15

We conducted a phase I clinical trial of a cancer vaccine using a 20-mer NY-ESO-1f peptide (NY-ESO-1 91-110) that includes multiple epitopes recognized by antibodies, and CD4 and CD8 T cells. Ten patients were immunized with 600 μg of NY-ESO-1f peptide mixed with 0.2 KE Picibanil OK-432 and 1.25 ml Montanide ISA-51. Primary end points of the study were safety and immune response. Subcutaneous injection of the NY-ESO-1f peptide vaccine was well tolerated. Vaccine-related adverse events observed were fever (Grade 1), injection-site reaction (Grade 1 or 2) and induration (Grade 2). Vaccination with the NY-ESO-1f peptide resulted in an increase or induction of NY-ESO-1 antibody responses in nine of ten patients. The sera reacted with recombinant NY-ESO-1 whole protein as well as the NY-ESO-1f peptide. An increase in CD4 and CD8 T cell responses was observed in nine of ten patients. Vaccine-induced CD4 and CD8 T cells responded to NY-ESO-1 91-108 in all patients with various HLA types with a less frequent response to neighboring peptides. The findings indicate that the 20-mer NY-ESO-1f peptide includes multiple epitopes recognized by CD4 and CD8 T cells with distinct specificity. Of ten patients, two with lung cancer and one with esophageal cancer showed stable disease. Our study shows that the NY-ESO-1f peptide vaccine was well tolerated and elicited humoral, CD4 and CD8 T cell responses in immunized patients. Copyright © 2011 UICC.

[JAK2 V617F and exon 12 genetic variations in Korean patients with BCR/ABL1-negative myeloproliferative neoplasms].

Science.gov (United States)

Kim, Jeong Tae; Cho, Yong Gon; Choi, Sam Im; Lee, Young Jin; Kim, Hye Ran; Jang, Sook Jin; Moon, Dae Soo; Park, Young Jin; Park, Geon

2010-12-01

JAK2 genetic variations have been described in a high proportion of patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN). This study was designed to analyze the frequencies of JAK2 V617F and exon 12 variations, and their correlations with clinical characteristics of Korean patients with BCR/ABL1-negative MPN. We examined a total of 154 patients with BCR/ABL1-negative MPN that included 24, 26, 89, and 15 patients with polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), and unclassified myeloproliferative neoplasms (MPNU), respectively. We performed allele-specific PCR to detect V617F in all BCR/ABL1-negative patients, and performed direct sequencing to detect exon 12 variations in 47 V617F-negative MPN patients. JAK2 c.1641+179_183del5 variation was detected by restriction fragment length polymorphism assay in 176 healthy subjects. JAK2 V617F was detected in 91 patients (59.1%): PV (91.6%), PMF (46.2%), ET (52.8%), and MPNU (66.7%). In V617F-negative MPN patients, no mutations were found in exon 12. The c.1641+179_183del5 was detected in 68.1% of V617F-negative MPN patients and 45.4% of healthy subjects (P=0.008). JAK2 V617F was closely correlated with age and leukocytosis in BCR/ABL1-negative MPN patients (P<0.05). However, c.1641+179_183del5 was not related to age, sex, or complete blood cell count parameters in V617F-negative MPN patients and healthy subjects. The c.1641+179_183del5 was associated with an increased odds ratio for MPN (odds ratio, 2.6; 95% confidences interval, 1.3-5.1; P=0.007). Frequencies of V617F are similar to reported results. JAK2 exon 12 mutations may be rare and c.1641+179_183del5 may influence the occurrence of MPN in Korean patients with V6 17F-negative MPN.

Soft tissue metastases from differentiated thyroid cancer diagnosed by {sup 18}F FDG PET-CT

Energy Technology Data Exchange (ETDEWEB)

Califano, Ines; Quildrian, Sergio; Otero, Jose; Coduti, Martin; Califano, Leonardo; Rojas Bilbao, Erica, E-mail: ines.m.califano@gmail.com [Instituto de Oncologia Angel H. Roffo, Universidad de Buenos Aires (Argentina)

2013-06-15

Distant metastases of differentiated thyroid cancer are unusual; lung and bones are the most frequently affected sites. Soft tissue metastases (STM) are extremely rare. We describe two cases of patients with differentiated thyroid cancer metastasizing to soft tissues. Both patients had widespread metastatic disease; clinically asymptomatic soft tissue metastases were found by 18-Fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F FDG PET-CT), and confirmed by cytological and/or histopathological studies. These findings underscore the ability of {sup 18}F FDG PET-CT in accurately assessing the extent of the disease, as well as the utility of the method to evaluate regions of the body that are not routinely explored. (author)

The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1+ progenitors and Ngn3+ endocrine precursors

Science.gov (United States)

Kim, So Yoon; Rane, Sushil G.

2011-01-01

Cell division and cell differentiation are intricately regulated processes vital to organ development. Cyclin-dependent kinases (Cdks) are master regulators of the cell cycle that orchestrate the cell division and differentiation programs. Cdk1 is essential to drive cell division and is required for the first embryonic divisions, whereas Cdks 2, 4 and 6 are dispensable for organogenesis but vital for tissue-specific cell development. Here, we illustrate an important role for Cdk4 in regulating early pancreas development. Pancreatic development involves extensive morphogenesis, proliferation and differentiation of the epithelium to give rise to the distinct cell lineages of the adult pancreas. The cell cycle molecules that specify lineage commitment within the early pancreas are unknown. We show that Cdk4 and its downstream transcription factor E2f1 regulate mouse pancreas development prior to and during the secondary transition. Cdk4 deficiency reduces embryonic pancreas size owing to impaired mesenchyme development and fewer Pdx1+ pancreatic progenitor cells. Expression of activated Cdk4R24C kinase leads to increased Nkx2.2+ and Nkx6.1+ cells and a rise in the number and proliferation of Ngn3+ endocrine precursors, resulting in expansion of the β cell lineage. We show that E2f1 binds and activates the Ngn3 promoter to modulate Ngn3 expression levels in the embryonic pancreas in a Cdk4-dependent manner. These results suggest that Cdk4 promotes β cell development by directing E2f1-mediated activation of Ngn3 and increasing the pool of endocrine precursors, and identify Cdk4 as an important regulator of early pancreas development that modulates the proliferation potential of pancreatic progenitors and endocrine precursors. PMID:21490060

[Patients with ICD-10 disorders F3 and F4 in psychiatric and psychosomatic in-patient units - who is treated where? : Allocation features from the PfAD study].

Science.gov (United States)

Bichescu-Burian, D; Cerisier, C; Czekaj, A; Grempler, J; Hund, S; Jaeger, S; Schmid, P; Weithmann, G; Steinert, T

2017-01-01

In Germany, in-patient treatment of patients with depressive, neurotic, anxiety, and somatoform disorders (ICD-10 F3, F4) is carried out in different settings in psychiatry and psychosomatics. Which patient characteristics determine referral to one or the other specialty is a crucial question in mental health policy and is a matter of ongoing controversy. However, comparative data on patient populations are widely lacking. In the study of Treatment Pathways of Patients with Anxiety and Depression (PfAD study), a total of 320 patients with ICD-10 F3/F4 clinical diagnoses were consecutively recruited from four treatment settings (psychiatric depression ward, psychiatric crisis intervention ward, psychiatric day hospitals, or psychosomatic hospital units; 80 participants per setting) and investigated. In all treatment settings, patients with considerable severity of illness and chronicity were treated. Female gender, higher education, and higher income predicted referral to psychosomatic units; male gender, transfer from another hospital or emergency hospitalization, co-morbidity with a personality disorder, higher general psychiatric co-morbidity, and danger to self at admission predicted referral to psychiatric unit. Patients in psychosomatic units had neither more psychosomatic disorders nor more somatic problems. There is considerable overlap between the clientele of psychiatric and psychosomatic units. Referral and allocation appears to be determined by aspects of severity and social status.

Isolation and expression analysis of FTZ-F1 encoding gene of black rock fish ( Sebastes schlegelii)

Science.gov (United States)

Shafi, Muhammad; Wang, Yanan; Zhou, Xiaosu; Ma, Liman; Muhammad, Faiz; Qi, Jie; Zhang, Quanqi

2013-03-01

Sex related FTZ-F1 is a transcriptional factor regulating the expression of fushi tarazu (a member of the orphan nuclear receptors) gene. In this study, FTZ-F1 gene ( FTZ-F1) was isolated from the testis of black rockfish ( Sebastes schlegeli) by homology cloning. The full-length cDNA of S. schlegeli FTZ-F1 ( ssFTZ-F1) contained a 232bp 5' UTR, a 1449bp ORF encoding FTZ-F1 (482 amino acid residules in length) with an estimated molecular weight of 5.4kD and a 105bp 3' UTR. Sequence, tissue distribution and phylogenic analysis showed that ssFTZ-F1 belonged to FTZ group, holding highly conserved regions including I, II and III FTZ-F1 boxes and an AF-2 hexamer. Relatively high expression was observed at different larva stages. In juveniles (105 days old), the transcript of ssFTZ-F1 can be detected in all tissues and the abuncance of the gene transcript in testis, ovary, spleen and brain was higher than that in other tissues. In mature fish, the abundance of gene transcript was higher in testis, ovary, spleen and brain than that in liver (trace amount), and the gene was not transcribed in other tissues. The highest abundance of gene transcript was always observed in gonads of both juvenile and mature fish. In addition, the abundance of gene transcript in male tissues were higher than that in female tissue counterparts ( P<0.05).

Low free triiodothyronine levels predict symptomatic intracranial hemorrhage and worse short-term outcome of thrombolysis in patients with acute ischemia stroke.

Science.gov (United States)

Qiu, Mingjing; Fang, Min; Liu, Xueyuan

2017-11-01

The aim of the study was to determine whether thyroid hormones level on admission in patients with ischemic stroke, treated with intravenous recombinant tissue type plasminogen activator (rtPA), was associated with symptomatic intracranial hemorrhage (sICH) and worse outcomes at 3 months.Patients with acute ischemic stroke (AIS) receiving intravenous rtPA thrombolytic treatment on our stroke unit between January 2015 and June 2016 were included in this study. Serum-free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (tT3), total thyroxine (tT4), and thyroid-stimulating hormone (TSH) were detected on admission. The endpoints were sICH, and poor functional outcomes at 3 and 6 months.In all, 159 patients (106 males; mean age 65.36 ± 10.02 years) were included. FT3 was independently associated with sICH (odds ratio [OR] 0.204, 95% confidence interval [CI] 0.065-0.642) and poor outcomes at 3 months (OR 0.396, 95% CI 0.180-1.764). The cut-off values of fT3 for sICH was 3.54 pg/mL (sensitivity 83%; specificity 83%; area under the curve 0.88). FT3 values ≤3.54 pg/mL increased risk for sICH by 3.16-fold (95% CI 0.75-1.0) compared with fT3 values >3.54 pg/mL.Low fT3 levels at admission were independently associated with sICH and worse outcomes at 3 months in AIS patients receiving rtPA thrombolytic therapy.

Estimation of patient dose in 18 F-FDG and 18 F-FDOPA PET/CT examinations

Directory of Open Access Journals (Sweden)

Aruna Kaushik

2013-01-01

Full Text Available Purpose: To estimate specific organ and effective doses to patients resulting from the 18 F-FDG ( 18 F-2-deoxy-D-glucose and 18 F-FDOPA (6-fluoro-( 18 F-L-3, 4-dihydroxyphenylalanine PET/CT examinations for whole body and brain. Materials and Methods: Three protocols for whole body and three for brain PET/CT were used. The CTDI values were measured using standard head and body CT phantoms and also computed using a software CT-Expo for dose evaluation from the CT component. OLINDA software based on MIRD method was used for estimating doses from the PET component of the PET/CT examination. Results: The organ doses from 18 F-FDG and 18 F-FDOPA whole body and brain PET/CT studies were estimated. The total effective dose from a typical protocol of whole body PET/CT examination was 14.4 mSv for females and 11.8 mSv for male patients from 18 F-FDG, whereas it was 11 mSv for female and 9.1 mSv for male patients from 18 F-FDOPA. The total effective doses from a typical protocol for PET/CT studies of brain was 6.5 mSv for females and 5.1 mSv for males from 18 F-FDG whereas it was 3.7 mSv for females and 2.8 mSv for males from 18 F-FDOPA. Conclusions: The effective radiation doses from whole body PET/CT examination was approximately 4-8 times higher than the background radiation dose from both 18 F-FDG and 18 F-FDOPA scans, while it was 1-3 times the background radiation dose from PET/CT scans of brain.

The Prevalence and Characteristics of Brown Adipose Tissue in an 18F-FDG PET Study of Koreans

International Nuclear Information System (INIS)

Park, Joon Yeun; Lim, Jung Sub; Park, Eun Young; Cho, A Ra; Kim, Byeong Il; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo

2010-01-01

The object of this study was to evaluate the prevalence and characteristics of brown adipose tissue (BAT) in Korean subjects using 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET). Six thousand and five consecutive 18 F-FDG PET/CT scans of 5,115 patients (3,007 females and 2,108 males, mean age 53.5 years) were retrospectively reviewed. We characterized the nature of BAT, such as tis location, and we assessed the influence of sex, age, body mass index (BMI), and temperature on BAT. The prevalence of BAT in Koreans in a single 18 F-FDG PET/CT scan in average conditions was 1.07%. The BAT detection rate was higher in females than males (1.32% vs 0.73%), and also with younger age (7.94% vs 0.73%), and lower BMI (BMI with BAT, 21.1 vs BMI without BAT, 23.15) and cold outdoor temperature (1.65% vs 0.49%). The most frequent location of BAT was the supraclavicular area (left, 0.91%; right, 0.88%) and ventral neck area (left, 0.62%; right, 0.63%). Conclusions The characteristics of BAT in Koreans are not different from those described for Caucasians. However, the low prevalence of BAT in our study might be related to some scan condition like ambient temperature, but further study is needed.

Dissociation Between Brown Adipose Tissue 18F-FDG Uptake and Thermogenesis in Uncoupling Protein 1-Deficient Mice.

Science.gov (United States)

Hankir, Mohammed K; Kranz, Mathias; Keipert, Susanne; Weiner, Juliane; Andreasen, Sille G; Kern, Matthias; Patt, Marianne; Klöting, Nora; Heiker, John T; Brust, Peter; Hesse, Swen; Jastroch, Martin; Fenske, Wiebke K

2017-07-01

18 F-FDG PET imaging is routinely used to investigate brown adipose tissue (BAT) thermogenesis, which requires mitochondrial uncoupling protein 1 (UCP1). It remains uncertain, however, whether BAT 18 F-FDG uptake is a reliable surrogate measure of UCP1-mediated heat production. Methods: UCP1 knockout (KO) and wild-type (WT) mice housed at thermoneutrality were treated with the selective β3 adrenergic receptor agonist CL 316, 243 and underwent metabolic cage, infrared thermal imaging and 18 F-FDG PET/MRI experiments. Primary brown adipocytes were additionally examined for their bioenergetics by extracellular flux analysis as well as their uptake of 2-deoxy- 3 H-glucose. Results: In response to CL 316, 243 treatments, oxygen consumption, and BAT thermogenesis were diminished in UCP1 KO mice, but BAT 18 F-FDG uptake was fully retained. Isolated UCP1 KO brown adipocytes exhibited defective induction of uncoupled respiration whereas their glycolytic flux and 2-deoxy- 3 H-glucose uptake rates were largely unaffected. Conclusion: Adrenergic stimulation can increase BAT 18 F-FDG uptake independently of UCP1 thermogenic function. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Ion conductivities of ZrF4-BaF2-CsF glasses

International Nuclear Information System (INIS)

Kawamoto, Yoji; Nohara, Ichiro

1987-01-01

The glass-forming region in the ZrF 4 -BaF 2 -CsF glass system has been determined and the ac conductivity and the transport number of fluoride ions have been measured. The conductivities of compounds β-Cs 2 ZrF 6 , α-SrZrF 6 , α-BaZrF 6 , β-BaZrF 6 and α-PbZrF 6 have also been measured. These results and a previous study of ZrF 4 -BaF 2 -MF n (M: the groups I-IV metals) glasses revealed the following: (1) the ZrF 4 -BaF 2 -CsF glasses are exclusively fluoride-ion conductors; (2) the ionic conductivities of ZrF 4 -based glasses are predominantly determined by the activation energies for conduction; (3) the activation energy for conduction decreases with an increase in the average polarizability of glass-constituting cations; (4) a decrease in average Zr-F bond length and a lowering of the average F coordination number of Zr are presumed to increase the activation energy for conduction. Principles of developing ZrF 4 -based glasses with higher conductivities have also been proposed. (Auth.)

Thermodynamic assessment of the LiF–NaF–BeF{sub 2}–ThF{sub 4}–UF{sub 4} system

Energy Technology Data Exchange (ETDEWEB)

Capelli, E.; Beneš, O., E-mail: ondrej.benes@ec.europa.eu; Konings, R.J.M.

2014-06-01

The present study describes the full thermodynamic assessment of the LiF–NaF–BeF{sub 2}–ThF{sub 4}–UF{sub 4} system which is one of the key systems considered for a molten salt reactor fuel. The work is an extension of the previously assessed LiF–NaF–ThF{sub 4}–UF{sub 4} system with addition of BeF{sub 2} which is characterized by very low neutron capture cross section and a relatively low melting point. To extend the database the binary BeF{sub 2}–ThF{sub 4} and BeF{sub 2}–UF{sub 4} systems were optimized and the novel data were used for the thermodynamic assessment of BeF{sub 2} containing ternary systems for which experimental data exist in the literature. The obtained database is used to optimize the molten salt reactor fuel composition and to assess its properties with the emphasis on the melting behaviour.

Radionuclide fistulogram (RnF) in hemodialysis patients

Energy Technology Data Exchange (ETDEWEB)

Seo, I.S.; Sy, W.M.; Heneghan, W.; Manoli, A.; Gozum, M.

1984-01-01

Prosthetic graft A-V fistulae (AVf) (10 adults) and internal AVf (14 adults) as avenues of hemodialysis were created surgically in the limbs of 24 renal failure patients. AVf can malfunction or become obstructed and to date only contrast fistulography (CnF) is used to document such problems. Thirty-three RnF's were performed in 24 patients and CnF's in seven patients. Eleven had clinical features of AVf malfunction and 13 were asymptomatic. 99mTc compounds, TcO/sup -//sub 4/ or MDP (20 mCi) were injected into the AVf through a 19-gauge butterfly. 2 sec. dynamic images (qualitative data) and simultaneous computer acquisition in 64 x 64 byte mode with 0.5 sec/frame for 120 frames (quantitative data) were obtained. Normal qualitative and quantitative criteria were established. 10/11 symptomatic and 2/13 asymptomatic patients showed abnormal scintigraphic features and time activity curves indicating AVf malfunction. All 12 patients demonstrated abnormal collateral formation; 8/12 had stenosis, 3/12 showed equivocal stenosis and in 1/12 no stenosis was shown. In these 12 patients the S/sub 2/ (second circulation)/S/sub 1/ (initial circulation) ratio was below 10%. In 5/12 whose S/sub 2//S/sub 1/ ratio was less than 1%, the CnF and surgical repair confirmed the presence of stenosis. RnF appears to be a simple, benign, and accurate imaging procedure in the evaluation of AVf malfunction.

Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site-Inhibited Factor VII.

Science.gov (United States)

Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E; Jensen, Mette M; Kristensen, Lotte K; Madsen, Jacob; Petersen, Lars C; Kjaer, Andreas

2016-01-01

Tissue factor (TF) is upregulated in many solid tumors, and its expression is linked to tumor angiogenesis, invasion, metastasis, and prognosis. A noninvasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII is the natural ligand to TF. Here we report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of factor VII. Active site-inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4-(18)F-fluorobenzoate and purified. The corresponding product, (18)F-FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small-animal PET/CT imaging 1, 2, and 4 h after injection. Ex vivo biodistribution was performed after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by enzyme-linked immunosorbent assay and correlated with the uptake of (18)F-FVIIai in the tumors measured in vivo by PET imaging. The PET images showed high uptake of (18)F-FVIIai in the tumor regions, with a mean uptake of 2.5 ± 0.3 percentage injected dose per gram (%ID/g) (mean ± SEM) 4 h after injection of 7.3-9.3 MBq of (18)F-FVIIai and with an average maximum uptake in the tumors of 7.1 ± 0.7 %ID/g at 4 h. In comparison, the muscle uptake was 0.2 ± 0.01 %ID/g at 4 h. At 4 h, the tumors had the highest uptake of any organ. Blocking with FVIIai significantly reduced the uptake of (18)F-FVIIai from 2.9 ± 0.1 to 1.4 ± 0.1 %ID/g (P < 0.001). The uptake of (18)F-FVIIai measured in vivo by PET imaging correlated (r = 0.72, P < 0.02) with TF protein level measured ex vivo. (18)F-FVIIai is a promising PET tracer for

Mutated and Bacteriophage T4 Nanoparticle Arrayed F1-V Immunogens from Yersinia pestis as Next Generation Plague Vaccines

Science.gov (United States)

Tao, Pan; Mahalingam, Marthandan; Kirtley, Michelle L.; van Lier, Christina J.; Sha, Jian; Yeager, Linsey A.; Chopra, Ashok K.; Rao, Venigalla B.

2013-01-01

Pneumonic plague is a highly virulent infectious disease with 100% mortality rate, and its causative organism Yersinia pestis poses a serious threat for deliberate use as a bioterror agent. Currently, there is no FDA approved vaccine against plague. The polymeric bacterial capsular protein F1, a key component of the currently tested bivalent subunit vaccine consisting, in addition, of low calcium response V antigen, has high propensity to aggregate, thus affecting its purification and vaccine efficacy. We used two basic approaches, structure-based immunogen design and phage T4 nanoparticle delivery, to construct new plague vaccines that provided complete protection against pneumonic plague. The NH2-terminal β-strand of F1 was transplanted to the COOH-terminus and the sequence flanking the β-strand was duplicated to eliminate polymerization but to retain the T cell epitopes. The mutated F1 was fused to the V antigen, a key virulence factor that forms the tip of the type three secretion system (T3SS). The F1mut-V protein showed a dramatic switch in solubility, producing a completely soluble monomer. The F1mut-V was then arrayed on phage T4 nanoparticle via the small outer capsid protein, Soc. The F1mut-V monomer was robustly immunogenic and the T4-decorated F1mut-V without any adjuvant induced balanced TH1 and TH2 responses in mice. Inclusion of an oligomerization-deficient YscF, another component of the T3SS, showed a slight enhancement in the potency of F1-V vaccine, while deletion of the putative immunomodulatory sequence of the V antigen did not improve the vaccine efficacy. Both the soluble (purified F1mut-V mixed with alhydrogel) and T4 decorated F1mut-V (no adjuvant) provided 100% protection to mice and rats against pneumonic plague evoked by high doses of Y. pestis CO92. These novel platforms might lead to efficacious and easily manufacturable next generation plague vaccines. PMID:23853602

Mutated and bacteriophage T4 nanoparticle arrayed F1-V immunogens from Yersinia pestis as next generation plague vaccines.

Directory of Open Access Journals (Sweden)

Pan Tao

Full Text Available Pneumonic plague is a highly virulent infectious disease with 100% mortality rate, and its causative organism Yersinia pestis poses a serious threat for deliberate use as a bioterror agent. Currently, there is no FDA approved vaccine against plague. The polymeric bacterial capsular protein F1, a key component of the currently tested bivalent subunit vaccine consisting, in addition, of low calcium response V antigen, has high propensity to aggregate, thus affecting its purification and vaccine efficacy. We used two basic approaches, structure-based immunogen design and phage T4 nanoparticle delivery, to construct new plague vaccines that provided complete protection against pneumonic plague. The NH₂-terminal β-strand of F1 was transplanted to the COOH-terminus and the sequence flanking the β-strand was duplicated to eliminate polymerization but to retain the T cell epitopes. The mutated F1 was fused to the V antigen, a key virulence factor that forms the tip of the type three secretion system (T3SS. The F1mut-V protein showed a dramatic switch in solubility, producing a completely soluble monomer. The F1mut-V was then arrayed on phage T4 nanoparticle via the small outer capsid protein, Soc. The F1mut-V monomer was robustly immunogenic and the T4-decorated F1mut-V without any adjuvant induced balanced TH1 and TH2 responses in mice. Inclusion of an oligomerization-deficient YscF, another component of the T3SS, showed a slight enhancement in the potency of F1-V vaccine, while deletion of the putative immunomodulatory sequence of the V antigen did not improve the vaccine efficacy. Both the soluble (purified F1mut-V mixed with alhydrogel and T4 decorated F1mut-V (no adjuvant provided 100% protection to mice and rats against pneumonic plague evoked by high doses of Y. pestis CO92. These novel platforms might lead to efficacious and easily manufacturable next generation plague vaccines.

(18)F-FDG dynamic PET/CT in patients with multiple myeloma: patterns of tracer uptake and correlation with bone marrow plasma cell infiltration rate.

Science.gov (United States)

Sachpekidis, Christos; Mai, Elias K; Goldschmidt, Hartmut; Hillengass, Jens; Hose, Dirk; Pan, Leyun; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2015-06-01

The value of F-FDG PET in the diagnostic approach of multiple myeloma (MM) remains incompletely elicited. Little is known about the kinetics of F-FDG in the bone marrow and extramedullary sites in MM. This study aimed to evaluate quantitative data on kinetics and distribution patterns of F-FDG in MM patients with regard to pelvic bone marrow plasma cell infiltration. The study included 40 patients with primary MM. Dynamic PET/CT scanning of the lower lumbar spine and pelvis was performed after the administration of F-FDG. Whole-body PET/CT studies were performed. Sites of focal increased tracer uptake were considered as highly suggestive of myelomatous involvement after taking into account the patient history and CT findings. Bone marrow of the os ilium without pathologic tracer accumulation served as reference. The evaluation of dynamic PET/CT studies was based in addition to the conventional visual (qualitative) assessment, on semiquantitative (SUV) calculations, as well as on absolute quantitative estimations after application of a 2-tissue compartment model and a noncompartmental approach. F-FDG quantitative information and corresponding distribution patterns were correlated with pelvic bone marrow plasma cell infiltration. Fifty-two myelomatous lesions were detected in the pelvis. All parameters in suspected MM lesions ranged in significantly higher levels than in reference tissue (P PET/CT imaging demonstrated 4 patterns of tracer uptake; these are as follows: negative, focal, diffuse, and mixed (focal/diffuse) tracer uptake. Patients with a mixed pattern of radiotracer uptake had the highest mean plasma cell infiltration rate in their bone marrow, whereas those with negative PET/CT scans demonstrated the lowest bone marrow plasma cell infiltration. In total, 265 focal myeloma-indicative F-FDG-avid lesions were detected, 129 of which correlated with low-dose CT osteolytic findings. No significant correlation between the number of focal lesions detected in PET

Measurements of low photon doses using LiF:Mg,Cu,P and CaF{sub 2}:Cu dosimeters

Energy Technology Data Exchange (ETDEWEB)

Prokert, K [Dresden Univ. of Technology (Germany). Inst. of Radiation Protection Physics; Mann, G [Dresden Univ. of Technology (Germany). Inst. of Radiation Protection Physics

1997-03-01

The new thermoluminophors LiF:Mg, Cu, P and CaF{sub 2}:Cu in form of pellets exhibit a significantly higher TL-response than the well-known dosimeters of the types TLD-100 (LiF:Mg, Ti), TLD-400 (CaF{sub 2}:Mn), TLD-900 (CaSO{sub 4}:Dy), etc. Furthermore, the thermoluminophor LiF:Mg, Cu, P shows besides its high sensitivity a good tissue equivalence and therefore, only a small variation of the dose response with the photon energy. The lower limits of detection of these new materials are about 5 {mu}Gy and 0.2 {mu}Gy resp. Therefore, short term measurements of absorbed dose can be realised in radiation fields at very low dose rates (environmental radiation, scattering radiation at medical equipment`s etc.) with an accuracy of {+-}10%. In the field of environmental monitoring the period of exposure can be limited to about 10 days. Using CaF{sub 2}:Cu detectors an exposure of 24 hours is sufficient for dose measurements with lower accuracy. The reusability of CaF{sub 2}:Cu pellets is guaranteed without loss of sensitivity independently of the application of different reading and annealing procedures. In the case of LiF:Mg, Cu, P detectors special procedures are needed in order to keep constant TL-properties. The results of dose measurements at low dose levels in different radiation fields demonstrate the advantages of these detector types. (orig.)

