Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)-adenine derivatives.

Science.gov (United States)

Stojković, Marijana Radić; Skugor, Marko; Dudek, Lukasz; Grolik, Jarosław; Eilmes, Julita; Piantanida, Ivo

2014-01-01

An investigation of the interactions of two novel and several known DBTAA-adenine conjugates with double-stranded DNA and RNA has revealed the DNA/RNA groove as the dominant binding site, which is in contrast to the majority of previously studied DBTAA analogues (DNA/RNA intercalators). Only DBTAA-propyladenine conjugates revealed the molecular recognition of AT-DNA by an ICD band pattern > 300 nm, whereas significant ICD bands did not appear for other ds-DNA/RNA. A structure-activity relation for the studied series of compounds showed that the essential structural features for the ICD recognition are a) the presence of DNA-binding appendages (adenine side chain and positively charged side chain) on both DBTAA side chains, and b) the presence of a short propyl linker, which does not support intramolecular aromatic stacking between DBTAA and adenine. The observed AT-DNA-ICD pattern differs from previously reported ss-DNA (poly dT) ICD recognition by a strong negative ICD band at 350 nm, which allows for the dynamic differentiation between ss-DNA (poly dT) and coupled ds-AT-DNA.

ON THE INTERACTION OF ADENINE WITH IONIZING RADIATION: MECHANISTICAL STUDIES AND ASTROBIOLOGICAL IMPLICATIONS

International Nuclear Information System (INIS)

Evans, Nicholas L.; Ullrich, Susanne; Bennett, Chris J.; Kaiser, Ralf I.

2011-01-01

The molecular inventory available on the prebiotic Earth was likely derived from both terrestrial and extraterrestrial sources. A complete description of which extraterrestrial molecules may have seeded early Earth is therefore necessary to fully understand the prebiotic evolution which led to life. Galactic cosmic rays (GCRs) are expected to cause both the formation and destruction of important biomolecules-including nucleic acid bases such as adenine-in the interstellar medium within the ices condensed on interstellar grains. The interstellar ultraviolet (UV) component is expected to photochemically degrade gas-phase adenine on a short timescale of only several years. However, the destruction rate is expected to be significantly reduced when adenine is shielded in dense molecular clouds or even within the ices of interstellar grains. Here, biomolecule destruction by the energetic charged particle component of the GCR becomes important as it is not fully attenuated. Presented here are results on the destruction rate of the nucleobase adenine in the solid state at 10 K by energetic electrons, as generated in the track of cosmic ray particles as they penetrate ices. When both UV and energetic charged particle destructive processes are taken into account, the half-life of adenine within dense interstellar clouds is found to be ∼6 Myr, which is on the order of a star-forming molecular cloud. We also discuss chemical reaction pathways within the ices to explain the production of observed species, including the formation of nitriles (R-C≡N), epoxides (C-O-C), and carbonyl functions (R-C=O).

Adenine N6-methylation in diverse fungi

NARCIS (Netherlands)

Seidl, Michael F.

2017-01-01

A DNA modification - methylation of cytosines and adenines - has important roles in diverse processes such as regulation of gene expression and genome stability, yet until recently adenine methylation had been considered to be only a hallmark of prokaryotes. A new study identifies abundant

hREV3 is essential for error-prone translesion synthesis past UV or benzo[a]pyrene diol epoxide-induced DNA lesions in human fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Li Ziqiang; Zhang Hong; McManus, Terrence P.; McCormick, J. Justin; Lawrence, Christopher W.; Maher, Veronica M

2002-12-29

In S. cerevisiae, the REV3 gene, encoding the catalytic subunit of polymerase zeta, is involved in translesion synthesis and required for the production of mutations induced by ultraviolet radiation (UV) photoproducts and other DNA fork-blocking lesions, and for the majority of spontaneous mutations. To determine whether hREV3, the human homolog of yeast REV3, is similarly involved in error-prone translesion synthesis past UV photoproducts and other lesions that block DNA replication, an hREV3 antisense construct under the control of the TetP promoter was transfected into an infinite life span human fibroblast cell strain that expresses a high level of tTAk, the activator of that promoter. Three transfectant strains expressing high levels of hREV3 antisense RNA were identified and compared with their parental cell strain for sensitivity to the cytotoxic and mutagenic effects of UV. The three hREV3 antisense-expressing cell strains were not more sensitive than the parental strain to the cytotoxic effect of UV, but the frequency of mutants induced by UV in their HPRT gene was significantly reduced, i.e. to 14% that of the parent. Two of these hREV3 antisense-expressing cell strains were compared with the parental strain for sensitivity to ({+-})-7{beta},8{alpha}-dihydroxy-9{alpha},10{alpha}-epoxy-7,8,9,10-tetrahydro= benzo[a]pyrene (BPDE). They were not more sensitive than the parent strain to the cytotoxic effect of BPDE, but the frequency of mutants induced was significantly reduced, i.e. in one strain, to 17% that of the parent, and in the other, to 24%. DNA sequencing showed that the kinds of mutations induced by BPDE in the parental and the derivative strains did not differ and were similar to those found previously with finite life span human fibroblasts. The data strongly support the hypothesis that hRev3 plays a critical role in the induction of mutations by UV or BPDE. Because the level of hRev3 protein in human fibroblasts is below the level of antibody

Sensitive and selective detection of adenine using fluorescent ZnS nanoparticles

International Nuclear Information System (INIS)

Meerabai Devi, L; Negi, Devendra P S

2011-01-01

We have used fluorescent ZnS nanoparticles as a probe for the determination of adenine. A typical 2 x 10 -7 M concentration of adenine quenches 39.3% of the ZnS fluorescence. The decrease in ZnS fluorescence as a function of adenine concentration was found to be linear in the concentration range 5 x 10 -9 -2 x 10 -7 M. The limit of detection (LOD) of adenine by this method is 3 nM. Among the DNA bases, only adenine quenched the fluorescence of ZnS nanoparticles in the submicromolar concentration range, thus adding selectivity to the method. The amino group of adenine was important in determining the quenching efficiency. Steady-state fluorescence experiments suggest that one molecule of adenine is sufficient to quench the emission arising from a cluster of ZnS consisting of about 20 molecules. Time-resolved fluorescence measurements indicate that the adenine molecules block the sites on the surface of ZnS responsible for emission with the longest lifetime component. This method may be applied for the determination of adenine in biological samples since the measurements have been carried out at pH 7.

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)–adenine derivatives

Science.gov (United States)

Stojković, Marijana Radić; Škugor, Marko; Dudek, Łukasz; Grolik, Jarosław; Eilmes, Julita

2014-01-01

Summary An investigation of the interactions of two novel and several known DBTAA–adenine conjugates with double-stranded DNA and RNA has revealed the DNA/RNA groove as the dominant binding site, which is in contrast to the majority of previously studied DBTAA analogues (DNA/RNA intercalators). Only DBTAA–propyladenine conjugates revealed the molecular recognition of AT-DNA by an ICD band pattern > 300 nm, whereas significant ICD bands did not appear for other ds-DNA/RNA. A structure–activity relation for the studied series of compounds showed that the essential structural features for the ICD recognition are a) the presence of DNA-binding appendages (adenine side chain and positively charged side chain) on both DBTAA side chains, and b) the presence of a short propyl linker, which does not support intramolecular aromatic stacking between DBTAA and adenine. The observed AT-DNA-ICD pattern differs from previously reported ss-DNA (poly dT) ICD recognition by a strong negative ICD band at 350 nm, which allows for the dynamic differentiation between ss-DNA (poly dT) and coupled ds-AT-DNA. PMID:25246976

Influence of Magnetic Microparticles Isolation on Adenine Homonucleotides Structure

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Monika Kremplova

2014-02-01

Full Text Available The electroactivity of purine and pyrimidine bases is the most important property of nucleic acids that is very useful for determining oligonucleotides using square wave voltammetry. This study was focused on the electrochemical behavior of adenine-containing oligonucleotides before and after their isolation using paramagnetic particles. Two peaks were detected—peak A related to the reduction of adenine base and another peak B involved in the interactions between individual adenine strands and contributes to the formation of various spatial structures. The influence of the number of adenine bases in the strand in the isolation process using paramagnetic particles was investigated too.

Persistence of urinary excretion products of benzo(a)pyrene

International Nuclear Information System (INIS)

Uziel, M.; Haglund, R.; White, D.A.

1988-01-01

Persistence of DNA-adducts has been observed in a variety of experimental circumstances and has been suggested as one potential mechanism for explaining the long-term delay before expression of proliferative disease. In this concept, a stable DNA-adduct, which is a remnant of a prior exposure in a nondividing cell, would not express the genotoxic effect until the cells were stimulated to divide, and thus explain the long-term delay in expression of cancer. An alternative view of the observation of persistent DNA-adducts, described in this communication, is the continuing replenishment of DNA adducts by formation and turnover of these adducts from exposure to a constant supply of the ultimate carcinogenic species derived from a prior exposure. It is of interest to note that virtually all experiments where ''persistent'' adducts have been observed have been high dose exposures. During the course of experiments designed to develop improved methods for detection of DNA adducts and related derivatives derived from polynuclear aromatic hydrocarbons (PAH), we observed that there was a continuous excretion of urinary derivatives of the injected benzo(a)pyrene (BaP) beyond the initial burst of detoxification. This report describes the time dependent distribution of those derivatives in blood, urine, feces, and at the site of injection. 11 refs., 5 figs., 4 tabs

Nucleoside adducts from the in vitro reaction of benzo[a]pyrene-7,8-dihydrodiol 9,10-oxide or benzo[a]pyrene 4,5-oxide with nucleic acids.

Science.gov (United States)

Jennette, K W; Jeffrey, A M; Blobstein, S H; Beland, F A; Harvey, R G; Weinstein, I B

1977-03-08

The covalent binding of benzo[a]pyrene 4,5-oxide and benzo[a]pyrene-7,8-dihydrodiol 9,10-oxide isomer I and isomer II to nucleic acids in aqueous acetone solution has been investigated. Benzo[a]pyrene 4,5-oxide reacted preferentially with guanosine residues. On the other hand, benzo[a]pyrene-7,8-dihydrodiol 9,10-oxide isomer I and II reacted extensively with guanosine, adenosine, and cytidine residues. Time course studies showed that the reactivity of isomer I or isomer II with homopolyribonucleotides followed the order poly(G) greater than poly(A) greater than poly(C). Alkaline or enzymatic hydrolysis of the modified nucleic acids and subsequent chromatography on Sephadex LH-20 columns yielded benzo[a]pyrene-nucleotide adducts. These were enzymatically converted to the corresponding nucleosides which were resolved into several distinct components by high-pressure liquid chromatography. Evidence was obtained for the presence of multiple nucleoside adducts of guanosine, adenosine, cytidine, deoxyguanosine, deoxyadenosine, and deoxycytidine. The HPLC profiles of adducts formed with isomer I were different from the corresponding profiles of adducts formed with isomer II. Structural aspects of these nucleoside adducts are discussed.

A rat organo-typic model for identifying and characterizing Ρ53 mutations induced by benzo(a)pyrene treatment

International Nuclear Information System (INIS)

Le Rhun, Y.; Duthu, A.; May, E.; Paris, F.; Martin, M.

1997-01-01

A p53 wild-type cell line was established from embryo rat lung treated by the benzo(a)pyrene. Two different p53 mutant cell lines were derived from this parental cell line and showed different characteristics including tumor induction, radiosensitivity and chemo-sensitivity. This system is a useful tools for analysing the effect of various p53 mutants in neoplastic development. (authors)

{8-14C}-Adenine and {1-14C}-isopentenyl pyrophosphate - precursors for root-produced cytokinins in the tomato (Lycopersicon esculentum mill.)

International Nuclear Information System (INIS)

Dickinson, J.R.

1985-01-01

Following the detection of reasonable levels of biologically active cytokinin-like compounds in one-month-old tomato plants, the possible involvement of {8- 14 C}-adenine and {1- 14 C}-isopentenyl pyrophosphate in the biosynthetic pathway leading to an accumulation of free zeatin derivatives, was studied. Intact tomato plants were used for a time-course study involving the uptake of {8- 14 C}-adenine and the tentative identification of compounds into which the 14 C became incorporated. Using high performance liquid chromatography, radioactive trans-zeatin was identified as being present in the Dowex 50 root extract. The 12-hour time interval was used and the roots of the tomato plants were immersed in a more heavily radiolabelled medium. Modified separation techniques were used to achieve enhanced radioactivity recovery rates. This experiment demonstrated the presence of relatively high levels of tentatively identified radioactive zeatin in the Dowex 50 root and stem extracts. Radioactivity in the aqueous extracts was found not to be contributed by cytokinin nucleotides. A final experiment was carried out using decapitated root systems to determine if the root tissue alone could be implicated in the synthesis of cytokinins. Decapitated tomato root systems were supplied with either {8- 14 C}-adenine or {1- 14 C}-isopentenyl pyrophosphate. The ratio of incorporation of {1- 14 C}-isopentenyl pyrophosphate into identified cytokinins was higher than for {8- 14 C}-adenine. It was concluded that both adenine and isopentenyl pyrophosphate are involved in the biosynthetic pathway leading to an accumulation of free zeatin derivatives in tomato roots

Fluorometric detection of adenine in target DNA by exciplex formation with fluorescent 8-arylethynylated deoxyguanosine.

Science.gov (United States)

Saito, Yoshio; Kugenuma, Kenji; Tanaka, Makiko; Suzuki, Azusa; Saito, Isao

2012-06-01

We demonstrated an intriguing method to discriminate adenine by incident appearance of an intense new emission via exciplex formation in hybridization of target DNA with newly designed fluorescent 8-arylethynylated deoxyguanosine derivatives. We described the synthesis of such highly electron donating fluorescent guanosine derivatives and their incorporation into DNA oligomers which may be used for the structural study and the fluorometric analysis of nucleic acids. Copyright © 2012 Elsevier Ltd. All rights reserved.

Formation of diastereomeric benzo[a]pyrene diol epoxide-guanine adducts in p53 gene-derived DNA sequences.

Science.gov (United States)

Matter, Brock; Wang, Gang; Jones, Roger; Tretyakova, Natalia

2004-06-01

G --> T transversion mutations in the p53 tumor suppressor gene are characteristic of smoking-related lung tumors, suggesting that these genetic changes may result from exposure to tobacco carcinogens. It has been previously demonstrated that the diol epoxide metabolites of bay region polycyclic aromatic hydrocarbons present in tobacco smoke, e.g., benzo[a]pyrene diol epoxide (BPDE), preferentially bind to the most frequently mutated guanine nucleotides within p53 codons 157, 158, 248, and 273 [Denissenko, M. F., Pao, A., Tang, M., and Pfeifer, G. P. (1996) Science 274, 430-432]. However, the methodology used in that work (ligation-mediated polymerase chain reaction in combination with the UvrABC endonuclease incision assay) cannot establish the chemical structures and stereochemical identities of BPDE-guanine lesions. In the present study, we employ a stable isotope-labeling HPLC-MS/MS approach [Tretyakova, N., Matter, B., Jones, R., and Shallop, A. (2002) Biochemistry 41, 9535-9544] to analyze the formation of diastereomeric N(2)-BPDE-dG lesions within double-stranded oligodeoxynucleotides representing p53 lung cancer mutational hotspots and their surrounding DNA sequences. (15)N-labeled dG was placed at defined positions within DNA duplexes containing 5-methylcytosine at all physiologically methylated sites, followed by (+/-)-anti-BPDE treatment and enzymatic hydrolysis of the adducted DNA to 2'-deoxynucleosides. Capillary HPLC-ESI(+)-MS/MS was used to establish the amounts of (-)-trans-N(2)-BPDE-dG, (+)-cis-N(2)-BPDE-dG, (-)-cis-N(2)-BPDE-dG, and (+)-trans-N(2)-BPDE-dG originating from the (15)N-labeled bases. We found that all four N(2)-BPDE-dG diastereomers were formed preferentially at the methylated CG dinucleotides, including the frequently mutated p53 codons 157, 158, 245, 248, and 273. The contributions of individual diastereomers to the total adducts number at a given site varied between 70.8 and 92.9% for (+)-trans-N(2)-BPDE-dG, 5.6 and 16.7% for

A novel baseline-correction method for standard addition based derivative spectra and its application to quantitative analysis of benzo(a)pyrene in vegetable oil samples.

Science.gov (United States)

Li, Na; Li, Xiu-Ying; Zou, Zhe-Xiang; Lin, Li-Rong; Li, Yao-Qun

2011-07-07

In the present work, a baseline-correction method based on peak-to-derivative baseline measurement was proposed for the elimination of complex matrix interference that was mainly caused by unknown components and/or background in the analysis of derivative spectra. This novel method was applicable particularly when the matrix interfering components showed a broad spectral band, which was common in practical analysis. The derivative baseline was established by connecting two crossing points of the spectral curves obtained with a standard addition method (SAM). The applicability and reliability of the proposed method was demonstrated through both theoretical simulation and practical application. Firstly, Gaussian bands were used to simulate 'interfering' and 'analyte' bands to investigate the effect of different parameters of interfering band on the derivative baseline. This simulation analysis verified that the accuracy of the proposed method was remarkably better than other conventional methods such as peak-to-zero, tangent, and peak-to-peak measurements. Then the above proposed baseline-correction method was applied to the determination of benzo(a)pyrene (BaP) in vegetable oil samples by second-derivative synchronous fluorescence spectroscopy. The satisfactory results were obtained by using this new method to analyze a certified reference material (coconut oil, BCR(®)-458) with a relative error of -3.2% from the certified BaP concentration. Potentially, the proposed method can be applied to various types of derivative spectra in different fields such as UV-visible absorption spectroscopy, fluorescence spectroscopy and infrared spectroscopy.

Degradation of adenine in aqueous solution containing 3HHO

International Nuclear Information System (INIS)

Yamamoto, Osamu; Fuji, Izumi

1986-01-01

Aqueous adenine solutions of 5 x 10 -4 M (containing 14 C-adenine and buffered pH 7.0) were irradiated with 60 Co gamma-rays and 3 H beta-rays from tritiated water in the presence of N 2 , O 2 , N 2 O or t-BuOH-N 2 . Thin-layer chromatography (TLC) was carried out bidimensionally for separation of the radiolytically produced products and autoradiography was performed. Considerable differences were observed in the dose-yield curves for the decomposition of adenine and for the product formation between gamma- and beta-radiolyses. As for the degradation yield, oxygen enhancement ratios, 3.19 in gamma-irradiation and 1.08 in beta-irradiation, were obtained at a dose of 3.0 x 10 3 Gy. Similar products were produced both under N 2 and O 2 , but there were found a specific reaction of t-butanol radical with adenine, the high yield of hypoxanthine under N 2 O, and the higher degradation of the TLC origin-fixed products in beta-irradiation. The present results on adenine suggest, as reported previously for thymine, that a specific oxidative species is produced from water in beta-radiolysis but not in gamma-radiolysis. (author)

Synthesis of adenine-modified reduced graphene oxide nanosheets.

Science.gov (United States)

Cao, Huaqiang; Wu, Xiaoming; Yin, Gui; Warner, Jamie H

2012-03-05

We report here a facile strategy to synthesize the nanocomposite of adenine-modified reduced graphene oxide (AMG) via reaction between adenine and GOCl which is generated from SOCl(2) reacted with graphite oxide (GO). The as-synthesized AMG was characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), UV-vis absorption spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, Raman spectroscopy, thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV), and galvanostatic discharge analysis. The AMG owns about one adenine group per 53 carbon atoms on a graphene sheet, which improves electronic conductivity compared with reduced graphene oxide (RGO). The AMG displays enhanced supercapacitor performance compared with RGO accompanying good stability and good cycling behavior in the supercapacitor.

Solubility of Benzo[a]pyrene and Organic Matter of Soil in Subcritical Water

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Svetlana Sushkova

2015-12-01

Full Text Available A dynamic subcritical water extraction method of benzo[a]pyrene from soils is under consideration. The optimum conditions for benzo[a]pyrene extraction from soil are described including the soil treatment by subcritical water at 250 °C and 100 atm for 30 min. The effectiveness of developed method was determined using the matrix spiking recovery technique. A comparative analysis was made to evaluate the results of benzo[a]pyrene extraction from soils using the subcritical water and organic solvents. The advantages of the subcritical water extraction involve the use of ecologically friendly solvent, a shorter time for the analysis and a higher amount of benzo[a]pyrene extracted from soil (96 %. The influence of subcritical water extraction on soil properties was measured the investigation of the processes occurring within soil under the influence the high temperature and pressure. Under appropriate conditions of the experiment there is the destruction of the soil organic matter while the composition of the soil mineral fraction remains practically unchanged.

Purine nucleotide synthesis from exogenous adenine and guanine in rodent small intestine

International Nuclear Information System (INIS)

Gross, C.J.; Karlberg, P.K.; Savaiano, D.A.

1986-01-01

14 C-Adenine and 14 C-guanine uptake was studied in isolated guinea pig enterocytes. Cells were incubated in Hank's buffer and separated from the medium by centrifugation through silicone oil into 1M PCA. Uptake was temperature and concentration dependent. Both compounds were incorporated into nucleotides as measured by HPLC and HVE. Adenine was more extensively incorporated into nucleotides than was guanine. Adenine nucleotides accounted for about 70% of the intracellular label after 30 min with a majority being ADP and ATP (medium concentration = 10 μM). Guanine nucleotides accounted for only 30% of the intracellular label after 30 min. Labeled intracellular free adenine or guanine were not detected. Significantly more guanine vs. adenine was converted to uric acid. After 30 min, 11.5 +/- 3.9% (n=3) and 83.0 +/- 8.4% (n=4) of the label was present as uric acid in the medium when adenine and guanine, respectively, were the substrate. After 1 min, 34.8 +/- 3.4% (n=4) of the label in the medium was present as uric acid when guanine was the substrate. Decreasing the concentration of adenine resulted in an increase in the percent of uric acid in the medium. 14 C-adenine (75 nmol) was injected into 1 gm segments of rat jejunum. After 5 min., segments were quickly flushed and the tissue homogenized in 1M PCA. Only uric acid was present after 5 min (n=6). In contrast, in animals fasted 3 to 5 days, less conversion to uric acid was observed in the intestinal content (50-80% of the same dose was still present as adenine after 5 min) and nucleotide formation was observed in the tissue. The results indicate that uric acid and nucleotide synthesis from exogenous adenine and guanine are concentration dependent and affected by nutritional state

Catalytic Mechanism and Three-Dimensional Structure of Adenine Deaminase

Energy Technology Data Exchange (ETDEWEB)

Kamat, S.S.; Swaminathan, S.; Bagaria, A.; Kumaran, D.; Holmes-Hampton, G. P.; Fan, H.; Sali, A.; Sauder, J. M.; Burley, S. K.; Lindahl, P. A.; Raushel, F. M.

2011-03-22

Adenine deaminase (ADE) catalyzes the conversion of adenine to hypoxanthine and ammonia. The enzyme isolated from Escherichia coli using standard expression conditions was low for the deamination of adenine (k{sub cat} = 2.0 s{sup -1}; k{sub cat}/K{sub m} = 2.5 x 10{sup 3} M{sup -1} s{sup -1}). However, when iron was sequestered with a metal chelator and the growth medium was supplemented with Mn{sup 2+} prior to induction, the purified enzyme was substantially more active for the deamination of adenine with kcat and kcat/Km values of 200 s{sup -1} and 5 x 10{sup 5} M{sup -1} s{sup -1}, respectively. The apoenzyme was prepared and reconstituted with Fe{sup 2+}, Zn{sup 2+}, or Mn{sup 2+}. In each case, two enzyme equivalents of metal were necessary for reconstitution of the deaminase activity. This work provides the first example of any member of the deaminase subfamily of the amidohydrolase superfamily to utilize a binuclear metal center for the catalysis of a deamination reaction. [Fe{sup II}/Fe{sup II}]-ADE was oxidized to [Fe{sup III}/Fe{sup III}]-ADE with ferricyanide with inactivation of the deaminase activity. Reducing [Fe{sup III}/Fe{sup III}]-ADE with dithionite restored the deaminase activity, and thus, the diferrous form of the enzyme is essential for catalytic activity. No evidence of spin coupling between metal ions was evident by electron paramagnetic resonance or Moessbauer spectroscopy. The three-dimensional structure of adenine deaminase from Agrobacterium tumefaciens (Atu4426) was determined by X-ray crystallography at 2.2 {angstrom} resolution, and adenine was modeled into the active site on the basis of homology to other members of the amidohydrolase superfamily. On the basis of the model of the adenine-ADE complex and subsequent mutagenesis experiments, the roles for each of the highly conserved residues were proposed. Solvent isotope effects, pH-rate profiles, and solvent viscosity were utilized to propose a chemical reaction mechanism and the

Studies on mixed ligand complexes of adenine and xanthine with some rare earth ions

International Nuclear Information System (INIS)

Rastogi, P.R.; Singh, Mamta; Nayan, Ram

1993-01-01

Interactions of 6-aminopurine (adenine, HA) and 2,6-dihydroxypurine (xanthine, HB) with trivalent rare earth ions Y, Tb, Dy, Ho, Er and Tm, have been studied by pH-titration methods in aqueous solution at 20 o (μ = 0.1 M KNO 3 ). The ligands in their mixtures with tripositive rare earth ions (M 3+ ) form a number of mixed ligand complexes, M 3+ -adenine-xanthine, M 3+ -(adenine) 2 -xanthine, M 3+ -adenine-(xanthine) 2 in addition to the binary complexes, M 3+ -(adenine), M 3+ -(adenine) 2 , M 3+ -(adenine) 3 , M 3+ -(xanthine), M 3+ -(xanthine) 2 and M 3+ -(xanthine) 3 . The stability constants of these complexes have been evaluated and the results discussed. (author). 13 refs., 1 fig., 1 tab

Adenine and 2-aminopurine: paradigms of modern theoretical photochemistry.

Science.gov (United States)

Serrano-Andrés, Luis; Merchán, Manuela; Borin, Antonio C

2006-06-06

Distinct photophysical behavior of nucleobase adenine and its constitutional isomer, 2-aminopurine, has been studied by using quantum chemical methods, in particular an accurate ab initio multiconfigurational second-order perturbation theory. After light irradiation, the efficient, ultrafast energy dissipation observed for nonfluorescent 9H-adenine is explained here by the nonradiative internal conversion process taking place along a barrierless reaction path from the initially populated 1(pipi* La) excited state toward a low-lying conical intersection (CI) connected with the ground state. In contrast, the strong fluorescence recorded for 2-aminopurine at 4.0 eV with large decay lifetime is interpreted by the presence of a minimum in the 1(pipi* La) hypersurface lying below the lowest CI and the subsequent potential energy barrier required to reach the funnel to the ground state. Secondary deactivation channels were found in the two systems related to additional CIs involving the 1(pipi* Lb) and 1(npi*) states. Although in 9H-adenine a population switch between both states is proposed, in 7H-adenine this may be perturbed by a relatively larger barrier to access the 1(npi*) state, and, therefore, the 1(pipi* Lb) state becomes responsible for the weak fluorescence measured in aqueous adenine at approximately 4.5 eV. In contrast to previous models that explained fluorescence quenching in adenine, unlike in 2-aminopurine, on the basis of the vibronic coupling of the nearby 1(pipi*) and 1(npi*) states, the present results indicate that the 1(npi*) state does not contribute to the leading photophysical event and establish the prevalence of a model based on the CI concept in modern photochemistry.

The catalase activity of diiron adenine deaminase

Energy Technology Data Exchange (ETDEWEB)

Kamat S. S.; Swaminathan S.; Holmes-Hampton, G. P.; Bagaria, A.; Kumaran, D.; Tichy, S. E.; Gheyi, T.; Zheng, X.; Bain, K.; Groshong, C.; Emtage, S.; Sauder, J. M.; Burley, S. K.; Lindahl, P. A.; Raushel, F. M.

2011-12-01

Adenine deaminase (ADE) from the amidohydrolase superfamily (AHS) of enzymes catalyzes the conversion of adenine to hypoxanthine and ammonia. Enzyme isolated from Escherichia coli was largely inactive toward the deamination of adenine. Molecular weight determinations by mass spectrometry provided evidence that multiple histidine and methionine residues were oxygenated. When iron was sequestered with a metal chelator and the growth medium supplemented with Mn{sup 2+} before induction, the post-translational modifications disappeared. Enzyme expressed and purified under these conditions was substantially more active for adenine deamination. Apo-enzyme was prepared and reconstituted with two equivalents of FeSO{sub 4}. Inductively coupled plasma mass spectrometry and Moessbauer spectroscopy demonstrated that this protein contained two high-spin ferrous ions per monomer of ADE. In addition to the adenine deaminase activity, [Fe{sup II}/Fe{sup II}]-ADE catalyzed the conversion of H{sub 2}O{sub 2} to O{sub 2} and H{sub 2}O. The values of k{sub cat} and k{sub cat}/K{sub m} for the catalase activity are 200 s{sup -1} and 2.4 x 10{sup 4} M{sup -1} s{sup -1}, respectively. [Fe{sup II}/Fe{sup II}]-ADE underwent more than 100 turnovers with H{sub 2}O{sub 2} before the enzyme was inactivated due to oxygenation of histidine residues critical for metal binding. The iron in the inactive enzyme was high-spin ferric with g{sub ave} = 4.3 EPR signal and no evidence of anti-ferromagnetic spin-coupling. A model is proposed for the disproportionation of H{sub 2}O{sub 2} by [Fe{sup II}/Fe{sup II}]-ADE that involves the cycling of the binuclear metal center between the di-ferric and di-ferrous oxidation states. Oxygenation of active site residues occurs via release of hydroxyl radicals. These findings represent the first report of redox reaction catalysis by any member of the AHS.

Catalytic Mechanism and Three-Dimensional Structure of Adenine Deaminase

Energy Technology Data Exchange (ETDEWEB)

S Kamat; A Bagaria; D Kumaran; G Holmes-Hampton; H Fan; A Sali; J Sauder; S Burley; P Lindahl; et. al.

2011-12-31

Adenine deaminase (ADE) catalyzes the conversion of adenine to hypoxanthine and ammonia. The enzyme isolated from Escherichia coli using standard expression conditions was low for the deamination of adenine (k{sub cat} = 2.0 s{sup -1}; k{sub cat}/K{sub m} = 2.5 x 10{sup 3} M{sup -1} s{sup -1}). However, when iron was sequestered with a metal chelator and the growth medium was supplemented with Mn{sup 2+} prior to induction, the purified enzyme was substantially more active for the deamination of adenine with k{sub cat} and k{sub cat}/K{sub m} values of 200 s{sup -1} and 5 x 10{sup 5} M{sup -1} s{sup -1}, respectively. The apoenzyme was prepared and reconstituted with Fe{sup 2+}, Zn{sup 2+}, or Mn{sup 2+}. In each case, two enzyme equivalents of metal were necessary for reconstitution of the deaminase activity. This work provides the first example of any member of the deaminase subfamily of the amidohydrolase superfamily to utilize a binuclear metal center for the catalysis of a deamination reaction. [Fe{sup II}/Fe{sup II}]-ADE was oxidized to [Fe{sup III}/Fe{sup III}]-ADE with ferricyanide with inactivation of the deaminase activity. Reducing [Fe{sup III}/Fe{sup III}]-ADE with dithionite restored the deaminase activity, and thus, the diferrous form of the enzyme is essential for catalytic activity. No evidence of spin coupling between metal ions was evident by electron paramagnetic resonance or Moessbauer spectroscopy. The three-dimensional structure of adenine deaminase from Agrobacterium tumefaciens (Atu4426) was determined by X-ray crystallography at 2.2 {angstrom} resolution, and adenine was modeled into the active site on the basis of homology to other members of the amidohydrolase superfamily. On the basis of the model of the adenine-ADE complex and subsequent mutagenesis experiments, the roles for each of the highly conserved residues were proposed. Solvent isotope effects, pH-rate profiles, and solvent viscosity were utilized to propose a chemical reaction

The role of hRev7, the accessory subunit of hPolζ, in translesion synthesis past DNA damage induced by benzo[a]pyrene diol epoxide (BPDE

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Maher Veronica M

2010-12-01

Full Text Available Abstract Background DNA polymerase zeta (Polζ is a specialized DNA polymerase that, unlike classical replicative polymerases, is capable of replicating past DNA lesions, i.e. of performing translesion synthesis (TLS. The catalytic subunit of hPolζ, hRev3, has been shown to play a critical role in DNA damage-induced mutagenesis in human cells, but less is known about the role of hRev7, the accessory subunit of hPolζ, in such mutagenesis. To address this question, we recently generated human fibroblasts with very significantly reduced levels of hRev7 protein and demonstrated that hRev7 is required to protect cells from ultraviolet(254 nm (UV radiation-induced cytotoxicity and mutagenesis (McNally et al., DNA Repair 7 (2008 597-604. The goal of the present study was to determine whether hRev7 is similarly involved in the tolerance of DNA damage induced by benzo[a]pyrene diol epoxide (BPDE, the reactive form of the widespread environmental carcinogen benzo[a]pyrene. Methods To determine whether hRev7 also plays a role in protecting human cells from the cytotoxicity and mutagenesis induced by benzo[a]pyrene diol epoxide (BPDE, cell strains with reduced hRev7 were compared to their parental strain and a vector control strain for the effect of BPDE on cell survival, induction of mutations, and the ability to progress through the cell cycle. Results The results show that cell strains with reduced hRev7 are more sensitive to the cytotoxic effect of BPDE than the control strains, and progress through S-phase at a slower rate than the control cells following BPDE treatment, indicating that hRev7, and likely hPolζ, is required for efficient bypass of BPDE-induced DNA lesions. However, neither the frequency nor kinds of mutations induced by BPDE in cells with reduced hRev7 differ significantly from those induced in the control strains, suggesting that hPolζ is not essential for inserting nucleotides opposite BPDE-induced DNA damage. Conclusions Taken

Frontal dermoid cyst coexisting with suprasellar craniopharyngioma: a spectrum of ectodermally derived epithelial-lined cystic lesions?

Science.gov (United States)

Abou-Al-Shaar, Hussam; Abd-El-Barr, Muhammad M; Zaidi, Hasan A; Russell-Goldman, Eleanor; Folkerth, Rebecca D; Laws, Edward R; Chiocca, E Antonio

2016-12-01

There is a wide group of lesions that may exist in the sellar and suprasellar regions. Embryologically, there is varying evidence that many of these entities may in fact represent a continuum of pathology deriving from a common ectodermal origin. The authors report a case of a concomitant suprasellar craniopharyngioma invading the third ventricle with a concurrent frontal lobe cystic dermoid tumor. A 21-year-old man presented to the authors' service with a 3-day history of worsening headache, nausea, vomiting, and blurry vision. Magnetic resonance imaging depicted a right frontal lobe lesion associated with a separate suprasellar cystic lesion invading the third ventricle. The patient underwent a right pterional craniotomy for resection of both lesions. Gross-total resection of the right frontal lesion was achieved, and subtotal resection of the suprasellar lesion was accomplished with some residual tumor adherent to the walls of the third ventricle. Histopathological examination of the resected right frontal lesion documented a diagnosis of dermoid cyst and, for the suprasellar lesion, a diagnosis of adamantinomatous craniopharyngioma. The occurrence of craniopharyngioma with dermoid cyst has not been reported in the literature before. Such an association might indeed suggest the previously reported hypothesis that these lesions represent a spectrum of ectodermally derived epithelial-lined cystic lesions.

Systemic excretion of benzo(a)pyrene in the control and microsomally induced rat: the influence of plasma lipoproteins and albumin as carrier molecules

International Nuclear Information System (INIS)

Shu, H.P.; Bymun, E.N.

1983-01-01

In vitro studies have previously indicated that benzo(a)pyrene distributes primarily into the plasma lipoprotein fraction when incubated with whole plasma. Hydroxylated metabolites of benzo(a)pyrene distribute increasingly into the albumin fraction as the degree of metabolite hydroxylation increases. This report assesses the influence of plasma lipoproteins and albumin as carriers for benzo(a)pyrene on carcinogen excretion in the control and microsomally induced rat. Male Sprague-Dawley rats cannulated in the bile duct received i.v. injections of radiolabeled benzo(a)pyrene noncovalently bound to the very-low-density, low-density, or high-density lipoproteins in equimolar amounts. Bile was collected and measured for radioactivity. Cumulative biliary excretions of benzo(a)pyrene complexed with rat lipoproteins were 39.6 +/- 9.7 (S.D.), 24.6 +/- 1.3, and 21.2 +/- 8.8% for very low-density, low-density, and high-density lipoprotein, respectively. Values for excretion of benzo(a)pyrene complexed with rat or human lipoproteins were comparable. These data suggest that the transport molecule can effect a 2-fold difference in benzo(a)pyrene excretion under conditions of the present study. Thus, excretion increased as the degree of benzo(a)pyrene hydroxylation increased. The effect of microsomal enzyme induction on excretion of lipoprotein-bound benzo(a)pyrene was also assessed. Contrary to expectation, excretion of benzo(a)pyrene bound to the very-low-density, low-density, or high-density lipoproteins in Aroclor-induced rats was not greater than that of control animals. Hence, under the conditions of the present study, 60 to 80% of the injected benzo(a)pyrene and 50 to 60% of the injected benzo(a)pyrene metabolites were not excreted immediately in control or microsomally induced animals. This benzo(a)pyrene may represent a carcinogen pool that is slowly excreted

Identification of blue staining vaccine-derived material in inflammatory lesions using cultured canine macrophages.

Science.gov (United States)

Scruggs, Jennifer L; LeBlanc, Casey J

2015-03-01

Vaccine reactions are described in cytology textbooks as having eosinophilic to magenta colored globules within and admixed with inflammatory cells. Recently, we have seen increased numbers of inflammatory lesions containing blue to blue-gray globular material, with historical information suggesting an association with rabies vaccination. The purpose of the study was to confirm the blue-gray and the eosinophilic material observed microscopically in some inflammatory lesions as being vaccine-derived. Three different vaccines were cytocentrifuged and Wright stained. Vaccine aliquots were also added to the culture media of canine-derived macrophages for 24 hours and the cells subsequently harvested, cytocentrifuged, and Wright stained. The globular material present in both preparations was compared to that observed in vaccine-induced inflammatory lesions. Morin staining was used to identify metal within vaccine material in both in vitro- and in vivo-derived cytology samples. Vaccine-derived material has a characteristic color and appearance. Appearance of the material was consistent in cytologic samples, in cells incubated with the vaccine, and in cytocentrifuged preparations of the vaccine vial contents. The blue-gray globules stained positively for Morin stain, while the eosinophilic material did not stain. Vaccine-induced inflammatory lesions may contain blue to blue-gray or magenta stained globular material. Blue-gray material was associated with administration of rabies vaccine Imrab 3 TF and the observed material may be metal-containing adjuvant. Magenta material was associated with other vaccines and negative for Morin stain, suggesting a metal-free adjuvant. © 2014 American Society for Veterinary Clinical Pathology.

Adenine and guanine nucleotide metabolism during platelet storage at 22 degree C

International Nuclear Information System (INIS)

Edenbrandt, C.M.; Murphy, S.

1990-01-01

Adenine and guanine nucleotide metabolism of platelet concentrates (PCs) was studied during storage for transfusion at 22 +/- 2 degrees C over a 7-day period using high-pressure liquid chromatography. There was a steady decrease in platelet adenosine triphosphate (ATP) and adenosine diphosphate (ADP), which was balanced quantitatively by an increase in plasma hypoxanthine. As expected, ammonia accumulated along with hypoxanthine but at a far greater rate. A fall in platelet guanosine triphosphate (GTP) and guanosine diphosphate (GDP) paralleled the fall in ATP + ADP. When adenine was present in the primary anticoagulant, it was carried over into the PC and metabolized. ATP, GTP, total adenine nucleotides, and total guanine nucleotides declined more slowly in the presence of adenine than in its absence. With adenine, the increase in hypoxanthine concentration was more rapid and quantitatively balanced the decrease in adenine and platelet ATP + ADP. Plasma xanthine rose during storage but at a rate that exceeded the decline in GTP + GDP. When platelet ATP + ADP was labeled with 14C-adenine at the initiation of storage, half of the radioactivity was transferred to hypoxanthine (45%) and GTP + GDP + xanthine (5%) by the time storage was completed. The isotopic data were consistent with the presence of a radioactive (metabolic) and a nonradioactive (storage) pool of ATP + ADP at the initiation of storage with each pool contributing approximately equally to the decline in ATP + ADP during storage. The results suggested a continuing synthesis of GTP + GDP from ATP + ADP, explaining the slower rate of fall of GTP + GDP relative to the rate of rise of plasma xanthine. Throughout storage, platelets were able to incorporate 14C-hypoxanthine into both adenine and guanine nucleotides but at a rate that was only one fourth the rate of hypoxanthine accumulation

Dissociative Excitation of Adenine by Electron Impact

Science.gov (United States)

McConkey, J. William; Trocchi, Joshuah; Dech, Jeffery; Kedzierski, Wladek

2017-04-01

Dissociative excitation of adenine (C6H5NH2) into excited atomic fragments has been studied in the electron impact energy range from threshold to 300 eV. A crossed beam system coupled to a vacuum ultraviolet (VUV) monochromator is used to study emissions in the wavelength range from 110 to 200 nm. The beam of adenine vapor from a stainless steel oven is crossed at right angles by the electron beam and the resultant UV radiation is detected in a mutually orthogonal direction. The strongest feature in the spectrum is H Lyman- α. Financial support from NSERC and CFI, Canada, is gratefully acknowledged.

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Cancer risk assessment of polycyclic aromatic hydrocarbon contaminated soils determined using bioassay-derived levels of benzo[a]pyrene equivalents.

Science.gov (United States)

Lemieux, Christine L; Long, Alexandra S; Lambert, Iain B; Lundstedt, Staffan; Tysklind, Mats; White, Paul A

2015-02-03

Here we evaluate the excess lifetime cancer risk (ELCR) posed by 10 PAH-contaminated soils using (i) the currently advocated, targeted chemical-specific approach that assumes dose additivity for carcinogenic PAHs and (ii) a bioassay-based approach that employs the in vitro mutagenic activity of the soil fractions to determine levels of benzo[a]pyrene equivalents and, by extension, ELCR. Mutagenic activity results are presented in our companion paper.1 The results show that ELCR values for the PAH-containing fractions, determined using the chemical-specific approach, are generally (i.e., 8 out of 10) greater than those calculated using the bioassay-based approach; most are less than 5-fold greater. Only two chemical-specific ELCR estimates are less than their corresponding bioassay-derived values; differences are less than 10%. The bioassay-based approach, which permits estimation of ELCR without a priori knowledge of mixture composition, proved to be a useful tool to evaluate the chemical-specific approach. The results suggest that ELCR estimates for complex PAH mixtures determined using a targeted, chemical-specific approach are reasonable, albeit conservative. Calculated risk estimates still depend on contentious PEFs and cancer slope factors. Follow-up in vivo mutagenicity assessments will be required to validate the results and their relevance for human health risk assessment of PAH-contaminated soils.

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Spectrum of lesions derived from branchial arches occurring in the thyroid: from solid cell nests to tumors.

Science.gov (United States)

Srbecka, Kristyna; Michalova, Kvetoslava; Curcikova, Radmila; Michal, Michael; Dubova, Magdalena; Svajdler, Marian; Michal, Michal; Daum, Ondrej

2017-09-01

There is a group of lesions in the head and neck region derived from branchial arches and related structures which, when inflamed, are characterized by the formation of cysts lined by squamous or glandular epithelium and surrounded by a heavy inflammatory infiltrate rich in germinal centers. In the thyroid, the main source of various structures which may cause diagnostic dilemma is the ultimobranchial body. To investigate the spectrum of such thyroid lesions, the consultation files were reviewed for thyroid samples containing pathological structures regarded to arise from the ultimobranchial body. Positive reaction with antibodies against CK5/6, p63, galectin 3, and CEA, and negative reaction with antibodies against thyroglobulin, TTF-1, and calcitonin were used to confirm the diagnosis. The specific subtype of the ultimobranchial body-derived lesion was then determined based on histological examination of H&E-stained slides. Twenty-one cases of ultimobranchial body-derived lesions were retrieved from the consultation files, 20 of them along with clinical information (M/F = 6/14, mean age 55 years, range 36-68 years). Lesions derived from the ultimobranchial body were classified as follows: (hyperplastic) solid cell nests (nine cases), solid cell nests with focal cystic change (five cases), cystic solid cell nests (two cases), branchial cleft-like cyst (four cases), and finally a peculiar Warthin tumor-like lesion (one case). We suggest that the common denominator of these structures is that they all arise due to activation of inflammatory cells around the vestigial structures, which leads to cystic dilatation and proliferation of the epithelial component.

Bacillus subtilis is a Potential Degrader of Pyrene and Benzo[a]pyrene

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Lynette Ekunwe

2005-08-01

Full Text Available Polycyclic Aromatic Hydrocarbons (PAHs are a group of compounds that pose many health threats to human and animal life. They occur in nature as a result of incomplete combustion of organic matter, as well as from many anthropogenic sources including cigarette smoke and automobile exhaust. PAHs have been reported to cause liver damage, red blood cell damage and a variety of cancers. Because of this, methods to reduce the amount of PAHs in the environment are continuously being sought. The purpose of this study was to find soil bacteria capable of degrading high molecular weight PAHs, such as pyrene (Pyr and benzo[a]pyrene (BaP, which contain more than three benzene rings and so persist in the environment. Bacillus subtilis, identified by fatty acid methyl ester (FAME analysis, was isolated from PAH contaminated soil. Because it grew in the presence of 33μg/ml each of pyrene, 1-AP and 1-HP, its biodegradation capabilities were assessed. It was found that after a four-day incubation period at 30oC in 20μg/ml pyrene or benzo[a]pyrene, B. subtilis was able to transform approximately 40% and 50% pyrene and benzo[a]pyrene, respectively. This is the first report implicating B. subtilis in PAH degradation. Whether or not the intermediates resulting from the transformation are more toxic than their parent compounds, and whether B. subtilis is capable of mineralizing pyrene or benzo[a]pyrene to carbon dioxide and water, remains to be evaluated.

Investigation of biological destruction of benzo[a]pyrene andpolycyclic aromatic hydrocarbons of biochar in soil

Science.gov (United States)

Okunev, R. V.; Smirnova, E. V.; Sharipova, A. R.; Gilmutdinova, I. M.; Giniyatullin, K. G.

2018-01-01

The biological decomposition of benzo[a]pyrene in the concentrations exceeding the MAC (maximum permissible concentration) level in soils by 2, 5 and 10 times was studied in laboratory conditions. The gray forest soil samples were contaminated with benzo[a]pyrene and incubated in optimum for bacterial growth soil moisture for 30 and 60 days. The residual amount of contaminant was monitored by HPLC after extraction with acetone-cyclohexane (2:1). Soil microbial activity was evaluated by measuring basal respiration (BR) and substrate-induced respiration (SID) rates of the soil by gas chromatography. The results of the experiment showed that in 60 days the amount of benzo[a]pyrene in contaminated soils decreased; however, this time was not enough for complete decomposition of pollutant. In this case, benzo[a]pyrene has a negative effect on the BR and SIR rates. Soil contamination affected the BR rate only at high doses (10 MPC), whereas the SIR was a more sensitive indicator of the toxic effect of the pollutant and significantly reacts already at concentrations at the level of 2 MPC. The combination of PAHs isolated from biochar has a strong negative effect on the values of BR and SIR.

De novo synthesis of adenine nucleotides in different skeletal muscle fiber types

International Nuclear Information System (INIS)

Tullson, P.C.; John-Alder, H.B.; Hood, D.A.; Terjung, R.L.

1988-01-01

Management of adenine nucleotide catabolism differs among skeletal muscle fiber types. This study evaluated whether there are corresponding differences in the rates of de novo synthesis of adenine nucleotide among fiber type sections of skeletal muscle using an isolated perfused rat hindquarter preparation. Label incorporation into adenine nucleotides from the [1-14C]glycine precursor was determined and used to calculate synthesis rates based on the intracellular glycine specific radioactivity. Results show that intracellular glycine is closely related to the direct precursor pool. Rates of de novo synthesis were highest in fast-twitch red muscle (57.0 +/- 4.0, 58.2 +/- 4.4 nmol.h-1.g-1; deep red gastrocnemius and vastus lateralis), relatively high in slow-twitch red muscle (47.0 +/- 3.1; soleus), and low in fast-twitch white muscle (26.1 +/- 2.0 and 21.6 +/- 2.3; superficial white gastrocnemius and vastus lateralis). Rates for four mixed muscles were intermediate, ranging between 32.3 and 37.3. Specific de novo synthesis rates exhibited a strong correlation (r = 0.986) with muscle section citrate synthase activity. Turnover rates (de novo synthesis rate/adenine nucleotide pool size) were highest in high oxidative muscle (0.82-1.06%/h), lowest in low oxidative muscle (0.30-0.35%/h), and intermediate in mixed muscle (0.44-0.55%/h). Our results demonstrate that differences in adenine nucleotide management among fiber types extends to the process of de novo adenine nucleotide synthesis

A novel approach to adenine-induced chronic kidney disease associated anemia in rodents.

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Asadur Rahman

Full Text Available To date, good experimental animal models of renal anemia are not available. Therefore, the purpose of this study was to establish a novel approach to induce chronic kidney disease (CKD with severe anemia by oral administration of adenine in rodents. Adenine was administered to 6-week-old male C57BL/6 mice (25 and 50 mg/kg body weight by oral gavage daily for 28 days. Serum creatinine and BUN as well as hematocrit, hemoglobin (Hb and plasma erythropoietin (EPO levels were monitored to assess renal function and anemia, respectively. Adenine at 25 mg/kg for 28 days slightly increased plasma creatinine levels, but did not induce anemia. In contrast, 50 mg/kg of adenine daily for 28 days showed severe renal dysfunction (plasma creatinine 1.9 ± 0.10 mg/dL and anemia (hematocrit 36.5 ± 1.0% and EPO 28 ± 2.4 pg/mL as compared with vehicle-treated mice (0.4 ± 0.02 mg/dL, 49.6 ± 1.6% and 61 ± 4.0 pg/mL, respectively. At the end of experiment, level of Hb also significantly reduced in 50 mg/kg adenine administration group. Remarkable histological changes of kidney tissues characterized by interstitial fibrosis and cystic appearance in tubules were observed in 50 mg/kg of adenine treatment group. These results have demonstrated that oral dosing with adenine at 50 mg/kg for 28 days is suitable to induce a stable anemia associated with CKD in mice.

Watson-Crick Base Pairing, Electronic and Photophysical Properties of Triazole Modified Adenine Analogues: A Computational Study

KAUST Repository

Das, Shubhajit

2015-09-17

We employ first-principles Density Functional Theory (DFT) and time-dependent DFT (TDDFT) to elucidate structural, electronic and optical properties of a few recently reported triazole adenine nucleobase analogues. The results are compared against the findings obtained for both natural adenine nucleobase and available experimental data. The optical absorption of these adenine analogues are calculated both in gas-phase and in solvent (methanol) using Polarized Continuum Model (PCM). We find that all the analogues show a red-shifted absorption profile as compared to adenine. Our simulated emission spectra in solvent compare fairly well with experimentally observed results. We investigate base paring ability of these adenine analogues with thymine. The calculations on the intrinsic stability of these base pairs ascertain that all the adenine analogues form the hydrogen bonded Watson-Crick base pair with similar H-bonding energy as obtained for natural adenine-thymine base pair. In our study, we provide a microscopic origin of the low-energy absorption and emission peaks, observed experimentally.

Watson-Crick Base Pairing, Electronic and Photophysical Properties of Triazole Modified Adenine Analogues: A Computational Study

KAUST Repository

Das, Shubhajit; Samanta, Pralok Kumar; Pati, Swapan

2015-01-01

We employ first-principles Density Functional Theory (DFT) and time-dependent DFT (TDDFT) to elucidate structural, electronic and optical properties of a few recently reported triazole adenine nucleobase analogues. The results are compared against the findings obtained for both natural adenine nucleobase and available experimental data. The optical absorption of these adenine analogues are calculated both in gas-phase and in solvent (methanol) using Polarized Continuum Model (PCM). We find that all the analogues show a red-shifted absorption profile as compared to adenine. Our simulated emission spectra in solvent compare fairly well with experimentally observed results. We investigate base paring ability of these adenine analogues with thymine. The calculations on the intrinsic stability of these base pairs ascertain that all the adenine analogues form the hydrogen bonded Watson-Crick base pair with similar H-bonding energy as obtained for natural adenine-thymine base pair. In our study, we provide a microscopic origin of the low-energy absorption and emission peaks, observed experimentally.

Mechanism-based inactivation of benzo[a]pyrene hydroxylase by aryl acetylenes and aryl olefins

International Nuclear Information System (INIS)

Gan, L.S.; Lu, J.Y.L.; Alworth, W.L.

1986-01-01

A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxgenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene, 3-ethynylperylene, 2-ethynylfluorene, methyl 1-pyrenyl acetylene, cis- and trans-1-(2-bromovinyl)pyrene, and 1-allylpyrene serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo[a]pyrene hydroxylase, while 1-vinylpyrene and phenyl 1-pyrenyl acetylene do not cause a detectable suicide inhibition of benzo[a]pyrene hydroxylase. The mechanism-based loss of benzo[a]pyrene hydroxylase caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes (suicide destruction). The suicide inhibition by these aryl acetylenes therefore does not involve covalent binding to the heme moiety of the monooxygenase. Nevertheless, in the presence of NADPH, 3 H-labeled 1-ethynylpyrene becomes covalently attached to the cytochrome P-450 protein; the measured stoichiometry of binding is one 1-ethynylpyrene per P-450 heme unit. The authors conclude that the inhibition of benzo[a]pyrene hydroxylase produced by 1-ethynylpyrene may be related to the mechanism of suicide inhibition of P-450 activity by chloramphenicol rather than the mechanism of suicide destruction of P-450 previously described for acetylene and propyne

Lung Oxidative Stress, DNA Damage, Apoptosis, and Fibrosis in Adenine-Induced Chronic Kidney Disease in Mice

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Abderrahim Nemmar

2017-11-01

Full Text Available It is well-established that there is a crosstalk between the lung and the kidney, and several studies have reported association between chronic kidney disease (CKD and pulmonary pathophysiological changes. Experimentally, CKD can be caused in mice by dietary intake of adenine. Nevertheless, the consequence of such intervention on the lung received only scant attention. Here, we assessed the pulmonary effects of adenine (0.2% w/w in feed for 4 weeks-induced CKD in mice by assessing various physiological histological and biochemical endpoints. Adenine treatment induced a significant increase in urine output, urea and creatinine concentrations, and it decreased the body weight and creatinine clearance. It also increased proteinuria and the urinary levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Compared with control group, the histopathological evaluation of lungs from adenine-treated mice showed polymorphonuclear leukocytes infiltration in alveolar and bronchial walls, injury, and fibrosis. Moreover, adenine caused a significant increase in lung lipid peroxidation and reactive oxygen species and decreased the antioxidant catalase. Adenine also induced DNA damage assessed by COMET assay. Similarly, adenine caused apoptosis in the lung characterized by a significant increase of cleaved caspase-3. Moreover, adenine induced a significant increase in the expression of nuclear factor erythroid 2–related factor 2 (Nrf2 in the lung. We conclude that administration of adenine in mice induced CKD is accompanied by lung oxidative stress, DNA damage, apoptosis, and Nrf2 expression and fibrosis.

Electron transfer driven decomposition of adenine and selected analogs as probed by experimental and theoretical methods

Science.gov (United States)

Cunha, T.; Mendes, M.; Ferreira da Silva, F.; Eden, S.; García, G.; Bacchus-Montabonel, M.-C.; Limão-Vieira, P.

2018-04-01

We report on a combined experimental and theoretical study of electron-transfer-induced decomposition of adenine (Ad) and a selection of analog molecules in collisions with potassium (K) atoms. Time-of-flight negative ion mass spectra have been obtained in a wide collision energy range (6-68 eV in the centre-of-mass frame), providing a comprehensive investigation of the fragmentation patterns of purine (Pu), adenine (Ad), 9-methyl adenine (9-mAd), 6-dimethyl adenine (6-dimAd), and 2-D adenine (2-DAd). Following our recent communication about selective hydrogen loss from the transient negative ions (TNIs) produced in these collisions [T. Cunha et al., J. Chem. Phys. 148, 021101 (2018)], this work focuses on the production of smaller fragment anions. In the low-energy part of the present range, several dissociation channels that are accessible in free electron attachment experiments are absent from the present mass spectra, notably NH2 loss from adenine and 9-methyl adenine. This can be understood in terms of a relatively long transit time of the K+ cation in the vicinity of the TNI tending to enhance the likelihood of intramolecular electron transfer. In this case, the excess energy can be redistributed through the available degrees of freedom inhibiting fragmentation pathways. Ab initio theoretical calculations were performed for 9-methyl adenine (9-mAd) and adenine (Ad) in the presence of a potassium atom and provided a strong basis for the assignment of the lowest unoccupied molecular orbitals accessed in the collision process.

Suppression of feline immunodeficiency virus infection in vivo by 9-(2-phosphonomethoxyethyl)adenine

NARCIS (Netherlands)

Horzinek, M.C.; Egberink, H.F.; Borst, M.; Niphuis, H.; Balzarini, J.; Neu, H.; Schellekens, H.; Clercq, H. de; Koolen, M.J.M.

1990-01-01

The acyclic purine nucleoside analogue 9-(2-phosphonomethoxyethyl)adenine [PMEA; formerly referred to as 9-(2-phosphonylmethoxyethyl)adenine] is a potent and selective inhibitor of human immunodeficiency virus replication in vitro and of Moloney murine sarcoma virus-induced tumor formation in mice.

Hydration properties of natural and synthetic DNA sequences with methylated adenine or cytosine bases in the R.DpnI target and BDNF promoter studied by molecular dynamics simulations

Science.gov (United States)

Shanak, Siba; Helms, Volkhard

2014-12-01

Adenine and cytosine methylation are two important epigenetic modifications of DNA sequences at the levels of the genome and transcriptome. To characterize the differential roles of methylating adenine or cytosine with respect to their hydration properties, we performed conventional MD simulations and free energy perturbation calculations for two particular DNA sequences, namely the brain-derived neurotrophic factor (BDNF) promoter and the R.DpnI-bound DNA that are known to undergo methylation of C5-methyl cytosine and N6-methyl adenine, respectively. We found that a single methylated cytosine has a clearly favorable hydration free energy over cytosine since the attached methyl group has a slightly polar character. In contrast, capping the strongly polar N6 of adenine with a methyl group gives a slightly unfavorable contribution to its free energy of solvation. Performing the same demethylation in the context of a DNA double-strand gave quite similar results for the more solvent-accessible cytosine but much more unfavorable results for the rather buried adenine. Interestingly, the same demethylation reactions are far more unfavorable when performed in the context of the opposite (BDNF or R.DpnI target) sequence. This suggests a natural preference for methylation in a specific sequence context. In addition, free energy calculations for demethylating adenine or cytosine in the context of B-DNA vs. Z-DNA suggest that the conformational B-Z transition of DNA transition is rather a property of cytosine methylated sequences but is not preferable for the adenine-methylated sequences investigated here.

Cytokinins and urea derivatives stimulate seed germination in Lotus corniculatus L.

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Nikolić Radomirka

2007-01-01

Full Text Available We studied the effects of various cytokinins and urea derivatives on germination of aged seeds of in Lotus corniculatus L. The following substances were applied: N6-isoprenoid cytokinins (isopentenyl adenine and zeatin, adenine sulfate, N6-aromatic cytokinins (kinetin, benzyladenine and their N9-ribosides, N-benzyl-9-(2- tetrahydropyranyladenine, and urea derivatives (diphenylurea, thidiazuron, and chloro-pyridyl phenylurea. With the exception of adenine sulfate, all cytokinins increased the percentage of seed germination up to twofold, depending on their kind and concentration. It is concluded that cytokinins may be among the missing factors in aged seeds of L. corniculatus contributing to the implementation of their full germination potential. They could be used to improve germination of both freshly harvested and aged seed samples, if necessary. .

Life history traits and the activity of antioxidative enzymes in Lymantria dispar L. (lepidoptera, lymantriidae) larvae exposed to benzo[a]pyrene.

Science.gov (United States)

Ilijin, Larisa; Mrdaković, Marija; Todorović, Dajana; Vlahović, Milena; Gavrilović, Anja; Mrkonja, Aleksandra; Perić-Mataruga, Vesna

2015-11-01

Increased presence of benzo[a]pyrene in the environment underlines the need for development of sensitive biomarkers for monitoring. Antioxidative enzymes could be used as early-warning signals because of their sensitivity and applicability. The activity of 2 antioxidative enzymes, superoxide dismutase (SOD) and catalase (CAT), were measured in midgut tissues of fifth instar Lymantria dispar larvae exposed to different concentrations of benzo[a]pyrene: 2 ng, 10 ng, 20 ng, 100 ng, 200 ng, and 2000 ng benzo[a]pyrene/g dry food weight. Larval development, larval mass, and relative growth rate were also monitored. The authors detected prolonged larval development, as well as reduced larval mass and relative growth rate in larvae exposed to all benzo[a]pyrene concentrations. The L. dispar midgut SOD activity was significantly increased, and 2 SOD isoforms were detected on native polyacrylamide gel electrophoresis in larvae fed on artificial diet supplemented with benzo[a]pyrene. In contrast, the control group had only 1 isoform. Catalase activity was significantly increased in all benzo[a]pyrene-treated larvae. Native gel electrophoresis showed that a switch in active CAT isoforms occurred after benzo[a]pyrene treatment. Thus, SOD and CAT in polyphagous herbivorous L. dispar larvae are very sensitive to low concentrations of benzo[a]pyrene. Therefore, they could be used as biomarkers for exposure and effects of this toxic polycyclic aromatic hydrocarbon. © 2015 SETAC.

Benzo[a]pyrene co-metabolism in the presence of plant root extracts and exudates: Implications for phytoremediation

International Nuclear Information System (INIS)

Rentz, Jeremy A.; Alvarez, Pedro J.J.; Schnoor, Jerald L.

2005-01-01

Benzo[a]pyrene, a high molecular weight (HMW) polycyclic aromatic hydrocarbon (PAH) was removed from solution by Sphingomonas yanoikuyae JAR02 while growing on root products as a primary carbon and energy source. Plant root extracts of osage orange (Maclura pomifera), hybrid willow (Salix albaxmatsudana), or kou (Cordia subcordata), or plant root exudates of white mulberry (Morus alba) supported 15-20% benzo[a]pyrene removal over 24 h that was similar to a succinate grown culture and an unfed acetonitrile control. No differences were observed between the different root products tested. Mineralization of 14 C-7-benzo[a]pyrene by S. yanoikuyae JAR02 yielded 0.2 to 0.3% 14 CO 2 when grown with plant root products. Collectively, these observations were consistent with field observations of enhanced phytoremediation of HMW PAH and corroborated the hypothesis that co-metabolism may be a plant/microbe interaction important to rhizoremediation. However, degradation and mineralization was much less for root product-exposed cultures than salicylate-induced cultures, and suggested the rhizosphere may not be an optimal environment for HMW PAH degradation by Sphingomonas yanoikuyae JAR02. - Bacterial benzo[a]pyrene cometabolism, a plant-microbe interaction affecting polycyclic aromatic hydrocarbon phytoremediation was demonstrated with Sphingomonas yanoikuyae JAR02 that utilized plant root extracts and exudates as primary substrates

Determination of adenine based on the fluorescence recovery of the L-Tryptophan-Cu(2+) complex.

Science.gov (United States)

Duan, Ruilin; Li, Chunyan; Liu, Shaopu; Liu, Zhongfang; Li, Yuanfang; Yuan, Yusheng; Hu, Xiaoli

2016-01-05

A simple and sensitive method for determination of adenine was developed based on fluorescence quenching and recovery of L-Tryptophan (L-Trp). The fluorescence of L-Trp could efficiently quenched by copper ion compared with other common metal ions. Upon addition of adenine (Ade) in L-Trp-Cu(II) system, the fluorescence was reoccurred. Under the optimum conditions, the recovery fluorescence intensity was linearly correlated with the concentration of adenine in the range from 0.34 to 25.0μmolL(-1), with a correlation coefficient (R(2)) of 0.9994. The detection limit (3σ/k) was 0.046μmolL(-1), indicating that this method could applied to detect trace adenine. In this study, amino acids including L-Trp, D-Trp, L-Tyr, D-Tyr, L-Phe, D-Phe were investigated and only L-Trp could well chelated copper ion. Additionally, the mechanism of quench and recovery also were discussed and the method was successfully applied to detect the adenine in DNA with satisfactory results. Copyright © 2015 Elsevier B.V. All rights reserved.

Adenine nucleotide depletion from endothelial cells exposed to xanthine oxidase

International Nuclear Information System (INIS)

Aalto, T.K.; Raivio, K.O.

1990-01-01

Hypoxia causes breakdown of cellular nucleotides, accumulation of hypoxanthine (HX), and conversion of xanthine dehydrogenase into xanthine oxidase (XO). Upon reoxygenation, the HX-XO reaction generates free radicals, one potential mechanism of tissue damage. Because endothelial cells contain XO and are exposed to circulating HX, they are a likely target for damage. We studied the effect of XO and/or HX at physiologically relevant concentrations on nucleotide metabolism of cultured endothelial cells from human umbilical veins. Cells were labeled with [14C]adenine and incubated for up to 6 h with HX, XO, or both, in the absence or presence of serum. Adenine nucleotides from cell extracts and nucleotide breakdown products (HX, xanthine, and urate) from the medium were separated and counted. HX alone had no effect. XO (80 mU/ml) alone caused a 70% (no serum) or 40% (with serum) fall in adenine nucleotides and an equivalent increase of xanthine and urate. The combination of HX and XO caused a 90% (no serum) or 70% (with serum) decrease in nucleotides, decrease in energy charge, and detachment of cells from the culture plate. Nucleotide depletion was not accounted for by proteolytic activity in the XO preparation. Albumin was only half as effective as serum in preventing nucleotide loss. Thus exogenous XO, in the presence of endogenous HX, triggers adenine nucleotide catabolism, but endogenous XO activity is too low to influence nucleotide levels even at high exogenous HX concentrations. Serum limits the catabolic effect of XO and thus protects cells from free radical damage

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)–adenine derivatives

OpenAIRE

Stojković, Marijana Radić; Škugor, Marko; Dudek, Łukasz; Grolik, Jarosław; Eilmes, Julita; Piantanida, Ivo

2014-01-01

Summary An investigation of the interactions of two novel and several known DBTAA–adenine conjugates with double-stranded DNA and RNA has revealed the DNA/RNA groove as the dominant binding site, which is in contrast to the majority of previously studied DBTAA analogues (DNA/RNA intercalators). Only DBTAA–propyladenine conjugates revealed the molecular recognition of AT-DNA by an ICD band pattern > 300 nm, whereas significant ICD bands did not appear for other ds-DNA/RNA. A structure–activity...

Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure

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Abderrahim Nemmar

2016-05-01

Full Text Available Background/Aims: Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Methods: Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks, which is known to involve inflammation and oxidative stress. DEP (0.5m/kg was intratracheally (i.t. instilled every 4th day for 4 weeks (7 i.t. instillation. Four days following the last exposure to either DEP or saline (control, various renal endpoints were measured. Results: While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Conclusion: Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic

Synthesis of adenine mediated superparamagnetic colloidal β-FeOOH nanostructure(s): study of their morphological changes and magnetic behavior

International Nuclear Information System (INIS)

Kumar, Anil; Gupta, Sudhir Kumar

2013-01-01

This paper describes the synthesis of adenine-mediated superparamagnetic β-FeOOH nanostructures in aqueous medium. Capping by adenine provides a synthetic control to manipulate their size, morphology, optical and magnetization properties. β-FeOOH binds to adenine mainly through –NH 2 , N(3); N(9)H and N(7) of the pyridine and imidazole rings, respectively. At low [adenine], it produces nanorods, but at higher [adenine] (>1 × 10 −2 mol dm −3 ), increasing numbers of spherical nanoparticles encapsulating β-FeOOH with an average diameter of 2.5 nm in the core and adenine molecules in the shell are obtained, causing an increase in the specific surface area by about twofold. Dynamic light scattering technique also depicts a regular decrease in their hydrodynamic size with increasing [adenine] and exhibits the highest stability with a zeta potential of ∼67 mV for the sample containing 2 × 10 −2 mol dm −3 adenine (SP5). An increasing [adenine] from 1 × 10 −3 to 2 × 10 −2 mol dm −3 in these samples enhanced the value of saturation magnetization (M S ), due to β-FeOOH, gradually from 2.0 to 6.9 emu g −1 at 300 K, but at S at 300 K having potential for environmental and biological applications.