Characterisation of five candidate genes within the ETEC F4ab/ac candidate region in pigs

DEFF Research Database (Denmark)

Jacobsen, Mette Juul; Cirera Salicio, Susanna; Joller, David

2011-01-01

by haplotype sharing to a 2.5 Mb region on pig chromosome 13, a region containing 18 annotated genes. FINDINGS: The coding regions of five candidate genes for susceptibility to ETEC F4ab/ac infection (TFRC, ACK1, MUC20, MUC4 and KIAA0226), all located in the 2.5 Mb region, were investigated for the presence...... polymorphism in exon 22 of KIAA0226. Transcriptional profiles of the five genes were investigated in a porcine tissue panel including various intestinal tissues. All five genes were expressed in intestinal tissues at different levels but none of the genes were found differentially expressed between ETEC F4ab/ac...... of the amino acids composition. However, we cannot exclude that the five tested genes are bona fide candidate genes for susceptibility to ETEC F4ab/ac infection since the identified polymorphism might affect the translational apparatus, alternative splice forms may exist and post translational mechanisms might...

Neodymium-doped Sr5(PO4)3F and Sr5(VO4)3F

International Nuclear Information System (INIS)

Corker, D.L.; Nicholls, J.; Loutts, G.B.

1995-01-01

Neodymium-doped Sr 5 (PO 4 ) 3 F [neodymium strontium fluoride phosphate, (Nd,Sr) 5 (PO 4 ) 3 F] and neodymium-doped Sr 5 (VO 4 ) 3 F [neodymium strontium fluoride vanadate, (Nd,Sr) 5 (VO 4 ) 3 F] crystallize in space group P6 3 /m and are isostructural with calcium fluorophosphate, Ca 5 (PO 4 ) 3 F. There are two different Sr sites in Sr 5 (XO 4 ) 3 F, denoted Sr(1) and Sr(2). Using single-crystal X-ray diffraction the two structures were refined to R factors of 2.3 and 2.2%, respectively, showing that Nd is present at both Sr sites in (Sr,Nd) 5 (VO 4 ) 3 F but only at the Sr(2) site in (Sr,Nd) 5 (PO 4 ) 3 F. (orig.)

Reconstructive phase transition in (NH4)3TiF7 accompanied by the ordering of TiF6 octahedra.

Science.gov (United States)

Molokeev, Maxim; Misjul, S V; Flerov, I N; Laptash, N M

2014-12-01

An unusual phase transition P4/mnc → Pa\\bar 3 has been detected after cooling the (NH4)3TiF7 compound. Some TiF6 octahedra, which are disordered in the room-temperature tetragonal structure, become ordered in the low-temperature cubic phase due to the disappearance of the fourfold axis. Other TiF6 octahedra undergo large rotations resulting in huge displacements of the F atoms by 1.5-1.8 Å that implies a reconstructive phase transition. It was supposed that phases P4/mbm and Pm\\bar 3m could be a high-temperature phase and a parent phase, respectively, in (NH4)3TiF7. Therefore, the sequence of phase transitions can be written as Pm\\bar 3m → P4/mbm → P4/mnc → Pa\\bar 3. The interrelation between (NH4)3TiF7, (NH4)3GeF7 and (NH4)3PbF7 is found, which allows us to suppose phase transitions in relative compounds.

Gas phase UV and IR absorption spectra of CxF2x+1CHO (x=1-4)

DEFF Research Database (Denmark)

Hashikawa, Y; Kawasaki, M; Waterland, RL

2004-01-01

The UV and IR spectra of CxF2x+1 CHO (x = 1-4) were investigated using computational and experimental techniques. CxF2x+1CHO (x = 1-4) have broad UV absorption features centered at 300-310 nm. The maximum absorption cross-section increases significantly and shifts slightly to the red with increased...

Frequency-dependent changes in amplitude of low-frequency oscillations in depression: A resting-state fMRI study.

Science.gov (United States)

Wang, Li; Kong, Qingmei; Li, Ke; Su, Yunai; Zeng, Yawei; Zhang, Qinge; Dai, Wenji; Xia, Mingrui; Wang, Gang; Jin, Zhen; Yu, Xin; Si, Tianmei

2016-02-12

We conducted this fMRI study to examine whether the alterations in amplitudes of low-frequency oscillation (LFO) of major depressive disorder (MDD) patients were frequency dependent. The LFO amplitudes (as indexed by amplitude of low-frequency fluctuation [ALFF] and fractional ALFF [fALFF]) within 4 narrowly-defined frequency bands (slow-5: 0.01-0.027Hz, slow-4: 0.027-0.073Hz, slow-3: 0.073-0.198Hz, and slow-2: 0.198-0.25Hz) were computed using resting-state fMRI data of 35 MDD patients and 32 healthy subjects. Repeated-measures analysis of variance (ANOVA) was performed on ALFF and fALFF both within the low frequency bands of slow-4 and slow-5 and within all of the four bands. We observed significant main effects of group and frequency on ALFF and fALFF in widely distributed brain regions. Importantly, significant group and frequency interaction effects were observed in the ventromedial prefrontal cortex, inferior frontal gyrus, precentral gyrus, in a left-sided fashion, the bilateral posterior cingulate and precuneus, during ANOVA both within slow-4 and slow-5 bands and within all the frequency bands. The results suggest that the alterations of LFO amplitudes in specific brain regions in MDD patients could be more sensitively detected in the slow-5 rather than the slow-4 bands. The findings may provide guidance for the frequency choice of future resting-state fMRI studies of MDD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

HE4 Tissue Expression and Serum HE4 Levels in Healthy Individuals and Patients with Benign or Malignant Tumors

DEFF Research Database (Denmark)

Karlsen, Nikoline S; Karlsen, Mona A; Høgdall, Claus K

2014-01-01

, this review aims to systematically outline published results of HE4 tissue expression and serum HE4 levels in healthy individuals and patients with benign or malignant tumors. Our findings suggest scientific basis for a potential diagnostic ability of HE4 in gynecologic cancer and lung cancer, and further...

Synthesis and X-ray crystal structure of (OsO(3)F(2))(2)2XeOF(4) and the Raman spectra of (OsO(3)F(2))(infinity), (OsO(3)F(2))(2), and (OsO(3)F(2))(2)2XeOF(4).

Science.gov (United States)

Hughes, Michael J; Mercier, Hélène P A; Schrobilgen, Gary J

2009-05-18

The adduct, (OsO(3)F(2))(2)2XeOF(4), was synthesized by dissolution of the infinite chain polymer, (OsO(3)F(2))(infinity), in XeOF(4) solvent at room temperature followed by removal of excess XeOF(4) under dynamic vacuum at 0 degrees C. Continued pumping at 0 degrees C resulted in removal of associated XeOF(4), yielding (OsO(3)F(2))(2), a new low-temperature phase of OsO(3)F(2). Upon standing at 25 degrees C for 1(1)/(2) h, (OsO(3)F(2))(2) underwent a phase transition to the known monoclinic phase, (OsO(3)F(2))(infinity). The title compounds, (OsO(3)F(2))(infinity), (OsO(3)F(2))(2), and (OsO(3)F(2))(2)2XeOF(4) have been characterized by low-temperature (-150 degrees C) Raman spectroscopy. Crystallization of (OsO(3)F(2))(2)2XeOF(4) from XeOF(4) solution at 0 degrees C yielded crystals suitable for X-ray structure determination. The structural unit contains the (OsO(3)F(2))(2) dimer in which the OsO(3)F(3) units are joined by two Os---F---Os bridges having fluorine bridge atoms that are equidistant from the osmium centers (2.117(5) and 2.107(4) A). The dimer coordinates to two XeOF(4) molecules through Os-F...Xe bridges in which the Xe...F distances (2.757(5) A) are significantly less than the sum of the Xe and F van der Waals radii (3.63 A). The (OsO(3)F(2))(2) dimer has C(i) symmetry in which each pseudo-octahedral OsO(3)F(3) unit has a facial arrangement of oxygen ligands with XeOF(4) molecules that are only slightly distorted from their gas-phase C(4v) symmetry. Quantum-chemical calculations using SVWN and B3LYP methods were employed to calculate the gas-phase geometries, natural bond orbital analyses, and vibrational frequencies of (OsO(3)F(2))(2), (OsO(3)F(2))(2)2XeOF(4), XeOF(4), OsO(2)F(4), and (mu-FOsO(3)F(2))(2)OsO(3)F(-) to aid in the assignment of the experimental vibrational frequencies of (OsO(3)F(2))(2), (OsO(3)F(2))(2)2XeOF(4), and (OsO(3)F(2))(infinity). The vibrational modes of the low-temperature polymeric phase, (OsO(3)F(2))(infinity), have been

M2-F1 in flight during low-speed car tow

Science.gov (United States)

1963-01-01

The M2-F1 shown in flight during a low-speed car tow runs across the lakebed. Such tests allowed about two minutes to test the vehicle's handling in flight. NASA Flight Research Center (later redesignated the Dryden Flight Research Center) personnel conducted as many as 8 to 14 ground-tow flights in a single day either to test the vehicle in preparation for air tows or to train pilots to fly the vehicle before they undertook air tows. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30

MO-F-CAMPUS-J-05: Toward MRI-Only Radiotherapy: Novel Tissue Segmentation and Pseudo-CT Generation Techniques Based On T1 MRI Sequences

Energy Technology Data Exchange (ETDEWEB)

Aouadi, S; McGarry, M; Hammoud, R; Torfeh, T; Perkins, G; Al-Hammadi, N [Hamad Medical Corporation, NCCCR, Doha (Qatar)

2015-06-15

Purpose: To develop and validate a 4 class tissue segmentation approach (air cavities, background, bone and soft-tissue) on T1 -weighted brain MRI and to create a pseudo-CT for MRI-only radiation therapy verification. Methods: Contrast-enhanced T1-weighted fast-spin-echo sequences (TR = 756ms, TE= 7.152ms), acquired on a 1.5T GE MRI-Simulator, are used.MRIs are firstly pre-processed to correct for non uniformity using the non parametric, non uniformity intensity normalization algorithm. Subsequently, a logarithmic inverse scaling log(1/image) is applied, prior to segmentation, to better differentiate bone and air from soft-tissues. Finally, the following method is enrolled to classify intensities into air cavities, background, bone and soft-tissue:Thresholded region growing with seed points in image corners is applied to get a mask of Air+Bone+Background. The background is, afterward, separated by the scan-line filling algorithm. The air mask is extracted by morphological opening followed by a post-processing based on knowledge about air regions geometry. The remaining rough bone pre-segmentation is refined by applying 3D geodesic active contours; bone segmentation evolves by the sum of internal forces from contour geometry and external force derived from image gradient magnitude.Pseudo-CT is obtained by assigning −1000HU to air and background voxels, performing linear mapping of soft-tissue MR intensities in [-400HU, 200HU] and inverse linear mapping of bone MR intensities in [200HU, 1000HU]. Results: Three brain patients having registered MRI and CT are used for validation. CT intensities classification into 4 classes is performed by thresholding. Dice and misclassification errors are quantified. Correct classifications for soft-tissue, bone, and air are respectively 89.67%, 77.8%, and 64.5%. Dice indices are acceptable for bone (0.74) and soft-tissue (0.91) but low for air regions (0.48). Pseudo-CT produces DRRs with acceptable clinical visual agreement to CT

Pilot prospective evaluation of {sup 18}F-FPPRGD{sub 2} PET/CT in patients with cervical and ovarian cancer

Energy Technology Data Exchange (ETDEWEB)

Minamimoto, Ryogo; Jamali, Mehran; Gambhir, Sanjiv Sam [Stanford University, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford, CA (United States); Stanford University, Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford, CA (United States); Karam, Amer; Dorigo, Oliver [Stanford University, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford, CA (United States); Barkhodari, Amir; Iagaru, Andrei [Stanford University, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford, CA (United States)

2016-06-15

We report the effect of antiangiogenic therapy on the biodistribution of {sup 18}F-FPPRGD{sub 2} (a surrogate biomarker of integrin α{sub v}β{sub 3} expression), and the potential of {sup 18}F-FPPRGD{sub 2} to predict the prognosis in patients with cervical cancer and ovarian cancer in this clinical scenario. Data from six women, age range 30 - 59 years (mean ± SD 44.0 ± 12.5 years), who had undergone a {sup 18}F-FPPRGD{sub 2} PET/CT scan and bevacizumab-containing therapy were prospectively collected and analyzed. We compared baseline {sup 18}F-FPPRGD{sub 2} and {sup 18}F-FDG uptake in the lesions and tumor-to-background (T/B) ratios. The maximum and mean {sup 18}F-FPPRGD{sub 2} standardized uptake values (SUV{sub max} and SUV{sub mean}) were recorded for 13 normal organs, as well as in all the identified malignant lesions on the pretreatment scan and the 1-week post-treatment scan. We also measured changes in {sup 18}F-FPPRGD{sub 2} uptake from before to 1 week after treatment{sub ,} and compared them to the changes in {sup 18}F-FDG uptake from before to 6 weeks after treatment. Treatment outcomes were correlated with these changes. The uptake in lesions and T/B ratio of {sup 18}F-FPPRGD{sub 2} were lower than those of {sup 18}F-FDG (SUV{sub max} 3.7 ± 1.3 vs. 6.0 ± 1.8, P < 0.001; SUV{sub mean} 2.6 ± 0.7 vs. 4.2 ± 1.3, P < 0.001; T/B ratio based on SUV{sub max} 2.4 ± 1.0 vs. 2.6 ± 1.0, P < 0.04; T/B ratio based on SUV{sub mean} 1.9 ± 0.6 vs. 2.4 ± 1.0, P < 0.003). One patient did not return for the follow-up scan and in another patient no lesions were identified on the pretreatment scan. {sup 18}F-FPPRGD{sub 2} uptake in lesions in the remaining four patients had significantly changed 1 week after treatment (SUV{sub mean} 3.3 ± 1.0 vs. 2.7 ± 1.0, P < 0.001), while uptake in all normal tissues analyzed was not affected by treatment. One patient with clinical disease progression had a decrease in lesional {sup 18}F-FPPRGD{sub 2} SUV{sub mean} of 1

ANTIBODIES TO BENZO[A]PYRENE AND POLYMORPHISMS OF CYP1A1*2A, CYP1A2*1F, GSTT1, AND GSTM1 GENES IN HEALTHY MEN AND LUNG CANCER PATIENTS

Directory of Open Access Journals (Sweden)

A. N. Glushkov

2016-01-01

Full Text Available Some genetic polymorphisms of CYP and GST enzymes metabolizing low-molecular weight xenobiotics may represent endogenous risk factors for carcinogenesis. However, possible relationships between the enzyme activities, amounts of carcinogen adducts and synthesis of anticarcinogen antibodies in humans (including cancer patients are still poorly studied. The purpose of this study was to identify possible associations between occurrence of antibodies against benzo[a]pyrene, and frequency of genetic polymorphisms of CYP1A1*2A, CYP1A2*1F, GSTT1, GSTM1 in healthy men and in lung cancer patients. Materials and methods. We have examined 203 men with non-small cell lung cancer and 267 apparently healthy donors without respiratory diseases. A non-competitive solid phase immunoassay of antibodies to benzo[a]pyrene was performed. Analysis of polymorphic loci within CYP1A1 (rs4646903, CYP1A2 (rs762551, GSTP1 (rs1695, rs1138272 was performed by means of real-time PCR using TaqMan technology. Null-alleles of GSTM1 (del, GSTT1 (del genes were detected by multiplex PCR with real-time fluorescent assay. Results. Among the lung cancer patients, the proportion of cases with a high level of IgG antibodies to benzo[a]pyrene in carriers of GSTT1+ and GSTM1+ in conjunction with the CYP1A2*1F C allele was significantly greater than in AA homozygotes CYP1A2*1F. The risk of lung cancer was increased to 5.5 in carriers of CYP1A2*1F C allele combined with GSTT1+ and GSTM1+ at high levels of IgG antibodies to benzo [a] pyrene. In healthy male donors, we have not found differences between the incidence of low and high levels of IgG anti-benzo[a]pyrene antibodies in the carriers of certain CYP1A1*2A, CYP1A2*1F, GSTT1 and GSTM1 genotypes. Conclusions. We have first reported a relationship between CYP1 and GST gene polymorphisms and specific immune response to chemical carcinogens in lung cancer patients. Immunoassays of IgG antibodies to benzo[a]pyrene combined with molecular

Adrenergic pathway activation enhances brown adipose tissue metabolism: A [18 F]FDG PET/CT study in mice

International Nuclear Information System (INIS)

Mirbolooki, M. Reza; Upadhyay, Sanjeev Kumar; Constantinescu, Cristian C.; Pan, Min-Liang; Mukherjee, Jogeshwar

2014-01-01

Objective: Pharmacologic approaches to study brown adipocyte activation in vivo with a potential of being translational to humans are desired. The aim of this study was to examine pre- and postsynaptic targeting of adrenergic system for enhancing brown adipose tissue (BAT) metabolism quantifiable by [ 18 F]fluoro-2-deoxyglucose ([ 18 F]FDG) positron emission tomography (PET)/computed tomography (CT) in mice. Methods: A β 3 -adrenoreceptor selective agonist (CL 316243), an adenylyl cyclase enzyme activator (forskolin) and a potent blocker of presynaptic norepinephrine transporter (atomoxetine), were injected through the tail vein of Swiss Webster mice 30 minutes before intravenous (iv) administration of [ 18 F]FDG. The mice were placed on the PET/CT bed for 30 min PET acquisition followed by 10 min CT acquisition for attenuation correction and anatomical delineation of PET images. Results: Activated interscapular (IBAT), cervical, periaortic and intercostal BAT were observed in 3-dimentional analysis of [ 18 F]FDG PET images. CL 316243 increased the total [ 18 F]FDG standard uptake value (SUV) of IBAT 5-fold greater compared to that in placebo-treated mice. It also increased the [ 18 F]FDG SUV of white adipose tissue (2.4-fold), and muscle (2.7-fold), as compared to the control. There was no significant difference in heart, brain, spleen and liver uptakes between groups. Forskolin increased [ 18 F]FDG SUV of IBAT 1.9-fold greater than that in placebo-treated mice. It also increased the [ 18 F]FDG SUV of white adipose tissue (2.2-fold) and heart (5.4-fold) compared to control. There was no significant difference in muscle, brain, spleen, and liver uptakes between groups. Atomoxetine increased [ 18 F]FDG SUV of IBAT 1.7-fold greater than that in placebo-treated mice. There were no significant differences in all other organs compared to placebo-treated mice except liver (1.6 fold increase). A positive correlation between SUV levels of IBAT and CT Hounsfield unit (HU

Tissue dose in thorotrast patients

International Nuclear Information System (INIS)

Kaul, A.; Noffz, W.

1978-01-01

Absorbed doses to the liver, spleen, red marrow, lungs, kidneys, and to various parts of bone tissue were calculated for long-term burdens of intravascularly injected Thorotrast. The estimates were performed for typical injection levels of 10, 30, 50 and 100 ml, based upon best estimates of 232 Th tissue distribution, and steady state activity ratios between the subsequent daughters. Correcting for the α-particle self absorption within Thorotrast aggregates, the mean α-dose to a standard 70-kg man at 30 yr after the injection 0f 25 ml of Thorotrast is 750 rad to the liver, 2100 rad to the spleen, 270 rad to the red marrow, 60-620 rad in various parts of the lung, and 13 rad to the kidneys. Dose rates to various parts of bone tissue (bone surface, compact, and cancellous bone) were estimated by applying the ICRP model on alkaline earth metabolism to the continuous translocation of thorium daughters to bone and to the formation of thorium daughters by decay within bone tissue. The average dose to calcified bone from translocated 224 Ra with its daughters is 18 rad at 30 yr after the injection of 25 ml of Thorotrast. Considering the Spiess-Mays risk coefficient of 0.9-1.7% bone sarcoma/ 100 rad of average skeletal dose from 224 Ra and its daughters, the induction of 1.6-3.1 bone sarcomas per 1000 Thorotrast patients is predicted. (author)

Initial and mid-term results of a 4F compatible self-expanding low strut profile nitinol stent in the superficial femoral artery

International Nuclear Information System (INIS)

Muehlenbruch, G.; Brock, H.; Das, M.; Hohl, C.; Mahnken, A.H.; Wildberger, J.; Guenther, R.W.; Haage, P.

2007-01-01

Purpose: To evaluate the initial and mid-term results of a new self-expanding low strut profile nitinol stent for treatment of atherosclerotic lesions stenoses and occlusions in the superficial femoral artery (SFA). Materials and Methods: In 8 patients (4 male, 4 female, mean age 74.8 ± 8.8 years) with SFA lesions and non-satisfying results after PTA treatment alone, 10 self-expanding nitinol Xpert stents were deployed via a 4 F sheath. Stent characteristics and handling were graded by the interventionalist. Fontaine classification, duplex flow measurements and ankle brachial index (ABI) at rest and stress were taken prior and one day after stent placement. Patients were followed 3, 6 and 12 months after the procedure obtaining the same parameters at each appointment. Results: Initial stent treatment was successful in all patients. Stent handling and positioning were rated very good and safe. All patients improved clinically by at least one Fontaine stage (range before treatment: stage IIb to IV). The mean ABI at rest (stress) improved initially from 0.68 (0.70) to 1.07 (0.99). During a mean follow-up period of 8.3 months no case of clinically relevant in-stent stenosis was observed with stable values of ABI at rest and stress. (orig.)

Repeatability of hypoxia PET imaging using [{sup 18}F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial

Energy Technology Data Exchange (ETDEWEB)

Zegers, Catharina M.L.; Elmpt, Wouter van; Lambin, Philippe [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Szardenings, Katrin [Threshold Pharmaceuticals, South San Francisco, CA (United States); Kolb, Hartmuth; Chien, David [Siemens Medical Solutions USA, Inc., Siemens Molecular Imaging Biomarker Research, Culver City, CA (United States); Waxman, Alan [Cedars-Sinai Medical Center, Los Angeles, CA (United States); Subramaniam, Rathan M. [Boston University School of Medicine, Boston, MA (United States); Johns Hopkins Medical Institutions, Division of Nuclear Medicine, Russell H Morgan Department of Radiology and Radiologic Sciences, Baltimore, MD (United States); Moon, Dae Hyuk [University of Ulsan College of Medicine, Department of Nuclear Medicine, Asan Medical Center, Seoul (Korea, Republic of); Brunetti, Jacqueline C. [Holy Name Medical Center, Teaneck, NJ (United States); Srinivas, Shyam M. [Cleveland Clinic, Department of Nuclear Medicine, Imaging Institute, Cleveland, OH (United States)

2015-11-15

Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [{sup 18}F]HX4 in patients with head and neck and lung cancer. Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [{sup 18}F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUV{sub max} and SUV{sub mean}) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV{sub 1.2}). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient. All parameters of [{sup 18}F]HX4 uptake were significantly correlated between scans: SUV{sub max} (r = 0.958, p < 0.001), SUV{sub mean} (r = 0.946, p < 0.001), TBR{sub max} (r = 0.962, p < 0.001) and HV{sub 1.2} (r = 0.995, p < 0.001). The relative coefficients of repeatability were 15 % (SUV{sub mean}), 17 % (SUV{sub max}) and 17 % (TBR{sub max}). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65 ± 0.14. Repeated hypoxia PET scans with [{sup 18}F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [{sup 18}F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments. (orig.)

Atmospheric chemistry of n-CxF2x+1CHO (x = 1, 2, 3, 4)

DEFF Research Database (Denmark)

Hurley, M. D.; Ball, J. C.; Wallington, T. J.

2006-01-01

Smog chamber/FTIR techniques were used to study the atmospheric fate of n-C(x)F(2)(x)(+1)C(O) (x = 1, 2, 3, 4) radicals in 700 Torr O(2)/N(2) diluent at 298 +/- 3 K. A competition is observed between reaction with O(2) to form n-C(x)()F(2)(x)()(+1)C(O)O(2) radicals and decomposition to form n-C(x...... to the atmospheric chemistry of n-C(x)F(2)(x)(+1)C(O) radicals and their possible role in contributing to the formation of perfluorocarboxylic acids in the environment....

Spectroscopic analysis of LiHoF4 and LiErF4

DEFF Research Database (Denmark)

Christensen, H.P.

1979-01-01

The polarized absorption spectra for Ho3+ and Er3+ in LiHoF4 and LiErF4, respectively, have been recorded in the spectral interval 4000-26 000 cm-1 at 2 K. Parts of the spectra were examined at higher temperatures. The experimental levels for Ho3+ and Er3+ in LiRF4 were close to those found in Li...

Combined 18F-NaF and 18F-FDG PET/CT in the Evaluation of Sarcoma Patients.

Science.gov (United States)

Jackson, Tatianie; Mosci, Camila; von Eyben, Rie; Mittra, Erik; Ganjoo, Kristen; Biswal, Sandip; Gambhir, Sanjiv Sam; Iagaru, Andrei

2015-09-01

The combined administration of F-NaF and F-FDG in a single PET/CT scan has the potential to improve patient convenience and cancer detection. Here we report the use of this approach for patients with sarcomas. This is a retrospective review of 21 patients (12 men, 9 women; age, 19-66 years) with biopsy-proven sarcomas who had separate F-NaF PET/CT, F-FDG PET/CT, and combined F-NaF/F-FDG PET/CT scans for evaluation of malignancy. Two board-certified nuclear medicine physicians and 1 board-certified musculoskeletal radiologist were randomly assigned to review the scans. Results were analyzed for sensitivity and specificity, using linear regression and receiver operating characteristics. A total of 13 patients had metastatic disease on F-NaF PET/CT, F-FDG PET/CT, and combined F-NaF/F-FDG PET/CT. Skeletal disease was more extensive on the F-NaF PET/CT scan than on the F-FDG PET/CT in 3 patients, whereas in 1 patient, F-FDG PET/CT showed skeletal disease and the F-NaF PET/CT was negative. Extraskeletal lesions were detected on both F-FDG and combined F-NaF/F-FDG PET/CT in 20 patients, with 1 discordant finding in the lung. The combined F-NaF/F-FDG PET/CT scan allows for accurate evaluation of sarcoma patients. Further evaluation of this proposed imaging modality is warranted to identify the most suitable clinical scenarios, including initial treatment strategy and evaluation of response to therapy.

Tissue and ontogenic expression profiles of FATP1 and FATP4 ...

African Journals Online (AJOL)

ARL4

2012-08-23

an, Sichuan Province, 625014, China. 2Institute of ... tissue-specific fat deposition in poultry has been one of focused .... At 1, 14, 21, 28, 35, 42, 49, 56 and 63 days, 5 .... low density lipoprotein in production in avian species.

18F-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in insulinoma

International Nuclear Information System (INIS)

Kiesewetter, Dale O.; Ma, Ying; Niu, Gang; Quan, Qimeng; Guo, Ning; Chen, Xiaoyuan; Gao, Haokao

2012-01-01

Glucagon-like peptide type 1 (GLP-1) is an incretin peptide that augments glucose-stimulated insulin release following oral consumption of nutrients. Its message is transmitted via a G protein-coupled receptor called GLP-1R, which is colocalized with pancreatic β-cells. The GLP-1 system is responsible for enhancing insulin release, inhibiting glucagon production, inhibiting hepatic gluconeogenesis, inhibiting gastric mobility, and suppression of appetite. The abundance of GLP-1R in pancreatic β-cells in insulinoma, a cancer of the pancreas, and the activity of GLP-1 in the cardiovascular system have made GLP-1R a target for molecular imaging. We prepared 18 F radioligands for GLP-1R by the reaction of [ 18 F]FBEM, a maleimide prosthetic group, with [Cys 0 ] and [Cys 40 ] analogs of exendin-4. The binding affinity, cellular uptake and internalization, in vitro stability, and uptake and specificity of uptake of the resulting compounds were determined in an INS-1 xenograft model in nude mice. The [ 18 F]FBEM-[Cys x ]-exendin-4 analogs were obtained in good yield (34.3 ± 3.4%, n = 11), based on the starting compound [ 18 F]FBEM, and had a specific activity of 45.51 ± 16.28 GBq/μmol (1.23 ± 0.44 Ci/μmol, n = 7) at the end of synthesis. The C-terminal isomer, [ 18 F]FBEM-[Cys 40 ]-exendin-4, had higher affinity for INS-1 tumor cells (IC 50 1.11 ± 0.057 nM) and higher tumor uptake (25.25 ± 3.39 %ID/g at 1 h) than the N-terminal isomer, [ 18 F]FBEM-[Cys 0 ]-exendin-4 (IC 50 2.99 ± 0.06 nM, uptake 7.20 ± 1.26 %ID/g at 1 h). Uptake of both isomers into INS-1 tumor, pancreas, stomach, and lung could be blocked by preinjection of nonradiolabeled [Cys x ]-exendin-4 (p 18 F]FBEM-[Cys 40 ]-exendin-4 and [ 18 F]FBEM-[Cys 0 ]-exendin-4 have high affinity for GLP-1R and display similar in vitro cell internalization. The higher uptake into INS-1 xenograft tumors exhibited by [ 18 F]FBEM-[Cys 40 ]-exendin-4 suggests that this compound would be the better tracer for imaging

Expression of DMP-1 in the human pulp tissue using low level laser therapy

International Nuclear Information System (INIS)

Neto, Natalino Lourenço; Teixeira Marques, Nádia Carolina; Fernandes, Ana Paula; Silva, Thiago Cruvinel; Andrade Moreira Machado, Maria Aparecida; Oliveira, Thais Marchini; Rodini, Camila Oliveira

2015-01-01

This study aimed to evaluate the effects of low-level laser therapy (LLLT) on DMP-1 expression in pulp tissue repair of human primary teeth. Twenty mandibular primary molars were randomly assigned into the following groups: Group I—Buckley’s Formocresol (FC); Group II—Calcium Hydroxide (CH); Group III—LLLT + CH and Group IV—LLLT + Zinc oxide/Eugenol. The teeth at the regular exfoliation period were extracted for histological analysis and immunolocalization of DMP-1. Descriptive analysis was performed on the dentin pulp complex. Histopathological assessment showed internal resorption in group FC. Groups CH and LLLT + CH provided better pulpal repair due to the absence of inflammation and the formation of hard tissue barrier. These two groups presented odontoblastic layer expressing DMP-1. According to this study, low level laser therapy preceding the use of calcium hydroxide exhibited satisfactory bio-inductive activity on pulp tissue repair of human primary teeth. However, other histological and cellular studies are needed to confirm the laser tissue action and efficacy. (paper)

Tumor cell-released TLR4 ligands stimulate Gr-1+CD11b+F4/80+ cells to induce apoptosis of activated T cells.

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Liu, Yan-Yan; Sun, Ling-Cong; Wei, Jing-Jing; Li, Dong; Yuan, Ye; Yan, Bin; Liang, Zhi-Hui; Zhu, Hui-Fen; Xu, Yong; Li, Bo; Song, Chuan-Wang; Liao, Sheng-Jun; Lei, Zhang; Zhang, Gui-Mei; Feng, Zuo-Hua

2010-09-01

Gr-1(+)CD11b(+)F4/80(+) cells play important roles in tumor development and have a negative effect on tumor immunotherapy. So far, the mechanisms underlying the regulation of their immunosuppressive phenotype by classical and alternative macrophage activation stimuli are not well elucidated. In this study, we found that molecules from necrotic tumor cells (NTC-Ms) stimulated Gr-1(+)CD11b(+)F4/80(+) cells to induce apoptosis of activated T cells but not nonstimulated T cells. The apoptosis-inducing capacity was determined by higher expression levels of arginase I and IL-10 relative to those of NO synthase 2 and IL-12 in Gr-1(+)CD11b(+)F4/80(+) cells, which were induced by NTC-Ms through TLR4 signaling. The apoptosis-inducing capacity of NTC-Ms-stimulated Gr-1(+)CD11b(+)F4/80(+) cells could be enhanced by IL-10. IFN-gamma may reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells only if their response to IFN-gamma was not attenuated. However, the potential of Gr-1(+)CD11b(+)F4/80(+) cells to express IL-12 in response to IFN-gamma could be attenuated by tumor, partially due to the existence of active STAT3 in Gr-1(+)CD11b(+)F4/80(+) cells and NTC-Ms from tumor. In this situation, IFN-gamma could not effectively reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells. Tumor immunotherapy with 4-1BBL/soluble programmed death-1 may significantly reduce, but not abolish the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells in local microenvironment. Blockade of TLR4 signaling could further reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and enhance the suppressive effect of 4-1BBL/soluble form of programmed death-1 on tumor growth. These findings indicate the relationship of distinct signaling pathways with apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and emphasize the importance of blocking TLR4 signaling to prevent the induction of T cell apoptosis by Gr-1(+)CD11b(+)F4/80(+) cells.

Analysis of gene expression profiles of hepatocellular carcinomas with regard to 18F-fluorodeoxyglucose uptake pattern on positron emission tomography

International Nuclear Information System (INIS)

Lee, Jong Doo; Yun, Mijin; Lee, Jae Myun; Choi, Youjeong; Choi, Youn-Hee; Kim, Ji Su; Kim, Se Jong; Park, Jeon Han; Kim, Kyung Sik; Lee, Woo Jung; Yang, Woo Ick; Park, Young Nyun; Han, Kwang-Hyub; Yoo, Naechun; Lim, Sang Moo

2004-01-01

18 F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumour aggressiveness and prognosis in various types of cancer. In this study, the gene expression profiles of hepatocellular carcinomas (HCCs) were evaluated to determine whether HCCs with high 18 F-FDG uptake have more aggressive biological potential than those with low uptake. Surgical specimens were obtained from ten patients with HCC (six males and four females, age range 38-68 years). The tumour samples were divided into two groups based on the 18 F-FDG PET scan findings: high 18 F-FDG uptake (n=4) and low 18 F-FDG uptake (n=6). The pathological tumour grade was closely correlated with the 18 F-FDG uptake pattern: HCCs with high 18 F-FDG uptake were pathologically Edmondson-Steiner grade III, while those with low uptake were either grade II or grade II with a focal area of grade III. The total RNA was extracted from the frozen tissues of all HCCs (n=10) and adjacent non-cancerous tissue (n=7). The gene expression profiles were evaluated using an oligoDNA microarray. The HCCs with high 18 F-FDG uptake showed increased expression of 11 genes - including vascular cell adhesion molecule-1, vinexin beta and core 1 UDP-galactose: N-acetylgalactosamine-alpha-R-beta 1,3-galactosyltransferase and the natural killer cell inhibitory receptor - compared to those with low uptake (p 18 F-FDG uptake appear to have more aggressive biological properties than those with low uptake. (orig.)

26 CFR 1.672(f)-4 - Recharacterization of purported gifts.

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2010-04-01

... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Recharacterization of purported gifts. 1.672(f...)-4 Recharacterization of purported gifts. (a) In general—(1) Purported gifts from partnerships... purported gift or bequest (as defined in paragraph (d) of this section) from a partnership, the purported...

Intra-individual comparison of F-18-FLT PET and F-18 FET PET in brain tumor patients

International Nuclear Information System (INIS)

Kim, S.; Cheon, G.J.; Cho, Y.S.; Kwak, H.S.; Lee, C.H.; Choi, C.W.; Lim, S.M.

2004-01-01

Full text: The nucleoside analogue 18F-3'-deoxy-3'-fluorothymidine (FLT) for cellular proliferation and the amino acid analogue O- (2'18F-fluoroethyl)-L-tyrosine (FET) are recently developed PET-tracer for tumor imaging. Previous studies have demonstrated that the diagnostic ability of FET PET better than FDG PET in patient with newly diagnosed or recurrent brain tumors after radiation therapy. To compare findings on FLT PET with FET PET, we prospectively undertook FLT, FET and FDG PET in same patient with suspected primary/metastatic and recurrent brain tumors. Seventeen studies (FLT +FET + FDG: 13, FLT+FDG: 3, FLT +FET: 1) in 16 consecutive patients (47 ± 8.3 years, M: F 10: 6) with brain tumor (3 for initial diagnosis, 6 for therapeutic response, 6 for detecting recurrence, 1 for diagnosis and recurrence both) were included. Brain tumors were 14 gliomas (6 high-grade, 9 low-grade by the WHO classification), 2 metastatic brain tumors and 1 CNS lymphoma. 18F-FDG, FLT and FET PET were performed within two weeks. Attenuation-corrected brain images were acquired 30 minutes after injection of 370-555 MBq FDG, FLT and FET with a dedicated PET scanner (ECAT HR+ scanner, Siemens-CTI, Knoxville, Tenn., USA). Maximum SUV (max SUV) and relative uptake defined by FLT and FET accumulation within the tumor in relation to a contra lateral control region (max SUV for tumor/mean SUV for contra lateral normal gray matter) were calculated. A total of 26 tumor foci (26 on FLT and FDG, 22 on FET) in 17 studies were analysed. In most of tumor foci (20 of 22) FLT and FET PET images showed a similar extent of tumor activity. In 2 tumor foci discrepant findings were noticed; intense FLT uptake with negative FLT uptake in primary CNS lymphoma and negative FLT uptake with mild FET uptake in low-grade astrocytoma. Overall positive FLT, FET and FDG uptakes were 85 % (22/26), 90 % (18/ 20) and 58 % (15/26) respectively. Max SUV and relative FLT/FET uptake: The mean max SUV of FLT (0.97 ± 0

Arachidonic acid and lipoxin A4 attenuate alloxan-induced cytotoxicity to RIN5F cells in vitro and type 1 diabetes mellitus in vivo.

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Gundala, Naveen K V; Naidu, Vegi G M; Das, Undurti N

2017-03-01

We studied whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5F) cells against alloxan-induced apoptosis in vitro and type 1 diabetes mellitus (type 1 DM) in vivo and if so, mechanism of this beneficial action. In vitro study was conducted using RIN5F cells while in vivo study was performed in Wistar rats. The effect of PUFAs, cyclo-oxygenase and lipoxygenase inhibitors, various eicosanoids and PUFAs metabolites: lipoxin A4 (LXA4), resolvin D2 and protectin against alloxan-induced cytotoxicity to RIN5F cells and type 1 DM was studied. Expression of PDX1, P65 NF-kB and IKB in RIN5F cells and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue and plasma glucose, insulin and tumor necrosis factor-α and antioxidants, lipid peroxides and nitric oxide were measured. Of all, arachidonic acid (AA) was found to be the most effective against alloxan-induced cytotoxicity to RIN5F cells and preventing type 1 DM. Both cyclo-oxygenase and lipoxygenase inhibitors did not block the beneficial actions of AA in vitro and in vivo. Alloxan inhibited LXA4 production by RIN5F cells and in alloxan-induced type 1 DM Wistar rats. AA-treatment restored LXA4 levels to normal both in vitro and in vivo. LXA4 protected RIN5F cells against alloxan-induced cytotoxicity and prevented type 1 DM and restored expression of Nrf2, Glut2, COX2, and iNOS genes and abnormal antioxidants to near normal. AA seems to bring about its beneficial actions against alloxan-induced cytotoxicity and type 1 DM by enhancing the production of LXA4. © 2016 BioFactors, 43(2):251-271, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

Abnormal baseline brain activity in patients with neuromyelitis optica: A resting-state fMRI study

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Liu Yaou; Liang Peipeng; Duan Yunyun; Jia Xiuqin; Wang Fei; Yu Chunshui; Qin Wen; Dong Huiqing; Ye Jing; Li Kuncheng

2011-01-01

Purpose: Recent immunopathologic and MRI findings suggest that tissue damage in neuromyelitis optica (NMO) is not limited to spinal cord and optic nerve, but also in brain. Baseline brain activity can reveal the brain functional changes to the tissue damages and give clues to the pathophysiology of NMO, however, it has never been explored by resting-state functional MRI (fMRI). We used regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI to investigate how baseline brain activity changes in patients with NMO. Methods: Resting-state fMRIs collected from seventeen NMO patients and seventeen age- and sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration were further explored. Results: Our results showed that NMO patients had significantly decreased ALFF in precuneus, posterior cingulate cortex (PCC) and lingual gyrus; and increased ALFF in middle frontal gyrus, caudate nucleus and thalamus, compared to normal controls. Moderate negative correlations were found between the EDSS and ALFF in the left middle frontal gyrus (r = -0.436, p = 0.040) and the left caudate (r = -0.542, p = 0.012). Conclusion: The abnormal baseline brain activity shown by resting-state fMRI in NMO is relevant to cognition, visual and motor systems. It implicates a complex baseline brain status of both functional impairments and adaptations caused by tissue damages in these systems, which gives clues to the pathophysiology of NMO.

Abnormal baseline brain activity in patients with neuromyelitis optica: A resting-state fMRI study

Energy Technology Data Exchange (ETDEWEB)

Liu Yaou [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Liang Peipeng [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); International WIC institute, Beijing University of Technology, Beijing 100024 (China); Duan Yunyun; Jia Xiuqin; Wang Fei; Yu Chunshui; Qin Wen [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Dong Huiqing; Ye Jing [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Li Kuncheng, E-mail: likuncheng1955@yahoo.com.cn [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

2011-11-15

Purpose: Recent immunopathologic and MRI findings suggest that tissue damage in neuromyelitis optica (NMO) is not limited to spinal cord and optic nerve, but also in brain. Baseline brain activity can reveal the brain functional changes to the tissue damages and give clues to the pathophysiology of NMO, however, it has never been explored by resting-state functional MRI (fMRI). We used regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI to investigate how baseline brain activity changes in patients with NMO. Methods: Resting-state fMRIs collected from seventeen NMO patients and seventeen age- and sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration were further explored. Results: Our results showed that NMO patients had significantly decreased ALFF in precuneus, posterior cingulate cortex (PCC) and lingual gyrus; and increased ALFF in middle frontal gyrus, caudate nucleus and thalamus, compared to normal controls. Moderate negative correlations were found between the EDSS and ALFF in the left middle frontal gyrus (r = -0.436, p = 0.040) and the left caudate (r = -0.542, p = 0.012). Conclusion: The abnormal baseline brain activity shown by resting-state fMRI in NMO is relevant to cognition, visual and motor systems. It implicates a complex baseline brain status of both functional impairments and adaptations caused by tissue damages in these systems, which gives clues to the pathophysiology of NMO.

F-18 FDG PET/CT findings in a patient with bilateral orbital and gastric mucosa-associated lymphoid tissue lymphomas.

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Suga, Kazuyoshi; Yasuhiko, Kawakami; Hiyama, Atsuto; Takeda, Koumei; Matsunaga, Naofumi

2009-09-01

Orbital mucosa-associated lymphoid tissue (MALT) lymphoma is an uncommon disease, while the incidence is recently increasing. We describe the F-18 fluorodeoxyglucose positron emission tomography computerized tomography (FDG PET/CT) findings in a case of bilateral orbital MALT lymphomas with a coexisting gastric lesion. Although only the lesion in the left orbit was initially identified on MR imaging, FDG PET/CT scan unexpectedly and additionally could identify the tiny lesion of the contralateral orbit and the gastric lesion. This patient received radiotherapy to all these lesions, with a combination of rituximab monoclonal antibody therapy. The follow-up PET/CT studies at 3, 6, and 9 months and 1.5 years after treatment showed regression or disappearance of all these FDG-avid lesions. Accurate localization and staging are crucial to select an adequate treatment in MALT lymphoma at any location. This case indicates the feasibility of FDG PET/CT scan for accurate localization and staging and also for monitoring treatment in patients with orbital MALT lymphoma.

Pathogenicity of IgG in patients with IgG4-related disease.

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Shiokawa, Masahiro; Kodama, Yuzo; Kuriyama, Katsutoshi; Yoshimura, Kenichi; Tomono, Teruko; Morita, Toshihiro; Kakiuchi, Nobuyuki; Matsumori, Tomoaki; Mima, Atsushi; Nishikawa, Yoshihiro; Ueda, Tatsuki; Tsuda, Motoyuki; Yamauchi, Yuki; Minami, Ryuki; Sakuma, Yojiro; Ota, Yuji; Maruno, Takahisa; Kurita, Akira; Sawai, Yugo; Tsuji, Yoshihisa; Uza, Norimitsu; Matsumura, Kazuyoshi; Watanabe, Tomohiro; Notohara, Kenji; Tsuruyama, Tatsuaki; Seno, Hiroshi; Chiba, Tsutomu

2016-08-01

IgG4-related disease (IgG4-RD) is a systemic disease characterised by elevated serum IgG4 and IgG4-positive lymphoplasmacytic infiltration in the affected tissues. The pathogenic role of IgGs, including IgG4, in patients with IgG4-RD, however, is unknown. We examined the pathogenic activity of circulating IgGs in patients with IgG4-RD by injecting their IgGs into neonatal male Balb/c mice. Binding of patient IgGs to pancreatic tissue was also analysed in an ex vivo mouse organ culture model and in tissue samples from patients with autoimmune pancreatitis (AIP). Subcutaneous injection of patient IgG, but not control IgG, resulted in pancreatic and salivary gland injuries. Pancreatic injury was also induced by injecting patient IgG1 or IgG4, with more destructive changes induced by IgG1 than by IgG4. The potent pathogenic activity of patient IgG1 was significantly inhibited by simultaneous injection of patient IgG4. Binding of patient IgG, especially IgG1 and IgG4, to pancreatic tissue was confirmed in both the mouse model and AIP tissue samples. IgG1 and IgG4 from patients with IgG4-RD have pathogenic activities through binding affected tissues in neonatal mice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays

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Chan Koon H

2010-09-01

Full Text Available Abstract Background Neuromyelitis optica spectrum disorders (NMOSD are severe central nervous system inflammatory demyelinating disorders (CNS IDD characterized by monophasic or relapsing, longitudinally extensive transverse myelitis (LETM and/or optic neuritis (ON. A significant proportion of NMOSD patients are seropositive for aquaporin-4 (AQP4 autoantibodies. We compared the AQP4 autoantibody detection rates of tissue-based indirect immunofluorescence assay (IIFA and cell-based IIFA. Methods Serum of Chinese CNS IDD patients were assayed for AQP4 autoantibodies by tissue-based IIFA using monkey cerebellum and cell-based IIFA using transfected HEK293 cells which express human AQP4 on their cell membranes. Results In total, 128 CNS IDD patients were studied. We found that 78% of NMO patients were seropositive for AQP4 autoantibodies by cell-based IIFA versus 61% by tissue-based IFA (p = 0.250, 75% of patients having relapsing myelitis (RM with LETM were seropositive by cell-based IIFA versus 50% by tissue-based IIFA (p = 0.250, and 33% of relapsing ON patients were seropositive by cell-based IIFA versus 22% by tissue-based IIFA (p = 1.000; however the differences were not statistically significant. All patients seropositive by tissue-based IIFA were also seropositive for AQP4 autoantibodies by cell-based IIFA. Among 29 NMOSD patients seropositive for AQP4 autoantibodies by cell-based IIFA, 20 (69% were seropositive by tissue-based IIFA. The 9 patients seropositive by cell-based IIFA while seronegative by tissue-based IIFA had NMO (3, RM with LETM (3, a single attack of LETM (1, relapsing ON (1 and a single ON attack (1. Among 23 NMO or RM patients seropositive for AQP4 autoantibodies by cell-based IIFA, comparison between those seropositive (n = 17 and seronegative (n = 6 by tissue-based IIFA revealed no differences in clinical and neuroradiological characteristics between the two groups. Conclusion Cell-based IIFA is slightly more sensitive

Initial results of hypoxia imaging using 1-α-d-(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole (18F-FAZA)

International Nuclear Information System (INIS)

Postema, Ernst J.; McEwan, Alexander J.B.; Riauka, Terence A.; Kumar, Piyush; Richmond, Dacia A.; Abrams, Douglas N.; Wiebe, Leonard I.

2009-01-01

Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-α-d-(5-deoxy-5-[ 18 F]-fluoroarabinofuranosyl)-2-nitroimidazole ( 18 F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study. Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of 18 F-FAZA, then scanned 2-3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal 18 F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded. Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of 18 F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of 18 F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin's lymphoma and 6 with Hodgkin's disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased 18 F-FAZA uptake in the primary lung tumour. No side effects of the administration of 18 F-FAZA were observed. This study suggests that 18 F-FAZA may be a very useful radiopharmaceutical

Elevated 18F-NaF uptake in cricoid cartilage in a patient with laryngeal carcinoma: A case report and literature review.

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Xia, Yuxiao; Qi, Chi; Zhang, Shumao; Huang, Zhanwen; Chen, Yue

2017-12-01

Laryngeal cancer is aggressive tumor that arises from the tissues of the larynx. Although any bone can be affected, involvement of cricoid cartilage was reported very rarely, and there has been no report of 18F-sodium fluoride positron emission tomography-computed tomography (F-NaF PET-CT) and 3D PET-CT for the evaluation of cricoid cartilage invasion. A 54-year-old male discovered a protruding mass in the right anterior neck, which had rapidly increased in size over a period of 2 months. Subsequently, hoarseness, dysphagia, and dyspnea were gradually developed. F-FDG PET-CT demonstrated that the abnormal activity was located in a soft tissue mass, which was about 4.2 cm × 3.8 cm × 3.6 cm in largest dimension in the laryngeal cavity of supraglottic portion (SUVmax: 23.6). A swollen lymph node was revealed in the right submandibular region, which had intense FDG activity with a SUVmax of 18.4. However, there is a high uptake of F-FDG in the region near the bone, which is uncertain whether there is any skeletal invasion. NaF PET-CT and 3D PET-CT demonstrated increased uptake in the right side of cricoid cartilage (SUVmax: 13.2). The histopathologic examination confirmed squamous cell carcinoma of larynx. The patient underwent tracheotomy and received anti-infective treatment to relieve symptoms of dyspnea and prevent asphyxia. Clinical follow up of the patient revealed that dyspnea was significantly relieved. The case report shows the imaging features of cricoid cartilage invasion, including F-FDG PET/CT, 18F-sodium fluoride positron emission tomography-computed tomography (F-NaF PET-CT), and 3D PET-CT. Precise understanding of the invasion scope, accurately staging of laryngeal carcinoma, and choosing of the most suitable surgical scheme are the factors that lead to the optimal treatment of laryngeal neoplasms.

Tissue culture-induced genetic and epigenetic alterations in rice pure-lines, F1 hybrids and polyploids.

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Wang, Xiaoran; Wu, Rui; Lin, Xiuyun; Bai, Yan; Song, Congdi; Yu, Xiaoming; Xu, Chunming; Zhao, Na; Dong, Yuzhu; Liu, Bao

2013-05-05

Genetic and epigenetic alterations can be invoked by plant tissue culture, which may result in heritable changes in phenotypes, a phenomenon collectively termed somaclonal variation. Although extensive studies have been conducted on the molecular nature and spectrum of tissue culture-induced genomic alterations, the issue of whether and to what extent distinct plant genotypes, e.g., pure-lines, hybrids and polyploids, may respond differentially to the tissue culture condition remains poorly understood. We investigated tissue culture-induced genetic and epigenetic alterations in a set of rice genotypes including two pure-lines (different subspecies), a pair of reciprocal F1 hybrids parented by the two pure-lines, and a pair of reciprocal tetraploids resulted from the hybrids. Using two molecular markers, amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified polymorphism (MSAP), both genetic and DNA methylation alterations were detected in calli and regenerants from all six genotypes, but genetic alteration is more prominent than epigenetic alteration. While significant genotypic difference was observed in frequencies of both types of alterations, only genetic alteration showed distinctive features among the three types of genomes, with one hybrid (N/9) being exceptionally labile. Surprisingly, difference in genetic alteration frequencies between the pair of reciprocal F1 hybrids is much greater than that between the two pure-line subspecies. Difference also exists in the pair of reciprocal tetraploids, but is to a less extent than that between the hybrids. The steady-state transcript abundance of genes involved in DNA repair and DNA methylation was significantly altered in both calli and regenerants, and some of which were correlated with the genetic and/or epigenetic alterations. Our results, based on molecular marker analysis of ca. 1,000 genomic loci, document that genetic alteration is the major cause of somaclonal variation in rice

Photoluminescent properties of LiSrxBa1-xPO4:RE3+ (RE = Sm3+, Eu3+) f-f transition phosphors

International Nuclear Information System (INIS)

Tu Dong; Liang Yujun; Liu Rong; Cheng Zheng; Yang Fan; Yang Wenlong

2011-01-01

Highlights: → Novel phosphors LiSr x Ba 1-x PO 4 : Sm 3+ and LiSr x Ba 1-x PO 4 : Eu 3+ have been synthesized by solid-state reaction method. → The LiSr x Ba 1-x PO 4 : Sm 3+ and LiSr x Ba 1-x PO 4 : Eu 3+ phosphors may be potential f-f transition phosphors used in LED. → The emission intensity of the LiSr x Ba 1-x PO 4 : Sm 3+ and LiSr x Ba 1-x PO 4 : Eu 3+ phosphors can be enhanced by increasing the value of x. - Abstract: Rare-earth ions (Sm 3+ or Eu 3+ ) doped LiSr x Ba 1-x PO 4 (x = 0, 0.2, 0.4, 0.6, 0.8, 1.0) f-f transition phosphor powders were prepared by a high temperature solid-state reaction. The resulted phosphors were characterized by X-ray diffraction (XRD) and photoluminescence (PL) spectroscopy. The results of XRD indicate that the phase structure of the sample changes from LiBaPO 4 to LiSrPO 4 when x changes from 0 to 1.0. The excitation spectra indicate that only direct excitation of rare earth ions (Sm 3+ or Eu 3+ ) can be observed. The doped rare earth ions show their characteristic emission in LiSr x Ba 1-x PO 4 , i.e., Eu 3+5 D 0 - 7 F J (J = 0, 1, 2, 3, 4), Sm 3+4 G 5/2 → 6 H J (J = 5/2, 7/2, 9/2, 11/2), respectively. The dependence of the emission intensities of the LiSr x Ba 1-x PO 4 :Sm 3+ and LiSr x Ba 1-x PO 4 :Eu 3+ phosphors on the x value and Ln 3+ (Ln 3+ = Sm 3+ , Eu 3+ ) concentration is also investigated.

Short-term carcinogenicity testing of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) in E mu-pim-1 transgenic mice

DEFF Research Database (Denmark)

Sørensen, Ilona Kryspin; Mortensen, Alicja; Kristiansen, E.

1996-01-01

The usefulness of transgenic E mu-pim-1 mice over-expressing the pim-1 oncogene in lymphoid tissues, as sensitive test organisms was studied in a short-term carcinogenicity study. The mice were fed standard diet Altromin 1314 supplemented either with 0.03% 2-amino-1-methyl-6-phenylimidazo[4,5-b......]pyridine (PhIP) for 7 months or with 0.03% 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for 6 months, PhIP and IQ are heterocyclic amines formed during cooking of meat and fish and are mutagenic to bacteria and cultured mammalian cells, PhIP is a potent mouse lymphomagen, while IQ is a liver carcinogen...... to non-transgenic mice. Our results suggest that the transgenic E mu-pim-1 mouse may be a useful model for short-term carcinogenicity screening of potential genotoxic carcinogens having the lymphoid system as target tissue, The carcinogen IQ which does not have the lymphoid system as a target...

Coherent and conventional gravidynamic quantum 1/f noise

Science.gov (United States)

Handel, Peter H.; George, Thomas F.

2008-04-01

Quantum 1/f noise is a fundamental fluctuation of currents, physical cross sections or process rates, caused by infrared coupling of the current carriers to very low frequency (soft) quanta, also known as infraquanta. The latter are soft gravitons in the gravidynamic case with the coupling constant g= pGM2/Nch considered here -- soft photons in the electrodynamic case and soft transversal piezo-phonons in the lattice-dynamical case. Here p=3.14 and F=psi. Quantum 1/f noise is a new aspect of quantum mechanics expressed mainly through the coherent quantum 1/f effect 2g/pf derived here for large systems, and mainly through the conventional quantum 1/f effect for small systems or individual particles. Both effects are present in general, and their effects are superposed in a first approximation with the help of a coherence (weight) parameter s" that will be derived elsewhere for the gravitational case. The spectral density of fractional fluctuations S(dj/j,f) for j=e(hk/2pm)|F|2 is S(F2,f)/ = S(j,f)/2 = [4ps"/(1+s")]GM2/pfNch = 4.4 10E9 M2/(pfNgram2). Here s" = 2N'GM/c2=N'rs, where N' is the number of particles of mass M per unit length of the current, rs their Schwarzschild radius, and s" is our coherence (weight) parameter giving the ratio of coherent to conventional quantum 1/f contributions.

Long-term follow-up of HIV-1-infected adults who received the F4/AS01B HIV-1 vaccine candidate in two randomised controlled trials.