Benzo[a]pyrene co-metabolism in the presence of plant root extracts and exudates: Implications for phytoremediation

Energy Technology Data Exchange (ETDEWEB)

Rentz, Jeremy A [Civil and Environmental Engineering, University of Iowa, Iowa City, IA 52242 (United States); Alvarez, Pedro J.J. [Civil and Environmental Engineering, Rice University, Houston, TX 77251 (United States); Schnoor, Jerald L [Civil and Environmental Engineering, University of Iowa, Iowa City, IA 52242 (United States)

2005-08-15

Benzo[a]pyrene, a high molecular weight (HMW) polycyclic aromatic hydrocarbon (PAH) was removed from solution by Sphingomonas yanoikuyae JAR02 while growing on root products as a primary carbon and energy source. Plant root extracts of osage orange (Maclura pomifera), hybrid willow (Salix albaxmatsudana), or kou (Cordia subcordata), or plant root exudates of white mulberry (Morus alba) supported 15-20% benzo[a]pyrene removal over 24 h that was similar to a succinate grown culture and an unfed acetonitrile control. No differences were observed between the different root products tested. Mineralization of {sup 14}C-7-benzo[a]pyrene by S. yanoikuyae JAR02 yielded 0.2 to 0.3% {sup 14}CO{sub 2} when grown with plant root products. Collectively, these observations were consistent with field observations of enhanced phytoremediation of HMW PAH and corroborated the hypothesis that co-metabolism may be a plant/microbe interaction important to rhizoremediation. However, degradation and mineralization was much less for root product-exposed cultures than salicylate-induced cultures, and suggested the rhizosphere may not be an optimal environment for HMW PAH degradation by Sphingomonas yanoikuyae JAR02. - Bacterial benzo[a]pyrene cometabolism, a plant-microbe interaction affecting polycyclic aromatic hydrocarbon phytoremediation was demonstrated with Sphingomonas yanoikuyae JAR02 that utilized plant root extracts and exudates as primary substrates.

Heat-processed ginseng saponin ameliorates the adenine-induced renal failure in rats

OpenAIRE

Kim, Eun Jin; Oh, Hyun-A; Choi, Hyuck Jai; Park, Jeong Hill; Kim, Dong-Hyun; Kim, Nam Jae

2013-01-01

To evaluate the effect of the saponin of heat-processed ginseng (Sun ginseng, SG), we investigated the protective effect of SG total saponin fraction against adenine-induced chronic renal failure in rats. SG saponin significantly decreased the levels of urea nitrogen and creatinine in the serum, but increased the urinary excretion of urea nitrogen and creatinine, indicating an improvement of renal function. SG saponin also inhibited adenine-induced kidney hypertrophy and edema. SG saponin red...

Long-term engraftment of bone marrow-derived cells in the intimal hyperplasia lesion of autologous vein grafts.

Science.gov (United States)

Diao, Yanpeng; Guthrie, Steve; Xia, Shen-Ling; Ouyang, Xiaosen; Zhang, Li; Xue, Jing; Lee, Pui; Grant, Maria; Scott, Edward; Segal, Mark S

2008-03-01

Intimal hyperplasia of autologous vein grafts is a critical problem affecting the long-term patency of many types of vascular reconstruction. Within intimal hyperplasia lesions, smooth muscle cells are a major component, playing an essential role in the pathological process. Given that bone marrow-derived cells may differentiate into smooth muscle cells in the neointima of injured arteries, we hypothesized that the bone marrow may serve as a source for some of the smooth muscle cells within intimal hyperplasia lesions of vein grafts. To test this hypothesis, we used an established mouse model for intimal hyperplasia in wild-type mice that had been transplanted with bone marrow from a green fluorescent protein (GFP+/+) transgenic mouse. High-resolution confocal microscopy analysis performed 2 and 8 weeks after grafting demonstrated expression of GFP in 5.4 +/- 0.8% and 11.9 +/- 2.3%, respectively, of smooth muscle cells within intimal hyperplasia lesions. By 16 weeks, GFP expression in smooth muscle cells was not detected by immunohistochemistry; however, real-time PCR revealed that 20.2 +/- 1.7% of the smooth muscle cells captured from the neointima lesion by laser capture microdissection at 16 weeks contained GFP DNA. Our results suggest that bone marrow-derived cells differentiated into smooth muscle cells within the intimal lesion and may provide a novel clinical approach for decreasing intimal hyperplasia in vein grafts.

Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure.

Science.gov (United States)

Nemmar, Abderrahim; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Hamadi, Naserddine Kamel; Ali, Badreldin H

2016-01-01

Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP) on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks), which is known to involve inflammation and oxidative stress. DEP (0.5m/kg) was intratracheally (i.t.) instilled every 4th day for 4 weeks (7 i.t. instillation). Four days following the last exposure to either DEP or saline (control), various renal endpoints were measured. While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Our data provide biological plausibility that air

LC/MSMS STUDY OF BENZO[A]PYRENE-7,8-QUINONE ADDUCTION TO GLOBIN TRYPTIC PEPTIDES AND N-ACETYLAMINO ACIDS

Science.gov (United States)

Benzo[a]pyrene-7,8-quinone (BPQ) is regarded as a reactive genotoxic compound enzymatically formed from a xenobiotic precursor benzo[a]pyrene-7,8-diol by aldo-keto-reductase family of enzymes. Because BPQ, a Michael electrophile, was previously shown to react with oligonucleotide...

Effect of AST-120 on Endothelial Dysfunction in Adenine-Induced Uremic Rats

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Yuko Inami

2014-01-01

Full Text Available Aim. Chronic kidney disease (CKD represents endothelial dysfunction. Monocyte adhesion is recognized as the initial step of arteriosclerosis. Indoxyl sulfate (IS is considered to be a risk factor for arteriosclerosis in CKD. Oral adsorbent AST-120 retards deterioration of renal function, reducing accumulation of IS. In the present study, we determined the monocyte adhesion in the adenine-induced uremic rats in vivo and effects of AST-120 on the adhesion molecules. Methods. Twenty-four rats were divided into control, control+AST-120, adenine, and adenine+AST-120 groups. The number of monocytes adherent to the endothelium of thoracic aorta by imaging the entire endothelial surface and the mRNA expressions of adhesion and atherosclerosis-related molecules were examined on day 49. The mRNA expressions of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells were also examined. Results. Adenine increased the number of adherent monocytes, and AST-120 suppressed the increase. The monocyte adhesion was related to serum creatinine and IS in sera. Overexpression of VCAM-1 and TGF-β1 mRNA in the arterial walls was observed in uremic rats. IS induced increase of the ICAM-1 and VCAM-1 mRNA expressions in vitro. Conclusion. It appears that uremic condition introduces the monocyte adhesion to arterial wall and AST-120 might inhibit increasing of the monocyte adherence with CKD progression.

Structure-wise discrimination of adenine and guanine by proteins on the basis of their nonbonded interactions.

Science.gov (United States)

Usha, S; Selvaraj, S

2015-01-01

We have analyzed the nonbonded interactions of the structurally similar moieties, adenine and guanine forming complexes with proteins. The results comprise (a) the amino acid-ligand atom preferences, (b) solvent accessibility of ligand atoms before and after complex formation with proteins, and (c) preferred amino acid residue atoms involved in the interactions. We have observed that the amino acid preferences involved in the hydrogen bonding interactions vary for adenine and guanine. The structural variation between the purine atoms is clearly reflected by their burial tendency in the solvent environment. Correlation of the mean amino acid preference values show the variation that exists between adenine and guanine preferences of all the amino acid residues. All our observations provide evidence for the discriminating nature of the proteins in recognizing adenine and guanine.

Factors controlling benzo(a)pyrene concentration in aerosols in the urbanized coastal zone. A case study: Gdynia, Poland (Southern Baltic Sea).

Science.gov (United States)

Staniszewska, Marta; Graca, Bożena; Bełdowska, Magdalena; Saniewska, Dominika

2013-06-01

Annual study on the benzo(a)pyrene (BaP) concentration in aerosols in the coastal zone of the Gulf of Gdansk (southern Baltic) has been performed at Gdynia station. Combustion processes, especially domestic heating of both local and regional origin, were identified as the main sources of benzo(a)pyrene in this area. Concentrations observed during the heating season (mean 2.18 ng m(-3)) were significantly higher than these recorded in the non-heating season (mean 0.05 ng m(-3)). High benzo(a)pyrene concentrations were associated with low temperature and high humidity. Whereas high levels of precipitation usually decreased the BaP concentration in aerosols. The concentration of this factor in the studied area depended also on the wind direction and air masses trajectories. During heating season, continental air masses (coming from S, SE, SW) seemed to increase benzo(a)pyrene concentration, while maritime air masses (from N, NE, NW) caused its decrease. The differences in the BaP concentration resulting from potentially different emission levels of this compound during working and non-working days were not clearly pronounced.

Removal of pyrene and benzo(a)pyrene micropollutant from water via adsorption by green synthesized iron oxide nanoparticles

Science.gov (United States)

Hassan, Saad S. M.; Abdel-Shafy, Hussein I.; Mansour, Mona S. M.

2018-03-01

Polycyclic aromatic hydrocarbons (PAHs) in water are classified as organic micropollutants, which are carcinogenic even in very low concentration (ppb). In this study the green synthesized iron oxide nanoparticles (IONPs) were green synthesized at room temperature by using pomegranate peel extract. The green synthesized IONPs were used for adsorbing benzo(a)pyrene and pyrene (PAHs) from water. Factors affecting the adsorption were investigated. These factors are: nanoparticles dose, pH, temperature, and initial concentration of PAHs. The overall results showed that the maximum adsorption capacities of IONPs towards pyrene and benzo(a)pyrene were 2.8 and 0.029 mg g-1, respectively. The thermodynamic study indicated an exothermic adsorption process of pyrene and benzo(a)pyrene. The kinetic and isotherm studies were carried out. The obtained data revealed that the adsorption process follows a pseudo-second order mechanism and obeys Langmuir isotherm model. In addition, the IONPs proved to be a potential candidate for the adsorption of pyrene and benzo(a)pyrene even after five cycles of use and regeneration. The investigation was extended using semi-pilot plant to remove the studied PAHs from artificially contaminated water. The results showed that the IONPs was capable to remove the pyrene and benzo (a) pyrene at the rate of 98.5 and 99%, respectively. It also can be used as disinfectant.

Effect of atracylodes rhizome polysaccharide in rats with adenine-induced chronic renal failure.

Science.gov (United States)

Yang, C; Liu, C; Zhou, Q; Xie, Y C; Qiu, X M; Feng, X

2015-01-01

The aim of the study was to elucidate the therapeutic effects of Atracylodes rhizome polysaccharide on adenine-induced chronic renal failure in rats. Fifty male Sprague Dawley rats were selected and randomly divided in to 5 groups (n=10 rats per group): The normal control group, the chronic renal failure pathological control group, the dexamethasone treatment group and two Atracylodes rhizome polysaccharide treatment groups, treated with two different concentrations of the polysaccharide, the Atracylodes rhizome polysaccharide high group and the Atracylodes rhizome polysaccharide low group. All the rats, except those in the normal control group were fed adenine-enriched diets, containing 10 g adenine per kg food for 3 weeks. After being fed with adenine, the dexamethasone treatment group, Atracylodes rhizome polysaccharide high group and Atracylodes rhizome polysaccharide low group rats were administered the drug orally for 2 weeks. On day 35, the kidney coefficient of the rats and the serum levels of creatinine, blood urea nitrogen, total protein and hemalbumin were determined. Subsequent to experimentation on a model of chronic renal failure in rats, the preparation was proven to be able to reduce serum levels of creatinine, blood urea nitrogen and hemalbumin levels (Prenal function. Atracylodes rhizome polysaccharide had reversed the majority of the indices of chronic renal failure in rats.

Design, synthesis, and characterization of 0-D, 1-D, and 2-D Zinc–Adeninate coordination assemblies

Energy Technology Data Exchange (ETDEWEB)

An, Ji Hyun [Dept. of Chemistry Education, Seoul National University, Seoul (Korea, Republic of); Geib, Steven J. [Dept. of Chemistry, University of Pittsburgh, Pittsburgh (United States); Kim, Myung Gil [Dept. of Chemistry, Chungang University, Seoul (Korea, Republic of)

2015-08-15

In this study, we demonstrate the synthesis and characterization of zinc– adeninate coordination polymers with 0-D, 1-D, and 2-D structures. We describe methods for controlling the structure of these materials by applying different synthetic conditions and discuss their structural relationships. 0-D, 1-D, and 2-D zinc–adeninate coordination polymers with the same metal–adeninate coordination mode were synthesized and characterized. By controlling the temperature, a material with 0-D macrocycle or 1-D chain coordination polymer was prepared. A replacement of pyridine with bipyridine formed 2-D sheet structure by connecting 1-D chains with each other. They exhibited an interesting relationship between synthetic methods and structures. Further study of metal–adeninate coordination chemistry will render a precise control of the structure in synthesis and will open a new venue to new materials with fascinating properties.

Cleavage of nicotinamide adenine dinucleotide by the ribosome-inactivating protein from Momordica charantia.

Science.gov (United States)

Vinkovic, M; Dunn, G; Wood, G E; Husain, J; Wood, S P; Gill, R

2015-09-01

The interaction of momordin, a type 1 ribosome-inactivating protein from Momordica charantia, with NADP(+) and NADPH has been investigated by X-ray diffraction analysis of complexes generated by co-crystallization and crystal soaking. It is known that the proteins of this family readily cleave the adenine-ribose bond of adenosine and related nucleotides in the crystal, leaving the product, adenine, bound to the enzyme active site. Surprisingly, the nicotinamide-ribose bond of oxidized NADP(+) is cleaved, leaving nicotinamide bound in the active site in the same position but in a slightly different orientation to that of the five-membered ring of adenine. No binding or cleavage of NADPH was observed at pH 7.4 in these experiments. These observations are in accord with current views of the enzyme mechanism and may contribute to ongoing searches for effective inhibitors.

Time to enhancement derived from ultrafast breast MRI as a novel parameter to discriminate benign from malignant breast lesions

International Nuclear Information System (INIS)

Mus, Roel D.; Borelli, Cristina; Bult, Peter; Weiland, Elisabeth; Karssemeijer, Nico; Barentsz, Jelle O.; Gubern-Mérida, Albert; Platel, Bram; Mann, Ritse M.

2017-01-01

Highlights: • New view-sharing sequences (e.g. TWIST) enable ultrafast dynamic breast MRI. • TWIST sequences accurately characterize the inflow of contrast in breast lesions. • TTE evaluation allows breast lesion classification with very high accuracy. • The use of TTE significantly increases the specificity of breast MRI. • TWIST imaging may increase the potential of breast MRI as screening tool. - Abstract: Objectives: To investigate time to enhancement (TTE) as novel dynamic parameter for lesion classification in breast magnetic resonance imaging (MRI). Methods: In this retrospective study, 157 women with 195 enhancing abnormalities (99 malignant and 96 benign) were included. All patients underwent a bi-temporal MRI protocol that included ultrafast time-resolved angiography with stochastic trajectory (TWIST) acquisitions (1.0 × 0.9 × 2.5 mm, temporal resolution 4.32 s), during the inflow of contrast agent. TTE derived from TWIST series and relative enhancement versus time curve type derived from volumetric interpolated breath-hold examination (VIBE) series were assessed and combined with basic morphological information to differentiate benign from malignant lesions. Receiver operating characteristic analysis and kappa statistics were applied. Results: TTE had a significantly better discriminative ability than curve type (p < 0.001 and p = 0.026 for reader 1 and 2, respectively). Including morphology, sensitivity of TWIST and VIBE assessment was equivalent (p = 0.549 and p = 0.344, respectively). Specificity and diagnostic accuracy were significantly higher for TWIST than for VIBE assessment (p < 0.001). Inter-reader agreement in differentiating malignant from benign lesions was almost perfect for TWIST evaluation (κ = 0.86) and substantial for conventional assessment (κ = 0.75). Conclusions: TTE derived from ultrafast TWIST acquisitions is a valuable parameter that allows robust differentiation between malignant and benign breast lesions with high

Time to enhancement derived from ultrafast breast MRI as a novel parameter to discriminate benign from malignant breast lesions

Energy Technology Data Exchange (ETDEWEB)

Mus, Roel D., E-mail: aroel.mus@radboudumc.nl [Department of Radiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA Nijmegen (Netherlands); Borelli, Cristina, E-mail: cristinaborelli@hotmail.it [Department of Radiology, Scientific Institute “Casa Sollievo della Sofferenza” Hospital, Viale Cappuccini 1, 71013, San Giovanni Rotondo, Foggia (Italy); Department of Radiology, Radboud University Medical Center (internal address 766), Geert Grooteplein Zuid 10, 6525GA Nijmegen (Netherlands); Bult, Peter, E-mail: peter.bult@radboudumc.nl [Department of Pathology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA Nijmegen (Netherlands); Weiland, Elisabeth, E-mail: elisabeth.weiland@siemens.com [Siemens Healthcare, Erlangen (Germany); Karssemeijer, Nico, E-mail: nico.karssemeijer@radboudumc.nl [Department of Radiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA Nijmegen (Netherlands); Barentsz, Jelle O., E-mail: jelle.barentsz@radboudumc.nl [Department of Radiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA Nijmegen (Netherlands); Gubern-Mérida, Albert, E-mail: albert.gubernmerida@radboudumc.nl [Department of Radiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA Nijmegen (Netherlands); Platel, Bram, E-mail: bram.platel@radboudumc.nl [Department of Radiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA Nijmegen (Netherlands); Mann, Ritse M., E-mail: ritse.mann@radboudumc.nl [Department of Radiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA Nijmegen (Netherlands)

2017-04-15

Highlights: • New view-sharing sequences (e.g. TWIST) enable ultrafast dynamic breast MRI. • TWIST sequences accurately characterize the inflow of contrast in breast lesions. • TTE evaluation allows breast lesion classification with very high accuracy. • The use of TTE significantly increases the specificity of breast MRI. • TWIST imaging may increase the potential of breast MRI as screening tool. - Abstract: Objectives: To investigate time to enhancement (TTE) as novel dynamic parameter for lesion classification in breast magnetic resonance imaging (MRI). Methods: In this retrospective study, 157 women with 195 enhancing abnormalities (99 malignant and 96 benign) were included. All patients underwent a bi-temporal MRI protocol that included ultrafast time-resolved angiography with stochastic trajectory (TWIST) acquisitions (1.0 × 0.9 × 2.5 mm, temporal resolution 4.32 s), during the inflow of contrast agent. TTE derived from TWIST series and relative enhancement versus time curve type derived from volumetric interpolated breath-hold examination (VIBE) series were assessed and combined with basic morphological information to differentiate benign from malignant lesions. Receiver operating characteristic analysis and kappa statistics were applied. Results: TTE had a significantly better discriminative ability than curve type (p < 0.001 and p = 0.026 for reader 1 and 2, respectively). Including morphology, sensitivity of TWIST and VIBE assessment was equivalent (p = 0.549 and p = 0.344, respectively). Specificity and diagnostic accuracy were significantly higher for TWIST than for VIBE assessment (p < 0.001). Inter-reader agreement in differentiating malignant from benign lesions was almost perfect for TWIST evaluation (κ = 0.86) and substantial for conventional assessment (κ = 0.75). Conclusions: TTE derived from ultrafast TWIST acquisitions is a valuable parameter that allows robust differentiation between malignant and benign breast lesions with high

CeO{sub 2} nanoparticles decorated multi-walled carbon nanotubes for electrochemical determination of guanine and adenine

Energy Technology Data Exchange (ETDEWEB)

Wei Yan [College of Chemistry and Materials Sciences, Anhui Normal University, Wuhu 241000 (China); Department of Chemistry, Wannan Medical College, Wuhu 241002 (China); Huang Qinan [Department of Chemistry, Wannan Medical College, Wuhu 241002 (China); Li Maoguo [College of Chemistry and Materials Sciences, Anhui Normal University, Wuhu 241000 (China); Huang Xingjiu [Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei 230031 (China); Fang Bin, E-mail: binfang_47@yahoo.com.cn [College of Chemistry and Materials Sciences, Anhui Normal University, Wuhu 241000 (China); Wang Lun, E-mail: wanglun@mail.ahnu.edu.cn [College of Chemistry and Materials Sciences, Anhui Normal University, Wuhu 241000 (China)

2011-10-01

Sub-10 nm CeO{sub 2} nanoparticles decorated multi-walled carbon nanotubes has been constructed for electrochemial determination of guanine and adenine. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) were used to characterize the nanoparticles CeO{sub 2}/MWCNTs. Electrochemical impedance spectroscopy (EIS) was used to characterize the electrode modifying process. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to study the electrocatalytic activity toward the electrochemical oxidation of guanine and adenine. The detection limit (S/N = 3) for adenine and guanine was found to be 20 and 10 nM, respectively. The obtained sensitivity toward guanine and adenine was 1.26 and 1.13 {mu}A/{mu}M in the linear concentration range 5-50 {mu}M and 5-35 {mu}M, respectively. These results demonstrate that the carbon nanotubes could provide huge locations and facilitate the adsorptive accumulation of the guanine and adenine, and the CeO{sub 2} nanoparticles are promising substrates for the development of high-performance electrocatalysts for biosensing.

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

Directory of Open Access Journals (Sweden)

Xue-ying Chang

2017-01-01

Full Text Available Background. This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d, 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS/p38 mitogen activated protein kinase (p38MAPK pathway was determined to explore the potential mechanism. Results. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA and creatinine levels, malonaldehyde (MDA content, and superoxide dismutase (SOD activity in serum and the increases of calcium and alkaline phosphatase (ALP activity in the aorta (P<0.05 and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Conclusions. Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

Radiological protection optimization derived from radiation induced lesions in interventional cardiology finding

International Nuclear Information System (INIS)

Vano, E.; Arranz, L.; Sastre, J.M.; Ferrer, N.

1997-01-01

Interventional Cardiology is one of the specialties in which patients are submitted to the greatest radiation doses with x ray systems used for diagnostic purposes and then, it is also a specialty of high occupational radiation risk. In the last years, several cases of radiation induced lesions produced on patients derived of new complex interventional procedures have been described. As consequence, different rules for avoiding this kind of incidents have been recommended by International Organisations and regulatory Bodies. Nevertheless it has been devoted relatively few attention to the evaluation of the occupational risks that inevitably are also high in these facilities. In this work, some cases of radioinduced skin lesions produced on patients submitted to cardiac ablation procedures are described. Radiological protection considerations of interest for the regulatory Bodies are made, that permit to minimize the probability of these incidents, in what to the X-rays equipment is referred as well as to the operation procedures and level of radiation protection training of the medical specialists. (author)

Human hair follicle benzo(a)pyrene and benzo(a)pyrene 7, 8-diol metabolism: effect of exposure to a coal tar-containing shampoo

Energy Technology Data Exchange (ETDEWEB)

Merk, H.F.; Mukhtar, H.; Kaufmann, I.; Das, M.; Bickers, D.R.

1987-01-01

Hair follicles are a readily available source of human epithelial tissue and offer an excellent system with which to study carcinogen metabolism in human populations. In this study hair follicles were employed to measure the metabolism of benzo(a)pyrene (BP), benzo(a)pyrene - 7,8-diol (BP 7,8-diol) and the enzyme mediated binding of /sup 3/H-BP to DNA. The effect of human exposure to a crude coal tar (CCT) - containing shampoo, a preparation rich in polycyclic aromatic hydrocarbons (PAHs on these parameters was also evaluated. It was found that aryl hydrocarbon hydroxylase (AHH) activity increased after use of the shampoo and enhancement of enzyme-mediated binding of BP to DNA was detected in most subjects. Hair follicles were shown to convert BP to several metabolic species and BP, 7,8-diol was also metabolised. Clotrimazole, a known inhibitor of the metabolism of BP was found to inhibit AHH and the metabolism of BP and BP 7,8-diol in human hair follicles, as were other imidazole compounds. The studies show that hair follicles represent an accessible tissue suitable for assessing the extent of PAH carcinogen metabolism in human subjects. Furthermore enzyme activity critical to cancer induction by PAHs was shown to be inducible following the use of a CCT-containing shampoo. Imidazole compounds were shown to be possible effective anti-carcinogens in human populations. 29 refs.

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats.

Science.gov (United States)

Chang, Xue-Ying; Cui, Lei; Wang, Xing-Zhi; Zhang, Lei; Zhu, Dan; Zhou, Xiao-Rong; Hao, Li-Rong

2017-01-01

This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta ( P chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

Science.gov (United States)

Chang, Xue-ying; Cui, Lei; Wang, Xing-zhi; Zhang, Lei; Zhu, Dan

2017-01-01

Background This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Results Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta (P chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway. PMID:28691026

Synthesis, spectroscopic, structural and thermal characterizations of vanadyl(IV) adenine complex prospective as antidiabetic drug agent

Science.gov (United States)

El-Megharbel, Samy M.; Hamza, Reham Z.; Refat, Moamen S.

2015-01-01

The vanadyl(IV) adenine complex; [VO(Adn)2]ṡSO4; was synthesized and characterized. The molar conductivity of this complex was measured in DMSO solution that showed an electrolyte nature. Spectroscopic investigation of the green solid complex studied here indicate that the adenine acts as a bidentate ligand, coordinated to vanadyl(IV) ions through the nitrogen atoms N7 and nitrogen atom of amino group. Thus, from the results presented the vanadyl(IV) complex has square pyramid geometry. Further characterizations using thermal analyses and scanning electron techniques was useful. The aim of this paper was to introduce a new drug model for the diabetic complications by synthesized a novel mononuclear vanadyl(IV) adenine complex to mimic insulin action and reducing blood sugar level. The antidiabetic ability of this complex was investigated in STZ-induced diabetic mice. The results suggested that VO(IV)/adenine complex has antidiabetic activity, it improved the lipid profile, it improved liver and kidney functions, also it ameliorated insulin hormone and blood glucose levels. The vanadyl(IV) complex possesses an antioxidant activity and this was clear through studying SOD, CAT, MDA, GSH and methionine synthase. The current results support the therapeutic potentiality of vanadyl(IV)/adenine complex for the management and treatment of diabetes.

Effect of dietary factors on mutagenesis, metabolism, and binding to DNA of benzo[a]pyrene and benzo[a]pyrene 7,8-dihydrodiol

International Nuclear Information System (INIS)

Vance, R.E.

1988-01-01

Ellagic acid (EA), a naturally occurring plant phenol, at concentrations of 5 to 50 μg/plate, inhibited rate liver S9 protein dependent benzo[a]pyrene (B[a]P)-induced mutagenesis in Salmonella typhimurium TA 100 by 30-81% and B[a]P 7,8-dihydrodiol (DHD)-induced mutagenesis by 29 to 75%. EA did not significantly affect the metabolism of B[a]P or B[a]P 7,8-DHD as determined by high performance liquid chromatographic analysis of the organosoluble fraction and by the quantification of water-soluble conjugates. At these concentrations EA inhibited the covalent binding of [ 3 H] B[a]P and [ 3 H] B[a]P 7,8-DHD metabolites to calf thymus DNA by 5 to 42% and 27 to 64%, respectively. Formation of benzo[a]pyrene 7,8-dihydrodiol-9,10-epoxide:deoxyguanosine (BPDE:dG) adducts was inhibited by 13 to 56% for B[a]P for B[a]P and 11 to 38% for B[a]P 7,8-DHD. These results suggest that the antimutagenic effect of EA and its inhibition of B[a]P and B[a]P 7,8-DHD metabolite-binding to DNA is not due to the inhibition of S9-mediated metabolism of these compounds. The inhibitory effect may be by previously described scavenging mechanism or by a DNA-affinity binding mechanism that prevents BPDE:DNA adduct formation

Electrochemical behaviors and simultaneous determination of guanine and adenine based on graphene–ionic liquid–chitosan composite film modified glassy carbon electrode

International Nuclear Information System (INIS)

Niu Xiuli; Yang Wu; Ren Jie; Guo Hao; Long Shijia; Chen Jiaojiao; Gao Jinzhang

2012-01-01

Highlights: ► This work developed a novel electrochemical biosensors for guanine and adenine detection simultaneously. ► A disposable electrode based on graphene sheets, ionic liquid and chitosan was proposed. ► The presented method was also applied to simultaneous determination of guanine and adenine in denatured DNA samples with satisfying results. ► Easy fabrication, high sensitivity, excellent reproducibility and long-term stability. - Abstract: A graphene sheets (GS), ionic liquid (IL) and chitosan (CS) modified electrode was fabricated and the modified electrode displayed excellent electrochemical catalytic activities toward guanine and adenine. The transfer electron number (n) and the charge transfer coefficient (α) were calculated with the result as n = 2, α = 0.58 for guanine, and n = 2, α = 0.51 for adenine, which indicated the electrochemical oxidation of guanine and adenine on GS/IL/CS modified electrode was a two-electron and two-proton process. The oxidation overpotentials of guanine and adenine were decreased significantly compared with those obtained at the bare glassy carbon electrode and multi-walled carbon nanotubes modified electrode. The modified electrode exhibited good analytical performance and was successfully applied for individual and simultaneous determination of guanine and adenine. Low detection limits of 0.75 μM for guanine and 0.45 μM for adenine were obtained, with the linear calibration curves over the concentration range 2.5–150 μM and 1.5–350 μM, respectively. At the same time, the proposed method was successfully applied for the determination of guanine and adenine in denatured DNA samples with satisfying results. Moreover, the GS/IL/CS modified electrode exhibited good sensitivity, long-term stability and reproducibility for the determination of guanine and adenine.

Toward a non-invasive screening tool for differentiation of pancreatic lesions based on intra-voxel incoherent motion derived parameters

Energy Technology Data Exchange (ETDEWEB)

Graf, Markus; Simon, Dirk; Mang, Sarah [Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Software Development for Integrated Therapy and Diagnostics; Lemke, Andreas [Heidelberg Univ., Mannheim (Germany). Dept. of Computer Assisted Clinical Medicine; Gruenberg, Katharina [Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Dept. of Radiology

2013-03-01

Early recognition of and differential diagnosis between pancreatic cancer and chronic pancreatitis is an important step in successful therapy. Parameters of the IVIM (intra-voxel incoherent motion) theory can be used to differentiate between those lesions. The objective of this work is to evaluate the effects of rigid image registration on IVIM derived parameters for differentiation of pancreatic lesions such as pancreatic cancer and solid mass forming pancreatitis. The effects of linear image registration methods on reproducibility and accuracy of IVIM derived parameters were quantified on MR images of ten volunteers. For this purpose, they were evaluated statistically by comparison of registered and unregistered parameter data. Further, the perfusion fraction f was used to differentiate pancreatic lesions on eleven previously diagnosed patient data sets. Its diagnostic power with and without rigid registration was evaluated using receiver operating curves (ROC) analysis. The pancreas was segmented manually on MR data sets of healthy volunteers as well as the patients showing solid pancreatic lesions. Diffusion weighted imaging was performed in 10 blocks of breath-hold phases. Linear registration of the weighted image stack leads to a 3.7% decrease in variability of the IVIM derived parameter f due to an improved anatomical overlap of 5%. Consequently, after registration the area under the curve in the ROC-analysis for the differentiation approach increased by 2.7%. In conclusion, rigid registration improves the differentiation process based on f-values. (orig.)

Toward a non-invasive screening tool for differentiation of pancreatic lesions based on intra-voxel incoherent motion derived parameters

International Nuclear Information System (INIS)

Graf, Markus; Simon, Dirk; Mang, Sarah; Lemke, Andreas; Gruenberg, Katharina

2013-01-01

Early recognition of and differential diagnosis between pancreatic cancer and chronic pancreatitis is an important step in successful therapy. Parameters of the IVIM (intra-voxel incoherent motion) theory can be used to differentiate between those lesions. The objective of this work is to evaluate the effects of rigid image registration on IVIM derived parameters for differentiation of pancreatic lesions such as pancreatic cancer and solid mass forming pancreatitis. The effects of linear image registration methods on reproducibility and accuracy of IVIM derived parameters were quantified on MR images of ten volunteers. For this purpose, they were evaluated statistically by comparison of registered and unregistered parameter data. Further, the perfusion fraction f was used to differentiate pancreatic lesions on eleven previously diagnosed patient data sets. Its diagnostic power with and without rigid registration was evaluated using receiver operating curves (ROC) analysis. The pancreas was segmented manually on MR data sets of healthy volunteers as well as the patients showing solid pancreatic lesions. Diffusion weighted imaging was performed in 10 blocks of breath-hold phases. Linear registration of the weighted image stack leads to a 3.7% decrease in variability of the IVIM derived parameter f due to an improved anatomical overlap of 5%. Consequently, after registration the area under the curve in the ROC-analysis for the differentiation approach increased by 2.7%. In conclusion, rigid registration improves the differentiation process based on f-values. (orig.)

Cancer risk estimation for mixtures of coal tars and benzo(a)pyrene

International Nuclear Information System (INIS)

Gaylor, D.W.; Culp, S.J.; Goldstein, L.S.; Beland, F.A.

2000-01-01

Two-year chronic bioassays were conducted by using B6C3F1 female mice fed several concentrations of two different mixtures of coal tars from manufactured gas waste sites or benzo(a)pyrene (BaP). The purpose of the study was to obtain estimates of cancer potency of coal tar mixtures, by using conventional regulatory methods, for use in manufactured gas waste site remediation. A secondary purpose was to investigate the validity of using the concentration of a single potent carcinogen, in this case benzo(a)pyrene, to estimate the relative risk for a coal tar mixture. The study has shown that BaP dominates the cancer risk when its concentration is greater than 6,300 ppm in the coal tar mixture. In this case the most sensitive tissue site is the forestomach. Using low-dose linear extrapolation, the lifetime cancer risk for humans is estimated to be: Risk -4 (ppm coal tar in total diet) + 240 x 10 -4 (ppm BaP in total diet), based on forestomach tumors. If the BaP concentration in the coal tar mixture is less than 6,300 ppm, the more likely case, then lung tumors provide the largest estimated upper limit of risk, Risk -4 (ppm coal tar in total diet), with no contribution of BaP to lung tumors. The upper limit of the cancer potency (slope factor) for lifetime oral exposure to benzo(a)pyrene is 1.2 x 10 -3 per microg per kg body weight per day from this Good Laboratory Practice (GLP) study compared with the current value of 7.3 x 10 -3 per microg per kg body weight per day listed in the US EPA Integrated Risk Information System

Protection of Chinese herbs against Adenine-induced chronic renal ...

African Journals Online (AJOL)

The aim of the study is to evaluate the efficacy of Chinese herbs (Angelica sinensis, Ligusticum wallichii, Salvia miltiorrhiza, Rhizoma dioscoreae, Rhodiola crenilata, Astragalus membranaceus and Angelica sinensis) on adenine-induced chronic renal failure in rats. 30 age-matched male Wistar rats were divided into three ...

Nonselective enrichment for yeast adenine mutants by flow cytometry

Science.gov (United States)

Bruschi, C. V.; Chuba, P. J.

1988-01-01

The expression of certain adenine biosynthetic mutations in the yeast Saccharomyces cerevisiae results in a red colony color. This phenomenon has historically provided an ideal genetic marker for the study of mutation, recombination, and aneuploidy in lower eukaryotes by classical genetic analysis. In this paper, it is reported that cells carrying ade1 and/or ade2 mutations exhibit primary fluorescence. Based on this observation, the nonselective enrichment of yeast cultures for viable adenine mutants by using the fluorescence-activated cell sorter has been achieved. The advantages of this approach over conventional genetic analysis of mutation, recombination, and mitotic chromosomal stability include speed and accuracy in acquiring data for large numbers of clones. By using appropriate strains, the cell sorter has been used for the isolation of both forward mutations and chromosomal loss events in S. cerevisiae. The resolving power of this system and its noninvasiveness can easily be extended to more complex organisms, including mammalian cells, in which analogous metabolic mutants are available.

Protective Effect of Mulberry (Morus alba L.) Extract against Benzo[a]pyrene Induced Skin Damage through Inhibition of Aryl Hydrocarbon Receptor Signaling.

Science.gov (United States)

Woo, Hyunju; Lee, JungA; Park, Deokhoon; Jung, Eunsun

2017-12-20

Benzo[a]pyrene (B[a]P), a type of polycyclic aromatic hydrocarbon, is present in the atmosphere surrounding our environment. Although B[a]P is a procarcinogen, enzymatically metabolized benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) could intercalate into DNA to form bulky BPDE-DNA adducts as an ultimate carcinogenic product in human keratinocytes. The aim of this study was to evaluate the protective effect of mulberry extract, purified from the fruit of Morus Alba L., on B[a]P-induced cytotoxicity in human keratinocytes and its mechanisms of action. In this study, we confirmed that B[a]P induced nuclear translocation and the activation of aryl hydrocarbon receptor (AhR) were decreased by pretreatment of mulberry extract. Mulberry extract could decrease DNA damage through the suppression of B[a]P derived DNA adduct formation and restoration of cell cycle retardation at S phase in a dose-dependent manner. Additionally, cyanidin-3-glucoside (C3G), a major active compound of mulberry extract, showed biological activities to protect the cells from B[a]P exposure, similar to the effectivity of the mulberry extract. These results indicated that the inhibitory effect of C3G against B[a]P inducing skin cancer is attributable to repress the AhR signaling pathway.

On the carcinogenic polycyclic aromatic hydrocarbon benzo(a)pyrene in volcano exhausts.

Science.gov (United States)

Ilnitsky, A P; Belitsky, G A; Shabad, L M

1976-05-01

The content of benzo(a)pyrene in the juvenile ashes of the volcano Tyatya (Kunashir Island, Kuriles) and in the soil, vegetation and volcanic mud collected near volcanos in Kamchatka was studied. It was concluded that volcanic activity does not play a large role in forming the background level of this carcinogen in the human environment.

Breast lesion characterization using whole-lesion histogram analysis with stretched-exponential diffusion model.

Science.gov (United States)

Liu, Chunling; Wang, Kun; Li, Xiaodan; Zhang, Jine; Ding, Jie; Spuhler, Karl; Duong, Timothy; Liang, Changhong; Huang, Chuan

2018-06-01

Diffusion-weighted imaging (DWI) has been studied in breast imaging and can provide more information about diffusion, perfusion and other physiological interests than standard pulse sequences. The stretched-exponential model has previously been shown to be more reliable than conventional DWI techniques, but different diagnostic sensitivities were found from study to study. This work investigated the characteristics of whole-lesion histogram parameters derived from the stretched-exponential diffusion model for benign and malignant breast lesions, compared them with conventional apparent diffusion coefficient (ADC), and further determined which histogram metrics can be best used to differentiate malignant from benign lesions. This was a prospective study. Seventy females were included in the study. Multi-b value DWI was performed on a 1.5T scanner. Histogram parameters of whole lesions for distributed diffusion coefficient (DDC), heterogeneity index (α), and ADC were calculated by two radiologists and compared among benign lesions, ductal carcinoma in situ (DCIS), and invasive carcinoma confirmed by pathology. Nonparametric tests were performed for comparisons among invasive carcinoma, DCIS, and benign lesions. Comparisons of receiver operating characteristic (ROC) curves were performed to show the ability to discriminate malignant from benign lesions. The majority of histogram parameters (mean/min/max, skewness/kurtosis, 10-90 th percentile values) from DDC, α, and ADC were significantly different among invasive carcinoma, DCIS, and benign lesions. DDC 10% (area under curve [AUC] = 0.931), ADC 10% (AUC = 0.893), and α mean (AUC = 0.787) were found to be the best metrics in differentiating benign from malignant tumors among all histogram parameters derived from ADC and α, respectively. The combination of DDC 10% and α mean , using logistic regression, yielded the highest sensitivity (90.2%) and specificity (95.5%). DDC 10% and α mean derived from

DNA adenine methylation modulates pathogenicity of Klebsiella pneumoniae genotype K1

Directory of Open Access Journals (Sweden)

Chi-Tai Fang

2017-08-01

Conclusion: Our results support the view that DNA adenine methylation plays an important role in modulating the pathogenicity of K. pneumoniae genotype K1. The incomplete attenuation indicates the existence of other regulatory factors.

Coexposure to benzo[a]pyrene plus UVA induced DNA double strand breaks: visualization of Ku assembly in the nucleus having DNA lesions

International Nuclear Information System (INIS)

Toyooka, Tatsushi; Ibuki, Yuko; Koike, Manabu; Ohashi, Norio; Takahashi, Sentaro; Goto, Rensuke

2004-01-01

Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant with potential carcinogenicity. It has been shown that BaP, upon UVA irradiation, synergistically induced oxidative DNA damage, but other DNA damage was not confirmed. In this study, we examined whether coexposure to BaP plus UVA induces double strand breaks (DSBs) using xrs-5 cells, deficient in the repair of DSBs (Ku80 mutant), and whether Ku translocates involving the formation of DSBs. BaP plus UVA had a significant cytotoxic effect on CHO-K1 cells and an even more drastic effect on Ku80-deficient, xrs-5 cells, suggesting that the DSBs were generated by coexposure to BaP plus UVA. The DSBs were repaired in CHO-K1 cells within 30 min, but not in xrs-5 cells, indicating the involvement of a non-homologous end joining, which needs Ku proteins. Furthermore, we succeeded in visualizing that Ku80 rapidly assembled to the exposed region, in which DSBs might be generated, and clarified that the presence of both Ku70 and Ku80 was important for their accumulation

The effect of caffeine and adenine on radiation induced suppression of DNA synthesis, and cell survival

International Nuclear Information System (INIS)

Wilcoxson, L.T.; Griffiths, T.D.

1984-01-01

Exposure of cultured mammalian cells to ionizing radiation or UV light results in a transient decrease in the rate of DNA synthesis. This depression in synthetic rate may be attenuated or deferred via a post-irradiation treatment with caffeine or adenine. It has been suggested that this attenuation may increase the fixation of damage and, therefore, increase radiation sensitivity. However, it has been previously reported that, for V79 cells treated with caffeine or adenine, no correlation exists between the extent of depression and cell survival. The present investigation expands upon these findings by examining the effect of caffeine or adenine post-irradiation treatment on two cell lines with normal UV sensitivity, mouse 3T3 and CHO AA8 cells, and one UV sensitive cell line, CHO UV5 cells. Both caffeine and adenine have been found to reduce, or delay, the suppression in DNA synthesis in all three cell lines. Surprisingly, caffeine appeared to induced even the UV5 cells to recover DNA synthetic ability. The amount of reduction in suppression of DNA synthesis, however, varies between the different cell lines and no consistent relationship with cell survival has emerged

An experimental and theoretical vibrational study of interaction of adenine and thymine with artificial seawaters: A prebiotic chemistry experiment.

Science.gov (United States)

Anizelli, Pedro R; Baú, João P T; Nabeshima, Henrique S; da Costa, Marcello F; de Santana, Henrique; Zaia, Dimas A M

2014-05-21

Nucleic acid bases play important roles in living beings. Thus, their interaction with salts the prebiotic Earth could be an important issue for the understanding of origin of life. In this study, the effect of pH and artificial seawaters on the structure of adenine and thymine was studied via parallel determinations using FT-IR, Raman spectroscopy and theoretical calculations. Thymine and adenine lyophilized in solutions at basic and acidic conditions showed characteristic bands of the enol-imino tautomer due to the deprotonation and the hydrochloride form due to protonation, respectively. The interaction of thymine and adenine with different seawaters representative of different geological periods on Earth was also studied. In the case of thymine a strong interaction with Sr(2+) promoted changes in the Raman and infrared spectra. For adenine changes in infrared and Raman spectra were observed in the presence of salts from all seawaters tested. The experimental results were compared to theoretical calculations, which showed structural changes due to the presence of ions Na(+), Mg(2+), Ca(2+) and Sr(2+) of artificial seawaters. For thymine the bands arising from C4=C5 and C6=O stretching were shifted to lower values, and for adenine, a new band at 1310cm(-1) was observed. The reactivity of adenine and thymine was studied by comparing changes in nucleophilicity and energy of the HOMO orbital. Copyright © 2014 Elsevier B.V. All rights reserved.

Metabolic activation and DNA binding of benzo(a)pyrene in cultured human bronchus

DEFF Research Database (Denmark)

Yang, Shen K.; Gelboin, Harry V.; Trump, Benjamin F.

1977-01-01

. The predominant metabolite formed by human bronchus from the (-)-trans-7,8-diol is found by high-pressure liquid chromatographic analysis to be the diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahy-drobenzo(a)pyrene. The results suggest that this diol-epoxide is the major benzo(a)pyrene metabolite bound...

Hydrothermal stability of adenine under controlled fugacities of N2, CO2 and H2.

Science.gov (United States)

Franiatte, Michael; Richard, Laurent; Elie, Marcel; Nguyen-Trung, Chinh; Perfetti, Erwan; LaRowe, Douglas E

2008-04-01

An experimental study has been carried out on the stability of adenine (one of the five nucleic acid bases) under hydrothermal conditions. The experiments were performed in sealed autoclaves at 300 degrees C under fugacities of CO(2), N(2) and H(2) supposedly representative of those in marine hydrothermal systems on the early Earth. The composition of the gas phase was obtained from the degradation of oxalic acid, sodium nitrite and ammonium chloride, and the oxidation of metallic iron. The results of the experiments indicate that after 200 h, adenine is still present in detectable concentration in the aqueous phase. In fact, the concentration of adenine does not seem to be decreasing after approximately 24 h, which suggests that an equilibrium state may have been established with the inorganic constituents of the hydrothermal fluid. Such a conclusion is corroborated by independent thermodynamic calculations.

PA0148 from Pseudomonas aeruginosa Catalyzes the Deamination of Adenine

Energy Technology Data Exchange (ETDEWEB)

Goble, A.M.; Swaminathan, S.; Zhang, Z.; Sauder, J. M.; Burley, S. K.; Raushel, F. M.

2011-08-02

Four proteins from NCBI cog1816, previously annotated as adenosine deaminases, have been subjected to structural and functional characterization. Pa0148 (Pseudomonas aeruginosa PAO1), AAur1117 (Arthrobacter aurescens TC1), Sgx9403e, and Sgx9403g have been purified and their substrate profiles determined. Adenosine is not a substrate for any of these enzymes. All of these proteins will deaminate adenine to produce hypoxanthine with k{sub cat}/K{sub m} values that exceed 10{sup 5} M{sup -1} s{sup -1}. These enzymes will also accept 6-chloropurine, 6-methoxypurine, N-6-methyladenine, and 2,6-diaminopurine as alternate substrates. X-ray structures of Pa0148 and AAur1117 have been determined and reveal nearly identical distorted ({beta}/{alpha}){sub 8} barrels with a single zinc ion that is characteristic of members of the amidohydrolase superfamily. Structures of Pa0148 with adenine, 6-chloropurine, and hypoxanthine were also determined, thereby permitting identification of the residues responsible for coordinating the substrate and product.

Quantitative 2- and 3-dimensional analysis of pharmacokinetic model-derived variables for breast lesions in dynamic, contrast-enhanced MR mammography

International Nuclear Information System (INIS)

Hauth, E.A.M.; Jaeger, H.J.; Maderwald, S.; Muehler, A.; Kimmig, R.; Forsting, M.

2008-01-01

Purpose: 2- and 3-dimensional evaluation of quantitative pharmacokinetic parameters derived from the Tofts model modeling dynamic contrast enhancement of lesions in MR mammography. Materials and methods: In 95 patients, MR mammography revealed 127 suspicious lesions. The initial rate of enhancement was coded by color intensity, the post-initial enhancement change is coded by color hue. 2D and 3D analysis of distribution of color hue and intensity, vascular permeability and extracellular volume were performed. Results: In 2D, malignant lesions showed significant higher number of bright red, medium red, dark red, bright green, medium green, dark green and bright blue pixels than benign lesions. In 3D, statistical significant differences between malignant and benign lesions was found for all this parameters. Vascular permeability was significant higher in malignant lesions than in benign lesions. Regression model using the 3D data found that the best discriminator between malignant and benign lesions was combined number of voxels and medium green pixels, with a sensitivity of 79.4% and a specificity of 83.1%. Conclusions: Quantitative analysis of pharmacokinetic variables of contrast kinetics showed significant differences between malignant and benign lesions. 3D analysis showed superior diagnostic differentiation between malignant and benign lesions than 2D analysis. The parametric analysis using a pharmacokinetic model allows objective analysis of contrast enhancement in breast lesions

Pulmonary preservation studies: effects on endothelial function and pulmonary adenine nucleotides.

Science.gov (United States)

Paik, Hyo Chae; Hoffmann, Steven C; Egan, Thomas M

2003-02-27

Lung transplantation is an effective therapy plagued by a high incidence of early graft dysfunction, in part because of reperfusion injury. The optimal preservation solution for lung transplantation is unknown. We performed experiments using an isolated perfused rat lung model to test the effect of lung preservation with three solutions commonly used in clinical practice. Lungs were retrieved from Sprague-Dawley rats and flushed with one of three solutions: modified Euro-Collins (MEC), University of Wisconsin (UW), or low potassium dextran and glucose (LPDG), then stored cold for varying periods before reperfusion with Earle's balanced salt solution using the isolated perfused rat lung model. Outcome measures were capillary filtration coefficient (Kfc), wet-to-dry weight ratio, and lung tissue levels of adenine nucleotides and cyclic AMP. All lungs functioned well after 4 hr of storage. By 6 hr, UW-flushed lungs had a lower Kfc than LPDG-flushed lungs. After 8 hr of storage, only UW-flushed lungs had a measurable Kfc. Adenine nucleotide levels were higher in UW-flushed lungs after prolonged storage. Cyclic AMP levels correlated with Kfc in all groups. Early changes in endothelial permeability seemed to be better attenuated in lungs flushed with UW compared with LPDG or MEC; this was associated with higher amounts of adenine nucleotides. MEC-flushed lungs failed earlier than LPDG-flushed or UW-flushed lungs. The content of the solution may be more important for lung preservation than whether the ionic composition is intracellular or extracellular.

Rapid field multiplication of plantains using benzyl adenine or ...

African Journals Online (AJOL)

Une technique appropriee et moins chere pour la multiplication rapide sur Ie terrain de deux varietes locales de plantain Apantu (une corne fausse) et Asamienu (une come veritable) a ete obtenue par injection de 6 ou 8 ml du jus de noix de coco mur sec apres L' ebullition et la filtration ou de 4 ml 10-2 M benzyle adenine ...

Effect of various chemicals on the metabolism of benzo(a)pyrene by cultured rat colon

DEFF Research Database (Denmark)

Autrup, Herman; Harris, Curtis C.; Fugaro, Steven

1977-01-01

The effect of various co- and anti-carcinogens of colon carcinogenesis on the metabolism of benzo(a)pyrene (BP) in cultured rat colon is reported. Rat colon enzymatically converted BP into metabolites which bind to cellular macromolecules i.e., DNA and protein. Activity of aryl hydrocarbon...

Separation of water-soluble metabolites of benzo[a]pyrene formed by cultured human colon

DEFF Research Database (Denmark)

Autrup, Herman

1979-01-01

A method has been developed to separate conjugated metabolites of benzo[a]pyrene into three major fractions: sulfate esters, glucuronides and glutathione conjugates. In cultured human colon, formation of sulfate esters and glutathione conjugates is the major conjugation pathway, while formation......-hydroxybenzo[a]pyrene were the major substrates for sulfotransferase in cultured human colon....

Quantification of DNA in Neonatal Dried Blood Spots by Adenine Tandem Mass Spectrometry.

Science.gov (United States)

Durie, Danielle; Yeh, Ed; McIntosh, Nathan; Fisher, Lawrence; Bulman, Dennis E; Birnboim, H Chaim; Chakraborty, Pranesh; Al-Dirbashi, Osama Y

2018-01-02

Newborn screening programs have expanded to include molecular-based assays as first-tier tests and the success of these assays depends on the quality and yield of DNA extracted from neonatal dried blood spots (DBS). To meet high throughput and rapid turnaround time requirements, newborn screening laboratories adopted rapid DNA extraction methods that produce crude extracts. Quantification of DNA in neonatal DBS is not routinely performed due to technical challenges; however, this may enhance the performance of assays that are sensitive to amounts of input DNA. In this study, we developed a novel high throughput method to quantify total DNA in DBS. It is based on specific acid-catalyzed depurination of DNA followed by mass spectrometric quantification of adenine. The amount of adenine was used to calculate DNA quantity per 3.2 mm DBS. Reference intervals were established using archived, neonatal DBS (n = 501) and a median of 130.6 ng of DNA per DBS was obtained, which is in agreement with literature values. The intra- and interday variations were quantification were 12.5 and 37.8 nmol/L adenine, respectively. We demonstrated that DNA from neonatal DBS can be successfully quantified in high throughput settings using instruments currently deployed in NBS laboratories.

Ethanol-induced activation of adenine nucleotide turnover. Evidence for a role of acetate

International Nuclear Information System (INIS)

Puig, J.G.; Fox, I.H.

1984-01-01

Consumption of alcohol causes hyperuricemia by decreasing urate excretion and increasing its production. Our previous studies indicate that ethanol administration increases uric acid production by increasing ATP degradation to uric acid precursors. To test the hypothesis that ethanol-induced increased urate production results from acetate metabolism and enhanced adenosine triphosphate turnover, we gave intravenous sodium acetate, sodium chloride and ethanol (0.1 mmol/kg per min for 1 h) to five normal subjects. Acetate plasma levels increased from 0.04 +/- 0.01 mM (mean +/- SE) to peak values of 0.35 +/- 0.07 mM and to 0.08 +/- 0.01 mM during acetate and ethanol infusions, respectively. Urinary oxypurines increased to 223 +/- 13% and 316 +/- 44% of the base-line values during acetate and ethanol infusions, respectively. Urinary radioactivity from the adenine nucleotide pool labeled with [8-14C] adenine increased to 171 +/- 27% and to 128 +/- 8% of the base-line values after acetate and ethanol infusions. These data indicate that both ethanol and acetate increase purine nucleotide degradation by enhancing the turnover of the adenine nucleotide pool. They support the hypothesis that acetate metabolism contributes to the increased production of urate associated with ethanol intake

Red blood cell aging markers during storage in citrate-phosphate-dextrose-saline-adenine-glucose-mannitol.

Science.gov (United States)

Antonelou, Marianna H; Kriebardis, Anastasios G; Stamoulis, Konstantinos E; Economou-Petersen, Effrosini; Margaritis, Lukas H; Papassideri, Issidora S

2010-02-01

It has been suggested that red blood cell (RBC) senescence is accelerated under blood bank conditions, although neither protein profile of RBC aging nor the impact of additive solutions on it have been studied in detail. RBCs and vesicles derived from RBCs in both citrate-phosphate-dextrose (CPD)-saline-adenine-glucose-mannitol (SAGM) and citrate-phosphate-dextrose-adenine (CPDA) were evaluated for the expression of cell senescence markers (vesiculation, protein aggregation, degradation, activation, oxidation, and topology) through immunoblotting technique and immunofluorescence or immunoelectron microscopy study. A group of cellular stress proteins exhibited storage time- and storage medium-related changes in their membrane association and exocytosis. The extent, the rate, and the expression of protein oxidation, Fas oligomerization, caspase activation, and protein modifications in Band 3, hemoglobin, and immunoglobulin G were less conspicuous and/or exhibited significant time retardation under storage in CPD-SAGM, compared to the CPDA storage. There was evidence for the localization of activated caspases near to the membrane of both cells and vesicles. We provide circumstantial evidence for a lower protein oxidative damage in CPD-SAGM-stored RBCs compared to the CPDA-stored cells. The different expression patterns of the senescence markers in the RBCs seem to be accordingly related to the oxidative stress management of the cells. We suggest that the storage of RBCs in CPD-SAGM might be more alike the in vivo RBC aging process, compared to storage in CPDA, since it is characterized by a slower stimulation of the recognition signaling pathways that are already known to trigger the erythrophagocytosis of senescent RBCs.

Prevention of injury by resveratrol in a rat model of adenine-induced ...

African Journals Online (AJOL)

phosphorous, and fibroblast growth factor-23 (FGF-23) in rat urine samples after 2 months of adenine ... parathyroid hormone, phosphorous and FGF-23 levels (p < 0.002). In rats ... cartilage degradation in animal models of arthritis. [11].

Effect of Adenine Concentration on the Corrosion Inhibition of Aisi ...

African Journals Online (AJOL)

This gave a surface coverage of 0.8956 and corrosion penetration rate of 0.022132mm/yr. Hence, the best adenine concentration for the corrosion inhibition of alloys 304L in 1.0M sulphuric acid solution to obtain optimum inhibition efficiency is 0.011M. Keywords: Corrosion, AISI 304L Steel, Inhibition efficiency, Degree of ...

Pharmacological response of systemically derived focal epileptic lesions

Energy Technology Data Exchange (ETDEWEB)

Remler, M.P.; Sigvardt, K.; Marcussen, W.H.

1986-11-01

Focal epileptic lesions were made in rats by systemic focal epileptogenesis. In this method, a focal lesion of the blood-brain barrier (BBB) is produced by focal alpha irradiation followed by repeated systemic injection of a convulsant drug that cannot cross the normal BBB, resulting in a chronic epileptic focus. Changes in the spike frequency of these foci in response to various drugs was recorded. The controls, saline and chlorpromazine, produced no change. Phenytoin, phenobarbital, chlordiazepoxide, and valproic acid produced the expected decrease in spike frequency. Pentobarbital and diazepam produced a paradoxical increase in spike frequency.

Enzymatic synthesis of 13N-β-nicotinamide adenine dinucleotide

International Nuclear Information System (INIS)

Lambrecht, R.H.D.; Slegers, G.; Claeys, A.; Vandecasteele, C.

1985-01-01

Nitrogen-13-labelled β-nicotinamide adenine dinucleotide ( 13 N-NAD) is an interesting new compound for positron emission tomography. A semi-automatic production method is developed that yields a solution of 13 N-NAD of radiopharmaceutical quality, suitable for human intravenous administration. The 13 N-NAD is prepared enzymatically in one step from cyclotron-produced 13 NH 3 and nicotinic acid adenine dinucleotide (deamido-NAD). The enzyme NAD synthetase (E.C. 6.3.1.5), catalysing this reaction, is extracted and purified from Escherichia coli. The purified enzyme is immobilized by glutaraldehyde coupling to γ-aminopropylsilane-coated porous glass beads. The enzyme-loaded glass beads are packed in a column. The kinetic properties of the column are optimized. For synthetizing 13 N-NAD, the mixture of co-factors and substrates, containing 13 NH 3 , is pumped over the enzyme column. The unreacted 13 NH 3 is separated from 13 N-NAD by on-line passage over a cation exchanger. After passing over a millipore filter, a sterile solution of radiochemically pure 13 N-NAD is obtained, containing 70 mCi in 10 mL. The total synthesis time is 10 minutes. The specific activity is about 120 mCi/μmol at EOB. Quality control includes sterility and pyrogen tests, HPLC and HPTLC analysis. (author)

Multimedia transport of particle-bound organics: benzo(a)pyrene test case

Energy Technology Data Exchange (ETDEWEB)

Ryan, P A; Cohen, Y

1986-01-01

A screening multimedia-compartmental (MCM) modeling approach is presented for predicting the distribution of particle-bound pollutants within an environment consisting of the atmosphere, surface water, and surface soil compartments. An MCM model was used to simulate the dynamic distribution of Benzo(a)Pyrene (B(a)P) for a study region located in southeast Ohio. The model incorporates theoretical estimates of the dry deposition velocity and a new semi-empirical model for rain scavenging of B(a)P. The predicted concentrations of B(a)P compared favorably with available field data.

Attenuation of Red Blood Cell Storage Lesions with Vitamin C

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Kimberly Sanford

2017-07-01

Full Text Available Stored red blood cells (RBCs undergo oxidative stress that induces deleterious metabolic, structural, biochemical, and molecular changes collectively referred to as “storage lesions”. We hypothesized that vitamin C (VitC, reduced or oxidized would reduce red cell storage lesions, thus prolonging their storage duration. Whole-blood-derived, leuko-reduced, SAGM (saline-adenine-glucose-mannitol-preserved RBC concentrates were equally divided into four pediatric storage bags and the following additions made: (1 saline (saline; (2 0.3 mmol/L reduced VitC (Lo VitC; (3 3 mmol/L reduced VitC (Hi VitC; or (4 0.3 mmol/L oxidized VitC (dehydroascorbic acid, DHA as final concentrations. Biochemical and rheological parameters were serially assessed at baseline (prior to supplementation and Days 7, 21, 42, and 56 for RBC VitC concentration, pH, osmotic fragility by mechanical fragility index, and percent hemolysis, LDH release, glutathione depletion, RBC membrane integrity by scanning electron microscopy, and Western blot for β-spectrin. VitC exposure (reduced and oxidized significantly increased RBC antioxidant status with varying dynamics and produced trends in reduction in osmotic fragility and increases in membrane integrity. Conclusion: VitC partially protects RBC from oxidative changes during storage. Combining VitC with other antioxidants has the potential to improve long-term storage of RBC.

The role of HUCB derived stem cells therapy in repair of renal ...

African Journals Online (AJOL)

Dr Olaleye Samuel

and improvement of renal function in cisplatin-induced ARF model. Forty four rats ... 88.9% of animals in MSCs treated rats versus 87.5% in CD34+ cells treated rats. HUCB derived .... containing 5 ml of citrate phosphate dextrose adenine-1.

Kinetic analysis of Yersinia pestis DNA adenine methyltransferase activity using a hemimethylated molecular break light oligonucleotide.

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Robert J Wood

Full Text Available BACKGROUND: DNA adenine methylation plays an important role in several critical bacterial processes including mismatch repair, the timing of DNA replication and the transcriptional control of gene expression. The dependence of bacterial virulence on DNA adenine methyltransferase (Dam has led to the proposal that selective Dam inhibitors might function as broad spectrum antibiotics. METHODOLOGY/PRINCIPAL FINDINGS: Herein we report the expression and purification of Yersinia pestis Dam and the development of a continuous fluorescence based assay for DNA adenine methyltransferase activity that is suitable for determining the kinetic parameters of the enzyme and for high throughput screening against potential Dam inhibitors. The assay utilised a hemimethylated break light oligonucleotide substrate containing a GATC methylation site. When this substrate was fully methylated by Dam, it became a substrate for the restriction enzyme DpnI, resulting in separation of fluorophore (fluorescein and quencher (dabcyl and therefore an increase in fluorescence. The assays were monitored in real time using a fluorescence microplate reader in 96 well format and were used for the kinetic characterisation of Yersinia pestis Dam, its substrates and the known Dam inhibitor, S-adenosylhomocysteine. The assay has been validated for high throughput screening, giving a Z-factor of 0.71+/-0.07 indicating that it is a sensitive assay for the identification of inhibitors. CONCLUSIONS/SIGNIFICANCE: The assay is therefore suitable for high throughput screening for inhibitors of DNA adenine methyltransferases and the kinetic characterisation of the inhibition.

Observations on human smooth muscle cell cultures from hyperplastic lesions of prosthetic bypass grafts: Production of a platelet-derived growth factor-like mitogen and expression of a gene for a platelet-derived growth factor receptor--a preliminary study

International Nuclear Information System (INIS)

Birinyi, L.K.; Warner, S.J.; Salomon, R.N.; Callow, A.D.; Libby, P.

1989-01-01

Prosthetic bypass grafts placed to the distal lower extremity often fail because of an occlusive tissue response in the perianastomotic region. The origin of the cells that comprise this occlusive lesion and the causes of the cellular proliferation are not known. To increase our understanding of this process we cultured cells from hyperplastic lesions obtained from patients at the time of reexploration for lower extremity graft failure, and we studied their identity and growth factor production in tissue culture. These cultures contain cells that express muscle-specific actin isoforms, shown by immunohistochemical staining, consistent with vascular smooth muscle origin. These cultures also released material that stimulated smooth muscle cell growth. A portion of this activity was similar to platelet-derived growth factor, since preincubation with antibody-to-human platelet-derived growth factor partially blocked the mitogenic effect of medium conditioned by human anastomotic hyperplastic cells. These conditioned media also contained material that competed with platelet-derived growth factor for its receptor, as measured in a radioreceptor assay. Northern blot analysis showed that these cells contain messenger RNA that encodes the A chain but not the B chain of platelet-derived growth factor. In addition, these cells contain messenger RNA that encodes a platelet-derived growth factor receptor. We conclude that cultured smooth muscle cells from human anastomotic hyperplastic lesions express genes for platelet-derived growth factor A chain and a platelet-derived growth factor receptor and secrete biologically active molecules similar to platelet-derived growth factor

Topical chlorophyll-pheophytin derivative-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premaligant lesions: an in vivo study

Science.gov (United States)

Hsu, Yih-Chih; Chiang, Chung-Pin; Chen, Jian Wen; Lee, Jeng-Woei; How, Mon-Hsin

2010-02-01

In Taiwan, oral cancer has become a prominent cancer because of its highest annual increase rate among all cancer diseases. Betel quid chewing habit is a major risk factor for oral precancerous and cancerous lesions and there are more than two million people who have this habit in Taiwan. Our previous studies showed that chlorophyll-pheophytin derivative (CPD)-mediated PDT is very effective for killing of SCC-4 cell lines in vitro. In order to decrease the systemic phototoxic effect of CPD, this study was designed to use a topical CPD-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions of moderate to severe dysplasia were induced and proven by histological examination. These induced precancerous lesions were used for testing the efficacy of topical CPD-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when CPD reached its peak level in the lesional epithelial cells after topical application of CPD gel. We found that CPD reached its peak level in precancerous lesions about 1 hour (range, 0 to 30 hours) after topical application of CPD gel. The precancerous lesions in hamsters were then treated with topical CPD-mediated PDT (fluence rate: 200 mW/cm2; light exposure dose 100 J/cm2) using the portable WonderLight LED 635 nm fiber-guided light device once or twice a week. Visual and histological examination demonstrated that topical CPD-mediated PDT was partially effective treatment modality for DMBA-induced hamster buccal pouch precancerous lesions.

Voltammetric study of adenine complex with copper on mercury electrode

Czech Academy of Sciences Publication Activity Database

Jelen, František; Kouřilová, Alena; Hasoň, Stanislav; Kizek, R.; Trnková, L.

2009-01-01

Roč. 21, 3-5 (2009), s. 439-444 ISSN 1040-0397 R&D Projects: GA AV ČR(CZ) IAA100040602; GA AV ČR(CZ) IAA400040804; GA AV ČR(CZ) KAN200040651 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : cyclic voltammetry * elimination voltammetry * copper-adenine complex Subject RIV: BO - Biophysics Impact factor: 2.630, year: 2009

Hasse diagram as a green analytical metrics tool: ranking of methods for benzo[a]pyrene determination in sediments.

Science.gov (United States)

Bigus, Paulina; Tsakovski, Stefan; Simeonov, Vasil; Namieśnik, Jacek; Tobiszewski, Marek

2016-05-01

This study presents an application of the Hasse diagram technique (HDT) as the assessment tool to select the most appropriate analytical procedures according to their greenness or the best analytical performance. The dataset consists of analytical procedures for benzo[a]pyrene determination in sediment samples, which were described by 11 variables concerning their greenness and analytical performance. Two analyses with the HDT were performed-the first one with metrological variables and the second one with "green" variables as input data. Both HDT analyses ranked different analytical procedures as the most valuable, suggesting that green analytical chemistry is not in accordance with metrology when benzo[a]pyrene in sediment samples is determined. The HDT can be used as a good decision support tool to choose the proper analytical procedure concerning green analytical chemistry principles and analytical performance merits.

High-NaCl diet impairs dynamic renal blood flow autoregulation in rats with adenine-induced chronic renal failure

DEFF Research Database (Denmark)

Saeed, Aso; DiBona, Gerald F; Grimberg, Elisabeth

2014-01-01

This study examined the effects of 2 wk of high-NaCl diet on kidney function and dynamic renal blood flow autoregulation (RBFA) in rats with adenine-induced chronic renal failure (ACRF). Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without...... arterial pressure variability (SAPV), and heart rate variability were assessed by spectral analytical techniques. Rats with ACRF showed marked reductions in glomerular filtration rate and renal blood flow (RBF), whereas mean arterial pressure and SAPV were significantly elevated. In addition, spontaneous...... adenine (controls). After 10 wk, rats were randomized to either remain on the same diet (0.6% NaCl) or to be switched to high 4% NaCl chow. Two weeks after randomization, renal clearance experiments were performed under isoflurane anesthesia and dynamic RBFA, baroreflex sensitivity (BRS), systolic...

In vitro propagation of Calla lily: adenine sulphate and 6-benzilaminopurine

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Márcia De Nazaré Oliveira Ribeiro

2014-09-01

Full Text Available Calla lily [Zantedeschia aethiopica (L. Spreng.] belonging to the Araceae family is appreciated as cut flower and in com­position of gardens. However, the conventional propagation of this plants shows a poor productive. Thus, tissue culture besides allowing fast clonal propagation also provides healthy and uniforms plants. The aim was study the influence of the differents concentrations of 6-benzilaminopurine (BAP and adenine sulphate (AS on in vitro multiplication of Calla lily. The explants were maintained in MS medium added with BAP (0.0, 8.9, 17.8 and 26.7 μM and adenine sulphate (0, 54, 108 and 162 μM. The plants were transferred to growth room and maintained at 25±1ºC and photoperiod of 16 hours for 60 days, under luminous intensity of 35 μmol m-2 s-1, for a period of 60 days. The experimental design was entirely randomized with four repetitions of three seedlings each, resulting in twelve plants per treatment, each tube with one plant. The statistics analysis showed interactive effects for quantify of BAP and AS for leaves number and fresh mass of the aerial parts. The highest number of leaves (4.8 and fresh mass of aerial parts (0.73 g was obtained with 26.7 μM of BAP combined with 108 μM of AS, highest number of shoots (2.6 was obtained with 22,19 μM of BAP and highest lengh of sprouts (5.0 cm was observed in the absence of BAP. The addition of BAP increased the number of shoots per explant. The use of adenine sulphate in combination with BAP had a positive effect for the accumulation of fresh weight and number of leaves in vitro culture.

DNA synthesis and cell survival after X-irradiation of mammalian cells treated with caffeine or adenine

International Nuclear Information System (INIS)

Griffiths, T.D.; Carpenter, J.G.; Dahle, D.B.

1978-01-01

The expression of the transient depression in the rate of DNA synthesis normally observed after exposure of randomly-dividing Chinese hamster V-79 or Chinese hamster CHO cells to ionizing radiation could be postponed by a post-irradiation treatment with 1.0 to 2.0 mM adenine or 1.5 mM caffeine. Caffeine may exert its effect by creating additional sites for replication in irradiated cells. Cells treated with caffeine or adenine for 2 or 4 hours after exposure to 3000 rad of 300 kVp X-rays exhibited depressed synthesis only after the removal of caffeine or adenine. These alterations in the timing of the X-ray-induced depression of the rate of DNA synthesis had no effect on X-ray-induced cell killing. Although a 4 hour post-irradiation treatment of randomly-dividing Chinese hamster V-79 cells with 1.0 or 2.0 mM caffeine potentiated X-ray-induced cell killing, this reduction in survival was due primarily to effects on cells not in S-phase. (author)

Benzo(a)pyrene activation and detoxification by human pulmonary alveolar macrophages and lymphocytes

International Nuclear Information System (INIS)

Marshall, M.V.; McLemore, T.L.; Martin, R.R.; Marshall, M.H.; Wray, N.P.; Busbee, D.L.; Cantrell, E.T.; Arnott, M.S.; Griffin, A.C.

1980-01-01

Comparisons of pulmonary alveolar macrophages and circulating lymphocytes from five smokers and five nonsmokers for their ability to metabolize benzo(a)pyrene as determined by high pressure liquid chromatography were carried out. Utilizing this approach, further investigation of activation and detoxification by several human cell types could provide the basis for more precise and comprehensive studies of carcinogen and drug metabolism in the human lung, and for a better assessment of cancer risk in selected populations

Determination of Benzo(a)pyrene in Malaysian commercialized coffee powder using solid phase extraction and gas chromatography

International Nuclear Information System (INIS)

Noraini Kasim; Rozita Osman; Norashikin Saim; Licaberth Ismail

2012-01-01

Roasting is a critical process in coffee production as it enables the development of flavor and aroma. Benzo[a]pyrene (BaP) is a non desirable product of incomplete combustion at temperatures between 300 and 600 degree Celsius and may be produced during roasting step. In this study, selected samples of roasted coffee powder were analysed for BaP. Extraction of BaP was achieved using C 18 solid phase extraction (SPE) prior to analysis by gas chromatography. Calibration curve prepared with concentrations ranged between 3 - 50 ppm showed good linearity with r = 0.999. The limit of detection (LOD) was 0.25 ppm and the limit of quantification (LOQ) was 0.85 ppm. Recovery of BaP obtained from spiked sample (3 ppm) was 88.7 % with RSD (n=3) of 5.4 %. Benzo[a]pyrene was detected in all samples, at level ranging from 0.14 to 0.62 ppb. (author)

Overexpression of Cholesteryl Ester Transfer Protein Increases Macrophage-Derived Foam Cell Accumulation in Atherosclerotic Lesions of Transgenic Rabbits

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Shoucui Gao

2017-01-01

Full Text Available High levels of plasma high-density lipoprotein-cholesterol (HDL-C are inversely associated with the risk of atherosclerosis and other cardiovascular diseases; thus, pharmacological inhibition of cholesteryl ester transfer protein (CETP is considered to be a therapeutic method of raising HDL-C levels. However, many CETP inhibitors have failed to achieve a clinical benefit despite raising HDL-C. In the study, we generated transgenic (Tg rabbits that overexpressed the human CETP gene to examine the influence of CETP on the development of atherosclerosis. Both Tg rabbits and their non-Tg littermates were fed a high cholesterol diet for 16 weeks. Plasma lipids and body weight were measured every 4 weeks. Gross lesion areas of the aortic atherosclerosis along with lesional cellular components were quantitatively analyzed. Overexpression of human CETP did not significantly alter the gross atherosclerotic lesion area, but the number of macrophages in lesions was significantly increased. Overexpression of human CETP did not change the plasma levels of total cholesterol or low-density lipoprotein cholesterol but lowered plasma HDL-C and increased triglycerides. These data revealed that human CETP may play an important role in the development of atherosclerosis mainly by decreasing HDL-C levels and increasing the accumulation of macrophage-derived foam cells.

Effect of aqueous extract and anthocyanins of calyces of Hibiscus sabdariffa (Malvaceae) in rats with adenine-induced chronic kidney disease.

Science.gov (United States)

Ali, Badreldin H; Cahliková, Lucie; Opletal, Lubomir; Karaca, Turan; Manoj, Priyadarsini; Ramkumar, Aishwarya; Al Suleimani, Yousuf M; Al Za'abi, Mohammed; Nemmar, Abderrahim; Chocholousova-Havlikova, Lucie; Locarek, Miroslav; Siatka, Tomas; Blunden, Gerald

2017-09-01

The aim of this work was to assess the possible beneficial effects of aqueous extracts of Hibiscus sabdariffa L. calyces and anthocyanins isolated therefrom in an adenine-induced chronic kidney disease (CKD) model. Rats were orally given, for 28 consecutive days, either adenine alone or together with either aqueous extract of H. sabdariffa calyces (5 and 10%) or anthocyanins (50, 100 and 200 mg/kg of anthocyanin concentrate). For comparative purposes, two groups of rats were given lisinopril (10 mg/kg). When either H. sabdariffa aqueous extract or the anthocyanins isolated from it was administered along with adenine, the adverse effects of adenine-induced CKD were significantly lessened, mostly in a dose-dependent manner. The positive effects were similar to those obtained by administration of lisinopril. The results obtained show that both H. sabdariffa and its anthocyanins could be considered as possible promising safe dietary agents that could be used to attenuate the progression of human CKD. This could have added significance as H. sabdariffa tea is widely consumed in many parts of Africa and Asia and is thus readily available. © 2017 Royal Pharmaceutical Society.

Metabolism of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene in cultured human bronchus and pancreatic duct

DEFF Research Database (Denmark)

Harris, Curtis C.; Autrup, Herman; Stoner, Gary

1977-01-01

The metabolism of two carcinogenic polynuclear aro matic hydrocarbons, benzo[a]pyrene (BP) and 7,12-dimethylbenz[a]anthracene, was studied in expiants of human pancreatic duct and bronchus cultured in a chemically defined medium. In cultured human bronchial mucosa, activity of aryl hydrocarbon hy...

High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

DEFF Research Database (Denmark)

Kashioulis, Pavlos; Hammarsten, Ola; Marcussen, Niels

2016-01-01

AIMS: To examine the effects of 2 weeks of high-NaCl diet on left ventricular (LV) morphology and serum levels of cardiac troponin T (cTnT) in rats with adenine-induced chronic renal failure (ACRF). METHODS: Male Sprague-Dawley rats either received chow containing adenine or were pair......-fed an identical diet without adenine [controls (C)]. Approximately 10 weeks after the beginning of the study, the rats were randomized to either remain on a normal NaCl diet (NNa; 0.6%) or to be switched to high-NaCl chow (HNa; 4%) for 2 weeks, after which acute experiments were performed. RESULTS: Rats with ACRF...... showed statistically significant increases (p rats (p

On the existence of the H3 tautomer of adenine in aqueous solution. Rationalizations based on hybrid quantum mechanics/molecular mechanics predictions

DEFF Research Database (Denmark)

Aidas, Kestutis; Mikkelsen, Kurt V; Kongsted, Jacob

2010-01-01

The (15)N NMR spectrum of adenine in aqueous solution has been modeled using high-level combined density functional theory/molecular mechanics techniques coupled to a dynamical averaging scheme. The explicit consideration of the three lowest-energy tautomers of adenine-H9, H7 and H3-allows...

Gum acacia mitigates genetic damage in adenine-induced chronic renal failure in rats.

Science.gov (United States)

Ali, B H; Al Balushi, K; Al-Husseini, I; Mandel, P; Nemmar, A; Schupp, N; Ribeiro, D A

2015-12-01

Subjects with chronic renal failure (CRF) exhibit oxidative genome damage, which may predispose to carcinogenesis, and Gum acacia (GumA) ameliorates this condition in humans and animals. We evaluated here renal DNA damage and urinary excretion of four nucleic acid oxidation adducts namely 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxoguanosine (8-oxoGuo) and 8-hydroxy-2-deoxyguanisone (8-OHdg) in rats with adenine (ADE)-induced CRF with and without GumA treatment. Twenty-four rats were divided into four equal groups and treated for 4 weeks. The first group was given normal food and water (control). The second group was given normal food and GumA (15% w/v) in drinking water. The third group was fed powder diet containing adenine (ADE) (0·75% w/w in feed). The fourth group was fed like in the third group, plus GumA in drinking water (15%, w/v). ADE feeding induced CRF (as measured by several physiological, biochemical and histological indices) and also caused a significant genetic damage and significant decreases in urinary 8-oxo Gua and 8-oxoGuo, but not in the other nucleic acids. However, concomitant GumA treatment reduced the level of genetic damage in kidney cells as detected by Comet assay and significantly reversed the effect of adenine on urinary 8-oxoGuo. Treatment with GumA is able to mitigate genetic damage in renal tissues of rats with ADE-induced CRF. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Circular dichroism spectroscopy of conformers of (guanine + adenine) repeat strands of DNA

Czech Academy of Sciences Publication Activity Database

Kejnovská, Iva; Kypr, Jaroslav; Vorlíčková, Michaela

2003-01-01

Roč. 15, č. 7 (2003), s. 584-592 ISSN 0899-0042 R&D Projects: GA AV ČR IAA4004201; GA ČR GA204/01/0561 Institutional research plan: CEZ:AV0Z5004920 Keywords : DNA conformation * (guanine + adenine) repeats * homoduplexes Subject RIV: BO - Biophysics Impact factor: 1.793, year: 2003

Ischemic lesion volume determination on diffusion weighted images vs. apparent diffusion coefficient maps.

Science.gov (United States)

Bråtane, Bernt Tore; Bastan, Birgul; Fisher, Marc; Bouley, James; Henninger, Nils

2009-07-07

Though diffusion weighted imaging (DWI) is frequently used for identifying the ischemic lesion in focal cerebral ischemia, the understanding of spatiotemporal evolution patterns observed with different analysis methods remains imprecise. DWI and calculated apparent diffusion coefficient (ADC) maps were serially obtained in rat stroke models (MCAO): permanent, 90 min, and 180 min temporary MCAO. Lesion volumes were analyzed in a blinded and randomized manner by 2 investigators using (i) a previously validated ADC threshold, (ii) visual determination of hypointense regions on ADC maps, and (iii) visual determination of hyperintense regions on DWI. Lesion volumes were correlated with 24 hour 2,3,5-triphenyltetrazoliumchloride (TTC)-derived infarct volumes. TTC-derived infarct volumes were not significantly different from the ADC and DWI-derived lesion volumes at the last imaging time points except for significantly smaller DWI lesions in the pMCAO model (p=0.02). Volumetric calculation based on TTC-derived infarct also correlated significantly stronger to volumetric calculation based on last imaging time point derived lesions on ADC maps than DWI (pdetermined lesion volumes on ADC maps and DWI by both investigators correlated significantly with threshold-derived lesion volumes on ADC maps with the former method demonstrating a stronger correlation. There was also a better interrater agreement for ADC map analysis than for DWI analysis. Ischemic lesion determination by ADC was more accurate in final infarct prediction, rater independent, and provided exclusive information on ischemic lesion reversibility.

Development of a simple and efficient method for assaying cytidine monophosphate sialic acid synthetase activity using an enzymatic reduced nicotinamide adenine dinucleotide/oxidized nicotinamide adenine dinucleotide converting system.

Science.gov (United States)

Fujita, Akiko; Sato, Chihiro; Münster-Kühnel, Anja-K; Gerardy-Schahn, Rita; Kitajima, Ken

2005-02-01

A new reliable method to assay the activity of cytidine monophosphate sialic acid (CMP-Sia) synthetase (CSS) has been developed. The activation of sialic acids (Sia) to CMP-Sia is a prerequisite for the de novo synthesis of sialoglycoconjugates. In vertebrates, CSS has been cloned from human, mouse, and rainbow trout, and the crystal structure has been resolved for the mouse enzyme. The mouse and rainbow trout enzyme have been compared with respect to substrate specificity, demonstrating that the mouse enzyme exhibits a pronounced specificity for N-acetylneuraminic acid (Neu5Ac), while the rainbow trout CSS is equally active with either of three Sia species, Neu5Ac, N-glycolylneuraminic acid (Neu5Gc), and deaminoneuraminic acid (KDN). However, molecular details that explain the pronounced substrate specificities are unknown. Understanding the catalytic mechanisms of these enzymes is of major importance, since CSSs play crucial roles in cellular sialylation patterns and thus are potential drug targets in a number of pathophysiological situations. The availability of the cDNAs and the obtained structural data enable rational approaches; however, these efforts are limited by the lack of a reliable high-throughput assay system. Here we describe a new assay system that allows product quantification in a reduced nicotinamide adenine dinucleotide (NADH)-dependent color reaction. The activation reaction catalyzed by CSS, CTP+Sia-->CMP-Sia+pyrophosphate, was evaluated by a consumption of Sia, which corresponds to that of NADH on the following two successive reactions: (i) Sia-->pyruvate+ManNAc (or Man), catalyzed by a sialic acid lyase (SAL), and (ii) pyruvate+NADH-->lactate+oxidized nicotinamide adenine dinucleotide (NAD+), catalyzed by a lactate dehydrogenase (LDH). Consumption of NADH can be photometrically monitored on a microtiter plate reader for a number of test samples at the same time. Furthermore, based on the quantification of CSS used in the SAL/LDH assay

Induction of micronuclei by X radiation and various chemical agents in red blood cells of Pleurodeles waltl. Uptake, release and excretion of one of them: benzo(a)pyrene

International Nuclear Information System (INIS)

Grinfeld, S.

1983-11-01

The first part of the study is concerned with the effects of X radiation and of various substances dissolved in the breeding water (carbaryl, N-nitrosocarbaryl, benzo(a)pyrene, formol, cafeine, colchicine...) on the formation of micronuclei in red blood cells of Pleurodele larvae. The curves of the dose-effect relationships and of the kinetics of micronuclei formation are established for X radiation and benzo(a)pyrene. In the second part, a scintigraphic study concerning benzo(a)pyrene uptake, release and excretion by larvae, is presented. This study enables the dose-effect curve and the kinetics of micronuclei formation for this substance, to be interpreted. This study must allow the development of a cytogenetic test for the detection of radiomimetic substances in aqueous medium. Pleurodele is proposed as a new animal for the study of genetic toxicology [fr

SERS, XPS, and DFT Study of Adenine Adsorption on Silver and Gold Surfaces.

Science.gov (United States)

Pagliai, Marco; Caporali, Stefano; Muniz-Miranda, Maurizio; Pratesi, Giovanni; Schettino, Vincenzo

2012-01-19

The adsorption of adenine on silver and gold surfaces has been investigated combining density functional theory calculations with surface-enhanced Raman scattering and angle-resolved X-ray photoelectron spectroscopy measurements, obtaining useful insight into the orientation and interaction of the nucleobase with the metal surfaces.

Probing adenine rings and backbone linkages using base specific isotope-edited Raman spectroscopy: application to group II intron ribozyme domain V.

Science.gov (United States)

Chen, Yuanyuan; Eldho, Nadukkudy V; Dayie, T Kwaku; Carey, Paul R

2010-04-27

Raman difference spectroscopy is used to probe the properties of a 36-nt RNA molecule, "D5", which lies at the heart of the catalytic apparatus in group II introns. For D5 that has all of its adenine residues labeled with (13)C and (15)N and utilizing Raman difference spectroscopy, we identify the conformationally sensitive -C-O-P-O-C- stretching modes of the unlabeled bonds adjacent to adenine bases, as well as the adenine ring modes themselves. The phosphodiester modes can be assigned to individual adenine residues based on earlier NMR data. The effect of Mg(2+) binding was explored by analyzing the Raman difference spectra for [D5 + Mg(2+)] minus [D5 no Mg(2+)], for D5 unlabeled, or D5 labeled with (13)C/(15)N-enriched adenine. In both sets of data we assign differential features to G ring modes perturbed by Mg(2+) binding at the N7 position. In the A-labeled spectra we attribute a Raman differential near 1450 cm(-1) and changes of intensity at 1296 cm(-1) to Mg binding at the N7 position of adenine bases. The A and G bases involved in Mg(2+) binding again can be identified using earlier NMR results. For the unlabeled D5, a change in the C-O-P-O-C stretch profile at 811 cm(-1) upon magnesium binding is due to a "tightening up" (in the sense of a more rigid molecule with less dynamic interchange among competing ribose conformers) of the D5 structure. For adenine-labeled D5, small changes in the adenine backbone bond signatures in the 810-830 cm(-1) region suggest that small conformational changes occur in the tetraloop and bulge regions upon binding of Mg(2+). The PO(2)(-) stretching vibration, near 1100 cm(-1), from the nonbridging phosphate groups, probes the effect of Mg(2+)-hydrate inner-sphere interactions that cause an upshift. In turn, the upshift is modulated by the presence of monovalent cations since in the presence of Na(+) and Li(+) the upshift is 23 +/- 2 cm(-1) while in the presence of K(+) and Cs(+) it is 13 +/- 3 cm(-1), a finding that correlates

Metabolism of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in cultured human fetal aortic smooth muscle cells

International Nuclear Information System (INIS)

Bond, J.A.; Kocan, R.M.; Benditt, E.P.; Juchau, M.R.

1979-01-01

Cultured human fetal aortic smooth muscle cells derived from the abdominal aorta converted benzo[a]pyrene (BaP) and 7,12-dimethylbenz[a]anthracene (DMBA) via cytochrome P-450-dependent monooxygenation to metabolites detectable by both a highly sensitive radiometric assay and high pressure liquid chromatography (HPLC). Cells incubated with 3 H-BaP transformed this substrate primarily to phenols. 14 C-DMBA was converted to metabolites that cochromatographed with 12-hydroxymethyl-methylbenz[a]anthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene, 7- 7,12-dihydroxymethylbenz[a]anthracene, and trans-8,9-dihydrodiol-7,12-DMBA. Exposure of cells in culture to 13 μM 1,2-benz[a]anthracene resulted in increased oxidative metabolism of both BaP and DMBA. In the case of BaP, total phenol formation was increased, while with DMBA all metabolites detected by HPLC were increased. Support for the potential role of metabolism of polycyclic aromatic hydrocarbons by aortic smooth muscle cells in the etiology of atherosclerosis was obtained

Serum levels of brain-derived neurotrophicfactor correlate with the number of T2 MRI lesions in multiple sclerosis

Directory of Open Access Journals (Sweden)

E.R. Comini-Frota

2012-01-01

Full Text Available The objective of the present study was to determine if there is a relationship between serum levels of brain-derived neurotrophic factor (BDNF and the number of T2/fluid-attenuated inversion recovery (T2/FLAIR lesions in multiple sclerosis (MS. The use of magnetic resonance imaging (MRI has revolutionized the study of MS. However, MRI has limitations and the use of other biomarkers such as BDNF may be useful for the clinical assessment and the study of the disease. Serum was obtained from 28 MS patients, 18-50 years old (median 38, 21 women, 0.5-10 years (median 5 of disease duration, EDSS 1-4 (median 1.5 and 28 healthy controls, 19-49 years old (median 33, 19 women. BDNF levels were measured by ELISA. T1, T2/FLAIR and gadolinium-enhanced lesions were measured by a trained radiologist. BDNF was reduced in MS patients (median [range] pg/mL; 1160 [352.6-2640] compared to healthy controls (1640 [632.4-4268]; P = 0.03, Mann-Whitney test and was negatively correlated (Spearman correlation test, r = -0.41; P = 0.02 with T2/FLAIR (11-81 lesions, median 42. We found that serum BDNF levels were inversely correlated with the number of T2/FLAIR lesions in patients with MS. BDNF may be a promising biomarker of MS.

Synthesis and Characterization of Oligodeoxyribonucleotides Modified with 2'-Amino-α-l-LNA Adenine Monomers

DEFF Research Database (Denmark)

Andersen, Nicolai K; Anderson, Brooke A; Wengel, Jesper

2013-01-01

The development of conformationally restricted nucleotide building blocks continues to attract considerable interest because of their successful use within antisense, antigene, and other gene-targeting strategies. Locked nucleic acid (LNA) and its diastereomer α-l-LNA are two interesting examples...... (ONs) modified with 2'-amino-α-l-LNA adenine monomers W-Z. The synthesis of the target phosphoramidites 1-4 is initiated from pentafuranose 5, which upon Vorbrüggen glycosylation, O2'-deacylation, O2'-activation and C2'-azide introduction yields nucleoside 8. A one-pot tandem Staudinger....... ONs modified with pyrene-functionalized 2'-amino-α-l-LNA adenine monomers X-Z display greatly increased affinity toward DNA targets (ΔTm/modification up to +14 °C). Results from absorption and fluorescence spectroscopy suggest that the duplex stabilization is a result of pyrene intercalation...

Effects of low-molecular-weight-chitosan on the adenine-induced chronic renal failure rats in vitro and in vivo

Science.gov (United States)

Zhi, Xuan; Han, Baoqin; Sui, Xianxian; Hu, Rui; Liu, Wanshun

2015-02-01

The effects of low-molecular-weight-chitosan (LMWC) on chronic renal failure (CRF) rats induced by adenine were investigated in vivo and in vitro. Chitosan were hydrolyzed using chitosanase at pH 6-7 and 37° for 24 h to obtain LMWC. In vitro, the effect of LMWC on the proliferation of renal tubular epithelial cells (RTEC) showed that it had no cytotoxic effect and could promote cell growth. For the in vivo experiment, chronic renal failure rats induced by adenine were randomly divided into control group, Niaoduqing group, and high-, medium- and low-dose LMWC groups. For each group, we detected serum creatinine (SCR), blood urea nitrogen (BUN), and total superoxide dismutase (T-SOD), glutathione oxidase (GSH-Px) activities of renal tissue, and obtained the ratio of kidney weight/body weight, pathological changes of kidney. The levels of serum SCR, BUN were higher in the adenine-induced rats than those in the control group, indicating that the rat chronic renal failure model worked successfully. The results after treatment showed that LMWC could reduce the SCR and BUN levels and enhance the activities/levels of T-SOD and GSH-PX in kidney compared to control group. Histopathological examination revealed that adenine-induced renal alterations were restored by LMWC at three tested dosages, especially at the low dosage of 100 mg kg-1 d-1.

Effect of adenine on bacterial translocation using technetium-99m labeled E. coli in an intestinal obstruction model in rats

International Nuclear Information System (INIS)

Ugur Oflaz; Fatma Yurt Lambrecht; Osman Yilmaz; Cetin Pekcetin

2013-01-01

This study aims to investigate effects of adenine on bacterial translocation (BT) using 99m Tc-labeled E. coli in an intestinal obstruction rat model. In the study twenty-one rats were used. The rats were divided into three groups according to different feeding patterns. The control group (CG) was fed with a standard chow diet for 7 days. Group A1 and group A2 were fed with adenine supplemented chow diet for 7 days. At the end of the feeding period, after all groups was submitted intestinal obstruction. 99m Tc-E. coli was injected into the rats' terminal ileum under anesthetic. The rats were sacrificed under aseptic conditions at 24th h after the surgery. The uptake of 99m Tc-E. coli was determined in organs such as the liver, mesenteric lymph nodes, spleen and ileum. Group A1 and group A2 results show that the uptake of 99m Tc-E. coli decreased in the blood and organs comparing to the CG. As a result, it was observed that adenine reduced the level of BT when compared with CG. The beneficial effect of adenine on BT in intestinal obstruction was observed. However, further studies are needed to more clearly assess how this benefit can be achieved. (author)

Adenine radicals generated in alternating AT duplexes by direct absorption of low-energy UV radiation.

Science.gov (United States)

Banyasz, Akos; Ketola, Tiia; Martínez-Fernández, Lara; Improta, Roberto; Markovitsi, Dimitra

2018-04-17

There is increasing evidence that the direct absorption of photons with energies that are lower than the ionization potential of nucleobases may result in oxidative damage to DNA. The present work, which combines nanosecond transient absorption spectroscopy and quantum mechanical calculations, studies this process in alternating adenine-thymine duplexes (AT)n. We show that the one-photon ionization quantum yield of (AT)10 at 266 nm (4.66 eV) is (1.5 ± 0.3) × 10-3. According to our PCM/TD-DFT calculations carried out on model duplexes composed of two base pairs, (AT)1 and (TA)1, simultaneous base pairing and stacking does not induce important changes in the absorption spectra of the adenine radical cation and deprotonated radical. The adenine radicals, thus identified in the time-resolved spectra, disappear with a lifetime of 2.5 ms, giving rise to a reaction product that absorbs at 350 nm. In parallel, the fingerprint of reaction intermediates other than radicals, formed directly from singlet excited states and assigned to AT/TA dimers, is detected at shorter wavelengths. PCM/TD-DFT calculations are carried out to map the pathways leading to such species and to characterize their absorption spectra; we find that, in addition to the path leading to the well-known TA* photoproduct, an AT photo-dimerization path may be operative in duplexes.

The Effects of Foliar Application of Benzyl Adenine, Ascorbic Acid and Thiamine on Some Morphological and Biochemical Characteristics of Petunia (Petunia hybrida

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M. Salehi

2016-05-01

Full Text Available The improvement of growth and flowering of petunia as one of the most popular and cultivated bedding plants in Iran, is of significant importance. Thus, a CRD experiment with five replications was conducted at the Research Greenhouse of Shahid Bahonar University, Kerman, Iran.  From 48 days after sowing, when the seedlings had 5-6 true leaves, the seedlings were sprayed with  thiamine (0 and 100 mgL-1, ascorbic acid (0 and 100 mg L-1 and benzyl adenine (0 and 200 mg L-1 at 4 steps during  growth and development. The results indicated that the treatment of ascorbic acid with thiamine and benzyl adenine led to 2.5 and 3.5-fold increases in the number and length of lateral shoots compared to control treatment. The greatest fresh weight was obtained with ascorbic acid with thiamine and benzyl adenine treatment which led to a 2.5-fold increase in this trait, compared to the control. The highest dry weight was achieved in benzyl adenine treatment. The greatest vase-life and flower diameter were found with ascorbic acid (100 mg L-1, thiamine (100 mg L-1 and benzyl adenine (200 mg L-1 treatments in an extent that the flower longevity and diameter were increased by 83% and 72%, respectively, in comparison to control. Furthermore, chlorophyll a, chlorophyll b, total chlorophyll, carotenoids and reduced sugars concentrations were significantly increased by the foliar-applied compounds compared to control.

Determination of the major tautomeric form of the covalently modified adenine in the (+)-CC-1065-DNA adduct by 1H and 15N NMR studies

International Nuclear Information System (INIS)

Lin, Chin Hsiung; Hurley, L.H.

1990-01-01

(+)-CC-1065 is an extremely potent antitumor antibiotic produced by Streptomyces zelensis. The potent cytotoxic effects of the drug are thought to be due to the formation of a covalent adduct with DNA through N3 of adenine. Although the covalent linkage sites between (+)-CC-1065 and DNA have been determined, the tautomeric form of the covalently modified adenine in the (+)-CC-1065-DNA duplex adduct was not defined. The [6- 15 N]deoxyadenosine-labeled 12-mer duplex adduct was then studied by 1 H and 15 N NMR. One-dimensional NOE difference and two-dimensional NOESY 1 H NMR experiments on the nonisotopically labeled 12-mer duplex adduct demonstrate that the 6-amino protons of the covalently modified adenine exhibit two signals at 9.19 and 9.08 ppm. Proton NMR experiments on the [6- 15 N]deoxyadenosine-labeled 12-mer duplex adduct show that the two resonance signals for adenine H6 observed on the nonisotopically labeled duplex adduct were split into doublets by the 15 N nucleus with coupling constants of 91.3 Hz for non-hydrogen-bonded and 86.8 Hz for hydrogen-bonded amino protons. The authors conclude that the covalently modified adenine N6 of the (+)-CC-1065-12-mer duplex adduct is predominantly in the doubly protonated form, in which calculations predict that the C6-N6 bond is shortened and the positive charge is delocalized over the entire adenine molecule

Synthesis of metal-adeninate frameworks with high separation capacity on C{sub 2}/C{sub 1} hydrocarbons

Energy Technology Data Exchange (ETDEWEB)

He, Yan-Ping, E-mail: hyp041@163.com [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China); Zhou, Nan [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China); Hunan GuangYi Experimental Middle School, Changsha, Hunan 410014 (China); Tan, Yan-Xi; Wang, Fei; Zhang, Jian [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002 (China)

2016-06-15

By introducing isophthalic acid or 2,5-thiophenedicarboxylic acid to assemble with adenine and cadmium salt, two isostructural and anionic porous metal-organic frameworks (1 and 2) possessing the novel (4,8)-connected sqc topology are presented here. 1 shows permanent porosity with Langmuir surface area of 770.1 m{sup 2}/g and exhibits high separation capacity on C{sub 2}/C{sub 1} hydrocarbons. - Graphical abstract: The assembly between isophthalic acid, adenine ligands and Cd{sup 2+} ions leads to an anionic porous metal-organic frameworks, which shows permanent porosity and exhibits high C{sub 2}/C{sub 1} hydrocarbons separation capacity. Display Omitted.

Renal and Myocardial Histopathology and Morphometry in Rats with Adenine - Induced Chronic Renal Failure: Influence of Gum Acacia

Directory of Open Access Journals (Sweden)

Badreldin H. Ali

2014-08-01

Full Text Available Background/Aim: Chronic kidney disease (CKD is associated with increased occurrence of cardiovascular system dysfunction. Previous studies have revealed a number of alterations in the kidneys and heart during CKD. However, unbiased quantitative studies on these structures in this disease have so far not been addressed. Materials and Methods: We induced CKD in rats by feeding adenine (0.75% w/w, four weeks and using unbiased stereological methods, investigated the effect of the ensuing CKD on the kidneys and left ventricular structure. Since gum acacia (GA has previously been shown to ameliorate the severity of CKD in humans and rodents, we investigated the effect of giving GA (15% w/v in the drinking water concomitantly with adenine on the kidneys and left ventricular structure using the above model. Results: The CKD was confirmed by standard biochemical indices in plasma and urine and by accumulation of the uremic toxin indoxyl sulfate. Additionally, it increased blood pressure. In rats with CKD absolute volume of left ventricle was significantly increased, and the volume density and absolute volume of myocardial capillaries were decreased, whilst the same parameters of myocardium and interstitial tissue were increased. Renal morphometry demonstrated significant increase in kidney volume and interstitial tissue in adenine- treated rats. Similarly, glomerular Bowman's capsule was significantly thickened. The myocardial and renal changes were significantly mitigated by GA treatment. Conclusions: These results add to our existing knowledge of the pathophysiology of adenine - CKD and provides plausible histopathological and morphometric evidence for the usefulness of GA in CKD.

Intramolecular stacking interactions in ternary copper(II) complexes formed by a heteroaromatic amine and 9-[2-(2-phosphonoethoxy)ethyl]adenine, a relative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine

Czech Academy of Sciences Publication Activity Database

Fernández-Botello, A.; Holý, Antonín; Moreno, V.; Sigel, H.

2004-01-01

Roč. 98, - (2004), s. 2114-2124 ISSN 0162-0134 R&D Projects: GA MŠk OC D20.002 Institutional research plan: CEZ:AV0Z4055905 Keywords : adenine nucleotide analogues * intramolecular equilibria * isomeric complexes Subject RIV: CC - Organic Chemistry Impact factor: 2.225, year: 2004

Post-radiotherapeutic heart lesions

International Nuclear Information System (INIS)

Testart, F.M.

1979-05-01

Heart structures have traditionally been considered radioresistant. In fact all tissues subjected to radiotherapy can develop lesions. Possible damage includes: - pericardiac fibrosis, the commonest and best individualized, associated with a constriction this leads to a stoppage pattern usually occurring late, around the 18th month. Its frequency depends directly on the total radiation dose; - fibrous myocarditis by direct damage to the heart muscle; - stenosis type lesions of the large coronary trunks; - in exceptional cases lesions of the aorta: hyperplastic degenerescence of the intima and adventitia or of the aortic sigmoid valvules and the mitral valves. Three observations are reported, concerning a coronary, a pericardiac and a coronary, myocardiac and pericardiac lesion. Following this account the irradiation techniques and main experimental data are reviewed and the prophylactic and therapeutic consequences to be derived from our observations and those of the literature are examined [fr

New uracil derivatives and their biological activity

International Nuclear Information System (INIS)

Hudecova, D.; Striganova, J.; Chovanec, P.; Uher, M.

1998-01-01

Present study is concentrated to the research of antimicrobial activity of some derivatives of the uracil and 1,3-dimethyluracyl. The antimicrobial effects of these compounds have been tested on various strains of bacteria, yeasts, and filamentous fungi. The highest antimicrobial effects were found with dithiocarbamato-derivatives, which were effective against pathogenic and non-pathogenic bacteria (IC 50 = 7-25 μg cm -3 ), yeasts (IC 50 = 9-60 μg cm -3 ) and filamentous fungi.The most sensitive fungus to dithiocarbamato-derivatives was Botritis cinerea. It seems to be apparent that the presence of the -NH-C(S)-S- group in molecules of derivatives of uracil and and 1,3-dimethyluracyl influencing the incorporation rate [ 14 ]-adenine and 14 ]-leucine into the biomolecules and also markedly inhibits oxygen consumption (IC 50 = 58 μg cm -3 ). The same derivative demonstrated no mutagenic activity. (authors)

In vitro investigations of α-amylase mediated hydrolysis of cyclodextrins in the presence of ibuprofen, flurbiprofen, or benzo[a]pyrene

DEFF Research Database (Denmark)

Riisager, Ludmilla Lumholdt; Holm, R.; Jørgensen, E. B.

2012-01-01

-γ-cyclodextrins have different biopharmaceutical behaviours than the other evaluated cyclodextrins. The rate of degradation was affected by the addition of the inclusion complex forming additives flurbiprofen, ibuprofen and benzo[a]pyrene. This effect between the degradation dynamics and the included additives...

Serum levels of brain-derived neurotrophic factor correlate with the number of T2 MRI lesions in multiple sclerosis

International Nuclear Information System (INIS)

Comini-Frota, E.R.; Rodrigues, D.H.; Miranda, E.C.; Brum, D.G.; Kaimen-Maciel, D.R.; Donadi, E.A.; Teixeira, A.L.

2011-01-01

The objective of the present study was to determine if there is a relationship between serum levels of brain-derived neurotrophic factor (BDNF) and the number of T2/fluid-attenuated inversion recovery (T2/FLAIR) lesions in multiple sclerosis (MS). The use of magnetic resonance imaging (MRI) has revolutionized the study of MS. However, MRI has limitations and the use of other biomarkers such as BDNF may be useful for the clinical assessment and the study of the disease. Serum was obtained from 28 MS patients, 18-50 years old (median 38), 21 women, 0.5-10 years (median 5) of disease duration, EDSS 1-4 (median 1.5) and 28 healthy controls, 19-49 years old (median 33), 19 women. BDNF levels were measured by ELISA. T1, T2/FLAIR and gadolinium-enhanced lesions were measured by a trained radiologist. BDNF was reduced in MS patients (median [range] pg/mL; 1160 [352.6-2640]) compared to healthy controls (1640 [632.4-4268]; P = 0.03, Mann-Whitney test) and was negatively correlated (Spearman correlation test, r = -0.41; P = 0.02) with T2/FLAIR (11-81 lesions, median 42). We found that serum BDNF levels were inversely correlated with the number of T2/FLAIR lesions in patients with MS. BDNF may be a promising biomarker of MS

Serum levels of brain-derived neurotrophic factor correlate with the number of T2 MRI lesions in multiple sclerosis

Energy Technology Data Exchange (ETDEWEB)

Comini-Frota, E.R. [Unidade de Neurologia, Hospital Universitário, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Rodrigues, D.H. [Laboratório de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Miranda, E.C. [Ecoar Diagnostic Center, Belo Horizonte, MG (Brazil); Brum, D.G. [Hospital das Clínicas,Faculdade de Medicina de Ribeirão Preto,Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Kaimen-Maciel, D.R. [Unidade de Neurologia, Hospital Universitário, Universidade Estadual de Londrina, Londrina, PR (Brazil); Donadi, E.A. [Hospital das Clínicas,Faculdade de Medicina de Ribeirão Preto,Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Teixeira, A.L. [Unidade de Neurologia, Hospital Universitário, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Laboratório de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

2011-11-23

The objective of the present study was to determine if there is a relationship between serum levels of brain-derived neurotrophic factor (BDNF) and the number of T2/fluid-attenuated inversion recovery (T2/FLAIR) lesions in multiple sclerosis (MS). The use of magnetic resonance imaging (MRI) has revolutionized the study of MS. However, MRI has limitations and the use of other biomarkers such as BDNF may be useful for the clinical assessment and the study of the disease. Serum was obtained from 28 MS patients, 18-50 years old (median 38), 21 women, 0.5-10 years (median 5) of disease duration, EDSS 1-4 (median 1.5) and 28 healthy controls, 19-49 years old (median 33), 19 women. BDNF levels were measured by ELISA. T1, T2/FLAIR and gadolinium-enhanced lesions were measured by a trained radiologist. BDNF was reduced in MS patients (median [range] pg/mL; 1160 [352.6-2640]) compared to healthy controls (1640 [632.4-4268]; P = 0.03, Mann-Whitney test) and was negatively correlated (Spearman correlation test, r = -0.41; P = 0.02) with T2/FLAIR (11-81 lesions, median 42). We found that serum BDNF levels were inversely correlated with the number of T2/FLAIR lesions in patients with MS. BDNF may be a promising biomarker of MS.

NMR studies of the fate of adenine nucleotides in glucose-starved erythrocytes

International Nuclear Information System (INIS)

Bubb, W.A.; Mulquiney, P.J.; Kuchel, P.W.; Rohwer, J.; De Atauri, P.

2002-01-01

Full text: As a consequence of many refinements during the past 30 years, we now have a detailed understanding of the glycolytic pathway in human erythrocytes. By comparison, and notwithstanding their central importance to four key steps in erythrocyte glycolysis, our knowledge of the catabolism of adenine nucleotides remains relatively limited. In particular, the mechanism for the degradation of AMP, whose concentration rises under conditions of oxidative stress or glucose deprivation, remains poorly understood, AMP degradation may proceed via two possible pathways which converge in the production of inosine. Analysis of the key intermediates for the respective pathways, adenosine and AMP, as well as determination of end products is not straightforward. High-resolution NMR spectroscopy affords a potentially simple analytical solution to this problem but is complicated by spectral overlap and the sensitivity of key resonances to variations in pH and the concentrations of cations such as Mg 2+ . We describe a multinuclear NMR approach towards characterising the intermediates and end-products of adenine nucleotide metabolism in glucose-starved human erythrocytes. Assignments based on homo- and heteronuclear correlation experiments for both 13 C and 31 P are presented

Metabolism of benzo(a)pyrene and identification of the major benzo(a)pyrene-DNA adducts in cultured human colon

DEFF Research Database (Denmark)

Autrup, Herman; Harris, Curtis C.; Trump, Benjamin F.

1978-01-01

The metabolism of benzo(a)pyrene in cultured human colon has been investigated. Nontumorous colonie tissue was collected at the time of either surgery or "immediate autopsy" from patients with or without colonic cancer. After 24 hr in culture the expiants were exposed to [3H]benzo(a)pyrene for an...

Synthetic models related to DNA-intercalating molecules. Interactions between 8-alkoxypsoralen and adenine

International Nuclear Information System (INIS)

Decout, J.L.; Lhomme, J.

1983-01-01

To investigate the interactions and the photoreactions between furocoumarins and adenine, compounds in which a psoralen molecule is linked by different polymethylene bridges have been synthesised. Ring-ring intramolecular interactions are observed by UV spectroscopy. Thermodynamic parameters of these hydrophobic interactions are determined by the study of the variation of the hypochromic effect with temperature. (author)

Inhibitory action of certain cyclophosphate derivatives of cAMP on cAMP-dependent protein kinases

NARCIS (Netherlands)

Wit, René J.W. de; Hekstra, Doeke; Jastorff, Bernd; Stec, Wojciech J.; Baraniak, Janina; Driel, Roel van; Haastert, Peter J.M. van

1984-01-01

A series cAMP derivatives with modifications in the adenine, ribose and cyclophosphate moiety were screened for their binding affinity for the two types of cAMP-binding sites in mammalian protein kinase type I. In addition, the activation of the kinase by these analogs was monitored. The binding

Pd-catalyzed versus uncatalyzed, PhI(OAc)2-mediated cyclization reactions of N6-([1,1'-biaryl]-2-yl)adenine nucleosides.

Science.gov (United States)

Satishkumar, Sakilam; Poudapally, Suresh; Vuram, Prasanna K; Gurram, Venkateshwarlu; Pottabathini, Narender; Sebastian, Dellamol; Yang, Lijia; Pradhan, Padmanava; Lakshman, Mahesh K

2017-11-09

In this work we have assessed reactions of N 6 -([1,1'-biaryl]-2-yl)adenine nucleosides with Pd(OAc) 2 and PhI(OAc) 2 , via a Pd II /Pd IV redox cycle. The substrates are readily obtained by Pd/Xantphos-catalyzed reaction of adenine nucleosides with 2-bromo-1,1'-biaryls. In PhMe, the N 6 -biarylyl nucleosides gave C6-carbazolyl nucleoside analogues by C-N bond formation with the exocyclic N 6 nitrogen atom. In the solvent screening for the Pd-catalyzed reactions, an uncatalyzed process was found to be operational. It was observed that the carbazolyl products could also be obtained in the absence of a metal catalyst by reaction with PhI(OAc) 2 in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). Thus, under Pd catalysis and in HFIP, reactions proceed to provide carbazolyl nucleoside analogues, with some differences. If reactions of N 6 -biarylyl nucleoside substrates were conducted in MeCN, formation of aryl benzimidazopurinyl nucleoside derivatives was observed in many cases by C-N bond formation with the N 1 ring nitrogen atom of the purine (carbazole and benzimidazole isomers are readily separated by chromatography). Whereas Pd II /Pd IV redox is responsible for carbazole formation under the metal-catalyzed conditions, in HFIP and MeCN radical cations and/or nitrenium ions can be intermediates. An extensive set of radical inhibition experiments was conducted and the data are presented.

NMR solution structure of an N2-guanine DNA adduct derived from the potent tumorigen dibenzo[a,l]pyrene: Intercalation from the minor groove with ruptured Watson-Crick base pairing

Science.gov (United States)

Tang, Yijin; Liu, Zhi; Ding, Shuang; Lin, Chin H.; Cai, Yuqin; Rodriguez, Fabian A.; Sayer, Jane M.; Jerina, Donald M.; Amin, Shantu; Broyde, Suse; Geacintov, Nicholas E.

2012-01-01

The most potent tumorigen identified among the polycyclic aromatic hydrocarbons (PAH) is the non-planar fjord region dibenzo[a,l]pyrene (DB[a,l]P). It is metabolically activated in vivo through the widely-studied diol epoxide (DE) pathway to form covalent adducts with DNA bases, predominantly guanine and adenine. The (+)-11S,12R,13R,14S DE enantiomer forms adducts via its C14-position with the exocyclic amino group of guanine. Here, we present the first NMR solution structure of a DB[a,l]P-derived adduct, the 14R (+)-trans-anti-DB[a,l]P–N2-dG (DB[a,l]P-dG) lesion in double-stranded DNA. In contrast to the stereochemically identical benzo[a]pyrene-derived N2-dG adduct (B[a]P-dG) in which the B[a]P rings reside in the B-DNA minor groove on the 3’-side of the modifed deoxyguanosine, in the DB[a,l]P-derived adduct the DB[a,l]P rings intercalate into the duplex on the 3’-side of the modified base from the sterically crowded minor groove. Watson-Crick base pairing of the modified guanine with the partner cytosine is broken, but these bases retain some stacking with the bulky DB[a,l]P ring system. This new theme in PAH DE - DNA adduct conformation differs from: (1) the classical intercalation motif where Watson-Crick base-pairing is intact at the lesion site, and (2) the base-displaced intercalation motif in which the damaged base and its partner are extruded from the helix . The structural considerations that lead to the intercalated conformation of the DB[a,l]P-dG lesion in contrast to the minor groove alignment of the B[a]P-dG adduct, and the implications of the DB[a,l]P-dG conformational motif for the recognition of such DNA lesions by the human nucleotide excision repair apparatus, are discussed. PMID:23121427

Characterization and fine mapping of a light-dependent leaf lesion mimic mutant 1 in rice.

Science.gov (United States)

Wang, Jing; Ye, Bangquan; Yin, Junjie; Yuan, Can; Zhou, Xiaogang; Li, Weitao; He, Min; Wang, Jichun; Chen, Weilan; Qin, Peng; Ma, Bintian; Wang, Yuping; Li, Shigui; Chen, Xuewei

2015-12-01

Plants that spontaneously produce lesion mimics or spots, without any signs of obvious adversity, such as pesticide and mechanical damage, or pathogen infection, are so-called lesion mimic mutants (lmms). In rice, many lmms exhibit enhanced resistance to pathogens, which provides a unique opportunity to uncover the molecular mechanism underlying lmms. We isolated a rice light-dependent leaf lesion mimic mutant 1 (llm1). Lesion spots appeared in the leaves of the llm1 mutant at the tillering stage. Furthermore, the mutant llm1 had similar agronomic traits to wild type rice. Trypan blue and diamiobenzidine staining analyses revealed that the lesion spot formation on the llm1 mutant was due to programmed cell death and reactive oxygen species. The chloroplasts were severely damaged in the llm1 mutant, suggesting that chloroplast damage was associated with the formation of lesion spots in llm1. More importantly, llm1 exhibited enhanced resistance to bacterial blight pathogens within increased expression of pathogenesis related genes (PRs). Using a map-based cloning approach, we delimited the LLM1 locus to a 121-kb interval between two simple sequence repeat markers, RM17470 and RM17473, on chromosome 4. We sequenced the candidate genes on the interval and found that a base mutation had substituted adenine phosphate for thymine in the last exon of LOC_Os04g52130, which led to an amino acid change (Asp(388) to Val) in the llm1 mutant. Our investigation showed that the putative coproporphyrinogen III oxidase (CPOX) encoded by LOC_Os04g52130 was produced by LLM1 and that amino acid Asp(388) was essential for CPOX function. Our study provides the basis for further investigations into the mechanism underlying lesion mimic initiation associated with LLM1. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Dermal bioavailability of benzo[a]pyrene on lampblack: implications for risk assessment.

Science.gov (United States)

Stroo, Hans F; Roy, Timothy A; Liban, Cris B; Kreitinger, Joseph P

2005-06-01

Lampblack is the principal source of contamination in soils at manufactured gas plant (MGP) sites where oil was used as the feedstock. Risks and cleanup criteria at these sites are determined primarily by the total carcinogenic polynuclear aromatic hydrocarbon (PAH) content, particularly the concentration of benzo[a]pyrene (BaP). Dermal contact with soils at oil-gas MGP sites is a significant component of the overall risks. Seven samples were collected from oil-gas MGP sites and the steady-state dermal fluxes were measured over 96 h in vitro. The standard dermal bioassay technique (in which 3H-BaP is added to the soil matrix) was modified to allow direct measurement of the dermal absorption of the native BaP in the samples. The experimentally derived dermal absorption factors for BaP were 14 to 107 times lower than the default assumption of 15% over 24 h (55-fold lower on average). The dermal fluxes were correlated positively to the total BaP and total carbon concentrations. The measured dermal absorption factors were compared to the default risk-assessment calculations for all seven samples. The calculated excess cancer risk was reduced as a result of using the measured absorption factors by 97% on average (with reductions ranging from 93 to 99%). This work indicates the risks at oil-gas MGP sites currently are overestimated by one to two orders of magnitude, and provides a protocol for the testing and data analysis needed to generate site-specific cleanup levels.

Synthesis of coenzyme A and nicotineamide-adenine dinucleotide labelled with tritium

International Nuclear Information System (INIS)

Sidorov, G.V.; Zverkov, Yu.B.; Myasoedov, N.F.

1999-01-01

Isotopic exchange in solution with tritium water and with gaseous tritium and solid-phase reaction of isotopic exchange of NAD with tritium were investigated. For synthesis of labelled with tritium coenzyme A solid-phase reaction of isotopic exchange with gaseous tritium was used. It was determined that 98% of tritium was contained in nicotineamide part of molecule of NAD. In the case of coenzyme A studying of intramolecular distribution of tritium demonstrated that 90% of tritium were localized in adenine fragment [ru

Determination of lead, zinc and benzo(a)pyrene in incineration flue gas

International Nuclear Information System (INIS)

Han Baohua; Gao Zhuqin; Guo Qian

2003-01-01

An analitical method was developed for the determination of lead(Pb), zinc(Zn) and benzo(a)pyrene (BaP) in flue gas of radwaste pyroysis incinerator, respectively using Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) and High Performance Liquid Chromatography (HPLC). The sample preparation and the influence of major components in back-ground were researched. Interference correction coefficient for Pb and Zn are given in this article. The recovery of Pb, Zn and BaP are all above 84.0% and the relative standard deviation (RSD) were 3.51% for Pb, 7.28% for Zn and 4.50% for BaP, respectively. It shows that this analytical method can meet the incineration processes. (authors)

Nanoswitches based on DNA base pairs: why adenine-thymine is less suitable than guanine-cytosine

NARCIS (Netherlands)

Fonseca Guerra, C.; van der Wijst, T.; Bickelhaupt, F.M.

2006-01-01

Substituted Watson-Crick guanine-cytosine (GC) base pairs were recently shown to yield robust three-state nanoswitches. Here, we address the question: Can such supramolecular switches also be based on Watson-Crick adenine-thymine (AT) base pairs? We have theoretically analyzed AT pairs in which

Compartmental analysis of benzo[a]pyrene toxicokinetics

International Nuclear Information System (INIS)

Bevan, D.R.; Weyand, E.H.

1986-01-01

A multicompartmental model to describe quantitatively the toxicokinetics of benzo[a]pyrene (B[a]P) was developed using SAAM (Simulation, Analysis and Modeling). [ 3 H]-B[a]P dissolved in triethylene glycol was administered intratracheally to male Sprague-Dawley rats, and amounts of [ 3 H] were quantified in various tissues at selected times up to 6 hr after administration. Elimination of [ 3 H]-B[a]P and/or metabolites from lungs was biphasic, with half-times of 5.3 min. and 116 min. [ 3 H]-B[a]P and/or metabolites were subsequently distributed primarily to liver and carcass (muscle, bones, fat, skin and associated blood). Carcass contained about 20% of administered [ 3 H] at 6 hr after administration, and agreement between the model and experimental data required that the carcass be modeled as two compartments, one with rapid and one with slow exchange. Approximately 50% of the administered dose was excreted in feces in 6 hr and only 2% appeared in urine. Enterohepatic circulation was accounted for in the model. The model was then used to predict amounts of [ 3 H]-B[a]P and/or metabolites which would be excreted into bile in animals with bile duct cannulas, and good agreement between the model and data was observed

Influence of gamma irradiation and benzyl adenine on keeping quality of custard apple fruits during storage

International Nuclear Information System (INIS)

Chouksey, Swati; Singh, Alpana; Thakur, Rajendra Singh; Deshmukh, Reena

2013-01-01

The custard apple (Annona squamosa) fruits were procured from local market, irradiated with radiation doses 0, 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75 kGy and then treated with benzyl adenine (50 and 100 part per million) and stored at ambient temperature (25±5 °C, Relative Humidity 90±2%) for 12 days. The treated fruits were evaluated for sensory (viz; flavour, texture, internal and external colour) and chemical constituents (viz; Total Soluble Solids, titrable acidity, ascorbic acid, free soluble sugar, reducing sugar, non reducing sugar, carbohydrate) during storage. The study concluded that radiation dose of 1.5 kilo Gray along with 50 ppm benzyl adenine enhanced in shelf-life of custard apple fruits by 6 days at ambient temperature with good pulp texture, flavour, colour and nutritional quality as compared to control. (author)

Phthalic acid and benzo[a]pyrene in soil-plant-water systems amended with contaminated sewage sludge

DEFF Research Database (Denmark)

Mougin, C.; Dappozze, F.; Brault, A.

2006-01-01

We studied the fate of C-14-labelled phthalic acid and benzo[a]pyrene applied to the soil by the way of contaminated sewage sludge in model ecosystems allowing the simultaneous assessment of physicochemical and biological descriptors. Here we show that the mineralisation of phthalic acid is highe......[a]pyrene is recalcitrant to biodegradation whatever the type of soil contamination. We show also that the chemicals present in the sludge are poorly transferred to soil leachates and plant seedlings....

Nuclear magnetic resonance solution structure of an N(2)-guanine DNA adduct derived from the potent tumorigen dibenzo[a,l]pyrene: intercalation from the minor groove with ruptured Watson-Crick base pairing.

Science.gov (United States)

Tang, Yijin; Liu, Zhi; Ding, Shuang; Lin, Chin H; Cai, Yuqin; Rodriguez, Fabian A; Sayer, Jane M; Jerina, Donald M; Amin, Shantu; Broyde, Suse; Geacintov, Nicholas E

2012-12-04

The most potent tumorigen identified among the polycyclic aromatic hydrocarbons (PAH) is the nonplanar fjord region dibenzo[a,l]pyrene (DB[a,l]P). It is metabolically activated in vivo through the widely studied diol epoxide (DE) pathway to form covalent adducts with DNA bases, predominantly guanine and adenine. The (+)-11S,12R,13R,14S DE enantiomer forms adducts via its C14 position with the exocyclic amino group of guanine. Here, we present the first nuclear magnetic resonance solution structure of a DB[a,l]P-derived adduct, the 14R-(+)-trans-anti-DB[a,l]P-N(2)-dG (DB[a,l]P-dG) lesion in double-stranded DNA. In contrast to the stereochemically identical benzo[a]pyrene-derived N(2)-dG adduct (B[a]P-dG) in which the B[a]P rings reside in the B-DNA minor groove on the 3'-side of the modifed deoxyguanosine, in the DB[a,l]P-derived adduct the DB[a,l]P rings intercalate into the duplex on the 3'-side of the modified base from the sterically crowded minor groove. Watson-Crick base pairing of the modified guanine with the partner cytosine is broken, but these bases retain some stacking with the bulky DB[a,l]P ring system. This new theme in PAH DE-DNA adduct conformation differs from (1) the classical intercalation motif in which Watson-Crick base pairing is intact at the lesion site and (2) the base-displaced intercalation motif in which the damaged base and its partner are extruded from the helix. The structural considerations that lead to the intercalated conformation of the DB[a,l]P-dG lesion in contrast to the minor groove alignment of the B[a]P-dG adduct, and the implications of the DB[a,l]P-dG conformational motif for the recognition of such DNA lesions by the human nucleotide excision repair apparatus, are discussed.

Absorption by DNA single strands of adenine isolated in vacuo: The role of multiple chromophores

DEFF Research Database (Denmark)

Nielsen, L.M.; Pedersen, S.O.; Kirketerp, M.-B.S.

2012-01-01

to that for the adenine molecule and the dAMP mononucleotide. Desolvation has little effect on the bandwidth, which implies that inhomogenous broadening of the absorption bands in aqueous solution is of minor importance compared to, e.g., conformational disorder. Finally, at high photon energies, internal conversion...

High-NaCl diet impairs dynamic renal blood flow autoregulation in rats with adenine-induced chronic renal failure.

Science.gov (United States)

Saeed, Aso; DiBona, Gerald F; Grimberg, Elisabeth; Nguy, Lisa; Mikkelsen, Minne Line Nedergaard; Marcussen, Niels; Guron, Gregor

2014-03-15

This study examined the effects of 2 wk of high-NaCl diet on kidney function and dynamic renal blood flow autoregulation (RBFA) in rats with adenine-induced chronic renal failure (ACRF). Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without adenine (controls). After 10 wk, rats were randomized to either remain on the same diet (0.6% NaCl) or to be switched to high 4% NaCl chow. Two weeks after randomization, renal clearance experiments were performed under isoflurane anesthesia and dynamic RBFA, baroreflex sensitivity (BRS), systolic arterial pressure variability (SAPV), and heart rate variability were assessed by spectral analytical techniques. Rats with ACRF showed marked reductions in glomerular filtration rate and renal blood flow (RBF), whereas mean arterial pressure and SAPV were significantly elevated. In addition, spontaneous BRS was reduced by ∼50% in ACRF animals. High-NaCl diet significantly increased transfer function fractional gain values between arterial pressure and RBF in the frequency range of the myogenic response (0.06-0.09 Hz) only in ACRF animals (0.3 ± 4.0 vs. -4.4 ± 3.8 dB; P renal failure by facilitating pressure transmission to the microvasculature.

Distinctive Spectral Features of Exciton and Excimer States in the Ultrafast Electronic Deactivation of the Adenine Dinucleotide

Science.gov (United States)

Stuhldreier, Mayra C.; Röttger, Katharina; Temps, Friedrich

We report the observation by transient absorption spectroscopy of distinctive spectro-temporal signatures of delocalized exciton versus relaxed, weakly bound excimer states in the ultrafast electronic deactivation after UV photoexcitation of the adenine dinucleotide.

A click chemistry approach to pleuromutilin derivatives. Part 3

DEFF Research Database (Denmark)

Dreier, Ida; Hansen, Lykke H; Nielsen, Poul

2014-01-01

Five promising pleuromutilin derivatives from our former studies, all containing adenine on various linkers, were supplemented with two new compounds. The binding to Escherichia coli ribosomes was verified by extensive chemical footprinting analysis. The ability to inhibit bacterial growth was in...... was investigated on two Staphylococcus aureus strains and compared to the pleuromutilin drugs tiamulin and valnemulin. Three of the compounds show an effect similar to tiamulin and one compound shows an excellent effect similar to valnemulin....

Ultrafast deactivation processes in the 2-aminopyridine dimer and the adenine-thymine base pair: Similarities and differences

International Nuclear Information System (INIS)

Ai Yuejie; Zhang Feng; Cui Ganglong; Fang Weihai; Luo Yi

2010-01-01

2-aminopyridine dimer has frequently been used as a model system for studying photochemistry of DNA base pairs. We examine here the relevance of 2-aminopyridine dimer for a Watson-Crick adenine-thymine base pair by studying UV-light induced photodynamics along two main hydrogen bridges after the excitation to the localized 1 ππ* excited-state. The respective two-dimensional potential-energy surfaces have been determined by time-dependent density functional theory with Coulomb-attenuated hybrid exchange-correlation functional (CAM-B3LYP). Different mechanistic aspects of the deactivation pathway have been analyzed and compared in detail for both systems, while the related reaction rates have also be obtained from Monte Carlo kinetic simulations. The limitations of the 2-aminopyridine dimer as a model system for the adenine-thymine base pair are discussed.

Adenine ribbon stabilized by Watson–Crick and Hoogsteen hydrogen Bonds: WFT and DFT study

Czech Academy of Sciences Publication Activity Database

Zierkiewicz, W.; Michalska, D.; Hobza, Pavel

2010-01-01

Roč. 12, č. 12 (2010), s. 2888-2894 ISSN 1463-9076 R&D Projects: GA MŠk LC512 Grant - others:Wroclaw University of Technology(PL) 343974/Z0304 Institutional research plan: CEZ:AV0Z40550506 Keywords : adenine ribbon * ab initio correlated calculations * self- organization Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.454, year: 2010

Measurement of urinary Benzo[a]pyrene tetrols and their relationship to other polycyclic aromatic hydrocarbon metabolites and cotinine in humans.

Science.gov (United States)

Hilton, Donald C; Trinidad, Debra A; Hubbard, Kendra; Li, Zheng; Sjödin, Andreas

2017-12-01

Biomonitoring of exposure to polycyclic aromatic hydrocarbons (PAHs) typically uses measurement of metabolites of PAHs with four or less aromatic rings, such as 1-hydroxypyrene, even though interest may be in exposure to larger and carcinogenic PAHs, such as benzo[a]pyrene (B[a]P). An improved procedure for measuring two tetrol metabolites of B[a]P has been developed. Using 2 mL urine, the method includes enzymatic deconjugation of the tetrol conjugates, liquid-liquid extraction, activated carbon solid phase extraction (SPE) and Strata-X SPE, and gas chromatography-electron capture negative ionization-tandem mass spectrometric determination. Limits of detection were 0.026 pg/mL (benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, BPT I-1) and 0.090 pg/mL (benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol, BPT II-1). We quantified BPT I-1 and BPT II-1 in urine from a volunteer who consumed one meal containing high levels of PAHs (barbequed chicken). We also measured urinary concentrations of BPT I-1 and BPT II-1 in smokers and nonsmokers, and compared these concentrations with those of monohydroxy PAHs (OH-PAHs) and cotinine. Urinary elimination of BPT I-1 and BPT II-1 as a function of time after dietary exposure was similar to that observed previously for OH-PAHs. While the median BPT I-1 concentration in smokers' urine (0.069 pg/mL) significantly differs from nonsmokers (0.043 pg/mL), BPT I-1 is only weakly correlated with cotinine. The urinary concentration of BPT I-1 shows a weaker relationship to tobacco smoke than metabolites of smaller PAHs, suggesting that other routes of exposure such as for example dietary routes may be of larger quantitative importance. Published by Elsevier Ltd.

Influence of gamma irradiation and benzyl adenine on keeping quality of custard apple fruits during storage.

Science.gov (United States)

Chouksey, Swati; Singh, Alpana; Thakur, Rajendra Singh; Deshmukh, Reena

2013-10-01

The custard apple (Annona squamosa) fruits were procured from local market, irradiated with radiation doses 0, 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 1.75 kGy and then treated with benzyl adenine (50 and 100 part per million) and stored at ambient temperature (25 ± 5 °C, Relative Humidity 90 ± 2%) for 12 days. The treated fruits were evaluated for sensory (viz; flavour, texture, internal and external colour) and chemical constituents (viz; Total Soluble Solids, titrable acidity, ascorbic acid, free soluble sugar, reducing sugar. non reducing sugar, carbohydrate) during storage. The study concluded that radiation dose of 1.5 kilo Gray along with 50 ppm benzyl adenine enhanced in shelf-life of custard apple fruits by 6 days at ambient temperature with good pulp texture, flavour, colour and nutritional quality as compared to control.

Probing electronic coupling between adenine bases in RNA strands from synchrotron radiation circular dichroism experiments

DEFF Research Database (Denmark)

Nielsen, Lisbeth Munksgård; Hoffmann, Søren Vrønning; Nielsen, Steen Brøndsted

2012-01-01

Circular dichroism spectra (176–330 nm) of RNA adenine oligomers, (rA)n (n = 1–10, 12, 15, and 20), reveal electronic coupling between two bases in short strands. The number of interacting bases in long strands is more and larger than that reported previously for the corresponding DNA strands....

Can an Excess Electron Localise on a Purine Moiety in the Adenine-thymine Watson-Crick Base Pair? A Computational Study

International Nuclear Information System (INIS)

Mazurkiewicz, Kamil; Haranczyk, Maciej; Gutowski, Maciej S.; Rak, Janusz

2007-01-01

The electron affinity and the propensity to electron-induced proton transfer (PT) of hydrogen-bonded complexes between the Watson-Crick adenine-thymine pair (AT) and simple organic acid (HX), attached to adenine in the Hoogsteen-type configuration, were studied at the B3LYP/6-31+G** level. Although the carboxyl group is deprotonated at physiological pH, its neutral form, COOH, resembles the peptide bond or the amide fragment in the side chain of asparagine (Asn) or glutamine (Gln). Thus, these complexes mimic the interaction between the DNA environment (e.g., proteins) and nucleobase pairs incorporated in the biopolymer. Electron attachment is thermodynamically feasible and adiabatic electron affinities range from 0.41 to 1.28 eV, while the vertical detachment energies of the resulting anions span the range of 0.39-2.88 eV. Low-energy activation barriers separate the anionic minima: aHX(AT) from the more stable single-PT anionic geometry, aHX(AT)-SPT, and aHX(AT)-SPT from the double-PT anionic geometry, aHX(AT)-DPT. Interaction between the adenine of the Watson-Crick AT base pair with an acidic proton donor probably counterbalances the larger EA of isolated thymine, as SOMO is almost evenly delocalized over both types of nucleic bases in the aHX(AT) anions. Moreover, as a result of PT the excess electron localizes entirely on adenine. Thus, in DNA interacting with its physiological environment, damage induced by low-energy electrons could begin, contrary to the current view, with the formation of purine anions, which are not formed in isolated DNA because of the greater stability of anionic pyrimidines.

Binding of p-mercaptobenzoic acid and adenine to gold-coated electroless etched silicon nanowires studied by surface-enhanced Raman scattering.

Science.gov (United States)

Mohaček-Grošev, Vlasta; Gebavi, Hrvoje; Bonifacio, Alois; Sergo, Valter; Daković, Marko; Bajuk-Bogdanović, Danica

2018-04-10

Modern diagnostic tools ever aim to reduce the amount of analyte and the time needed for obtaining the result. Surface-enhanced Raman spectroscopy is a method that could satisfy both of these requirements, provided that for each analyte an adequate substrate is found. Here we demonstrate the ability of gold-sputtered silicon nanowires (SiNW) to bind p-mercaptobenzoic acid in 10 -3 , 10 -4 and 10 -5 M and adenine in 30 and 100μM concentrations. Based on the normal mode analysis, presented here for the first time, the binding of p-mercaptobenzoic acid is deduced. The intensity enhancement of the 1106cm -1 band is explained by involvement of the CS stretching deformation, and the appearance of the broad 300cm -1 band attributed to SAu stretching mode. Adenine SERS spectra demonstrate the existence of the 7H tautomer since the strongest band observed is at 736cm -1 . The adenine binding is likely to occur in several ways, because the number of observed bands in the 1200-1600cm -1 interval exceeds the number of observed bands in the normal Raman spectrum of the free molecule. Copyright © 2018 Elsevier B.V. All rights reserved.