Science.gov (United States)

Harrer, Thomas; Dinges, Warren; Roman, François

2018-05-03

This Phase I/II, open, long-term follow-up study was conducted in antiretroviral therapy (ART)-naïve (N = 212) and ART-treated (N = 19) human immunodeficiency virus 1 (HIV-1)-infected adults, who received an HIV-1 investigational vaccine (F4/AS01 B ) or placebo in two previous studies (NCT00814762 and NCT01218113). After a minimum of two years and a maximum of four years of follow-up post-vaccination per patient, no significant differences were observed between F4/AS01 B and placebo groups in terms of viral load, CD4 + T-cell count and incidence of specific clinical events. Vaccine-induced polyfunctional CD4 + T-cells persisted up to study end and no relevant vaccine-related safety events were reported in F4/AS01 B groups. This study has been registered at ClinicalTrials.gov (NCT01092611). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Usefulness of {sup 18}F-FDG-PET/CT in Evaluating a Brainstem Glioma in an Adult Patient with Neurofibromatosis Type 1

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Treglia, Giorgio [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland); Muoio, Barbara; Del Ciello, Annemilia [Univ. of the Sacred, Rome (Italy); Bertagna, Francesco [Univ. of Brescia, Brescia (Italy)

2013-09-15

We describe a case of a brainstem glioma (BSG) occurred in an adult patient with neurofibromatosis type 1 (NF1) and evaluated by Flourine-18-Fluorodeoxyglucose-positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT). A 32-year-old male patient with NF1 underwent brain magnetic resonance imaging (MRI) for the onset of diplopia, facial paresis and cerebellar signs and symptoms. MRI showed a brainstem lesion compatible with BSG. Biopsy was not performed. {sup 18}F-FDG-PET/CT demonstrated intense {sup 18}F-FDG uptake in the brainstem lesion, suggesting an aggressive neoplasm. The patient was referred to radiotherapy but he developed rapid disease progression. In this case, {sup 18}F-FDG-PET/CT provided useful information about this rare NF1-associated tumor. Subsequently, the patient was referred to radiotherapy, but he developed rapid disease progression and died 3 months later. NF-1 is an autosomal dominant disorder characterized by multiple cafe-au-lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, and iris Lisch nodules. NF-1 is also characterized by low-grade tumors of the central and peripheral nervous system. There is also an increased risk of developing malignant tumors such as malignant peripheral nerve sheath tumors or central nervous system high-grade gliomas. NF1-associated BSGs are less common than NF1-associated optic gliomas (OGs) and seem to represent a particular entity which tend, as a whole, to have a more favorable prognosis and a more indolent course than BSGs in patients without NF1; nevertheless, some NF1-associted BSG may rapidly progress. {sup 18}F-FDG-PET/CT has demonstrated to provide useful information to the surveillance of OGs in children with NF1, particularly to identify progressive, symptomatic tumors. To the best of our knowledge, there are no data about the usefulness of {sup 18}F-FDG-PET/CT in adult patients with NF1-associated BSG. In our case, {sup 18}F-FDG-PET/CT has been useful in

Primary endobronchial marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue: CT findings 7 patients

International Nuclear Information System (INIS)

Yoon, Ra Gyoung; Kim, Mi Young; Song, Jae Woo; Chae, Eun Jin; Choi, Chang Min; Jang, Se Jin

2013-01-01

To investigate CT and 1 8F -fluorodeoxyglucose (1 8F -FDG) positron-emission tomography/CT findings of primary endobronchial marginal zone B-cell lymphoma of the bronchus-associated lymphoid tissue (BALT). From June 2006 through April 2012, seven patients (six female, one male; age range, 21-61 years; mean age, 49 years) were examined who were pathologically diagnosed with the primary endobronchial marginal zone B-cell lymphoma of BALT. We evaluated the locations and characteristics of the lesions on CT and 1 8F -FDG-PET/CT scans. The lesions were classified into the following three patterns: 1) solitary intraluminal nodule; 2) several tiny nodular protrusions; and 3) diffuse wall thickening. A solitary intraluminal nodule was observed in four patients (57.1%), several tiny nodular protrusion in two patients (28.6%), and diffuse wall thickening in one patient (14.3%). The lesions were categorized into 3 major locations: confined to the trachea (n 3), confined to the lobar bronchus (n = 2), and diffuse involvement of the trachea and both main bronchi (n = 2). All lesions demonstrated homogeneous iso-attenuation as compared with muscle on pre- and post-enhancement scans. Secondary findings in the lungs (n = 3; 42.9%) included postobstructive lobar atelectasis (n = 1), air trapping (n = 1), and pneumonia (n = 1). On 1 8F -FDG-PET/CT (n = 5), 4 lesions showed homogeneous uptake with maximum standardized uptake values (mSUV), ranging 2.3-5.7 (mean mSUV: 3.3). One lesion showed little FDG uptake. Primary endobronchial marginal zone B-cell lymphoma of the BALT manifests as three distinct patterns on CT, with the solitary intraluminal nodule presenting as the main pattern. Most lesions demonstrate homogeneous but weak FDG uptake on 1 8F -FDG-PET/CT.

Primary endobronchial marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue: CT findings 7 patients

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Yoon, Ra Gyoung; Kim, Mi Young; Song, Jae Woo; Chae, Eun Jin; Choi, Chang Min; Jang, Se Jin [University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2013-04-15

To investigate CT and 1{sup 8F}-fluorodeoxyglucose (1{sup 8F}-FDG) positron-emission tomography/CT findings of primary endobronchial marginal zone B-cell lymphoma of the bronchus-associated lymphoid tissue (BALT). From June 2006 through April 2012, seven patients (six female, one male; age range, 21-61 years; mean age, 49 years) were examined who were pathologically diagnosed with the primary endobronchial marginal zone B-cell lymphoma of BALT. We evaluated the locations and characteristics of the lesions on CT and 1{sup 8F}-FDG-PET/CT scans. The lesions were classified into the following three patterns: 1) solitary intraluminal nodule; 2) several tiny nodular protrusions; and 3) diffuse wall thickening. A solitary intraluminal nodule was observed in four patients (57.1%), several tiny nodular protrusion in two patients (28.6%), and diffuse wall thickening in one patient (14.3%). The lesions were categorized into 3 major locations: confined to the trachea (n 3), confined to the lobar bronchus (n = 2), and diffuse involvement of the trachea and both main bronchi (n = 2). All lesions demonstrated homogeneous iso-attenuation as compared with muscle on pre- and post-enhancement scans. Secondary findings in the lungs (n = 3; 42.9%) included postobstructive lobar atelectasis (n = 1), air trapping (n = 1), and pneumonia (n = 1). On 1{sup 8F}-FDG-PET/CT (n = 5), 4 lesions showed homogeneous uptake with maximum standardized uptake values (mSUV), ranging 2.3-5.7 (mean mSUV: 3.3). One lesion showed little FDG uptake. Primary endobronchial marginal zone B-cell lymphoma of the BALT manifests as three distinct patterns on CT, with the solitary intraluminal nodule presenting as the main pattern. Most lesions demonstrate homogeneous but weak FDG uptake on 1{sup 8F}-FDG-PET/CT.

Analysis of TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 in autosomal recessive congenital ichthyosis from Galicia (NW Spain): evidence of founder effects.

Science.gov (United States)

Rodríguez-Pazos, L; Ginarte, M; Fachal, L; Toribio, J; Carracedo, A; Vega, A

2011-10-01

  Mutations in six genes have been identified in autosomal recessive congenital ichthyosis (ARCI). To date, few studies have analysed the spectrum of these mutations in specific populations. We have studied the characteristics of patients with ARCI in Galicia (NW Spain). Methods  We recruited patients by contacting all dermatology departments of Galicia and the Spanish patient organization for ichthyosis. TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 were analysed in the patients and their relatives. We identified 23 patients with ARCI and estimated a prevalence of 1 : 122 000. Twenty of the patients were studied. Seventeen of them were clinically categorized as having lamellar ichthyosis (LI) and three as having congenital ichthyosiform erythroderma (CIE). TGM1 and ALOXE3 mutations were identified in 12/16 (75%) probands whereas no ALOX12B, NIPAL4 and CYP4F22 mutations were found. TGM1 mutations were found in 11/13 (85%) of LI probands. ALOXE3 mutations were identified in a single patient with CIE. Remarkably, mutations p.Arg760X, p.Asp408ValfsX21 and c.984+1G>A of TGM1 were present in six, four and two families, accounting for 41%, 23% and 14% of all TGM1 mutant alleles, respectively. The high percentage of patients with the same TGM1 mutations, together with the high number of homozygous probands (64%), indicates the existence of a strong founder effect in our population. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

F4/80 as a Major Macrophage Marker: The Case of the Peritoneum and Spleen.

Science.gov (United States)

Dos Anjos Cassado, Alexandra

2017-01-01

Tissue macrophages are a heterogeneous cell population residing in all body tissues that contribute to the maintenance of homeostasis and trigger immune activation in response to injurious stimuli. This heterogeneity may be associated with tissue-specific functions; however, the presence of distinct macrophage populations within the same microenvironment indicates that macrophage heterogeneity may also be influenced outside of tissue specialization. The F4/80 molecule was established as a unique marker of murine macrophages when a monoclonal antibody was found to recognize an antigen exclusively expressed by these cells. However, recent research has shown that F4/80 is expressed by other immune cells and is not equivalently expressed across tissue-specific macrophage lineages, including those residing in the same microenvironment, such as the peritoneum and spleen. In this context, two murine macrophage subtypes with distinct F4/80 expression patterns were recently found to coexist in the peritoneum, termed large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs). However, the presence of phenotypic and functional heterogeneous macrophage subpopulations in the spleen was already known. Thus, although F4/80 surface expression continues to be the best method to identify tissue macrophages, additional molecules must also be examined to distinguish these cells from other immune cells.

Expression of human Piwi-like genes is associated with prognosis for soft tissue sarcoma patients

International Nuclear Information System (INIS)

Greither, Thomas; Taubert, Helge; Koser, Franziska; Kappler, Matthias; Bache, Matthias; Lautenschläger, Christine; Göbel, Steffen; Holzhausen, Hans-Jürgen; Wach, Sven; Würl, Peter

2012-01-01

Argonaute genes are essential for RNA interference, stem cell maintenance and differentiation. The Piwi-like genes, a subclass of the Argonaute genes, are expressed mainly in the germline. These genes may be re-expressed in tumors, and expression of the Piwi-like genes is associated with prognosis in several types of tumors. We measured the expression of Piwi-like mRNAs (Piwi-like 2–4) in 125 soft tissue sarcoma (STS) samples by qPCRs. Statistical tests were applied to study the correlation of expression levels with tumor-specific survival for STS patients. In multivariate Cox’s regression analyses, we showed that low Piwi-like 2 and Piwi-like 4 mRNA expression were significantly associated with a worse prognosis (RR = 1.87; p = 0.032 and RR = 1.82; p = 0.039). Low expression of both genes was associated with a 2.58-fold increased risk of tumor-related death (p = 0.01). Piwi-like 4 and combined Piwi-like 2 and 4 mRNA levels correlated significantly with prognosis (RR = 3.53; p = 0.002 and RR = 5.23; p = 0.004) only for female but not for male patients. However, combined low Piwi-like 2 and 3 transcript levels were associated with worse survival (RR = 5.90; p = 0.02) for male patients. In this study, we identified a significant association between the expression of Piwi-like 2 and 4 mRNAs and the tumor-specific survival of soft tissue sarcoma patients. Furthermore, a connection between sex and the impact of Piwi-like mRNA expressions on STS patients’ prognosis was shown for the first time

28 CFR 55.5 - Coverage under section 4(f)(4).

Science.gov (United States)

2010-07-01

... THE VOTING RIGHTS ACT REGARDING LANGUAGE MINORITY GROUPS Nature of Coverage § 55.5 Coverage under section 4(f)(4). (a) Coverage formula. Section 4(f)(4) applies to any State or political subdivision in...) Coverage may be determined with regard to section 4(f)(4) on a statewide or political subdivision basis. (1...

Synthesis and Molecular Structure of 6-Amino-3-benzylmercapto-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H-one

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Gene-Hsiang Lee

2006-03-01

Full Text Available The title compound 6-amino-3-benzylmercapto-1,2,4-triazolo[3,4-f][1,2,4]-triazin-8(7H-one (4, molecular formula C11H10N6OS, was obtained by the reaction of3-amino-2-benzyl-6-hydrazino-1,2,4-triazin-5(2H-one (3 with carbon disulfide in awater/pyridine mixture. Compound 4 can also be synthesized by reacting6-amino-3(2Hmercapto-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H-one (7 with benzylbromide in methanolic ammonia water. The compound crystallizes in the monoclinicspace group P21/c with a = 7.2926(15, b = 14.456(2, c = 11.436(2 å, β = 105.30(2°, V= 1162.9(4 å3 and Z = 4, resulting in a density Dcalc of 1.567 g/cm3. Molecules of 4 arelinked by extensive intermolecular N-H···N and N-H···O hydrogen bonding [graph set R22 (9]. The structure is further stabilized by π-π stacking interactions. 2

A low-fat Diet improves insulin sensitivity in patients with type 1 diabetes

DEFF Research Database (Denmark)

Rosenfalck, AM; Almdal, Thomas Peter; Viggers, Lone

2006-01-01

diet (P = 0.039). The daily protein and carbohydrate intake increased (+4.4% of total energy intake, P = 0.0049 and +2.5%, P = 0.34, respectively), while alcohol intake decreased (-3.2% of total energy intake, P = 0.02). There was a significant improvement in insulin sensitivity on the isocaloric, low-fat......AIMS: To compare the effects on insulin sensitivity, body composition and glycaemic control of the recommended standard weight-maintaining diabetes diet and an isocaloric low-fat diabetes diet during two, 3-month periods in patients with Type 1 diabetes. METHODS: Thirteen Type 1 patients were...... by the insulin clamp technique at baseline and after each of the diet intervention periods. RESULTS: On an isocaloric low-fat diet, Type 1 diabetic patients significantly reduced the proportion of fat in the total daily energy intake by 12.1% (or -3.6% of total energy) as compared with a conventional diabetes...

Tissue inhibitor of metalloproteinases-1 in breast cancer

DEFF Research Database (Denmark)

Würtz, Sidse Ørnbjerg; Rasmussen, Anne-Sofie Schrohl; Sørensen, Nanna Møller

2005-01-01

Whether patients diagnosed with primary breast cancer are offered adjuvant systemic therapy following surgical removal of the tumor is based on prognosis. Prognosis is estimated in every patient using established prognostic variables. Unfortunately, when using the currently available prognostic...... parameters a significant proportion of patients are over-treated. Thus, in order to improve stratification of breast cancer patients, additional prognostic factors need to be identified. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is one of the promising candidates for new prognostic markers in breast...... cancer, as a number of studies have demonstrated an association between high tumor-tissue levels of TIMP-1 mRNA as well as TIMP-1 protein and a poor prognosis of breast cancer patients. TIMP-1 is a member of the TIMP family, currently comprising four members (TIMP-1-4), and its main function...

Characterizing IgG4-related disease with 18F-FDG PET/CT: a prospective cohort study

International Nuclear Information System (INIS)

Zhang, Jingjing; Ma, Yanru; Niu, Na; Wang, Xinwei; Li, Fang; Zhu, Zhaohui; Chen, Hua; Lin, Wei; Zhang, Fengchun; Zhang, Wen; Xiao, Yu; Liang, Zhiyong

2014-01-01

IgG4-related disease (IgG4-RD) is an increasingly recognized clinicopathological disorder with immune-mediated inflammatory lesions mimicking malignancies. A cohort study was prospectively designed to investigate the value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in characterizing IgG4-RD. Thirty-five patients diagnosed with IgG4-RD according to the consensus criteria were enrolled with informed consent. All patients underwent baseline 18 F-FDG PET/CT evaluation. Among them, 29 patients underwent a second 18 F-FDG PET/CT scan after 2 to 4 weeks of steroid-based therapy. All 35 patients were found with 18 F-FDG-avid hypermetabolic lesion(s); 97.1 % (34/35) of these patients showed multi-organ involvement. Among the 35 patients, 71.4 % (25/35) patients were found with more organ involvement on 18 F-FDG PET/CT than conventional evaluations including physical examination, ultrasonography, and computed tomography (CT). 18 F-FDG PET/CT demonstrated specific image characteristics and pattern of IgG4-RD, including diffusely elevated 18 F-FDG uptake in the pancreas and salivary glands, patchy lesions in the retroperitoneal region and vascular wall, and multi-organ involvement that cannot be interpreted as metastasis. Comprehensive understanding of all involvement aided the biopsy-site selection in seven patients and the recanalization of ureteral obstruction in five patients. After 2 to 4 weeks of steroid-based therapy at 40 mg to 50 mg prednisone per day, 72.4 % (21/29) of the patients showed complete remission, whereas the others exhibited > 81.8 % decrease in 18 F-FDG uptake. F-FDG PET/CT is a useful tool for assessing organ involvement, monitoring therapeutic response, and guiding interventional treatment of IgG4-RD. The image pattern is suggested to be updated into the consensus diagnostic criteria for IgG4-RD. (orig.)

Diagnostic value of tissue polypeptide specific antigen in serum for patients with pancreatic carcinoma

International Nuclear Information System (INIS)

Lu Yun; Liu Xingdang; Li Ding; Dei Shouzhen

2009-01-01

Objective: To compare the diagnostic value of tissue polypeptide specific antigen (TPS) in serum, with the carbohydrate antigens (CA) 19-9, CA50, CA125 and CA242 in pancreatic carcinoma. Methods: Serum TPS was measured with enzyme linked immunosorbent assay (ELISA). CA19-9 and CA125 were measured with chemiluminescent immunoassay. CAS0 and CA242 were measured with immunoradiometric assay in 33 patients with pancreatitis, 34 patients with pathologically proven pancreatic carcinoma, and 35 patients with non-pancreatic malignancies. Statistic analysis was carried out with SPSS 9.0 software. Results: Patients with pancreatic carcinoma had relatively higher levels of TPS [(386.5 ± 315. 1) U/L] and CA19-9 [(10 820.9 ± 389.7) kU/L] when compared with patients with pancreatitis [(86. 2 ± 28.1) U/L and (61.5 ± 24.7) kU/L, respectively; F = 936. 42, P < 0. 001 ; F = 2217. 09, P < 0. 001], with a sensitivity and a specificity of 70.6% (48/68) and 57.4% (39/68), respectively, for TPS, and 82.4% (28/34) and 77.9% (53/68), respectively, for CA19-9. Diagnostic performance was further improved when TPS was assayed in combination with CA19-9, CA50, CA125 and CA242. Conclusion: Serum TPS has an incremental value in complementing CA19-9 in the diagnosis of pancreatic carcinoma. (authors)

Density Functional Study of Structures and Electron Affinities of BrO4F/BrO4F-

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Wei Li

2009-07-01

Full Text Available The structures, electron affinities and bond dissociation energies of BrO4F/BrO4F− species have been investigated with five density functional theory (DFT methods with DZP++ basis sets. The planar F-Br…O2…O2 complexes possess 3A' electronic state for neutral molecule and 4A' state for the corresponding anion. Three types of the neutral-anion energy separations are the adiabatic electron affinity (EAad, the vertical electron affinity (EAvert, and the vertical detachment energy (VDE. The EAad value predicted by B3LYP method is 4.52 eV. The bond dissociation energies De (BrO4F → BrO4-mF + Om (m = 1-4 and De- (BrO4F- → BrO4-mF- + Om and BrO4F- → BrO4-mF + Om- are predicted. The adiabatic electron affinities (EAad were predicted to be 4.52 eV for F-Br…O2…O2 (3A'← 4A' (B3LYP method.

{sup 18}F-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in insulinoma

Energy Technology Data Exchange (ETDEWEB)

Kiesewetter, Dale O.; Ma, Ying; Niu, Gang; Quan, Qimeng; Guo, Ning; Chen, Xiaoyuan [National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), Bethesda, MD (United States); Gao, Haokao [National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), Bethesda, MD (United States); Fourth Military Medical University, Department of Cardiology, Xijing Hospital, Xi' an (China)

2012-03-15

Glucagon-like peptide type 1 (GLP-1) is an incretin peptide that augments glucose-stimulated insulin release following oral consumption of nutrients. Its message is transmitted via a G protein-coupled receptor called GLP-1R, which is colocalized with pancreatic {beta}-cells. The GLP-1 system is responsible for enhancing insulin release, inhibiting glucagon production, inhibiting hepatic gluconeogenesis, inhibiting gastric mobility, and suppression of appetite. The abundance of GLP-1R in pancreatic {beta}-cells in insulinoma, a cancer of the pancreas, and the activity of GLP-1 in the cardiovascular system have made GLP-1R a target for molecular imaging. We prepared {sup 18}F radioligands for GLP-1R by the reaction of [{sup 18}F]FBEM, a maleimide prosthetic group, with [Cys{sup 0}] and [Cys{sup 40}] analogs of exendin-4. The binding affinity, cellular uptake and internalization, in vitro stability, and uptake and specificity of uptake of the resulting compounds were determined in an INS-1 xenograft model in nude mice. The [{sup 18}F]FBEM-[Cys{sup x}]-exendin-4 analogs were obtained in good yield (34.3 {+-} 3.4%, n = 11), based on the starting compound [{sup 18}F]FBEM, and had a specific activity of 45.51 {+-} 16.28 GBq/{mu}mol (1.23 {+-} 0.44 Ci/{mu}mol, n = 7) at the end of synthesis. The C-terminal isomer, [{sup 18}F]FBEM-[Cys{sup 40}]-exendin-4, had higher affinity for INS-1 tumor cells (IC{sub 50} 1.11 {+-} 0.057 nM) and higher tumor uptake (25.25 {+-} 3.39 %ID/g at 1 h) than the N-terminal isomer, [{sup 18}F]FBEM-[Cys{sup 0}]-exendin-4 (IC{sub 50} 2.99 {+-} 0.06 nM, uptake 7.20 {+-} 1.26 %ID/g at 1 h). Uptake of both isomers into INS-1 tumor, pancreas, stomach, and lung could be blocked by preinjection of nonradiolabeled [Cys{sup x}]-exendin-4 (p < 0.05). [{sup 18}F]FBEM-[Cys{sup 40}]-exendin-4 and [{sup 18}F]FBEM-[Cys{sup 0}]-exendin-4 have high affinity for GLP-1R and display similar in vitro cell internalization. The higher uptake into INS-1 xenograft tumors

SU-G-IeP4-07: Feasibility of Low Dose 18FDG PET in Pediatric Oncology Patients

International Nuclear Information System (INIS)

Zhang, J; Binzel, K; Hall, NC; Natwa, M; Knopp, MI; Knopp, MV

2016-01-01

Purpose: To evaluate and demonstrate the feasibility of low dose FDG PET in pediatric oncology patients using virtual dose reduction as well as true patients PET/CT scans. Methods: Wholebody 18F-FDG PET/CT of 39 clinical pediatric patients (0.16±0.06MBq/kg) were scanned on a Gemini TF 64 system at 75±5 min post FDG injection using 3min/bed. Based on the 180s/bed listmode PET data, subsets of total counts in 120s, 90s, 60s, 30s and 15s per bed position were extracted for PET reconstruction to simulate lower dose PET at 2/3th, 1/2th, 1/3th, 1/6th and 1/12th dose levels. PET/CT scans of Jaszczak PET phantom with 6 hot hollow spheres varying with sizes and contrast ratios were performed (real PET versus simulated PET) to validate the methodology of virtual dose PET simulation. Region of interests (ROIs) were placed on lesions and normal anatomical tissues with quantitative and qualitative assessment performed. Significant lower FDG dose PET/CT of 5 research adolescents were scanned to validate the proposal and low dose PET feasibility. Results: Although all lesions are visible on the 1/12th dose PET, overall PET image quality appears to be influenced in a multi-factorial way. 30%–60% dose reduction from current standard of care FDG PET is recommended to maintain equivalent quality and PET quantification. An optimized BMI-based FDG administration is recommended (from 1.1±0.5 mCi for BMI 30). A linear lowest “Dose-BMI” relationship is given. SUVs from 1/12th to full dose PETs were identified as consistent (R2 = 1.08, 0.99, 1.01, 1.00 and 0.98). No significant variances of count density, SUV and SNR were found across certain dose ranges (p<0.01). Conclusion: Pediatric PET/CT can be performed using current time-of-flight systems at substantially lower PET doses (30–60%) than the standard of care PET/CT without compromising qualitative and quantitative image quality in clinical.

Radiosynthesis of (S)-["1"8F]T1: The first PET radioligand for molecular imaging of α3β4 nicotinic acetylcholine receptors

International Nuclear Information System (INIS)

Sarasamkan, Jiradanai; Fischer, Steffen; Deuther-Conrad, Winnie; Ludwig, Friedrich-Alexander; Scheunemann, Matthias; Arunrungvichian, Kuntarat; Vajragupta, Opa; Brust, Peter

2017-01-01

Recent pharmacologic data revealed the implication of α3β4 nicotinic acetylcholine receptors (nAChRs) in nicotine and drug addiction. To image α3β4 nAChRs in vivo, we aimed to establish the synthesis of a ["1"8F]-labelled analog of the highly affine and selective α3β4 ligand (S)-3-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)quinuclidine ((S)-T1). (S)-["1"8F]T1 was synthesized from ethynyl-4-["1"8F]fluorobenzene (["1"8F]5) and (S)-azidoquinuclidine by click reaction. After a synthesis time of 130 min (S)-["1"8F]T1 was obtained with a radiochemical yield (non-decay corrected) of 4.3±1.3%, a radiochemical purity of >99% and a molar activity of >158 GBq/μmol. The brain uptake and the brain-to-blood ratio of (S)-["1"8F]T1 in mice at 30 min post injection were 2.02 (SUV) and 6.1, respectively. According to an ex-vivo analysis, the tracer remained intact (>99%) in brain. Only one major radiometabolite was detected in plasma and urine samples. In-vitro autoradiography on pig brain slices revealed binding of (S)-["1"8F]T1 to brain regions associated with the expression of α3β4 nAChRs, which could be reduced by the α3β4 nAChR selective drug AT-1001. These findings make (S)-["1"8F]T1 a potential tool for the non-invasive imaging of α3β4 nAChRs in the brain by PET. - Highlights: • (S)-["1"8F]T1 is a promising α3ß4 nAChR ligand for PET imaging. • The novel radioligand (S)-["1"8F]T1 was synthesized by click reaction. • The potential of (S)-["1"8F]T1 was shown by in vitro autoradiography and in vivo evaluation in mice.

EPIDEMIOLOGY AND SURVIVAL OF PATIENTS WITH MALIGNANT TUMORS OF CONNECTIVE AND SOFT TISSUE

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V. M. Merabishvili

2015-01-01

Full Text Available Introduction. Malignant tumors of connective and soft tissue are met relatively rare, although in general in Russia each year more than 1.500 new cases are registered. On five administrative territories of Russia during a year there are recorded less than 5 new cases of malignant tumors of connective and soft tissue (Yamal-Nenets A.R. – 4; Tuva Republic – 0, Magadan Region – 3; Chukotka A.R. – 0; Jewish A.R. – 4. More seldom data on these patients’ survival are published. Purpose of study. To estimate dynamics of incidence of malignant tumors of connective and soft tissue on the basis of public reporting, to calculate the index accuracy and observed and relative survival rates by histological forms, including sarcomas. Material and methods. To perform a detailed study there were selected, for two periods of observation, respectively 1054 patients (1995–2001 and 919 patients (2002–2008. Estimation of survival was carried out using software, which had been developed together with Ltd. «Novel» (Director – T.L.Tsvetkova, Ph.D.. results of study. The most typical incidence rate for of malignant tumors of connective and soft tissue (S47, 49 that are presented by  cancer registries of different countries is from 1.5 to 2.5 0/   in men and 1.5–2.0 0/   in women. Dynamics  of morbidity of the Russian population, Moscow and St. Petersburg indicates that the level of standardized  incidence rates is in the range of 2.0 0/   in men and within 1.5 0/   in women. The mortality rate in 2013  was respectively for men and women in Russia in total 1.7 0/   and 1.13 0/   , in Moscow – 1.42 0/   and  1.24 0/   , in St. Petersburg – 1.88 0/   and 1.26 0/   . The index accuracy for both sexes in Russia is 0.88,  in Moscow – 1.2; in St. Petersburg – 1.4. This index should be used for the site of these diseases with high fatality. According to official data a one-year lethality of patients with tumors of connective and soft

CT-based compartmental quantification of adipose tissue versus body metrics in colorectal cancer patients

International Nuclear Information System (INIS)

Nattenmueller, Johanna; Hoegenauer, Hanna; Grenacher, Lars; Kauczor, Hans-Ulrich; Boehm, Juergen; Ulrich, Cornelia; Scherer, Dominique; Paskow, Michael; Gigic, Biljana; Schrotz-King, Petra

2016-01-01

While obesity is considered a prognostic factor in colorectal cancer (CRC), there is increasing evidence that not simply body mass index (BMI) alone but specifically abdominal fat distribution is what matters. As part of the ColoCare study, this study measured the distribution of adipose tissue compartments in CRC patients and aimed to identify the body metric that best correlates with these measurements as a useful proxy for adipose tissue distribution. In 120 newly-diagnosed CRC patients who underwent multidetector computed tomography (CT), densitometric quantification of total (TFA), visceral (VFA), intraperitoneal (IFA), retroperitoneal (RFA), and subcutaneous fat area (SFA), as well as the M. erector spinae and psoas was performed to test the association with gender, age, tumor stage, metabolic equivalents, BMI, waist-to-height (WHtR) and waist-to-hip ratio (WHR). VFA was 28.8 % higher in men (p_V_F_A<0.0001) and 30.5 % higher in patients older than 61 years (p_V_F_A<0.0001). WHtR correlated best with all adipose tissue compartments (r_V_F_A=0.69, r_T_F_A=0.84, p<0.0001) and visceral-to-subcutaneous-fat-ratio (VFR, r_V_F_R=0.22, p=<0.05). Patients with tumor stages III/IV showed significantly lower overall adipose tissue than I/II. Increased M. erector spinae mass was inversely correlated with all compartments. Densitometric quantification on CT is a highly reproducible and reliable method to show fat distribution across adipose tissue compartments. This distribution might be best reflected by WHtR, rather than by BMI or WHR. (orig.)