3-Methylcholanthrene does not induce in vitro xenobiotic metabolism in spiny lobster hepatopancreas, or affect in vivo disposition of benzo(a)pyrene

Energy Technology Data Exchange (ETDEWEB)

James, M O; Little, P J

1984-01-01

Administration of 3-methylcholanthrene (10 mg/kg) i.m. to spiny lobsters, Panulirus argus, did not cause induction of the cytochrome P-450 content of hepatopancreas microsomes. The rate of oxidation of benzo(a)pyrene or 7-ethoxyresorufin in reductase-fortified preparations of hepatopancreas microsomes was the same for corn oil-treated or 3-methylcholanthrene-treated lobsters. Administration of 3-methylcholanthrene (10 mg/kg) i.m. to spiny lobsters one week prior to an i.v. dose of (/sup 14/C)benzo(a)pyrene (1 mg/kg) did not influence the disposition of the radiolabelled benzo(a)pyrene in lobsters. At one week after the dose of (/sup 14/C)benzo(a)pyrene, approximately 40% of the dose of (/sup 14/C)benzo(a)pyrene remained in the lobsters, regardless of treatment. The digestive tract (hepatopancreas, intestinal contents, stomach and intestine) contained most (86%) of the /sup 14/C remaining in the lobsters.

Monitoring of radiolytic degradation of benzo(a)pyrene using γ-rays in aqueous media by HPLC

International Nuclear Information System (INIS)

Butt, S. Bilal; Qureshi, Rashid N.; Ahmed, Shafaat

2005-01-01

Poly nuclear aromatic hydrocarbons (PAHs) are generated in the environment by various industrial processes and anthropogenic activities. These compounds are quite stable and persist in the environment due to the aromatic bonding within the rings. Benzo(a)pyrene (B(a)P) is a potential carcinogenic and conditions for its degradation have been optimized by investigating γ-ray dose intensity, its concentration effect and the influence of surfactant presence. HPLC has been used to monitor the degree of degradation of B(a)P under the optimum conditions

Mechanism-based inactivation of cytochrome P-450 dependent benzo[a]pyrene hydroxylase activity by acetylenic and olefinic polycyclic arylhydrocarbons

International Nuclear Information System (INIS)

Gan, L.S.

1986-01-01

A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxygenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene (EP), 3-ethynylperylene (EPL), cis- and trans-1-(2-bromo-vinyl)pyrene (c-BVP and t-BVP), and 1-allylpyrene (AP) serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo(a)pyrene (BP) hydroxylase, while 1-vinyl-pyrene (VP) and phenyl 1-pyrenyl acetylene (PPA) do not cause a detectable suicide inhibition of the BP hydroxylase. The mechanism-based loss of BP hydroxylase activity caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes. In the presence of NADPH, 3 H-labeled EP covalently attached to P-450 isozymes with a measured stoichiometry of one mole of EP per mole of the P-450 heme. The results of the effects of these aryl derivatives in the mammalian cell-mediated mutagenesis assay and toxicity assay show that none of the compounds examined nor any of the their metabolites produced in the incubation system are cytotoxic to V79 cells

Effect of single intralesional treatment of surgically induced equine superficial digital flexor tendon core lesions with adipose-derived mesenchymal stromal cells : a controlled experimental trial

NARCIS (Netherlands)

Geburek, Florian; Roggel, Florian; van Schie, Hans T M; Beineke, Andreas; Estrada, Roberto; Weber, Kathrin; Hellige, Maren; Rohn, Karl; Jagodzinski, Michael; Welke, Bastian; Hurschler, Christof; Conrad, Sabine; Skutella, Thomas; van de Lest, Chris; van Weeren, René; Stadler, Peter M

2017-01-01

BACKGROUND: Adipose tissue is a promising source of mesenchymal stromal cells (MSCs) for the treatment of tendon disease. The goal of this study was to assess the effect of a single intralesional implantation of adipose tissue-derived mesenchymal stromal cells (AT-MSCs) on artificial lesions in

Multiphoton spectral analysis of benzo[a]pyrene uptake and metabolism in a rat liver cell line

International Nuclear Information System (INIS)

Barhoumi, Rola; Mouneimne, Youssef; Ramos, Ernesto; Morisseau, Christophe; Hammock, Bruce D.; Safe, Stephen; Parrish, Alan R.; Burghardt, Robert C.

2011-01-01

Dynamic analysis of the uptake and metabolism of polycyclic aromatic hydrocarbons (PAHs) and their metabolites within live cells in real time has the potential to provide novel insights into genotoxic and non-genotoxic mechanisms of cellular injury caused by PAHs. The present work, combining the use of metabolite spectra generated from metabolite standards using multiphoton spectral analysis and an 'advanced unmixing process', identifies and quantifies the uptake, partitioning, and metabolite formation of one of the most important PAHs (benzo[a]pyrene, BaP) in viable cultured rat liver cells over a period of 24 h. The application of the advanced unmixing process resulted in the simultaneous identification of 8 metabolites in live cells at any single time. The accuracy of this unmixing process was verified using specific microsomal epoxide hydrolase inhibitors, glucuronidation and sulfation inhibitors as well as several mixtures of metabolite standards. Our findings prove that the two-photon microscopy imaging surpasses the conventional fluorescence imaging techniques and the unmixing process is a mathematical technique that seems applicable to the analysis of BaP metabolites in living cells especially for analysis of changes of the ultimate carcinogen benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide. Therefore, the combination of the two-photon acquisition with the unmixing process should provide important insights into the cellular and molecular mechanisms by which BaP and other PAHs alter cellular homeostasis.

The incorporation of 14C-adenine into the oocytes of Asellus aquaticus as studied by autoradiography

NARCIS (Netherlands)

Broek, C.J.H. van den; Tates, A.D.

Asellus aquaticus females were injected with 8-14C-adenine, fixed after 3 hours and sectioned. In coated autoradiographs, the number of β-tracks from 14C were counted over nucleolus, nucleus and cytoplasm of the oocytes at various stages of their development. Incorporation into nucleolar RNA, being

Few-layer graphene sheets with embedded gold nanoparticles for electrochemical analysis of adenine

Directory of Open Access Journals (Sweden)

Biris AR

2013-04-01

Full Text Available Alexandru R Biris,1 Stela Pruneanu,1 Florina Pogacean,1 Mihaela D Lazar,1 Gheorghe Borodi,1 Stefania Ardelean,1 Enkeleda Dervishi,2 Fumiya Watanabe,2 Alexandru S Biris2 1National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj-Napoca, Romania; 2Center for Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, Little Rock, AR, USA Abstract: This work describes the synthesis of few-layer graphene sheets embedded with various amounts of gold nanoparticles (Gr-Au-x over an Aux/MgO catalytic system (where x = 1, 2, or 3 wt%. The sheet-like morphology of the Gr-Au-x nanostructures was confirmed by transmission electron microscopy and high resolution transmission electron microscopy, which also demonstrated that the number of layers within the sheets varied from two to seven. The sample with the highest percentage of gold nanoparticles embedded within the graphitic layers (Gr-Au-3 showed the highest degree of crystallinity. This distinct feature, along with the large number of edge-planes seen in high resolution transmission electron microscopic images, has a crucial effect on the electrocatalytic properties of this material. The reaction yields (40%–50% and the final purity (96%–98% of the Gr-Au-x composites were obtained by thermogravimetric analysis. The Gr-Au-x composites were used to modify platinum substrates and subsequently to detect adenine, one of the DNA bases. For the bare electrode, no oxidation signal was recorded. In contrast, all of the modified electrodes showed a strong electrocatalytic effect, and a clear peak for adenine oxidation was recorded at approximately +1.05 V. The highest increase in the electrochemical signal was obtained using a platinum/Gr-Au-3-modified electrode. In addition, this modified electrode had an exchange current density (I0, obtained from the Tafel plot one order of magnitude higher than that of the bare platinum electrode, which also confirmed that

When should fractional flow reserve be performed to assess the significance of borderline coronary artery lesions: Derivation of a simplified scoring system.

Science.gov (United States)

Matar, Fadi A; Falasiri, Shayan; Glover, Charles B; Khaliq, Asma; Leung, Calvin C; Mroue, Jad; Ebra, George

2016-11-01

To derive a simplified scoring system (SSS) that can assist in selecting patients who would benefit from the application of fractional flow reserve (FFR). Angiographers base decisions to perform FFR on their interpretation of % diameter stenosis (DS), which is subject to variability. Recent studies have shown that the amount of myocardium at jeopardy is an important factor in determining the degree of hemodynamic compromise. We conducted a retrospective multivariable analysis to identify independent predictors of hemodynamic compromise in 289 patients with 317 coronary vessels undergoing FFR. A SSS was derived using the odds ratios as a weighted factor. The receiver operator characteristics curve was used to identify the optimal cutoff (≥3) to discern a functionally significant lesion (FFR≤0.8). Male gender, left anterior descending artery apical wrap, disease proximal to lesion, minimal lumen diameter and % DS predicted abnormal FFR (≤0.8) and lesion location in the left circumflex predicted a normal FFR. Using a cutoff score of ≥3 on the SSS, a specificity of 90.4% (95% CI: 83.0-95.3) and a sensitivity of 38.0% (95% CI: 31.5-44.9) was generated with a positive predictive value of 89.0% (95% CI: 80.7%-94.6%) and negative predictive value of 41.6% (95% CI: 35.1%-48.3%). The decision to use FFR should be based not only on the % DS but also the size of the myocardial mass jeopardized. A score of ≥3 on the SSS should prompt further investigation with a pressure wire. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Benzo[a]pyrene in urban environments of eastern Moscow: pollution levels and critical loads

Science.gov (United States)

Kasimov, Nikolay S.; Kosheleva, Natalia E.; Nikiforova, Elena M.; Vlasov, Dmitry V.

2017-02-01

Polycyclic aromatic hydrocarbons (PAHs), particularly benzo[a]pyrene (BaP), are toxic compounds emitted from various anthropogenic sources. Understanding the BaP concentrations, dynamics and decomposition in soil is required to assess the critical loads of BaP in urban environments. This study is the first attempt to evaluate all major input and output components of benzo[a]pyrene (BaP) balance and to calculate the permissible load on the urban environment in different land-use zones in the Eastern district of Moscow. BaP contamination of the snow cover in the Eastern district of Moscow was related to daily BaP fallout from the atmosphere. In 2010, the mean content of the pollutant in the snow dust was 1942 ng g-1, whereas the average intensity of its fallout was 7.13 ng m-2 per day. Across the territory, BaP winter fallout intensities varied from 0.3 to 1100 ng m-2 per day. The average BaP content in the surface (0-10 cm) soil horizons was 409 ng g-1, which is 83 times higher than the local background value and 20 times higher than the maximum permissible concentration (MPC) accepted in Russia. The variations in soil and snow BaP concentrations among different land-use zones were examined. A significant contribution of BaP from the atmosphere to urban soils was identified. Based on the measurements of BaP atmospheric fallout and BaP reserves in the soils, the critical loads of BaP for the land-use zones in the Eastern district were calculated for different values of degradation intensity and different exposure times. It was established that at an annual degradation intensity of 1-10 %, ecologically safe BaP levels in the soils of all land-use zones, excluding the agricultural zone, will only be reached after many decades or centuries.

32P-postlabeling assay in mice of transplacental DNA damage induced by the environmental carcinogens safrole, 4-aminobiphenyl, and benzo(a)pyrene

International Nuclear Information System (INIS)

Lu, L.J.; Disher, R.M.; Reddy, M.V.; Randerath, K.

1986-01-01

Transplacental exposure of fetuses to carcinogens is known to induce tumors in the offspring, often with a high incidence and short latency. While covalent adduction of DNA appears to be essential for tumor initiation, little is known about the binding of carcinogens to the DNA of fetal tissues. A sensitive 32 P-postlabeling method enabled us to study the binding of the environmental carcinogens safrole (600 mumol/kg p.o.), 4-aminobiphenyl (800 mumol/kg), and benzo(a)pyrene (200 mumol/kg) to the DNA of various maternal and fetal tissues after administration of test carcinogens to pregnant ICR mice on day 18 of gestation. The results show that these carcinogens bound to the DNA of maternal and fetal liver, lung, kidney, heart, brain, intestine, skin, maternal uterus, and placenta, with organ-specific quantitative and qualitative differences. It was possible for the first time to analyze DNA adduct patterns in minute amounts of tissue, for example those available from fetal heart. The covalent binding index 24 h after safrole treatment was estimated for the different organs and ranged from 0.1 to 247 and 0.1 to 5.8 for maternal and fetal DNA, respectively. Covalent binding index values of 0.2 to 13 and 0.1 to 0.3 for maternal and fetal DNA, respectively, were found for 4-aminobiphenyl. Benzo(a)pyrene treatment yielded covalent binding index values of 0.6 to 6.5 and 0.3 to 0.7 for maternal and fetal DNA, respectively. In both maternal and fetal tissues, safrole exhibited preferential binding to liver DNA. 4-Aminobiphenyl bound preferentially to DNA of maternal liver and kidney but showed no preference among fetal tissues. Benzo(a)pyrene exhibited weak tissue preference in both maternal and fetal organs

Premalignant lesions skew spleen cell responses to immune modulation by adipocytes.

Science.gov (United States)

Vielma, Silvana A; Klein, Richard L; Levingston, Corinne A; Young, M Rita I

2013-05-01

Obesity can promote a chronic inflammatory state and is associated with an increased risk for cancer. Since adipocytes can produce mediators that can regulate conventional immune cells, this study sought to determine if the presence of premalignant oral lesions would skew how immune cells respond to adipocyte-derived mediators to create an environment that may be more favorable for their progression toward cancer. While media conditioned by adipocytes stimulated normal spleen cell production of the T helper (Th) type-1 cytokines interleukin (IL)-2, interferon-γ (IFN-γ), IL-12 and granulocyte-monocyte colony-stimulating factor (GM CSF), media from premalignant lesion cells either blocked or had no added affect on the adipocyte-stimulated Th1 cytokine production. In contrast, media conditioned by premalignant lesion cells exacerbated adipocyte-stimulated spleen cell production of the Th2 cytokines IL-10 and IL-13, although it did not further enhance the adipocyte-stimulated spleen cell production of IL-4 and TGF-β. The premalignant lesion environment also heightened the adipocyte-stimulated spleen cell production of the inflammatory mediators IL 1α, IL-1β, IL-6 and IL-9, although it did not further increase the adipocyte-stimulated production of tumor necrosis factor-α (TNF-α). IL 17 production was unaffected by the adipocyte-derived mediators, but was synergistically triggered by adding media from premalignant lesion cells. These stimulatory effects on spleen cell production of Th2 and inflammatory mediators were not induced in the absence of media conditioned by adipocytes. In contrast, media conditioned by adipocytes did not stimulate production of predominantly monocyte-derived chemokine C-X-C motif ligand (CXCL)9, chemokine C-C motif ligand (CCL)3 or CCL4, although it stimulated production of CCL2 and the predominantly T cell-derived chemokine CCL5, which was the only chemokine whose production was further increased by media from premalignant lesions

Chlorophyll catalyse the photo-transformation of carcinogenic benzo[a]pyrene in water

Science.gov (United States)

Luo, Lijuan; Lai, Xueying; Chen, Baowei; Lin, Li; Fang, Ling; Tam, Nora F. Y.; Luan, Tiangang

2015-01-01

Algal blooms cause great damage to water quality and aquaculture. However, this study showed that dead algal cells and chlorophyll could accelerate the photo-transformation of benzo[a]pyrene (BaP), a ubiquitous and persistent pollutant with potently mutagenic and carcinogenic toxicities, under visible light irradiation. Chlorophyll was found to be the major active substance in dead algal cells, and generated a high level of singlet oxygen to catalyse the photo-transformation of BaP. According to various BaP metabolites formed, the degradation mechanism was proposed as that chlorophyll in dead algal cells photo-oxidized BaP to quinones via photocatalytic generation of singlet oxygen. The results provided a good insight into the role of chlorophyll in the photo-transformation of organic contaminants and could be a possible remediation strategy of organic pollutants in natural environment. PMID:26239357

Validity of T2 mapping in characterization of the regeneration tissue by bone marrow derived cell transplantation in osteochondral lesions of the ankle

Energy Technology Data Exchange (ETDEWEB)

Battaglia, M., E-mail: milva.battaglia@ior.it [Service of Ecography and Radiology, Rizzoli Orthopaedic Institute, via Pupilli n. 1, 40136 Bologna (Italy); Rimondi, E. [Service of Ecography and Radiology, Rizzoli Orthopaedic Institute, via Pupilli n. 1, 40136 Bologna (Italy); Monti, C. [Service of CT and MRI, Casa di Cura Madre Fortunata Toniolo, Bologna (Italy); Guaraldi, F. [Department of Pathology, The Johns Hopkins University, School of Medicine, Baltimore, MD (United States); Sant' Andrea, A. [Service of CT and MRI, Casa di Cura Madre Fortunata Toniolo, Bologna (Italy); Buda, R.; Cavallo, M.; Giannini, S.; Vannini, F. [Clinical Orthopaedic and Traumatology Unit II, Rizzoli Orthopaedic Institute, Bologna (Italy)

2011-11-15

Objective: Bone marrow derived cell transplantation (BMDCT) has been recently suggested as a possible surgical technique to repair osteochondral lesions. To date, no qualitative MRI studies have evaluated its efficacy. The aim of our study is to investigate the validity of MRI T2-mapping sequence in characterizing the reparative tissue obtained and its ability to correlate with clinical results. Methods and materials: 20 patients with an osteochondral lesion of the talus underwent BMDCT and were evaluated at 2 years follow up using MRI T2-mapping sequence. 20 healthy volunteers were recruited as controls. MRI images were acquired using a protocol suggested by the International Cartilage Repair Society, MOCART scoring system and T2 mapping. Results were then correlated with AOFAS clinical score. Results: AOFAS score increased from 66.8 {+-} 14.5 pre-operatively to 91.2 {+-} 8.3 (p < 0.0005) at 2 years follow-up. T2-relaxation time value of 35-45 ms was derived from healthy ankles evaluation and assumed as normal hyaline cartilage value and used as a control. Regenerated tissue with a T2-relaxation time value comparable to hyaline cartilage was found in all the cases treated, covering a mean of 78% of the repaired lesion area. A high clinical score was related directly to isointense signal in DPFSE fat sat (p = 0.05), and percentage of regenerated hyaline cartilage (p = 0.05), inversely to the percentage of regenerated fibrocartilage. Lesion's depth negatively related to the integrity of the repaired tissue's surface (tau = -0.523, p = 0.007), and to the percentage of regenerated hyaline cartilage (rho = -0.546, p = 0.013). Conclusions: Because of its ability to detect cartilage's quality and to correlate to the clinical score, MRI T2-mapping sequence integrated with Mocart score represent a valid, non-invasive technique for qualitative cartilage assessment after regenerative surgical procedures.

The conserved baculovirus protein p33 (Ac92) is a flavin adenine dinucleotide-linked sulfhydryl oxidase

International Nuclear Information System (INIS)

Long, C.M.; Rohrmann, G.F.; Merrill, G.F.

2009-01-01

Open reading frame 92 of the Autographa californica baculovirus (Ac92) is one of about 30 core genes present in all sequenced baculovirus genomes. Computer analyses predicted that the Ac92 encoded protein (called p33) and several of its baculovirus orthologs were related to a family of flavin adenine dinucleotide (FAD)-linked sulfhydryl oxidases. Alignment of these proteins indicated that, although they were highly diverse, a number of amino acids in common with the Erv1p/Alrp family of sulfhydryl oxidases are present. Some of these conserved amino acids are predicted to stack against the isoalloxazine and adenine components of FAD, whereas others are involved in electron transfer. To investigate this relationship, Ac92 was expressed in bacteria as a His-tagged fusion protein, purified, and characterized both spectrophotometrically and for its enzymatic activity. The purified protein was found to have the color (yellow) and absorption spectrum consistent with it being a FAD-containing protein. Furthermore, it was demonstrated to have sulfhydryl oxidase activity using dithiothreitol and thioredoxin as substrates.

Chemical sensing of Benzo[a]pyrene using Corchorus depressus fluorescent flavonoids.

Science.gov (United States)

Ahmad, Wajiha; Rana, Nosheen Fatima; Riaz, Sundus; Ahmad, Nasir Mehmood; Hameed, Maryam; Naeem, Ayesha; Tahir, Rabbiya

2018-04-01

Plant phytochemicals, such as flavonoids are in use for the development of optical biosensor. Benzo[a]pyrene (B[a]P), is a pervasive environmental and dietary carcinogen. A fluorescent assay is developed using plant isolated flavonoid for the detection of B[a]P. High content saponins are excluded from the flavonoid-containing methanolic extract of Corchorus depressus by implying reduction of silver ions by saponins resulting in formation of silver nanoparticles. Isolated plant flavonoids are used to develop a spectrofluorometric assay for the detection of B[a]P. Decrease in the flavonoid fluorescence intensity by B[a]P is found to be based on both static and dynamic quenching. Specificity of the assay for B[a]P was tested for other carcinogens belonging to different classes of compounds. Flavonoids-mediated sensing can be implied for the development of new generation of nanoparticle-based biosensors that can be more sensitive and less susceptible to external factors, such as temperature and humidity.

Development and Uses of Offline and Web-Searchable Metabolism Databases - The Case of Benzo[a]pyrene.

Science.gov (United States)

Rendic, Slobodan P; Guengerich, Frederick P

2018-01-01

The present work describes development of offline and web-searchable metabolism databases for drugs, other chemicals, and physiological compounds using human and model species, prompted by the large amount of data published after year 1990. The intent was to provide a rapid and accurate approach to published data to be applied both in science and to assist therapy. Searches for the data were done using the Pub Med database, accessing the Medline database of references and abstracts. In addition, data presented at scientific conferences (e.g., ISSX conferences) are included covering the publishing period beginning with the year 1976. Application of the data is illustrated by the properties of benzo[a]pyrene (B[a]P) and its metabolites. Analysis show higher activity of P450 1A1 for activation of the (-)- isomer of trans-B[a]P-7,8-diol, while P4501B1 exerts higher activity for the (+)- isomer. P450 1A2 showed equally low activity in the metabolic activation of both isomers. The information collected in the databases is applicable in prediction of metabolic drug-drug and/or drug-chemical interactions in clinical and environmental studies. The data on the metabolism of searched compound (exemplified by benzo[a]pyrene and its metabolites) also indicate toxicological properties of the products of specific reactions. The offline and web-searchable databases had wide range of applications (e.g. computer assisted drug design and development, optimization of clinical therapy, toxicological applications) and adjustment in everyday life styles. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Potassium cyanate-induced modification of toxic and mutagenic effects of gamma-radiation and benzo(A)-pyrene

International Nuclear Information System (INIS)

Serebryanyj, A.M.; Sal'nikova, L.E.; Bakhitova, L.M.; Pashin, Yu.V.; AN SSSR, Moscow

1989-01-01

In experiments with CHO-AT3-2 cell culture, a study was made of the effect of potassium cyanate (KNCO) on the effect of gamma-radiation and benzo(a)pyrene (BP) by the following tests: cell viability, induction of cells with micronuclei and fragmentated nuclei and mutations by thymidinekinase (TK) and Na + /K + -ATPase loci. Some tests have revealed the increase in the effect of gamma-radiation and BP produced by potassium cyanate. It is suggested that sensitizing effects are related to repair system inhibition and/or changes in the cell chromatin structure produced by KNCO

Erhuang Formula ameliorates renal damage in adenine-induced chronic renal failure rats via inhibiting inflammatory and fibrotic responses.

Science.gov (United States)

Zhang, Chun-Yan; Zhu, Jian-Yong; Ye, Ying; Zhang, Miao; Zhang, Li-Jun; Wang, Su-Juan; Song, Ya-Nan; Zhang, Hong

2017-11-01

The present study aimed to evaluate the protective effects of Erhuang Formula (EHF) and explore its pharmacological mechanisms on adenine-induced chronic renal failure (CRF). The compounds in EHF were analyzed by HPLC/MS. Adenine-induced CRF rats were administrated by EHF. The effects were evaluated by renal function examination and histology staining. Immunostaining of some proteins related cell adhesion was performedin renal tissues, including E-cadherin, β-catenin, fibronectin and laminin. The qRT-PCR was carried out determination of gene expression related inflammation and fibrosis including NF-κB, TNF-α, TGF-β1, α-SMA and osteopontin (OPN). Ten compounds in EHF were identified including liquiritigenin, farnesene, vaccarin, pachymic acid, cycloastragenol, astilbin, 3,5,6,7,8,3',4'-heptemthoxyflavone, physcion, emodin and curzerene. Abnormal renal function and histology had significant improvements by EHF treatment. The protein expression of β-catenin, fibronectin and laminin were significantly increased and the protein expression of E-cadherin significantly decreased in CRF groups. However, these protein expressions were restored to normal levels in EHF group. Furthermore, low expression of PPARγ and high expression of NF-κB, TNF-α, TGF-β1, α-SMA and OPN were substantially restored by EHF treatment in a dose-dependent manner. EHF ameliorated renal damage in adenine-induced CRF rats, and the mechanisms might involve in the inhibition of inflammatory and fibrotic responses and the regulation of PPARγ, NF-κB and TGF-β signaling pathways. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Linking embryo toxicity with genotoxic responses in the freshwater snail Physa acuta: single exposure to benzo(a)pyrene, fluoxetine, bisphenol A, vinclozolin and exposure to binary mixtures with benzo(a)pyrene.

Science.gov (United States)

Sánchez-Argüello, Paloma; Aparicio, Natalia; Fernández, Carlos

2012-06-01

Genotoxic effects on fauna after waterborne pollutant exposure have been demonstrated by numerous research programmes. Less effort has been focused on establishing relationship between genotoxicity and long-term responses at higher levels of biological organization. Taking into account that embryos may be more sensitive indicators of reproductive impairment than alterations in fertility, we have developed two assays in multiwell plates to address correlations between embryo toxicity and genotoxicity. The potential teratogenicity was assessed by analyzing abnormal development and mortality of Physa acuta at embryonic stage. Genotoxicity was measured by the micronucleus (MN) test using embryonic cells. Our results showed that linkage between genotoxicity and embryo toxicity depends on mechanisms of action of compounds under study. Embryo toxic responses showed a clear dose-related tendency whereas no clear dose-dependent effect was observed in micronucleus induction. The higher embryo toxicity was produced by benzo(a)pyrene exposure followed by fluoxetine and bisphenol A. Vinclozolin was the lower embryo toxic compound. Binary mixtures with BaP always resulted in higher embryo toxicity than single exposures but antagonistic effects were observed for MN induction. Benzo(a)pyrene produced the higher MN induction at 0.04 mg/L, which also produced clear embryo toxic effects. Fluoxetine did not induce cytogenetic effects but 0.25mg/L altered embryonic development. Bisphenol A significantly reduced hatchability at 0.5mg/L while MN induction appeared with higher treatments than those that start causing teratogenicity. Much higher concentration of vinclozolin (5mg/L) reduced hatchability and induced maximum MN formation. In conclusion, while validating one biomarker of genotoxicity and employing one ecologically relevant effect, we have evaluated the relative sensitivity of a freshwater mollusc for a range of chemicals. The embryo toxicity test is a starting point for the

Photochemical decoration of gold nanoparticles on polymer stabilized magnetic microspheres for determination of adenine by surface-enhanced Raman spectroscopy

International Nuclear Information System (INIS)

Alula, Melisew Tadele; Yang, Jyisy

2015-01-01

Magnetic microspheres decorated with gold nanoparticles (AuNPs) were prepared and used for the determination of adenine by surface-enhanced Raman scattering (SERS). Magnetic particles were first synthesized by coprecipitation of solutions containing iron(II) and iron(III) ions with ammonium hydroxide. Subsequently, the magnetic particles were suspended into a solution of poly(divinylbenzene-co-methyl methacrylate) to yield polymer-stabilized magnetic microspheres. These were further decorated with AuNPs via a new photochemical reduction method. The magnetic microspheres were characterized by XRD patterns and SEM images. They are shown to represent highly SERS-active substrates by giving an enhancement by almost 7 orders of magnitude compared to conventional Raman spectroscopy. Several factors that affect the photochemical reduction to form the AuNPs were examined. It is found that the concentration of gold ion, UV irradiation time, and citrate concentration have more impact on the reaction rate than on the morphologies of the AuNPs. The gold-decorated magnetic microspheres are highly stable in aqueous solution and capable of concentrating nucleobases. A linear response of the SERS signal to adenine in concentrations up to 10 μM is found, with a linear regression coefficient of 0.997. The detection limit is estimated to a few hundreds of nM (at an SNR of 3). Based on its specific Raman peak at 734 cm −1 , adenine can be selectively determined without interference by other nucleobases, and a recovery higher than 95 % could be obtained. (author)

The effect of solvation on the radiation damage rate constants for adenine

DEFF Research Database (Denmark)

Milhøj, Birgitte Olai; Sauer, Stephan P. A.

2016-01-01

in calculations of Gibbs free energies and reaction rates for the reaction between the OH radical and the DNA nucleobase adenine using Density Functional Theory at the ωB97X-D/6-311++G(2df,2pd) level with the Eckart tunneling correction. The solvent, water, has been included through either the implicit...... polarizable continuum model (PCM) or through explicit modelling of micro-solvation by a single water molecule at the site of reaction as well as the combination of both. Scrutiny of the thermodynamics and kinetics of the individual sub-reactions suggests that the qualitative differences introduced...

A level set method for multiple sclerosis lesion segmentation.

Science.gov (United States)

Zhao, Yue; Guo, Shuxu; Luo, Min; Shi, Xue; Bilello, Michel; Zhang, Shaoxiang; Li, Chunming

2018-06-01

In this paper, we present a level set method for multiple sclerosis (MS) lesion segmentation from FLAIR images in the presence of intensity inhomogeneities. We use a three-phase level set formulation of segmentation and bias field estimation to segment MS lesions and normal tissue region (including GM and WM) and CSF and the background from FLAIR images. To save computational load, we derive a two-phase formulation from the original multi-phase level set formulation to segment the MS lesions and normal tissue regions. The derived method inherits the desirable ability to precisely locate object boundaries of the original level set method, which simultaneously performs segmentation and estimation of the bias field to deal with intensity inhomogeneity. Experimental results demonstrate the advantages of our method over other state-of-the-art methods in terms of segmentation accuracy. Copyright © 2017 Elsevier Inc. All rights reserved.

Modeling the high-energy electronic state manifold of adenine: Calibration for nonlinear electronic spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Nenov, Artur, E-mail: Artur.Nenov@unibo.it; Giussani, Angelo; Segarra-Martí, Javier; Jaiswal, Vishal K. [Dipartimento di Chimica “G. Ciamician,” Università di Bologna, Via Selmi 2, IT-40126 Bologna (Italy); Rivalta, Ivan [Université de Lyon, CNRS, Institut de Chimie de Lyon, École Normale Supérieure de Lyon, 46 Allée d’Italie, F-69364 Lyon Cedex 07 (France); Cerullo, Giulio [Dipartimento di Fisica, Politecnico di Milano, IFN-CNR, Piazza Leonardo Da Vinci 32, IT-20133 Milano (Italy); Mukamel, Shaul [Department of Chemistry, University of California, Irvine, California 92697-2025 (United States); Garavelli, Marco, E-mail: marco.garavelli@unibo.it, E-mail: marco.garavelli@ens-lyon.fr [Dipartimento di Chimica “G. Ciamician,” Università di Bologna, Via Selmi 2, IT-40126 Bologna (Italy); Université de Lyon, CNRS, Institut de Chimie de Lyon, École Normale Supérieure de Lyon, 46 Allée d’Italie, F-69364 Lyon Cedex 07 (France)

2015-06-07

Pump-probe electronic spectroscopy using femtosecond laser pulses has evolved into a standard tool for tracking ultrafast excited state dynamics. Its two-dimensional (2D) counterpart is becoming an increasingly available and promising technique for resolving many of the limitations of pump-probe caused by spectral congestion. The ability to simulate pump-probe and 2D spectra from ab initio computations would allow one to link mechanistic observables like molecular motions and the making/breaking of chemical bonds to experimental observables like excited state lifetimes and quantum yields. From a theoretical standpoint, the characterization of the electronic transitions in the visible (Vis)/ultraviolet (UV), which are excited via the interaction of a molecular system with the incoming pump/probe pulses, translates into the determination of a computationally challenging number of excited states (going over 100) even for small/medium sized systems. A protocol is therefore required to evaluate the fluctuations of spectral properties like transition energies and dipole moments as a function of the computational parameters and to estimate the effect of these fluctuations on the transient spectral appearance. In the present contribution such a protocol is presented within the framework of complete and restricted active space self-consistent field theory and its second-order perturbation theory extensions. The electronic excited states of adenine have been carefully characterized through a previously presented computational recipe [Nenov et al., Comput. Theor. Chem. 1040–1041, 295-303 (2014)]. A wise reduction of the level of theory has then been performed in order to obtain a computationally less demanding approach that is still able to reproduce the characteristic features of the reference data. Foreseeing the potentiality of 2D electronic spectroscopy to track polynucleotide ground and excited state dynamics, and in particular its expected ability to provide

hREV3 is essential for error-prone translesion synthesis past UV or benzo[a]pyrene diol epoxide-induced DNA lesions in human fibroblasts

International Nuclear Information System (INIS)

Li Ziqiang; Zhang Hong; McManus, Terrence P.; McCormick, J. Justin; Lawrence, Christopher W.; Maher, Veronica M.

2002-01-01

In S. cerevisiae, the REV3 gene, encoding the catalytic subunit of polymerase zeta, is involved in translesion synthesis and required for the production of mutations induced by ultraviolet radiation (UV) photoproducts and other DNA fork-blocking lesions, and for the majority of spontaneous mutations. To determine whether hREV3, the human homolog of yeast REV3, is similarly involved in error-prone translesion synthesis past UV photoproducts and other lesions that block DNA replication, an hREV3 antisense construct under the control of the TetP promoter was transfected into an infinite life span human fibroblast cell strain that expresses a high level of tTAk, the activator of that promoter. Three transfectant strains expressing high levels of hREV3 antisense RNA were identified and compared with their parental cell strain for sensitivity to the cytotoxic and mutagenic effects of UV. The three hREV3 antisense-expressing cell strains were not more sensitive than the parental strain to the cytotoxic effect of UV, but the frequency of mutants induced by UV in their HPRT gene was significantly reduced, i.e. to 14% that of the parent. Two of these hREV3 antisense-expressing cell strains were compared with the parental strain for sensitivity to (±)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). They were not more sensitive than the parent strain to the cytotoxic effect of BPDE, but the frequency of mutants induced was significantly reduced, i.e. in one strain, to 17% that of the parent, and in the other, to 24%. DNA sequencing showed that the kinds of mutations induced by BPDE in the parental and the derivative strains did not differ and were similar to those found previously with finite life span human fibroblasts. The data strongly support the hypothesis that hRev3 plays a critical role in the induction of mutations by UV or BPDE. Because the level of hRev3 protein in human fibroblasts is below the level of antibody detection, it was not

Application of whole-lesion histogram analysis of pharmacokinetic parameters in dynamic contrast-enhanced MRI of breast lesions with the CAIPIRINHA-Dixon-TWIST-VIBE technique.

Science.gov (United States)

Li, Zhiwei; Ai, Tao; Hu, Yiqi; Yan, Xu; Nickel, Marcel Dominik; Xu, Xiao; Xia, Liming

2018-01-01

To investigate the application of whole-lesion histogram analysis of pharmacokinetic parameters for differentiating malignant from benign breast lesions on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). In all, 92 women with 97 breast lesions (26 benign and 71 malignant lesions) were enrolled in this study. Patients underwent dynamic breast MRI at 3T using a prototypical CAIPIRINHA-Dixon-TWIST-VIBE (CDT-VIBE) sequence and a subsequent surgery or biopsy. Inflow rate of the agent between plasma and interstitium (K trans ), outflow rate of agent between interstitium and plasma (K ep ), extravascular space volume per unit volume of tissue (v e ) including mean value, 25th/50th/75th/90th percentiles, skewness, and kurtosis were then calculated based on the whole lesion. A single-sample Kolmogorov-Smirnov test, paired t-test, and receiver operating characteristic curve (ROC) analysis were used for statistical analysis. Malignant breast lesions had significantly higher K trans , K ep , and lower v e in mean values, 25th/50th/75th/90th percentiles, and significantly higher skewness of v e than benign breast lesions (all P 0.05). The 90th percentile of K trans , the 90th percentile of K ep , and the 50th percentile of v e showed the greatest areas under the ROC curve (AUC) for each pharmacokinetic parameter derived from DCE-MRI. The 90th percentile of K ep achieved the highest AUC value (0.927) among all histogram-derived values. The whole-lesion histogram analysis of pharmacokinetic parameters can improve the diagnostic accuracy of breast DCE-MRI with the CDT-VIBE technique. The 90th percentile of K ep may be the best indicator in differentiation between malignant and benign breast lesions. 4 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2018;47:91-96. © 2017 International Society for Magnetic Resonance in Medicine.

Control of box C/D snoRNP assembly by N6-methylation of adenine.

Science.gov (United States)

Huang, Lin; Ashraf, Saira; Wang, Jia; Lilley, David Mj

2017-09-01

N 6 -methyladenine is the most widespread mRNA modification. A subset of human box C/D snoRNA species have target GAC sequences that lead to formation of N 6 -methyladenine at a key trans Hoogsteen-sugar A·G base pair, of which half are methylated in vivo The GAC target is conserved only in those that are methylated. Methylation prevents binding of the 15.5-kDa protein and the induced folding of the RNA Thus, the assembly of the box C/D snoRNP could in principle be regulated by RNA methylation at its critical first stage. Crystallography reveals that N 6 -methylation of adenine prevents the formation of trans Hoogsteen-sugar A·G base pairs, explaining why the box C/D RNA cannot adopt its kinked conformation. More generally, our data indicate that sheared A·G base pairs (but not Watson-Crick base pairs) are more susceptible to disruption by N 6 mA methylation and are therefore possible regulatory sites. The human signal recognition particle RNA and many related Alu retrotransposon RNA species are also methylated at N6 of an adenine that forms a sheared base pair with guanine and mediates a key tertiary interaction. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Kinetics and thermodynamics of the reaction between the •OH radical and adenine – a theoretical investigation

DEFF Research Database (Denmark)

Milhøj, Birgitte Olai; Sauer, Stephan P. A.

2015-01-01

the computational method is validated by considering the hydrogen abstraction from the heterocyclic N9 nitrogen in adenine as a test system. Geometries for all molecules in the reaction are optimised with four different DFT exchange-correlation functionals (B3LYP, BHandHLYP, M06-2X and wB97X-D), in combination...

Evaluation of Porin Interaction with Adenine Nucleotide Translocase and Cyclophilin-D Proteins after Brain Ischemia and Reperfusion

Directory of Open Access Journals (Sweden)

Mohammad Ali Atlasi

2011-01-01

Full Text Available Objective (s Porin is a mitochondrial outer membrane channel, which usually functions as the pathway for the movement of various substances in and out of the mitochondria and is considered to be a component of the permeability transition (PT pore complex that plays a role in the PT. We addressed the hypothesis that porin interacts with other mitochondrial proteins after ischemic injury.Materials and MethodsFor this purpose, we used in vivo 4-vessel occlusion model of rat brain and porin purification method by hydroxyapatite column. After SDS gel electrophoresis and silver nitrate staining, Western blotting was done for porin, adenine nucleotide translocase and cyclophilin-D proteins.Results Porin was purified from mitochondrial mixture in ischemic brain and control groups. Investigation of interaction of adenine nucleotide transposes (ANT and cyclophilin-D with porin by Western blotting showed no proteins co-purified with porin from injured tissues.Conclusion The present study implies that there may not be interaction between porin, and ANT or cyclophilin-D, and if there is any, it is not maintained during the purification procedure.

Optimization of PET system design for lesion detection

International Nuclear Information System (INIS)

Qi, Jinyi

2000-01-01

Traditionally, the figures of merit used in designing a PET scanner are spatial resolution, noise equivalent count rate, noise equivalent sensitivity, etc. These measures, however, do not directly reflect the lesion detectability using the PET scanner. Here we propose to optimize PET scanner design directly for lesion detection. The signal-to-noise ratio (SNR) of lesion detection can be easily computed using the theoretical expressions that we have previously derived. Because no time consuming Monte Carlo simulation is needed, the theoretical expressions allow evaluation of a large range of parameters. The PET system parameters can then be chosen to achieve the maximum SNR for lesion detection. The simulation study shown in this paper was focused a single ring PET scanner without depth of interaction measurement. Randoms and scatters were also ignored

Lesion detection and quantitation of positron emission mammography

International Nuclear Information System (INIS)

Qi, Jinyi; Huesman, Ronald H.

2001-01-01

A Positron Emission Mammography (PEM) scanner dedicated to breast imaging is being developed at our laboratory. We have developed a list mode likelihood reconstruction algorithm for this scanner. Here we theoretically study the lesion detection and quantitation. The lesion detectability is studied theoretically using computer observers. We found that for the zero-order quadratic prior, the region of interest observer can achieve the performance of the prewhitening observer with a properly selected smoothing parameter. We also study the lesion quantitation using the test statistic of the region of interest observer. The theoretical expressions for the bias, variance, and ensemble mean squared error of the quantitation are derived. Computer simulations show that the theoretical predictions are in good agreement with the Monte Carlo results for both lesion detection and quantitation

Adenine nucleotide translocator transports haem precursors into mitochondria.

Directory of Open Access Journals (Sweden)

Motoki Azuma

2008-08-01

Full Text Available Haem is a prosthetic group for haem proteins, which play an essential role in oxygen transport, respiration, signal transduction, and detoxification. In haem biosynthesis, the haem precursor protoporphyrin IX (PP IX must be accumulated into the mitochondrial matrix across the inner membrane, but its mechanism is largely unclear. Here we show that adenine nucleotide translocator (ANT, the inner membrane transporter, contributes to haem biosynthesis by facilitating mitochondrial accumulation of its precursors. We identified that haem and PP IX specifically bind to ANT. Mitochondrial uptake of PP IX was inhibited by ADP, a known substrate of ANT. Conversely, ADP uptake into mitochondria was competitively inhibited by haem and its precursors, suggesting that haem-related porphyrins are accumulated into mitochondria via ANT. Furthermore, disruption of the ANT genes in yeast resulted in a reduction of haem biosynthesis by blocking the translocation of haem precursors into the matrix. Our results represent a new model that ANT plays a crucial role in haem biosynthesis by facilitating accumulation of its precursors into the mitochondrial matrix.

Supra-molecular hydrogen-bonding patterns in the N(9)-H protonated and N(7)-H tautomeric form of an N(6) -benzoyl-adenine salt: N (6)-benzoyl-adeninium nitrate.

Science.gov (United States)

Karthikeyan, Ammasai; Jeeva Jasmine, Nithianantham; Thomas Muthiah, Packianathan; Perdih, Franc

2016-02-01

In the title molecular salt, C12H10N5O(+)·NO3 (-), the adenine unit has an N (9)-protonated N(7)-H tautomeric form with non-protonated N(1) and N(3) atoms. The dihedral angle between the adenine ring system and the phenyl ring is 51.10 (10)°. The typical intra-molecular N(7)-H⋯O hydrogen bond with an S(7) graph-set motif is also present. The benzoyl-adeninium cations also form base pairs through N-H⋯O and C-H⋯N hydrogen bonds involving the Watson-Crick face of the adenine ring and the C and O atoms of the benzoyl ring of an adjacent cation, forming a supra-molecular ribbon with R 2 (2)(9) rings. Benzoyl-adeninum cations are also bridged by one of the oxygen atoms of the nitrate anion, which acts as a double acceptor, forming a pair of N-H⋯O hydrogen bonds to generate a second ribbon motif. These ribbons together with π-π stacking inter-actions between the phenyl ring and the five- and six-membered adenine rings of adjacent mol-ecules generate a three-dimensional supra-molecular architecture.

Biofabrication of chitosan-silver composite SERS substrates enabling quantification of adenine by a spectroscopic shift

International Nuclear Information System (INIS)

Luo, X L; Bentley, W E; Buckhout-White, S; Rubloff, G W

2011-01-01

Surface-enhanced Raman scattering (SERS) has grown dramatically as an analytical tool for the sensitive and selective detection of molecules adsorbed on nano-roughened noble metal structures. Quantification with SERS based on signal intensity remains challenging due to the complicated fabrication process to obtain well-dispersed nanoparticles and well-ordered substrates. We report a new biofabrication strategy of SERS substrates that enable quantification through a newly discovered spectroscopic shift resulting from the chitosan-analyte interactions in solution. We demonstrate this phenomenon by the quantification of adenine, which is an essential part of the nucleic acid structure and a key component in pathways which generate signal molecules for bacterial communications. The SERS substrates were fabricated simply by sequential electrodeposition of chitosan on patterned gold electrodes and electroplating of a silver nitrate solution through the chitosan scaffold to form a chitosan-silver nanoparticle composite. Active SERS signals of adenine solutions were obtained in real time from the chitosan-silver composite substrates with a significant concentration-dependent spectroscopic shift. The Lorentzian curve fitting of the dominant peaks suggests the presence of two separate peaks with a concentration-dependent area percentage of the separated peaks. The chitosan-mediated composite SERS substrates can be easily biofabricated on predefined electrodes within microfluidic channels for real-time detection in microsystems.

Simultaneous quantification of porcine myocardial adenine nucleotides and creatine phosphate by ion-pair reverse-phase high-performance liquid chromatography

International Nuclear Information System (INIS)

Cordis, G.A.; Das, D.K.

1987-01-01

In order to follow the energy metabolism and the levels of high-energy phosphate compounds in porcine myocardium subjected to ischemic insult, it was necessary to develop a high-performance liquid chromatography (HPLC) method where creatine phosphate (CP) and the adenine nucleotides could be measured simultaneously in a single run. Currently available ion-pair reverse-phase HPLC methods require a separate injection with a change in wavelength and mobile phase in order to measure the creatine phosphate, while baseline separation of AMP is lacking. The ion-exchange HPLC method includes a simultaneous determination, but the baseline drifts due to the gradient and baseline separation of AMP is not achieved. In the following ion-pair reverse-phase HPLC method, simultaneous measurements of porcine myocardial adenine nucleotides and creatine phosphate were achieved along with a stable baseline and homogeneous baseline separation of each measured compound, allowing accurate quantification

Approach to the unfolding and folding dynamics of add A-riboswitch upon adenine dissociation using a coarse-grained elastic network model

Energy Technology Data Exchange (ETDEWEB)

Li, Chunhua [College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124 (China); Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 45108 (United States); Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin [College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124 (China); Su, Jiguo, E-mail: jiguosu@ysu.edu.cn, E-mail: zhng@umich.edu [College of Science, Yanshan University, Qinhuangdao 066004 (China); Zhang, Yang, E-mail: jiguosu@ysu.edu.cn, E-mail: zhng@umich.edu [Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 45108 (United States)

2016-07-07

Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.

Crystallization and preliminary X-ray diffraction study of recombinant adenine phosphoribosyltransferase from the thermophilic bacterium Thermus thermophilus strain HB27

Science.gov (United States)

Sinitsyna, E. V.; Timofeev, V. I.; Tuzova, E. S.; Kostromina, M. A.; Murav'eva, T. I.; Esipov, R. S.; Kuranova, I. P.

2017-07-01

Adenine phosphoribosyltransferase (APRT) belongs to the type I phosphoribosyltransferase family and catalyzes the formation of adenosine monophosphate via transfer of the 5-phosphoribosyl group from phosphoribosyl pyrophosphate to the nitrogen atom N9 of the adenine base. Proteins of this family are involved in a salvage pathway of nucleotide synthesis, thus providing purine base utilization and maintaining the optimal level of purine bases in the body. Adenine phosphoribosyltransferase from the extremely thermophilic Thermus thermophilus strain HB27 was produced using a highly efficient E. coli producer strain and was then purified by affinity and gel-filtration chromatography. This enzyme was successfully employed as a catalyst for the cascade biosynthesis of biologically important nucleotides. The screening of crystallization conditions for recombinant APRT from T. thermophilus HB27 was performed in order to determine the enzyme structure by X-ray diffraction. The crystallization conditions, which were found by the vapor-diffusion technique, were then optimized to apply the counter-diffusion technique. The crystals of the enzyme were grown by the capillary counter-diffusion method. The crystals belong to sp. gr. P1211 and have the following unitcell parameters: a = 69.86 Å, b = 82.16 Å, c = 91.39 Å, α = γ = 90°, β = 102.58°. The X-ray diffraction data set suitable for the determination of the APRT structure at 2.6 Å resolution was collected from the crystals at the SPring-8 synchrotron facility (Japan).

Whole-lesion histogram analysis metrics of the apparent diffusion coefficient as a marker of breast lesions characterization at 1.5 T.

Science.gov (United States)

Bougias, H; Ghiatas, A; Priovolos, D; Veliou, K; Christou, A

2017-05-01

To retrospectively assess the role of whole-lesion apparent diffusion coefficient (ADC) in the characterization of breast tumors by comparing different histogram metrics. 49 patients with 53 breast lesions underwent magnetic resonance imaging (MRI). ADC histogram parameters, including the mean, mode, 10th/50th/90th percentile, skewness, kurtosis, and entropy ADCs, were derived for the whole-lesion volume in each patient. Mann-Whitney U-test, area under the receiver-operating characteristic curve (AUC) were used for statistical analysis. The mean, mode and 10th/50th/90th percentile ADC values were significantly lower in malignant lesions compared with benign ones (all P histogram analysis could be a helpful index in the characterization and differentiation between benign and malignant breast lesions with the 10th and 50th percentile ADC be the most accurate discriminators. Copyright © 2017 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.

Conformational preferences of DNA following damage by aristolochic acids: Structural and energetic insights into the different mutagenic potential of the ALI and ALII-N(6)-dA adducts.

Science.gov (United States)

Kathuria, Preetleen; Sharma, Purshotam; Abendong, Minette N; Wetmore, Stacey D

2015-04-21

Aristolochic acids (AAI and AAII), produced by the Aristolochiaceae family of plants, are classified as group I (human) carcinogens by the International Agency for Research on Cancer. These acids are metabolized in cells to yield aristolactams (ALI and ALII, respectively), which further form bulky adducts with the purine nucleobases. Specifically, the adenine lesions are more persistent in cells and have been associated with chronic renal diseases and related carcinogenesis. To understand the structural basis of the nephrotoxicity induced by AAs, the ALI-N(6)-dA and ALII-N(6)-dA lesions are systematically studied using computational methods. Density functional theory calculations indicate that the aristolactam moiety intrinsically prefers a planar conformation with respect to adenine. Nucleoside and nucleotide models suggest that the anti and syn orientations about the glycosidic bond are isoenergetic for both adducts. Molecular dynamics simulations and free energy calculations reveal that the anti base-displaced intercalated conformation is the most stable conformer for both types of AL-N(6)-dA adducted DNA, which agrees with previous experimental work on the ALII-N(6)-dA adduct and thereby validates our approach. Interestingly, this conformer differs from the dominant conformations adopted by other N6-linked adenine lesions, including those derived from polycyclic aromatic hydrocarbons. Furthermore, the second most stable syn base-displaced intercalated conformation lies closer in energy to the anti base-displaced intercalated conformation for ALI-N(6)-dA compared to ALII-N(6)-dA. This indicates that a mixture of conformations may be detectable for ALI-N(6)-dA in DNA. If this enhanced conformational flexibility of double-stranded DNA persists when bound to a lesion-bypass polymerase, this provides a possible structural explanation for the previously observed greater nephrotoxic potential for the ALI versus ALII-N(6)-dA adduct. In addition, the structural

Urea derivatives on the move: cytokinin-like activity and adventitious rooting enhancement depend on chemical structure.

Science.gov (United States)

Ricci, A; Bertoletti, C

2009-05-01

Urea derivatives are synthetic compounds, some of which have proved to be positive regulators of cell division and differentiation. N-phenyl-N'-(2-chloro-4-pyridyl)urea (forchlorofenuron, CPPU) and N-phenyl-N'-(1,2,3-thiadiazol-5-yl)urea (thidiazuron, TDZ), well known urea cytokinin representatives, are extensively used in in vitro plant morphogenesis studies, as they show cytokinin-like activity often exceeding that of adenine compounds. In recent years, renewed interest in structure-activity relationship studies allowed identification of new urea cytokinins and other urea derivatives that specifically enhance adventitious root formation. In this review, we report the research history of urea derivatives, new insights into their biological activity, and recent progress on their mode of action.

Covalent functionalization of few-wall carbon nanotubes by ferrocene derivatives for bioelectrochemical devices

Energy Technology Data Exchange (ETDEWEB)

Allali, Naoual [Laboratoire de Chimie Physique et Microbiologie pour l' Environnement, UMR 7564 CNRS-Universite de Lorraine, 54602 Villers-les-Nancy (France); Laboratoire de Structure et Reactivite des Systemes Moleculaires Complexes, UMR 7565 CNRS-Universite de Lorraine, 54506 Vandoeuvre-les-Nancy (France); Department of Engineering Sciences and Mathematics, Luleaa University of Technology, 97187 Luleaa (Sweden); Urbanova, Veronika; Waldbock, Jeremy; Etienne, Mathieu; Mallet, Martine; Walcarius, Alain; Dossot, Manuel [Laboratoire de Chimie Physique et Microbiologie pour l' Environnement, UMR 7564 CNRS-Universite de Lorraine, 54602 Villers-les-Nancy (France); Mamane, Victor; Fort, Yves [Laboratoire de Structure et Reactivite des Systemes Moleculaires Complexes, UMR 7565 CNRS-Universite de Lorraine, 54506 Vandoeuvre-les-Nancy (France); Devaux, Xavier [Insitut Jean Lamour, Department P2M, UMR 7198 CNRS-Universite de Lorraine, Ecole des Mines, 54042 Nancy (France); Vigolo, Brigitte; McRae, Edward [Insitut Jean Lamour, Department CP2S, UMR 7198 CNRS-Universite de Lorraine, 54506 Vandoeuvre-les-Nancy (France); Noel, Maxime [Department of Engineering Sciences and Mathematics, Luleaa University of Technology, 97187 Luleaa (Sweden); Soldatov, Alexander V. [Department of Engineering Sciences and Mathematics, Luleaa University of Technology, 97187 Luleaa (Sweden); Department of Physics, Harvard University, Cambridge, MA 02138 (United States)

2012-12-15

The present work reports the covalent functionalization of few-wall CNTs (FWCNTs) by ferrocene derivatives to (i) improve their dispersion efficiency in water and (ii) graft electroactive chemical groups on their side-walls in order to promote electron transfer to biomolecules. The functionalized CNTs (f-CNTs) are used to modify a glassy carbon electrode and this modified electrode is used for oxidizing the cofactor NADH (dihydronicotinamide adenine dinucleotide). (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

An important role for adenine, cholera toxin, hydrocortisone and triiodothyronine in the proliferation, self-renewal and differentiation of limbal stem cells in vitro.

Science.gov (United States)

Yu, Min; Bojic, Sanja; Figueiredo, Gustavo S; Rooney, Paul; de Havilland, Julian; Dickinson, Anne; Figueiredo, Francisco C; Lako, Majlinda

2016-11-01

The cornea is a self-renewing tissue located at the front of the eye. Its transparency is essential for allowing light to focus onto the retina for visual perception. The continuous renewal of corneal epithelium is supported by limbal stem cells (LSCs) which are located in the border region between conjunctiva and cornea known as the limbus. Ex vivo expansion of LSCs has been successfully applied in the last two decades to treat patients with limbal stem cell deficiency (LSCD). Various methods have been used for their expansion, yet the most widely used culture media contains a number of ingredients derived from animal sources which may compromise the safety profile of human LSC transplantation. In this study we sought to understand the role of these components namely adenine, cholera toxin, hydrocortisone and triiodothyronine with the aim of re-defining a safe and GMP compatible minimal media for the ex vivo expansion of LSCs on human amniotic membrane. Our data suggest that all four components play a critical role in maintaining LSC proliferation and promoting LSC self-renewal. However removal of adenine and triiodothyronine had a more profound impact and led to LSC differentiation and loss of viability respectively, suggesting their essential role for ex vivo expansion of LSCs. Replacement of each of the components with GMP-grade reagents resulted in equal growth to non-GMP grade media, however an enhanced differentiation of LSCs was observed, suggesting that additional combinations of GMP grade reagents need to be tested to achieve similar or better level of LSC maintenance in the same manner as the traditional LSC media. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Chinese herbal medicine Shenqi Detoxification Granule inhibits fibrosis in adenine induced chronic renal failure rats.

Science.gov (United States)

Peng, Min; Cai, Pingping; Ma, Hongbo; Meng, Hongyan; Xu, Yuan; Zhang, Xiaoyi; Si, Guomin

2014-01-01

Progressive fibrosis accompanies all chronic renal disease, connective tissue growth factor (CTGF,) and platelet-derived growth factor-B, (PDGF-B,) play important roles in extra-cellular matrix abnormal accumulation, while endothelin-1 (ET-1) nitric oxide (NO,) are related to endothelial dysfunction, which mediates the progression of renal fibrosis. Shenqi Detoxification Granule (SDG), a traditional Chinese herbal formula, has been used for treatment of chronic renal failure in clinic for many years. In order to evaluate the efficacy, and explore the mechanism of SDG to inhibit the progression of renal fibrosis, study was carried out using the adenine-induced Wister rats as the CRF model, and losartan as postive control drug. Levels of serum creatinine [Scr], and blood urea nitrogen (BUN), albumin (ALB), 24hrs, urine protein (24hUP), triacylglycerol (TG), and cholesterol (CHO), together with ET-1, and NO were detected. Pathological changes of renal tissues were observed by HE, staining. In addition, CTGF and PDGF-B expression were analyzed by immuno-histo-chemistry. The results indicated that SDG can effectively reduce Scr, BUN, 24hUP, TG, and CHO levels, increase ALB levels, inhibit renal tissue damage in CRF rats, and the mechanism maybe reduce PDGF-B, CTGF expression and ET-1/NO. Shenqi Detoxification Granule is a beneficial treatment for chronic renal failure.

Polycyclic aromatic hydrocarbons and their nitrated derivatives associated with PM10 from Kraków city during heating season

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Styszko Katarzyna

2016-01-01

Full Text Available Polycyclic Aromatic Hydrocarbons (PAHs, their nitro-derivatives (NPAHs and hundreds of other organic compounds are present in ambient air in gas and particulate form. PAHs and NPAHs originate from diesel and gasoline exhaust emission and other combustion sources. NPAHs are also formed through the nitration of parent PAHs in the atmosphere. Concentrations of PAHs and NPAHs in the particulate matter fraction PM10 collected in the centre of Kraków (27.01.2014 – 17.02.2014 were investigated. The thirteen PAHs and four NPAHs: fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benzo[a]anthracene, benzo[a]pyrene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, indeno[1,2,3-c,d]pyrene, benzo[g,h,i]perylene, dibenz[a,h]anthracene, 2-nitrofluorene, 9-nitroanthracene, 3-nitrofluoranthene and 1-nitropyrene were extracted from particulate matter and analysed applying the GC/MS technique. Depending on the compounds the relative recoveries ranged from 72 to 94%. The concentrations of PM10 in the study period ranged between 23.5 and 153.8 μg·m-3. The average concentrations of PAHs and NPAHs ranged from 26.6 to 276.4 ng·m-3 and from 0.6 to 9.1 ng·m-3, respectively. The highest concentrations were observed for benzo[a]pyrene, benzo[a]anthracene, pyrene and fluoranthene. The average concentration of benzo[a]pyrene (BaP, which is a marker for the particle-bound atmospheric PAHs, was 9.5 ng·m-3. The concentrations of 3-nitrofluoranthene and 1-nitropyrene were below the quantification limits of the method (< MQL.

Combined effects of inhaled plutonium oxide and benzo[a]pyrene on lung carcinogenesis in rats

International Nuclear Information System (INIS)

Metivier, H.; Masse, R.; Wahrendorf, J.; Lafuma, J.

1986-01-01

This study describes the effect of two intratracheal instillations (5 mg each) of benzo[a]pyrene (BP) on lung carcinogenesis in rats that had previously inhaled three levels of 239 PuO 2 . The BP does not modify survival in the high-level 239 PuO 2 -exposed rats, but markedly reduces survival in the two other groups. Median survival time with BP alone is shorter (666 days) than for the control group (838 days). Tumor incidence was increased by BP exposure, and the tumors were usually fatal, whereas tumors observed after 239 PuO 2 inhalation alone were usually not fatal. Statistical analysis of these data poses a problem because of the need to compare incidental and fatal tumors. 22 refs., 5 figs., 7 tabs

Alterations to proteome and tissue recovery responses in fish liver caused by a short-term combination treatment with cadmium and benzo[a]pyrene

International Nuclear Information System (INIS)

Costa, P.M.; Chicano-Galvez, E.; Lopez Barea, J.; DelValls, T.A.; Costa, M.H.

2010-01-01

The livers of soles (Solea senegalensis) injected with subacute doses of cadmium (Cd), benzo[a]pyrene (B[a]P), or their combination, were screened for alterations to cytosolic protein expression patterns, complemented by cytological and histological analyses. Cadmium and B[a]P, but not combined, induced hepatocyte apoptosis and Kupfer cell hyperplasia. Proteomics, however, suggested that apoptosis was triggered through distinct pathways. Cadmium and B[a]P caused upregulation of different anti-oxidative enzymes (peroxiredoxin and glutathione peroxidase, respectively) although co-exposure impaired induction. Similarly, apoptosis was inhibited by co-exposure, to which may have contributed a synergistic upregulation of tissue metalloproteinase inhibitor, β-actin and a lipid transport protein. The regulation factors of nine out of eleven identified proteins of different types revealed antagonistic or synergistic effects between Cd and B[a]P at the prospected doses after 24 h of exposure. The results indicate that co-exposure to Cd and B[a]P may enhance toxicity by impairing specific responses and not through cumulative damage. - The interaction between cadmium and benzo[a]pyrene impairs specific responses to toxicity and tissue repair mechanisms.

When does the lung die? Kfc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung.

Science.gov (United States)

Jones, D R; Becker, R M; Hoffmann, S C; Lemasters, J J; Egan, T M

1997-07-01

Lungs harvested from cadaveric circulation-arrested donors may increase the donor pool for lung transplantation. To determine the degree and time course of ischemia-reperfusion injury, we evaluated the effect of O2 ventilation on capillary permeability [capillary filtration coefficient (Kfc)], cell viability, and total adenine nucleotide (TAN) levels in in situ circulation-arrested rat lungs. Kfc increased with increasing postmortem ischemic time (r = 0.88). Lungs ventilated with O2 1 h postmortem had similar Kfc and wet-to-dry ratios as controls. Nonventilated lungs had threefold (P Kfc at 30 and 60 min postmortem compared with controls. Cell viability decreased in all groups except for 30-min postmortem O2-ventilated lungs. TAN levels decreased with increasing ischemic time, particularly in nonventilated lungs. Loss of adenine nucleotides correlated with increasing Kfc values (r = 0.76). This study indicates that lungs retrieved 1 h postmortem may have normal Kfc with preharvest O2 ventilation. The relationship between Kfc and TAN suggests that vascular permeability may be related to lung TAN levels.

Post-synthetic modification of mesoporous zinc-adeninate framework with tris(2,2′-biprydine) ruthenium(II) complex and its electrochemiluminescence

Energy Technology Data Exchange (ETDEWEB)

Park, Ji Eun; Shin, Ik Soo [Dept. of Chemistry, Soongsil University, Seoul (Korea, Republic of); Oh, Hye Jae; An, Ji Hyun [Dept. of Chemistry Education, Seoul National University, Seoul (Korea, Republic of)

2017-04-15

Herein we report a redox-active metal-organic framework (MOF) via post-synthetic cation exchange with tris(2,2′-biprydine) ruthenium(II) complex (Ru(bpy){sub 3}{sup 2+}). A porous anionic zinc-adeninate framework (bMOF-100) is spacious enough to easily entrap 2.43 of Ru(bpy){sub 3}{sup 2+} cations within the mesopore. The encapsulation supported the framework structure preventing any distortion from a rapid solvent evaporation under SEM observation. Ru(bpy){sub 3}{sup 2+}@bMOF-100 was then immobilized on the surface of glassy carbon electrode, and its electrocatalytic and electrochemiluminescent (ECL) properties were investigated in aqueous and organic solution. Especially, Ru(bpy){sub 3}{sup 2+}@bMOF-100 showed the excellent electrochemical properties of Ru(bpy){sub 3}{sup 2+}, but gradual decomposition of the MOF structure was observed under electrochemical measurements because of the sluggish oxidation of adeninate ligand.

Damage to uracil- and adenine-containing bases, nucleosides, nucleotides and polynucleotides: quantum yields on irradiation at 193 and 254 nm

International Nuclear Information System (INIS)

Gurzadyan, G.G.; Goerner, H.

1994-01-01

Photoreactions, such as base release and decomposition of the base moeity, induced by either 20 ns laser pulses at 193 nm or continuous 254 nm irradiation, were studied for a series of uracil and adenine derivatives in neutral aqueous solution. The quantum yield of chromophore loss (Φ cl ) depends significantly on the nature of the nucleic acid constituent and the saturating gas (Ar, N 2 O or O 2 ). In the case of polynucleotides the destruction of nucleotides was measured by high-performance liquid chromatography after hydrolysis; the quantum yields (Φ dn ) are comparable to those of chromophore loss or larger. The Φ cl and Φ dn of 0.04-0.1 for poly(U) and poly(dU), obtained for both wavelengths of irradiation, are due to processes originating from the lowest excited singlet state, i.e. formation of photohydrates and photodimers, and a second part from photoionization using λ irr = 193 nm. Irradiation at 193 nm effectively splits pyrimidine dimers and thus reverts them into monomers. (author)

Schiff Base Metal Derivatives Enhance the Expression of HSP70 and Suppress BAX Proteins in Prevention of Acute Gastric Lesion

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Shahram Golbabapour

2013-01-01

Full Text Available Schiff base complexes have appeared to be promising in the treatment of different diseases and disorders and have drawn a lot of attention to their biological activities. This study was conducted to evaluate the regulatory effect of Schiff base metal derivatives on the expression of heat shock proteins (HSP 70 and BAX in protection against acute haemorrhagic gastric ulcer in rats. Rats were assigned to 6 groups of 6 rats: the normal control (Tween 20 5% v/v, 5 mL/kg, the positive control (Tween 20 5% v/v, 5 mL/kg, and four Schiff base derivative groups named Schiff_1, Schiff_2, Schiff_3, and Schiff_4 (25 mg/kg. After 1 h, all of the groups received ethanol 95% (5 mL/kg but the normal control received Tween 20 (Tween 20 5% v/v, 5 mL/kg. The animals were euthanized after 60 min and the stomachs were dissected for histology (H&E, immunohistochemistry, and western blot analysis against HSP70 and BAX proteins. The results showed that the Schiff base metal derivatives enhanced the expression of HSP70 and suppressed the expression of BAX proteins during their gastroprotection against ethanol-induced gastric lesion in rats.

Schiff base metal derivatives enhance the expression of HSP70 and suppress BAX proteins in prevention of acute gastric lesion.

Science.gov (United States)

Golbabapour, Shahram; Gwaram, Nura Suleiman; Al-Obaidi, Mazen M Jamil; Soleimani, A F; Ali, Hapipah Mohd; Abdul Majid, Nazia

2013-01-01

Schiff base complexes have appeared to be promising in the treatment of different diseases and disorders and have drawn a lot of attention to their biological activities. This study was conducted to evaluate the regulatory effect of Schiff base metal derivatives on the expression of heat shock proteins (HSP) 70 and BAX in protection against acute haemorrhagic gastric ulcer in rats. Rats were assigned to 6 groups of 6 rats: the normal control (Tween 20 5% v/v, 5 mL/kg), the positive control (Tween 20 5% v/v, 5 mL/kg), and four Schiff base derivative groups named Schiff_1, Schiff_2, Schiff_3, and Schiff_4 (25 mg/kg). After 1 h, all of the groups received ethanol 95% (5 mL/kg) but the normal control received Tween 20 (Tween 20 5% v/v, 5 mL/kg). The animals were euthanized after 60 min and the stomachs were dissected for histology (H&E), immunohistochemistry, and western blot analysis against HSP70 and BAX proteins. The results showed that the Schiff base metal derivatives enhanced the expression of HSP70 and suppressed the expression of BAX proteins during their gastroprotection against ethanol-induced gastric lesion in rats.