[PAL-1 5G/4G polymorphism in patients with systemic lupus erythematosus].

Science.gov (United States)

Savov, A; Andonova, S; Tanev, D; Robeva, R; Marincheva, Ts; Tomova, A; Kumanov, Ph; Rashkov, R; Kolarov, Zl

2014-01-01

Systemic lupus erythematosus (SLE) is a connective tissue disease affecting predominantly women that has been widely associated with obstetric complications. Inherited thrombophilias are significant risk factors for pregnancy loss, but their role in patients with SLE, and especially in those without concomitant secondary antiphospholipid syndrome (APS) has not been clarified. The aim of the present study was to study PAI-1 5G/4G polymorphism in women with lupus. A total of 103 SLE patients as well as 69 healthy volunteers were genotyped for PAI-1 5G/4G (rs1799889). No significant differences in the PAI-1 5G/4G genotype prevalence between patients and controls were found. After exclusion of the women with secondary APS, the frequency of pregnancies and spontaneous abortions, as well as the number of live births were similar in the studied patients with different PAI-1 genotype (p> 0.05). PAI-1 5G/4G polymorphism was not significantly related to any of the lupus ACR criteria or disease activity (p > 0.05), but it could influence the platelet number in the studied patients (263.52 ± 91.10 [5G/5G genotype] versus 210.12 ± 71.79 [4G/4G genotype], p = 0.023). In conclusion, our results showed that PAI-1 4G/5G polymorphism did not worsen the reproductive outcome in SLE women without secondary APS.

LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation.

Science.gov (United States)

Milkereit, Ruth; Persaud, Avinash; Vanoaica, Liviu; Guetg, Adriano; Verrey, Francois; Rotin, Daniela

2015-05-22

Mammalian target of rapamycin 1 (mTORC1), a master regulator of cellular growth, is activated downstream of growth factors, energy signalling and intracellular essential amino acids (EAAs) such as Leu. mTORC1 activation occurs at the lysosomal membrane, and involves V-ATPase stimulation by intra-lysosomal EAA (inside-out activation), leading to activation of the Ragulator, RagA/B-GTP and mTORC1 via Rheb-GTP. How Leu enters the lysosomes is unknown. Here we identified the lysosomal protein LAPTM4b as a binding partner for the Leu transporter, LAT1-4F2hc (SLC7A5-SLAC3A2). We show that LAPTM4b recruits LAT1-4F2hc to lysosomes, leading to uptake of Leu into lysosomes, and is required for mTORC1 activation via V-ATPase following EAA or Leu stimulation. These results demonstrate a functional Leu transporter at the lysosome, and help explain the inside-out lysosomal activation of mTORC1 by Leu/EAA.

  Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525)

DEFF Research Database (Denmark)

Rasmussen, Anne-Sofie Schrohl; Look, Maxime P.; Meijer-van Gelder, Marion E.

tumor tissue TIMP-1 concentrations are associated with decreased benefit from adjuvant chemotherapy. Especially in the group treated with anthracycline-based therapy, there is a strong tendency for TIMP-1 high tumors to be less sensitive to the treatment. The anthracycline-treated group, however...... Predictive markers are needed to guide planning of adjuvant therapy for patients with breast cancer. We have recently shown that high tumor tissue levels of TIMP-1 are associated with decreased response to chemotherapy in metastatic breast cancer patients (Schrohl et al, Clin Cancer Res, 2006......) suggesting that TIMP-1 may be a predictive marker in breast cancer patients. Purpose: This study investigates the association of tumor tissue TIMP-1 levels with response to adjuvant chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil) or an anthracycline-containing regimen. Patients...

Nuclear factor 1 regulates adipose tissue-specific expression in the mouse GLUT4 gene

International Nuclear Information System (INIS)

Miura, Shinji; Tsunoda, Nobuyo; Ikeda, Shinobu; Kai, Yuko; Cooke, David W.; Lane, M. Daniel; Ezaki, Osamu

2004-01-01

Previous studies demonstrated that an adipose tissue-specific element(s) (ASE) of the murine GLUT4 gene is located between -551 and -506 in the 5'-flanking sequence and that a high-fat responsive element(s) for down-regulation of the GLUT4 gene is located between bases -701 and -552. A binding site for nuclear factor 1 (NF1), that mediates insulin and cAMP-induced repression of GLUT4 in 3T3-L1 adipocytes is located between bases -700 and -688. To examine the role of NF1 in the regulation of GLUT4 gene expression in white adipose tissues (WAT) in vivo, we created two types of transgenic mice harboring mutated either 5' or 3' half-site of NF1-binding sites in GLUT4 minigene constructs. In both cases, the GLUT4 minigene was not expressed in WAT, while expression was maintained in brown adipose tissue, skeletal muscle, and heart. This was an unexpected finding, since a -551 GLUT4 minigene that did not have the NF1-binding site was expressed in WAT. We propose a model that explains the requirement for both the ASE and the NF1-binding site for expression of GLUT4 in WAT

Quantitative PET Imaging of Tissue Factor Expression Using 18F-labled Active Site Inhibited Factor VII

DEFF Research Database (Denmark)

Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E

2016-01-01

Tissue factor (TF) is up regulated in many solid tumors and its expression is linked to tumor angiogenesis, invasion, metastasis and prognosis. A non-invasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII (FVII) is the natural ligand to TF. Here we...... report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of FVII. METHODS: Active site inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4......-[(18)F]-fluorobenzoate ([(18)F]SFB) and purified. The corresponding product, [(18)F]FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small animal PET/CT imaging 1, 2 and 4 hours after injection. Ex vivo biodistribution was performed...

Evaluation of 4-[18F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds

International Nuclear Information System (INIS)

Kim, Dong Hyun; Choe, Yearn Seong; Kim, Byung-Tae

2010-01-01

Click chemistry is a useful approach for the preparation of novel radiopharmaceuticals. In this study, we evaluated 4-[ 18 F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds. Our results showed that nucleophilic substitution of 4-tosyloxy-1-butyne with K[ 18 F]F produces vinyl acetylene as well as 4-[ 18 F]fluoro-1-butyne, while the same reaction using 5-tosyloxy-1-pentyne gives exclusively 5-[ 18 F]fluoro-1-pentyne. Thus, ω-[ 18 F]fluoro-1-alkynes with chain lengths longer than four carbons may be better radiolabeled synthons for use in click chemistry.

Derivation of induced pluripotent stem cells from a familial Alzheimer's disease patient carrying the L282F mutation in presenilin 1

DEFF Research Database (Denmark)

Poon, Anna Fong-Yee; Li, Tong; Pires, Carlota

2016-01-01

Mutations in presenilin 1 (PSEN1) lead to the most aggressive form of familial Alzheimer's disease (AD). Human induced pluripotent stem cells (hiPSCs) derived from AD patients can be differentiated and used for disease modeling. Here, we derived hiPSC from skin fibroblasts obtained from an AD...... patient carrying a L282F mutation in PSEN1. We transfected skin fibroblasts with episomal iPSC reprogramming vectors targeting human OCT4, SOX2, L-MYC, KLF4, NANOG, LIN28, and short hairpin RNA against TP53. Our hiPSC line, L282F-hiPSC, displayed typical stem cell characteristics with consistent...... expression of pluripotency genes and the ability to differentiation into the three germ layers....

Efficiency, safety, and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog

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Shimizu Y

2015-03-01

Full Text Available Yoshie Shimizu,1 Shunsuke Nakakura,1 Makiko Nishiyama,1 Hitoshi Tabuchi,1 Yoshiaki Kiuchi2 1Department of Ophthalmology, Saneikai Tsukazaki Hospital, Himeji, 2Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan Background: We investigated the efficiency, safety and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog.Methods: We initially enrolled 44 eyes from 44 primary open angle glaucoma patients, and a total of 42 patients completed the study. All patients were under treatment with various prostaglandin F2α analogs and dorzolamide 1%/timolol 0.5%. While maintaining the prostaglandin F2α analog, dorzolamide 1%/timolol 0.5% was switched to brinzolamide 1%/timolol 0.5%. Conjunctival hyperemia, superficial punctate keratopathy, and intraocular pressure (IOP were evaluated at baseline and at 4, 12, and 24 weeks. Adverse events and patient preferences, measured using a questionnaire at study initiation and at 24 weeks, were also noted.Results: The IOP was 17.7±1.7, 16.8±2.6, 16.7±2.2, and 16.7±2.4 mmHg at baseline and at 4, 12, and 24 weeks, respectively, with no significant differences in IOP values at any time point (P=0.117, one-way analysis of variance. In addition, no significant differences were found in the incidence of conjunctival hyperemia or SPK score at any time point (all P>0.5, by Kruskal–Wallis test. Based on the evaluation of side effects using the questionnaire, stinging/burning was less common (P=0.042, while blurred vision was more common (P=0.003, after switching to brinzolamide 1%/timolol 0.5%. Regarding patient preferences, 13 patients (31% preferred dorzolamide 1%/timolol 0.5%, 12 patients (29% preferred brinzolamide 1%/timolol 0.5%, and 17 patients (40% preferred neither.Conclusion: When switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1

Comparisons of [18F]-1-deoxy-1-fluoro-scyllo-inositol with [18F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

International Nuclear Information System (INIS)

McLarty, Kristin; Moran, Matthew D.; Scollard, Deborah A.; Chan, Conrad; Sabha, Nesrin; Mukherjee, Joydeep; Guha, Abhijit; McLaurin, JoAnne; Nitz, Mark; Houle, Sylvain; Wilson, Alan A.; Reilly, Raymond M.; Vasdev, Neil

2011-01-01

Introduction: The aim of the study was to evaluate the uptake of [ 18 F]-1-deoxy-1-fluoro-scyllo-inositol ([ 18 F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [ 18 F]-2-fluoro-2-deoxy-D-glucose ([ 18 F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [ 18 F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [ 18 F]-scyllo-inositol and [ 18 F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. Results: The radiosynthesis of [ 18 F]-scyllo-inositol was automated with good radiochemical yields (24.6%±3.3%, uncorrected for decay, 65±2 min, n=5) and high specific activities (≥195 GBq/μmol at end of synthesis). Uptake of [ 18 F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [ 18 F]-FDG (4.6±0.5 vs. 5.5±2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [ 18 F]-scyllo-inositol in inflammation was lower than [ 18 F]-FDG. While uptake of [ 18 F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [ 18 F]-FDG, the tumour-to-brain ratio was significantly higher (10.6±2.5 vs. 2.1±0.6; P=.001). Conclusions: Consistent with biodistribution studies, uptake of [ 18 F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [ 18 F]-FDG. The tumour-to-brain ratio of [ 18 F]-scyllo-inositol was also significantly higher than that of [ 18 F]-FDG for visualizing intracranial glioma xenografts in NOD SCID mice, giving a better contrast. -- Graphical Abstract: Display Omitted

Initial results of hypoxia imaging using 1-{alpha}-d-(5-deoxy-5-[{sup 18}F]-fluoroarabinofuranosyl)-2-nitroimidazole ({sup 18}F-FAZA)

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Postema, Ernst J.; McEwan, Alexander J.B.; Riauka, Terence A.; Kumar, Piyush; Richmond, Dacia A.; Abrams, Douglas N. [University of Alberta, Department of Oncology, Edmonton, Alberta (Canada); Wiebe, Leonard I. [University of Alberta, Faculty of Pharmacy and Pharmaceutical Sciences, Edmonton, Alberta (Canada)

2009-10-15

Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-{alpha}-d-(5-deoxy-5-[{sup 18}F]-fluoroarabinofuranosyl)-2-nitroimidazole ({sup 18}F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study. Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of {sup 18}F-FAZA, then scanned 2-3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal {sup 18}F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded. Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of {sup 18}F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of {sup 18}F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin's lymphoma and 6 with Hodgkin's disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased {sup 18}F-FAZA uptake in the primary lung tumour. No side effects of the administration of {sup 18}F-FAZA were observed. This study suggests

Two-step photoconductivity in LiY x Lu1 - x F4:Ce,Yb crystals

Science.gov (United States)

Nurtdinova, L. A.; Korableva, S. L.; Leontiev, A. V.

2016-10-01

Photoconductivity of LiY x Lu1- x F4:Ce,Yb ( x = 0-1) crystals is measured under one- and two-step excitation. It is established that the photoconductivity is due to intra-center transitions from excited states of Ce3+ ions. The position of the ground 4 f-state of Ce3+ ion relative to the bottom of the conduction band is determined. The choice of pumping conditions to obtain the lasing on the 5 d-4 f transitions of trivalent cerium in these active media is substantiated.

Association between Low Free Triiodothyronine Levels and Poor Prognosis in Patients with Acute ST-Elevation Myocardial Infarction

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Yuanbin Song

2018-01-01

Full Text Available Background. Low free triiodothyronine (fT3 levels are generally associated with poor prognosis in patients with heart diseases, but this is controversial and there is a lack of data about ST-elevation myocardial infarction (STEMI in Chinese patients. Objective. To assess the association between fT3 levels and the prognosis of patients with STEMI. Methods. This was a prospective observational study of 699 consecutive patients with STEMI treated at the Xinqiao Hospital between January 1, 2013, and December 31, 2014. The patients were divided into the low fT3 (fT3 < 3.1 pmol/L; n=179, 27.5% and normal fT3 (fT3 ≥ 3.1 pmol/L; n=473, 72.5% groups according to fT3 levels at admission. Patients were followed up at 1, 3, 6, and 12 months for all-cause death and major adverse cardiac events (MACE. Results. During the 1-year follow-up, there were 70 all-cause deaths (39.1% in the low fT3 group and 40 (8.5% in the normal fT3 group (P<0.001. MACE occurred in 105 patients (58.7% in the low fT3 group and 74 (15.6% in the normal fT3 group (P<0.001. Multivariate Cox proportional hazards regression analysis indicated that fT3 levels were independently associated with 30-day and 1-year all-cause death [30-day: hazard ratio (HR = 0.702, 95% confidence interval (95% CI: 0.501–0.983, P=0.04; 1-year: HR = 0.557, 95% CI: 0.411–0.755, P<0.001] and MACE (30-day: HR = 0.719, 95% CI: 0.528–0.979, P=0.036; 1-year: HR = 0.557, 95% CI: 0.445–0.698, P<0.001. Conclusion. Low fT3 levels were strongly associated with poor prognosis in patients with STEMI. Measurement of fT3 levels may be a valuable and simple way to identify high-risk STEMI patients.

18F-氟化钠PET和PET-CT诊断肺癌骨转移的对比研究%Comparison between 18F-NaF PET and PET-CT to detect bone metastases in patients with lung cancer

Institute of Scientific and Technical Information of China (English)

王俊起; 高硕; 李彦生

2009-01-01

目的 对比研究18F-氟化钠(18F-NaF)PET和PET-CT对肺癌骨转移诊断的准确性.方法 34例初始诊断为肺癌的患者接受18F-NaF PET-CT检查,对PET和PET-CT图像分别进行解释,发现的病变分为恶性、良性和不确定三种.骨转移的综合评价方法包括MRI(34例)、18F-氟脱氧葡糖糖PET-CT(4例)、组织学活检(2例)和临床随访(6例).结果 按患者水平分析时,34例患者中的11例(32%)发生骨转移,其中,18F-NaF PET-CT准确诊断所有患者的骨转移,无假阳性和假阴性,而18F-NaF PET诊断真阳性8例、3例不能确定,18F-NaF PET确诊的8例骨转移患者中的4例PET没有显示全部转移病变(假阴性和不确定病变);按病变水平分析时,118个病变获得最终诊断,其中转移病变47个、良性病变71个,其中,18F-NaF PET诊断真阳性27个、真阴性64个、不确定病变24个、假阴性1个、假阳性2个,而18F-NaF PET-CT诊断真阳性46个、假阴性1个、真阴性71个.按患者水平分析,将不确定病变归为恶性时,18F-NaF PET-CT的特异性高于18F-NaF PET(100% vs 78%,χ2=10.78,P0.05);按病变水平分析时,得到与患者水平分析相似结果.结论 18F-NaF PET-CT诊断肺癌骨转移的准确性优于18F-NaF PET,PET-CT中的低剂量CT可进一步提高良、恶性病变的鉴别能力.%Objective To evaluate the effect of 18F-sodium fluoride(18F-NaF)PET-CT in the detection of bone metastases in patients with lung cancer.Methods Thirty-four patients with newly diagnosed lung cancer were performed with 18F-NaF PET-CT.18F-NaF PET and 18F-NaF PET-CT were interpreted separately.Lesions were categorized as malignant,benign or inconclusive.A panel of reference methods was used,including MRI(34 patients),18F-fluorodeoxyglucose PET-CT(4 patients),histopathology(2 patients),or clinical follow-up of at least 6 months(6 patients).Results In patient-based analysis,11 of 34 patients had bone metastases.18F-NaF PET-CT correctly diagnosed all 11 patients with

Apolipoprotein A-1 mimetic peptide 4F promotes endothelial repairing and compromises reendothelialization impaired by oxidized HDL through SR-B1

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Dan He

2018-05-01

Full Text Available Disruption of endothelial monolayer integrity is the primary instigating factor for many cardiovascular diseases. High density lipoprotein (HDL oxidized by heme enzyme myeloperoxidase (MPO is dysfunctional in promoting endothelial repair. Apolipoprotein A-1 mimetic 4F with its pleiotropic benefits has been proven effective in many in vivo models. In this study we investigated whether 4F promotes endothelial repair and restores the impaired function of oxidized HDL (Cl/NO2-HDL in promoting re-endothelialization. We demonstrate that 4F and Cl/NO2-HDL act on scavenger receptor type I (SR-B1 using human aorta endothelial cells (HAEC and SR-B1 (-/- mouse aortic endothelial cells. Wound healing, transwell migration, lamellipodia formation and single cell migration assay experiments show that 4F treatment is associated with a recovery of endothelial cell migration and associated with significantly increased endothelial nitric oxide synthase (eNOS activity, Akt phosphorylation and SR-B1 expression. 4F increases NO generation and diminishes oxidative stress. In vivo, 4F can stimulate cell proliferation and re-endothelialization in the carotid artery after treatment with Cl/NO2-HDL in a carotid artery electric injury model but fails to do so in SR-B1(-/- mice. These findings demonstrate that 4F promotes endothelial cell migration and has a potential therapeutic benefit against early endothelial injury in cardiovascular diseases.

Localization of microfibrillar-associated protein 4 (MFAP4 in human tissues: clinical evaluation of serum MFAP4 and its association with various cardiovascular conditions.

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Helle Wulf-Johansson

Full Text Available Microfibrillar-associated protein 4 (MFAP4 is located in the extracellular matrix (ECM. We sought to identify tissues with high levels of MFAP4 mRNA and MFAP4 protein expression. Moreover, we aimed to evaluate the significance of MFAP4 as a marker of cardiovascular disease (CVD and to correlate MFAP4 with other known ECM markers, such as fibulin-1, osteoprotegerin (OPG, and osteopontin (OPN. Quantitative real-time PCR demonstrated that MFAP4 mRNA was more highly expressed in the heart, lung, and intestine than in other elastic tissues. Immunohistochemical studies demonstrated high levels of MFAP4 protein mainly at sites rich in elastic fibers and within blood vessels in all tissues investigated. The AlphaLISA technique was used to determine serum MFAP4 levels in a clinical cohort of 172 patients consisting of 5 matched groups with varying degrees of CVD: 1: patients with ST elevation myocardial infarction (STEMI, 2: patients with non-STEMI, 3: patients destined for vascular surgery because of various atherosclerotic diseases (stable atherosclerotic disease, 4: apparently healthy individuals with documented coronary artery calcification (CAC-positive, and 5: apparently healthy individuals without signs of coronary artery calcification (CAC-negative. Serum MFAP4 levels were significantly lower in patients with stable atherosclerotic disease than CAC-negative individuals (p<0.05. Furthermore, lower serum MFAP4 levels were present in patients with stable atherosclerotic disease compared with STEMI and non-STEMI patients (p<0.05. In patients with stable atherosclerotic disease, positive correlations between MFAP4 and both fibulin-1 (ρ = 0.50; p = 0.0244 and OPG (ρ = 0.62; p = 0.0014 were found. Together, these results indicate that MFAP4 is mainly located in elastic fibers and is highly expressed in blood vessels. The present study suggests that serum MFAP4 varies in groups of patients with different cardiovascular conditions

PERFORMA NEUTRONIK BAHAN BAKAR LiF-BeF2-ThF4-UF4 PADA SMALL MOBILE-MOLTEN SALT REACTOR

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S. N. Rokhman

2015-04-01

Full Text Available Telah dilakukan analisis terhadap performa neutronik bahan bakar garam lebur LiF-BeF2-ThF4-UF4 pada Small Mobile-Molten Salt Reactor (SM-MSR. Penyesuaian konfigurasi teras dan temperatur operasi harus dilakukan untuk penggunaan bahan bakar baru tersebut agar mencapai keff > 1 dan CR (conversion ratio > 1 pada fraksi 0,5% 233U, 20% 232Th, 28% Li, 51,5% Be. Setelah didapat nilai keff ≈ 1 dan CR ≈ 1, dilakukan analisis pengaruh perubahan Th terhadap Be dan Be terhadap Li yang terlihat dalam perubahan parameter keff dan CR. Setelah itu fraksi 233U divariasi antara 0,5–0,46% untuk memperoleh keff > 1 dan CR > 1. Dalam perhitungan koefisien reaktifitas temperatur (αT, temperatur teras dinaikkan sebesar +25K dan +50K., dan untuk koefisien reaktifitas void (αV, densitas bahan bakar dikurangi hingga 90%. Hasil perhitungan menunjukkan bahwa pengurangan Th terhadap Be menyebabkan penurunan nilai CR dan naiknya keff akibat berkurangnya material fertil. Sebaliknya penambahan Be terhadap Li mengakibatkan terjadi kenaikan nilai keff dan menurunkan CR, akibat laju serapan Li lebih besar dari Be. Pada 5 (lima fraksi 233U dalam rentang 0,5–0,49%, hasil perhitungan keff dan CR masing-masing bervariasi dalam rentang 1,00001 - 1,00327 dan 1,00016 - 1,00731. Untuk faktor puncak daya (PPF, hasil perhitungan memberikan nilai dalam rentang 2,4311 -2,4714. Sedangkan untuk parameter keselamatan, koefisien reaktivitas temperatur (αT dan reaktivitas void (αV masingmasing bernilai negatif dalam rentang 4,972×10-5 - 5,909×10-5 dan 2,596×10-2- 2,8287×10-2 ∆k/k/K. Dapat disimpulkan bahwa teras SM-MSR memberikan nilai negatif di kedua koefisien reaktivitas tersebut untuk setiap fraksi,, sehingga memenuhi kriteria keselamatan dan keselamatan melekat. Kata kunci: SM-MSR (small mobile-molten salt reactor, bahan bakar LiF-BeF2-ThF4-UF4, keselamatan melekat, koefisien reaktivitas temperatur, koefisien reaktivitas void   The analysis of neutronic performance has

{sup 18}F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with {sup 18}F-FDG and {sup 11}C-Methionine PET

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Watabe, Tadashi [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan); Osaka University Graduate School of Medicine, PET Molecular Imaging Center, Osaka (Japan); Ikeda, Hayato; Aoki, Masanao [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan); Nagamori, Shushi; Wiriyasermkul, Pattama; Tanaka, Yoko; Hagiwara, Kohei; Kanai, Yoshikatsu [Osaka University Graduate School of Medicine, Department of Bio-system Pharmacology, Osaka (Japan); Naka, Sadahiro [Osaka University, Osaka University Graduate School of Medicine, Osaka University Hospital, Osaka (Japan); Kanai, Yasukazu [Osaka University Graduate School of Medicine, PET Molecular Imaging Center, Osaka (Japan); Osaka University Graduate School of Medicine, Department of Molecular Imaging in Medicine, Osaka (Japan); Shimosegawa, Eku [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan); Osaka University Graduate School of Medicine, PET Molecular Imaging Center, Osaka (Japan); Osaka University, Osaka University Graduate School of Medicine, Osaka University Hospital, Osaka (Japan); Hatazawa, Jun [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan); Osaka University Graduate School of Medicine, PET Molecular Imaging Center, Osaka (Japan); Osaka University, Immunology Frontier Research Center, Osaka (Japan)

2017-02-15

The purpose of this study was to evaluate the usefulness of L-4-borono-2-{sup 18}F-fluoro-phenylalanine ({sup 18}F-FBPA) as a tumor-specific probe, in comparison to {sup 18}F-FDG and {sup 11}C-methionine (Met), focusing on its transport selectivity by L-type amino acid transporter 1 (LAT1), which is highly upregulated in cancers. Cellular analyses of FBPA were performed to evaluate the transportability and K{sub m} value. PET studies were performed in rat xenograft models of C6 glioma (n = 12) and in rat models of turpentine oil-induced subcutaneous inflammation (n = 9). The kinetic parameters and uptake values on static PET images were compared using the one-tissue compartment model (K{sub 1}, k{sub 2}) and maximum standardized uptake value (SUVmax). The cellular analyses showed that FBPA had a lower affinity to a normal cell-type transporter LAT2 and induced less efflux through LAT2 among FBPA, Met, and BPA, while the efflux through LAT1 induced by FBPA was similar among the three compounds. The K{sub m} value of {sup 18}F-FBPA for LAT1 (196.8 ± 11.4 μM) was dramatically lower than that for LAT2 (2813.8 ± 574.5 μM), suggesting the higher selectivity of {sup 18}F-FBPA for LAT1. K{sub 1} and k{sub 2} values were significantly smaller in {sup 18}F-FBPA PET (K{sub 1} = 0.04 ± 0.01 ml/ccm/min and k{sub 2} = 0.07 ± 0.01 /min) as compared to {sup 11}C-Met PET (0.22 ± 0.09 and 0.52 ± 0.10, respectively) in inflammatory lesions. Static PET analysis based on the SUVmax showed significantly higher accumulation of {sup 18}F-FDG in the tumor and inflammatory lesions (7.2 ± 2.1 and 4.6 ± 0.63, respectively) as compared to both {sup 18}F-FBPA (3.2 ± 0.40 and 1.9 ± 0.19) and {sup 11}C-Met (3.4 ± 0.43 and 1.6 ± 0.11). No significant difference was observed between {sup 18}F-FBPA and {sup 11}C-Met in the static PET images. This study shows the utility of {sup 18}F-FBPA as a tumor-specific probe of LAT1 with low accumulation in the inflammatory lesions. (orig.)

Synthesis and preclinical characterization of 1-(6'-deoxy-6'-[18F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-6'-[18F]FAZAL) as a positron emission tomography radiotracer to assess tumor hypoxia.

Science.gov (United States)

Wanek, Thomas; Kreis, Katharina; Križková, Petra; Schweifer, Anna; Denk, Christoph; Stanek, Johann; Mairinger, Severin; Filip, Thomas; Sauberer, Michael; Edelhofer, Patricia; Traxl, Alexander; Muchitsch, Viktoria E; Mereiter, Kurt; Hammerschmidt, Friedrich; Cass, Carol E; Damaraju, Vijaya L; Langer, Oliver; Kuntner, Claudia

2016-11-01

Positron emission tomography (PET) using fluorine-18 ( 18 F)-labeled 2-nitroimidazole radiotracers has proven useful for assessment of tumor oxygenation. However, the passive diffusion-driven cellular uptake of currently available radiotracers results in slow kinetics and low tumor-to-background ratios. With the aim to develop a compound that is actively transported into cells, 1-(6'-deoxy-6'-[ 18 F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-[ 18 F]1), a putative nucleoside transporter substrate, was synthetized by nucleophilic [ 18 F]fluoride substitution of an acetyl protected labeling precursor with a tosylate leaving group (β-6) in a final radiochemical yield of 12±8% (n=10, based on [ 18 F]fluoride starting activity) in a total synthesis time of 60min with a specific activity at end of synthesis of 218±58GBq/μmol (n=10). Both radiolabeling precursor β-6 and unlabeled reference compound β-1 were prepared in multistep syntheses starting from 1,2:5,6-di-O-isopropylidene-α-d-allofuranose. In vitro experiments demonstrated an interaction of β-1 with SLC29A1 and SLC28A1/2/3 nucleoside transporter as well as hypoxia specific retention of β-[ 18 F]1 in tumor cell lines. In biodistribution studies in healthy mice β-[ 18 F]1 showed homogenous tissue distribution and excellent metabolic stability, which was unaffected by tissue oxygenation. PET studies in tumor bearing mice showed tumor-to-muscle ratios of 2.13±0.22 (n=4) at 2h after administration of β-[ 18 F]1. In ex vivo autoradiography experiments β-[ 18 F]1 distribution closely matched staining with the hypoxia marker pimonidazole. In conclusion, β-[ 18 F]1 shows potential as PET hypoxia radiotracer which merits further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gene Expression Signature in Adipose Tissue of Acromegaly Patients

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Hochberg, Irit; Tran, Quynh T.; Barkan, Ariel L.; Saltiel, Alan R.; Chandler, William F.; Bridges, Dave

2015-01-01

To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. PMID:26087292

Association of epicardial adipose tissue thickness and inflammation parameters with CHA2DS2-VASc score in patients with nonvalvular atrial fibrillation

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Akdag S

2015-11-01

Full Text Available Serkan Akdag, Hakki Simsek, Musa Sahin, Aytac Akyol, Ramazan Duz, Naci Babat Department of Cardiology, Yuzuncu Yil University Medical Faculty, Van, Turkey Background: Epicardial adipose tissue (EAT, mean platelet volume (MPV, platelet-to- lymphocyte ratio (PLR, and neutrophil-to-lymphocyte ratio (NLR have been shown to be helpful in predicting adverse cardiovascular events. However, to date, in the literature, there have been no studies demonstrating the relationship between EAT, MPV, PLR, NLR, and thromboembolism risk in atrial fibrillation (AF. Therefore, we examined the relationship between EAT, MPV, PLR, NLR, and CHA2DS2-VASc score used for the evaluation of thromboembolism risk in patients with AF.Methods: The study included 96 consecutive patients with AF and 52 age- and sex-matched control subjects. We calculated CHA2DS2-VASc risk score for each patient and measured baseline EAT thickness, MPV, PLR, NLR, left atrial volume index, and left ventricular ejection fraction.Results: The group with high CHA2DS2-VASc score had higher EAT (7.2±1.5 vs 5.9±1.2 mm, P<0.001, MPV (9.1±1.1 vs 8.4±1.0 fL, P=0.004, PLR (152.3±28.4 vs 126.7±25.4, P=0.001, and NLR (4.0±1.6 vs 3.2±1.3, P<0.001 compared to group with low-intermediate CHA2DS2-VASc score. Moreover, CHA2DS2-VASc score was found to be positively correlated with EAT (r=0.623, P<0.001, MPV (r=0.350, P=0.004, PLR (r=0.398, P=0.001, and NLR (r=0.518, P<0.001.Conclusion: Our study results demonstrated that EAT thickness, MPV, PLR, and NLR were associated with the thromboembolic risk exhibited by CHA2DS2-VASc score in patients with nonvalvular AF. Keywords: atrial fibrillation, epicardial adipose tissue, platelet, neutrophil, mean platelet volume

Radiosynthesis and pre-clinical evaluation of [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline

Energy Technology Data Exchange (ETDEWEB)

Smith, Graham [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Zhao Yongjun [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Leyton, Julius [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Shan Bo [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Nguyen, Quang-de; Perumal, Meg [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Turton, David [GE-Imanet, Hammersmith Hospital, Du Cane Road, London, W12 0NN (United Kingdom); Arstad, Erik; Luthra, Sajinder K.; Robins, Edward G. [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Aboagye, Eric O., E-mail: eric.aboagye@imperial.ac.u [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom)

2011-01-15

Introduction: Choline radiotracers are widely used for clinical PET diagnosis in oncology. [{sup 11}C]Choline finds particular utility in the imaging of brain and prostate tumor metabolic status, where 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ('FDG') shows high background uptake. More recently we have extended the clinical utility of [{sup 11}C]choline to breast cancer where radiotracer uptake correlates with tumor aggressiveness (grade). In the present study, a new choline analog, [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline, was synthesized and evaluated as a potential PET imaging probe. Methods: [{sup 18}F]Fluorocholine, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline were synthesized by alkylation of the relevant precursor with [{sup 18}F]fluorobromomethane or [{sup 18}F]fluoromethyl tosylate. Radiosynthesis of [{sup 18}F]fluoromethyl tosylate required extensive modification of the existing method. [{sup 18}F]Fluorocholine and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline were then subjected to in vitro oxidative stability analysis in a chemical oxidation model using potassium permanganate and an enzymatic model using choline oxidase. The two radiotracers, together with the corresponding di-deuterated compound, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline, were then evaluated in vivo in a time-course biodistribution study in HCT-116 tumor-bearing mice. Results: Alkylation with [{sup 18}F]fluoromethyl tosylate proved to be the most reliable radiosynthetic route. Stability models indicate that [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline possesses increased chemical and enzymatic (choline oxidase) oxidative stability relative to [{sup 18}F]fluorocholine. The distribution of the three radiotracers, [{sup 18}F]fluorocholine, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline, showed a similar uptake profile in most organs. Crucially, tumor uptake of [{sup 18}F

Whole-body {sup 18}F-FDG PET/CT for M staging in the patient with newly diagnosed nasopharyngeal carcinoma: Who needs?

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Ren, Yun-yan; Li, You-cai; Wu, Hu-bing, E-mail: wuhbym@163.com; Wang, Quan-shi; Han, Yan-jiang; Zhou, Wen-lan; Li, Hong-sheng

2017-04-15

Objective: Although whole-body fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET)/computed tomography (CT) ({sup 18}F-FDG PET/CT) is commonly used for M staging of newly diagnosed nasopharyngeal carcinoma (NPC), some patients may not benefit from this procedure. The present study investigated which patients require this modality for M staging. Methods: Whole-body {sup 18}F FDG PET/CT results and clinical data were collected for 264 patients with newly diagnosed NPC. The relationships between distant metastasis and age, gender, pathological type, lesion size, SUVmax-T, T staging, N staging, SUVmax-N and Epstein-Barr virus (EBV) quantity were retrospectively analysed to identify factors associated with increased risk. Results: Of the 264 patients, only 37 (14.0%) were diagnosed with distant metastasis. Using multiple logistic regression analysis, EBV-positivity (OR = 13.1; 95% CI:1.61,106.80), N staging (OR = 3.05; 95% CI:1.41,6.63) and T staging (OR = 2.16; 95% CI:1.10, 4.24) were significantly related to distant metastasis (all P < 0.05). EBV DNA levels ≥ 9000 copies/ml, N3 stage and T4 stage were identified as high risk factors. A low risk of distant metastasis was found in patients with 0–1 risk factors and in those with 2 specific risk factors, T3/T4 and N2/N3 staging. Patients with EBV DNA levels ≥9000 copies/ml and N3 or T4 staging and those with 3 risk factors had a medium or high risk, with a much higher incidence of distant metastasis (χ{sup 2} = 29.896, P = 0.000), and needed a whole-body {sup 18}F FDG PET/CT for M staging. Conclusions: Due to the low incidence of distant metastasis, only patients with medium or high risk need to undergo a whole-body scan.

Aryl-1H-imidazole[4,5f][1,10]phenanthroline Cu(II) complexes: Electrochemical and DNA interaction studies.

Science.gov (United States)

Rajebhosale, Bharati S; Dongre, Shivali N; Deshpande, Sameer S; Kate, Anup N; Kumbhar, Anupa A

2017-10-01

The reaction of aryl imidazo[4,5f] [1,10]phenanthrolines with Cu(NO 3 ) 2 lead to the formation of Cu(II) complexes of the type [Cu(L)(NO 3 ) 2 ] where L=PIP, 2-(phenyl) [4,5f] imidazo phenanthroline; HPIP=2-(2-hydroxyphenyl)imidazo [4,5f] phenanthroline and NIP=2-(naphthyl) [4,5f] imidazo phenanthroline. The interaction of these complexes with calf thymus DNA has been studied using viscosity measurements, UV-visible and fluorescence spectroscopy. Chemical nuclease activity of these complexes has also been investigated. All complexes cleave DNA via oxidative pathway involving singlet oxygen. Molecular docking studies revealed that these complexes bind to DNA through minor groove. Copyright © 2017 Elsevier Inc. All rights reserved.

A new three-dimensional conformal radiotherapy (3DCRT) technique for large breast and/or high body mass index patients: evaluation of a novel fields assessment aimed to reduce extra–target-tissue irradiation

Science.gov (United States)

Stimato, Gerardina; Ippolito, Edy; Silipigni, Sonia; Venanzio, Cristina Di; Gaudino, Diego; Fiore, Michele; Trodella, Lucio; D'Angelillo, Rolando Maria; Ramella, Sara

2016-01-01

Objective: To develop an alternative three-dimensional treatment plan with standardized fields class solution for whole-breast radiotherapy in patients with large/pendulous breast and/or high body mass index (BMI). Methods: Two treatment plans [tangential fields and standardized five-fields technique (S5F)] for a total dose of 50 Gy/25 fractions were generated for patients with large breasts [planning target volume (PTV) >1000 cm3 and/or BMI >25 kg m−2], supine positioned. S5F plans consist of two wedged tangential beams, anteroposterior: 20° for the right breast and 340° for the left breast, and posteroanterior: 181° for the right breast and 179° for the left breast. A field in field in medial–lateral beam and additional fields were added to reduce hot spot areas and extra–target-tissue irradiation and to improve dose distribution. The percentage of PTV receiving 95% of the prescribed dose (PTV V95%), percentage of PTV receiving 105% of the prescribed dose (PTV V105%), maximal dose to PTV (PTV Dmax), homogeneity index (HI) and conformity index were recorded. V10%, V20%, V105% and V107% of a “proper” normal tissue structure (body-PTV healthy tissue) were recorded. Statistical analyses were performed using SYSTAT v.12.0 (SPSS, Chicago, IL). Results: In 38 patients included, S5F improved HI (8.4 vs 10.1; p ≤ 0.001) and significantly reduced PTV Dmax and PTV V105%. The extra–target-tissue irradiation was significantly reduced using S5F for V105% (cm3) and V107% (cm3) with a very high difference in tissue irradiation (46.6 vs 3.0 cm3, p ≤ 0.001 for V105% and 12.2 vs 0.0 cm3, p ≤ 0.001 for V107% for tangential field and S5F plans, respectively). Only a slight increase in low-dose extra–target-tissue irradiation (V10%) was observed (2.2719 vs 1.8261 cm3, p = 0.002). Conclusion: The S5F technique in patients with large breast or high BMI increases HI and decreases hot spots in extra-target-tissues and can therefore be

Comparison of two threshold detection criteria methodologies for determination of probe positivity for intraoperative in situ identification of presumed abnormal 18F-FDG-avid tissue sites during radioguided oncologic surgery.

Science.gov (United States)

Chapman, Gregg J; Povoski, Stephen P; Hall, Nathan C; Murrey, Douglas A; Lee, Robert; Martin, Edward W

2014-09-13

Intraoperative in situ identification of (18)F-FDG-avid tissue sites during radioguided oncologic surgery remains a significant challenge for surgeons. The purpose of our study was to evaluate the 1.5-to-1 ratiometric threshold criteria method versus the three-sigma statistical threshold criteria method for determination of gamma detection probe positivity for intraoperative in situ identification of presumed abnormal (18)F-FDG-avid tissue sites in a manner that was independent of the specific type of gamma detection probe used. From among 52 patients undergoing appropriate in situ evaluation of presumed abnormal (18)F-FDG-avid tissue sites during (18)F-FDG-directed surgery using 6 available gamma detection probe systems, a total of 401 intraoperative gamma detection probe measurement sets of in situ counts per second measurements were cumulatively taken. For the 401 intraoperative gamma detection probe measurement sets, probe positivity was successfully met by the 1.5-to-1 ratiometric threshold criteria method in 150/401 instances (37.4%) and by the three-sigma statistical threshold criteria method in 259/401 instances (64.6%) (P < 0.001). Likewise, the three-sigma statistical threshold criteria method detected true positive results at target-to-background ratios much lower than the 1.5-to-1 target-to-background ratio of the 1.5-to-1 ratiometric threshold criteria method. The three-sigma statistical threshold criteria method was significantly better than the 1.5-to-1 ratiometric threshold criteria method for determination of gamma detection probe positivity for intraoperative in situ detection of presumed abnormal (18)F-FDG-avid tissue sites during radioguided oncologic surgery. This finding may be extremely important for reshaping the ongoing and future research and development of gamma detection probe systems that are necessary for optimizing the in situ detection of radioisotopes of higher-energy gamma photon emissions used during radioguided oncologic surgery.

Unsuspected Active Sarcoidosis Diagnosed by 18F-FDG PET/CT During the Search for a Primary Tumour in a Patient with Bone Lesions

International Nuclear Information System (INIS)

Caobelli, Federico; Pizzocaro, Claudio; Soffientini, Alberto; Guerra, Ugo Paolo; Gabanelli, Sara Vincenzina; Brucato, Antonio; Giubbini, Raffaele

2013-01-01

Sarcoidosis is a systemic chronic inflammatory disease of unknown aetiology, characterised by granulomatous lesions with heterogeneous clinical manifestations affecting multiple organs and tissues. Although the respiratory system is most commonly affected, the disease may also present with bone lesions. We report the case of a 31-year old woman who presented with low back pain and no history of cancer and who was found to have suspicious lesions involving the entire spine on magnetic resonance imaging (MRI). The patient underwent 18 F-fluorodeoxyglucose (FDG) PET/CT to search for a primary tumour and for staging purposes. 18 F-FDG PET/CT revealed a pattern of hypermetabolic activity in widespread skeletal lesions and in a single left cervical lymph node. The primary tumour was not found, thus suggesting a haematologic disorder. Subsequent biopsies of a cervical lymph node and of bone tissue from L4 revealed active sarcoidosis with no evidence of cancer. This underlines the importance of considering all alternatives when hypermetabolic lesions are found on 18 F-FDG PET/CT. Furthermore, 18 F-FDG PET can be very useful to indicate accessible sites for guiding fine-needle aspiration cytology (FNAC)

BCM1F Performance in 2012

CERN Document Server

CMS Collaboration

2013-01-01

The Fast Beam Condition Monitor BCM1F consists of 8 single-crystal CVD 5 mm x 5 mm diamonds positioned 1.8 m on either side of the interaction point at a radius of 4.5 cm from the beam pipe. The signal is read out, shaped by a frontend ASIC, and converted to an optical signal which is then transmitted to the backend electronics in USC55. The data travels parallel paths: a discriminator path registers the time of signal pulses and transfers this information to the readout electronics, while an ADC captures full orbits for monitoring studies but is prevented from acting as data readout by a high deadtime. BCM1F provides information on the condition of the beam and ensures that the inner detector occupancy is sufficiently low for data-taking. In addition to providing beam information, BCM1F also detects collisions and as such can be used as a luminometer. Effort was made to commission BCM1F as an online luminometer in 2012. In 2012 the Real-time Histogramming Unit (RHU) for BCM1F readout was introduced. The boar...

Atmospheric histories and growth trends of C4F10, C5F12, C6F14, C7F16 and C8F18

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R. F. Weiss

2012-05-01

Full Text Available Atmospheric observations and trends are presented for the high molecular weight perfluorocarbons (PFCs: decafluorobutane (C4F10, dodecafluoropentane (C5F12, tetradecafluorohexane (C6F14, hexadecafluoroheptane (C7F16 and octadecafluorooctane (C8F18. Their atmospheric histories are based on measurements of 36 Northern Hemisphere and 46 Southern Hemisphere archived air samples collected between 1973 to 2011 using the Advanced Global Atmospheric Gases Experiment (AGAGE "Medusa" preconcentration gas chromatography-mass spectrometry systems. A new calibration scale was prepared for each PFC, with estimated accuracies of 6.8% for C4F10, 7.8% for C5F12, 4.0% for C6F14, 6.6% for C7F16 and 7.9% for C8F18. Based on our observations the 2011 globally averaged dry air mole fractions of these heavy PFCs are: 0.17 parts-per-trillion (ppt, i.e., parts per 1012 for C4F10, 0.12 ppt for C5F12, 0.27 ppt for C6F14, 0.12 ppt for C7F16 and 0.09 ppt for C8F18. These atmospheric mole fractions combine to contribute to a global average radiative forcing of 0.35 mW m−2, which is 6% of the total anthropogenic PFC radiative forcing (Montzka and Reimann, 2011; Oram et al., 2012. The growth rates of the heavy perfluorocarbons were largest in the late 1990s peaking at 6.2 parts per quadrillion (ppq, i.e., parts per 1015 per year (yr for C4F10, at 5.0 ppq yr−1 for C5F12 and 16.6 ppq yr−1 for C6F14 and in the early 1990s for C7F16 at 4.7 ppq yr−1 and in the mid 1990s for C8F18 at 4.8 ppq yr−1. The 2011 globally averaged mean atmospheric growth rates of these PFCs are subsequently lower at 2.2 ppq yr−1 for C4F10, 1.4 ppq yr−1 for C5F12, 5.0 ppq yr−1 for C6F14, 3.4 ppq yr−1 for C7F16 and 0.9 ppq yr−1 for C8F18. The more recent slowdown in the growth rates suggests that emissions are declining as compared to the 1980s and 1990s.

A PET/MRI study towards finding the optimal ["1"8F]Fluciclovine PET protocol for detection and characterisation of primary prostate cancer

International Nuclear Information System (INIS)

Elschot, Mattijs; Sandsmark, Elise; Tessem, May-Britt; Selnaes, Kirsten M.; Bathen, Tone F.; Krueger-Stokke, Brage; Stoerkersen, Oeystein; Moestue, Siver A.; Bertilsson, Helena

2017-01-01

["1"8F]Fluciclovine PET imaging shows promise for the assessment of prostate cancer. The purpose of this PET/MRI study is to optimise the PET imaging protocol for detection and characterisation of primary prostate cancer, by quantitative evaluation of the dynamic uptake of ["1"8F]Fluciclovine in cancerous and benign tissue. Patients diagnosed with high-risk primary prostate cancer underwent an integrated ["1"8F]Fluciclovine PET/MRI exam before robot-assisted radical prostatectomy with extended pelvic lymph node dissection. Volumes-of-interest (VOIs) of selected organs (prostate, bladder, blood pool) and sub-glandular prostate structures (tumour, benign prostatic hyperplasia (BPH), inflammation, healthy tissue) were delineated on T2-weighted MR images, using whole-mount histology samples as a reference. Three candidate windows for optimal PET imaging were identified based on the dynamic curves of the mean and maximum standardised uptake value (SUV_m_e_a_n and SUV_m_a_x, respectively). The statistical significance of differences in SUV between VOIs were analysed using Wilcoxon rank sum tests (p<0.05, adjusted for multiple testing). Twenty-eight (28) patients [median (range) age: 66 (55-72) years] were included. An early (W1: 5-10 minutes post-injection) and two late candidate windows (W2: 18-23; W3: 33-38 minutes post-injection) were selected. Late compared with early imaging was better able to distinguish between malignant and benign tissue [W3, SUV_m_e_a_n: tumour vs. BPH 2.5 vs. 2.0 (p<0.001), tumour vs. inflammation 2.5 vs. 1.7 (p<0.001), tumour vs. healthy tissue 2.5 vs. 2.0 (p<0.001); W1, SUV_m_e_a_n: tumour vs. BPH 3.1 vs. 3.1 (p=0.771), tumour vs inflammation 3.1 vs. 2.2 (p=0.021), tumour vs. healthy tissue 3.1 vs. 2.5 (p<0.001)] as well as between high-grade and low/intermediate-grade tumours (W3, SUV_m_e_a_n: 2.6 vs. 2.1 (p=0.040); W1, SUV_m_e_a_n: 3.1 vs. 2.8 (p=0.173)). These differences were relevant to the peripheral zone, but not the central gland

Potential use of "1"8F-FDG-PET/CT to visualize hypermetabolism associated with muscle pain in patients with adult spinal deformity: a case report

International Nuclear Information System (INIS)

Taniguchi, Yuki; Takahashi, Miwako; Momose, Toshimitsu; Matsudaira, Ko; Oka, Hiroyuki

2016-01-01

Patients with adult spinal deformity (ASD) are surgically treated for pain relief; however, visualization of the exact origin of the pain with imaging modalities is still challenging. We report the first case of a 60-year-old female patient who presented with painful degenerative kyphoscoliosis and was evaluated with flourine-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ("1"8F-FDG-PET/CT) preoperatively. Because her low back pain was resistant to conservative treatment, she was treated with posterior spinal correction and fusion surgery from Th2 to the ilium. One year after the surgery, her low back pain had disappeared completely. In accordance with her clinical course, "1"8F-FDG-PET imaging revealed the uptake of "1"8F-FDG in the paravertebral muscles preoperatively and showed the complete absence of uptake at 1 year after surgery. The uptake site coincided with the convex part of each curve of the lumbar spine and was thought to be the result of the increased activity of paravertebral muscles due to their chronic stretched state in the kyphotic posture. This case report suggests the possibility of using "1"8F-FDG-PET/CT to visualize increased activity in paravertebral muscles and the ensuing pain in ASD patients. (orig.)

Functional correlates of TSH, fT3 and fT4 in Alzheimer disease: a F-18 FDG PET/CT study.

Science.gov (United States)

Chiaravalloti, Agostino; Ursini, Francesco; Fiorentini, Alessandro; Barbagallo, Gaetano; Martorana, Alessandro; Koch, Giacomo; Tavolozza, Mario; Schillaci, Orazio

2017-07-24

The present study was aimed to investigate the relationships between thyroid stimulating hormone (TSH), freeT3 (fT3) and freeT4 (fT4) and brain glucose consumption as detectable by means of 2-deoxy-2-(F-18) fluoro-D-glucose (F-18 FDG) Positron Emission Tomography/Computed Tomography (PET/CT) in a selected population with Alzheimer disease (AD). We evaluated 87 subjects (37 males and 50 females, mean age 70 (±6) years old) with AD. All of them were subjected to TSH, fT3 and fT4 assay and to cerebrospinal fluid amyloid (Aβ1-42) and tau [phosphorylated-tau (p-tau) and total-tau (t-tau)] assay prior PET/CT examination. Values for TSH, fT3 and fT4 were in the normal range. The relationships were evaluated by means of statistical parametric mapping (SPM8) using age, sex, MMSE, scholarship and CSF values of amyloid and tau as covariates. We found a significant positive correlation between TSH values and cortical glucose consumption in a wide portion of the anterior cingulate cortex bilaterally (BA32) and left frontal lobe (BA25) (p FWE-corr <0.001; p FDRcorr <0.000; cluster extent 66950). No significant relationships were found between cortical F-18 FDG uptake and T3 and T4 serum levels. The results of our study suggest that a cortical dysfunction in anterior cingulate and frontal lobes may affect serum values of TSH in AD patients.

A simplified one-pot synthesis of 9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F]FHPG) and 9-(4-[18F]Fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for gene therapy

International Nuclear Information System (INIS)

Shiue, Grace G.; Shiue, Chyng-Yann; Lee, Roland L.; MacDonald, Douglas; Hustinx, Roland; Eck, Stephen L.; Alavi, Abass A.

2001-01-01

9-[(3-[ 18 F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([ 18 F]FHPG, 2) has been synthesized by nucleophilic substitution of N 2 -(p-anisyldiphenylmethyl)-9-{[1-(p-anisyldiphenylmethoxy)-3 -toluenesulfonyloxy-2-propoxy]methyl}guanine (1) with potassium [ 18 F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 deg. C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 deg. C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 deg. C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[ 18 F]fluoro-3-hydroxymethylbutyl)guanine ([ 18 F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 deg. C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126±0.022, n=5 and 0.165±0.023, n=5, respectively). Although it contains non-radioactive ganciclovir (∼5-30 μg) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains ∼10-25 μg of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in good yield for routine clinical use, and the method is

Pilot Preclinical and Clinical Evaluation of (4S-4-(3-[18F]Fluoropropyl-L-Glutamate (18F-FSPG for PET/CT Imaging of Intracranial Malignancies.

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Erik S Mittra

Full Text Available (S-4-(3-[18F]Fluoropropyl-L-glutamic acid (18F-FSPG is a novel radiopharmaceutical for Positron Emission Tomography (PET imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies.For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years. After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers.In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7. 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model.18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors are planned.ClinicalTrials.gov NCT

E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2

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Fang, Zejun [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Gong, Chaoju [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058 (China); Liu, Hong [Zhejiang Normal University – Jinhua People' s Hospital Joint Center for Biomedical Research, Jinhua, Zhejiang, 321004 (China); Zhang, Xiaomin; Mei, Lingming [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Song, Mintao [Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS), School of Basic Medicine, Peking Union Medical College (PUMC), Beijing, 100005 (China); Qiu, Lanlan; Luo, Shuchai; Zhu, Zhihua; Zhang, Ronghui; Gu, Hongqian [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China); Chen, Xiang, E-mail: sychenxiang@126.com [Sanmen People' s Hospital of Zhejiang, Sanmen, Zhejiang, 317100 (China)

2015-08-21

As the ribonucleotide reductase small subunit, the high expression of ribonucleotide reductase small subunit M2 (RRM2) induces cancer and contributes to tumor growth and invasion. In several colorectal cancer (CRC) cell lines, we found that the expression levels of RRM2 were closely related to the transcription factor E2F1. Mechanistic studies were conducted to determine the molecular basis. Ectopic overexpression of E2F1 promoted RRM2 transactivation while knockdown of E2F1 reduced the levels of RRM2 mRNA and protein. To further investigate the roles of RRM2 which was activated by E2F1 in CRC, CCK-8 assay and EdU incorporation assay were performed. Overexpression of E2F1 promoted cell proliferation in CRC cells, which was blocked by RRM2 knockdown attenuation. In the migration and invasion tests, overexpression of E2F1 enhanced the migration and invasion of CRC cells which was abrogated by silencing RRM2. Besides, overexpression of RRM2 reversed the effects of E2F1 knockdown partially in CRC cells. Examination of clinical CRC specimens demonstrated that both RRM2 and E2F1 were elevated in most cancer tissues compared to the paired normal tissues. Further analysis showed that the protein expression levels of E2F1 and RRM2 were parallel with each other and positively correlated with lymph node metastasis (LNM), TNM stage and distant metastasis. Consistently, the patients with low E2F1 and RRM2 levels have a better prognosis than those with high levels. Therefore, we suggest that E2F1 can promote CRC proliferation, migration, invasion and metastasis by regulating RRM2 transactivation. Understanding the role of E2F1 in activating RRM2 transcription will help to explain the relationship between E2F1 and RRM2 in CRC and provide a novel predictive marker for diagnosis and prognosis of the disease. - Highlights: • E2F1 promotes RRM2 transactivation in CRC cells. • E2F1 promotes the proliferation of CRC cells by activating RRM2. • E2F1 promotes the migration and

Feasibility and repeatability of PET with the hypoxia tracer [18F]HX4 in oesophageal and pancreatic cancer

International Nuclear Information System (INIS)

Klaassen, Remy; Bennink, Roelof J.; Tienhoven, Geertjan van; Bijlsma, Maarten F.; Besselink, Marc G.H.; Berge Henegouwen, Mark I. van; Wilmink, Johanna W.; Nederveen, Aart J.; Windhorst, Albert D.; Hulshof, Maarten C.C.M.; Laarhoven, Hanneke W.M. van

2015-01-01

Background and purpose: To investigate the feasibility and to determine the repeatability of recurrent [ 18 F]HX4 PET scans in patients with oesophageal (EC) and pancreatic (PC) cancer. Materials and methods: 32 patients were scanned in total; seven patients (4 EC/3 PC) were scanned 2, 3 and 4 h post injection (PI) of [ 18 F]HX4 and 25 patients (15 EC/10 PC) were scanned twice 3.5 h PI, on two separate days (median 4, range 1–9 days). Maximum tumour to background ratio (TBRmax) and the tumour hypoxic volume (HV) (TBR > 1.0) were calculated. Repeatability was assessed using Bland–Altman analysis. Agreement in localization was calculated as the distance between the centres of mass in the HVs. Results: For EC, the TBRmax in the tumour (mean ± SD) was 1.87 ± 0.46 with a coefficient of repeatability (CoR) of 0.53 (28% of mean). The HV ranged from 3.4 to 98.8 ml with a CoR of 5.1 ml. For PC, the TBRmax was 1.72 ± 0.23 with a CoR of 0.27 (16% of mean). The HV ranged from 4.6 to 104.0 ml with a CoR of 7.8 ml. The distance between the centres of mass in the HV was 2.2 ± 1.3 mm for EC and 2.1 ± 1.5 mm for PC. Conclusions: PET scanning with [ 18 F]HX4 was feasible in both EC and PC patients. Amount and location of elevated [ 18 F]HX4 uptake showed good repeatability, suggesting [ 18 F]HX4 PET could be a promising tool for radiation therapy planning and treatment response monitoring in EC and PC patients

SDF-1/CXCR4 expression in bladder cancer tissue and the correlation with negative costimulatory molecule PD-L1, cell apoptosis and invasion

Directory of Open Access Journals (Sweden)

Ming-Bao Ye

2017-06-01

Full Text Available Objective: To study the SDF-1/CXCR4 expression in bladder cancer tissue and the correlation with negative costimulatory molecule PD-L1, cell apoptosis and invasion. Methods: A total of 118 cases of bladder cancer tissue and para-carcinoma tissue surgically removed in our hospital between May 2014 and May 2016 were selected as the research samples, the RNA was extracted and then reverse-transcribed into cDNA, and the expression levels of SDF-1/ CXCR4, PD-L1/PD-1, cell apoptosis-related molecules and cell invasion-related molecules were detected. Results: SDF-1 and CXCR4 mRNA expression in bladder cancer tissue were significantly higher than those in para-carcinoma tissue; PD-L1, PD-1, Rec1, Survivin, MRPS5, Nanog, BCAPP2Ac, TRPM8, TRPV2, ILK, β-catenin and GUGBP1 mRNA expression in bladder cancer tissue were significantly higher than those in para-carcinoma tissue and positively correlated with SDF-1 and CXCR4 mRNA expression. Conclusion: Highly expressed SDF-1/CXCR4 in bladder cancer tissue are closely related to the high expression of negative costimulatory molecule PD-L1, pro-proliferation molecules and proinvasion molecules, and SDF-1/CXCR4 can promote the immune escape, proliferation and invasion of bladder cancer cells.