Serum Level of Antibodies (IgG, IgM Against Benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA Adducts in Children Dermatologically Exposed to Coal Tar

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Pavel Borský

2017-06-01

Full Text Available Crude coal tar (CCT contains polycyclic aromatic hydrocarbons (PAHs. Benzo[a]pyrene (BaP is metabolized into a highly reactive metabolite benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE that is able to bind to DNA and creates BPDE-DNA adducts. Adducted DNA becomes immunogenic and induces immune response by production of antibodies against BPDE-DNA adducts (Ab-BPDE-DNA. Circulating Ab-BPDE-DNA was proposed as potential biomarker of genotoxic exposure to BaP (PAHs. Goeckerman therapy (GT of psoriasis uses dermal application of CCT ointment (PAHs. In presented study (children with psoriasis treated by GT; n = 19 the therapy significantly increased the level of Ab-BPDE-DNA (EI = 0.29/0.19–0.34 vs. 0.31/0.25–0.40; median/lower–upper quartile; p < 0.01. The results support the idea of Ab-BPDE-DNA level as a possible tentative indicator of exposure, effects and susceptibility of the organism to the exposure of BaP (PAHs.

Lesion progression in post-treatment persistent endodontic lesions.

Science.gov (United States)

Yu, Victoria Soo Hoon; Messer, Harold Henry; Shen, Liang; Yee, Robert; Hsu, Chin-ying Stephen

2012-10-01

Radiographic lesions related to root-filled teeth may persist for long periods after treatment and are considered to indicate failure of initial treatment. Persistent lesions are found in a proportion of cases, but information on lesion progression is lacking. This study examined the incidence of lesion improvement, remaining unchanged, and deterioration among persistent lesions in a group of patients recruited from a university-based clinic and identified potential predictors for lesion progression. Patients of a university clinic with persistent endodontic lesions at least 4 years since treatment and with original treatment radiographs available were recruited with informed consent. Data were obtained by interview and from dental records and clinical and radiographic examinations. Univariate and multivariate statistical analyses were carried out by using SPSS (version 19). One hundred fifty-one persistent lesions were identified in 114 patients. A majority of the lesions (107, 70.9%) received treatment between 4 and 5 years prior. Eighty-six lesions (57.0%) improved, 18 (11.9%) remained unchanged, and 47 (31.1%) deteriorated since treatment. Potential predictors for lesions that did not improve included recall lesion size, pain on biting at recall examination, history of a postobturation flare-up, and a non-ideal root-filling length (P < .05). Lesions that had persisted for a longer period appeared less likely to be improving (relative risk, 1.038; 95% confidence interval, 1.000-1.077). A specific time interval alone should not be used to conclude that a lesion will not resolve without intervention. This study identified several clinical factors that are associated with deteriorating persistent lesions, which should aid in identifying lesions that require further intervention. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Contrast-enhanced magnetic resonance imaging of the breast: the value of pharmacokinetic parameters derived from fast dynamic imaging during initial enhancement in classifying lesions

International Nuclear Information System (INIS)

Veltman, J.; Stoutjesdijk, M.; Mann, R.; Huisman, H.J.; Barentsz, J.O.; Blickman, J.G.; Boetes, C.

2008-01-01

The value of pharmacokinetic parameters derived from fast dynamic imaging during initial enhancement in characterizing breast lesions on magnetic resonance imaging (MRI) was evaluated. Sixty-eight malignant and 34 benign lesions were included. In the scanning protocol, high temporal resolution imaging was combined with high spatial resolution imaging. The high temporal resolution images were recorded every 4.1 s during initial enhancement (fast dynamic analysis). The high spatial resolution images were recorded at a temporal resolution of 86 s (slow dynamic analysis). In the fast dynamic evaluation pharmacokinetic parameters (K trans , V e and k ep ) were evaluated. In the slow dynamic analysis, each lesion was scored according to the BI-RADS classification. Two readers evaluated all data prospectively. ROC and multivariate analysis were performed. The slow dynamic analysis resulted in an AUC of 0.85 and 0.83, respectively. The fast dynamic analysis resulted in an AUC of 0.83 in both readers. The combination of both the slow and fast dynamic analyses resulted in a significant improvement of diagnostic performance with an AUC of 0.93 and 0.90 (P = 0.02). The increased diagnostic performance found when combining both methods demonstrates the additional value of our method in further improving the diagnostic performance of breast MRI. (orig.)

Human brain lesion-deficit inference remapped.

Science.gov (United States)

Mah, Yee-Haur; Husain, Masud; Rees, Geraint; Nachev, Parashkev

2014-09-01

Our knowledge of the anatomical organization of the human brain in health and disease draws heavily on the study of patients with focal brain lesions. Historically the first method of mapping brain function, it is still potentially the most powerful, establishing the necessity of any putative neural substrate for a given function or deficit. Great inferential power, however, carries a crucial vulnerability: without stronger alternatives any consistent error cannot be easily detected. A hitherto unexamined source of such error is the structure of the high-dimensional distribution of patterns of focal damage, especially in ischaemic injury-the commonest aetiology in lesion-deficit studies-where the anatomy is naturally shaped by the architecture of the vascular tree. This distribution is so complex that analysis of lesion data sets of conventional size cannot illuminate its structure, leaving us in the dark about the presence or absence of such error. To examine this crucial question we assembled the largest known set of focal brain lesions (n = 581), derived from unselected patients with acute ischaemic injury (mean age = 62.3 years, standard deviation = 17.8, male:female ratio = 0.547), visualized with diffusion-weighted magnetic resonance imaging, and processed with validated automated lesion segmentation routines. High-dimensional analysis of this data revealed a hidden bias within the multivariate patterns of damage that will consistently distort lesion-deficit maps, displacing inferred critical regions from their true locations, in a manner opaque to replication. Quantifying the size of this mislocalization demonstrates that past lesion-deficit relationships estimated with conventional inferential methodology are likely to be significantly displaced, by a magnitude dependent on the unknown underlying lesion-deficit relationship itself. Past studies therefore cannot be retrospectively corrected, except by new knowledge that would render them redundant

Determination of the recognition site for adenine-specific methylase of Shigella sonnei 47 by hydazinolysis of DNA, followed by separation of the purine oligonucleotides by thin-layer chromatography on DEAE-cellulose

International Nuclear Information System (INIS)

Lopatina, N.G.; Kirnos, M.D.; Suchkov, S.V.; Vanyushin, B.F.; Nikol'skaya, I.I.; Debov, S.S.

1985-01-01

A method has been developed for the separation of oligopurine units according to length and composition by two-dimensional thin-layer chromatography on plates with DEAE-cellulose, permitting a comparative analysis of the content of various purine isopliths in DNA of different origin. In the case of the analysis of methylated DNA, the method permits a comparison of the substrate specificity of various enzymes of methylation of the adenine residues in DNA. In conjunction with enzymatic treatment of labeled methylated isopliths, the method permits determination of the methylatable sequence and in a number of cases an ascertainment of the recognition site for adenine-specific methylase as a whole. The proposed method was used to establish the fact that the methylase Ssol recognizes the sequence 5'...G-A-A-T-T-C...3' and methylates the adenine residue closest to its 5'-end

Species differences in biliary excretion of benzo[a]pyrene

International Nuclear Information System (INIS)

Weyand, E.H.; Bevan, D.R.

1986-01-01

Biliary excretion of benzo[a]pyrene (B[a]P) was investigated in rats, hamsters, and guinea pigs following intratracheal administration. [ 3 H]-B[a]P, in amounts of approximately 150 ng or 350 μg, was instilled into lungs and amounts of radioactivity excreted in bile were monitored for six hrs following administration. Differences in biliary excretion of [ 3 H]-B[a]P and/or metabolites among species were observed at low doses but not at high doses. Six hours after instillation of a low dose of B[a]P, 70, 54, and 62% of the dose was excreted in bile of rats, hamsters, and guinea pigs, respectively. Upon administration of the higher dose of B[a]P, approximately 50% of the dose was excreted in bile in six hrs by all species. Thus, rats and guinea pigs exhibit differences in biliary excretion of low and high doses of B[a]P whereas hamsters do not. Profiles of phase II metabolites in rats and hamsters were similar at both low and high doses, with the majority of metabolites being glucuronides and thioether conjugates. However, differences in relative amounts of these conjugates were observed between the two doses, with a shift towards a greater proportion of glucuronides at the higher dose. Metabolites in bile from guinea pigs were primarily thioether conjugates, which accounted for 88% of metabolites at the low dose and 95% at the high dose

A software system for the simulation of chest lesions

Science.gov (United States)

Ryan, John T.; McEntee, Mark; Barrett, Saoirse; Evanoff, Michael; Manning, David; Brennan, Patrick

2007-03-01

We report on the development of a novel software tool for the simulation of chest lesions. This software tool was developed for use in our study to attain optimal ambient lighting conditions for chest radiology. This study involved 61 consultant radiologists from the American Board of Radiology. Because of its success, we intend to use the same tool for future studies. The software has two main functions: the simulation of lesions and retrieval of information for ROC (Receiver Operating Characteristic) and JAFROC (Jack-Knife Free Response ROC) analysis. The simulation layer operates by randomly selecting an image from a bank of reportedly normal chest x-rays. A random location is then generated for each lesion, which is checked against a reference lung-map. If the location is within the lung fields, as derived from the lung-map, a lesion is superimposed. Lesions are also randomly selected from a bank of manually created chest lesion images. A blending algorithm determines which are the best intensity levels for the lesion to sit naturally within the chest x-ray. The same software was used to run a study for all 61 radiologists. A sequence of images is displayed in random order. Half of these images had simulated lesions, ranging from subtle to obvious, and half of the images were normal. The operator then selects locations where he/she thinks lesions exist and grades the lesion accordingly. We have found that this software was very effective in this study and intend to use the same principles for future studies.

SYSTEM CONTROL OF SMOKING PROCESS AND MEASURING BENZO[A]PYRENE IN TRADITIONAL PRODUCTION OF BOSNIAN DRY CURED HAM (BOSANSKI PRŠUT BY IMPLEMENTING HACCP SYSTEM

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Almir Toroman

2013-08-01

Full Text Available As it is well known, traditional production of smoked meat products requires technological processes, which carry some food safety hazards (e.g. content of Benzo[a]pyrene. (B[a]P. “OMEGA COMERC Ltd.”, a member of the meat industry in Visoko region, has implemented food safety management system according to the recommendations from Codex Alimentarius CAC-RCP (9, recommended International Code of Practice - General Principles of Food Hygiene. By implementing HACCP system, the Company established adequate control measures in producing Bosnian dry cured ham (bosanski pršut on traditional way including the smoking process in the chambers. By doing this, they have created conditions to measure B[a]P content in the Bosnian dry cured ham and implement HACCP system without impairing traditional production and food safety of the final product.The aim of this study is to present the effect of the specific production process onto the meat smoking in order to preserve hygienic, nutritional and sensory values, and also to control B[a]P content in the final product.Key words: Bosnian dry cured ham, traditional production, smoking process, Benzo[a]pyrene, HACCP

Comparison of functional recovery of manual dexterity after unilateral spinal cord lesion or motor cortex lesion in adult macaque monkeys

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Florence eHoogewoud

2013-07-01

Full Text Available In relation to mechanisms involved in functional recovery of manual dexterity from cervical cord injury or from motor cortical injury, our goal was to determine whether the movements that characterize post-lesion functional recovery are comparable to original movement patterns or do monkeys adopt distinct strategies to compensate the deficits depending on the type of lesion? To this aim, data derived from earlier studies, using a skilled finger task (the modified Brinkman board from which pellets are retrieved from vertical or horizontal slots, in spinal cord and motor cortex injured monkeys were analyzed and compared. Twelve adult macaque monkeys were subjected to a hemi-section of the cervical cord (n=6 or to a unilateral excitotoxic lesion of the hand representation in the primary motor cortex (n=6. In addition, in each subgroup, one half of monkeys (n=3 were treated for 30 days with a function blocking antibody against the neurite growth inhibitory protein Nogo-A, while the other half (n=3 represented control animals. The motor deficits, and the extent and time course of functional recovery were assessed.For some of the parameters investigated (wrist angle for horizontal slots and movement types distribution for vertical slots after cervical injury; movement types distribution for horizontal slots after motor cortex lesion, post-lesion restoration of the original movement patterns (true recovery led to a quantitatively better functional recovery. In the motor cortex lesion groups, pharmacological reversible inactivation experiments showed that the peri-lesion territory of the primary motor cortex or re-arranged, spared domain of the lesion zone, played a major role in the functional recovery, together with the ipsilesional intact premotor cortex.

Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents

International Nuclear Information System (INIS)

Crowell, Susan Ritger; Amin, Shantu G.; Anderson, Kim A.; Krishnegowda, Gowdahalli; Sharma, Arun K.; Soelberg, Jolen J.; Williams, David E.; Corley, Richard A.

2011-01-01

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated as byproducts of natural and anthropogenic combustion processes. Despite significant public health concern, physiologically based pharmacokinetic (PBPK) modeling efforts for PAHs have so far been limited to naphthalene, plus simpler PK models for pyrene, nitropyrene, and benzo[a]pyrene (B[a]P). The dearth of published models is due in part to the high lipophilicity, low volatility, and myriad metabolic pathways for PAHs, all of which present analytical and experimental challenges. Our research efforts have focused upon experimental approaches and initial development of PBPK models for the prototypic PAH, B[a]P, and the more potent, albeit less studied transplacental carcinogen, dibenzo[def,p]chrysene (DBC). For both compounds, model compartments included arterial and venous blood, flow limited lung, liver, richly perfused and poorly perfused tissues, diffusion limited fat, and a two compartment theoretical gut (for oral exposures). Hepatic and pulmonary metabolism was described for both compounds, as were fractional binding in blood and fecal clearance. Partition coefficients for parent PAH along with their diol and tetraol metabolites were estimated using published algorithms and verified experimentally for the hydroxylated metabolites. The preliminary PBPK models were able to describe many, but not all, of the available data sets, comprising multiple routes of exposure (oral, intravenous) and nominal doses spanning several orders of magnitude. Supported by Award Number P42 ES016465 from the National Institute of Environmental Health Sciences. -- Highlights: ► We present PBPK models for benzo[a]pyrene (B[a]P) and dibenzo[def,p]chrysene (DBC). ► B[a]P model accurately predicts data from multiple sources over a wide dose range. ► DBC model was based on the B[a]P model as less chemical specific data is available. ► DBC model accurately predicted preliminary

Whole-lesion histogram analysis metrics of the apparent diffusion coefficient as a marker of breast lesions characterization at 1.5 T

International Nuclear Information System (INIS)

Bougias, H.; Ghiatas, A.; Priovolos, D.; Veliou, K.; Christou, A.

2017-01-01

Introduction: To retrospectively assess the role of whole-lesion apparent diffusion coefficient (ADC) in the characterization of breast tumors by comparing different histogram metrics. Methods: 49 patients with 53 breast lesions underwent magnetic resonance imaging (MRI). ADC histogram parameters, including the mean, mode, 10th/50th/90th percentile, skewness, kurtosis, and entropy ADCs, were derived for the whole-lesion volume in each patient. Mann–Whitney U-test, area under the receiver-operating characteristic curve (AUC) were used for statistical analysis. Results: The mean, mode and 10th/50th/90th percentile ADC values were significantly lower in malignant lesions compared with benign ones (all P < 0.0001), while skewness was significantly higher in malignant lesions P = 0.02. However, no significant difference was found between entropy and kurtosis values in malignant lesions compared with benign ones (P = 0.06 and P = 1.00, respectively). Univariate logistic regression showed that 10th and 50th percentile ADC yielded the highest AUC (0.985; 95% confidence interval [CI]: 0.902, 1.000 and 0.982; 95% confidence interval [CI]: 0.896, 1.000 respectively), whereas kurtosis value yielded the lowest AUC (0.500; 95% CI: 0.355, 0.645), indicating that 10th and 50th percentile ADC values may be more accurate for lesion discrimination. Conclusion: Whole-lesion ADC histogram analysis could be a helpful index in the characterization and differentiation between benign and malignant breast lesions with the 10th and 50th percentile ADC be the most accurate discriminators. - Highlights: • DWI is a noninvasive technique that allows quantification of water diffusion in tissues. • ADC histogram analysis is a useful index in the differentiation benign and malignant breast tumors. • The 10th, 50th percentile ADC values being the best discriminators between breast lesions.

Persistent changes in the initial rate of pyruvate transport by isolated rat liver mitochondria after preincubation with adenine nucleotides and calcium ions

NARCIS (Netherlands)

Vaartjes, W.J.; Breejen, J.N. den; Geelen, M.J.H.; Bergh, S.G. van den

1980-01-01

1. Preincubation of isolated rat-liver mitochondria in the presence of adenine nucleotides or Ca2+ results in definite and persistent changes in the initial rate of pyruvate transport. 2. These changes in the rate of pyruvate transport are accompanied by equally persistent changes in the opposite

Supra-molecular architecture in a co-crystal of the N(7)-H tautomeric form of N (6)-benzoyl-adenine with adipic acid (1/0.5).

Science.gov (United States)

Swinton Darious, Robert; Thomas Muthiah, Packianathan; Perdih, Franc

2016-06-01

The asymmetric unit of the title co-crystal, C12H9N5O·0.5C6H10O4, consists of one mol-ecule of N (6)-benzoyl-adenine (BA) and one half-mol-ecule of adipic acid (AA), the other half being generated by inversion symmetry. The dihedral angle between the adenine and phenyl ring planes is 26.71 (7)°. The N (6)-benzoyl-adenine mol-ecule crystallizes in the N(7)-H tautomeric form with three non-protonated N atoms. This tautomeric form is stabilized by intra-molecular N-H⋯O hydrogen bonding between the carbonyl (C=O) group and the N(7)-H hydrogen atom on the Hoogsteen face of the purine ring, forming an S(7) ring motif. The two carboxyl groups of adipic acid inter-act with the Watson-Crick face of the BA mol-ecules through O-H⋯N and N-H⋯O hydrogen bonds, generating an R 2 (2)(8) ring motif. The latter units are linked by N-H⋯N hydrogen bonds, forming layers parallel to (10-5). A weak C-H⋯O hydrogen bond is also present, linking adipic acid mol-ecules in neighbouring layers, enclosing R (2) 2(10) ring motifs and forming a three-dimensional structure. C=O⋯π and C-H⋯π inter-actions are also present in the structure.

Small white matter lesion detection in cerebral small vessel disease

Science.gov (United States)

Ghafoorian, Mohsen; Karssemeijer, Nico; van Uden, Inge; de Leeuw, Frank E.; Heskes, Tom; Marchiori, Elena; Platel, Bram

2015-03-01

Cerebral small vessel disease (SVD) is a common finding on magnetic resonance images of elderly people. White matter lesions (WML) are important markers for not only the small vessel disease, but also neuro-degenerative diseases including multiple sclerosis, Alzheimer's disease and vascular dementia. Volumetric measurements such as the "total lesion load", have been studied and related to these diseases. With respect to SVD we conjecture that small lesions are important, as they have been observed to grow over time and they form the majority of lesions in number. To study these small lesions they need to be annotated, which is a complex and time-consuming task. Existing (semi) automatic methods have been aimed at volumetric measurements and large lesions, and are not suitable for the detection of small lesions. In this research we established a supervised voxel classification CAD system, optimized and trained to exclusively detect small WMLs. To achieve this, several preprocessing steps were taken, which included a robust standardization of subject intensities to reduce inter-subject intensity variability as much as possible. A number of features that were found to be well identifying small lesions were calculated including multimodal intensities, tissue probabilities, several features for accurate location description, a number of second order derivative features as well as multi-scale annular filter for blobness detection. Only small lesions were used to learn the target concept via Adaboost using random forests as its basic classifiers. Finally the results were evaluated using Free-response receiver operating characteristic.

A novel twist on molecular interactions between thioredoxin and nicotinamide adenine dinucleotide phosphate-dependent thioredoxin reductase

DEFF Research Database (Denmark)

Kirkensgaard, Kristine Groth; Hägglund, Per; Shahpiri, Azar

2013-01-01

The ubiquitous disulfide reductase thioredoxin (Trx) regulates several important biological processes such as seed germination in plants. Oxidized cytosolic Trx is regenerated by nicotinamide adenine dinucleotide phosphate (NADPH)-dependent thioredoxin reductase (NTR) in a multistep transfer...... dinucleotide (FAD)-binding domain of HvNTR2 to strongly affect the interaction with Trx. In particular, Trp42 and Met43 play key roles for recognition of the endogenous HvTrxh2. Trx from Arabidopsis thaliana is also efficiently recycled by HvNTR2 but turnover in this case appears to be less dependent...

Lung lesion doubling times: values and variability based on method of volume determination

International Nuclear Information System (INIS)

Eisenbud Quint, Leslie; Cheng, Joan; Schipper, Matthew; Chang, Andrew C.; Kalemkerian, Gregory

2008-01-01

Purpose: To determine doubling times (DTs) of lung lesions based on volumetric measurements from thin-section CT imaging. Methods: Previously untreated patients with ≥ two thin-section CT scans showing a focal lung lesion were identified. Lesion volumes were derived using direct volume measurements and volume calculations based on lesion area and diameter. Growth rates (GRs) were compared by tissue diagnosis and measurement technique. Results: 54 lesions were evaluated including 8 benign lesions, 10 metastases, 3 lymphomas, 15 adenocarcinomas, 11 squamous carcinomas, and 7 miscellaneous lung cancers. Using direct volume measurements, median DTs were 453, 111, 15, 181, 139 and 137 days, respectively. Lung cancer DTs ranged from 23-2239 days. There were no significant differences in GRs among the different lesion types. There was considerable variability among GRs using different volume determination methods. Conclusions: Lung cancer doubling times showed a substantial range, and different volume determination methods gave considerably different DTs

Transcriptional profiles of benzo(a)pyrene exposure in normal human mammary epithelial cells in the absence or presence of chlorophyllin

International Nuclear Information System (INIS)

John, Kaarthik; Keshava, Channa; Richardson, Diana L.; Weston, Ainsley; Nath, Joginder

2008-01-01

Benzo(a)pyrene (BP) exposure causes alterations in gene expression in normal human mammary epithelial cells (NHMECs). This study used Affymetrix Hu-Gene133A arrays, with 14,500 genes represented, to evaluate modulation of BP-induced gene expression by chlorophyllin in six NHMEC strains derived from different donors. A major goal was to seek potential biomarkers of carcinogen exposure and how they behave in the presence of a chemopreventive agent. NHMECs (passage 6 and 70% confluence) were exposed for 24 h to either vehicle control, or BP, or chlorophyllin followed by BP and chlorophyllin together. BP exposure resulted in approximately 3-fold altered expression of 49 genes in at least one of the six NHMEC strains. When cells were exposed to chlorophyllin pre-treatment followed by BP plus chlorophyllin, expression of 125 genes was similarly altered. Genes in the functional categories of xenobiotic metabolism, cell signaling, cell motility, cell proliferation, cellular transcription, metabolism, cell cycle control, apoptosis and DNA repair were identified. Only CYP1B1 and ALDH1A3 were consistently up-regulated by ∼3-fold in most of the cell strains (at least 4) when exposed to BP. Cluster analysis identified a suite of 13 genes induced by BP where induction was mitigated in the presence of chlorophyllin. Additionally, cluster analysis identified a suite of 16 genes down-regulated by BP where induction was partially restored in the presence of chlorophyllin

Treatment of a Periodontic-Endodontic Lesion in a Patient with Aggressive Periodontitis

OpenAIRE

Fahmy, Mina D.; Luepke, Paul G.; Ibrahim, Mohamed S.; Guentsch, Arndt

2016-01-01

Case Description. This case report describes the successful management of a left mandibular first molar with a combined periodontic-endodontic lesion in a 35-year-old Caucasian woman with aggressive periodontitis using a concerted approach including endodontic treatment, periodontal therapy, and a periodontal regenerative procedure using an enamel matrix derivate. In spite of anticipated poor prognosis, the tooth lesion healed. This case report also discusses the rationale behind different tr...

Quantum-chemical studies on the favored and rare tautomers of neutral and redox adenine.

Science.gov (United States)

Raczyńska, Ewa D; Makowski, Mariusz; Zientara-Rytter, Katarzyna; Kolczyńska, Katarzyna; Stępniewski, Tomasz M; Hallmann, Małgorzata

2013-02-21

All possible twenty-three prototropic tautomers of neutral and redox adenine (nine amine and fourteen imine forms, including geometric isomerism of the exo ═NH group) were examined in vacuo {DFT(B3LYP)/6-311+G(d,p)}. The NH → NH conversions as well as those usually omitted, NH → CH and CH → CH, were considered. An interesting change of the tautomeric preference occurs when proceeding from neutral to reduced adenine. One-electron reduction favors the nonaromatic amine C8H-N10H tautomer. This tautomeric preference is similar to that (C2H) for reduced imidazole. Water molecules (PCM model) seem to not change this trend. They influence solely the relative energies. The DFT vertical detachment energy in the gas phase is positive for each tautomer, e.g., 0.03 eV for N9H-N10H and 1.84 eV for C8H-N10H. The DFT adiabatic electron affinity for the favored process, neutral N9H-N10H → reduced C8H-N10H (ground states), is equal to 0.18 eV at 0 K (ZPE included). One-electron oxidation does not change the tautomeric preference in the gas phase. The aromatic amine N9H-N10H tautomer is favored for the oxidized molecule similarly as for the neutral one. The DFT adiabatic ionization potential for the favored process, neutral N9H-N10H → oxidized N9H-N10H (ground states), is equal to 8.12 eV at 0 K (ZPE included). Water molecules (PCM model) seem to influence solely the composition of the tautomeric mixture and the relative energies. They change the energies of the oxidation and reduction processes by ca. 2 eV.

Modular kinetic analysis of the adenine nucleotide translocator-mediated effects of palmitoyl-CoA on the oxidative phosphorylation in isolated rat liver mitochondria

NARCIS (Netherlands)

Ciapaite, J; Van Eikenhorst, G; Bakker, SJL; Diamant, M; Heine, RJ; Wagner, MJ; Westerhoff, HV; Krab, K

To test whether long-chain fatty acyl-CoA esters link obesity with type 2 diabetes through inhibition of the mitochondrial adenine nucleotide translocator, we applied a system-biology approach, dual modular kinetic analysis, with mitochondrial membrane potential (Delta psi) and the fraction of

Comparison of equine platelet function and survival in whole blood collected in acid-citrate-dextrose solution or citrate-phosphate-dextrose-adenine solution.

Science.gov (United States)

Bozorgmanesh, Rana; Sutton-Burges, Julie W; Tablin, Fern

2017-06-01

Equine whole blood collection and storage methods have been evaluated to assess red blood cell viability; however, platelet (PLT) viability has not been comprehensively assessed. The purpose of the study was to compare viability of PLTs collected in whole blood into 2 different anticoagulants. Whole blood from 6 healthy adult Thoroughbred horses was collected into citrate-phosphate-dextrose-adenine (CPDA) or acid-citrate-dextrose (ACD). Platelet count, pH, and concentrations of glucose, lactate, carbon dioxide, oxygen, bicarbonate, sodium, potassium, and chloride were measured within 10 minutes of collection and then again one hour later at which time PLT aggregometry was performed to assess PLT function. Aggregometry mean amplitudes were significantly higher in CPDA compared to ACD. Blood glucose, pH, bicarbonate, sodium, and lactate concentrations were significantly higher in CPDA compared to ACD. Lactate concentration was higher following one hour in either anticoagulant. Potassium, oxygen, and carbon dioxide concentrations were significantly higher in ACD compared to CPDA at collection. Platelet aggregometry results suggest that CPDA is superior to ACD for maintaining PLT viability following whole blood collection. This may be associated with the higher, more neutral pH as well as an increase in glucose available for metabolism. Although lactate was increased in the CPDA samples it was not high enough to decrease pH and therefore may not have been high enough to cause morphologic lesions and loss of PLT viability. © 2017 American Society for Veterinary Clinical Pathology.

Prediction of radiofrequency ablation lesion formation using a novel temperature sensing technology incorporated in a force sensing catheter.

Science.gov (United States)

Rozen, Guy; Ptaszek, Leon; Zilberman, Israel; Cordaro, Kevin; Heist, E Kevin; Beeckler, Christopher; Altmann, Andres; Ying, Zhang; Liu, Zhenjiang; Ruskin, Jeremy N; Govari, Assaf; Mansour, Moussa

2017-02-01

Real-time radiofrequency (RF) ablation lesion assessment is a major unmet need in cardiac electrophysiology. The purpose of this study was to assess whether improved temperature measurement using a novel thermocoupling (TC) technology combined with information derived from impedance change, contact force (CF) sensing, and catheter orientation allows accurate real-time prediction of ablation lesion formation. RF ablation lesions were delivered in the ventricles of 15 swine using a novel externally irrigated-tip catheter containing 6 miniature TC sensors in addition to force sensing technology. Ablation duration, power, irrigation rate, impedance drop, CF, and temperature from each sensor were recorded. The catheter "orientation factor" was calculated using measurements from the different TC sensors. Information derived from all the sources was included in a mathematical model developed to predict lesion depth and validated against histologic measurements. A total of 143 ablation lesions were delivered to the left ventricle (n = 74) and right ventricle (n = 69). Mean CF applied during the ablations was 14.34 ± 3.55g, and mean impedance drop achieved during the ablations was 17.5 ± 6.41 Ω. Mean difference between predicted and measured ablation lesion depth was 0.72 ± 0.56 mm. In the majority of lesions (91.6%), the difference between estimated and measured depth was ≤1.5 mm. Accurate real-time prediction of RF lesion depth is feasible using a novel ablation catheter-based system in conjunction with a mathematical prediction model, combining elaborate temperature measurements with information derived from catheter orientation, CF sensing, impedance change, and additional ablation parameters. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Regulatory T cells with reduced repressor capacities are extensively amplified in pulmonary sarcoid lesions and sustain granuloma formation.

Science.gov (United States)

Rappl, Gunter; Pabst, Stefan; Riemann, Dagmar; Schmidt, Annette; Wickenhauser, Claudia; Schütte, Wolfgang; Hombach, Andreas A; Seliger, Barbara; Grohé, Christian; Abken, Hinrich

2011-07-01

Sarcoidosis can evolve into a chronic disease with persistent granulomas accompanied by progressive fibrosis. While an unlimited inflammatory response suggests an impaired immune control in sarcoid lesions, it stands in contrast to the massive infiltration with CD4(+)CD25(high)FoxP3(+) regulatory T cells. We here revealed that those Treg cells in affected lung lesions were mainly derived from activated natural Treg cells with GARP (LRRC32)-positive phenotype but exhibited reduced repressor capacities despite high IL-10 and TGF-beta 1 levels. The repressive capacity of blood Treg cells, in contrast, was not impaired compared to age-matched healthy donors. Treg derived cells in granuloma lesions have undergone extensive rounds of amplifications indicated by shortened telomeres compared to blood Treg cells of the same patient. Lesional Treg derived cells moreover secreted pro-inflammatory cytokines including IL-4 which sustains granuloma formation through fibroblast amplification and the activation of mast cells, the latter indicated by the expression of membrane-bound oncostatin M. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of benzo(a)pyrene exposure on the ATPase activity and calcium concentration in the hippocampus of neonatal rats.

Science.gov (United States)

Yang, Kai; Chen, Chengzhi; Cheng, Shuqun; Cao, Xianqing; Tu, Baijie

2017-03-30

To investigate whether postnatal benzo(a)pyrene (B(a)P) exposure caused the impairments on the process of neurodevelopment and the alteration in the calcium medium in the neonatal rats. Eighty neonatal Sprague Dawley (SD) rats were randomly divided into 5 groups (untreated control group, vehicle group, 0.02 mg/kg, 0.2 mg/kg and 2 mg/kg B(a)P-exposed group). Rats were treated with B(a)P by the intragastric administration from postnatal day (PND) 4 to 25. Morris water maze (MWM) was employed to observe the spatial memory of rats. The activity of calcium adenosine triphosphatase (Ca2+-ATPase), sodium-potassium adenosine triphosphatase (Na+-K+-ATPase) and calcium-magnesium adenosine triphosphatase (Ca2+-Mg2+-ATPase) in the hippocampus were detected by commercial kits. Fura-2 pentakis(acetoxymethyl) (Fura-2/AM) probe and reactive oxygen species (ROS) reagent kit were used for measuring the concentration of Ca2+ and ROS in the hippocampus synapse, respectively. Rats exposed to B(a)P resulted in the deficits in the spatial memory manifested by the increased escape latency and decreased number of crossing platform and time spent in target quadrant in comparison with the control groups. Benzo(a)pyrene exposure caused the significant decrease in the ATPase activity in the hippocampus and caused Ca2+ overload in the synaptic, besides, the ROS concentration increased significantly which may further induce neurobehavioral impairment of the neonatal rats. Our findings suggest that postnatal B(a)P exposure may cause the neurobehavioral impairments in the neonatal rats, which were mediated by the decreased ATPase activity and elevated Ca2+ concentration. Int J Occup Med Environ Health 2017;30(2):203-211. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Characterization of genetic miscoding lesions caused by postmortem damage

DEFF Research Database (Denmark)

Gilbert, M Thomas P; Hansen, Anders J; Willerslev, Eske

2002-01-01

The spectrum of postmortem damage in mitochondrial DNA was analyzed in a large data set of cloned sequences from ancient human specimens. The most common forms of damage observed are two complementary groups of transitions, termed "type 1" (adenine-->guanine/thymine-->cytosine) and "type 2...

Modular kinetic analysis of the adenine nucleotide translocator-mediated effects of palmitoyl-CoA on the oxidative phosphorylation in isolated rat liver mitochondria

NARCIS (Netherlands)

Ciapaite, J.; van Eikenhorst, G.; Bakker, S.J.L.; Diamant, M.; Heine, R.J.; Wagner, M.J.; Westerhoff, H.V.; Krab, K.

2005-01-01

To test whether long-chain fatty acyl-CoA esters link obesity with type 2 diabetes through inhibition of the mitochondrial adenine nucleotide translocator, we applied a system-biology approach, dual modular kinetic analysis, with mitochondrial membrane potential (Δψ) and the fraction of matrix ATP

Adenine phosphoribosyltransferase from Sulfolobus solfataricus is an enzyme with unusual kinetic properties and a crystal structure that suggests it evolved from a 6-oxopurine phosphoribosyltransferase.

Science.gov (United States)

Jensen, Kaj Frank; Hansen, Michael Riis; Jensen, Kristine Steen; Christoffersen, Stig; Poulsen, Jens-Christian Navarro; Mølgaard, Anne; Kadziola, Anders

2015-04-14

The adenine phosphoribosyltransferase (APRTase) encoded by the open reading frame SSO2342 of Sulfolobus solfataricus P2 was subjected to crystallographic, kinetic, and ligand binding analyses. The enzyme forms dimers in solution and in the crystals, and binds one molecule of the reactants 5-phosphoribosyl-α-1-pyrophosphate (PRPP) and adenine or the product adenosine monophosphate (AMP) or the inhibitor adenosine diphosphate (ADP) in each active site. The individual subunit adopts an overall structure that resembles a 6-oxopurine phosphoribosyltransferase (PRTase) more than known APRTases implying that APRT functionality in Crenarchaeotae has its evolutionary origin in this family of PRTases. Only the N-terminal two-thirds of the polypeptide chain folds as a traditional type I PRTase with a five-stranded β-sheet surrounded by helices. The C-terminal third adopts an unusual three-helix bundle structure that together with the nucleobase-binding loop undergoes a conformational change upon binding of adenine and phosphate resulting in a slight contraction of the active site. The inhibitor ADP binds like the product AMP with both the α- and β-phosphates occupying the 5'-phosphoribosyl binding site. The enzyme shows activity over a wide pH range, and the kinetic and ligand binding properties depend on both pH and the presence/absence of phosphate in the buffers. A slow hydrolysis of PRPP to ribose 5-phosphate and pyrophosphate, catalyzed by the enzyme, may be facilitated by elements in the C-terminal three-helix bundle part of the protein.

Quantitative determination of benzo[a]pyrene in foodstuffs using benzo[a]pyrene[G-3H

International Nuclear Information System (INIS)

Masuda, Yoshito; Shimamura, Kyoko; Yano, Hiroshige

1977-01-01

A method for quantitative determination of nano gram level of benzo(a)pyrene (BP) in foodstuffs using tritiated BP( 3 H-BP) was described. Extracts from foodstuffs, having been added a certain amount of 3 H-BP, were fractionated by column chromatography on Florisil, and thinlayer chromatography on acetylated cellulose. Concentration and radio activity of BP in the final fraction were determined by fluorescence spectrometry and liquid scintillation. Recovery ratio of each experiment was obtained by comparing the radio activities of added 3 H-BP and separated BP. Concentration of BP in the sample analyzed was calculated from the amount of isolated BP and the recovery ratio in each experiment. A quantitative limit of BP by this method was 0.2 ppb when 50 g of sample was used. By this method, contents of BO in each sample of Tenpura oil, salad oil, flour, and polished rice were determined as 0.6, 0.2, 0.1 and < 0.1 ppb on average, respectively. (auth.)

Treatment of a Periodontic-Endodontic Lesion in a Patient with Aggressive Periodontitis.

Science.gov (United States)

Fahmy, Mina D; Luepke, Paul G; Ibrahim, Mohamed S; Guentsch, Arndt

2016-01-01

Case Description. This case report describes the successful management of a left mandibular first molar with a combined periodontic-endodontic lesion in a 35-year-old Caucasian woman with aggressive periodontitis using a concerted approach including endodontic treatment, periodontal therapy, and a periodontal regenerative procedure using an enamel matrix derivate. In spite of anticipated poor prognosis, the tooth lesion healed. This case report also discusses the rationale behind different treatment interventions. Practical Implication. Periodontic-endodontic lesions can be successfully treated if dental professionals follow a concerted treatment protocol that integrates endodontic and periodontic specialties. General dentists can be the gatekeepers in managing these cases.

Treatment of a Periodontic-Endodontic Lesion in a Patient with Aggressive Periodontitis

Directory of Open Access Journals (Sweden)

Mina D. Fahmy

2016-01-01

Full Text Available Case Description. This case report describes the successful management of a left mandibular first molar with a combined periodontic-endodontic lesion in a 35-year-old Caucasian woman with aggressive periodontitis using a concerted approach including endodontic treatment, periodontal therapy, and a periodontal regenerative procedure using an enamel matrix derivate. In spite of anticipated poor prognosis, the tooth lesion healed. This case report also discusses the rationale behind different treatment interventions. Practical Implication. Periodontic-endodontic lesions can be successfully treated if dental professionals follow a concerted treatment protocol that integrates endodontic and periodontic specialties. General dentists can be the gatekeepers in managing these cases.

Kinetic and thermodynamic study of the reaction catalyzed by glucose-6-phosphate dehydrogenase with nicotinamide adenine dinucleotide

International Nuclear Information System (INIS)

Martin del Campo, Julia S.; Patino, Rodrigo

2011-01-01

Research highlights: → The reaction catalyzed by one enzyme of the pentose phosphate pathway was studied. → A spectrophotometric method is proposed for kinetic and thermodynamic analysis. → The pH and the temperature influences are reported on physical chemical properties. → Relative concentrations of substrates are also important in the catalytic process. - Abstract: The enzyme glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) from Leuconostoc mesenteroides has a dual coenzyme specificity with oxidized nicotinamide adenine dinucleotide (NAD ox ) and oxidized nicotinamide adenine dinucleotide phosphate as electron acceptors. The G6PD coenzyme selection is determined by the metabolic cellular prevailing conditions. In this study a kinetic and thermodynamic analysis is presented for the reaction catalyzed by G6PD from L. mesenteroides with NAD ox as coenzyme in phosphate buffer. For this work, an in situ spectrophotometric technique was employed based on the detection of one product of the reaction. Substrate and coenzyme concentrations as well as temperature and pH effects were evaluated. The apparent equilibrium constant, the Michaelis constant, and the turnover number were determined as a function of each experimental condition. The standard transformed Gibbs energy of reaction was determined from equilibrium constants at different initial conditions. For the product 6-phospho-D-glucono-1,5-lactone, a value of the standard Gibbs energy of formation is proposed, Δ f G o = -1784 ± 5 kJ mol -1 .

Kinetic and thermodynamic study of the reaction catalyzed by glucose-6-phosphate dehydrogenase with nicotinamide adenine dinucleotide

Energy Technology Data Exchange (ETDEWEB)

Martin del Campo, Julia S. [Departamento de Fisica Aplicada, Centro de Investigacion y de Estudios Avanzados - Unidad Merida, Carretera antigua a Progreso Km. 6, A.P. 73 Cordemex, 97310, Merida, Yucatan (Mexico); Patino, Rodrigo, E-mail: rtarkus@mda.cinvestav.mx [Departamento de Fisica Aplicada, Centro de Investigacion y de Estudios Avanzados - Unidad Merida, Carretera antigua a Progreso Km. 6, A.P. 73 Cordemex, 97310, Merida, Yucatan (Mexico)

2011-04-20

Research highlights: {yields} The reaction catalyzed by one enzyme of the pentose phosphate pathway was studied. {yields} A spectrophotometric method is proposed for kinetic and thermodynamic analysis. {yields} The pH and the temperature influences are reported on physical chemical properties. {yields} Relative concentrations of substrates are also important in the catalytic process. - Abstract: The enzyme glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) from Leuconostoc mesenteroides has a dual coenzyme specificity with oxidized nicotinamide adenine dinucleotide (NAD{sub ox}) and oxidized nicotinamide adenine dinucleotide phosphate as electron acceptors. The G6PD coenzyme selection is determined by the metabolic cellular prevailing conditions. In this study a kinetic and thermodynamic analysis is presented for the reaction catalyzed by G6PD from L. mesenteroides with NAD{sub ox} as coenzyme in phosphate buffer. For this work, an in situ spectrophotometric technique was employed based on the detection of one product of the reaction. Substrate and coenzyme concentrations as well as temperature and pH effects were evaluated. The apparent equilibrium constant, the Michaelis constant, and the turnover number were determined as a function of each experimental condition. The standard transformed Gibbs energy of reaction was determined from equilibrium constants at different initial conditions. For the product 6-phospho-D-glucono-1,5-lactone, a value of the standard Gibbs energy of formation is proposed, {Delta}{sub f}G{sup o} = -1784 {+-} 5 kJ mol{sup -1}.

Transepithelial transfer of phenanthrene, but not of benzo[a]pyrene, is inhibited by fatty acids in the proximal intestine of rainbow trout (Oncorhynchus mykiss).

Science.gov (United States)

de Gelder, Stefan; Sundh, Henrik; Pelgrim, Thamar N M; Rasinger, Josef D; van Daal, Lotte; Flik, Gert; Berntssen, Marc H G; Klaren, Peter H M

2018-01-01

The inclusion of vegetable oils in aquafeeds introduces contaminating polycyclic aromatic hydrocarbons (PAHs) in salmonids. Since lipophilic PAHs solubilize in micelles composed of lipids, bile salts and fatty acids, dietary lipid composition can alter intestinal transepithelial PAH transfer. We studied the uptake of two PAHs, viz. benzo[a]pyrene (BaP) and phenanthrene (PHE), in rainbow trout (Oncorhynchus mykiss) intestine. We also investigated the effects of two fatty acids, viz. fish oil-derived eicosapentaenoic acid (EPA, 20:5n-3) and vegetable oil-derived oleic acid (18:1n-9) on intestinal uptake. Radiolabeled PAHs were solubilized in micelles composed of tritiated EPA and oleic acid, respectively, and administrated to intestinal segments mounted in Ussing chambers. In the absence of micelles, PHE accumulation was two times higher than BaP in the mucosal and serosal layers of proximal and distal intestine. Administration of PHE in micelles composed of oleic acid resulted in a 50% lower accumulation of PHE in the mucosal layers of the proximal intestine compared to EPA-composed micelles. Accumulation of EPA and oleic acid in the proximal intestinal mucosa correlated negatively with the transepithelial transfer of these fatty acids across the proximal intestinal epithelium. Transepithelial PHE transfer across the proximal intestine was reduced by 30% in co-exposure with EPA-composed micelles compared to 80% with oleic acid micelles. BaP was not transferred across the intestine. We conclude that the lipid composition of an aquafeed is an important determinant of PAH bioavailability. Therefore, lipid composition should be an important consideration in choosing vegetable oils as alternatives for fish oil in aquafeeds. Copyright © 2017 Elsevier Inc. All rights reserved.

Benzo[a]pyrene and Benzo[k]fluoranthene in Some Processed Fish and Fish Products

Directory of Open Access Journals (Sweden)

Olatunde S. Olatunji

2015-01-01

Full Text Available In this study, the concentration levels of the probable carcinogenic PAH fractions, benzo[a]pyrene (BaP and benzo[k]fluoranthrene (BkF in fillets of some processed fish species were investigated. Fish species comprising Merluccius poli (hake, Tyrsites atun (snoek, Seriola lalandi (yellow-tail and Brama brama (angel fish were bought in fish shops at Gordon’s Bay, Western Cape, South Africa. The fish were gutted, filleted and prepared for edibility by frying, grilling and boiling. Polycyclic aromatic hydrocarbons were extracted from each homogenized fish sample, cleaned-up using solid phase extraction (SPE, and analysed for the PAH fractions, BaP and BkF using a Gas Chromatograph coupled with a Flame Ionization Detector (GC-FID. The sum of the two PAHs (∑2PAH i.e., BaP and BkF ranged between 0.56 and 1.46 µg/kg, in all boiled, grilled and fried fish species. The fried fish extracts showed significantly higher (p < 0.05 abundance of ∑2PAH, than grilled and boiled fish. Dietary safety and PAHs toxicity was also discussed.

Metabolism of benzo(a)pyrene, N-nitrosomethylamine, and N-nitrosopyrrolidine and identification of the major carcinogen-DNA adducts formed in cultured human esophagus

DEFF Research Database (Denmark)

Harris, Curtis C.; Autrup, Herman; Stoner, Gary D.

1979-01-01

The wide variation in the world-wide incidence of esophageal carcinoma suggests that environmental agents including chemicals cause this cancer. Since the interaction between chemical procarcinogens and human esophagus has not been studied previously, we examined the metabolic fate of benzo......(a)pyrene (BP), N-nitrosodimethylamine (DMN), and A/-nitrosopyrrolidine in cultured nontumorous esophagus from two patients with and six patients without esophageal carcinoma. Esophageal explants were cultured in a chemically defined medium for 7 days prior to adding [3H]BP (1.5 JUM),[14C]DMN (100 /IM), or [14C...

BENZO[A]PYRENE AND ITS K-REGION DIOL INDUCE DNA DAMAGE IN C3H10T1/2C18 CELLS AS MEASURED BY THE ALKALINE SINGLE CELL GEL (COMET) ASSAY

Science.gov (United States)

160. Benzo[a]pyrene and its K-region diol induce DNA damage in C3HlOTl/2Cl8 cells as measured by the alkaline single cell gel (Comet) assay In a continuing series of studies on the genotoxicity ofK-region dihydrodiols of polycyclic aromatic hydrocarbons, we have repo...

Base Sequence Context Effects on Nucleotide Excision Repair

Directory of Open Access Journals (Sweden)

Yuqin Cai

2010-01-01

Full Text Available Nucleotide excision repair (NER plays a critical role in maintaining the integrity of the genome when damaged by bulky DNA lesions, since inefficient repair can cause mutations and human diseases notably cancer. The structural properties of DNA lesions that determine their relative susceptibilities to NER are therefore of great interest. As a model system, we have investigated the major mutagenic lesion derived from the environmental carcinogen benzo[a]pyrene (B[a]P, 10S (+-trans-anti-B[a]P-2-dG in six different sequence contexts that differ in how the lesion is positioned in relation to nearby guanine amino groups. We have obtained molecular structural data by NMR and MD simulations, bending properties from gel electrophoresis studies, and NER data obtained from human HeLa cell extracts for our six investigated sequence contexts. This model system suggests that disturbed Watson-Crick base pairing is a better recognition signal than a flexible bend, and that these can act in concert to provide an enhanced signal. Steric hinderance between the minor groove-aligned lesion and nearby guanine amino groups determines the exact nature of the disturbances. Both nearest neighbor and more distant neighbor sequence contexts have an impact. Regardless of the exact distortions, we hypothesize that they provide a local thermodynamic destabilization signal for repair.

A Generative Probabilistic Model and Discriminative Extensions for Brain Lesion Segmentation - With Application to Tumor and Stroke

DEFF Research Database (Denmark)

Menze, Bjoern H.; Van Leemput, Koen; Lashkari, Danial

2016-01-01

jointly from the image data. It delineates lesion areas individually in each channel, allowing for differences in lesion appearance across modalities, an important feature of many brain tumor imaging sequences. We also propose discriminative model extensions to map the output of the generative model......), to estimate the label map for a new image. Our model augments the probabilistic atlas of the healthy tissues with a latent atlas of the lesion. We derive an estimation algorithm with closed-form EM update equations. The method extracts a latent atlas prior distribution and the lesion posterior distributions...

The effect of purine phosphonomethoxyalkyl derivatives on DNA synthesis in Cho Chinese hamster cells

Energy Technology Data Exchange (ETDEWEB)

Stetina, R [Institute of Experimental Medicine, Laboratory of Developmental Toxicology, Academy of Sciences of Czech Republic, 51783 Olesnice v Orlickych horach (Czech Republic); Votruba, I; Holy, A; Merta, A [Institute of Organic Chemistry and Biochemistry, Academy of Sciences of Czech Republic (Czech Republic)

1994-12-31

The inhibition of incorporation of {sup 3}H-thymidine and the changes of the rate of nascent DNA chain elongation were investigated in Cho Chinese hamster cells treated with (S)-(3-hydroxy-2-phosphonomethoxypropyl) (HPMP) and N-(2-phosphonomethoxyethyl) (PME) derivatives of adenine (A), guanine (G) and 2,6-diaminopurine (DAP). No direct correlation was observed in PME and HPMP derivatives between cytotoxicity, inhibition of {sup 3}H-thymidine incorporation and inhibition of nascent DNA chain elongation. The highest cytotoxicity and inhibition of DNA synthesis were caused by PMEG. The limited extent of inhibition of DNA elongation was encountered in the case of HPMPG and HPMPA. With PMEA, weak inhibition of elongation of DNA was observed only after a prolonged exposure (6 h). None of the investigated drugs induced DNA breaks. (author) 4 figs., 23 refs.

Formation of quinones by one-electron oxidation in the metabolism of benzo[a]pyrene and 6-fluorobenzo[a]pyrene

International Nuclear Information System (INIS)

Cavalieri, E.; Wong, A.; Cremonesi, P.; Warner, C.; Rogan, E.

1986-01-01

Metabolic activation of polycyclic aromatic hydrocarbons (PAH), as well as other chemical carcinogens, occurs by two major pathways: One-electron oxidation and two-electron oxidation, or monooxygenation. One-electron oxidation generates radical cations or radicals, depending on the molecule in which the oxidation occurs, whereas two-electron oxidation produces oxygenated metabolites. Radical cations of PAH are ultimate electrophilic metabolites capable of binding to cellular macromolecules to initiate the tumor process. In this paper the authors will provide evidence that one-electron oxidation is involved not only in PAH carcinogenesis, but also in the formation of certain metabolites. Metabolism of benzo[a]pyrene (BP) by cytochrome P-450 monooxygenase yields three classes of products: phenols, dihydrodiols and the quinones, 1,6-, 3,6- and 6,12- dione

Determination of benzo[a]pyrene in edible oils using phase-transfer-catalyst-assisted saponification and supramolecular solvent microextraction coupled to HPLC with fluorescence detection.

Science.gov (United States)

Wang, Jin; Liu, Laping; Shi, Ludi; Yi, Tingquan; Wen, Yuxia; Wang, Juanli; Liu, Shuhui

2017-01-01

For the analysis of edible oils, saponification is well known as a useful method for eliminating oil matrices. The conventional approach is conducted with alcoholic alkali; it consumes a large volume of organic solvents and impedes the retrieval of analytes by microextraction. In this study, a low-organic-solvent-consuming method has been developed for the analysis of benzo[a]pyrene in edible oils by high-performance liquid chromatography with fluorescence detection. Sample treatment involves aqueous alkaline saponification, assisted by a phase-transfer catalyst, and selective in situ extraction of the analyte with a supramolecular solvent. Comparison of the chromatograms of the oil extracts obtained by different microextraction methods showed that the supramolecular solvent has a better clean-up effect for the unsaponifiable matter from oil matrices. The method offered excellent linearity over a range of 0.03- 5.0 ng mL -1 (r > 0.999). Recovery rates varied from 94 to 102% (RSDs <5.0%). The detection limit and quantification limit were 0.06 and 0.19 μg kg -1 , respectively. The proposed method was applied for the analysis of 52 edible oils collected online in China; the analyte contents of 23 tested oil samples exceeded the maximum limit of 2 μg kg -1 for benzo[a]pyrene set by the Commission Regulation of the European Union. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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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

Interstrand cross-links arising from strand breaks at true abasic sites in duplex DNA

Science.gov (United States)

Yang, Zhiyu; Price, Nathan E.; Johnson, Kevin M.

2017-01-01

Abstract Interstrand cross-links are exceptionally bioactive DNA lesions. Endogenous generation of interstrand cross-links in genomic DNA may contribute to aging, neurodegeneration, and cancer. Abasic (Ap) sites are common lesions in genomic DNA that readily undergo spontaneous and amine-catalyzed strand cleavage reactions that generate a 2,3-didehydro-2,3-dideoxyribose sugar remnant (3’ddR5p) at the 3’-terminus of the strand break. Interestingly, this strand scission process leaves an electrophilic α,β-unsaturated aldehyde residue embedded within the resulting nicked duplex. Here we present evidence that 3’ddR5p derivatives generated by spermine-catalyzed strand cleavage at Ap sites in duplex DNA can react with adenine residues on the opposing strand to generate a complex lesion consisting of an interstrand cross-link adjacent to a strand break. The cross-link blocks DNA replication by ϕ29 DNA polymerase, a highly processive polymerase enzyme that couples synthesis with strand displacement. This suggests that 3’ddR5p-derived cross-links have the potential to block critical cellular DNA transactions that require strand separation. LC-MS/MS methods developed herein provide powerful tools for studying the occurrence and properties of these cross-links in biochemical and biological systems. PMID:28531327

Degradation of Adenine on the Martian Surface in the Presence of Perchlorates and Ionizing Radiation: A Reflectron Time-of-flight Mass Spectrometric Study

Energy Technology Data Exchange (ETDEWEB)

Góbi, Sándor; Bergantini, Alexandre; Kaiser, Ralf I., E-mail: ralfk@hawaii.edu [Department of Chemistry, University of Hawaii at Mānoa, Honolulu, HI 96822 (United States)

2017-04-01

The aim of the present work is to unravel the radiolytic decomposition of adenine (C{sub 5}H{sub 5}N{sub 5}) under conditions relevant to the Martian surface. Being the fundamental building block of (deoxy)ribonucleic acids, the possibility of survival of this biomolecule on the Martian surface is of primary importance to the astrobiology community. Here, neat adenine and adenine–magnesium perchlorate mixtures were prepared and irradiated with energetic electrons that simulate the secondary electrons originating from the interaction of the galactic cosmic rays with the Martian surface. Perchlorates were added to the samples since they are abundant—and therefore relevant oxidizers on the surface of Mars—and they have been previously shown to facilitate the radiolysis of organics such as glycine. The degradation of the samples were monitored in situ via Fourier transformation infrared spectroscopy and the electron ionization quadruple mass spectrometric method; temperature-programmed desorption profiles were then collected by means of the state-of-the-art single photon photoionization reflectron time-of-flight mass spectrometry (PI-ReTOF-MS), allowing for the detection of the species subliming from the sample. The results showed that perchlorates do increase the destruction rate of adenine by opening alternative reaction channels, including the concurrent radiolysis/oxidation of the sample. This new pathway provides a plethora of different radiolysis products that were identified for the first time. These are carbon dioxide (CO{sub 2}), isocyanic acid (HNCO), isocyanate (OCN{sup −}), carbon monoxide (CO), and nitrogen monoxide (NO); an oxidation product containing carbonyl groups (R{sub 1}R{sub 2}–C=O) with a constrained five-membered cyclic structure could also be observed. Cyanamide (H{sub 2}N–C≡N) was detected in both irradiated samples as well.

Degradation of Adenine on the Martian Surface in the Presence of Perchlorates and Ionizing Radiation: A Reflectron Time-of-flight Mass Spectrometric Study

International Nuclear Information System (INIS)

Góbi, Sándor; Bergantini, Alexandre; Kaiser, Ralf I.

2017-01-01

The aim of the present work is to unravel the radiolytic decomposition of adenine (C 5 H 5 N 5 ) under conditions relevant to the Martian surface. Being the fundamental building block of (deoxy)ribonucleic acids, the possibility of survival of this biomolecule on the Martian surface is of primary importance to the astrobiology community. Here, neat adenine and adenine–magnesium perchlorate mixtures were prepared and irradiated with energetic electrons that simulate the secondary electrons originating from the interaction of the galactic cosmic rays with the Martian surface. Perchlorates were added to the samples since they are abundant—and therefore relevant oxidizers on the surface of Mars—and they have been previously shown to facilitate the radiolysis of organics such as glycine. The degradation of the samples were monitored in situ via Fourier transformation infrared spectroscopy and the electron ionization quadruple mass spectrometric method; temperature-programmed desorption profiles were then collected by means of the state-of-the-art single photon photoionization reflectron time-of-flight mass spectrometry (PI-ReTOF-MS), allowing for the detection of the species subliming from the sample. The results showed that perchlorates do increase the destruction rate of adenine by opening alternative reaction channels, including the concurrent radiolysis/oxidation of the sample. This new pathway provides a plethora of different radiolysis products that were identified for the first time. These are carbon dioxide (CO 2 ), isocyanic acid (HNCO), isocyanate (OCN − ), carbon monoxide (CO), and nitrogen monoxide (NO); an oxidation product containing carbonyl groups (R 1 R 2 –C=O) with a constrained five-membered cyclic structure could also be observed. Cyanamide (H 2 N–C≡N) was detected in both irradiated samples as well.

Multiple-lesion track-structure model

International Nuclear Information System (INIS)

Wilson, J.W.; Cucinotta, F.A.; Shinn, J.L.

1992-03-01

A multilesion cell kinetic model is derived, and radiation kinetic coefficients are related to the Katz track structure model. The repair-related coefficients are determined from the delayed plating experiments of Yang et al. for the C3H10T1/2 cell system. The model agrees well with the x ray and heavy ion experiments of Yang et al. for the immediate plating, delaying plating, and fractionated exposure protocols employed by Yang. A study is made of the effects of target fragments in energetic proton exposures and of the repair-deficient target-fragment-induced lesions

Robust segmentation of focal lesions on multi-sequence MRI in multiple sclerosis

International Nuclear Information System (INIS)

Garcia-Lorenzo, Daniel

2010-01-01

Multiple sclerosis (MS) affects around 80.000 people in France. Magnetic resonance imaging (MRI) is an essential tool for diagnosis of MS and MRI-derived surrogate markers such as MS lesion volumes are often used as measures in MS clinical trials for the development of new treatments. The manual segmentation of these MS lesions is a time-consuming task that shows high inter- and intra-rater variability. We developed an automatic work flow for the segmentation of focal MS lesions on MRI. The segmentation method is based on the robust estimation of a parametric model of the intensities of the brain; lesions are detected as outliers to the model. We proposed two methods to include spatial information in the segmentation using mean shift and graph cut. We performed a quantitative evaluation of our work flow using synthetic and clinical images of two different centers to verify its accuracy and robustness. (author)

Rationalizing the structural variability of the exocyclic amino groups in nucleobases and their metal complexes: cytosine and adenine.

Science.gov (United States)

Fonseca Guerra, Célia; Sanz Miguel, Pablo J; Cebollada, Andrea; Bickelhaupt, F Matthias; Lippert, Bernhard

2014-07-28

The exocyclic amino groups of cytosine and adenine nucleobases are normally almost flat, with the N atoms essentially sp(2) hybridized and the lone pair largely delocalized into the heterocyclic rings. However, a change to marked pyramidality of the amino group (N then sp(3) hybridized, lone pair essentially localized at N) occurs during i) involvement of an amino proton in strong hydrogen bonding donor conditions or ii) with monofunctional metal coordination following removal of one of the two protons. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Specific bone region localization of osteolytic versus osteoblastic lesions in a patient-derived xenograft model of bone metastatic prostate cancer

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Takeshi Hirata

2016-10-01

Conclusion: PCSD1 cells reproducibly induced bone loss leading to osteolytic lesions at the ends of the femur, and, in contrast, induced aberrant bone formation leading to osteoblastic lesions along the femur shaft. Therefore, the interaction of PCSD1 cells with different bone region-specific microenvironments specified the type of bone lesion. Our approach can be used to determine if different bone regions support more therapy resistant tumor growth, thus, requiring novel treatments.

Impact of Lesion Length on Functional Significance in Intermediate Coronary Lesions

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Morteza Safi

2017-07-01

Full Text Available Introduction: The present study aimed at assessing the role of lesion length in predicting Fractional Flow Reserve (FFR value for physiological evaluation of intermediate coronary lesions.Methods: In the current study, 68 patients with 83 coronary lesions were enrolled. All of the patients in this study underwent routine coronary angiography, according to appropriate indications. To evaluate physiologically significant intermediate coronary stenosis (defined between 40% and 70% on visual estimation, the Fractional Flow Reserve (FFR study was performed and the Quantitative Coronary Angiography (QCA data were also assessed for measurement of lesion length. The correlation between QCA data and FFR values was also examined.Results: Eighty-three lesions were evaluated from 68 patients. Stenosis was considered physiologically significant when FFR was lower than 0.75. The FFR was significant in twelve lesions (14.5%. There was a negative correlation between FFR value and lesion length (r = -0.294 and P = 0.013. Moreover, lesion length in physiologically significant FFR group (21.07  ± 6.9 was greater than that of the non-significant FFR group (15.23 ± 6.5 (P value < 0.05. Furthermore, the correlation between QCA data and FFR values was also investigated, yet, there was only a positive correlation between FFR and Minimum Luminal Diameter (MLD values (r = 0.248 and P value = 0.04. The Receiver Operating Characteristic (ROC curve analysis for predicting the significant FFR value demonstrated that a lesion length greater than 17.5 mm was the best cut-off point for prediction of the significant FFR value with acceptable sensitivity and specificity of 83.3% and 68.8%, respectively.Conclusions: There is a negative correlation between lesion length and FFR value in intermediate coronary lesions. In addition, a lesion length greater than 17.5 mm is the best cut- off point for prediction of significant FFR values.

Metal-adeninate vertices for the construction of an exceptionally porous metal-organic framework.

Science.gov (United States)

An, Jihyun; Farha, Omar K; Hupp, Joseph T; Pohl, Ehmke; Yeh, Joanne I; Rosi, Nathaniel L

2012-01-03

Metal-organic frameworks comprising metal-carboxylate cluster vertices and long, branched organic linkers are the most porous materials known, and therefore have attracted tremendous attention for many applications, including gas storage, separations, catalysis and drug delivery. To increase metal-organic framework porosity, the size and complexity of linkers has increased. Here we present a promising alternative strategy for constructing mesoporous metal-organic frameworks that addresses the size of the vertex rather than the length of the organic linker. This approach uses large metal-biomolecule clusters, in particular zinc-adeninate building units, as vertices to construct bio-MOF-100, an exclusively mesoporous metal-organic framework. Bio-MOF-100 exhibits a high surface area (4,300 m(2) g(-1)), one of the lowest crystal densities (0.302 g cm(-3)) and the largest metal-organic framework pore volume reported to date (4.3 cm(3) g(-1)).

Animal models of pediatric chronic kidney disease. Is adenine intake an appropriate model?

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Débora Claramunt

2015-11-01

Full Text Available Pediatric chronic kidney disease (CKD has peculiar features. In particular, growth impairment is a major clinical manifestation of CKD that debuts in pediatric age because it presents in a large proportion of infants and children with CKD and has a profound impact on the self-esteem and social integration of the stunted patients. Several factors associated with CKD may lead to growth retardation by interfering with the normal physiology of growth plate, the organ where longitudinal growth rate takes place. The study of growth plate is hardly possible in humans and justifies the use of animal models. Young rats made uremic by 5/6 nephrectomy have been widely used as a model to investigate growth retardation in CKD. This article examines the characteristics of this model and analyzes the utilization of CKD induced by high adenine diet as an alternative research protocol.

Spinal focal lesion detection in multiple myeloma using multimodal image features

Science.gov (United States)

Fränzle, Andrea; Hillengass, Jens; Bendl, Rolf

2015-03-01

Multiple myeloma is a tumor disease in the bone marrow that affects the skeleton systemically, i.e. multiple lesions can occur in different sites in the skeleton. To quantify overall tumor mass for determining degree of disease and for analysis of therapy response, volumetry of all lesions is needed. Since the large amount of lesions in one patient impedes manual segmentation of all lesions, quantification of overall tumor volume is not possible until now. Therefore development of automatic lesion detection and segmentation methods is necessary. Since focal tumors in multiple myeloma show different characteristics in different modalities (changes in bone structure in CT images, hypointensity in T1 weighted MR images and hyperintensity in T2 weighted MR images), multimodal image analysis is necessary for the detection of focal tumors. In this paper a pattern recognition approach is presented that identifies focal lesions in lumbar vertebrae based on features from T1 and T2 weighted MR images. Image voxels within bone are classified using random forests based on plain intensities and intensity value derived features (maximum, minimum, mean, median) in a 5 x 5 neighborhood around a voxel from both T1 and T2 weighted MR images. A test data sample of lesions in 8 lumbar vertebrae from 4 multiple myeloma patients can be classified at an accuracy of 95% (using a leave-one-patient-out test). The approach provides a reasonable delineation of the example lesions. This is an important step towards automatic tumor volume quantification in multiple myeloma.

Studies on the analysis of benzo(a)pyrene and its metabolites in biological samples by using high performance liquid chromatography/fluorescence detection and gas chromatography/mass spectrometry

International Nuclear Information System (INIS)

Lee, Won; Hong, Jee Eun; Shin, Hye Seung; Pyo, Hee Soo; Kim, Yun Je

2003-01-01

An analytical method the determination of benzo(a)pyrene (BaP) and its hydroxylated metabolites, 1-hydroxybenzo(a)pyrene (1-OHBaP), 3-hydroxybenzo(a)pyrene (3-OHBaP), benzo(a)pyrene-4,5-dihydrodial(4,5-diolBaP) and benzo(a)pyrene-7,8-dihydrodiol (7,8-diolBaP), in rat urine and plasma has been developed by HPLC/FLD and GC/MS. The derivatization with alkyl iodide was employed to improve the resolution and the detection of two mono hydroxylated metabolites, 1-OHBaP and 3-OHBaP, in LC and GC. BaP and its four metabolites in spiked urine were successfully separated by gradient elution on reverse phase ODS C 18 column (4.6 mm I.D., 100 mm length, particle size 5μm) using a binary mixture of MeOH/H 2 O (85/15, v/v) as mobile phase after ethylation at 90 .deg. C for 10 min. The extraction recoveries of BaP and its metabolites in spiked samples with liquid-liquid extraction, which was better than solid phase extraction, were in the range of 90.3-101.6% in n-hexane for urine and 95.7-106.3% in acetone for plasma, respectively. The calibration curves has shown good linearity with the correlation coefficients (R 2 ) varying from 0.992 to 1.000 for urine and from 0.996 to 1.000 for plasma, respectively. The detection limits of all analytes were obtained in the range of 0.01-0.1 ng/mL for urine and 0.1-0.4ng/mL for plasma, respectively. The metabolites of BaP were excreted as mono hydroxy and dihydrodiol forms after intraperitoneal infection of 20 mg/kg of BaP to rats. The total amounts of BaP and four metabolites excreted in dosed rat urine were 3.79 ng over the 0 - 96 hr period from administration and the excretional recovery was less than 0.065% of the injection amounts of BaP. The proposed method was successfully applied to the determination of BaP and its hydroxylated metabolites in rat urine and plasma for the pharmacokinetic studies

Spectral studies of lanthanide-nucleic acid component interaction: complexes of adenine, adenosine, adenosine 5'-mono-, adenosine 5'-di- and adenosine 5' tri-phosphates with praseodymium(III)

International Nuclear Information System (INIS)

Joseph, George; Anjaiah, K.; Misra, S.N.