Increased frequency of co-existing JAK2 exon-12 or MPL exon-10 mutations in patients with low JAK2(V617F) allelic burden.

Science.gov (United States)

Nussenzveig, Roberto H; Pham, Ha T; Perkins, Sherrie L; Prchal, Josef T; Agarwal, Archana M; Salama, Mohamed E

2016-01-01

The frequency of co-existing JAK2(V617F)/MPL and JAK2(V617F)/JAK2 exon-12 mutations has not been previously investigated in MPNs. Poor survival was reported in primary myelofibrosis with low JAK2(V617F) allelic burden. However, mutational status of JAK2 exon-12 or MPL were not reported in these patients. This study developed a cost-effective multiplex high resolution melt assay that screens for mutations in JAK2 gene exons-12 and -14 ((V617F)) and MPL gene exon-10. Co-existing mutations with JAK2(V617F) were detected in 2.9% (6/208; two JAK2 exon-12 and four MPL exon-10) patient specimens with known JAK2(V617F) (allelic-burden range: 0.1-96.8%). Co-existing mutations were detected in specimens with MPL exon-10 mutation should be pursued.

SU-F-T-187: Quantifying Normal Tissue Sparing with 4D Robust Optimization of Intensity Modulated Proton Therapy

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Newpower, M; Ge, S; Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: To report an approach to quantify the normal tissue sparing for 4D robustly-optimized versus PTV-optimized IMPT plans. Methods: We generated two sets of 90 DVHs from a patient’s 10-phase 4D CT set; one by conventional PTV-based optimization done in the Eclipse treatment planning system, and the other by an in-house robust optimization algorithm. The 90 DVHs were created for the following scenarios in each of the ten phases of the 4DCT: ± 5mm shift along x, y, z; ± 3.5% range uncertainty and a nominal scenario. A Matlab function written by Gay and Niemierko was modified to calculate EUD for each DVH for the following structures: esophagus, heart, ipsilateral lung and spinal cord. An F-test determined whether or not the variances of each structure’s DVHs were statistically different. Then a t-test determined if the average EUDs for each optimization algorithm were statistically significantly different. Results: T-test results showed each structure had a statistically significant difference in average EUD when comparing robust optimization versus PTV-based optimization. Under robust optimization all structures except the spinal cord received lower EUDs than PTV-based optimization. Using robust optimization the average EUDs decreased 1.45% for the esophagus, 1.54% for the heart and 5.45% for the ipsilateral lung. The average EUD to the spinal cord increased 24.86% but was still well below tolerance. Conclusion: This work has helped quantify a qualitative relationship noted earlier in our work: that robust optimization leads to plans with greater normal tissue sparing compared to PTV-based optimization. Except in the case of the spinal cord all structures received a lower EUD under robust optimization and these results are statistically significant. While the average EUD to the spinal cord increased to 25.06 Gy under robust optimization it is still well under the TD50 value of 66.5 Gy from Emami et al. Supported in part by the NCI U19 CA021239.

Synthesis of carbon-11-labeled 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazine derivatives as new potential PET tracers for imaging of p38α mitogen-activated protein kinase.

Science.gov (United States)

Wang, Min; Gao, Mingzhang; Zheng, Qi-Huang

2014-08-15

The reference standards methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10b) and corresponding precursors 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11b) were synthesized from methyl crotonate and 3-amino-4-methylbenzoic acid in multiple steps with moderate to excellent yields. The target tracer [(11)C]methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate ([(11)C]10a) and [(11)C]methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate ([(11)C]10b) were prepared from their corresponding precursors with [(11)C]CH3OTf under basic condition through O-[(11)C]methylation and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields at end of bombardment (EOB) with 185-555 GBq/μmol specific activity at end of synthesis (EOS). Copyright © 2014 Elsevier Ltd. All rights reserved.

F2-isoprostanes and F4-neuroprostanes as markers of intracranial aneurysm development.

Science.gov (United States)

Syta-Krzyżanowska, Anna; Jarocka-Karpowicz, Iwona; Kochanowicz, Jan; Turek, Grzegorz; Rutkowski, Robert; Gorbacz, Krzysztof; Mariak, Zenon; Skrzydlewska, Elżbieta

2018-04-24

Intracranial aneurysms are common, occurring in about 1-2% of the population. Saccular aneurysm is a pouch-like pathological dilatation of an intracranial artery that develops when the cerebral artery wall becomes too weak to resist hemodynamic pressure and distends. The aim of this study was to determine whether the development of intracranial aneurysms and subarachnoid hemorrhage (SAH) affects neuronal phospholipid metabolism, and what influence different invasive treatments have on brain free radical phospholipid metabolism. The level of polyunsaturated fatty acid (PUFA) cyclization products - F2-isoprostanes and F4-neuroprostanes - was examined using liquid chromatography - mass spectrometry (LC-MS) in the plasma of patients with brain aneurysm and resulting subarachnoid hemorrhage. It was revealed that an aneurysm leads to the enhancement of lipid peroxidation with a significant increase in plasma F2-isoprostanes and F4-neuroprostanes (more than 3-fold and 11-fold, respectively) in comparison to healthy subjects. The rupture of an aneurysm results in hemorrhage and an additional increase in examined prostaglandin derivatives. The embolization and clipping of aneurysms contribute to a gradual restoration of metabolic homeostasis in brain cells, which is visible in the decrease in PUFA cyclization products. The results indicate that aneurysm development is associated with enhanced inflammation and oxidative stress, factors which favor lipid peroxidation, particularly in neurons, whose membranes are rich in docosahexaenoic acid, a precursor of F4-neuroprostanes.

Tumor tissue levels of tissue inhibitor of metalloproteinases-I (TIMP-I) and outcome following adjuvant chemotherapy in premenopausal lymph node-positive breast cancer patients

DEFF Research Database (Denmark)

Schrohl, Anne-Sofie; Look, Maxime P.; Gelder, Marion E. Meijer-van

2009-01-01

BACKGROUND: We have previously demonstrated that high tumor tissue levels of TIMP-1 are associated with no or limited clinical benefit from chemotherapy with CMF and anthracyclines in metastatic breast cancer patients. Here, we extend our investigations to the adjuvant setting studying outcome...... an association between shorter survival after treatment in TIMP-1 high patients compared with TIMP-1 low patients, especially in patients receiving anthracycline-based therapy. This suggests that high tumor tissue levels of TIMP-1 might be associated with reduced benefit from classical adjuvant chemotherapy. Our...... after adjuvant chemotherapy in premenopausal lymph node-positive patients. We hypothesize that TIMP-1 high tumors are less sensitive to chemotherapy and accordingly that high tumor tissue levels are associated with shorter survival. METHODS: From our original retrospectively collected tumor samples we...

Comparison of ESR1 Mutations in Tumor Tissue and Matched Plasma Samples from Metastatic Breast Cancer Patients

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Takashi Takeshita

2017-10-01

Full Text Available BACKGROUND: ESR1 mutation in circulating cell-free DNA (cfDNA is emerging as a noninvasive biomarker of acquired resistance to endocrine therapy, but there is a paucity of data comparing the status of ESR1 gene in cfDNA with that in its corresponding tumor tissue. The objective of this study is to validate the degree of concordance of ESR1 mutations between plasma and tumor tissue. METHODS: ESR1 ligand-binding domain mutations Y537S, Y537N, Y537C, and D538G were analyzed using droplet digital PCR in 35 patients with metastatic breast cancer (MBC (35 tumor tissue samples and 67 plasma samples. RESULTS: Of the 35 paired samples, 26 (74.3% were concordant: one patient had detectable ESR1 mutations both plasma (ESR1 Y537S/Y537N and tumor tissue (ESR1 Y537S/Y537C, and 25 had WT ESR1 alleles in both. Nine (25.7% had discordance between the plasma and tissue results: five had mutations detected only in their tumor tissue (two Y537S, one Y537C, one D538G, and one Y537S/Y537N/D538G, and four had mutations detected only in their plasma (one Y537S, one Y537N, and two Y537S/Y537N/D538G. Furthermore, longitudinal plasma samples from 19 patients were used to assess changes in the presence of ESR1 mutations during treatment. Eleven patients had cfDNA ESR1 mutations over the course of treatment. A total of eight of 11 patients with MBC with cfDNA ESR1 mutations (72.7% had the polyclonal mutations. CONCLUSION: We have shown the independent distribution of ESR1 mutations between plasma and tumor tissue in 35 patients with MBC.

Integrity of the oral tissues in patients with solid-organ transplants.

Science.gov (United States)

Rojas, Gonzalo; Bravo, Loreto; Cordero, Karina; Sepúlveda, Luis; Elgueta, Leticia; Díaz, Juan Carlos; Urzúa, Blanca; Morales, Irene

2012-01-01

The relationship between the use of immunosuppressants in solid-organ transplant patients and oral tissue abnormalities has been recognized. The objective of this study was to determine the state of oral tissue integrity in renal, heart, and liver transplant patients who are on continuous medical and dental control. Forty patients of both sexes were clinically evaluated at the Clinical Hospital of the University of Chile to identify pathologies of oral mucosa, gingival enlargement (GE), decayed, missing, filled teeth (DMFT) index, and salivary flow. The average age of the transplant subjects was 49.4 years, and the age range was 19 to 69 years. Most subjects maintained a good level of oral hygiene, and the rate mean of DMFT was 14.7. The degree of involvement of the oral mucosa and GE was low (10%). Unlike other studies, the frequency of oral mucosal diseases and GE was low despite the fact that these patients were immunosuppressed. Care and continuous monitoring seem to be of vital importance in maintaining the oral health of transplant patients.

Integrity of the Oral Tissues in Patients with Solid-Organ Transplants

Directory of Open Access Journals (Sweden)

Gonzalo Rojas

2012-01-01

Full Text Available The relationship between the use of immunosuppressants in solid-organ transplant patients and oral tissue abnormalities has been recognized. The objective of this study was to determine the state of oral tissue integrity in renal, heart, and liver transplant patients who are on continuous medical and dental control. Forty patients of both sexes were clinically evaluated at the Clinical Hospital of the University of Chile to identify pathologies of oral mucosa, gingival enlargement (GE, decayed, missing, filled teeth (DMFT index, and salivary flow. The average age of the transplant subjects was 49.4 years, and the age range was 19 to 69 years. Most subjects maintained a good level of oral hygiene, and the rate mean of DMFT was 14.7. The degree of involvement of the oral mucosa and GE was low (10%. Unlike other studies, the frequency of oral mucosal diseases and GE was low despite the fact that these patients were immunosuppressed. Care and continuous monitoring seem to be of vital importance in maintaining the oral health of transplant patients.

Oral administration of a select mixture of Bacillus probiotics generates Tr1 cells in weaned F4ab/acR pigs challenged with an F4+ ETEC/VTEC/EPEC strain

DEFF Research Database (Denmark)

Zhou, Dong; Zhang, Wei; Wang, Meng-Ling

2015-01-01

Although breeding of F4 receptor − negative (F4R−) pigs may prevent post-weaning diarrhea, the underlying immunity is poorly understood. Here, various doses of a Bacillus licheniformis and Bacillus subtilis mixture (BLS-mix) were orally administered to F4ab/acR− pigs for 1 week before F4 (K88) − ...... of BLS-mix during episodes of intestinal inflammation that is caused by enteric pathogens might prohibit clearance of the pathogen. Select probiotic mixtures may allow for tailoring strategies to prevent infectious diseases....

Comparisons of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol with [{sup 18}F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

Energy Technology Data Exchange (ETDEWEB)

McLarty, Kristin; Moran, Matthew D. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Scollard, Deborah A.; Chan, Conrad [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Sabha, Nesrin; Mukherjee, Joydeep; Guha, Abhijit [Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, University of Toronto, ON, M5G 1X8 (Canada); McLaurin, JoAnne [Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, M5S 3H2 (Canada); Nitz, Mark [Department of Chemistry, University of Toronto, Toronto, ON, M5S 3H6 (Canada); Houle, Sylvain; Wilson, Alan A. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Reilly, Raymond M., E-mail: raymond.reilly@utoronto.ca [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Toronto General Research Institute, University Health Network, Toronto, ON, M5G 2M9 (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Vasdev, Neil, E-mail: neil.vasdev@utoronto.ca [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

2011-10-15

Introduction: The aim of the study was to evaluate the uptake of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol ([{sup 18}F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [{sup 18}F]-2-fluoro-2-deoxy-D-glucose ([{sup 18}F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [{sup 18}F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [{sup 18}F]-scyllo-inositol and [{sup 18}F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. Results: The radiosynthesis of [{sup 18}F]-scyllo-inositol was automated with good radiochemical yields (24.6%{+-}3.3%, uncorrected for decay, 65{+-}2 min, n=5) and high specific activities ({>=}195 GBq/{mu}mol at end of synthesis). Uptake of [{sup 18}F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [{sup 18}F]-FDG (4.6{+-}0.5 vs. 5.5{+-}2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [{sup 18}F]-scyllo-inositol in inflammation was lower than [{sup 18}F]-FDG. While uptake of [{sup 18}F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [{sup 18}F]-FDG, the tumour-to-brain ratio was significantly higher (10.6{+-}2.5 vs. 2.1{+-}0.6; P=.001). Conclusions: Consistent with biodistribution studies, uptake of [{sup 18}F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [{sup 18}F]-FDG. The tumour-to-brain ratio of [{sup 18}F]-scyllo-inositol was also significantly higher than that of [{sup 18}F]-FDG for visualizing intracranial glioma xenografts in

Unsuspected Active Sarcoidosis Diagnosed by {sup 18}F-FDG PET/CT During the Search for a Primary Tumour in a Patient with Bone Lesions

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Caobelli, Federico; Pizzocaro, Claudio; Soffientini, Alberto; Guerra, Ugo Paolo [Fondazion Poliambulanza, Brescia (Italy); Gabanelli, Sara Vincenzina; Brucato, Antonio [Ospedali Riuniti, Bergamo (Italy); Giubbini, Raffaele [Univ. of Brescia, Brescia (Italy)

2013-09-15

Sarcoidosis is a systemic chronic inflammatory disease of unknown aetiology, characterised by granulomatous lesions with heterogeneous clinical manifestations affecting multiple organs and tissues. Although the respiratory system is most commonly affected, the disease may also present with bone lesions. We report the case of a 31-year old woman who presented with low back pain and no history of cancer and who was found to have suspicious lesions involving the entire spine on magnetic resonance imaging (MRI). The patient underwent {sup 18}F-fluorodeoxyglucose (FDG) PET/CT to search for a primary tumour and for staging purposes. {sup 18}F-FDG PET/CT revealed a pattern of hypermetabolic activity in widespread skeletal lesions and in a single left cervical lymph node. The primary tumour was not found, thus suggesting a haematologic disorder. Subsequent biopsies of a cervical lymph node and of bone tissue from L4 revealed active sarcoidosis with no evidence of cancer. This underlines the importance of considering all alternatives when hypermetabolic lesions are found on {sup 18}F-FDG PET/CT. Furthermore, {sup 18}F-FDG PET can be very useful to indicate accessible sites for guiding fine-needle aspiration cytology (FNAC)

Unsuspected muscle metastases detected with "1"8F-FDG PET/CT

International Nuclear Information System (INIS)

San Román, J.; Hovsepian, M.

2017-01-01

Objective: To assess the prevalence of unsuspected muscle metastases (MM) in patients with known malignant disease, examined with "1"8F-fluorodeoxyglucose positron emission tomography integrated with computed tomography ("1"8F-FDG PET/CT). Materials and methods: A total of 2,953 "1"8F-FDG PET/CT examinations were retrospectively analysed, looking for cases with MM. Primary neoplasm, number and location of MM and SUV max were recorded on each patient. Oncology patients with known histology and multiple secondary lesions were included. The "1"8F-FDG PET/CT was the reference method for detection of metastases. Results: MM were observed in 33 patients (prevalence: 1.12%) aged between 18 and 88 years. The primary tumours included: kidney in 7 cases, breast in 5, melanoma in 4, lung in 3, ovary in 3, thyroid in 3, sarcomas in 3, colorectal in 2, bladder in 2, and endometrial in 1. A total of 96 MM were observed in 33 patients, and located in: thigh muscles 24, gluteal 15, chest wall 13, iliopsoas 10, paravertebral muscles 10, abdominal wall 7, leg 7, arm 4, and other locations 6 (pelvis, neck, etc.). MM affected only one muscle in 22/33 patients and several muscles in 11/33. Hypermetabolic focus was the most frequent uptake pattern, with SUV max between 1.5 and 34. Discussion: Our series has a significant number of cases, and is consistent with other authors on the incidence and location of MM. Conclusion: MM are uncommon and may be overlooked. MM may be detected with "1"8F-FDG PET/CT as single or multiple hypermetabolic foci. (authors) [es

Advantages of 18F FDG-PET/CT over Conventional Staging for Sarcoma Patients.

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Németh, Zsuzsanna; Boér, Katalin; Borbély, Katalin

2017-10-09

The effective management of patients with sarcomas requires accurate diagnosis and staging. Imaging, such as ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI) are the most freqently used methods for the detection of the lesion location, size, morphology and structural changes to adjacent tissues; however, these modalities provide little information about tumour biology. MRI is a robust and useful modality in tumour staging of sarcomas, however metabolic-fluorodeoxyglucose positron emission tomography/ computer tomography ( 18 F-FDG PET/CT) provides greater accuracy to overall staging in combination with MRI [1]. The advantages of 18 F-FDG PET/CT method compared with CT and MRI is that it provides a whole body imaging, maps the viability of the tumour or the metabolic activity of the tissue. Additionally, PET detects the most agressive part of the tumour, demonstrates the biological behaviour of the tumour and therefore has a predictive value. Little data ara available on the role of 18 F-FDG PET/CT in the management of sarcomas. The present manuscript aims to provide a review of the major indications of 18 F-FDG PET/CT for diagnosis, staging, restaging and monitoring response to therapy and to compare its usefulness with the conventional imaging modalities in the management of patients with sarcomas.

PSEN1 L226F mutation in a patient with early-onset Alzheimer’s disease in Korea

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Bagyinszky E

2016-10-01

Full Text Available Eva Bagyinszky,1,* Sun Ah Park,2,* Hyung Jun Kim,2 Seong Hye Choi,3 Seong Soo A An,1 SangYun Kim4 1Department of BioNano Technology, Gachon University, Seongnam-si, 2Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, 3Department of Neurology, Inha University School of Medicine, Incheon, 4Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea *These authors contributed equally to this work Abstract: In this study, we report a first 226leucine (Leu mutation to phenylalanine (Phe in (PSEN1, CTC>TTC, L226F in Asia from a Korean early-onset Alzheimer’s disease (EOAD patient. Polymerase chain reaction (PCR–single strand conformation polymorphism, sequencing, and in silico predictions were performed. Previously, L226F was reported in EOAD patients by Zekanowski et al and Gómez-Tortosa et al. Disease phenotypes appeared in their thirties, and family history was positive in both cases. In our patient, age of onset was similar (37 years of age, but the mutation seemed to be de novo, since no affected family member was found. This leucine to phenylalanine substitution may cause additional stresses inside the transmembrane region due to large aromatic side chain and increased hydrophobic interactions with hydrocarbon chains in the membrane and its binding partners. Clinical phenotype of the mutation was aggressive progression into neurodegeneration, resulting in rapid cognitive decline. One of the patients was initially diagnosed with frontotemporal dementia, but the diagnosis was revised to AD upon postmortem studies in which Aβ plaques were seen. A second mutation, L226R, was found for the L226 residue. Similar to L226F, the patient with L226R also developed the first symptoms in his 30s, but EOAD was diagnosed in his 40s. These findings suggested that L226 might be an important residue in PSEN1

First experience with early dynamic 18F-NaF-PET/CT in patients with chronic osteomyelitis

International Nuclear Information System (INIS)

Freesmeyer, M.; Stecker, F.F.; Schierz, J.-H.; Winkens, T.; Hofmann, G.O.

2014-01-01

This study investigates whether early dynamic positron emission tomography/computed tomography (ed-PET/CT) using 18 F-sodium fluoride-( 18 F-NaF) is feasible in depicting early phases of radiotracer distribution in patients with chronic osteomyelitis (COM). A total of 12 ed 18 F-NaF-PET/CT examinations were performed on 11 consecutive patients (2 female, 9 male; age 53 ± 12 years) in list mode over 5 min starting with radiopharmaceutical injection before standard late 18 F-NaF-PET/CT. Eight consecutive time intervals (frames) were reconstructed for each patient: four 15 s, then four 60 s. Several volumes of interest (VOI) were selected, representing the affected area as well as different reference areas within the bone and soft tissue. Maximum and mean ed standardized uptake values (edSUV max , edSUV mean , respectively) were calculated in each VOI during each frame to measure early fluoride influx and accumulation. Results were compared between affected and non-affected (contralateral) bones. Starting in the 31-45 s frame, the affected bone area showed significantly higher edSUV max and edSUV mean compared to the healthy contralateral region. The affected bone areas also significantly differed from non-affected contralateral regions in conventional late 18 F-NaF-PET/CT. This pilot study suggests that, in patients with COM, ed 18 F-NaF-PET offers additional information about early radiotracer distribution to standard 18 F-NaF-PET/CT, similar to a three-phase bone scan. The results should be validated in larger trials which directly compare ed 18 F-NaF-PET to a three-phase bone scan. (author)

Efficiency, safety, and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog.

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Shimizu, Yoshie; Nakakura, Shunsuke; Nishiyama, Makiko; Tabuchi, Hitoshi; Kiuchi, Yoshiaki

2015-01-01

We investigated the efficiency, safety and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog. We initially enrolled 44 eyes from 44 primary open angle glaucoma patients, and a total of 42 patients completed the study. All patients were under treatment with various prostaglandin F2α analogs and dorzolamide 1%/timolol 0.5%. While maintaining the prostaglandin F2α analog, dorzolamide 1%/timolol 0.5% was switched to brinzolamide 1%/timolol 0.5%. Conjunctival hyperemia, superficial punctate keratopathy, and intraocular pressure (IOP) were evaluated at baseline and at 4, 12, and 24 weeks. Adverse events and patient preferences, measured using a questionnaire at study initiation and at 24 weeks, were also noted. The IOP was 17.7±1.7, 16.8±2.6, 16.7±2.2, and 16.7±2.4 mmHg at baseline and at 4, 12, and 24 weeks, respectively, with no significant differences in IOP values at any time point (P=0.117, one-way analysis of variance). In addition, no significant differences were found in the incidence of conjunctival hyperemia or SPK score at any time point (all P>0.5, by Kruskal-Wallis test). Based on the evaluation of side effects using the questionnaire, stinging/burning was less common (P=0.042), while blurred vision was more common (P=0.003), after switching to brinzolamide 1%/timolol 0.5%. Regarding patient preferences, 13 patients (31%) preferred dorzolamide 1%/timolol 0.5%, 12 patients (29%) preferred brinzolamide 1%/timolol 0.5%, and 17 patients (40%) preferred neither. When switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5%, the IOP values and incidence of superficial punctate keratopathy and conjunctival hyperemia were sustained throughout the 24-week observation period, and the patient preferences were similar for the two regimens. However, differences were observed in the ocular sensations of stinging/burning with dorzolamide 1%/timolol 0

Automated synthesis of ["1"8F](2S,4R)-4-fluoroglutamine on a GE TRACERlab™ FX-N Pro module

International Nuclear Information System (INIS)

Zhang, Xiang; Basuli, Falguni; Shi, Zhen-Dan; Xu, Biying; Blackman, Burchelle; Choyke, Peter L.; Swenson, Rolf E.

2016-01-01

Glutamine (Gln) and its analogues may serve as imaging agents for tumor diagnosis using positron emission tomography (PET), especially for tumors with negative ["1"8F]FDG scan. We report the first automated synthesis of ["1"8F](2S,4R)-4-fluoroglutamine (["1"8F]FGln) on a GE TRACERlab™ FX-N Pro module. ["1"8F]FGln was obtained in 80±3 min with a radiochemical yield of 21±3% (n=5, uncorrected). The radiochemical purity was >98%, and optical purity 90±5%. The synthesis is highly reproducible with good chemical purity, radiochemical yield, and is suitable for translation to cGMP production. - Highlights: • The radiosynthesis of ["1"8F]fluoroglutamine was optimized with improved yield and purity. • Fully automated synthesis was established on a GE TRACERlab™ FX-N Pro module. • Radiochemical yield of 21±3% (uncorrected, n=5) was obtained with good reproducibility. • The automation could be easily adapted to cGMP production for routine clinical use.

F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity.

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Miller, C H; Benson, J; Ellingsen, D; Driggers, J; Payne, A; Kelly, F M; Soucie, J M; Craig Hooper, W

2012-05-01

Both genetic and treatment-related risk factors contribute to the development of inhibitors in haemophilia. An inhibitor surveillance system piloted at 12 US sites has the goal of assessing risk factors through prospective data collection. This report examines the relationship of genotype and race/ethnicity to history of inhibitor in a large cohort of US haemophilia patients. Mutation analysis was performed on 676 haemophilia A (HA) and 153 haemophilia B (HB) patients by sequencing, Multiplex Ligation-dependent Probe Amplification, and PCR for inversions in F8 introns 22 (inv22) and 1 (inv1). Two HB patients with deletions had history of inhibitor. In severe HA, frequency of history of inhibitor was: large deletion 57.1%, splice site 35.7%, inv22 26.8%, nonsense 24.5%, frameshift 12.9%, inv1 11.1% and missense 9.5%. In HA, 19.6% of 321 White non-Hispanics (Whites), 37.1% of 35 Black non-Hispanics (Blacks) and 46.9% of 32 Hispanics had history of inhibitor (P = 0.0003). Mutation types and novel mutation rates were similar across ethnicities. When F8 haplotypes were constructed, Whites and Hispanics showed only H1 and H2. Within H1, history of inhibitor was 12.4% in Whites, 40.0% in Blacks (P = 0.009) and 32.4% in Hispanics (P = 0.002). Inhibitor frequency is confirmed to vary by mutation type and race in a large US population. White patients with history of inhibitor did not exhibit rare F8 haplotypes. F8 gene analysis did not reveal a cause for the higher inhibitor frequencies in Black and Hispanic patients. © 2011 Blackwell Publishing Ltd.

Expression of inflammation-related genes is altered in gastric tissue of patients with advanced stages of NAFLD.

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Mehta, Rohini; Birerdinc, Aybike; Neupane, Arpan; Shamsaddini, Amirhossein; Afendy, Arian; Elariny, Hazem; Chandhoke, Vikas; Baranova, Ancha; Younossi, Zobair M

2013-01-01

Obesity is associated with chronic low-grade inflammation perpetuated by visceral adipose. Other organs, particularly stomach and intestine, may also overproduce proinflammatory molecules. We examined the gene expression patterns in gastric tissue of morbidly obese patients with nonalcoholic fatty liver disease (NAFLD) and compared the changes in gene expression in different histological forms of NAFLD. Stomach tissue samples from 20 morbidly obese NAFLD patients who were undergoing sleeve gastrectomy were profiled using qPCR for 84 genes encoding inflammatory cytokines, chemokines, their receptors, and other components of inflammatory cascades. Interleukin 8 receptor-beta (IL8RB) gene overexpression in gastric tissue was correlated with the presence of hepatic steatosis, hepatic fibrosis, and histologic diagnosis of nonalcoholic steatohepatitis (NASH). Expression levels of soluble interleukin 1 receptor antagonist (IL1RN) were correlated with the presence of NASH and hepatic fibrosis. mRNA levels of interleukin 8 (IL8), chemokine (C-C motif) ligand 4 (CCL4), and its receptor chemokine (C-C motif) receptor type 5 (CCR5) showed a significant increase in patients with advanced hepatic inflammation and were correlated with the severity of the hepatic inflammation. The results of our study suggest that changes in expression patterns for inflammatory molecule encoding genes within gastric tissue may contribute to the pathogenesis of obesity-related NAFLD.

Low vitamin K1 intake in haemodialysis patients.

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Fusaro, Maria; D'Alessandro, Claudia; Noale, Marianna; Tripepi, Giovanni; Plebani, Mario; Veronese, Nicola; Iervasi, Giorgio; Giannini, Sandro; Rossini, Maurizio; Tarroni, Giovanni; Lucatello, Sandro; Vianello, Alberto; Santinello, Irene; Bonfante, Luciana; Fabris, Fabrizio; Sella, Stefania; Piccoli, Antonio; Naso, Agostino; Ciurlino, Daniele; Aghi, Andrea; Gallieni, Maurizio; Cupisti, Adamasco

2017-04-01

Vitamin K acts as a coenzyme in the γ-carboxylation of vitamin K-dependent proteins, including coagulation factors, osteocalcin, matrix Gla protein (MGP), and the growth arrest-specific 6 (GAS6) protein. Osteocalcin is a key factor for bone matrix formation. MGP is a local inhibitor of soft tissue calcification. GAS6 activity prevents the apoptosis of vascular smooth muscle cells. Few data on vitamin K intake in chronic kidney disease patients and no data in patients on a Mediterranean diet are available. In the present study, we evaluate the dietary intake of vitamin K1 in a cohort of patients undergoing haemodialysis. In this multi-centre controlled observational study, data were collected from 91 patients aged >18 years on dialysis treatment for at least 12 months and from 85 age-matched control subjects with normal renal function. Participants completed a food journal of seven consecutive days for the estimation of dietary intakes of macro- and micro-nutrients (minerals and vitamins). Compared to controls, dialysis patients had a significant lower total energy intake, along with a lower dietary intake of proteins, fats, carbohydrates, fibres, and of all the examined minerals (Ca, P, Fe, Na, K, Zn, Cu, and Mg). With the exception of vitamin B12, vitamins intake followed a similar pattern, with a lower intake in vitamin A, B1, B2, C, D, E, folates, K1 and PP. These finding were confirmed also when normalized for total energy intake or for body weight. In respect to the adequate intakes recommended in the literature, the prevalence of a deficient vitamin K intake was very high (70-90%) and roughly double than in controls. Multivariate logistic model identified vitamin A and iron intake as predictors of vitamin K deficiency. Haemodialysis patients had a significantly low intake in vitamin K1, which could contribute to increase the risk of bone fractures and vascular calcifications. Since the deficiency of vitamin K intake seems to be remarkable, dietary

Expression of the chemokine receptor CXCR4 on lymphocytes of leprosy patients

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V.A. Mendonça

2011-12-01

Full Text Available Leprosy is caused by Mycobacterium leprae, which induces chronic granulomatous infection of the skin and peripheral nerves. The disease ranges from the tuberculoid to the lepromatous forms, depending on the cellular immune response of the host. Chemokines are thought to be involved in the immunopathogenesis of leprosy, but few studies have investigated the expression of chemokine receptors on leukocytes of leprosy patients. In the present study, we evaluated 21 leprosy patients (M/F: 16/5 with a new diagnosis from the Dermatology Outpatient Clinic of the University Hospital, Federal University of Minas Gerais. The control group was composed of 20 healthy members (M/F: 15/5 of the community recruited by means of announcements. The expression of CCR2, CCR3, CCR5, and CXCR4 was investigated by flow cytometry on the surface of peripheral blood lymphocytes. There was a decrease in percentage of CD3+CXCR4+ and CD4+CXCR4+ lymphocytes in the peripheral blood of leprosy patients (median [range], 17.6 [2.7-41.9] and 65.3 [3.9-91.9], respectively compared to the control group (median [range], 43.0 [3.7-61.3] and 77.2 [43.6-93.5], respectively. The percentage of CD4+CXCR4+ was significantly lower in patients with the tuberculoid form (median [range], 45.7 [0.0-83.1] of the disease, but not in lepromatous patients (median [range], 81.5 [44.9-91.9]. The CXCR4 chemokine receptor may play a role in leprosy immunopathogenesis, probably directing cell migration to tissue lesions in tuberculoid leprosy patients.

Fluorescence F 0 of photosystems II and I in developing C3 and C 4 leaves, and implications on regulation of excitation balance.

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Peterson, Richard B; Oja, Vello; Eichelmann, Hillar; Bichele, Irina; Dall'Osto, Luca; Laisk, Agu

2014-10-01

This work addresses the question of occurrence and function of photosystem II (PSII) in bundle sheath (BS) cells of leaves possessing NADP-malic enzyme-type C4 photosynthesis (Zea mays). Although no requirement for PSII activity in the BS has been established, several component proteins of PSII have been detected in BS cells of developing maize leaves exhibiting O2-insensitive photosynthesis. We used the basal fluorescence emissions of PSI (F 0I) and PSII (F 0II) as quantitative indicators of the respective relative photosystem densities. Chl fluorescence induction was measured simultaneously at 680 and 750 nm. In mature leaves, the F m(680)/F 0(680) ratio was 10.5 but less in immature leaves. We propose that the lower ratio was caused by the presence of a distinct non-variable component, F c, emitting at 680 and 750 nm. After F c was subtracted, the fluorescence of PSI (F 0I) was detected as a non-variable component at 750 nm and was undetectably low at 680 nm. Contents of Chls a and b were measured in addition to Chl fluorescence. The Chl b/(a + b) was relatively stable in developing sunflower leaves (0.25-0.26), but in maize it increased from 0.09 to 0.21 with leaf tissue age. In sunflower, the F 0I/(F 0I + F 0II) was 0.39 ± 0.01 independent of leaf age, but in maize, this parameter was 0.65 in young tissue of very low Chl content (20-50 mg m(-2)) falling to a stable level of 0.53 ± 0.01 at Chl contents >100 mg m(-2). The values of F 0I/(F 0I + F 0II) showed that in sunflower, excitation was partitioned between PSII and PSI in a ratio of 2:1, but the same ratio was 1:1 in the C4 plant. The latter is consistent with a PSII:PSI ratio of 2:1 in maize mesophyll cells and PSI only in BS cells (2:1:1 distribution). We suggest, moreover, that redox mediation of Chl synthesis, rather than protein accumulation, regulates photosystem assembly to ensure optimum excitation balance between functional PSII and PSI. Indeed, the apparent necessity for two

Effects of prenatal low protein and postnatal high fat diets on visceral adipose tissue macrophage phenotypes and IL-6 expression in Sprague Dawley rat offspring

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Adipose tissue macrophages (ATM) are implicated in adipose tissue inflammation and obesity-related insulin resistance. Maternal low protein models result in fetal programming of obesity. However, it is not known whether maternal undernutrition increases ATM phenotypic expression in F1 offspring. Us...

Radiosynthesis, rodent biodistribution, and metabolism of 1-deoxy-1-[18F]fluoro-d-fructose

International Nuclear Information System (INIS)

Haradahira, Terushi; Tanaka, Akihiro; Maeda, Minoru; Kanazawa, Yoko; Ichiya, Yu-Ichi; Masuda, Kouji

1995-01-01

Fluorine-18 labeled analog of d-fructose, 1-deoxy-1-[ 18 F]fluoro-d-fructose (1-[ 18 F]FDFrc), was synthesized by nucleophilic substitution of [ 18 F]fluoride ion and the effect of the fluorine substitution on its in vivo metabolism was investigated. The tissue distributions of 1-[ 18 F]FDFrc in rats and tumor bearing mice showed initial high uptake and subsequent rapid washout of the radioactivity in the principal sites of d-fructose metabolism (kidneys, liver and small intestine). The uptakes in the brain and tumor (fibrosarcoma) were the lowest and moderate, respectively, but tended to increase with time. The in vivo metabolic studies of 1-[ 18 F]FDFrc and nonradiactive 1-FDFrc in mouse brain and tumor showed that the fluorinated analog remained unmetabolized in these tissues, indicating that the substitution of fluorine at the C-1 position produces a nonmetabolizable analog of d-fructose. Thus, 1-[ 18 F]FDFrc had no features of a metabolic trapping tracer without showing any appreciable organ or tumor specific localization

Association of HLA-DRB1 alleles with susceptibility to mixed connective tissue disease in Polish patients.

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Paradowska-Gorycka, A; Stypińska, B; Olesińska, M; Felis-Giemza, A; Mańczak, M; Czuszynska, Z; Zdrojewski, Z; Wojciechowicz, J; Jurkowska, M

2016-01-01

Mixed connective tissue disease (MCTD) is a systemic autoimmune disease, originally defined as a connective tissue inflammatory syndrome with overlapping features of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM) and systemic sclerosis (SSc), characterized by the presence of antibodies against components of the U1 small nuclear ribonucleoprotein (U1snRNP). The aim of the study was to assess the frequency of (high-resolution-typed) DRB1 alleles in a cohort of Polish patients with MCTD (n = 103). Identification of the variants potentially associated with risk and protection was carried out by comparison with the DKMS Polish Bone Marrow Donor Registry (41306 alleles). DRB1*15:01 (odds ratio (OR): 6.06; 95% confidence interval (CI) 4.55-8.06), DRB1*04 (OR: 3.69; 95% CI 2.69-5.01) and *09:01 (OR: 8.12; 95% CI 2.15-21.75) were identified as risk alleles for MCTD, while HLA-DRB1*07:01 allele was found to be protective (OR: 0.50; 95% CI 0.28-0.83). The carrier frequency of the DRB1*01 was higher in MCTD patients compared with controls, although the differences were not statistically significant. Our results confirm the modulating influence of HLA-DRB1 genotypes on development of connective tissue diseases such as MCTD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Regional distribution and kinetics of [18F]fluciclovine (anti-[18F]FACBC), a tracer of amino acid transport, in subjects with primary prostate cancer.

Science.gov (United States)

Sörensen, Jens; Owenius, Rikard; Lax, Michelle; Johansson, Silvia

2013-02-01

[(18)F]Fluciclovine (anti-[(18)F]FACBC) is a synthetic amino acid developed for PET assessment of the anabolic component of tumour metabolism in clinical routine. This phase 1 trial evaluated the safety, tracer stability and uptake kinetics of [(18)F]fluciclovine in patients. Six patients with biopsy-proven prostate cancer were investigated with 3-T MRI and PET/CT. All underwent dynamic [(18)F]fluciclovine PET/CT of the pelvic area for up to 120 min after injection of 418 ± 10 MBq of tracer with simultaneous blood sampling of radioactivity. The kinetics of uptake in tumours and normal tissues were evaluated using standardized uptake values (SUVs) and compartmental modelling. Tumour deposits as defined by MRI were clearly visualized by PET. Urine excretion was minimal and normal tissue background was low. Uptake of [(18)F]fluciclovine in tumour from the blood was rapid and the tumour-to-normal tissue contrast was highest between 1 and 15 min after injection with a 65 % reduction in mean tumour uptake at 90 min after injection. A one-compartment model fitted the tracer kinetics well. Early SUVs correlated well with both the influx rate constant (K (1)) and the volume of distribution of the tracer (V (T)). There were no signs of tracer metabolite formation. The product was well tolerated in all patients without significant adverse events. [(18)F]Fluciclovine shows high uptake in prostate cancer deposits and appears safe for use in humans. The production is robust and the formulation stable in vivo. An early imaging window seems to provide the best visual results. SUV measurements capture most of the kinetic information that can be obtained from more advanced models, potentially simplifying quantification in future studies.

Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

International Nuclear Information System (INIS)

Pires, L.A.; Hegg, R.; Freitas, F.R.; Tavares, E.R.; Almeida, C.P.; Baracat, E.C.; Maranhão, R.C.

2012-01-01

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy

Textural features of "1"8F-fluorodeoxyglucose positron emission tomography scanning in diagnosing aortic prosthetic graft infection

International Nuclear Information System (INIS)

Saleem, Ben R.; Zeebregts, Clark J.; Beukinga, Roelof J.; Slart, Riemer H.J.A.; Boellaard, Ronald; Glaudemans, Andor W.J.M.; Reijnen, Michel M.P.J.

2017-01-01

The clinical problem in suspected aortoiliac graft infection (AGI) is to obtain proof of infection. Although "1"8F-fluorodeoxyglucose ("1"8F-FDG) positron emission tomography scanning (PET) has been suggested to play a pivotal role, an evidence-based interpretation is lacking. The objective of this retrospective study was to examine the feasibility and utility of "1"8F-FDG uptake heterogeneity characterized by textural features to diagnose AGI. Thirty patients with a history of aortic graft reconstruction who underwent "1"8F-FDG PET/CT scanning were included. Sixteen patients were suspected to have an AGI (group I). AGI was considered proven only in the case of a positive bacterial culture. Positive cultures were found in 10 of the 16 patients (group Ia), and in the other six patients, cultures remained negative (group Ib). A control group was formed of 14 patients undergoing "1"8F-FDG PET for other reasons (group II). PET images were assessed using conventional maximal standardized uptake value (SUVmax), tissue-to-background ratio (TBR), and visual grading scale (VGS). Additionally, 64 different "1"8F-FDG PET based textural features were applied to characterize "1"8F-FDG uptake heterogeneity. To select candidate predictors, univariable logistic regression analysis was performed (α = 0.16). The accuracy was satisfactory in case of an AUC > 0.8. The feature selection process yielded the textural features named variance (AUC = 0.88), high grey level zone emphasis (AUC = 0.87), small zone low grey level emphasis (AUC = 0.80), and small zone high grey level emphasis (AUC = 0.81) most optimal for distinguishing between groups I and II. SUVmax, TBR, and VGS were also able to distinguish between these groups with AUCs of 0.87, 0.78, and 0.90, respectively. The textural feature named short run high grey level emphasis was able to distinguish group Ia from Ib (AUC = 0.83), while for the same task the TBR and VGS were not found to be predictive. SUVmax was found predictive

64Cu-DOTA-Anti-CTLA-4 mAb Enabled PET Visualization of CTLA-4 on the T-Cell Infiltrating Tumor Tissues

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Higashikawa, Kei; Yagi, Katsuharu; Watanabe, Keiko; Kamino, Shinichiro; Ueda, Masashi; Hiromura, Makoto; Enomoto, Shuichi

2014-01-01

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) targeted therapy by anti-CTLA-4 monoclonal antibody (mAb) is highly effective in cancer patients. However, it is extremely expensive and potentially produces autoimmune-related adverse effects. Therefore, the development of a method to evaluate CTLA-4 expression prior to CTLA-4-targeted therapy is expected to open doors to evidence-based and cost-efficient medical care and to avoid adverse effects brought about by ineffective therapy. In this study, we aimed to develop a molecular imaging probe for CTLA-4 visualization in tumor. First, we examined CTLA-4 expression in normal colon tissues, cultured CT26 cells, and CT26 tumor tissues from tumor-bearing BALB/c mice and BALB/c nude mice by reverse transcription polymerase chain reaction (RT-PCR) analysis and confirmed whether CTLA-4 is strongly expressed in CT26 tumor tissues. Second, we newly synthesized 64Cu-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-anti-mouse CTLA-4 mAb (64Cu-DOTA-anti-CTLA-4 mAb) and evaluated its usefulness in positron emission tomography (PET) and ex-vivo biodistribution analysis in CT26-bearing BALB/c mice. High CTLA-4 expression was confirmed in the CT26 tumor tissues of tumor-bearing BALB/c mice. However, CTLA-4 expression was extremely low in the cultured CT26 cells and the CT26 tumor tissues of tumor-bearing BALB/c nude mice. The results suggested that T cells were responsible for the high CTLA-4 expression. Furthermore, 64Cu-DOTA-anti-CTLA-4 mAb displayed significantly high accumulation in the CT26 tumor, thereby realizing non-invasive CTLA-4 visualization in the tumor. Together, the results indicate that 64Cu-DOTA-anti-CTLA-4 mAb would be useful for the evaluation of CTLA-4 expression in tumor. PMID:25365349

Evaluation of tumour hypoxia during radiotherapy using [{sup 18}F]HX4 PET imaging and blood biomarkers in patients with head and neck cancer

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Zegers, Catharina M.L.; Hoebers, Frank J.P.; Elmpt, Wouter van; Oellers, Michel C.; Eekers, Danielle; Balmaekers, Leo; Arts-Pechtold, Marlies; Lambin, Philippe [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Bons, Judith A. [Maastricht University Medical Centre, Central Diagnostic Laboratory, Maastricht (Netherlands); Troost, Esther G.C. [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Helmholtz Zentrum Dresden-Rossendorf, Dresden (Germany); Technische Universitaet Dresden, OncoRay, Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Dresden (Germany); Mottaghy, Felix M. [Maastricht University Medical Centre, Department of Nuclear Medicine, Maastricht (Netherlands); RWTH Aachen University, University Hospital, Department of Nuclear Medicine, Aachen (Germany)

2016-11-15

Increased tumour hypoxia is associated with a worse overall survival in patients with head and neck squamous cell carcinoma (HNSCC). The aims of this study were to evaluate treatment-associated changes in [{sup 18}F]HX4-PET, hypoxia-related blood biomarkers, and their interdependence. [{sup 18}F]HX4-PET/CT scans of 20 patients with HNSCC were acquired at baseline and after ±20 Gy of radiotherapy. Within the gross-tumour-volumes (GTV; primary and lymph nodes), mean and maximum standardized uptake values, the hypoxic fraction (HF) and volume (HV) were calculated. Also, the changes in spatial uptake pattern were evaluated using [{sup 18}F]HX4-PET/CT imaging. For all patients, the plasma concentration of CAIX, osteopontin and VEGF was assessed. At baseline, tumour hypoxia was detected in 69 % (22/32) of the GTVs. During therapy, we observed a significant decrease in all image parameters. The HF decreased from 21.7 ± 19.8 % (baseline) to 3.6 ± 10.0 % (during treatment; P < 0.001). Only two patients had a HV > 1 cm{sup 3} during treatment, which was located for >98 % within the baseline HV. During treatment, no significant changes in plasma CAIX or VEGF were observed, while osteopontin was increased. [{sup 18}F]HX4-PET/CT imaging allows monitoring changes in hypoxia during (chemo)radiotherapy whereas the blood biomarkers were not able to detect a treatment-associated decrease in hypoxia. (orig.)

Improving the Th1 cellular efficacy of the lead Yersinia pestis rF1-V subunit vaccine using SA-4-1BBL as a novel adjuvant.

Science.gov (United States)

Dinc, Gunes; Pennington, Jarrod M; Yolcu, Esma S; Lawrenz, Matthew B; Shirwan, Haval

2014-09-03

The lead candidate plague subunit vaccine is the recombinant fusion protein rF1-V adjuvanted with alum. While alum generates Th2 regulated robust humoral responses, immune protection against Yersinia pestis has been shown to also involve Th1 driven cellular responses. Therefore, the rF1-V-based subunit vaccine may benefit from an adjuvant system that generates a mixed Th1 and humoral immune response. We herein assessed the efficacy of a novel SA-4-1BBL costimulatory molecule as a Th1 adjuvant to improve cellular responses generated by the rF1-V vaccine. SA-4-1BBL as a single adjuvant had better efficacy than alum in generating CD4(+) and CD8(+) T cells producing TNFα and IFNγ, signature cytokines for Th1 responses. The combination of SA-4-1BBL with alum further increased this Th1 response as compared with the individual adjuvants. Analysis of the humoral response revealed that SA-4-1BBL as a single adjuvant did not generate a significant Ab response against rF1-V, and SA-4-1BBL in combination with alum did not improve Ab titers. However, the combined adjuvants significantly increased the ratio of Th1 regulated IgG2c in C57BL/6 mice to the Th2 regulated IgG1. Finally, a single vaccination with rF1-V adjuvanted with SA-4-1BBL+alum had better protective efficacy than vaccines containing individual adjuvants. Taken together, these results demonstrate that SA-4-1BBL improves the protective efficacy of the alum adjuvanted lead rF1-V subunit vaccine by generating a more balanced Th1 cellular and humoral immune response. As such, this adjuvant platform may prove efficacious not only for the rF1-V vaccine but also against other infections that require both cellular and humoral immune responses for protection. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tumor aggressiveness and patient outcome in cancer of the pancreas assessed by dynamic 18F-FDG PET/CT.

Science.gov (United States)

Epelbaum, Ron; Frenkel, Alex; Haddad, Riad; Sikorski, Natalia; Strauss, Ludwig G; Israel, Ora; Dimitrakopoulou-Strauss, Antonia

2013-01-01

This study aimed to assess the role of a quantitative dynamic PET model in pancreatic cancer as a potential index of tumor aggressiveness and predictor of survival. Seventy-one patients with (18)F-FDG-avid adenocarcinoma of the pancreas before treatment were recruited, including 27 with localized tumors (11 underwent pancreatectomy, and 16 had localized nonresectable tumors) and 44 with metastatic disease. Dynamic (18)F-FDG PET images were acquired over a 60-min period, followed by a whole-body PET/CT study. Quantitative data measurements were based on a 2-compartment model, and the following variables were calculated: VB (fractional blood volume in target area), K(1) and k(2) (kinetic membrane transport parameters), k(3) and k(4) (intracellular (18)F-FDG phosphorylation and dephosphorylation parameters, respectively), and (18)F-FDG INF (global (18)F-FDG influx). The single significant variable for overall survival (OS) in patients with localized disease was (18)F-FDG INF. Patients with a high (18)F-FDG INF (>0.033 min(-1)) had a median OS of 6 and 5 mo for nonresectable and resected tumors, respectively, versus 15 and 19 mo for a low (18)F-FDG INF in nonresectable and resected tumors, respectively (P measured by dynamic PET in newly diagnosed pancreatic cancer correlated with the aggressiveness of disease. The (18)F-FDG INF was the single most significant variable for OS in patients with localized disease, whether resectable or not.

Induction of Th1 polarized immune responses by thiolated Eudragit-coated F4 and F18 fimbriae of enterotoxigenic Escherichia coli.

Science.gov (United States)

Lee, Won-Jung; Cha, Seungbin; Shin, Minkyoung; Islam, Mohammad Ariful; Cho, Chong-su; Yoo, Han Sang

2011-10-01

Diarrhea in newborn and weaned piglets is mainly induced by enterotoxigenic Escherichia coli (ETEC) with fimbriae F4 (K88) and F18 (F107). In this study, we evaluated F4 and F18 coated with thiolated Eudragit microspheres (TEMS) as a candidate for an oral vaccine. The average particle sizes of TEMS, F4-loaded TEMS, and F18-loaded TEMS were measured as 4.2±0.75 μm, 4.7±0.50 μm, and 4.5±0.37 μm, respectively. F4 is more efficiently encapsulated than F18 in the loading with TEMS. In the release test, F4 and F18 fimbriae were protected in acidic circumstances, whereas most were released at pH 7.4 of intestine circumstances. Production of TNF-α and NO from RAW 264.7 cells was increased in a time-dependent manner after exposure to all groups, whereas only F4- or F18-loaded TEMS-stimulated IL-6 secretion. The levels of IFN-γ from mouse splenocytes after exposure to F4 or F18 were increased while IL-4 was not detectable. These results suggest that F4- and F18-loaded TEMS may effectively induce immune response with the efficient release of antigens to appropriate target sites. Copyright © 2011 Elsevier B.V. All rights reserved.

High plasma concentrations of transforming growth factor-β and tissue inhibitor of metalloproteinase-1. Potential non-invasive predictors for electroanatomical remodeling of atrium in patients with non-valvular atrial fibrillation

International Nuclear Information System (INIS)

Kim, Sook-Kyoung; Park, Jae-Hyung; Kim, Jong-Youn; Joung, Boyoung; Lee, Moon-Hyoung; Kim, Sung-Soon; Pak, Hui-Nam; Choi, Jong Il; Kim, Young-Hoon

2011-01-01

The degree of electroanatomical remodeling of the left atrial (LA) affects the clinical outcome after rhythm control of atrial fibrillation (AF). Our hypothesis was that plasma concentrations of transforming growth factor (TGF)-β and tissue inhibitor of metalloproteinase (TIMP)-1 reflect LA voltage and structural remodeling in patients with non-valvular AF. In the study, 242 patients (male 79.4%, 55.1±11.0 years old) with AF (155 paroxysmal AF, 87 persistent AF) underwent catheter ablation. Pre-ablation plasma concentrations of TGF-β and TIMP-1 and the degree of electroanatomical remodeling quantified by LA voltage map (NavX) and 3D-CT were evaluated. The mean LA voltage and volume were compared in patients with high TGF-β (±10.0 ng/ml, H-TGF) vs. low TGF-β ( 58%. In patients with non-valvular AF, high plasma concentrations TGF-β and TIMP-1 and low ejection fraction were closely related with electroanatomical remodeling of LA. (author)

Pilot Study on Genetic Polymorphisms CYP1A2*1F on Asthma Patients and Nonasthma in Indonesia

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Doddy de Queljoe

2015-03-01

Full Text Available Genetic polymorphisms of CYP1A2 is related to the theophylline metabolism that may affect drug levels in the blood, which can also affect incidence of adverse drug reaction (ADR and clinical outcomes of asthma therapy. The frequency of CYP1A2 polymorphism is known to vary among ethnic. Allegedly the Indonesian population has high frequency of gene variants of CYP1A2*1F. This study aims to determine the profile of CYP1A2*1F gene polymorphism in a sample of nonasthma and asthma in Indonesia with other populations based on the literature. Data were taken on January–June 2014. Blood samples were obtained from 29 nonasthma samples and 16 patients with asthma. After extraction of genomic DNA, CYP1A2*1F gene polymorphisms determined by PCR-RFLP. The results of this study indicate that the CYP1A2*1F gene polymorphism in nonasthma samples was 10.35% (3/29 for C/C, 37.93% (11/29 for the C/A, and 51.72% (15/29 for A/A. The asthmatics genotype have a frequency distribution of C/A genotype of 81.25% (13/16 and A/A of 18.75% (3/16. There was no significant difference (p=0.276 allele frequencies between samples of nonasthma and asthma patients. The frequency of CYP1A2*1F gene in Indonesian population is higher than the population of Egypt, Japan, and UK, but lower compared to Malaysia. It can be concluded that there is no difference in frequency.

Phase transitions in the mixed quadratic-layer antiferromagnets with competing anisotropies K2Cosub(x)Fesub(1-x)F4

International Nuclear Information System (INIS)

Vlak, W.A.H.M.

1985-09-01

The magnetic phases of the randomly mixed two-dimensional antiferromagnet K 2 Cosub(x)Fesub(1-x)F 4 have been explored, utilizing neutron diffraction, Moessbauer absorption spectroscopy, and nuclear magnetic resonance techniques. Ordered phases similar to those found in K 2 FeF 4 and K 2 CoF 4 have been detected for low and high x, respectively. By virtue of the competition between the orthogonal anisotropies of the Fe 2+ and Co 2+ ions a third ordered so-called oblique phase is found for 0.20 2+ and Co 2+ . Studies have been undertaken of the critical behavior, the sublattice magnetization and the magnetization of individual ions, and the magnetic excitations, for compositions x and temperatures T covering all relevant parts of the phase diagram. In addition, the magnetic structure of a system which enters the oblique phase is investigated in an external magnetic field. Strong nonequilibrium behavior, related to random-field effects, has been observed

Estimates of Health Detriments and Tissue Weighting Factors for Hong Kong Populations from Low Dose, Low Dose Rate and Low LET Ionising Radiation Exposure

International Nuclear Information System (INIS)

Lee, S.K.

1998-01-01

The total health detriments and the tissue weighting factors for the Hong Kong populations from low dose, low dose rate and low LET ionising radiation exposure are obtained according to the methodology recommended in ICRP Publication 60. The probabilities of fatal cancers for the general (ages 0-90) and working (ages 20-64) populations due to lifetime exposure at low dose and low dose rate are 4.9 x 10 -2 Sv -1 and 3.6 x 10 -2 Sv -1 respectively, comparing with the ICRP 60 estimates of 5.0 x 10 -2 Sv -1 and 4.0 x 10 -2 Sv -1 . The corresponding total health detriments for the general and working populations are 6.9 x 10 -2 Sv -1 and 4.9 x 10 -2 Sv -1 respectively comparing with the ICRP 60 estimates of 7.3 x 10 -2 Sv -1 and 5.6 x 10 -2 Sv -1 . Tissue weighting factors for the general population are 0.01 (bone surface and skin), 0.02 (liver, oesophagus and thyroid), 0.04 (bladder and breast), 0.08 (remainder), 0.10 (stomach), 0.11 (bone marrow), 0.15 (colon), 0.19 (lung) and 0.21 (gonads) and for the working population are 0.01 (bone surface and skin), 0.03 (liver, oesophagus and thyroid), 0.04 (breast), 0.06 (remainder), 0.07 (bladder), 0.08 (colon), 0.14 (bone marrow and stomach), 0.16 (lung) and 0.20 (gonads). (author)

of Nd3+ions in YLiF4 and LuLiF4 crystals

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