1990-01-01

The interactions of adenine, adenosine, adenosine 5'-mono-, adenosine 5'-di-and adenosine 5'-tri-phosphates with praseodymium(III) have been studied in different stoichiometries and at varying hydrogen ion concentrations by absorption spectral studies. The sharp bands in the spectra have been individually analysed by Gaussian curve analysis, and various spectral parameters have been computed using partial and multiple regression methods on an HP-1000/45 computer. The changes in and the magnitudes of these parameters have been correlated with the degrees of outer- and inner-sphere coordination around praseodymium(III). Crystalline complexes of the type: Pr(nucleotide) 2 (H 2 O) 2 (where nucleotide = AMP, ADP and ATP) have been characterized on the basis of analytical, IR and 1 H NMR spectral data. These studies indicate that the binding of the nucleotide is through phosphoric oxygen. These complexes in aqueous medium show significant ionization which supports the observed weak 4f-4f bands, lower values of nephelauxetic effect and the parameters derived from coulombic and spin-orbit interactions. (author). 3 t abs., 28 refs

Intravoxel Incoherent Motion MR Imaging in the Differentiation of Benign and Malignant Sinonasal Lesions: Comparison with Conventional Diffusion-Weighted MR Imaging.

Science.gov (United States)

Xiao, Z; Tang, Z; Qiang, J; Wang, S; Qian, W; Zhong, Y; Wang, R; Wang, J; Wu, L; Tang, W; Zhang, Z

2018-01-25

Intravoxel incoherent motion is a promising method for the differentiation of sinonasal lesions. This study aimed to evaluate the value of intravoxel incoherent motion in the differentiation of benign and malignant sinonasal lesions and to compare the diagnostic performance of intravoxel incoherent motion with that of conventional DWI. One hundred thirty-one patients with histologically proved solid sinonasal lesions (56 benign and 75 malignant) who underwent conventional DWI and intravoxel incoherent motion were recruited in this study. The diffusion coefficient ( D ), pseudodiffusion coefficient ( D *), and perfusion fraction ( f ) values derived from intravoxel incoherent motion and ADC values derived from conventional DWI were measured and compared between the 2 groups using the Student t test. Receiver operating characteristic curve analysis, logistic regression analysis, and 10-fold cross-validation were performed to evaluate the diagnostic performance of single-parametric and multiparametric models. The mean ADC and D values were significantly lower in malignant sinonasal lesions than in benign sinonasal lesions (both P benign and malignant sinonasal lesions. © 2018 by American Journal of Neuroradiology.

Structural Probing of Off-Target G Protein-Coupled Receptor Activities within a Series of Adenosine/Adenine Congeners

Science.gov (United States)

Paoletta, Silvia; Tosh, Dilip K.; Salvemini, Daniela; Jacobson, Kenneth A.

2014-01-01

We studied patterns of off-target receptor interactions, mostly at G protein-coupled receptors (GPCRs) in the µM range, of nucleoside derivatives that are highly engineered for nM interaction with adenosine receptors (ARs). Because of the considerable interest of using AR ligands for treating diseases of the CNS, we used the Psychoactive Drug Screening Program (PDSP) for probing promiscuity of these adenosine/adenine congeners at 41 diverse receptors, channels and a transporter. The step-wise truncation of rigidified, trisubstituted (at N6, C2, and 5′ positions) nucleosides revealed unanticipated interactions mainly with biogenic amine receptors, such as adrenergic receptors and serotonergic receptors, with affinities as high as 61 nM. The unmasking of consistent sets of structure activity relationship (SAR) at novel sites suggested similarities between receptor families in molecular recognition. Extensive molecular modeling of the GPCRs affected suggested binding modes of the ligands that supported the patterns of SAR at individual receptors. In some cases, the ligand docking mode closely resembled AR binding and in other cases the ligand assumed different orientations. The recognition patterns for different GPCRs were clustered according to which substituent groups were tolerated and explained in light of the complementarity with the receptor binding site. Thus, some likely off-target interactions, a concern for secondary drug effects, can be predicted for analogues of this set of substructures, aiding the design of additional structural analogues that either eliminate or accentuate certain off-target activities. Moreover, similar analyses could be performed for unrelated structural families for other GPCRs. PMID:24859150

Human papillomavirus in oral lesions Virus papiloma humano en lesiones orales

Directory of Open Access Journals (Sweden)

Joaquín V. Gónzalez

2007-08-01

Full Text Available Growing evidence suggests a role for human papillomavirus (HPV in oral cancer; however its involvement is still controversial. This study evaluates the frequency of HPV DNA in a variety of oral lesions in patients from Argentina. A total of 77 oral tissue samples from 66 patients were selected (cases; the clinical-histopathological diagnoses corresponded to: 11 HPV- associated benign lesions, 8 non-HPV associated benign lesions, 33 premalignant lesions and 25 cancers. Sixty exfoliated cell samples from normal oral mucosa were used as controls. HPV detection and typing were performed by polymerase chain reaction (PCR using primers MY09, 11, combined with RFLP or alternatively PCR using primers GP5+, 6+ combined with dot blot hybridization. HPV was detected in 91.0% of HPV- associated benign lesions, 14.3% of non-HPV associated benign lesions, 51.5% of preneoplasias and 60.0% of cancers. No control sample tested HPV positive. In benign HPV- associated lesions, 30.0% of HPV positive samples harbored high-risk types, while in preneoplastic lesions the value rose to 59.9%. In cancer lesions, HPV detection in verrucous carcinoma was 88.9% and in squamous cell carcinoma 43.8%, with high-risk type rates of 75.5% and 85.6%, respectively. The high HPV frequency detected in preneoplastic and neoplastic lesions supports an HPV etiological role in at least a subset of oral cancers.Crecientes evidencias sugieren que el virus Papiloma humano (HPV tiene un rol en el cáncer oral; sin embargo su participación es todavía controvertida. Este estudio evalúa la frecuencia de ADN de HPV en una variedad de lesiones orales de pacientes de Argentina. Se seleccionaron 77 muestras de tejido oral de 66 pacientes (casos; el diagnóstico histo-patológico correspondió a: 11 lesiones benignas asociadas a HPV, 8 lesiones benignas no asociadas a HPV, 33 lesiones premalignas y 25 cánceres. Como controles se usaron 60 muestras de células exfoliadas de mucosa oral normal. La

Intraosseous osteolytic lesions

Energy Technology Data Exchange (ETDEWEB)

Adler, C.P.; Wenz, W.

1981-10-01

Any pathological damage occurring in a bone will produce either an osteolytic or osteosclerotic lesion which can be seen in the macroscopic specimen as well as in the roentgenogram. Various bone lesions may lead to local destructions of the bone. An osteoma or osteoplastic osteosarcoma produces an osteosclerotic lesion showing a dense mass in the roentgenogram; a chondroblastoma or an osteoclastoma, on the other hand, induces an osteolytic focal lesion. This paper presents examples of different osteolytic lesions of the humerus. An osteolytic lesion seen in the roentgenogram may be either produced by an underlying non-ossifying fibroma of the bone, by fibrous dysplasia, osteomyelitis or Ewing's sarcoma. Differential diagnostic considerations based on the radiological picture include eosinophilic bone granuloma, juvenile or aneurysmal bone cyst, multiple myeloma or bone metastases. Serious differential diagnostic problems may be involved in case of osteolytic lesions occurring in the humerus. Cases of this type involving complications have been reported and include the presence of an teleangiectatic osteosarcoma as well as that of a hemangiosarcoma of the bone.

Periodontal bone lesions

International Nuclear Information System (INIS)

Linden, L.W.J. van der.

1985-01-01

In the course of life the periodontum is subject to changes which may be physiological or pathological. Intraoral radiographs give insight into the hard structures of the dentomaxillar region and provides information on lesions in the bone of the periodontum in that they show radiopacities and radiolucencies caused by such lesions. In this thesis the relation is investigated between the true shape and dimensions of periodontal bone lesions and their radiographic images. A method is developed and tested of making standardized and reproducible radiographs suitable for longitudinal studies of periodontal lesions. Also the possibility is demonstrated of an objective and reproducible interpretation of radiographic characteristics of periodontal bone lesions. (Auth.)

Computerized tomography of orbital lesions

International Nuclear Information System (INIS)

Kuroiwa, Mayumi

1981-01-01

Two different types of computerized tomography scanners (CT scanner), i.e. a whole-body CT scanner (GE-CT/T8800) and a cerebral CT scanner (EMI-1010), were compared in the assessment and diagnosis of various orbital lesions. The whole-body CT scanner was found to be advantageous over the cerebral CT scanner for the following reasons: (1) CT images were more informative due to thinner slices associated with smaller-sized and larger-numbered matrices; (2) less artifacts derived from motion of the head or eyeball were produced because of the shorter scanning time; (3) with a devised gantry, coronal dissections were available whenever demanded. (author)

Managing Carious Lesions

DEFF Research Database (Denmark)

Schwendicke, F; Frencken, J E; Bjørndal, L

2016-01-01

should be prioritized, while in shallow or moderately deep lesions, restoration longevity becomes more important. For teeth with shallow or moderately deep cavitated lesions, carious tissue removal is performed according toselective removal to firm dentine.In deep cavitated lesions in primary......The International Caries Consensus Collaboration undertook a consensus process and here presents clinical recommendations for carious tissue removal and managing cavitated carious lesions, including restoration, based on texture of demineralized dentine. Dentists should manage the disease dental...

Human papillomavirus in oral lesions Virus papiloma humano en lesiones orales

OpenAIRE

Joaquín V. Gónzalez; Rafael A. Gutiérrez; Alicia Keszler; Maria Del Carmen Colacino; Lidia V. Alonio; Angélica R. Teyssie; Maria Alejandra Picconi

2007-01-01

Growing evidence suggests a role for human papillomavirus (HPV) in oral cancer; however its involvement is still controversial. This study evaluates the frequency of HPV DNA in a variety of oral lesions in patients from Argentina. A total of 77 oral tissue samples from 66 patients were selected (cases); the clinical-histopathological diagnoses corresponded to: 11 HPV- associated benign lesions, 8 non-HPV associated benign lesions, 33 premalignant lesions and 25 cancers. Sixty exfoliated cell ...

Liquid biopsy in the diagnosis of HPV DNA in breast lesions.

Science.gov (United States)

Carolis, Sabrina De; Pellegrini, Alice; Santini, Donatella; Ceccarelli, Claudio; De Leo, Antonio; Alessandrini, Federica; Arienti, Chiara; Pignatta, Sara; Tesei, Anna; Mantovani, Vilma; Zamagni, Claudio; Taffurelli, Mario; Sansone, Pasquale; Bonafé, Massimiliano; Cricca, Monica

2018-02-01

HPV DNA has never been investigated in nipple discharges (ND) and serum-derived extracellular vesicles, although its presence has been reported in ductal lavage fluids and blood specimens. We analyzed 50 ND, 22 serum-derived extracellular vesicles as well as 51 pathologic breast tissues for the presence of 16 HPV DNA types. We show that the presence of HPV DNA in the ND is predictive of HPV DNA-positive breast lesions and that HPV DNA is more represented in intraductal papillomas. We also show the presence of HPV DNA in the serum-derived extracellular vesicles. Our data supports the use of liquid biopsy to detect HPV DNA in breast pathology.

Interconnection of Key Microbial Functional Genes for Enhanced Benzo[a]pyrene Biodegradation in Sediments by Microbial Electrochemistry.

Science.gov (United States)

Yan, Zaisheng; He, Yuhong; Cai, Haiyuan; Van Nostrand, Joy D; He, Zhili; Zhou, Jizhong; Krumholz, Lee R; Jiang, He-Long

2017-08-01

Sediment microbial fuel cells (SMFCs) can stimulate the degradation of polycyclic aromatic hydrocarbons in sediments, but the mechanism of this process is poorly understood at the microbial functional gene level. Here, the use of SMFC resulted in 92% benzo[a]pyrene (BaP) removal over 970 days relative to 54% in the controls. Sediment functions, microbial community structure, and network interactions were dramatically altered by the SMFC employment. Functional gene analysis showed that c-type cytochrome genes for electron transfer, aromatic degradation genes, and extracellular ligninolytic enzymes involved in lignin degradation were significantly enriched in bulk sediments during SMFC operation. Correspondingly, chemical analysis of the system showed that these genetic changes resulted in increases in the levels of easily oxidizable organic carbon and humic acids which may have resulted in increased BaP bioavailability and increased degradation rates. Tracking microbial functional genes and corresponding organic matter responses should aid mechanistic understanding of BaP enhanced biodegradation by microbial electrochemistry and development of sustainable bioremediation strategies.

Adenine phosphoribosyltransferase from Sulfolobus solfataricus is an enzyme with unusual kinetic properties and a crystal structure that suggests it evolved from a 6-oxopurine phosphoribosyltransferase

DEFF Research Database (Denmark)

Jensen, Kaj Frank; Hansen, Michael Riis; Jensen, Kristine Steen

2015-01-01

The adenine phosphoribosyltransferase (APRTase) encoded by the open reading frame SSO2342 of Sulfolobus solfataricus P2, was subjected to crystallographic, kinetic and ligand binding analyses. The enzyme forms dimers in solution and in the crystals, and binds one molecule of the reactants 5...

Human atopic dermatitis skin-derived T cells can induce a reaction in mouse keratinocytes in vivo

DEFF Research Database (Denmark)

Martel, Britta C; Blom, Lars; Dyring-Andersen, Beatrice

2015-01-01

. In comparison, blood -derived in vitro differentiated Th2 cells only induced a weak response in a few of the mice. Thus, we conclude that human AD skin-derived T cells can induce a reaction in mouse skin through induction of a proliferative response in the mouse keratinocytes. This article is protected......In atopic dermatitis (AD), the inflammatory response between skin infiltrating T cells and keratinocytes is fundamental to the development of chronic lesional eczema. The aim of this study was to investigate whether skin-derived T cells from AD patients could induce an inflammatory response in mice...... through keratinocyte activation and consequently cause development of eczematous lesions. Punch biopsies of lesional skin from AD patients were used to establish skin-derived T cell cultures and which were transferred into NOD.Cg-Prkd(scid) Il2rg(tm1Sug) /JicTac (NOG) mice. We found that subcutaneous...

Prenatal induction of benzo(a)pyrene hydroxylases in mice

International Nuclear Information System (INIS)

Neubert, D.; Tapken, S.

1988-01-01

1. Benzo(a)pyrene hydroxylase (BPH) activity was measured in homogenates of fetal liver (day 18) or of whole-embryos of mice on day 9, 10 or 12 of gestation after maternal pretreatment with B(a)P on 3 consecutive days. A 3 H-liberation assay with 3 H-B(a)P labelled either generally or at the 6-position was used. The values obtained with the embryonic/fetal tissues were compared with those found in maternal liver. 2. Three oral doses of 17.5 mg B(a)P/kg body wt were found to just significantly induce BPH in maternal liver. An induction was observed after pretreatment with 24 mg B(a)P/kg body wt in 9, 10 or 12-day-old whole-embryos, but the V max reached was only 10-20% (1% on day 9) of that of adult non-induced liver. The K m (6-hydroxylation) for all tissues tested were in the same range (600-900 nM). The induction was demonstrable in embryos at tissue levels about one order of magnitude lower than those required for induction in maternal liver. 3. Treatment with 25 mg B(a)P/kg body wt on 3 consecutive days was required to induce BPH in fetal liver on day 18 of gestation. The required B(a)P tissue concentrations were about one half of those necessary for induction in maternal liver. 4. Among a variety of other polycyclic hydrocarbons only chrysene showed an inducing potency similar to that of B(a)P in adult and fetal liver. For all compounds tested there was no correlation found in the inducing potency between adult and fetal liver (e.g. coronene). 5. The doses required to induce BPH in the maternal or fetal liver or in whole embryos of rodents are significantly higher (mg range) than those of usual average human exposure or those taken up by smokers (ng range). (orig.)

Segmenting Multiple Sclerosis Lesions using a Spatially Constrained K-Nearest Neighbour approach

DEFF Research Database (Denmark)

Lyksborg, Mark; Larsen, Rasmus; Sørensen, Per Soelberg

2012-01-01

We propose a method for the segmentation of Multiple Sclerosis lesions. The method is based on probability maps derived from a K-Nearest Neighbours classication. These are used as a non parametric likelihood in a Bayesian formulation with a prior that assumes connectivity of neighbouring voxels. ...

Benign fibroosseous lesions

Directory of Open Access Journals (Sweden)

Cansu Köseoğlu Seçgin

2016-05-01

Full Text Available Benign fibroosseous lesions represent a group of lesions that share the same basic evolutive mechanism and are characterized by replacement of normal bone with a fibrous connective tissue that gradually undergoes mineralization. These lesions are presented by a variety of diseases including developmental, reactive-dysplastic processes and neoplasms. Depending on the nature and amount of calcified tissue, they can be observed as radiolucent, mixed or radiopaque. Their radiographic features could be well-defined or indistinguishable from the surrounding bone tissue. They can be asymptomatic as in osseous dysplasias and can be detected incidentally on radiographs, or they can lead to expansion in the affected bone as in ossifying fibroma. All fibroosseous lesions seen in the jaws and face are variations of the same histological pattern. Therefore, detailed clinical and radiographic evaluation in differential diagnosis is important. In this review, fibroosseous benign lesions are classified as osseous dysplasia, fibrous dysplasia and fibroosseous tumors; and radiographic features and differential diagnosis of these lesions are reviewed taking into account this classification.

Antimutagenic activity of some naturally occurring compounds towards cigarette-smoke condensate and benzo(a)pyrene in the Salmonella/microsome assay

Energy Technology Data Exchange (ETDEWEB)

Terwel, L.; van der Hoeven, J.C.

1985-10-01

Several compounds, occurring in food, were tested for antimutagenic activity towards cigarette-smoke condensate (CSC) and benzo(a)pyrene (BaP). Antimutagenicity was determined in the Salmonella/microsome test, with tester strain TA98, in the presence of rat-liver homogenate. Dose-response curves did show reduction of CSC- and BaP-induced mutagenicity by ellagic acid, riboflavin and chlorophyllin. Chlorophyll a and chlorophyll b, although less distinct, also inhibited CSC- and BaP-induced mutagenicity. Ascorbic acid, beta-carotene, tocopherol acetate, chlorogenic acid and butyl hydroxyanisole did not have any influence on the mutagenicity of CSC and BaP. The similarity in results for cigarette-smoke condensate and for BaP indicates that a general mechanism may be involved in the inhibition of CSC- and BaP-induced mutagenicity.

Lesions of juxtacortical origin (surface lesions of bone)

International Nuclear Information System (INIS)

Kenan, S.; Abdelwahab, I.F.; Klein, M.J.; Hermann, G.; Lewis, M.M.

1993-01-01

A large variety of tumor and tumor-like conditions have been shown to originate from the surface of bone. Most surface lesions are associated with periosteal reaction. The periosteum is a multipotential membrane. Its cellular composition may give rise to a variety of both neoplasms and tumor-like conditions. To avoid misinterpretation, the orthopedist, radiologist, and pathologist should be familiar with the entire spectrum of surface lesions. A better understanding of the natural history and biological behavior at different lesional maturity stages and correlation of the history with the radiographic and pathological findings is essential to establish the correct diagnosis. A history of injury of blunt trauma is very important. A stress fracture may produce a periosteal reaction acd callus that can be difficult to distinguish from osteosarcoma. In this review article, the authors wish to describe and define each term by its anatomy and radiographic features while discussing the entire spectrum of surface lesions. All the illustrative cases in this review article have been proven histologically. (orig.)

Flow cytometric measurement of the metabolism of benzo [a] pyrene by mouse liver cells in culture

International Nuclear Information System (INIS)

Bartholomew, J.C.; Wade, C.G.; Dougherty, K.

1984-01-01

The metabolism of benzo[a]pyrene in individual cells was monitored by flow cytometry. The measurements are based on the alterations that occur in the fluorescence emission spectrum of benzo[a]pyrene when it is converted to various metabolities. Using present instrumentation the technique could easily detect 1 x 10/sup 6/ molecules per cells of benzo [a]pyrene and 1 x 10/sup 7/ molecules per cell of the diol epoxide. The analysis of C3H IOT 1/2 mouse fibroblasts growing in culture indicated that there was heterogeneity in the conversion of the parent compound into diol epoxide derivative suggesting that some variation in sensitivity to transformation by benzo[a]pyrene may be due to differences in cellular metabolism

Energy-responsive timekeeping

Indian Academy of Sciences (India)

2008-12-31

Dec 31, 2008 ... involved lesions of the parabrachial nucleus in rats (David- son et al. 2000); however .... loops (figure 2). The current model involves a primary loop with CLOCK and .... of reduced to oxidized nicotinamide adenine dinucleotide.

Synthesis and characterization of zinc adeninate metal-organic frameworks (bioMOF1) as potential anti-inflammatory drug delivery material

Science.gov (United States)

Usman, Ken Aldren S.; Buenviaje, Salvador C.; Razal, Joselito M.; Conato, Marlon T.; Payawan, Leon M.

2018-05-01

Zn8(ad)4(BPDC)6O•2Me2NH2 (bioMOF1), a porous metal-organic framework with zinc-adeninate secondary building units (SBUs), interconnected via biphenyldicarboxylate linkers, shows great potential for drug delivery applications due to its non-toxic and biocompatible components (zinc and adenine). In this study, bioMOF1 crystals synthesized solvothermally at 130°C for 24 hours, were characterized thoroughly and loaded with a known anti-inflammatory drug, nimesulide (NIM). The crystalline nature of the material was confirmed using powder x-ray diffraction crystallography (PXRD) along with morphology assessment using focused-ion beam/field emission scanning electron microscopy (FIB/FESEM). NIM was introduced to the crystals via solvent exchange accompanied with vigorous stirring and quantified using thermogravimetric analysis (TGA) with loading saturation of ˜30% attained during the 2nd to 3rd day of drug immersion. Drug release in phosphate buffer saline and in deionized water was done to monitor the kinetic of drug release in vitro. The drug release showed a controlled discharge profile which slowed down at the 24th and 48th hour of release. Drug release in buffer showed a faster release of drug from the material, which means that the presence of cations in the solution could further trigger the release of drug. Slow drug release was observed for all of the set-ups with maximum % drug release of 24.47%, and 16.14% for the bioMOF1 in buffer and bioMOF1 in water respectively for the span of 48 hours.

Comparison of Regenerative Tissue Quality following Matrix-Associated Cell Implantation Using Amplified Chondrocytes Compared to Synovium-Derived Stem Cells in a Rabbit Model for Cartilage Lesions

DEFF Research Database (Denmark)

Schmal, Hagen; Kowal, Justyna M; Kassem, Moustapha

2018-01-01

Known problems of the autologous chondrocyte implantation motivate the search for cellular alternatives. The aim of the study was to test the potential of synovium-derived stem cells (SMSC) to regenerate cartilage using a matrix-associated implantation. In an osteochondral defect model of the med......Known problems of the autologous chondrocyte implantation motivate the search for cellular alternatives. The aim of the study was to test the potential of synovium-derived stem cells (SMSC) to regenerate cartilage using a matrix-associated implantation. In an osteochondral defect model...... of the medial femoral condyle in a rabbit, a collagen membrane was seeded with either culture-expanded allogenic chondrocytes or SMSC and then transplanted into the lesion. A tailored piece synovium served as a control. Rabbit SMSC formed typical cartilage in vitro. Macroscopic evaluation of defect healing...... and the thickness of the regenerated tissue did not reveal a significant difference between the intervention groups. However, instantaneous and shear modulus, reflecting the biomechanical strength of the repair tissue, was superior in the implantation group using allogenic chondrocytes (p

Interstrand cross-links arising from strand breaks at true abasic sites in duplex DNA.

Science.gov (United States)

Yang, Zhiyu; Price, Nathan E; Johnson, Kevin M; Wang, Yinsheng; Gates, Kent S

2017-06-20

Interstrand cross-links are exceptionally bioactive DNA lesions. Endogenous generation of interstrand cross-links in genomic DNA may contribute to aging, neurodegeneration, and cancer. Abasic (Ap) sites are common lesions in genomic DNA that readily undergo spontaneous and amine-catalyzed strand cleavage reactions that generate a 2,3-didehydro-2,3-dideoxyribose sugar remnant (3'ddR5p) at the 3'-terminus of the strand break. Interestingly, this strand scission process leaves an electrophilic α,β-unsaturated aldehyde residue embedded within the resulting nicked duplex. Here we present evidence that 3'ddR5p derivatives generated by spermine-catalyzed strand cleavage at Ap sites in duplex DNA can react with adenine residues on the opposing strand to generate a complex lesion consisting of an interstrand cross-link adjacent to a strand break. The cross-link blocks DNA replication by ϕ29 DNA polymerase, a highly processive polymerase enzyme that couples synthesis with strand displacement. This suggests that 3'ddR5p-derived cross-links have the potential to block critical cellular DNA transactions that require strand separation. LC-MS/MS methods developed herein provide powerful tools for studying the occurrence and properties of these cross-links in biochemical and biological systems. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Study on preventive effects of i.v. administration of flavin adenine dinucleotide (FAD) before irradiation on radiation stomatitis

International Nuclear Information System (INIS)

Nagai, Masao; Houzawa, Jiro; Hakamada, Masaru

1984-01-01

In order to compare the preventive effect on radiation stomatitis, flavin adenine dinucleotide (FAD) or vitamin C was administered intravenously until the blood level reached the maximum at the time of irradiation. Thirtyfive patients with cranial or cervical tumors were allocated into the group with FAD (15), the group with vitamin C (10), and the group with irradiation alone (10). The incidence of stomititis was significantly lower and the number of patients in whom the drug was withdrawn due to stomatitis was extremely smaller in the group with FAD than in the other groups. FAD administered before irradiation was considered very useful in preventing radiation stomatitis. (Namekawa, K.)

Omega-3 polyunsaturated Fatty acids suppress the cystic lesion formation of peritoneal endometriosis in transgenic mouse models.

Directory of Open Access Journals (Sweden)

Kensuke Tomio

Full Text Available Omega-3 polyunsaturated fatty acids (omega-3 PUFAs play a role in controlling pathological inflammatory reactions. Endometriosis is characterized by the presence of endometrial tissue on the peritoneum and an exaggerated inflammatory environment around ectopic tissues. Here peritoneal endometriosis was reproduced using a mouse model in which murine endometrial fragments were inoculated into the peritoneal cavity of mice. Fat-1 mice, in which omega-6 can be converted to omega-3 PUFAs, or wild type mice, in which it cannot, were used for the endometriosis model to address the actions of omega-3 PUFAs on the development of endometriotic lesions. The number and weight of cystic endometriotic lesions in fat-1 mice two weeks after inoculation were significantly less than half to those of controls. Mediator lipidomics revealed that cystic endometriotic lesions and peritoneal fluids were abundant in 12/15-hydroxyeicosapentaenoic acid (12/15-HEPE, derived from eicosapentaenoic acid (EPA, and their amount in fat-1 mice was significantly larger than that in controls. 12/15-Lipoxygenase (12/15-LOX-knockout (KO and control mice with or without EPA administration were assessed for the endometriosis model. EPA administration decreased the number of lesions in controls but not in 12/15-LOX-KO mice. The peritoneal fluids in EPA-fed 12/15-LOX-KO mice contained reduced levels of EPA metabolites such as 12/15-HEPE and EPA-derived resolvin E3 even after EPA administration. cDNA microarrays of endometriotic lesions revealed that Interleukin-6 (IL-6 expression in fat-1 mice was significantly lower than that in controls. These results suggest that both endogenous and exogenous EPA-derived PUFAs protect against the development of endometriosis through their anti-inflammatory effects and, in particular, the 12/15-LOX-pathway products of EPA may be key mediators to suppress endometriosis.

Omega-3 polyunsaturated Fatty acids suppress the cystic lesion formation of peritoneal endometriosis in transgenic mouse models.

Science.gov (United States)

Tomio, Kensuke; Kawana, Kei; Taguchi, Ayumi; Isobe, Yosuke; Iwamoto, Ryo; Yamashita, Aki; Kojima, Satoko; Mori, Mayuyo; Nagamatsu, Takeshi; Arimoto, Takahide; Oda, Katsutoshi; Osuga, Yutaka; Taketani, Yuji; Kang, Jing X; Arai, Hiroyuki; Arita, Makoto; Kozuma, Shiro; Fujii, Tomoyuki

2013-01-01

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) play a role in controlling pathological inflammatory reactions. Endometriosis is characterized by the presence of endometrial tissue on the peritoneum and an exaggerated inflammatory environment around ectopic tissues. Here peritoneal endometriosis was reproduced using a mouse model in which murine endometrial fragments were inoculated into the peritoneal cavity of mice. Fat-1 mice, in which omega-6 can be converted to omega-3 PUFAs, or wild type mice, in which it cannot, were used for the endometriosis model to address the actions of omega-3 PUFAs on the development of endometriotic lesions. The number and weight of cystic endometriotic lesions in fat-1 mice two weeks after inoculation were significantly less than half to those of controls. Mediator lipidomics revealed that cystic endometriotic lesions and peritoneal fluids were abundant in 12/15-hydroxyeicosapentaenoic acid (12/15-HEPE), derived from eicosapentaenoic acid (EPA), and their amount in fat-1 mice was significantly larger than that in controls. 12/15-Lipoxygenase (12/15-LOX)-knockout (KO) and control mice with or without EPA administration were assessed for the endometriosis model. EPA administration decreased the number of lesions in controls but not in 12/15-LOX-KO mice. The peritoneal fluids in EPA-fed 12/15-LOX-KO mice contained reduced levels of EPA metabolites such as 12/15-HEPE and EPA-derived resolvin E3 even after EPA administration. cDNA microarrays of endometriotic lesions revealed that Interleukin-6 (IL-6) expression in fat-1 mice was significantly lower than that in controls. These results suggest that both endogenous and exogenous EPA-derived PUFAs protect against the development of endometriosis through their anti-inflammatory effects and, in particular, the 12/15-LOX-pathway products of EPA may be key mediators to suppress endometriosis.

Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression

Directory of Open Access Journals (Sweden)

Rute M.M. Ferreira

2017-10-01

Full Text Available The cell of origin of pancreatic ductal adenocarcinoma (PDAC has been controversial. Here, we show that identical oncogenic drivers trigger PDAC originating from both ductal and acinar cells with similar histology but with distinct pathophysiology and marker expression dependent on cell of origin. Whereas acinar-derived tumors exhibited low AGR2 expression and were preceded by pancreatic intraepithelial neoplasias (PanINs, duct-derived tumors displayed high AGR2 and developed independently of a PanIN stage via non-mucinous lesions. Using orthotopic transplantation and chimera experiments, we demonstrate that PanIN-like lesions can be induced by PDAC as bystanders in adjacent healthy tissues, explaining the co-existence of mucinous and non-mucinous lesions and highlighting the need to distinguish between true precursor PanINs and PanIN-like bystander lesions. Our results suggest AGR2 as a tool to stratify PDAC according to cell of origin, highlight that not all PanIN-like lesions are precursors of PDAC, and add an alternative progression route to the current model of PDAC development.

Structural study and investigation of NMR tensors in interaction of dopamine with Adenine and guanine

Directory of Open Access Journals (Sweden)

Lingjia Xu

2007-04-01

Full Text Available The interaction of dopamine with adenine and guanine were studied at the Hartree-Fock level theory. The structural and vibrational properties of dopamine-4-N7GUA and dopamine-4-N3ADE were studied at level of HF/6-31G*. Interaction energies (ΔE were calculated to be -11.49 and -11.92 kcal/mol, respectively. Some of bond lengths, angels and tortions are compared. NBO studies were performed to the second-order and perturbative estimates of donor-acceptor interaction have been done. The procedures of gauge-invariant atomic orbital (GIAO and continuous-set-of-gauge-transformation (CSGT were employed to calculate isotropic shielding, chemical shifts anisotropy and chemical shifts anisotropy asymmetry and effective anisotropy using 6-31G* basis set. These calculations yielded molecular geometries in good agreement with available experimental data.

Effect of ageing on benzo[a]pyrene extractability in contrasting soils

Energy Technology Data Exchange (ETDEWEB)

Duan, Luchun [CERAR-Centre for Environmental Risk Assessment and Remediation and Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), Building X, University of South Australia, Mawson Lakes, SA 5095 (Australia); Naidu, Ravi, E-mail: Ravi.Naidu@newcastle.edu.au [CERAR-Centre for Environmental Risk Assessment and Remediation and Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), Building X, University of South Australia, Mawson Lakes, SA 5095 (Australia); Liu, Yanju; Palanisami, Thavamani; Dong, Zhaomin; Mallavarapu, Megharaj [CERAR-Centre for Environmental Risk Assessment and Remediation and Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE), Building X, University of South Australia, Mawson Lakes, SA 5095 (Australia); Semple, Kirk T. [Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ (United Kingdom)

2015-10-15

Highlights: • In vitro assessment of B[a]P in contaminated soils using 4 different methods. • An exponential kinetic model fits well with the extractability data. • Fitting parameter and {sup 14}C residue correlates with key soil properties. • Fractionation of B[a]P was obtained based on extractability by extractants. - Abstract: Changes in benzo[a]pyrene (B[a]P) extractability over 160 days ageing in four contrasting soils varying in organic matter content and clay mineralogy were investigated using dichloromethane: acetone 1:1 (DCM/Ace), 60 mM hydroxypropyl-β-cyclodextrin (HPCD) solution, 1-butanol (BuOH) and Milli-Q water. The B[a]P extractability by the four methods decreased with ageing and a first-order exponential model could be used to describe the kinetics of release. Correlation of the kinetic rate constant with major soil properties showed a significant effect of clay and sand contents and pore volume fraction (<6 nm) on sequestration of the desorbable fraction (by HPCD) and the water-extractable fraction. Analysis of {sup 14}C-B[a]P in soils after ageing showed a limited loss of B[a]P via degradation. Fractionation of B[a]P pools associated with the soil matrix was analysed according to extractability of B[a]P by the different extraction methods. A summary of the different fractions is proposed for the illustration of the effect of ageing on different B[a]P-bound fractions in soils. This study provides a better understanding of the B[a]P ageing process associated with different fractions and also emphasises the extraction capacity of the different methods employed.

Effect of ageing on benzo[a]pyrene extractability in contrasting soils

International Nuclear Information System (INIS)

Duan, Luchun; Naidu, Ravi; Liu, Yanju; Palanisami, Thavamani; Dong, Zhaomin; Mallavarapu, Megharaj; Semple, Kirk T.

2015-01-01

Highlights: • In vitro assessment of B[a]P in contaminated soils using 4 different methods. • An exponential kinetic model fits well with the extractability data. • Fitting parameter and 14 C residue correlates with key soil properties. • Fractionation of B[a]P was obtained based on extractability by extractants. - Abstract: Changes in benzo[a]pyrene (B[a]P) extractability over 160 days ageing in four contrasting soils varying in organic matter content and clay mineralogy were investigated using dichloromethane: acetone 1:1 (DCM/Ace), 60 mM hydroxypropyl-β-cyclodextrin (HPCD) solution, 1-butanol (BuOH) and Milli-Q water. The B[a]P extractability by the four methods decreased with ageing and a first-order exponential model could be used to describe the kinetics of release. Correlation of the kinetic rate constant with major soil properties showed a significant effect of clay and sand contents and pore volume fraction (<6 nm) on sequestration of the desorbable fraction (by HPCD) and the water-extractable fraction. Analysis of 14 C-B[a]P in soils after ageing showed a limited loss of B[a]P via degradation. Fractionation of B[a]P pools associated with the soil matrix was analysed according to extractability of B[a]P by the different extraction methods. A summary of the different fractions is proposed for the illustration of the effect of ageing on different B[a]P-bound fractions in soils. This study provides a better understanding of the B[a]P ageing process associated with different fractions and also emphasises the extraction capacity of the different methods employed

Localization of lesions in aphasia

International Nuclear Information System (INIS)

Hojo, Kei; Watanabe, Shunzo; Tasaki, Hiroichi; Sato, Tokijiro; Metoki, Hirobumi.

1984-01-01

Using a microcomputer, the locus and extent of the lesions, as demonstrated by computed tomography for 127 cases with various types of aphasia were superimposed onto standardized marices. The relationship between the foci of the lesions and the types of aphasia was investigated. Broca aphasics (n=39) : Since the accumulated site of the lesions highly involved the deep structures of the lower part of the precentral gyrus as well as the insula and lenticular nucleus, only 60% of the Broca aphasics had lesions on these areas. This finding has proved to have little localizing value. Wernicke aphasics (n=23) : The size of the lesion was significantly smaller than Broca's aphasia. At least 70% of the patients had the superior temporal lesions involving Wernicke's area and subcortical lesions of the superior and middle temporal gyri. Amnestic aphasics (n=18) : The size of the lesion was smaller than any other types. While there was some concentration of the lesions (maximum 40%) in the area of the subcortical region of the anterior temporal gyrus adjacent to Wernicke's area and the lenticular nucleus, the lesions were distributed throughout the left hemisphere. Amnestic aphasia was thought to be the least localizable. Conduction aphasics (n=11) : The lesions were relatively small in size. Many patients had posterior speech area lesions involving at least partially Wernicke's area. In particular, more than 80% of the conduction aphasics had lesions of the supramarginal gyrus and it's adjacent deep structures. Global aphasics (n=36) : In general, the size of the lesion was very large and 70% of the global aphasics had extensive lesions involving both Broca's and Wernicke's areas. However, there were observations showing that the lesions can be small and confined. (J.P.N.)

Analysis of pulmonary coin lesions

International Nuclear Information System (INIS)

Kim, O; Kim, K. H.; Oh, K. K.; Park, C. Y.

1979-01-01

For A long time the solitary pulmonary nodule has remained a difficult problem to solve and has attracted a great deal of attension in recent years. Circumscribed coin lesions of the lung were generally peripheral in location with respect to the pulmonary hilus. Because of this, important clinical problem in management and diagnosis arise. Such a lesion is discovered through roentgenologic examination. So the roentgenologists is the first be in a position to offer advise. This presentation is an attempt to correlate a useful diagnosis with roentgenologic findings of pulmonary coin lesion which enables us to get differential diagnosis of benign and malignant lesion. Histologically proven 120 cases of the pulmonary coin lesion during the period of 8 years were reviewed through plain film, tomogram, bronchoscopy, variable laboratory findings, and clinical history. The results are as follows: 1. Male to female sex ratio was 3 : 1. In age distribution, most of the malignant pulmonary coin lesion appeared in 6th decade (39%) and 5th decade (27%). In benign lesion, the most cases were in 3 rd decade. 2. Pathological cell type are as follows: Primary bronchogenic cancer 43.3%, tuberculoma 25.8%, inflammatory lesion 17.5%, benign tumor 10%, and bronchial adenoma, harmartoma, A.V. malformation, mesothelioma, are 1 case respectively. As a result benign and malignant lesion showed equal distribution (49.1% : 50.3%). 3. In symptom analysis ; cough is the most common (43.5%) symptom in malignant lesion, next follows hemoptysis (20.9%) and chest pain (14.5%). In benign lesion, most of the patient (32.7%) did not complain any symptom. 4. In malignant lesion, the most common nodular size was 4 cm (32.3%), and in benign lesion 2 cm sized coin was most common (39.3%). 5. In general, margin of nodule was very sharp and well demarcated in benign lesion (83.3%), and in malignant lesion that was less demarcated and poorly defined. 6. Most case of calcification (82.7%) was seen in benign

An investigation of endocrine disrupting effects and toxic mechanisms modulated by benzo[a]pyrene in female scallop Chlamys farreri

Energy Technology Data Exchange (ETDEWEB)

Tian, Shuangmei; Pan, Luqing, E-mail: panlq@ouc.edu.cn; Sun, Xiaohua

2013-11-15

Highlights: •B[a]P disturbed progesterone, 17β-estradiol and testosterone production in scallop. •B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD expression after a 10-day exposure. •B[a]P of lower dose elevated AHR-CYP1A expression but high dose B[a]P inhibited them. •ER and vitellogenin transcription was consistent with AHR after B[a]P exposure. •B[a]P exposure induced relatively developmental delay and impairment of ovary. -- Abstract: The purpose of this study was to investigate the endocrine disrupting effects induced by benzo[a]pyrene (B[a]P) and explore the underlying mechanisms in mollusks. In this study, sexually mature female Chlamys farreri were exposed to benzo[a]pyrene for 10 days at four different concentrations as 0, 0.025, 0.5 and 10 μg/L. Sex steroids were identified and quantified by electrochemiluminescence immunoassay (ECLIA) method and results showed that exposure to B[a]P exerts great suppression on 17β-estradiol, testosterone production and disrupts progesterone levels in ovary. Transcription of genes were detected and measured by real-time RT-PCR. It showed that at day 10 B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD mRNA expression in a dose-dependent manner, which suggests that they could be potential targets of B[a]P that disrupt steroidogenic machinery. Moreover, 0.025 μg/L B[a]P activated transcription of aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), CYP1A1 and estrogen receptor (ER), while 10 μg/L B[a]P suppressed all of them. The consistency of their responses to B[a]P exposure implies that AHR action may be involved in invertebrate CYP regulation and ER transcription despite of unknown mechanisms. Additionally, B[a]P exposure could induce ovarian impairment and developmental delay in C. farreri. Overall, sensitivity of C. farreri to endocrine disruption and toxicity suggests that C. farreri is a suitable species for study of endocrine-disrupting effects in marine invertebrates. This study will form a

An investigation of endocrine disrupting effects and toxic mechanisms modulated by benzo[a]pyrene in female scallop Chlamys farreri

International Nuclear Information System (INIS)

Tian, Shuangmei; Pan, Luqing; Sun, Xiaohua

2013-01-01

Highlights: •B[a]P disturbed progesterone, 17β-estradiol and testosterone production in scallop. •B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD expression after a 10-day exposure. •B[a]P of lower dose elevated AHR-CYP1A expression but high dose B[a]P inhibited them. •ER and vitellogenin transcription was consistent with AHR after B[a]P exposure. •B[a]P exposure induced relatively developmental delay and impairment of ovary. -- Abstract: The purpose of this study was to investigate the endocrine disrupting effects induced by benzo[a]pyrene (B[a]P) and explore the underlying mechanisms in mollusks. In this study, sexually mature female Chlamys farreri were exposed to benzo[a]pyrene for 10 days at four different concentrations as 0, 0.025, 0.5 and 10 μg/L. Sex steroids were identified and quantified by electrochemiluminescence immunoassay (ECLIA) method and results showed that exposure to B[a]P exerts great suppression on 17β-estradiol, testosterone production and disrupts progesterone levels in ovary. Transcription of genes were detected and measured by real-time RT-PCR. It showed that at day 10 B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD mRNA expression in a dose-dependent manner, which suggests that they could be potential targets of B[a]P that disrupt steroidogenic machinery. Moreover, 0.025 μg/L B[a]P activated transcription of aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), CYP1A1 and estrogen receptor (ER), while 10 μg/L B[a]P suppressed all of them. The consistency of their responses to B[a]P exposure implies that AHR action may be involved in invertebrate CYP regulation and ER transcription despite of unknown mechanisms. Additionally, B[a]P exposure could induce ovarian impairment and developmental delay in C. farreri. Overall, sensitivity of C. farreri to endocrine disruption and toxicity suggests that C. farreri is a suitable species for study of endocrine-disrupting effects in marine invertebrates. This study will form a

Recognition and repair of the CC-1065-(N3-Adenine)-DNA adduct by the UVRABC nuclease

International Nuclear Information System (INIS)

Tang, M.; Lee, C.S.; Doisy, R.; Ross, L.; Needham-VanDevanter, D.R.; Hurley, L.H.

1988-01-01

The recognition and repair of the helix-stabilizing and relatively nondistortive CC-1065-(N3-adenine)-DNA adduct by UVRABC nuclease has been investigated both in vivo with phi X174RFI DNA by a transfection assay and in vitro by a site-directed adduct in a 117 base pair fragment from M13mp1. CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis which binds within the minor groove of DNA through N3 of adenine. In contrast to the helix-destabilizing and distortive modifications of DNA caused by ultraviolet light or N-acetoxy-2-(acetylamino)fluorene, CC-1065 increases the melting point of DNA and decreases the S1 nuclease activity. Using a viral DNA-Escherichia coli transfection system, the authors have found that the uvrA, uvrB, and uvrC genes, which code for the major excision repair proteins for UV- and NAAAF-induced DNA damage, are also involved in the repair of CC-1065-DNA adducts. In contrast, the uvrD gene product, which has been found to be involved in the repair of UV damage, has no effect in repairing CC-1065-DNA adducts. Purified UVRA, UVRB, and UVRC proteins must work in concert to incise the drug-modified phi X174RFI DNA. Using a site-directed and multiple CC-1065 modified (MspI-BstNI) 117 base pair fragment from M13mp1, they have found that UVRABC nuclease incises at the eight phosphodiester bond on the 5' side of the CC-1065-DNA adduct on the drug-modified strand. The enzymes do not cut the noncovalently modified strand. The DNA sequence and/or helix-stabilizing effect of multiple adducts may determine the recognition and/or incision of the drug-DNA adduct by UVRABC nuclease. These results are discussed in relation to the structure of the CC-1065-DNA adduct and the effect of drug binding on local DNA structure

Uterine Vascular Lesions

Science.gov (United States)

Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

2013-01-01

Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

Gas-phase spectroscopy of protonated adenine, adenosine 5′-monophosphate and monohydrated ions

DEFF Research Database (Denmark)

Pedersen, S.O.; Støchkel, K.; Byskov, C.S.

2013-01-01

. The yields of these were measured as a function of the wavelength of the light from 210 nm to 300 nm, and they were combined to obtain the total photoinduced dissociation at each wavelength (i.e., action spectrum). A broad band between 230 nm and 290 nm and the tail of a band with maximum below 210 nm (high......-energy band) are seen. In the case of AdeH+(H2O), the dominant dissociation channel after photoexcitation in the low-energy band was simply loss of H2O while photodissociation of protonated AMP revealed two dominant dissociation channels associated with the formation of either AdeH+ or loss of H3PO4....... The action spectra of AdeH+, AdeH+(H2O), and AMPH+ are almost identical in the 230–290 nm region, and they resemble the absorption spectrum of protonated adenine in aqueous solution recorded at low pH. Hence from our work it is firmly established that the lowest-energy transitions are independent...

Investigation of relations between skin cancer lesions' images and their fluorescent spectra

Science.gov (United States)

Pavlova, P.; Borisova, E.; Avramov, L.; Petkova, El.; Troyanova, P.

2010-03-01

This investigation is based on images obtained from healthy tissue and skin cancer lesions and their fluorescent spectra of cutaneous lesions derived after optical stimulation. Our analyses show that the lesions’ spectra of are different of those, obtained from normal tissue and the differences depend on the type of cancer. We use a comparison between these “healthy” and “unhealthy” spectra to define forms of variations and corresponding diseases. However, the value of the emitted light varies not only between the patients, but also depending on the position of the tested area inside of one lesion. These variations could be result from two reasons: different degree of damaging and different thickness of the suspicious lesion area. Regarded to the visible image of the lesion, it could be connected with the chroma of colour of the tested area and the lesion homogeneity that corresponds to particular disease. For our investigation, images and spectra of three non-melanoma cutanous malignant tumors are investigated, namely—basal cell carcinoma, squamous cell carcinoma, and keratoacanthoma. The images were processed obtaining the chroma by elimination of the background—healthy tissue, and applying it as a basic signal for transformation from RGB to Lab colorimetric model. The chroma of the areas of emission is compared with the relative value of fluorescence spectra. Specific spectral features are used to develop hybrid diagnostic algorithm (including image and spectral features) for differentiation of these three kinds of malignant cutaneous pathologies.

Differentiating between benign and malignant sinonasal lesions using dynamic contrast-enhanced MRI and intravoxel incoherent motion.

Science.gov (United States)

Jiang, Jingxuan; Xiao, Zebin; Tang, Zuohua; Zhong, Yufeng; Qiang, Jinwei

2018-01-01

To explore the value of dynamic contrast-enhanced MRI (DCE-MRI) and intravoxel incoherent motion (IVIM) for distinguishing between benign and malignant sinonasal lesions and investigate the correlations between the two methods. Patients with sinonasal lesions (42 benign and 31 malignant) who underwent DCE-MRI and IVIM before confirmation by histopathology were enrolled in this prospective study. Parameters derived from DCE-MRI and IVIM were measured, the optimal cut-off values for differential diagnosis were determined, and the correlations between the two methods were evaluated. Statistical analyses were performed using the Wilcoxon rank sum test, receiver operating characteristic (ROC) curve analysis, and Spearman's rank correlation. Significantly higher K trans and K ep values but lower D and f values were found in malignant lesions than in benign lesions (all pbenign and malignant sinonasal lesions. IVIM findings correlate with DCE-MRI results and may represent an alternative to DCE-MRI. Copyright © 2017 Elsevier B.V. All rights reserved.

Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis.

OpenAIRE

Moreadith, R W; Batshaw, M L; Ohnishi, T; Kerr, D; Knox, B; Jackson, D; Hruban, R; Olson, J; Reynafarje, B; Lehninger, A L

1984-01-01

We report the case of an infant with hypoglycemia, progressive lactic acidosis, an increased serum lactate/pyruvate ratio, and elevated plasma alanine, who had a moderate to profound decrease in the ability of mitochondria from four organs to oxidize pyruvate, malate plus glutamate, citrate, and other NAD+-linked respiratory substrates. The capacity to oxidize the flavin adenine dinucleotide-linked substrate, succinate, was normal. The most pronounced deficiency was in skeletal muscle, the le...

Gastroprotection studies of Schiff base zinc (II) derivative complex against acute superficial hemorrhagic mucosal lesions in rats.

Science.gov (United States)

Golbabapour, Shahram; Gwaram, Nura Suleiman; Hassandarvish, Pouya; Hajrezaie, Maryam; Kamalidehghan, Behnam; Abdulla, Mahmood Ameen; Ali, Hapipah Mohd; Hadi, A Hamid A; Majid, Nazia Abdul

2013-01-01

The study was carried out to assess the gastroprotective effect of the zinc (II) complex against ethanol-induced acute hemorrhagic lesions in rats. The animals received their respective pre-treatments dissolved in tween 20 (5% v/v), orally. Ethanol (95% v/v) was orally administrated to induce superficial hemorrhagic mucosal lesions. Omeprazole (5.790×10(-5) M/kg) was used as a reference medicine. The pre-treatment with the zinc (II) complex (2.181×10(-5) and 4.362×10(-5) M/kg) protected the gastric mucosa similar to the reference control. They significantly increased the activity levels of nitric oxide, catalase, superoxide dismutase, glutathione and prostaglandin E2, and decreased the level of malondialdehyde. The histology assessments confirmed the protection through remarkable reduction of mucosal lesions and increased the production of gastric mucosa. Immunohistochemistry and western blot analysis indicated that the complex might induced Hsp70 up-regulation and Bax down-regulation. The complex moderately increased the gastroprotectiveness in fine fettle. The acute toxicity approved the non-toxic characteristic of the complex (<87.241×10(-5) M/kg). The gastroprotective effect of the zinc (II) complex was mainly through its antioxidant activity, enzymatic stimulation of prostaglandins E2, and up-regulation of Hsp70. The gastric wall mucus was also a remarkable protective mechanism.

Mechanisms of interaction of radiation with matter

International Nuclear Information System (INIS)

Geacintov, N.E.; Pope, M.

1993-01-01

This project is concerned with the mechanisms by which polynuclear aromatic (PNA) compounds on the one hand, and ionizing radiation on the other, cause damage to DNA. PNA compounds constitute an important class of environmental pollutants derived from energy-related sources which, upon metabolic activation to diolepoxide derivatives, produce bulky PNA-DNA lesions interfere with the normal DNA replication and transcription processes, and give rise to mutations and the initiation of tumors. Chiral and other stereochemical effects play a key role in determining the biological effects of a given PNA diol epoxide and the potentially mutagenic lesions which are formed. New and efficient methods for synthesizing stereochemically pure and precisely positioned PNA diol epoxide-DNA lesions in small DNA fragments are reported here. We have elucidated the structures of three stereoisomeric benzo[a]pyrene diol epoxide-DNA adducts. How these adducts affect on DNA polymerase fidelity, transcription, and DNA repair are currently being investigated with respect to detailed structure-biological activity correlations. Spectroscopic techniques such as circular dichroism, fluorescence, and photoionization play an important role in the characterizations of the PNA adducts. A new method was developed for measuring the lifetimes as well as the energies of picosecond duration electronically excited states. Using this technique, it is proposed that short-lived (15 ps) charge-transfer (CT) states in the PNA compound tetracene are activated by a 20 ps laser pulse; an unusual external photoemission echo do to the recombination of CT states is observed 85 ps after the pulse

Characterization and mapping of complementary lesion-mimic genes lm1 and lm2 in common wheat.

Science.gov (United States)

Yao, Qin; Zhou, Ronghua; Fu, Tihua; Wu, Weiren; Zhu, Zhendong; Li, Aili; Jia, Jizeng

2009-10-01

A lesion-mimic phenotype appeared in a segregating population of common wheat cross Yanzhan 1/Zaosui 30. The parents had non-lesion normal phenotypes. Shading treatment and histochemical analyses showed that the lesions were caused by light-dependent cell death and were not associated with pathogens. Studies over two cropping seasons showed that some lines with more highly expressed lesion-mimic phenotypes exhibited significantly lower grain yields than those with the normal phenotype, but there were no significant effects in the lines with weakly expressed lesion-mimic phenotypes. Among yield traits, one-thousand grain weight was the most affected by lesion-mimic phenotypes. Genetic analysis indicated that this was a novel type of lesion mimic, which was caused by interaction of recessive genes derived from each parent. The lm1 (lesion mimic 1) locus from Zaosui 30 was flanked by microsatellite markers Xwmc674 and Xbarc133/Xbarc147 on chromosome 3BS, at genetic distances of 1.2 and 3.8 cM, respectively, whereas lm2 from Yanzhan 1 was mapped between microsatellite markers Xgwm513 and Xksum154 on chromosome 4BL, at genetic distances of 1.5 and 3 cM, respectively. The linked microsatellite makers identified in this study might be useful for evaluating whether potential parents with normal phenotype are carriers of lesion-mimic alleles.

Levels of adenine nucleotides (ATP, ADP, AMP) and of inorganic phosphate in needles of Picea abies, representing different stages of development and of pollution dependence

Energy Technology Data Exchange (ETDEWEB)

Benz, T; Hampp, R; Horsch, F; Filby, G; Fund, N; Gross, S; Hanisch, B; Kilz, E; Seidel, A [comps.

1986-04-01

Levels of adenine nucleotides (ATP, ADP, AMP) and of inorganic phosphate in needles of Picea abies, representing different stages of development and of pollution dependence. Lyophilized needles of Picea abies (Kaelbelescheuer, southern Black Forest) were analyzed for their content of adenine nucleotides (ATP, ADP, AMP: AdN) and of inorganic phosphate (Psub(i)). The metabolite levels were related to needle age, vegetation period and degree of damage (chlorophyll content). The results were as follows: 1) With increasing needle age there is a general decrease in the total AdN-pool. This decrease is most pronounced in very young needles and occurs in both healthy and damaged tissue. 2) The ATP/ADP-ratio of damaged needle is significantly higher than that of healthy ones. 3) Both phosphorylation potential (ATP.(ADP.Psub(i))/sup -1/) and adenylate energy charge ((ATP + 0.5.ADP).(AdN)/sup -1/) are significantly reduced in damaged needles. This is due to relatively higher levels of Psub(i) and of AMP. The results, although incomplete and preliminary, indicate metabolic alterations which have been described for other tissues in response to pollution by photooxidants.

Biological composting of petroleum waste organics using the white rot fungus Phanerochaete chrysosporium

International Nuclear Information System (INIS)

McFarland, M.J.; Xiu J, Qiu; Aprill, W.A.; Sims, R.C.

1990-01-01

Environmental enrichment of the white rot fungus Phanerochaete chrysosporium in biological compost soil reactors was effective in enhancing the rates of Benzo(a)pyrene removal over that observed under natural soil conditions. In contaminated soil compost systems amended with fungal inoculum and primary substrate, maximum Benzo(a)pyrene removal rates of 0.31 mg B(a)p/kg compost material-day (0.25 mgB(a)p/kg soil-day) were observed while in unamended soil conditions, maximum removal rates of 0.13 mg B(a)p/kg soil-day were recorded. Additions of primary substrate without any fungal inoculum gave compound removal rates similar to soil only conditions (i.e., 14 mg B(a)p/kg soil-day). Differences in contaminant and radioactivity ( 14 C) removal rates indicated that Benzo(a)pyrene derived carbon was being incorporated into nonvolatile materials within the compost environment. Contaminated soil pH had a significant effect on Benzo(a)pyrene removal rates during composting treatment. With acid soils (pH-4.8), a maximum Benzo(a)pyrene removal rate of 0.11 mg B(a)p/kg compost material-day was determined compared to 0.31 mg B(a)p/kg compost material-day in alkaline (pH-8.0) soil. Oxygen availability appeared to be one of the most important process variables influencing both fungal growth and Benzo(a)pyrene removal. Periodic pulses of oxygen equivalent to a three volume turnover of reactor headspace every three days resulted in increasing the Benzo(a)pyrene removal rate from 0.31 mg B(a)p/kg compost material-day to 0.85 mg B(a)p/kg compost material day

Clinical experiences of NBI laryngoscope in diagnosis of laryngeal lesions

Science.gov (United States)

Qi, Xinmeng; Yu, Dan; Zhao, Xue; Jin, Chunshun; Sun, Changling; Liu, Xueshibojie; Cheng, Jinzhang; Zhang, Dejun

2014-01-01

Endoscopy is essential for the diagnosis and treatment of cancers derived from the larynx. However, a laryngoscope with conventional white light (CWL) has technical limitations in detecting small or superficial lesions on the mucosa. Narrow band imaging especially combined with magnifying endoscopy (ME) is useful for the detection of superficial squamous cell carcinoma (SCC) within the oropharynx, hypopharynx, and oral cavity. A total of 3675 patients who have come to the outpatient clinic and complained of inspiratory stridor, dyspnea, phonation problems or foreign body sensation, were enrolled in this study. We describe the glottic conditions of the patients. All 3675 patients underwent laryngoscopy equipped with conventional white light (CWL) and NBI system. 1149 patients received a biopsy process. And 1153 lesions were classified into different groups according to their histopathological results. Among all the 1149 patients, 346 patients (312 males, 34 females; mean age 62.2±10.5 years) were suspected of having a total of 347 precancerous or cancerous (T1 or T2 without lymphnode involvement) lesions of the larynx under the CWL. Thus, we expected to attain a complete vision of what laryngeal lesions look like under the NBI view of a laryngoscope. The aim was to develop a complete description list of each laryngeal conditions (e.g. polyps, papilloma, leukoplakia, etc.), which can serve as a criteria for further laryngoscopic examinations and diagnosis. PMID:25419362

Persistent changes in the initial rate of pyruvate transport by isolated rat liver mitochondria after preincubation with adenine nucleotides and calcium ions

OpenAIRE

Vaartjes, W.J.; Breejen, J.N. den; Geelen, M.J.H.; Bergh, S.G. van den

1980-01-01

1. Preincubation of isolated rat-liver mitochondria in the presence of adenine nucleotides or Ca2+ results in definite and persistent changes in the initial rate of pyruvate transport. 2. These changes in the rate of pyruvate transport are accompanied by equally persistent changes in the opposite direction of the activity of pyruvate dehydrogenase (EC. 1.2.4.1). 3. Changes of the transmembrane pH gradient and of the membrane potential, brought about by the pretreatments of the mitochondria, c...

Rosuvastatin reduces atherosclerotic lesions and promotes progenitor cell mobilisation and recruitment in apolipoprotein E knockout mice.

Science.gov (United States)

Schroeter, Marco R; Humboldt, Tim; Schäfer, Katrin; Konstantinides, Stavros

2009-07-01

Statins enhance incorporation of bone marrow-derived cells into experimental neointimal lesions. However, the contribution of progenitor cells to progression of spontaneous atherosclerotic plaques, and the possible modulatory role of statins in this process, remain poorly understood. We compared the effects of rosuvastatin (1 and 10mg/kg BW) and pravastatin (10mg/kg) on progenitor cell mobilisation, recruitment into atherosclerotic plaques, and lesion growth. Statins were administered over 8 weeks to apolipoprotein E knockout mice on atherogenic diet. In addition, mice were lethally irradiated, followed by transplantation of bone marrow from LacZ transgenic mice. Rosuvastatin reduced lesion area and intima-to-media ratio at the brachiocephalic artery compared to vehicle, while both parameters were not significantly altered by pravastatin. Rosuvastatin also augmented endothelialisation (P<0.05) and reduced the smooth muscle cells (SMC) content (P=0.042) of lesions. Numbers of c-kit, sca-1 and flk-1, sca-1 double-positive progenitor cells were significantly increased in rosuvastatin compared to control-treated mice, both in the bone marrow and the peripheral blood. Similarly, the number of spleen-derived acLDL, lectin double-positive progenitor cells (P=0.001) and colony-forming units (P=0.0104) was significantly increased in mice treated with rosuvastatin compared to vehicle alone. In the bone marrow, increased Akt and p42/44 MAP kinase phosphorylation and upregulated SDF1alpha mRNA expression were observed. Importantly, rosuvastatin treatment also increased the plasma levels of c-kit ligand (P=0.003), and the number of c-kit-positive cells within atherosclerotic lesions (P=0.041). Our findings suggest that rosuvastatin reduces the size of atherosclerotic plaques, and this effect appears to involve progenitor cell mobilisation and recruitment into vascular lesions.

Ghost cell lesions

Directory of Open Access Journals (Sweden)

E Rajesh

2015-01-01

Full Text Available Ghost cells have been a controversy for a long time. Ghost cell is a swollen/enlarged epithelial cell with eosnophilic cytoplasm, but without a nucleus. In routine H and E staining these cells give a shadowy appearance. Hence these cells are also called as shadow cells or translucent cells. The appearance of these cells varies from lesion to lesion involving odontogenic and nonodontogenic lesions. This article review about the origin, nature and significance of ghost cells in different neoplasms.

The effectiveness of chemical carcinogens to induce atherosclerosis in the white carneau pigeon

International Nuclear Information System (INIS)

Revis, N.W.; Bull, R.; Laurie, D.; Schiller, C.A.

1984-01-01

The frequency of atherosclerotic lesions of the abdominal aorta has been reported to increase significantly in chickens exposed to benzo(a)pyrene and 7,12-dimethylbenz(a,h)anthracene. The present studies were performed to determine in another experimental model frequently used in atherosclerotic studies (i.e. White Carneau Pigeons) whether these and other chemical carcinogens enhance atherosclerosis. The induction and enhancement of atherosclerotic lesions were observed in pigeons treated with 7,12-dimethylbenz(a,h)anthracene, benzo(a)pyrene and 3-methylcholanthrene. The number and size of plaques in the aorta were frequently greater in pigeons treated with the higher concentrations (i.e. 100 mg/kg) of these 3 polycyclic aromatic hydrocarbons. Benzo(e)pyrene and 2,4,6-trichlorophenol were ineffective in the induction or enhancement of atherosclerosis in the pigeons. The results of the present and previous studies suggest that the polycyclic aromatic hydrocarbons (excluding benzo(e)pyrene) may be the only potential atherogens in avian atherosclerosis. This relationship may be associated with how these hydrocarbons are transported in the plasma (i.e. by lipoproteins) as demonstrated by the present distribution studies (author)

Crystal structure of an intermolecular 2:1 complex between adenine and thymine. Evidence for both Hoogsteen and 'quasi-Watson-Crick' interactions.

Science.gov (United States)

Chandrasekhar, Sosale; Naik, Tangali R Ravikumar; Nayak, Susanta K; Row, Tayur N Guru

2010-06-15

The titled complex, obtained by co-crystallization (EtOH/25 degrees C), is apparently the only known complex of the free bases. Its crystal structure, as determined by X-ray diffraction at both 90 K and 313 K, showed that one A-T pair involves a Hoogsteen interaction, and the other a Watson-Crick interaction but only with respect to the adenine unit. The absence of a clear-cut Watson-Crick base pair raises intriguing questions about the basis of the DNA double helix. Copyright 2010 Elsevier Ltd. All rights reserved.

In vitro metabolism of benzo[a]pyrene-7,8-dihydrodiol and dibenzo[def,p]chrysene-11,12 diol in rodent and human hepatic microsomes

Energy Technology Data Exchange (ETDEWEB)

Smith, Jordan N.; Mehinagic, Denis; Nag, Subhasree; Crowell, Susan R.; Corley, Richard A.

2017-03-01

Polycyclic aromatic hydrocarbons (PAHs) are contaminants that are ubiquitously found in the environment, produced through combustion of organic matter or petrochemicals, and many of which are procarcinogens. The prototypic PAH, benzo[a]pyrene (B[a]P) and the highly carcinogenic dibenzo[def,p]chrysene (DBC) are metabolically activated by isoforms of the P450 enzyme superfamily producing benzo[a]pyrene-7,8-dihydrodiol (B[a]P diol), dibenzo[def,p]chrysene-11,12 diol (DBC diol). Each of these diols can be further metabolized by cytochrome P450 enzymes to highly reactive diol-epoxide metabolites that readily react with DNA or by phase II conjugation facilitating excretion. To complement prior in vitro metabolism studies with parent B[a]P and DBC, both phase I metabolism and phase II glucuronidation of B[a]P diol and DBC diol were measured in hepatic microsomes from female B6129SF1/J mice, male Sprague-Dawley rats, and female humans. Metabolic parameters, including intrinsic clearance and Michaelis-Menten kinetics were calculated from substrate depletion data. Mice and rats demonstrated similar B[a]P diol phase I metabolic rates. Compared to rodents, human phase I metabolism of B[a]P diol demonstrated lower overall metabolic capacity, lower intrinsic clearance at higher substrate concentrations (>0.14 µM), and higher intrinsic clearance at lower substrate concentrations (<0.07 µM). Rates of DBC diol metabolism did not saturate in mice or humans and were highest overall in mice. Higher affinity constants and lower capacities were observed for DBC diol glucuronidation compared to B[a]P diol glucuronidation; however, intrinsic clearance values for these compounds were consistent within each species. Kinetic parameters reported here will be used to extend physiologically based pharmacokinetic (PBPK) models to include the disposition of B[a]P and DBC metabolites in animal models and humans to support future human health risk assessments.

Oral White Lesions: Presentation and Comparison of Oral Submucous Fibrosis with Other Lesions

International Nuclear Information System (INIS)

Maqsood, A.; Aman, N.

2013-01-01

Objective: To compare oral submucous fibrosis with other white oral lesions for presentation and associated factors. Study Design: Cross-sectional study. Place and Duration of Study: The Departments of Oral Medicine and Oral and Maxillofacial Surgery, Dr. Ishrat-ul-Ibad Institute of Oral Health Sciences (DIKIOHS), Karachi, from May 2008 to May 2009. Methodology: Patients presenting with oral white lesions were selected by consecutive non-purposive sampling and clinico-demographic data was collected. For patients with oral submucous fibrosis (OSF), additional information like duration of habits, maximal incisal opening (MIO), presence of any other associated lesion were noted. OSF was compared with other white lesions for any association between characteristic of subjects. Chi-square and independent t-tests for determining the statistical significance at p < 0.05. Results: OSF was present in 59.6% (n = 106) of the 178 patients; other white lesions were 40.4% (n = 72). The mean age of patients with OSF was 34 +- 12.7 years and 45.81 +- 16.2 years in patients with other white lesions, (p < 0.0001). Items containing areca nut were consumed more by patients with OSF, with a significant (p < 0.0001) compared to patients with other white lesions. Conclusion: OSF was the predominant white lesion in patients examined at DIKIOHS. Areca nut was found to be chewed more by patients with OSF and still longer by patients with SCC. (author)

Skeletal and tissue lesions resulting from exposure to radium and fission products

International Nuclear Information System (INIS)

Warren, S.

1973-01-01

The chief effects of absorbed radionuclides and external radiation are radiation osteitis, disturbed bone growth, myelofibrosis, and bone tumors. The lesions in part are dependent on localization and character of the radiation, in part on dose. Data on radium were derived from dial painters, radium chemists and those treated some years ago by oral or parenteral administration. (U.S.)

Parametric imaging for characterizing focal liver lesions in contrast-enhanced ultrasound.

Science.gov (United States)

Rognin, Nicolas G; Arditi, Marcel; Mercier, Laurent; Frinking, Peter J A; Schneider, Michel; Perrenoud, Geneviève; Anaye, Anass; Meuwly, Jean-Yves; Tranquart, François

2010-11-01

The differentiation between benign and malignant focal liver lesions plays an important role in diagnosis of liver disease and therapeutic planning of local or general disease. This differentiation, based on characterization, relies on the observation of the dynamic vascular patterns (DVP) of lesions with respect to adjacent parenchyma, and may be assessed during contrast-enhanced ultrasound imaging after a bolus injection. For instance, hemangiomas (i.e., benign lesions) exhibit hyper-enhanced signatures over time, whereas metastases (i.e., malignant lesions) frequently present hyperenhanced foci during the arterial phase and always become hypo-enhanced afterwards. The objective of this work was to develop a new parametric imaging technique, aimed at mapping the DVP signatures into a single image called a DVP parametric image, conceived as a diagnostic aid tool for characterizing lesion types. The methodology consisted in processing a time sequence of images (DICOM video data) using four consecutive steps: (1) pre-processing combining image motion correction and linearization to derive an echo-power signal, in each pixel, proportional to local contrast agent concentration over time; (2) signal modeling, by means of a curve-fitting optimization, to compute a difference signal in each pixel, as the subtraction of adjacent parenchyma kinetic from the echopower signal; (3) classification of difference signals; and (4) parametric image rendering to represent classified pixels as a support for diagnosis. DVP parametric imaging was the object of a clinical assessment on a total of 146 lesions, imaged using different medical ultrasound systems. The resulting sensitivity and specificity were 97% and 91%, respectively, which compare favorably with scores of 81 to 95% and 80 to 95% reported in medical literature for sensitivity and specificity, respectively.

Benzo[a]pyrene treatment leads to changes in nuclear protein expression and alternative splicing

Energy Technology Data Exchange (ETDEWEB)

Yan Chunlan; Wu Wei [Department of Toxicology, Zhejiang University School of Public Health, 388 Yu-Hang-Tang Road, Hangzhou, Zhejiang 310058 (China); Li Haiyan [Department of Toxicology, Zhejiang University School of Public Health, 388 Yu-Hang-Tang Road, Hangzhou, Zhejiang 310058 (China); Huzhou Maternity and Child Care Hospital, Huzhou, Zhejiang 313000 (China); Zhang Guanglin [Department of Toxicology, Zhejiang University School of Public Health, 388 Yu-Hang-Tang Road, Hangzhou, Zhejiang 310058 (China); Duerksen-Hughes, Penelope J. [Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92354 (United States); Zhu Xinqiang, E-mail: zhuxq@zju.edu.cn [Department of Toxicology, Zhejiang University School of Public Health, 388 Yu-Hang-Tang Road, Hangzhou, Zhejiang 310058 (China); Yang Jun, E-mail: gastate@zju.edu.cn [Department of Toxicology, Zhejiang University School of Public Health, 388 Yu-Hang-Tang Road, Hangzhou, Zhejiang 310058 (China); Zhejiang-California International Nanosystems Institute, Hangzhou, Zhejiang 310029 (China)

2010-04-01

Benzo[a]pyrene (BaP) is a potent pro-carcinogen generated from the combustion of fossil fuel and cigarette smoke. Previously, using a proteomic approach, we have shown that BaP can induce changes in the expression of many cellular proteins, including transcription regulators. In the present study, using a similar approach, we examined the nuclear protein response to BaP in HeLa cells and found that BaP treatment caused expression changes in many nuclear proteins. Twenty-four of these proteins were successfully identified, several of which are involved in the alternative splicing of mRNA, DNA replication, recombination, and repair. The changed expression levels were further confirmed by immunoblot analysis using specific antibodies for two proteins, Lamin A and mitotic checkpoint protein Bub3. The nuclear localization of these two proteins was also confirmed by confocal microscopy. To determine whether alternative splicing was activated following BaP treatment, we examined Fas and CD44, two genes previously shown to be targets of alternative splicing in respond to DNA damage. While no significant activation of alternative splicing was observed for Fas, CD44 splicing variants were found after BaP treatment. Together, these data show that DNA damage induces dramatic changes in nuclear protein expression, and that alternative splicing might be involved in the cellular response to DNA damage.

[Hematotoxic lesions caused by non-steroidal antirheumatic agents].

Science.gov (United States)

Stobbe, H; Hüge, W

1980-12-01

Among the lesions of haematopoiesis conditioned by medicaments the lesions by non-steroidal antirheumatic drugs occupy the first place. They get their significance by the fact that they are not so infrequently irreparable and thus show an unfavourable prognosis. On principle in pathogenetic respect lesions by immunologic reactions which vastly do not depend on the dosage, are to be demarcated from the toxically conditioned side-effects which depend on dosage. Conditioned by drugs aplastic syndromes of the bone marrow are not in every case strongly depending on dosage. For this is to be assumed an individual, particular sensitivity of the haematopoietic stem cells (stem cell defect). Of the anti-rheumatic drugs used for the basic therapy chloroquine derivations, gold, D-penicillamine, immunosuppressives and levamisol may effect disturbances of the haematopoiesis, for which facts are examples are given. This concerns also the symptomatically acting antirheumatic drugs. An overestimation of rare side-effects of drugs should not block the application of certain medicaments, however, they should be given only in such a high dosage as it is necessary. In combinations of antirheumatic drugs every individual drug is considered as causative factor. Interactions are particularly be taken into consideration. Control programmes, particularly with certain laboratory parameters, give the early recognition of side-effects and render possible to avoid severe effects.

Imaging review of lipomatous musculoskeletal lesions

Directory of Open Access Journals (Sweden)

Burt Ashley M.

2017-01-01

Full Text Available Lipomatous lesions are common musculoskeletal lesions that can arise within the soft tissues, bone, neurovascular structures, and synovium. The majority of these lesions are benign, and many of the benign lesions can be diagnosed by radiologic evaluation. However, radiologic differences between benign and malignant lipomatous lesions may be subtle and pathologic correlation is often needed. The use of sonography, computed tomography (CT, and magnetic resonance imaging (MRI is useful not only in portraying fat within the lesion, but also for evaluating the presence and extent of soft tissue components. Lipomas make up most soft tissue lipomatous lesions, but careful evaluation must be performed to distinguish these lesions from a low-grade liposarcoma. In addition to the imaging appearance, the location of the lesion and the patient demographics can be utilized to help diagnose other soft tissue lipomatous lesions, such as elastofibroma dorsi, angiolipoma, lipoblastoma, and hibernoma. Osseous lipomatous lesions such as a parosteal lipoma and intraosseous lipoma occur less commonly as their soft tissue counterpart, but are also benign. Neurovascular and synovial lipomatous lesions are much rarer lesions but demonstrate more classic radiologic findings, particularly on MRI. A review of the clinical, radiologic, and pathologic characteristics of these lesions is presented.

Hock lesions and free-stall design.

Science.gov (United States)

Weary, D M; Taszkun, I

2000-04-01

We compared the prevalence and severity of skin lesions on the hocks of lactating dairy cows in southern British Columbia, comparing 20 farms using three common bedding surfaces: sawdust, sand, and geotextile mattresses. Skin lesions were scored at five positions on the hock. For each position we noted if the lesion showed inflammatory attributes, and then assigned a severity score. Of the 1752 lactating cows scored, 1267 cows (73%) had at least one hock lesion. Of those cows with lesions, 87% had lesions on both legs, 76% had lesions on more than one location on the hock, and 78% had a lesion of at least moderate severity (i.e., evidence of skin breakage or an area of hair loss >10 cm2). Lesions were most prevalent on farms that used geotextile mattresses (91% of cows) and least common on farms that used sand (24% of cows). Moreover, lesions on cows from farms using mattresses were more numerous and more severe than those on cows from sand-bedded farms. The prevalence and severity of lesions on farms using sawdust was intermediate. Lesions also varied in relation to location on the hock. For farms using geotextile mattresses, lesions were more common and more severe on the lateral surfaces of both the tuber calcis and the tarsal joint. On farms using sawdust, lesions were common on the dorsal surface of the tuber calcis and the lateral surfaces of both the tuber calcis and the tarsal joint. Lesions were rare on all five positions for cows from sand-bedded farms. Among the 10 farms sampled using sawdust, we found a significant negative relationship between the length of the stall and severity of lesions. For cows with lesions, the number and severity of lesions increased with age.

Characterization of Adrenal Lesions on Unenhanced MRI Using Texture Analysis: A Machine-Learning Approach.

Science.gov (United States)

Romeo, Valeria; Maurea, Simone; Cuocolo, Renato; Petretta, Mario; Mainenti, Pier Paolo; Verde, Francesco; Coppola, Milena; Dell'Aversana, Serena; Brunetti, Arturo

2018-01-17

Adrenal adenomas (AA) are the most common benign adrenal lesions, often characterized based on intralesional fat content as either lipid-rich (LRA) or lipid-poor (LPA). The differentiation of AA, particularly LPA, from nonadenoma adrenal lesions (NAL) may be challenging. Texture analysis (TA) can extract quantitative parameters from MR images. Machine learning is a technique for recognizing patterns that can be applied to medical images by identifying the best combination of TA features to create a predictive model for the diagnosis of interest. To assess the diagnostic efficacy of TA-derived parameters extracted from MR images in characterizing LRA, LPA, and NAL using a machine-learning approach. Retrospective, observational study. Sixty MR examinations, including 20 LRA, 20 LPA, and 20 NAL. Unenhanced T 1 -weighted in-phase (IP) and out-of-phase (OP) as well as T 2 -weighted (T 2 -w) MR images acquired at 3T. Adrenal lesions were manually segmented, placing a spherical volume of interest on IP, OP, and T 2 -w images. Different selection methods were trained and tested using the J48 machine-learning classifiers. The feature selection method that obtained the highest diagnostic performance using the J48 classifier was identified; the diagnostic performance was also compared with that of a senior radiologist by means of McNemar's test. A total of 138 TA-derived features were extracted; among these, four features were selected, extracted from the IP (Short_Run_High_Gray_Level_Emphasis), OP (Mean_Intensity and Maximum_3D_Diameter), and T 2 -w (Standard_Deviation) images; the J48 classifier obtained a diagnostic accuracy of 80%. The expert radiologist obtained a diagnostic accuracy of 73%. McNemar's test did not show significant differences in terms of diagnostic performance between the J48 classifier and the expert radiologist. Machine learning conducted on MR TA-derived features is a potential tool to characterize adrenal lesions. 4 Technical Efficacy: Stage 2 J

Effect of Soil Aging on the Phytoremediation Potential of Zea mays in Chromium and Benzo[a]Pyrene Contaminated Soils.

Science.gov (United States)

Chigbo, Chibuike

2015-06-01

This study compared the phytoremediation potential of Zea mays in soil either aged or freshly amended with chromium (Cr) and benzo[a]pyrene (B[a]P). Z. mays showed increased shoot biomass in aged soils than in freshly spiked soils. The shoot biomass in contaminated soils increased by over 50% in aged soil when compared to freshly amended soils, and over 29% more Cr was accumulated in the shoot of Z. mays in aged soil than in freshly amended soil. Planting Z. mays in aged soil helped in the dissipation of more than 31% B[a]P than in freshly spiked soil, but in the absence of plants, there seemed to be no difference between the dissipation rates of B[a]P in freshly and aged co-contaminated soil. Z. mays seemed to enhance the simultaneous removal of Cr and B[a]P in aged soil than in freshly spiked soil and hence can be a good plant choice for phytoremediation of co-contaminated soils.

Oropharynx lesion biopsy

Science.gov (United States)

... as papilloma) Fungal infections (such as candida) Histoplasmosis Oral lichen planus Precancerous sore (leukoplakia) Viral infections (such as Herpes simplex) Risks Risks of the procedure may ... Throat lesion biopsy; Biopsy - mouth or throat; Mouth lesion biopsy; Oral cancer - biopsy ...

TU-AB-BRA-05: Repeatability of [F-18]-NaF PET Imaging Biomarkers for Bone Lesions: A Multicenter Study

International Nuclear Information System (INIS)

Lin, C; Bradshaw, T; Perk, T; Harmon, S; Jeraj, R; Liu, G

2015-01-01

Purpose: Quantifying the repeatability of imaging biomarkers is critical for assessing therapeutic response. While therapeutic efficacy has been traditionally quantified by SUV metrics, imaging texture features have shown potential for use as quantitative biomarkers. In this study we evaluated the repeatability of quantitative "1"8F-NaF PET-derived SUV metrics and texture features in bone lesions from patients in a multicenter study. Methods: Twenty-nine metastatic castrate-resistant prostate cancer patients received whole-body test-retest NaF PET/CT scans from one of three harmonized imaging centers. Bone lesions of volume greater than 1.5 cm"3 were identified and automatically segmented using a SUV>15 threshold. From each lesion, 55 NaF PET-derived texture features (including first-order, co-occurrence, grey-level run-length, neighbor gray-level, and neighbor gray-tone difference matrix) were extracted. The test-retest repeatability of each SUV metric and texture feature was assessed with Bland-Altman analysis. Results: A total of 315 bone lesions were evaluated. Of the traditional SUV metrics, the repeatability coefficient (RC) was 12.6 SUV for SUVmax, 2.5 SUV for SUVmean, and 4.3 cm"3 for volume. Their respective intralesion coefficients of variation (COVs) were 12%, 17%, and 6%. Of the texture features, COV was lowest for entropy (0.03%) and highest for kurtosis (105%). Lesion intraclass correlation coefficient (ICC) was lowest for maximum correlation coefficient (ICC=0.848), and highest for entropy (ICC=0.985). Across imaging centers, repeatability of texture features and SUV varied. For example, across imaging centers, COV for SUVmax ranged between 11–23%. Conclusion: Many NaF PET-derived SUV metrics and texture features for bone lesions demonstrated high repeatability, such as SUVmax, entropy, and volume. Several imaging texture features demonstrated poor repeatability, such as SUVtotal and SUVstd. These results can be used to establish response criteria

Inter-algorithm lesion volumetry comparison of real and 3D simulated lung lesions in CT

Science.gov (United States)

Robins, Marthony; Solomon, Justin; Hoye, Jocelyn; Smith, Taylor; Ebner, Lukas; Samei, Ehsan

2017-03-01

The purpose of this study was to establish volumetric exchangeability between real and computational lung lesions in CT. We compared the overall relative volume estimation performance of segmentation tools when used to measure real lesions in actual patient CT images and computational lesions virtually inserted into the same patient images (i.e., hybrid datasets). Pathologically confirmed malignancies from 30 thoracic patient cases from Reference Image Database to Evaluate Therapy Response (RIDER) were modeled and used as the basis for the comparison. Lesions included isolated nodules as well as those attached to the pleura or other lung structures. Patient images were acquired using a 16 detector row or 64 detector row CT scanner (Lightspeed 16 or VCT; GE Healthcare). Scans were acquired using standard chest protocols during a single breath-hold. Virtual 3D lesion models based on real lesions were developed in Duke Lesion Tool (Duke University), and inserted using a validated image-domain insertion program. Nodule volumes were estimated using multiple commercial segmentation tools (iNtuition, TeraRecon, Inc., Syngo.via, Siemens Healthcare, and IntelliSpace, Philips Healthcare). Consensus based volume comparison showed consistent trends in volume measurement between real and virtual lesions across all software. The average percent bias (+/- standard error) shows -9.2+/-3.2% for real lesions versus -6.7+/-1.2% for virtual lesions with tool A, 3.9+/-2.5% and 5.0+/-0.9% for tool B, and 5.3+/-2.3% and 1.8+/-0.8% for tool C, respectively. Virtual lesion volumes were statistically similar to those of real lesions (.05 in most cases. Results suggest that hybrid datasets had similar inter-algorithm variability compared to real datasets.

Investigating the use of texture features for analysis of breast lesions on contrast-enhanced cone beam CT

Science.gov (United States)

Wang, Xixi; Nagarajan, Mahesh B.; Conover, David; Ning, Ruola; O'Connell, Avice; Wismueller, Axel

2014-04-01

Cone beam computed tomography (CBCT) has found use in mammography for imaging the entire breast with sufficient spatial resolution at a radiation dose within the range of that of conventional mammography. Recently, enhancement of lesion tissue through the use of contrast agents has been proposed for cone beam CT. This study investigates whether the use of such contrast agents improves the ability of texture features to differentiate lesion texture from healthy tissue on CBCT in an automated manner. For this purpose, 9 lesions were annotated by an experienced radiologist on both regular and contrast-enhanced CBCT images using two-dimensional (2D) square ROIs. These lesions were then segmented, and each pixel within the lesion ROI was assigned a label - lesion or non-lesion, based on the segmentation mask. On both sets of CBCT images, four three-dimensional (3D) Minkowski Functionals were used to characterize the local topology at each pixel. The resulting feature vectors were then used in a machine learning task involving support vector regression with a linear kernel (SVRlin) to classify each pixel as belonging to the lesion or non-lesion region of the ROI. Classification performance was assessed using the area under the receiver-operating characteristic (ROC) curve (AUC). Minkowski Functionals derived from contrastenhanced CBCT images were found to exhibit significantly better performance at distinguishing between lesion and non-lesion areas within the ROI when compared to those extracted from CBCT images without contrast enhancement (p < 0.05). Thus, contrast enhancement in CBCT can improve the ability of texture features to distinguish lesions from surrounding healthy tissue.

The Vitamin D Analogue Calcipotriol Reduces the Frequency of CD8+IL-17+ T Cells in Psoriasis Lesions

DEFF Research Database (Denmark)

Dyring-Andersen, B; Bonefeld, C M; Bzorek, M

2015-01-01

(+) T cells and innate lymphoid cells (ILC) and their production of IL-17A, IFN-γ and IL-22 in psoriasis lesions in patients with chronic plaque psoriasis. Eighteen patients with psoriasis were included, and two similar psoriasis lesions were chosen for each patient. One lesion was treated......The vitamin D analogue calcipotriol is an immunomodulatory drug widely used to treat psoriasis; however, how calcipotriol affects the immune cells in psoriasis lesions is not fully understood. The aim of this study was to investigate the effect of calcipotriol on the frequency of CD4(+) and CD8...... with calcipotriol (50 μg/g) and the other with vehicle twice a day for 14 days. The clinical effect was measured by degree of erythema, scaling and induration in each lesion (SUM score). Skin biopsies were collected for histological and immunohistochemical analyses. Skin-derived cells were isolated and analysed...

Dependence of mitochondrial and cytosolic adenine nucleotides on oxygen partial pressure in isolated hepatocytes. Application of a new rapid high pressure filtration technique for fractionation.

OpenAIRE

Hummerich, H; de Groot, H; Noll, T; Soboll, S

1988-01-01

By using a new rapid high pressure filtration technique, mitochondrial and cytosolic ATP and ADP contents were determined in isolated hepatocytes at different oxygen partial pressures. At 670 mmHg, subcellular adenine nucleotide contents and ATP/ADP ratios were comparable with values obtained with the digitonin fractionation technique. However at lower oxygen partial pressure ADP appears to be rephosphorylated during digitonin fractionation whereas with high pressure filtration fractionation ...

Formation and repair of physically and chemically induced DNA damage in human cells. Final report, September 1, 1976-November 30, 1978

International Nuclear Information System (INIS)

Cerutti, P.A.

1979-01-01

The major topic was the study of the formation and repair of DNA damage by energy related physical and chemical agents in cultured human cells. Two pathways of damage production were distinguished: (1) indirect action, i.e., attack of DNA by active oxygen species which are formed by the reaction of the primary agent with a non-DNA target; and (2) direct action, i.e., reaction of the primary agent or a chemical derivative of the primary agent with DNA usually resulting in the formation of a covalent adduct. Near-ultraviolet light and ionizing radiation were studied as agents which operate at least in part via indirect action and benzo(a)pyrene as chemical carcinogen operating mostly by direct action. The formation of monomeric thymine damage of the 5,6-dihydroxy-dihydrothymine type by γ-rays and ultraviolet light was investigated. Indirect action of near-ultraviolet light is also responsible for the induction of DNA single strand breaks. Their formation and repair following exposure to 313 nm light was studied in skin fibroblasts from patients with the hereditary disease Xeroderma pigmentosum (XP). Excision repair of γ-ray induced 5,6-dihydroxy-dihydrothymine type lesions was studied in fibroblasts from Ataxia telangiectasia (AT) patients. The formation and repair of covalent purine adducts was studied in actively metabolizing rodent and human cells following treatment with the procarcinogen benzo(a)pyrene and with the ultimate metabolite benzo(a)pyrene-diol-epoxide I

Assessment of sediment quality based on toxic equivalent benzo[a]Pyrene concentration

International Nuclear Information System (INIS)

King, T.L.; Lee, K.

2004-01-01

This study examined benzo[a]pyrene (B[a]P) as an indicator and its thresholds for polycyclic aromatic hydrocarbons (PAH) in sediments. The indicator, based on toxicity and carcinogenic effects, was selected to assess the marine environment and changes in marine environmental quality (MEQ) in Sydney Harbour, Nova Scotia. It was shown that the bioavailability of B[a]P and other PAHs is greatly affected by the quality and quantity of dissolved organic matter and organic carbon content. Two coal coke facilities were constructed on the shore of Sydney Harbour in the 19th century. For many years, the coke-ovens discharged toxic liquid effluent through the Tar Ponds into the harbour, contaminating the ground and surface water with arsenic, lead and other toxins. It also led to the accumulation of PAHs and polychlorinated biphenyls. A recent assessment of PAH contamination of Sydney Harbour has focused on the exposure of organisms to contaminants as well as the biological effects on the organisms. All samples collected from the South Arm of Sydney Harbour exceeded the upper threshold of established regulatory guidelines. Samples from the Northwest Arm were within regulatory limits, suggesting that industrial and municipal sources were the primary sources of pollution. PAH concentrations were used to identify sediments that exceed effects thresholds based on MEQ guidelines. The results were compared to actual observations of biological effects. Toxic equivalency factors were established for B[a]P and other PAHs in order to estimate cumulative exposure levels. The concentrations can be compared to regulatory sediment quality guidelines established in Canada and the United States for the protection of marine life. 34 refs., 6 tabs., 2 figs

Lesion-induced increase in survival and migration of human neural progenitor cells releasing GDNF

Science.gov (United States)

Behrstock, Soshana; Ebert, Allison D.; Klein, Sandra; Schmitt, Melanie; Moore, Jeannette M.; Svendsen, Clive N.

2009-01-01

The use of human neural progenitor cells (hNPC) has been proposed to provide neuronal replacement or astrocytes delivering growth factors for brain disorders such as Parkinson’s and Huntington’s disease. Success in such studies likely requires migration from the site of transplantation and integration into host tissue in the face of ongoing damage. In the current study, hNPC modified to release glial cell line derived neurotrophic factor (hNPCGDNF) were transplanted into either intact or lesioned animals. GDNF release itself had no effect on the survival, migration or differentiation of the cells. The most robust migration and survival was found using a direct lesion of striatum (Huntington’s model) with indirect lesions of the dopamine system (Parkinson’s model) or intact animals showing successively less migration and survival. No lesion affected differentiation patterns. We conclude that the type of brain injury dictates migration and integration of hNPC which has important consequences when considering transplantation of these cells as a therapy for neurodegenerative diseases. PMID:19044202

Ebselen induces mitochondrial permeability transition because of its interaction with adenine nucleotide translocase.

Science.gov (United States)

Pavón, Natalia; Correa, Francisco; Buelna-Chontal, Mabel; Hernández-Esquivel, Luz; Chávez, Edmundo

2015-10-15

Mitochondrial permeability transition is a process established through massive Ca(2+) load in addition to an inducer reagent. Ebselen (Ebs), an antioxidant seleno compound, has been introduced as a reagent which inhibits mitochondrial dysfunction induced by permeability transition. Paradoxically enough, it has been shown that Ebs may also be able to induce the opening of the mitochondrial non-selective pores. This study was performed with the purpose of establishing the membrane system involved in Ebs-induced pore opening. Permeability transition was appraised by analyzing the following: i) matrix Ca(2+) release, and mitochondrial swelling, ii) efflux of cytochrome c, and iii) the inhibition of superoxide dismutase. All of these adverse reactions were inhibited by N-ethylmaleimide and cyclosporin A. At concentrations from 5 to 20 μM, we found that Ebs induces non-specific membrane permeability. Remarkably, Ebs blocks the binding of the fluorescent reagent eosin-5-maleimide to the thiol groups of the adenine nucleotide translocase. Based on the above, it is tempting to hypothesize that Ebs induces pore opening through its binding to the ADP/ATP carrier. Copyright © 2015 Elsevier Inc. All rights reserved.

Lesion activity assessment

DEFF Research Database (Denmark)

Ekstrand, K R; Zero, D T; Martignon, S

2009-01-01

in response to cariogenic plaque as well as lesion arrest. Based on this understanding, different clinical scoring systems have been developed to assess the severity/depth and activity of lesions. A recent system has been devised by the International Caries Detection and Assessment System Committee...

Bone marrow-derived CD13+ cells sustain tumor progression

Science.gov (United States)

Dondossola, Eleonora; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2014-01-01

Non-malignant cells found within neoplastic lesions express alanyl (membrane) aminopeptidase (ANPEP, best known as CD13), and CD13-null mice exhibit limited tumor growth and angiogenesis. We have recently demonstrated that a subset of bone marrow-derived CD11b+CD13+ myeloid cells accumulate within neoplastic lesions in several murine models of transplantable cancer to promote angiogenesis. If these findings were confirmed in clinical settings, CD11b+CD13+ myeloid cells could become a non-malignant target for the development of novel anticancer regimens. PMID:25339996

Alterations in the metabolism of benzo[a]pyrene in syrian hamster embryo (SHE) cells pretreated with phenolic antioxidants

International Nuclear Information System (INIS)

Strniste, G.F.; Okinaka, R.T.; Chen, D.J.

1983-01-01

Inhibition of chemical- or radiation-induced neoplasia has been observed in animals whose diets were supplemented with antioxidants commonly used as food additives. Inhibition of the carcinogenicity of benzo[a]pyrene (BaP) or of 7,12-dimenthylbenz[a]anthracene (DMBA) - in rats has been achieved by the addition of the phenolic antioxidants butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) to the diet. Our data suggest that in SHE cells antioxidants inhibit the overall metabolism of BaP to its various oxidized moieties including 7,8-diol- and 7,8,9,10-tetrol-BaP. A plausible explanation for our results with SHE cells is that the antioxidants interact directly with AHH, thus inhibiting AHH metabolic capacity. From analysis of nuclear material from SHE cells (+- antioxidants) incubated for 36 hours with BaP at 1 μg/ml, it is calculated that 4.6, 2.4 and 2.9 pmol BaP are bound to the DNA isolated from 10 7 nuclei of control, BHA-(20 μg/ml) and p-MP-(10 μg/ml) treated cultures, respectively

Screening of Lactobacillus strains for their ability to bind benzo(a)pyrene and the mechanism of the process.

Science.gov (United States)

Zhao, Hongfei; Zhou, Fang; Qi, Yeqiong; Dziugan, Piotr; Bai, Fengling; Walczak, Piotr; Zhang, Bolin

2013-09-01

In order to investigate the binding ability of Lactobacillus strains to Benzo(a)pyrene (BaP), 15 strains were analysed. L. plantarum CICC 22135 and L. pentosus CICC 23163 exhibited high efficiency in removing BaP from aqueous medium; the binding rates were 66.76% and 64.31%, respectively. This process was affected by temperature, incubation time and pH, and cell viability was not necessary for the binding ability. Additionally, both strains, especially strain CICC 23163 showed high specificity in binding BaP. The cell-BaP complexes were stable in aqueous medium. The mechanism of binding was investigated by examining the binding ability of different components of the microorganism cells. The results revealed that peptidoglycans played an important role in binding BaP and its structural integrity was required. Consequently, we proposed that the mechanism of this process was a physisorption and peptidoglycan was the main binding site. These two strains may be used for dietary detoxification in human diet and animal feed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Nitration of benzo[a]pyrene adsorbed on coal fly ash particles by nitrogen dioxide: role of thermal activation.

Science.gov (United States)

Kristovich, Robert L; Dutta, Prabir K

2005-09-15

Nitration of benzo[a]pyrene (BaP) by nitrogen dioxide (NO2) adsorbed on the surface of thermally activated coal fly ash and model aluminosilicate particles led to the formation of nitrobenzo[a]pyrenes as verified by extraction and gas chromatography/mass spectrometry (GC/MS). In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) was utilized to follow the nitration reaction on the surface of zeolite Y. Nitrobenzo[a]pyrene formation was observed along with the formation of nitrous acid and nitrate species. The formation of the BaP radical cation was also observed on thermally activated aluminosilicate particles by electron spin resonance (ESR) spectroscopy. On the basis of GC/MS, DRIFTS, and ESR spectroscopy results, a mechanism of nitration involving intermediate BaP radical cations generated on thermally activated aluminosilicate particles is proposed. These observations have led to the hypothesis that nitration of adsorbed polyaromatic hydrocarbons on coal fly ash by reaction with nitrogen oxides can occur in the smokestack, but with the aging of the fly ash particles, the extent of the nitration reaction will be diminished.

MALIGNANCY IN LARGE COLORECTAL LESIONS

Directory of Open Access Journals (Sweden)

Carlos Eduardo Oliveira dos SANTOS

2014-09-01

Full Text Available Context The size of colorectal lesions, besides a risk factor for malignancy, is a predictor for deeper invasion Objectives To evaluate the malignancy of colorectal lesions ≥20 mm. Methods Between 2007 and 2011, 76 neoplasms ≥20 mm in 70 patients were analyzed Results The mean age of the patients was 67.4 years, and 41 were women. Mean lesion size was 24.7 mm ± 6.2 mm (range: 20 to 50 mm. Half of the neoplasms were polypoid and the other half were non-polypoid. Forty-two (55.3% lesions were located in the left colon, and 34 in the right colon. There was a high prevalence of III L (39.5% and IV (53.9% pit patterns. There were 72 adenomas and 4 adenocarcinomas. Malignancy was observed in 5.3% of the lesions. Thirty-three lesions presented advanced histology (adenomas with high-grade dysplasia or early adenocarcinoma, with no difference in morphology and site. Only one lesion (1.3% invaded the submucosa. Lesions larger than 30 mm had advanced histology (P = 0.001. The primary treatment was endoscopic resection, and invasive carcinoma was referred to surgery. Recurrence rate was 10.6%. Conclusions Large colorectal neoplasms showed a low rate of malignancy. Endoscopic treatment is an effective therapy for these lesions.

Simultaneous determination of adenine guanine and thymine at multi-walled carbon nanotubes incorporated with poly(new fuchsin) composite film

Energy Technology Data Exchange (ETDEWEB)

Tang Ching; Yogeswaran, Umasankar [Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No.1, Section 3, Chung-Hsiao East Road, Taipei 106, Taiwan (China); Chen, S.-M. [Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, No.1, Section 3, Chung-Hsiao East Road, Taipei 106, Taiwan (China)], E-mail: smchen78@ms15.hinet.net

2009-03-16

A composite film (MWCNTs-PNF) which contains multi-walled carbon nanotubes (MWCNTs) along with the incorporation of poly(new fuchsin) (PNF) has been synthesized on glassy carbon electrode (GCE), gold (Au) and indium tin oxide (ITO) by potentiostatic methods. The presence of MWCNTs in the composite film enhances surface coverage concentration ({gamma}) of PNF to {approx}176.5%, and increases the electron transfer rate constant (k{sub s}) to {approx}346%. The composite film also exhibits promising enhanced electrocatalytic activity towards the mixture of biochemical compounds such as adenine (AD), guanine (GU) and thymine (THY). The surface morphology of the composite film deposited on ITO has been studied using scanning electron microscopy and atomic force microscopy. These two techniques reveal that the PNF incorporated on MWCNTs. Electrochemical quartz crystal microbalance study reveals the enhancement in the functional properties of MWCNTs and PNF. The electrocatalytic responses of analytes at MWCNTs and MWCNTs-PNF films were measured using both cyclic voltammetry (CV) and differential pulse voltammetry (DPV). From electrocatalysis studies, well separated voltammetric peaks have been obtained at the composite film for AD, GU and THY, with the peak separation of 320.3 and 132.7 mV between GU-AD and AD-THY respectively. The sensitivity of the composite film towards AD, GU and THY in DPV technique is 218.18, 12.62 and 78.22 mA M{sup -1} cm{sup -2} respectively, which are higher than MWCNTs film. Further, electroanalytical studies of AD, GU and THY present in single-strand deoxyribonucleic acid (ssDNA) have been carried out using semi-derivative CV and DPV.

Cytotoxic and mutagenic effects of specific carcinogen-DNA adducts in diploid human fibroblasts

International Nuclear Information System (INIS)

McCormick, J.J.; Maher, V.M.

1985-01-01

A comparison of the cytotoxicity and mutagenicity of a series of carcinogens in normal diploid human fibroblasts and in cells deficient in one or more DNA repair processes has provided insight into the specific DNA adduct(s) responsible for these biological effects. The carcinogens tested include ultraviolet radiation; reactive derivatives of structurally related aromatic amides; metabolites of benzo(a)pyrene; the simple alkylating agents N-methyl-N'-nitro-N-nitrosoguanidine and N-ethyl-N-nitrosourea; and aflatoxin B 1 dichloride, a model for the reactive 2,3-epoxide of aflatoxin B 1 . Exponentially growing cells were exposed to agents and assayed for mutations and cell killing. Cells deficient in repair of particular DNA adducts or lesions proved more sensitive to the agent causing those lesions than did normally repairing cells. Many of the carcinogens were compared for their mutagenic and/or cytotoxic effect, not only as a function of dose administered, but also as a function of the initial number of adducts or photoproducts induced in DNA and the number remaining at critical times posttreatment. The results demonstrated a high correlation between the number of DNA lesions remaining unexcised at the time the DNA was replicated and frequency of mutations induced. Comparative studies of the frequency of UV-induced transformation of normal and repair-deficient cells showed this also to be true for transformation

CT diagnosis of sellar and juxtasellar lesions, 3. Non-tumorous lesions

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, Tatsuya [Nagoya Univ. (Japan). Faculty of Medicine

1982-08-01

A study is made of the usefulness and limitations of the CT diagnosis of sellar and juxtasellar lesions other than tumors. This study is based on 112 verified cases at Nagoya University Hospital from October, 1976, to December, 1981. The lesions included in this study are classified into four groups: vascular, inflammatory, traumatic lesion, and congenital anomaly. Although cerebral angiography is the cardinal method for the diagnosis of vascular lesions, CT is useful for the evaluation of a giant aneurysm, the localization of bleeding, or infarction by a ruptured aneurysm. Radiation brain necrosis, a special form of vascular lesion, can also be diagnosed if the critical analysis is made after previous irradiation. CT findings are helpful for the local diagnosis of acute inflammatory lesions, such as basal meningitis or abscess, but specific diagnosis is made on the basis of clinical signs and CSF study. Abnormal CT findings are obtained from a chronic inflammatory process, such as arachnoiditis adhesiva, glanuloma, or mucocele. Differential diagnosis is necessary with brain tumors. The CT findings of an arachnoid cyst are often diagnostic. Metrizamide or air cisternography, either combined with CT or without it, is important for the diagnosis of basal meningoencephalocele and hypothalamic hamaroma. Pneumocephalus and an intracranial foreign body resulting from a head injury can be diagnosed by plain skull and CT. The diagnosis of CSF leakage or prolapse cerebri associated with a skull-base fracture has been most difficult, but even it is possible by a combination of polytomography and high-resolution CT with metrizamide cisternography.

Bone marrow-derived cells and biophysical stimulation for talar osteochondral lesions: a randomized controlled study.

Science.gov (United States)

Cadossi, Matteo; Buda, Roberto Emanuele; Ramponi, Laura; Sambri, Andrea; Natali, Simone; Giannini, Sandro

2014-10-01

Osteochondral lesions of the talus (OLT) frequently occur after ankle sprains in young patients participating in sports activities. These injuries may lead to chronic pain, joint swelling, and finally osteoarthritis, therefore, surgical repair is frequently needed. A collagen scaffold seeded with bone marrow-derived cells (BMDCs) harvested from patient's iliac crest and implanted into the OLT through a single arthroscopic procedure has been recently proposed as an effective treatment option. Nevertheless, BMDCs, embedded in an inflammatory environment, tend to differentiate toward a fibroblast phenotype with a consequential loss of mechanical characteristics. Biophysical stimulation with pulsed electromagnetic fields (PEMFs) has been shown to promote anabolic chondrocyte activity, stimulate proteoglycan synthesis, and reduce the release of the most relevant pro-inflammatory cytokines. The aim of this randomized controlled trial was to evaluate the effects of PEMFs on clinical outcome in patients who underwent BMDCs transplantation for OLT. Thirty patients affected by grade III and IV Outerbridge OLT underwent BMDCs transplantation. After surgery, patients were randomly assigned to either experimental group (PEMFs 4 hours per day for 60 days starting within 3 days after operation) or control group. Clinical outcome was evaluated with (American Orthopaedic Foot and Ankle Society) AOFAS score, Visual Analog Scale (VAS), and Short Form-36 (SF-36). Significantly higher AOFAS score was recorded in the experimental group both at 6 or 12 months follow-up. At 60 days and 6 and 12 months follow-up, significant lower pain was observed in the experimental group. No significant difference was found in SF-36 between groups. A superior clinical outcome was found in the experimental group with more than 10 points higher AOFAS score at final follow-up. Biophysical stimulation started soon after surgery aided patient recovery leading to pain control and a better clinical outcome

Selective inhibitory effects of (S)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)adenine and 1-(2'-deoxy-2'-fluoro-ß-D-arabinofuranosyl)-5-iodouracil on seal herpesvirus (Phocid herpesvirus 1) infection in vitro.

NARCIS (Netherlands)

A.D.M.E. Osterhaus (Albert); J. Groen (Jan); E. de Clercq

1987-01-01

textabstractFrom a selection of 25 antiviral compounds with specific anti-herpes activity or broad-spectrum antiviral properties, two compounds, namely (S)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)adenine and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil, appeared particularly effective

Expression of ABCG2 and Bmi-1 in oral potentially malignant lesions and oral squamous cell carcinoma

International Nuclear Information System (INIS)

Dalley, Andrew J; Pitty, Luke P; Major, Aidan G; AbdulMajeed, Ahmad A; Farah, Camile S

2014-01-01

Early diagnosis is vital for effective treatment of oral squamous cell carcinoma (OSCC). The optimal time for clinical intervention is prior to malignancy when patients present with oral potentially malignant lesions such as leukoplakia or erythroplakia. Transformation rates for oral dysplasia vary greatly and more rigorous methods are needed to predict the malignant potential of oral lesions. We hypothesized that the expression of two putative stem cell markers, ABCG2 and Bmi-1, would correlate with disease severity for non diseased, potentially malignant and OSCC specimens and cell lines derived from an equivalent range of tissues. We compared immunoreactive protein and relative gene expression of ABCG2 and Bmi-1 in eight cell lines derived from source tissues ranging in disease severity from normal (OKF6-TERT2) through mild and moderate/severe dysplasia (DOK, POE-9n) to OSCC (PE/CA-PJ15, SCC04, SCC25, SCC09, SCC15). We also analyzed immunoreactive protein expression of ABCG2 and Bmi-1 in 189 tissue samples with the same range of disease severity. A trend between oral lesion severity to ABCG2 and Bmi-1 immunostain intensity was observed. Flow cytometry of oral cell lines confirmed this trend and gave good correlation with RT-PCR results for ABCG2 (r = 0.919, P = 0.001; Pearson) but not Bmi-1 (r = −0.311). The results provide evidence of increased density of ABCG2 and Bmi-1-positive populations in malignant and oral potentially malignant lesions and derived cell lines, but that intragroup variability within IHC, flow cytometry, and RT-PCR results compromise the diagnostic potential of these techniques for discriminating oral dysplasia from normal tissue or OSCC

Functional expression of human adenine nucleotide translocase 4 in Saccharomyces cerevisiae.

Directory of Open Access Journals (Sweden)

Takashi Hamazaki

2011-04-01

Full Text Available The adenine nucleotide translocase (ANT mediates the exchange of ADP and ATP across the inner mitochondrial membrane. The human genome encodes multiple ANT isoforms that are expressed in a tissue-specific manner. Recently a novel germ cell-specific member of the ANT family, ANT4 (SLC25A31 was identified. Although it is known that targeted depletion of ANT4 in mice resulted in male infertility, the functional biochemical differences between ANT4 and other somatic ANT isoforms remain undetermined. To gain insight into ANT4, we expressed human ANT4 (hANT4 in yeast mitochondria. Unlike the somatic ANT proteins, expression of hANT4 failed to complement an AAC-deficient yeast strain for growth on media requiring mitochondrial respiration. Moreover, overexpression of hANT4 from a multi-copy plasmid interfered with optimal yeast growth. However, mutation of specific amino acids of hANT4 improved yeast mitochondrial expression and supported growth of the AAC-deficient yeast on non-fermentable carbon sources. The mutations affected amino acids predicted to interact with phospholipids, suggesting the importance of lipid interactions for function of this protein. Each mutant hANT4 and the somatic hANTs exhibited similar ADP/ATP exchange kinetics. These data define common and distinct biochemical characteristics of ANT4 in comparison to ANT1, 2 and 3 providing a basis for study of its unique adaptation to germ cells.

A Method for Extracting Suspected Parotid Lesions in CT Images using Feature-based Segmentation and Active Contours based on Stationary Wavelet Transform

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Wu, T. Y.; Lin, S. F.

2013-10-01

Automatic suspected lesion extraction is an important application in computer-aided diagnosis (CAD). In this paper, we propose a method to automatically extract the suspected parotid regions for clinical evaluation in head and neck CT images. The suspected lesion tissues in low contrast tissue regions can be localized with feature-based segmentation (FBS) based on local texture features, and can be delineated with accuracy by modified active contour models (ACM). At first, stationary wavelet transform (SWT) is introduced. The derived wavelet coefficients are applied to derive the local features for FBS, and to generate enhanced energy maps for ACM computation. Geometric shape features (GSFs) are proposed to analyze each soft tissue region segmented by FBS; the regions with higher similarity GSFs with the lesions are extracted and the information is also applied as the initial conditions for fine delineation computation. Consequently, the suspected lesions can be automatically localized and accurately delineated for aiding clinical diagnosis. The performance of the proposed method is evaluated by comparing with the results outlined by clinical experts. The experiments on 20 pathological CT data sets show that the true-positive (TP) rate on recognizing parotid lesions is about 94%, and the dimension accuracy of delineation results can also approach over 93%.

Purification and partial characterization of peroxidase from human term placenta of non-smokers: metabolism of benzo(a)pyrene-7, 8-dihydrodiol.

Science.gov (United States)

Madhavan, N D; Naidu, K A

2000-01-01

Peroxidase (Donor: H(2)O(2)oxidoreductase EC 1.11.1.7) from human term placentae of non-smokers was purified to homogeneity by a combination of NH(4)Cl extraction, affinity chromatography, (NH(4))(2)SO(4)precipitation, ion-exchange and gel filtration chromatography. The homogeneity of purified human placental peroxidase (HTPP) was confirmed by gel filtration, reverse phase high performance liquid chromatography (HPLC) and SDS-PAGE. Peroxidase was found to be a membrane bound enzyme. A high concentration of NH(4)Cl (1.2 m) was needed to extract and solublize the enzyme. Removal of the salt resulted in irreversible precipitation of the enzyme. The protein exhibited a molecular mass of 126 000 kDa according to gel filtration and approximately 60 000 kDa by SDS-PAGE, indicating that the peroxidase is a homodimer. The purified peroxidase showed an optimum pH range of 7 to 8.5 and the K(m)for H(2)O(2)and guaiacol were found to be 0.08 m m and 10.0 m m, respectively. The purified peroxidase oxidized several substrates, namely potassium iodide, tetramethyl benzidine, guaiacol, ortho dianisidne and tyrosine. The enzyme was resistant to thermal denaturation up to 70 degrees C and also to chaotropic agents, guanidinium chloride and urea. Spectral properties indicated the presence of Soret band at 433 which shifted to 451 nm on complexation with cyanide. The circular dichroism studies showed that HTPP has a predominantly helical secondary structure. The enzyme showed similarities to the myeloperoxidase with regard to spectral and catalytical properties but differed significantly in amino acid composition, the R(z)value and molecular mass. Purified HTPP differed from eosinophil peroxidase in all physico-chemical properties indicating that it is not of eosinophil origin, but may represent a distinct, constitutive peroxidase in human placenta. Further, purified peroxidase catalyzed oxidation of benzo(a)pyrene-7, 8-dihydrodiol in presence of tyrosine and hydrogen peroxide to BP

DNA alterations photosensitized by tetracycline and some of its derivatives

International Nuclear Information System (INIS)

Piette, J.; Decuyper, J.; Van de Vorst, A.

1986-01-01

Bacteriophage M13 mp10 DNA were irradiated with near-UV light in the presence of tetracycline derivatives and primed with synthetic oligonucleotide to be used for DNA synthesis using Escherichia coli DNA polymerase. Chain terminations were observed by denaturing polyacrylamide gel electrophoresis and mapped precisely. All the synthesis stops occurred before or at the level of guanine residues, showing that the photoreaction mediated by tetracycline derivatives led to a preferential alteration of guanine residues. These lesions were demonstrated to be induced in DNA through a pathway involving singlet oxygen. Tetracycline derivatives also photoinduced the breakage of the DNA sugar-phosphate backbone monitored by the conversion of supercoiled phi X174 DNA to a relaxed form. This lesion was shown to be initiated by hydroxyl radicals. The production of this free radical has been confirmed by electron paramagnetic resonance (EPR) spin trapping experiments using 5,5-dimethyl-1-pyrroline-N-oxide as spin trap. In addition to the EPR signal due to OH radicals trapping another unassigned signal has been detected

Concordance between fine-needle aspiration and core biopsies for osseous lesions by lesion imaging appearance and CT attenuation.

Science.gov (United States)

Li, John; Weissberg, Zoe; Bevilacqua, Thomas A; Yu, Gordon; Weber, Kristy; Sebro, Ronnie

2018-04-01

To compare the concordance between fine-needle aspiration and core biopsies for osseous lesions by lesion imaging appearance and CT attenuation. Retrospective review of 215 FNAs of osseous lesions performed in conjunction with core biopsy at our institution over a 6-year period (2011-2016). FNAs were interpreted independently of core biopsies. We assessed if FNA in conjunction with core biopsy increased diagnostic accuracy compared to core biopsy alone. We also calculated the concordance between FNA and core biopsy by lesion appearance, lesion CT attenuation, lesion histology, lesion location and FNA needle gauge size. Core biopsy alone provided the diagnosis in 207/215 cases (96.3%), however, the FNA provided the diagnosis in the remaining 8/215 cases (3.7%) where the core biopsy was non-diagnostic. There were 154 (71.6%) lytic lesions, 21 (9.8%) blastic lesions, 25 (11.6%) mixed lytic and blastic lesions and 15 (7.0%) lesions that were neither lytic nor blastic. The concordance between FNA and core biopsy for lytic osseous lesions (136/154 cases, 88.3%) was statistically significantly higher than that for blastic osseous lesions (13/21 cases, 61.9%) [P = 4.2 × 10 -3 ; 95% CI (0.02, 0.50)]. The concordance between FNA and core biopsy was higher for low-attenuation- (110/126) than high-attenuation (58/77) lesions (P = 0.028). The concordance between FNA and core biopsy was also higher for metastases (102/119 cases, 85.7%) than non-metastases (78/96, 81.3%) [P = 0.487; 95% CI (- 0.15, 0.065)]. There was no difference in the rate of concordance between FNA and core biopsy by lesion location or FNA needle gauge size (P > 0.05). FNA with core biopsy increases diagnostic rate compared to core biopsy alone or FNA alone. The concordance between FNA and core biopsy is higher for lytic lesions than for blastic lesions; and higher for low-attenuation lesions than for high-attenuation lesions.

Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis.

Science.gov (United States)

Smeets, Bart; Angelotti, Maria Lucia; Rizzo, Paola; Dijkman, Henry; Lazzeri, Elena; Mooren, Fieke; Ballerini, Lara; Parente, Eliana; Sagrinati, Costanza; Mazzinghi, Benedetta; Ronconi, Elisa; Becherucci, Francesca; Benigni, Ariela; Steenbergen, Eric; Lasagni, Laura; Remuzzi, Giuseppe; Wetzels, Jack; Romagnani, Paola

2009-12-01

Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner surface of Bowman's capsule can regenerate podocytes, but whether dysregulated proliferation of these progenitors contributes to crescent formation is unknown. In this study, we used confocal microscopy, laser capture microdissection, and real-time quantitative reverse transcriptase-PCR to demonstrate that hypercellular lesions of different podocytopathies and crescentic glomerulonephritis consist of three distinct populations: CD133(+)CD24(+)podocalyxin (PDX)(-)nestin(-) renal progenitors, CD133(+)CD24(+)PDX(+)nestin(+) transitional cells, and CD133(-)CD24(-)PDX(+)nestin(+) differentiated podocytes. In addition, TGF-beta induced CD133(+)CD24(+) progenitors to produce extracellular matrix, and these were the only cells to express the proliferation marker Ki67. Taken together, these results suggest that glomerular hyperplastic lesions derive from the proliferation of renal progenitors at different stages of their differentiation toward mature podocytes, providing an explanation for the pathogenesis of hyperplastic lesions in podocytopathies and crescentic glomerulonephritis.

Epidermal hydrogen peroxide is not increased in lesional and non-lesional skin of vitiligo.

Science.gov (United States)

Zailaie, Mohammad Z

2017-01-01

It is widely believed that the loss of the epidermal melanocytes in vitiligo is basically due to excessive oxidative stress. Previous research work described abnormal elevation of the absolute concentration of the epidermal hydrogen peroxide (H 2 O 2 ) in lesional and non-lesional skin of vitiligo. Based on this finding, our primary research objective was to use this feature as a screening marker in individuals at a great risk of developing vitiligo. Ninety-six patients of non-segmental vitiligo (NSV) of varying durations, skin phototypes, and treatment modalities (psoralen UVA-, narrow band UVB-treated) were recruited for this study. Raman spectroscopic measurements, using an external probehead, of the lesional and non-lesional skin were obtained, and the resulting spectra were analyzed using the Opus software package of the MultiRam spectrometer and the intensity of the peak at 875 cm -1 that represents the absolute concentration of H 2 O 2 was calculated. Contrary to previous reports, in patients of skin phototype IV, the absolute concentrations of H 2 O 2 in non-lesional and lesional NSV of all groups were non-significantly decreased compared to normal control. In patients of NSV of skin phototype V, the decrease in the absolute concentrations of H 2 O 2 was not significant in the untreated group, and a slight non-significant increase in the NBUVB-treated group was noted. However, in the PUVA-treated group, the non-lesional skin demonstrated significant increase in the absolute concentration of H 2 O 2 , whereas the lesional skin showed only a slight non-significant increase compared to normal control. In NSV patients of skin phototype VI who were previously treated with PUVA, the non-lesional skin showed a slight non-significant increase in the absolute concentration of H 2 O 2 ; however, the lesional skin showed a marked significant decrease compared to normal control and the non-lesional skin. Thereof, one can conclude that the epidermal H 2 O 2 is not

Complexity of the ultraviolet mutation frequency response curve in Escherichia coli B/r: SOS induction, one-lesion and two-lesion mutagenesis

International Nuclear Information System (INIS)

Doudney, C.O.

1976-01-01

Three distinct sections of the ultraviolet mutation frequency response (MFR) curve toward tryptophan prototrophy have been demonstrated in Escherichia coli B/r WP2 trp thy and its uvrA derivative in log-phase growth in minimal medium. The initial section, which appears fluence-squared, may reflect the necessity, if mutation is to result, for induction of two lesions, one located within the potentially mutated genetic locus and the other damaging deoxyribonucleic acid replication and resulting in induction of the error-prone SOS repair function. A second linear section is ascribed to the continued induction, after exposure above that sufficient for complete SOS expression, of isolated lesions which lead to mutation in potentially mutated loci. The third section demonstrates an increased rate of mutagenesis and suggests the induction of two lesions in proximity which result in additional mutations. Split-exposure studies support the inducible nature of the SOS function and suggest that mutation frequency decline (MFD) is due to excision resulting from or related to the prevention of SOS induction by inhibition of protein synthesis. Preirradiation tryptophan starvation of the uvr + strain for 30 min decreases MFR in the first and second sections of the curve. Reduction of MFR in the third section requires more prestarvation time and is blocked by nalidixic acid. The decreased MFR of the first and second sections is ascribed to promotion of postirradiation MFD based on excision and that of the third section to completion of the chromosome during the prestarvation period

Mixed adenine/guanine quartets with three trans-a2 Pt(II) (a=NH(3) or MeNH(2)) cross-links: linkage and rotational isomerism, base pairing, and loss of NH(3).

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Albertí, Francisca M; Rodríguez-Santiago, Luis; Sodupe, Mariona; Mirats, Andrea; Kaitsiotou, Helena; Sanz Miguel, Pablo J; Lippert, Bernhard

2014-03-17

Of the numerous ways in which two adenine and two guanines (N9 positions blocked in each) can be cross-linked by three linear metal moieties such as trans-a2 Pt(II) (with a=NH3 or MeNH2 ) to produce open metalated purine quartets with exclusive metal coordination through N1 and N7 sites, one linkage isomer was studied in detail. The isomer trans,trans,trans-[{Pt(NH3 )2 (N7-9-EtA-N1)2 }{Pt(MeNH2 )2 (N7-9-MeGH)}2 ][(ClO4 )6 ]⋅3H2 O (1) (with 9-EtA=9-ethyladenine and 9-MeGH=9-methylguanine) was crystallized from water and found to adopt a flat Z-shape in the solid state as far as the trinuclear cation is concerned. In the presence of excess 9-MeGH, a meander-like construct, trans,trans,trans-[{Pt(NH3 )2 (N7-9-EtA-N1)2 }{Pt(MeNH2 )2 (N7-9-MeGH)2 }][(ClO4 )6 ]⋅[(9-MeGH)2 ]⋅7 H2 O (2) is formed, in which the two extra 9-MeGH nucleobases are hydrogen bonded to the two terminal platinated guanine ligands of 1. Compound 1, and likewise the analogous complex 1 a (with NH3 ligands only), undergo loss of an ammonia ligand and formation of NH4 (+) when dissolved in [D6 ]DMSO. From the analogy between the behavior of 1 and 1 a it is concluded that a NH3 ligand from the central Pt atom is lost. Addition of 1-methylcytosine (1-MeC) to such a DMSO solution reveals coordination of 1-MeC to the central Pt. In an analogous manner, 9-MeGH can coordinate to the central Pt in [D6 ]DMSO. It is proposed that the proton responsible for formation of NH4 (+) is from one of the exocyclic amino groups of the two adenine bases, and furthermore, that this process is accompanied by a conformational change of the cation from Z-form to U-form. DFT calculations confirm the proposed mechanism and shed light on possible pathways of this process. Calculations show that rotational isomerism is not kinetically hindered and that it would preferably occur previous to the displacement of NH3 by DMSO. This displacement is the most energetically costly step, but it is compensated by the proton

Polycyclic aromatic hydrocarbons degradation by marine-derived basidiomycetes: optimization of the degradation process.

Science.gov (United States)

Vieira, Gabriela A L; Magrini, Mariana Juventina; Bonugli-Santos, Rafaella C; Rodrigues, Marili V N; Sette, Lara D

2018-05-03

Pyrene and benzo[a]pyrene (BaP) are high molecular weight polycyclic aromatic hydrocarbons (PAHs) recalcitrant to microbial attack. Although studies related to the microbial degradation of PAHs have been carried out in the last decades, little is known about degradation of these environmental pollutants by fungi from marine origin. Therefore, this study aimed to select one PAHs degrader among three marine-derived basidiomycete fungi and to study its pyrene detoxification/degradation. Marasmiellus sp. CBMAI 1062 showed higher levels of pyrene and BaP degradation and was subjected to studies related to pyrene degradation optimization using experimental design, acute toxicity, organic carbon removal (TOC), and metabolite evaluation. The experimental design resulted in an efficient pyrene degradation, reducing the experiment time while the PAH concentration applied in the assays was increased. The selected fungus was able to degrade almost 100% of pyrene (0.08mgmL -1 ) after 48h of incubation under saline condition, without generating toxic compounds and with a TOC reduction of 17%. Intermediate metabolites of pyrene degradation were identified, suggesting that the fungus degraded the compound via the cytochrome P450 system and epoxide hydrolases. These results highlight the relevance of marine-derived fungi in the field of PAH bioremediation, adding value to the blue biotechnology. Copyright © 2018. Published by Elsevier Editora Ltda.

Targeting eradication of malignant cells derived from human bone marrow mesenchymal stromal cells

Energy Technology Data Exchange (ETDEWEB)

Yang, Yingbin [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); School of Life Science, Southwest University, Chongqing 400715 (China); Cai, Shaoxi, E-mail: sxcai@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Yang, Li [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); College of Pharmacy, Jinan University, Guangzhou 510632 (China); Yu, Shuhui [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Library of Southwest University, Chongqing 400715 (China); Jiang, Jiahuan; Yan, Xiaoqing [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Zhang, Haoxing [School of Life Science, Southwest University, Chongqing 400715 (China); Liu, Lan [Department of Laboratory of Medicine, Children' s Hospital of Chongqin Medical University, Chongqing 400014 (China); Liu, Qun [College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041 (China); Du, Jun [Center of Microbiology, Biochemistry, and Pharmacology, School of Pharmaceutical Science, Sun Yat-Sen University, Guangzhou 510080 (China); Cai, Shaohui [College of Pharmacy, Jinan University, Guangzhou 510632 (China); Sung, K.L. Paul [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Departments of Orthopaedic Surgery and Bioengineering, University of California, SD 0412 (United States)

2010-12-10

Human bone marrow mesenchymal stromal cells (hBMSC) have been shown to participate in malignant transformation. However, hampered by the low frequency of malignant transformation of hBMSC, we do not yet know how to prevent malignant transformation of implanted hBMSC. In this study, in order to establish a model for the eradication of hBMSC-derived malignant cells, a gene fusion consisting of a human telomerase (hTERT) promoter modified with both c-Myc and myeloid zinc finger protein2 (MZF-2) binding elements and followed by the E. coli cytosine deaminase (CD) and luciferase genes was stably transferred into hBMSC via lentiviral transduction; n-phosphonacelyl-L-aspartic acid (PALA) selection was used to generate malignant cell colonies derived from transduced hBMSC after treatment with the carcinogenic reagent BPDE. Cells that were amplified after PALA selection were used for transplantation and 5-FC pro-drug cytotoxicity tests. The results showed that PALA-resistant malignant cells could be generated from hBMSC co-induced with lentiviral transduction and treatment with Benzo(a)pyrene Diol Epoxide (BPDE); the modification of c-Myc and MZF-2 binding elements could remarkably enhance the transcriptional activities of the hTERT promoter in malignant cells, whereas transcriptional activity was depressed in normal hBMSC; malignant cells stably expressing CD under the control of the modified hTERT promoter could be eliminated by 5-FC administration. This study has provided a method for targeted eradication of malignant cells derived from hBMSC.

Targeting eradication of malignant cells derived from human bone marrow mesenchymal stromal cells

International Nuclear Information System (INIS)

Yang, Yingbin; Cai, Shaoxi; Yang, Li; Yu, Shuhui; Jiang, Jiahuan; Yan, Xiaoqing; Zhang, Haoxing; Liu, Lan; Liu, Qun; Du, Jun; Cai, Shaohui; Sung, K.L. Paul

2010-01-01

Human bone marrow mesenchymal stromal cells (hBMSC) have been shown to participate in malignant transformation. However, hampered by the low frequency of malignant transformation of hBMSC, we do not yet know how to prevent malignant transformation of implanted hBMSC. In this study, in order to establish a model for the eradication of hBMSC-derived malignant cells, a gene fusion consisting of a human telomerase (hTERT) promoter modified with both c-Myc and myeloid zinc finger protein2 (MZF-2) binding elements and followed by the E. coli cytosine deaminase (CD) and luciferase genes was stably transferred into hBMSC via lentiviral transduction; n-phosphonacelyl-L-aspartic acid (PALA) selection was used to generate malignant cell colonies derived from transduced hBMSC after treatment with the carcinogenic reagent BPDE. Cells that were amplified after PALA selection were used for transplantation and 5-FC pro-drug cytotoxicity tests. The results showed that PALA-resistant malignant cells could be generated from hBMSC co-induced with lentiviral transduction and treatment with Benzo(a)pyrene Diol Epoxide (BPDE); the modification of c-Myc and MZF-2 binding elements could remarkably enhance the transcriptional activities of the hTERT promoter in malignant cells, whereas transcriptional activity was depressed in normal hBMSC; malignant cells stably expressing CD under the control of the modified hTERT promoter could be eliminated by 5-FC administration. This study has provided a method for targeted eradication of malignant cells derived from hBMSC.

Cyclo-(trp-phe diketopiperazines from the endophytic fungus Aspergillus versicolor isolated from Piper aduncum

Directory of Open Access Journals (Sweden)

Juliana R. Gubiani

Full Text Available Six known compounds, three peptide derivatives: cyclo-(tryptophyl-phenylalanyl (2, diketopiperazine dimer WIN 64821 (3 and 3-hydroxy-15H-tryptophenaline (4, one adenine derivative: 2-hydroxy-6-N-isopentenyl-adenine (5, one phtalide derivative: 4-methoxyphtalide (1 and one benzoic acid derivative: 3-hydroxy-4-(1-hydroxy-1,5-dimethyl-hexyl benzoic acid (6, were isolated from the ethyl acetate extract of the endophytic fungus Aspergillus versicolor associated with the Piper aduncum plant. Their structures were determined on the basis of detailed interpretation of 1 D and 2D NMR spectra and in comparison with works reported in the literature. This paper, in effect, deals with the first report of these compounds in A. versicolor.

Prediction of benzo[a]pyrene content of smoked sausage using back-propagation artificial neural network.

Science.gov (United States)

Chen, Yan; Cai, Kezhou; Tu, Zehui; Nie, Wen; Ji, Tuo; Hu, Bing; Chen, Conggui; Jiang, Shaotong

2017-11-29

Benzo[a]pyrene (BaP), a potent mutagen and carcinogen, is reported to be present in processed meat products and, in particular, in smoked meat. However, few methods exist for predictive determination of the BaP content of smoked meats such as sausage. In this study, an artificial neural network (ANN) model based on the back-propagation (BP) algorithm was used to predict the BaP content of smoked sausage. The results showed that the BP network based on the Levenberg-Marquardt algorithm was the best suited for creating a nonlinear map between the input and output parameters. The optimal network structure was 3-7-1 and the learning rate was 0.6. This BP-ANN model allowed for accurate predictions, with the correlation coefficients (R) for the experimentally determined training, validation, test and global data sets being 0.94, 0.96, 0.95 and 0.95 respectively. The validation performance was 0.013, suggesting that the proposed BP-ANN may be used to predictively detect the BaP content of smoked meat products. An effective predictive model was constructed for estimation of the BaP content of smoked sausage using ANN modeling techniques, which shows potential to predict the BaP content in smoked sausage. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Improved efficiency in clinical workflow of reporting measured oncology lesions via PACS-integrated lesion tracking tool.

Science.gov (United States)

Sevenster, Merlijn; Travis, Adam R; Ganesh, Rajiv K; Liu, Peng; Kose, Ursula; Peters, Joost; Chang, Paul J

2015-03-01

OBJECTIVE. Imaging provides evidence for the response to oncology treatment by the serial measurement of reference lesions. Unfortunately, the identification, comparison, measurement, and documentation of several reference lesions can be an inefficient process. We tested the hypothesis that optimized workflow orchestration and tight integration of a lesion tracking tool into the PACS and speech recognition system can result in improvements in oncologic lesion measurement efficiency. SUBJECTS AND METHODS. A lesion management tool tightly integrated into the PACS workflow was developed. We evaluated the effect of the use of the tool on measurement reporting time by means of a prospective time-motion study on 86 body CT examinations with 241 measureable oncologic lesions with four radiologists. RESULTS. Aggregated measurement reporting time per lesion was 11.64 seconds in standard workflow, 16.67 seconds if readers had to register measurements de novo, and 6.36 seconds for each subsequent follow-up study. Differences were statistically significant (p workflow-integrated lesion management tool, especially for patients with multiple follow-up examinations, reversing the onetime efficiency penalty at baseline registration.

PET/MR imaging of bone lesions - implications for PET quantification from imperfect attenuation correction

International Nuclear Information System (INIS)

Samarin, Andrei; Burger, Cyrill; Crook, David W.; Burger, Irene A.; Schmid, Daniel T.; Schulthess, Gustav K. von; Kuhn, Felix P.; Wollenweber, Scott D.

2012-01-01

Accurate attenuation correction (AC) is essential for quantitative analysis of PET tracer distribution. In MR, the lack of cortical bone signal makes bone segmentation difficult and may require implementation of special sequences. The purpose of this study was to evaluate the need for accurate bone segmentation in MR-based AC for whole-body PET/MR imaging. In 22 patients undergoing sequential PET/CT and 3-T MR imaging, modified CT AC maps were produced by replacing pixels with values of >100 HU, representing mostly bone structures, by pixels with a constant value of 36 HU corresponding to soft tissue, thereby simulating current MR-derived AC maps. A total of 141 FDG-positive osseous lesions and 50 soft-tissue lesions adjacent to bones were evaluated. The mean standardized uptake value (SUVmean) was measured in each lesion in PET images reconstructed once using the standard AC maps and once using the modified AC maps. Subsequently, the errors in lesion tracer uptake for the modified PET images were calculated using the standard PET image as a reference. Substitution of bone by soft tissue values in AC maps resulted in an underestimation of tracer uptake in osseous and soft tissue lesions adjacent to bones of 11.2 ± 5.4 % (range 1.5-30.8 %) and 3.2 ± 1.7 % (range 0.2-4 %), respectively. Analysis of the spine and pelvic osseous lesions revealed a substantial dependence of the error on lesion composition. For predominantly sclerotic spine lesions, the mean underestimation was 15.9 ± 3.4 % (range 9.9-23.5 %) and for osteolytic spine lesions, 7.2 ± 1.7 % (range 4.9-9.3 %), respectively. CT data simulating treating bone as soft tissue as is currently done in MR maps for PET AC leads to a substantial underestimation of tracer uptake in bone lesions and depends on lesion composition, the largest error being seen in sclerotic lesions. Therefore, depiction of cortical bone and other calcified areas in MR AC maps is necessary for accurate quantification of tracer uptake

3D Quantitative tumour burden analysis in patients with hepatocellular carcinoma before TACE: comparing single-lesion vs. multi-lesion imaging biomarkers as predictors of patient survival

International Nuclear Information System (INIS)

Fleckenstein, Florian N.; Schernthaner, Ruediger E.; Duran, Rafael; Sohn, Jae Ho; Sahu, Sonia; Zhao, Yan; Hamm, Bernd; Gebauer, Bernhard; Lin, MingDe; Geschwind, Jean-Francois; Chapiro, Julius

2016-01-01

To compare the ability of single- vs. multi-lesion assessment on baseline MRI using 1D- and 3D-based measurements to predict overall survival (OS) in patients with hepatocellular carcinoma (HCC) before transarterial chemoembolization (TACE). This retrospective analysis included 122 patients. A quantitative 3D analysis was performed on baseline MRI to calculate enhancing tumour volume (ETV [cm 3 ]) and enhancing tumour burden (ETB [%]) (ratio between ETV [cm 3 ] and liver volume). Furthermore, enhancing and overall tumour diameters were measured. Patients were stratified into two groups using thresholds derived from the BCLC staging system. Statistical analysis included Kaplan-Meier plots, uni- and multivariate cox proportional hazard ratios (HR) and concordances. All methods achieved good separation of the survival curves (p < 0.05). Multivariate analysis showed an HR of 5.2 (95 % CI 3.1-8.8, p < 0.001) for ETV [cm 3 ] and HR 6.6 (95 % CI 3.7-11.5, p < 0.001) for ETB [%] vs. HR 2.6 (95 % CI 1.2-5.6, p = 0.012) for overall diameter and HR 3.0 (95 % CI 1.5-6.3, p = 0.003) for enhancing diameter. Concordances were highest for ETB [%], with no added predictive power for multi-lesion assessment (difference between concordances not significant). 3D quantitative assessment is a stronger predictor of survival as compared to diameter-based measurements. Assessing multiple lesions provides no substantial improvement in predicting OS than evaluating the dominant lesion alone. (orig.)

A disappearing neonatal skin lesion.

LENUS (Irish Health Repository)

Hawkes, Colin Patrick

2012-01-31

A preterm baby girl was noted at birth to have a firm, raised, non-tender skin lesion located over her right hip. She developed three similar smaller lesions on her ear, buttock and right knee. All lesions had resolved by 2 months of age.

Diffuse cavitary lung lesions

Energy Technology Data Exchange (ETDEWEB)

Grunzke, Mindy; Garrington, Timothy [University of Colorado Denver, Department of Pediatrics, Aurora, CO (United States); The Children' s Hospital, Rick Wilson Center for Cancer and Blood Disorders, Aurora, CO (United States); Hayes, Kari [The Children' s Hospital, Pediatric Radiology, Aurora, CO (United States); Bourland, Wendy [Children' s Hospital at St. Francis, Warren Clinic, Inc., Tulsa, OK (United States)

2010-02-15

An 11-year-old girl presented with a 2-month history of progressively worsening cough, daily fevers, and weight loss. A chest radiograph revealed multiple cystic cavitary lung lesions. An extensive infectious work-up was negative. Chest CT verified multiple cavitary lung lesions bilaterally, and [F-18]2-fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) positron emission tomography with CT (PET/CT) showed increased uptake in the lung lesions as well as regional lymph nodes. Subsequent biopsy of an involved lymph node confirmed classical Hodgkin lymphoma, nodular sclerosis type. This case represents an unusual presentation for a child with Hodgkin lymphoma and demonstrates a role for {sup 18}F-FDG PET/CT in evaluating a child with cavitary lung lesions. (orig.)

Diffuse cavitary lung lesions

International Nuclear Information System (INIS)

Grunzke, Mindy; Garrington, Timothy; Hayes, Kari; Bourland, Wendy

2010-01-01

An 11-year-old girl presented with a 2-month history of progressively worsening cough, daily fevers, and weight loss. A chest radiograph revealed multiple cystic cavitary lung lesions. An extensive infectious work-up was negative. Chest CT verified multiple cavitary lung lesions bilaterally, and [F-18]2-fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography with CT (PET/CT) showed increased uptake in the lung lesions as well as regional lymph nodes. Subsequent biopsy of an involved lymph node confirmed classical Hodgkin lymphoma, nodular sclerosis type. This case represents an unusual presentation for a child with Hodgkin lymphoma and demonstrates a role for 18 F-FDG PET/CT in evaluating a child with cavitary lung lesions. (orig.)

Somatic embryogenesis and plant regeneration in Carica papaya L. tissue culture derived from root explants.

Science.gov (United States)

Chen, M H; Wang, P J; Maeda, E

1987-10-01

The regeneration potential of shoot tip, stem, leaf, cotyledon and root explants of two papaya cultivars (Carica papaya cv. 'Solo' and cv. 'Sunrise') were studed. Callus induction of these two cultivars of papaya showed that the shoot tips and stems are most suitable for forming callus, while leaves, cotyledons and roots are comparatively difficult to induce callus. Callus induction also varied with the varities. Somatic embryogenesis was obtained from 3-month-old root cultures. A medium containing half strength of MS inorganic salts, 160 mg/l adenine sulfate, 1.0 mg/1 NAA, 0.5 mg/1 kinetin and 1.0 mg/1 GA3 was optimal for embryogenesis. The callus maintained high regenerative capacity after two years of culture on this medium. Plants derived from somatic embryos were obtained under green-house conditions.

The electrochemical reduction of the purines guanine and adenine at platinum electrodes in several room temperature ionic liquids

International Nuclear Information System (INIS)

Zanoni, Maria Valnice Boldrin; Rogers, Emma I.; Hardacre, Christopher; Compton, Richard G.

2010-01-01

The reduction of guanine was studied by microelectrode voltammetry in the room temperature ionic liquids (RTILs) N-hexyltriethylammonium bis (trifluoromethanesulfonyl) imide [N 6,2,2,2 ][N(Tf) 2 ], 1-butyl-3-methylimidazolium hexafluorosphosphate [C 4 mim][PF 6 ], N-butyl-N-methyl-pyrrolidinium bis(trifluoromethanesulfonyl)imide [C 4 mpyrr][N(Tf) 2 ], 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [C 4 mim][N(Tf) 2 ], N-butyl-N-methyl-pyrrolidinium dicyanamide [C 4 mpyrr][N(NC) 2 ] and tris(P-hexyl)-tetradecylphosphonium trifluorotris(pentafluoroethyl)phosphate [P 14,6,6,6 ][FAP] on a platinum microelectrode. In [N 6,2,2,2 ][NTf 2 ] and [P 14,6,6,6 ][FAP], but not in the other ionic liquids studied, guanine reduction involves a one-electron, diffusion-controlled process at very negative potential to produce an unstable radical anion, which is thought to undergo a dimerization reaction, probably after proton abstraction from the cation of the ionic liquid. The rate of this subsequent reaction depends on the nature of the ionic liquid, and it is faster in the ionic liquid [P 14,6,6,6 ][FAP], in which the formation of the resulting dimer can be voltammetrically monitored at less negative potentials than required for the reduction of the parent molecule. Adenine showed similar behaviour to guanine but the pyrimidines thymine and cytosine did not; thymine was not reduced at potentials less negative than required for solvent (RTIL) decomposition while only a poorly defined wave was seen for cytosine. The possibility for proton abstraction from the cation in [N 6,2,2,2 ][NTf 2 ] and [P 14,6,6,6 ][FAP] is noted and this is thought to aid the electrochemical dimerization process. The resulting rapid reaction is thought to shift the reduction potentials for guanine and adenine to lower values than observed in RTILs where the scope for proton abstraction is not present. Such shifts are characteristic of so-called EC processes where reversible electron transfer

Transfer of benzo[a]pyrene from microplastics to Artemia nauplii and further to zebrafish via a trophic food web experiment: CYP1A induction and visual tracking of persistent organic pollutants.

Science.gov (United States)

Batel, Annika; Linti, Frederic; Scherer, Martina; Erdinger, Lothar; Braunbeck, Thomas

2016-07-01

The uptake of microplastic particles and the transfer of potential harmful substances along with microplastics has been studied in a variety of organisms, especially invertebrates. However, the potential accumulation of very small microplastic particles along food webs ending with vertebrate models has not been investigated so far. Therefore, a simple artificial food chain with Artemia sp. nauplii and zebrafish (Danio rerio) was established to analyze the transfer of microplastic particles and associated persistent organic pollutants (POPs) between different trophic levels. Very small (1-20 μm) microplastic particles accumulated in Artemia nauplii and were subsequently transferred to fish. Virgin particles not loaded with POPs did not cause any observable physical harm in the intestinal tracts of zebrafish, although parts of the particles were retained within the mucus of intestinal villi and might even have been taken up by epithelial cells. The transfer of associated POPs was tested with the polycyclic aromatic hydrocarbon benzo[a]pyrene and an ethoxyresorufin-O-deethylase (EROD) assay for CYP1A induction in zebrafish liver as well as via fluorescence analyses. Whereas a significant induction in the EROD assay could not be shown, because of high individual variation and low sensitivity regarding substance concentration, the fluorescence tracking of benzo[a]pyrene indicates that food-borne microplastic-associated POPs may actually desorb in the intestine of fish and are thus transferred to the intestinal epithelium and liver. Environ Toxicol Chem 2016;35:1656-1666. © 2016 SETAC. © 2016 SETAC.

Epidemiological investigation of tattoo-like skin lesions among bottlenose dolphins in Shark Bay, Australia.

Science.gov (United States)

Powell, Sarah N; Wallen, Megan M; Bansal, Shweta; Mann, Janet

2018-07-15

Bottlenose dolphins are excellent bioindicators of ocean ecosystem health for three reasons: (a) as long-lived apex predators they accumulate biotoxins and contaminants; (b) they are visible, routinely appearing at the water's surface in coastal areas, often coming into close contact with humans; and, (c) they exhibit a range of pathogenic lesions attributable to environmental degradation. In this study, we analyzed tattoo-like skin lesions in a population of Tursiops aduncus studied for 30+years in Shark Bay, Australia, a UNESCO World Heritage Site. We provide important baseline data by documenting epidemiological patterns of tattoo-like skin lesions in a healthy, free-ranging population that builds on the previous data of tattoo skin disease (TSD) derived from free ranging, stranded, and dead dolphins. Individual dolphins were classified as symptomatic with tattoo-like skin disease if at least one photograph showed a lesion similar to TSD. The average age of infection was 26.6months (±34.8months) with the symptomatic period lasting 137±29.8days. Overall prevalence of tattoo-like skin disease in the population was 19.4%. Age, but not sex, was significant, with yearlings (1-2years) exhibiting tattoo-like lesions more than younger and older calves. Tattoo-like lesions were rare among juvenile and adult dolphins (N=68 calves, 4 juveniles, and 3 adults). We hypothesize that the lower prevalence in youngest calves (2years) have infection-acquired immunity, as reported for other small cetaceans. The low prevalence of tattoo-like lesions in Shark Bay compared to other populations with poxvirus is consistent with reproductive and demographic viability analyses. Furthermore, by documenting the demography of the disease, we can monitor changes in the prevalence of tattoo-like lesions as a sentinel indicator of ecosystem health. Copyright © 2018 Elsevier B.V. All rights reserved.

Functions of the left superior frontal gyrus in humans: a lesion study.

Science.gov (United States)

du Boisgueheneuc, Foucaud; Levy, Richard; Volle, Emmanuelle; Seassau, Magali; Duffau, Hughes; Kinkingnehun, Serge; Samson, Yves; Zhang, Sandy; Dubois, Bruno

2006-12-01

The superior frontal gyrus (SFG) is thought to contribute to higher cognitive functions and particularly to working memory (WM), although the nature of its involvement remains a matter of debate. To resolve this issue, methodological tools such as lesion studies are needed to complement the functional imaging approach. We have conducted the first lesion study to investigate the role of the SFG in WM and address the following questions: do lesions of the SFG impair WM and, if so, what is the nature of the WM impairment? To answer these questions, we compared the performance of eight patients with a left prefrontal lesion restricted to the SFG with that of a group of 11 healthy control subjects and two groups of patients with focal brain lesions [prefrontal lesions sparing the SFG (n = 5) and right parietal lesions (n = 4)] in a series of WM tasks. The WM tasks (derived from the classical n-back paradigm) allowed us to study the impact of the SFG lesions on domain (verbal, spatial, face) and complexity (1-, 2- and 3-back) processing within WM. As expected, patients with a left SFG lesion exhibited a WM deficit when compared with all control groups, and the impairment increased with the complexity of the tasks. This complexity effect was significantly more marked for the spatial domain. Voxel-to-voxel mapping of each subject's performance showed that the lateral and posterior portion of the SFG (mostly Brodmann area 8, rostral to the frontal eye field) was the subregion that contributed the most to the WM impairment. These data led us to conclude that (i) the lateral and posterior portion of the left SFG is a key component of the neural network of WM; (ii) the participation of this region in WM is triggered by the highest level of executive processing; (iii) the left SFG is also involved in spatially oriented processing. Our findings support a hybrid model of the anatomical and functional organization of the lateral SFG for WM, according to which this region is

Imaging inflammatory acne: lesion detection and tracking

Science.gov (United States)

Cula, Gabriela O.; Bargo, Paulo R.; Kollias, Nikiforos

2010-02-01

It is known that effectiveness of acne treatment increases when the lesions are detected earlier, before they could progress into mature wound-like lesions, which lead to scarring and discoloration. However, little is known about the evolution of acne from early signs until after the lesion heals. In this work we computationally characterize the evolution of inflammatory acne lesions, based on analyzing cross-polarized images that document acne-prone facial skin over time. Taking skin images over time, and being able to follow skin features in these images present serious challenges, due to change in the appearance of skin, difficulty in repositioning the subject, involuntary movement such as breathing. A computational technique for automatic detection of lesions by separating the background normal skin from the acne lesions, based on fitting Gaussian distributions to the intensity histograms, is presented. In order to track and quantify the evolution of lesions, in terms of the degree of progress or regress, we designed a study to capture facial skin images from an acne-prone young individual, followed over the course of 3 different time points. Based on the behavior of the lesions between two consecutive time points, the automatically detected lesions are classified in four categories: new lesions, resolved lesions (i.e. lesions that disappear completely), lesions that are progressing, and lesions that are regressing (i.e. lesions in the process of healing). The classification our methods achieve correlates well with visual inspection of a trained human grader.

Benzo(a)pyrene metabolism, DNA-binding and UV-induced repair of DNA damage in cultured skin fibroblasts from a patient with unilateral multiple basal cell carcinoma

International Nuclear Information System (INIS)

Don, P.S.C.; Mukhtar, H.; Das, M.; Berger, N.A.; Bickers, D.R.

1989-01-01

The metabolism of benzo(a)pyrene (BP), and its subsequent binding to DNA, and the repair of UV-induced DNA damage were studied in fibroblasts cultured from the skin of a 61-year-old male who had multiple basal cell carcinoma (BCC) (>100) on his left upper trunk. Results suggest that BP metabolism and repair of DNA are altered in tumor-bearing site (TSB) cells and that patients with this type of metabolic profile may be at higher risk of the development of cutaneous neoplasms. It is also possible that fibroblasts from tumour bearing skin undergo some as yet unexplained alteration in carcinogen metabolism as a consequence of the induction of neoplasia. (author)

Solitary sternal lesions in breast cancer. Lesiones esternales unicas en cancer de mama

Energy Technology Data Exchange (ETDEWEB)

Morales, R; Cano, R; Mendoza, G [Instituto Peruano de Energia Nuclear, Lima (Peru); Guzman, C; Cotrina, M; Aguilar, C [Instituto Nacional de Enfermedades Neoplasicas, Lima (Peru)

1993-12-01

In a retrospective review of bone scans performed in 1740 patients with breast cancer from January 1988 to April 1993, twenty had a solitary sternal lesion. Etiology was found correlating this finding with pathology, x-rays and/or final outcome. Nineteen lesions were due to metastases and one to infection. This experience suggests that solitary sternal lesions in breast cancer patients are uncommon and are most frequently (95%) associated with malignant etiology. (Authors). 10 refs., 2 figs.

Improved characterization of molecular phenotypes in breast lesions using 18F-FDG PET image homogeneity

Science.gov (United States)

Cao, Kunlin; Bhagalia, Roshni; Sood, Anup; Brogi, Edi; Mellinghoff, Ingo K.; Larson, Steven M.

2015-03-01

Positron emission tomography (PET) using uorodeoxyglucose (18F-FDG) is commonly used in the assessment of breast lesions by computing voxel-wise standardized uptake value (SUV) maps. Simple metrics derived from ensemble properties of SUVs within each identified breast lesion are routinely used for disease diagnosis. The maximum SUV within the lesion (SUVmax) is the most popular of these metrics. However these simple metrics are known to be error-prone and are susceptible to image noise. Finding reliable SUV map-based features that correlate to established molecular phenotypes of breast cancer (viz. estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression) will enable non-invasive disease management. This study investigated 36 SUV features based on first and second order statistics, local histograms and texture of segmented lesions to predict ER and PR expression in 51 breast cancer patients. True ER and PR expression was obtained via immunohistochemistry (IHC) of tissue samples from each lesion. A supervised learning, adaptive boosting-support vector machine (AdaBoost-SVM), framework was used to select a subset of features to classify breast lesions into distinct phenotypes. Performance of the trained multi-feature classifier was compared against the baseline single-feature SUVmax classifier using receiver operating characteristic (ROC) curves. Results show that texture features encoding local lesion homogeneity extracted from gray-level co-occurrence matrices are the strongest discriminator of lesion ER expression. In particular, classifiers including these features increased prediction accuracy from 0.75 (baseline) to 0.82 and the area under the ROC curve from 0.64 (baseline) to 0.75.

Quantitative assessment of multiple sclerosis lesion load using CAD and expert input

Science.gov (United States)

Gertych, Arkadiusz; Wong, Alexis; Sangnil, Alan; Liu, Brent J.

2008-03-01

Multiple sclerosis (MS) is a frequently encountered neurological disease with a progressive but variable course affecting the central nervous system. Outline-based lesion quantification in the assessment of lesion load (LL) performed on magnetic resonance (MR) images is clinically useful and provides information about the development and change reflecting overall disease burden. Methods of LL assessment that rely on human input are tedious, have higher intra- and inter-observer variability and are more time-consuming than computerized automatic (CAD) techniques. At present it seems that methods based on human lesion identification preceded by non-interactive outlining by CAD are the best LL quantification strategies. We have developed a CAD that automatically quantifies MS lesions, displays 3-D lesion map and appends radiological findings to original images according to current DICOM standard. CAD is also capable to display and track changes and make comparison between patient's separate MRI studies to determine disease progression. The findings are exported to a separate imaging tool for review and final approval by expert. Capturing and standardized archiving of manual contours is also implemented. Similarity coefficients calculated from quantities of LL in collected exams show a good correlation of CAD-derived results vs. those incorporated as expert's reading. Combining the CAD approach with an expert interaction may impact to the diagnostic work-up of MS patients because of improved reproducibility in LL assessment and reduced time for single MR or comparative exams reading. Inclusion of CAD-generated outlines as DICOM-compliant overlays into the image data can serve as a better reference in MS progression tracking.

A new lactoferrin- and iron-dependent lysosomal death pathway is induced by benzo[a]pyrene in hepatic epithelial cells

International Nuclear Information System (INIS)

Gorria, Morgane; Tekpli, Xavier; Rissel, Mary; Sergent, Odile; Huc, Laurence; Landvik, Nina; Fardel, Olivier; Dimanche-Boitrel, Marie-Therese; Holme, Jorn A.; Lagadic-Gossmann, Dominique

2008-01-01

While lysosomal disruption seems to be a late step of necrosis, a moderate lysosomal destabilization has been suggested to participate early in the apoptotic cascade. The origin of lysosomal dysfunction and its precise role in apoptosis or apoptosis-like process still needs to be clarified, especially upon carcinogen exposure. In this study, we focused on the implication of lysosomes in cell death induced by the prototype carcinogen benzo[a]pyrene (B[a]P; 50 nM) in rat hepatic epithelial F258 cells. We first demonstrated that B[a]P affected lysosomal morphology (increase in size) and pH (alkalinization), and that these changes were involved in caspase-3 activation and cell death. Subsequently, we showed that lysosomal modifications were partly dependent on mitochondrial dysfunction, and that lysosomes together with mitochondria participate in B[a]P-induced oxidative stress. Using two iron chelators (desferrioxamine and deferiprone) and siRNA targeting the lysosomal iron-binding protease lactoferrin, we further demonstrated that both lysosomal iron content and lactoferrin were required for caspase-3 activation and apoptosis-like cell death

Dynamic multislice helical CT of maxillomandibular lesions. Distinction of ameloblastomas from other cystic lesions

Energy Technology Data Exchange (ETDEWEB)

Tozaki, Mitsuhiro; Hayashi, Katsuhiko; Fukuda, Kunihiko [Jikei Univ., Tokyo (Japan). School of Medicine

2001-10-01

The purpose of this study was to evaluate the clinical usefulness of dynamic multislice helical CT in differentiating ameloblastoma from other cystic lesions in cases of maxillomandibular cystic lesions. The study included 32 patients with maxillomandibular cystic lesions (ameloblastoma [n=6], myxofibroma [n=1], odontogenic keratocyst [n=3], dentigerous cyst [n=11], radicular cyst [n=11], and paradental cyst [n=2]). Dynamic study was performed before and 30 sec, and 90 sec after intravenous contrast medium administration. CT density values and percentage of density increase were calculated at 30 and 90 sec. In five cases of ameloblastoma, a rapidly enhancing area was detected within the cystic lesions at 30 sec, while no apparent rapid enhancement was seen in the other cystic lesions. Three cysts showed gradual enhancement in the marginal area at 90 sec. Comparing ameloblastoma and other kinds of cysts, we found significant differences in the percentage of density increase at 30 sec (p<0.01) and 90 sec (p<0.05). Dynamic multislice helical CT is useful in the diagnosis of cystic lesions of the maxillomandibular region, especially in the detection of neovascularities in ameloblastoma. (author)

Dynamic multislice helical CT of maxillomandibular lesions. Distinction of ameloblastomas from other cystic lesions

International Nuclear Information System (INIS)

Tozaki, Mitsuhiro; Hayashi, Katsuhiko; Fukuda, Kunihiko

2001-01-01

The purpose of this study was to evaluate the clinical usefulness of dynamic multislice helical CT in differentiating ameloblastoma from other cystic lesions in cases of maxillomandibular cystic lesions. The study included 32 patients with maxillomandibular cystic lesions (ameloblastoma [n=6], myxofibroma [n=1], odontogenic keratocyst [n=3], dentigerous cyst [n=11], radicular cyst [n=11], and paradental cyst [n=2]). Dynamic study was performed before and 30 sec, and 90 sec after intravenous contrast medium administration. CT density values and percentage of density increase were calculated at 30 and 90 sec. In five cases of ameloblastoma, a rapidly enhancing area was detected within the cystic lesions at 30 sec, while no apparent rapid enhancement was seen in the other cystic lesions. Three cysts showed gradual enhancement in the marginal area at 90 sec. Comparing ameloblastoma and other kinds of cysts, we found significant differences in the percentage of density increase at 30 sec (p<0.01) and 90 sec (p<0.05). Dynamic multislice helical CT is useful in the diagnosis of cystic lesions of the maxillomandibular region, especially in the detection of neovascularities in ameloblastoma. (author)

Analysis of 200 food items for benzo[a]pyrene and estimation of its intake in an epidemiologic study.

Science.gov (United States)

Kazerouni, N; Sinha, R; Hsu, C H; Greenberg, A; Rothman, N

2001-05-01

Animal studies have shown that dietary intake of benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), causes increased levels of tumors at several sites, particularly in the upper gastrointestinal tract. However, the role of dietary intake of BaP and cancer in humans is not clear. We created a BaP database of selected food products that could be linked to Food Frequency Questionnaires (FFQs) to estimate BaP intake. BaP levels were measured for each food line-item (composite samples) which consisted of a variety of foods in a FFQ. Composite sample parts were derived from the Second National Health and Nutrition Examination Survey (NHANES II) which represents the most common food items consumed by the general population. Meat samples were cooked by different techniques in controlled conditions, and by various restaurants and fast-food chains. Non-meat products were purchased from the major national supermarket chains. The quantities of BaP were measured using a thin-layer chromatography (TLC)/spectrofluorometer technique and were highly correlated with both BaP (r=0.99) [corrected] and sum of carcinogenic PAH (r=0.98) measured by HPLC technique. We linked our database to the results from a FFQ and estimated the daily BaP intake of various food items in 228 subjects in the Washington, DC metropolitan area. The highest levels of BaP (up to about 4 ng BaP/g of cooked meat) were found in grilled/barbecued very well done steaks and hamburgers and in grilled/barbecued well done chicken with skin. BaP concentrations were lower in meats that were grilled/barbecued to medium done and in all broiled or pan-fried meat samples regardless of doneness level. The BaP levels in non-meat items were generally low. However, certain cereals and greens (e.g. kale, collard greens) had levels up to 0.5 ng/g. In our population, the bread/cereal/grain, and grilled/barbecued meat, respectively, contributed 29 and 21 percent to the mean daily intake of BaP. This database may be

FFA STUDY OF MACULAR LESIONS

Directory of Open Access Journals (Sweden)

K. Vinayagamurthy

2017-08-01

Full Text Available BACKGROUND Macula is an important portion of retina that occupies the posterior pole of retina. Any disease that affects macula results in significant loss of central vision, form vision and colour vision to an extent. Macular lesions can be hereditary as well as acquired. Macular lesions occur in both younger and older individuals. Anatomically, a macular lesions can vary from a simple lesion like an RPF defect to a vision-threatening lesions like choroidal neovascular membrane. Many screening tests that are sensitive and specific are available to assess the functioning of macula called as ‘macular function test’. But, the greater understanding of the retinal vascular led to the usage of fluorescein angiogram in the detection and screening of macular, retinovascular and optic disc lesions. Through fundus fluorescein angiogram is a thirty-year-old procedure; it is still in vogue in almost all parts of the world. It has its own merits. The aim of the study is to study the role of fluorescein angiography in the evaluation of macular lesions. MATERIALS AND METHODS A hospital-based prospective randomised study was done, which included 50 patients. Detailed patient history was taken and thorough ocular and systemic examination was done. All patients were examined by ophthalmoscopy (direct and indirect and slit-lamp examination with 90D followed by fluorescein angiography. Ophthalmoscopic and fluorescein angiography findings were analysed and categorised. Patients were advised proper ocular and systemic treatment and follow up. RESULTS 50 cases with macular lesions were analysed and categorised into conditions like ARMD, CSR, macular oedema, CME, degenerations and dystrophies and miscellaneous conditions. FFA altered the diagnosis in 8% cases and categorised the cases in all cases. 16% patients developed adverse reactions like allergy, vomiting and nausea. On statistical analysis, FFA proved to be cheap and superior diagnostic tool in confirming

Polycyclic aromatic hydrocarbons as skin carcinogens: Comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse

International Nuclear Information System (INIS)

Siddens, Lisbeth K.; Larkin, Andrew; Krueger, Sharon K.; Bradfield, Christopher A.; Waters, Katrina M.; Tilton, Susan C.; Pereira, Cliff B.; Löhr, Christiane V.; Arlt, Volker M.; Phillips, David H.; Williams, David E.

2012-01-01

The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4 nmol) was most potent, reaching 100% tumor incidence with a shorter latency to tumor formation, less than 20 weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400 nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b; mix 1) did not differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1 mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2 mg of cigarette smoke condensate (mix 3) did not alter the response with mix 2. PAH-DNA adducts measured in epidermis 12 h post initiation and analyzed by 32 P post‐labeling, did not correlate with tumor incidence. PAH‐dependent alteration in transcriptome of skin 12 h post initiation was assessed by microarray. Principal component analysis (sum of all treatments) of the 922 significantly altered genes (p < 0.05), showed DBC and BaP to cluster distinct from PAH mixtures and each other. BaP and mixtures up-regulated phase 1 and phase 2 metabolizing enzymes while DBC did not. The carcinogenicity with DBC and two of the mixtures was much greater than would be predicted based on published Relative Potency Factors (RPFs). -- Highlights: ► Dibenzo[def,p]chrysene (DBC), 3 PAH mixtures, benzo[a]pyrene (BaP) were compared. ► DBC and 2 PAH mixtures were more potent than Relative Potency Factor estimates. ► Transcriptome profiles 12 hours post initiation were analyzed by microarray. ► Principle components analysis of alterations revealed treatment-based clustering. ► DBC gave a unique pattern of

The position of imidazopyridine and metabolic activation are pivotal factors in the antimutagenic activity of novel imidazo[1,2-a]pyridine derivatives.

Science.gov (United States)

El-Sayed, Wael M; Hussin, Warda A; Al-Faiyz, Yasair S; Ismail, Mohamed A

2013-09-05

The antimutagenic activity of eight novel imidazo[1,2-a]pyridine derivatives (I-VIII) against sodium azide (NaN3) and benzo[a]pyrene (B[a]P) was evaluated using the Salmonella reverse mutation assay. At non-toxic concentrations (12.5-50 µM), imidazopyridines I, II, III, and V with a terminal imidazopyridine group were mutagenic, while derivatives VII and VIII with a central imidazopyridine group were not mutagenic. Compounds IV, VII, and VIII exerted a moderate antimutagenic activity against NaN3 under pre-exposure conditions, and a strong activity (>40%) against B[a]P in the presence of S9 under both pre- and co-exposure conditions and mostly independent on the dose. Imidazopyridines possibly inhibited the microsomal-dependent activation of B[a]P. The demethylated derivative VII was the most active antimutagen. All imidazopyridines had a low to moderate antioxidant activity. The antibacterial activity of imidazopyridines was sporadic and moderate probably due to the failure of bacteria to convert imidazopyridines into active metabolites. The position of imidazopyridine was a pivotal factor in the mutagenic/antimutagenic activity. The strong antimutagenic compounds were dicationic planar compounds with a centered imidazo[1,2-a]pyridine spacer. With LD50 of 60 mg/kg in mice for both derivatives VII and VIII, it is safe to investigate the anticancer activity of these derivatives in animal models. © 2013 Elsevier B.V. All rights reserved.

Kynureninase-type enzymes and the evolution of the aerobic tryptophan-to-nicotinamide adenine dinucleotide pathway

Energy Technology Data Exchange (ETDEWEB)

Gaertner, F.H.; Shetty, A.S.

1977-01-01

Kynureninase-type (L-kynurenine hydrolase, EC 3.7.1.3) activity has been found to be present in the livers of fish, amphibia, reptiles, and birds. In addition to past information concerning this enzyme activity in mammalian liver, it is now clear that all the major classes of vertebrates carry a highly specialized kynureninase-type enzyme, which we have termed a hydroxykynureninase. To compare the reactivities of these enzymes with L-kynurenine and L-3-hydroxykynurenine, ratios of tau values (K/sub m//V) were used. Based on this comparison, the bacterium Pseudomonas fluorescens carries the most efficient kynureninase, whereas the amphibian Xenopus laevis has the most efficient hydroxykynurenase. In these two cases, the ratio of tau values differs by a factor of 38,000. It is hypothesized that the tryptophan-to-nicotinamide adenine dinucleotide biosynthetic pathway evolved from a catabolic system of enzymes, and that the differences observed in the kynureninase-type enzymes between lower and higher organisms reflect the specialization of the function of these enzymes from a strictly catabolic role to an anabolic one during the course of evolution.

Quantitative angiography methods for bifurcation lesions

DEFF Research Database (Denmark)

Collet, Carlos; Onuma, Yoshinobu; Cavalcante, Rafael

2017-01-01

Bifurcation lesions represent one of the most challenging lesion subsets in interventional cardiology. The European Bifurcation Club (EBC) is an academic consortium whose goal has been to assess and recommend the appropriate strategies to manage bifurcation lesions. The quantitative coronary...... angiography (QCA) methods for the evaluation of bifurcation lesions have been subject to extensive research. Single-vessel QCA has been shown to be inaccurate for the assessment of bifurcation lesion dimensions. For this reason, dedicated bifurcation software has been developed and validated. These software...

Retrospective analysis of nonendodontic periapical lesions misdiagnosed as endodontic apical periodontitis lesions in a population of Taiwanese patients.

Science.gov (United States)

Huang, Hsun-Yu; Chen, Yuk-Kwan; Ko, Edward Cheng-Chuan; Chuang, Fu-Hsiung; Chen, Ping-Ho; Chen, Ching-Yi; Wang, Wen-Chen

2017-07-01

We aimed to evaluate nonendodontic periapical lesions clinically misdiagnosed as endodontic periapical pathoses in a population of Taiwanese patients. Cases (2000-2014) of histopathological diagnoses of nonendodontic periapical lesions were retrieved from all cases with a clinical diagnosis of radicular cyst, apical granuloma, or apical periodontitis in the institution. These cases were regarded as misdiagnosed nonendodontic periapical lesions, of which the types and frequencies, in addition to the demographic data, were determined. Four thousand and four specimens were clinically diagnosed as endodontically associated pathoses, of which 118 cases (2.95%) received a histopathological diagnosis of a nonendodontic pathologic entity, the most frequent lesion being keratocystic odontogenic tumor (KCOT, n = 38, 32.20%), followed by fibro-osseous lesion (n = 18, 15.25%), and dentigerous cyst (n = 13, 11.02%). Nine malignant lesions in the periapical area [squamous cell carcinoma (n = 7, 5.93%), adenoid cystic carcinoma (n = 1, 0.85%), and Langerhans cell histiocytosis (n = 1, 0.85%)] were also noted. A wide variety of histopathological diagnoses, including benign odontogenic and non-odontogenic cystic and tumorous lesions and infectious diseases, as well as malignant lesions, was noted in these 118 cases of nonendodontic periapical lesions. Squamous cell carcinoma was the most predominant malignancy of nonendodontic periapical lesions misdiagnosed as apical periodontitis lesions from imaging examination overlooking the clinical findings. The current data form a useful basis for clinicopathological investigation and educational teaching regarding nonendodontic periapical lesions misdiagnosed as endodontic apical periodontitis lesions.

Preclinical evidence of mitochondrial nicotinamide adenine dinucleotide as an effective alarm parameter under hypoxia

Science.gov (United States)

Shi, Hua; Sun, Nannan; Mayevsky, Avraham; Zhang, Zhihong; Luo, Qingming

2014-01-01

Early detection of tissue hypoxia in the intensive care unit is essential for effective treatment. Reduced nicotinamide adenine dinucleotide (NADH) has been suggested to be the most sensitive indicator of tissue oxygenation at the mitochondrial level. However, no experimental evidence comparing the kinetics of changes in NADH and other physiological parameters has been provided. The aim of this study is to obtain the missing data in a systematic and reliable manner. We constructed four acute hypoxia models, including hypoxic hypoxia, hypemic hypoxia, circulatory hypoxia, and histogenous hypoxia, and measured NADH fluorescence, tissue reflectance, cerebral blood flow, respiration, and electrocardiography simultaneously from the induction of hypoxia until death. We found that NADH was not always the first onset parameter responding to hypoxia. The order of responses was mainly affected by the cause of hypoxia. However, NADH reached its alarm level earlier than the other monitored parameters, ranging from several seconds to >10 min. As such, we suggest that the NADH can be used as a hypoxia indicator, although the exact level that should be used must be further investigated. When the NADH alarm is detected, the body still has a chance to recover if appropriate and timely treatment is provided.

Convergence Analysis of Micro-Lesions (CAML: An approach to mapping of diffuse lesions from carotid revascularization

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Allyson C. Rosen

Full Text Available Carotid revascularization (endarterectomy, stenting prevents stroke; however, procedure-related embolization is common and results in small brain lesions easily identified by diffusion weighted magnetic resonance imaging (DWI. A crucial barrier to understanding the clinical significance of these lesions has been the lack of a statistical approach to identify vulnerable brain areas. The problem is that the lesions are small, numerous, and non-overlapping. Here we address this problem with a new method, the Convergence Analysis of Micro-Lesions (CAML technique, an extension of the Anatomic Likelihood Analysis (ALE. The method combines manual lesion tracing, constraints based on known lesion patterns, and convergence analysis to represent regions vulnerable to lesions as probabilistic brain atlases. Two studies were conducted over the course of 12 years in an active, vascular surgery clinic. An analysis in an initial group of 126 patients at 1.5 T MRI was cross-validated in a second group of 80 patients at 3T MRI. In CAML, lesions were manually defined and center points identified. Brains were aligned according to side of surgery since this factor powerfully determines lesion distribution. A convergence based analysis, was performed on each of these groups. Results indicated the most consistent region of vulnerability was in motor and premotor cortex regions. Smaller regions common to both groups included the dorsolateral prefrontal cortex and medial parietal regions. Vulnerability of motor cortex is consistent with previous work showing changes in hand dexterity associated with these procedures. The consistency of CAML also demonstrates the feasibility of this new approach to characterize small, diffuse, non-overlapping lesions in patients with multifocal pathologies. Keywords: Embolization, DWI, ALE

Localization of lesions in aphasia, (2)

International Nuclear Information System (INIS)

Hojo, Kei; Watanabe, Shunzo; Tasaki, Hiroichi; Sato, Tokijiro; Metoki, Hirofumi.

1985-01-01

The relationship between the focus and the extent of the lesions and the various symptoms was investigated. 1. Broca aphasics: More than 80% of the group with obvious anarthric components had lesions of the third frontal gyrus involving Broca's area and the lower part of the precental gyrus as well as opercular and insular regions. The size of the lesions of this group was significantly larger than that of the group without marked anarthric components, and the latter was proved to have little localizing value. 2. Wernicke aphasics: The group with poor reading comprehension had cortical and/or subcortical lesions, involving posterior parts of both superior and middle temporal gyri as well as the supramarginal gyrus. On the other hand, lesions of the group with poor auditory comprehension were more anteriorly located and localized in the deep structures. Lesions of the group with poor Token test scores were large and scattered more anteriorly and/or posteriorly compared with those of the group with good Token test scores. 3. Amnestic aphaiscs: The group with poor naming scores had somewhat larger lesions than the group with good naming scores, and the lesions were scattered about the left hemisphere. The finding has proved that both groups had little localizing value. 4. Conduction aphasics: Lesions of the non-fluent type were significantly larger than those of the fluent type and distributed more anteriorly. However, highly involved lesions were located in the supramarginal gyrus and posterior parts of superior and/or middle temporal gyri. 5. Global aphasics: Lesions of the group with good articulation and prosody were observed to distribute more posteriorly in comparison with those of the other global aphasics. (J.P.N.)

Accumulation and altered localization of telomere-associated protein TRF2 in immortally transformed and tumor-derived human breast cells

Energy Technology Data Exchange (ETDEWEB)

Nijjar, Tarlochan; Bassett, Ekaterina; Garbe, James; Takenaka, Yasuhiro; Stampfer, Martha R.; Gilley, David; Yaswen, Paul

2004-12-23

We have used cultured human mammary epithelial cells (HMEC) and breast tumor-derived lines to gain information on defects that occur during breast cancer progression. HMEC immortalized by a variety of agents (the chemical carcinogen benzo(a)pyrene, oncogenes c-myc and ZNF217, and/or dominant negative p53 genetic suppressor element GSE22) displayed marked up regulation (10-15 fold) of the telomere binding protein, TRF2. Up-regulation of TRF2 protein was apparently due to differences in post-transcriptional regulation, as mRNA levels remained comparable in finite life span and immortal HMEC. TRF2 protein was not up-regulated by the oncogenic agents alone in the absence of immortalization, nor by expression of exogenously introduced hTERT genes. We found TRF2 levels to be at least 2-fold higher than in control cells in 11/15 breast tumor cell lines, suggesting that elevated TRF2 levels are a frequent occurrence during the transformation of breast tumor cells in vivo. The dispersed distribution of TRF2 throughout the nuclei in some immortalized and tumor-derived cells indicated that not all the TRF2 was associated with telomeres in these cells. The process responsible for accumulation of TRF2 in immortalized HMEC and breast tumor-derived cell lines may promote tumorigenesis by contributing to the cells ability to maintain an indefinite life span.

Bioavailability of benzo(a)pyrene and dehydroabietic acid from a few lake waters containing varying dissolved organic carbon concentrations to Daphnia magna

International Nuclear Information System (INIS)

Oikari, A.; Kukkonen, J.

1990-01-01

Dissolved organic carbon (DOC) in natural waters consists of a great variety of organic molecules. Some of these molecules have been identified but most of them cannot be identified. This unidentified group of heterogeneous organic macromolecules is considered as humic substances. The role of humic substances in water chemistry and in aquatic toxicology is receiving increasing attention. The effects of DOC on the bioavailability of organic pollutants have been demonstrated in several studies. A decreased bioavailability has been demonstrated in most cases. Both the quantity and the quality of DOC are suggested determinants of this apparent ecotoxicological buffer of inland waters worldwide. In this study, the authors measured the bioaccumulation of benzo(a)pyrene (BaP) and dehydroabietic acid (DHAA) in Daphnia magna using a wide range of naturally occurring DOC levels. Another objective was to associate the reduced bioavailability with the chemical characteristics of water and DOC

Unprecedented head-to-head right-handed cross-links between the antitumor bis(mu-N,N'-di-p-tolylformamidinate) dirhodium(II,II) core and the dinucleotide d(ApA) with the adenine bases in the rare imino form.

Science.gov (United States)

Chifotides, Helen T; Dunbar, Kim R

2007-10-17

Reactions of the anticancer active compound cis-[Rh2(DTolF)2(CH3CN)6](BF4)2 with 9-ethyladenine (9-EtAdeH) or the dinucleotide d(ApA) proceed with bridging adenine bases in the rare imino form (A*), spanning the Rh-Rh bond at equatorial positions via N7/N6. The inflection points for the pH-dependent H2 and H8 NMR resonance curves of cis-[Rh2(DTolF)2(9-EtAdeH)2](BF4)2 correspond to N1H deprotonation of the metal-stabilized rare imino tautomer, which takes place at pKa approximately 7.5 in CD3CN-d3, a considerably reduced value as compared to that of the imino form of 9-EtAdeH. Similarly, coordination of the metal atoms to the N7/N6 adenine sites in Rh2(DTolF)2{d(ApA)} induces formation of the rare imino tautomer of the bases with a concomitant substantial decrease in the basicity of the N1H sites (pKa approximately 7.0 in CD3CN-d3), as compared to the imino form of the free dinucleotide. The presence of the adenine bases in the rare imino form, due to bidentate metalation of the N6/N7 sites, is further corroborated by DQF-COSY H2/N1H and ROE N1H/N6H cross-peaks in the 2D NMR spectra of Rh2(DTolF)2{d(ApA)} in CD3CN-d3 at -38 degrees C. Due to the N7/N6 bridging mode of the adenine bases in Rh2(DTolF)2{d(ApA)}, only the anti orientation of the imino tautomer is possible. The imino form A* of adenine in DNA may result in AT-->CG transversions or AT-->GC transitions, which can eventually lead to lethal mutations. The HH arrangement of the bases in Rh2(DTolF)2{d(ApA)} is indicated by the H8/H8 NOE cross-peaks in the 2D ROESY NMR spectrum, whereas the formamidinate bridging groups dictate the presence of one right-handed conformer HH1R in solution. Complete characterization of Rh2(DTolF)2{d(ApA)} by 2D NMR spectroscopy and molecular modeling supports the presence of the HH1R conformer, anti orientation of both sugar residues about the glycosyl bonds, and N-type conformation for the 5'-A base.

Nora's lesion, a distinct radiological entity?

International Nuclear Information System (INIS)

Dhondt, E.; Oudenhoven, L.; Khan, S.; Kroon, H.M.; Hogendoorn, P.C.; Nieborg, A.; Bloem, J.L.; Schepper, A. de

2006-01-01

To describe the radiological findings of ''Bizarre parosteal osteochondromatous proliferation''(BPOP) - otherwise known as Nora's lesion, to describe the natural evolution of BPOP and to assess radiologically if BPOP is indeed part of a spectrum of reactive lesions including florid reactive periostitis and turret exostosis. Four experienced musculoskeletal radiologists studied plain radiographs and other imaging documents of histologically-proven Nora's lesions, looking for soft-tissue changes, periosteal reaction/calcification and calcified/ossified pseudotumours, and compared those findings with findings on pathology reviewed by a peer group of pathologists. Twenty-four Nora's lesions originating from a series of 200 consecutive, histologically-verified bone (pseudo)tumours of the hand, seen by the ''Netherlands Committee on Bone Tumours'' for review and second opinion. Nora's lesions have a recognised presentation on radiographs without specific MR characteristics. Natural evolution could be assessed retrospectively in four cases. Recurrent lesions were seen in seven cases and are difficult to differentiate from primary Lesions. (orig.)

Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits

Directory of Open Access Journals (Sweden)

Sarah Meyer

2016-01-01

Full Text Available The aim of this study was to investigate the relationship between stroke lesion location and the resulting somatosensory deficit. We studied exteroceptive and proprioceptive somatosensory symptoms and stroke lesions in 38 patients with first-ever acute stroke. The Erasmus modified Nottingham Sensory Assessment was used to clinically evaluate somatosensory functioning in the arm and hand within the first week after stroke onset. Additionally, more objective measures such as the perceptual threshold of touch and somatosensory evoked potentials were recorded. Non-parametric voxel-based lesion-symptom mapping was performed to investigate lesion contribution to different somatosensory deficits in the upper limb. Additionally, structural connectivity of brain areas that demonstrated the strongest association with somatosensory symptoms was determined, using probabilistic fiber tracking based on diffusion tensor imaging data from a healthy age-matched sample. Voxels with a significant association to somatosensory deficits were clustered in two core brain regions: the central parietal white matter, also referred to as the sensory component of the superior thalamic radiation, and the parietal operculum close to the insular cortex, representing the secondary somatosensory cortex. Our objective recordings confirmed findings from clinical assessments. Probabilistic tracking connected the first region to thalamus, internal capsule, brain stem, postcentral gyrus, cerebellum, and frontal pathways, while the second region demonstrated structural connections to thalamus, insular and primary somatosensory cortex. This study reveals that stroke lesions in the sensory fibers of the superior thalamocortical radiation and the parietal operculum are significantly associated with multiple exteroceptive and proprioceptive deficits in the arm and hand.

Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits.

Science.gov (United States)

Meyer, Sarah; Kessner, Simon S; Cheng, Bastian; Bönstrup, Marlene; Schulz, Robert; Hummel, Friedhelm C; De Bruyn, Nele; Peeters, Andre; Van Pesch, Vincent; Duprez, Thierry; Sunaert, Stefan; Schrooten, Maarten; Feys, Hilde; Gerloff, Christian; Thomalla, Götz; Thijs, Vincent; Verheyden, Geert

2016-01-01

The aim of this study was to investigate the relationship between stroke lesion location and the resulting somatosensory deficit. We studied exteroceptive and proprioceptive somatosensory symptoms and stroke lesions in 38 patients with first-ever acute stroke. The Erasmus modified Nottingham Sensory Assessment was used to clinically evaluate somatosensory functioning in the arm and hand within the first week after stroke onset. Additionally, more objective measures such as the perceptual threshold of touch and somatosensory evoked potentials were recorded. Non-parametric voxel-based lesion-symptom mapping was performed to investigate lesion contribution to different somatosensory deficits in the upper limb. Additionally, structural connectivity of brain areas that demonstrated the strongest association with somatosensory symptoms was determined, using probabilistic fiber tracking based on diffusion tensor imaging data from a healthy age-matched sample. Voxels with a significant association to somatosensory deficits were clustered in two core brain regions: the central parietal white matter, also referred to as the sensory component of the superior thalamic radiation, and the parietal operculum close to the insular cortex, representing the secondary somatosensory cortex. Our objective recordings confirmed findings from clinical assessments. Probabilistic tracking connected the first region to thalamus, internal capsule, brain stem, postcentral gyrus, cerebellum, and frontal pathways, while the second region demonstrated structural connections to thalamus, insular and primary somatosensory cortex. This study reveals that stroke lesions in the sensory fibers of the superior thalamocortical radiation and the parietal operculum are significantly associated with multiple exteroceptive and proprioceptive deficits in the arm and hand.

DNA oxidation and DNA repair in gills of zebra mussels exposed to cadmium and benzo(a)pyrene.

Science.gov (United States)

Michel, Cécile; Vincent-Hubert, Françoise

2015-11-01

Freshwater bivalve molluscs are considered as effective indicators of environmental pollution. The comet assay allows the detection of DNA damage such as DNA strand breaks and alkali-labile sites. The main oxidative lesion, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is a pre-mutagenic lesion, can be detected by the comet assay coupled with the hOGG1 DNA repair enzyme. With this modified assay we recently observed that BaP induced 8-oxodG lesions and with the modified comet-Fpg assay we observed that Cd induced oxidative DNA damage. The aim of this study was to determine the stability of DNA lesions in Cd and BaP exposed zebra mussels using the comet-hOGG1 assay. Mussels were exposed for 24 h to these two chemicals and then placed in clean water for 6 days. We observed that BaP (7, 12 and 18 µg/L) induced an increase of DNA strand break levels as soon as 6 h of exposure and that the two highest concentrations of BaP induced a low level of hOGG1-sensitive sites. After 2 days of depuration, BaP induced DNA lesions returned to the basal level, indicating an effective DNA repair. Cd (3, 32 and 81 µg/L) induced an increase of the DNA strand break levels and a low level of hOGG1-sensitive sites. This study revealed that BaP-induced DNA lesions are repaired more efficiently than Cd-induced DNA lesions. As the level of hOGG1 sensitive sites was increased in Cd and BaP exposed mussels, it seems that these chemicals induce 8-oxo-dG.

Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin

Science.gov (United States)

Huang, Yuanshen; Wang, Yang; Yu, Jie; Gao, Min; Levings, Megan; Wei, Shencai; Zhang, Shengquan; Xu, Aie; Su, Mingwan; Dutz, Jan; Zhang, Xuejun; Zhou, Youwen

2012-01-01

Background Vitiligo is characterized by the death of melanocytes in the skin. This is associated with the presence of T cell infiltrates in the lesional borders. However, at present, there is no detailed and systematic characterization on whether additional cellular or molecular changes are present inside vitiligo lesions. Further, it is unknown if the normal appearing non-lesional skin of vitiligo patients is in fact normal. The purpose of this study is to systematically characterize the molecular and cellular characteristics of the lesional and non-lesional skin of vitiligo patients. Methods and Materials Paired lesional and non-lesional skin biopsies from twenty-three vitiligo patients and normal skin biopsies from sixteen healthy volunteers were obtained with informed consent. The following aspects were analyzed: (1) transcriptome changes present in vitiligo skin using DNA microarrays and qRT-PCR; (2) abnormal cellular infiltrates in vitiligo skin explant cultures using flow cytometry; and (3) distribution of the abnormal cellular infiltrates in vitiligo skin using immunofluorescence microscopy. Results Compared with normal skin, vitiligo lesional skin contained 17 genes (mostly melanocyte-specific genes) whose expression was decreased or absent. In contrast, the relative expression of 13 genes was up-regulated. The up-regulated genes point to aberrant activity of the innate immune system, especially natural killer cells in vitiligo. Strikingly, the markers of heightened innate immune responses were also found to be up-regulated in the non-lesional skin of vitiligo patients. Conclusions and Clinical Implications As the first systematic transcriptome characterization of the skin in vitiligo patients, this study revealed previously unknown molecular markers that strongly suggest aberrant innate immune activation in the microenvironment of vitiligo skin. Since these changes involve both lesional and non-lesional skin, our results suggest that therapies targeting

Silent ischemic brain lesions after transcatheter aortic valve replacement : lesion distribution and predictors

NARCIS (Netherlands)

Samim, Mariam; Hendrikse, Jeroen; van der Worp, H. Bart; Agostoni, Pierfrancesco; Nijhoff, Freek; Doevendans, Pieter A.; Stella, Pieter R.

Silent ischemic brain lesions and ischemic stroke are known complications of transcatheter aortic valve replacement (TAVR). We aimed to investigate the occurrence and distribution of TAVR-related silent ischemic brain lesions using diffusion-weighted magnetic resonance imaging (DWI). Consecutive

l-carnitine as a Potential Additive in Blood Storage Solutions: A Study on Erythrocytes

OpenAIRE

Soumya, R.; Carl, H.; Vani, R.

2015-01-01

Erythrocytes undergo various changes during storage (storage lesion) that in turn reduces their functioning and survival. Oxidative stress plays a major role in the storage lesion and antioxidants can be used to combat this stress. This study elucidates the effects of l-carnitine (LC) on erythrocytes of stored blood. Blood was obtained from male Wistar rats and stored (4 °C) for 20 days in CPDA-1 (citrate phosphate dextrose adenine) solution. Samples were divided into–(i) controls (ii) LC 10 ...

Effect of the Apulia air quality plan on PM10 and benzo(apyrene exceedances

Directory of Open Access Journals (Sweden)

L. Trizio

2016-03-01

Full Text Available During the last years, several exceedances of PM10 and benzo(apyrene limit values exceedances were recorded in Taranto, a city in southern Italy included in so-called areas at high risk of environmental crisis because of the presence of a heavy industrial district including the largest steel factory in Europe. A study of these critical pollution events showed a close correlation with the wind coming from the industrial site to the adjacent urban area. During 2011, at monitoring sites closes to the industrial area, at least the 65% of PM10 exceedances were related to wind day conditions (characterized by at least 3 consecutive hours of wind coming from 270-360±2deg with an associated speed higher than 7 m/s. For this reason, in 2012 an integrated environmental permit and a regional air quality plan were enacted to reduce pollutant emissions from industrial plants. A study of PM10 levels registered during windy days was performed during critical episodes of pollution highlighting that the difference between windy days and no windy days’ concentrations reduces from 2012 to 2014 in industrial site. False negative events (verified ex-post by observed meteorological data not identified by the forecast model - did not show a significant influence on PM concentration: PM10 values were comparable and sometimes lower than windy days levels. It is reasonable that the new scenario with a relevant reduction emissions form Ilva plant reduced the pollutants contribution from industrial area, contributing to PM10 levels decrease, also in false negative events.

Sonographic Findings of Morel-Lavalle'e Lesions

International Nuclear Information System (INIS)

Oh, Yu Jin; Yang, Ik; Lee, Yul; Woo, Ji Young; Hong, Hye Suk; Jung, Ah Young; Jeh, Su Kyung

2011-01-01

We reviewed the sonographic features of Morel-Lavalle'e lesions by correlating the US image findings with a lesion's age. We obtained the sonography reports of 20 Morel-Lavalle'e lesions of the hip and extremities from 18 patients with a history of trauma. The US images were reviewed to characterize the echogenicity, shape, homogeneity, margins, location and size of the lesions. The results were correlated with the age of the lesions and the clinical histories. All the Morel-Lavalle'e lesions were hypoechoic or anechoic fluid collections located between the subcutaneous fat and the underlying fascia. Regarding the shape of the fluid collections, the lobular shaped lesions were all less than 21 days for the lesion's age, and the flat fluid collections were all greater than 1 month of age. Regarding the homogeneity, the heterogeneous fluid collections were all less than 25 days of age, and the homogeneous fluid collections were all greater than 1 month of age. A Morel-Lavalle'e lesion is seen as a posttraumatic fluid collection in the potential space between the subcutaneous fat and the underlying fascia on an ultrasound examination. Acute Morel-Lavalle'e lesions tended to be heterogeneous and lobular, and they became more homogeneous and flat in shape as the lesions evolved. Awareness of these imaging findings will help us to properly diagnose Morel- Lavalle'e lesions

Genetic ablation of soluble TNF does not affect lesion size and functional recovery after moderate spinal cord injury in mice

DEFF Research Database (Denmark)

Ellman, Ditte Gry; Degn, Matilda; Lund, Minna Christiansen

2016-01-01

Traumatic spinal cord injury (SCI) is followed by an instant increase in expression of the microglial-derived proinflammatory cytokine tumor necrosis factor (TNF) within the lesioned cord. TNF exists both as membrane-anchored TNF (mTNF) and as cleaved soluble TNF (solTNF). We previously demonstra......, and MHCII), lesion size, and functional outcome after moderate SCI were comparable between genotypes. Collectively, our data demonstrate that genetic ablation of solTNF does not significantly modulate postlesion outcome after SCI....

Solitary lucent epiphyseal lesions in children

Energy Technology Data Exchange (ETDEWEB)

Gardner, D.J.; Azouz, E.M.

1988-10-01

We evaluated retrospectively the varying radiographic appearances of 15 solitary lucent epiphyseal lesions occurring in children. Imaging modalities used included plain films, conventional tomography, nuclear scintigraphy, and computed tomography. 40% of the lesions (6) were due to osteomyelitis. The remaining lesions included tuberculosis (1), foreign body granuloma (1), chondroblastoma (2), chondromyoxid fibroma (1), enchondroma (1), osteoid osteoma (2), and eosinophilic granuloma (1). Although the radiographic appearances of such lesions may be particularly characteristic, pathologic correlation is frequently necessary. The high incidence of osteomyelitis in our cases emphasizes its importance as a cause for a lucent epiphyseal lesion.

Histomorphological spetrum of breast lesions.

Science.gov (United States)

Parajuli, S; Koirala, U; Khatri, R; Acharya, L; Suwal, A

2011-04-01

Cancer of the breast is the second most common cause of cancer in women. Mass in the breast, whether benign or malignant is a cause of anxiety to the patients and the family members. All breast lumps are considered to be carcinomas until proved otherwise and are the causes of concern both for the patient and surgeon. This is a retrospective study conducted in Kathmandu Model Hospital for a total duration of three years from August 2007 to August 2010. 114 sample of breast tissue sent for histopathology were studied. Peak incidence of benign lesion was in between 21-30 years and malignant lesions in between 31-50 years. No breast lesions were seen in the first decade of life. Cancer of the breast was seen in 12.28% of cases. Fibroadenoma and fibrocystic disease were the commonest benign lesion and infiltrating ductal carcinoma was the commonest malignant lesion. Specimens from 10 male breasts were received. Gynaecomastia was the most common lesion encountered in males. Infiltrating ductal carcinoma was seen in a 70 year old male. Breast cancer is one of the commonest causes of breast lump particularly in women and is growing public health problem in Nepal.

Petrous apex lesions in the pediatric population

Energy Technology Data Exchange (ETDEWEB)

Radhakrishnan, Rupa [University of Cincinnati College of Medicine, Department of Radiology, Cincinnati, OH (United States); Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Son, Hwa Jung [University of Cincinnati College of Medicine, Department of Otolaryngology-Head and Neck Surgery, Cincinnati, OH (United States); Koch, Bernadette L. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States)

2014-03-15

A variety of abnormal imaging findings of the petrous apex are encountered in children. Many petrous apex lesions are identified incidentally while images of the brain or head and neck are being obtained for indications unrelated to the temporal bone. Differential considerations of petrous apex lesions in children include ''leave me alone'' lesions, infectious or inflammatory lesions, fibro-osseous lesions, neoplasms and neoplasm-like lesions, as well as a few rare miscellaneous conditions. Some lesions are similar to those encountered in adults, and some are unique to children. Langerhans cell histiocytosis (LCH) and primary and metastatic pediatric malignancies such as neuroblastoma, rhabomyosarcoma and Ewing sarcoma are more likely to be encountered in children. Lesions such as petrous apex cholesterol granuloma, cholesteatoma and chondrosarcoma are more common in adults and are rarely a diagnostic consideration in children. We present a comprehensive pictorial review of CT and MRI appearances of pediatric petrous apex lesions. (orig.)

First International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

Science.gov (United States)

Rageth, Christoph J; O'Flynn, Elizabeth Am; Comstock, Christopher; Kurtz, Claudia; Kubik, Rahel; Madjar, Helmut; Lepori, Domenico; Kampmann, Gert; Mundinger, Alexander; Baege, Astrid; Decker, Thomas; Hosch, Stefanie; Tausch, Christoph; Delaloye, Jean-François; Morris, Elisabeth; Varga, Zsuzsanna

2016-09-01

The purpose of this study is to obtain a consensus for the therapy of B3 lesions. The first International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions) including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL), benign phyllodes tumors (PT), and radial scars (RS) took place in January 2016 in Zurich, Switzerland organized by the International Breast Ultrasound School and the Swiss Minimally Invasive Breast Biopsy group-a subgroup of the Swiss Society of Senology. Consensus recommendations for the management and follow-up surveillance of these B3 lesions were developed and areas of research priorities were identified. The consensus recommendation for FEA, LN, PL, and RS diagnosed on core needle biopsy or vacuum-assisted biopsy (VAB) is to therapeutically excise the lesion seen on imaging by VAB and no longer by open surgery, with follow-up surveillance imaging for 5 years. The consensus recommendation for ADH and PT is, with some exceptions, therapeutic first-line open surgical excision. Minimally invasive management of selected B3 lesions with therapeutic VAB is acceptable as an alternative to first-line surgical excision.

Morel-Lavallee lesion.

Science.gov (United States)

Li, Hui; Zhang, Fangjie; Lei, Guanghua

2014-01-01

To review current knowledge of the Morel-Lavallee lesion (MLL) to help clinicians become familiar with this entity. Familiarization may decrease missed diagnoses and misdiagnoses. It could also help steer the clinician to the proper treatment choice. A search was performed via PubMed and EMBASE from 1966 to July 2013 using the following keywords: Morel-Lavallee lesion, closed degloving injury, concealed degloving injury, Morel-Lavallee effusion, Morel-Lavallee hematoma, posttraumatic pseudocyst, posttraumatic soft tissue cyst. Chinese and English language literatures relevant to the subject were collected. Their references were also reviewed. Morel-Lavallee lesion is a relatively rare condition involving a closed degloving injury. It is characterized by a filled cystic cavity created by separation of the subcutaneous tissue from the underlying fascia. Apart from the classic location over the region of the greater trochanter, MLLs have been described in other parts of the body. The natural history of MLL has not yet been established. The lesion may decrease in volume, remain stable, enlarge progressively or show a recurrent pattern. Diagnosis of MLL was often missed or delayed. Ultrasonography, computed tomography, and magnetic resonance imaging have great value in the diagnosis of MLL. Treatment of MLL has included compression, local aspiration, open debridement, and sclerodesis. No standard treatment has been established. A diagnosis of MLL should be suspected when a soft, fluctuant area of skin or chronic recurrent fluid collection is found in a region exposed to a previous shear injury. Clinicians and radiologists should be aware of both the acute and chronic appearances to make the correct diagnosis. Treatment decisions should base on association with fractures, the condition of the lesion, symptom and desire of the patient.

Mammographic quantitative image analysis and biologic image composition for breast lesion characterization and classification

Energy Technology Data Exchange (ETDEWEB)

Drukker, Karen, E-mail: kdrukker@uchicago.edu; Giger, Maryellen L.; Li, Hui [Department of Radiology, University of Chicago, Chicago, Illinois 60637 (United States); Duewer, Fred; Malkov, Serghei; Joe, Bonnie; Kerlikowske, Karla; Shepherd, John A. [Radiology Department, University of California, San Francisco, California 94143 (United States); Flowers, Chris I. [Department of Radiology, University of South Florida, Tampa, Florida 33612 (United States); Drukteinis, Jennifer S. [Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612 (United States)

2014-03-15

Purpose: To investigate whether biologic image composition of mammographic lesions can improve upon existing mammographic quantitative image analysis (QIA) in estimating the probability of malignancy. Methods: The study population consisted of 45 breast lesions imaged with dual-energy mammography prior to breast biopsy with final diagnosis resulting in 10 invasive ductal carcinomas, 5 ductal carcinomain situ, 11 fibroadenomas, and 19 other benign diagnoses. Analysis was threefold: (1) The raw low-energy mammographic images were analyzed with an established in-house QIA method, “QIA alone,” (2) the three-compartment breast (3CB) composition measure—derived from the dual-energy mammography—of water, lipid, and protein thickness were assessed, “3CB alone”, and (3) information from QIA and 3CB was combined, “QIA + 3CB.” Analysis was initiated from radiologist-indicated lesion centers and was otherwise fully automated. Steps of the QIA and 3CB methods were lesion segmentation, characterization, and subsequent classification for malignancy in leave-one-case-out cross-validation. Performance assessment included box plots, Bland–Altman plots, and Receiver Operating Characteristic (ROC) analysis. Results: The area under the ROC curve (AUC) for distinguishing between benign and malignant lesions (invasive and DCIS) was 0.81 (standard error 0.07) for the “QIA alone” method, 0.72 (0.07) for “3CB alone” method, and 0.86 (0.04) for “QIA+3CB” combined. The difference in AUC was 0.043 between “QIA + 3CB” and “QIA alone” but failed to reach statistical significance (95% confidence interval [–0.17 to + 0.26]). Conclusions: In this pilot study analyzing the new 3CB imaging modality, knowledge of the composition of breast lesions and their periphery appeared additive in combination with existing mammographic QIA methods for the distinction between different benign and malignant lesion types.

Correlation of the SLAP lesion with lesions of the medial sheath of the biceps tendon and intra-articular subscapularis tendon

Directory of Open Access Journals (Sweden)

Bennett William

2009-01-01

Full Text Available Background: Superior labral anterior to posterior (SLAP lesions have been well described in the literature and are thought to be secondary to traction injuries to the biceps anchor and/or falls on the outstretched arm. The pulley has recently been described as a structure that aids in the prevention of biceps instability. The intra-articular subscapularis insertion (IASS has been noted to contribute to the robust nature of the medial sheath. The purpose of the study was to determine a potential correlation of SLAP lesions and pulley lesions with/without IASS lesions, (hereafter referred to as medial sheath as forces that can disrupt the biceps anchor and may also disrupt structures of the medial sheath or vice-versa. Materials and Methods: Three hundred and sixteen consecutive shoulder arthroscopies performed by one surgeon were reviewed retrospectively. Operative reports and arthroscopic pictures were carefully reviewed with particular attention paid to the labral and pulley pathology. Selection bias was noted as the author had never operated primarily for a Type 1 SLAP lesion. Following, however, and as such, the exclusion criteria, was a Type 1 SLAP. Results: There were a total of 30 SLAP lesions and a total of 126 medial sheath lesions. There were 13 patients who had both SLAP and medial sheath lesions. There were 17 patients who had a SLAP lesion without a medial sheath lesion. There were 96 medial sheath lesions without a SLAP. A comparison of rates between patients who had a medial sheath lesion with a SLAP and those who had a medial sheath lesion without a SLAP, for the 316 patients, and when tested with a Fisher exact test revealed that there was no statistical significance, P = 0.673. The prevalence of SLAP lesions in this population of 316 patients was 9.4%, Buford 1%, medial sheath lesions 39%, and SLAP and medial sheath lesions 4%. Interestingly, there were three Buford complexes, all associated with a SLAP and one Buford complex

Phytoremediation for co-contaminated soils of chromium and benzo[a]pyrene using Zea mays L.

Science.gov (United States)

Chigbo, Chibuike; Batty, Lesley

2014-02-01

A greenhouse experiment was carried out to investigate the single effect of benzo[a]pyrene (B[a]P) or chromium (Cr) and the joint effect of Cr-B[a]P on the growth of Zea mays, its uptake and accumulation of Cr, and the dissipation of B[a]P over 60 days. Results showed that single or joint contamination of Cr and B[a]P did not affect the plant growth relative to control treatments. However, the occurrence of B[a]P had an enhancing effect on the accumulation and translocation of Cr. The accumulation of Cr in shoot of plant significantly increased by ≥ 79 % in 50 mg kg(-1) Cr-B[a]P (1, 5, and 10 mg kg(-1)) treatments and by ≥ 86 % in 100 mg kg(-1) Cr-B[a]P (1, 5, and 10 mg kg(-1)) treatments relative to control treatments. The presence of plants did not enhance the dissipation of B[a]P in lower (1and 5 mg kg(-1)) B[a]P contaminated soils; however, over 60 days of planting Z. mays seemed to enhance the dissipation of B[a]P by over 60 % in 10 mg kg(-1) single contaminated soil and by 28 to 41 % in 10 mg kg(-1)B[a]P co-contaminated soil. This suggests that Z. mays might be a useful plant for the remediation of Cr-B[a]P co-contaminated soil.

Evaluating the agreement between tumour volumetry and the estimated volumes of tumour lesions using an algorithm

Energy Technology Data Exchange (ETDEWEB)

Laubender, Ruediger P. [German Cancer Consortium (DKTK), Heidelberg (Germany); University Hospital Munich - Campus Grosshadern, Institute of Medical Informatics, Biometry, and Epidemiology (IBE), Munich (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); Lynghjem, Julia; D' Anastasi, Melvin; Graser, Anno [University Hospital Munich - Campus Grosshadern, Institute for Clinical Radiology, Munich (Germany); Heinemann, Volker; Modest, Dominik P. [University Hospital Munich - Campus Grosshadern, Department of Medical Oncology, Munich (Germany); Mansmann, Ulrich R. [University Hospital Munich - Campus Grosshadern, Institute of Medical Informatics, Biometry, and Epidemiology (IBE), Munich (Germany); Sartorius, Ute; Schlichting, Michael [Merck KGaA, Darmstadt (Germany)

2014-07-15

To evaluate the agreement between tumour volume derived from semiautomated volumetry (SaV) and tumor volume defined by spherical volume using longest lesion diameter (LD) according to Response Evaluation Criteria In Solid Tumors (RECIST) or ellipsoid volume using LD and longest orthogonal diameter (LOD) according to World Health Organization (WHO) criteria. Twenty patients with metastatic colorectal cancer from the CIOX trial were included. A total of 151 target lesions were defined by baseline computed tomography and followed until disease progression. All assessments were performed by a single reader. A variance component model was used to compare the three volume versions. There was a significant difference between the SaV and RECIST-based tumour volumes. The same model showed no significant difference between the SaV and WHO-based volumes. Scatter plots showed that the RECIST-based volumes overestimate lesion volume. The agreement between the SaV and WHO-based relative changes in tumour volume, evaluated by intraclass correlation, showed nearly perfect agreement. Estimating the volume of metastatic lesions using both the LD and LOD (WHO) is more accurate than those based on LD only (RECIST), which overestimates lesion volume. The good agreement between the SaV and WHO-based relative changes in tumour volume enables a reasonable approximation of three-dimensional tumour burden. (orig.)

Changes in phosphorylation of adenosine phosphate and redox state of nicotinamide-adenine dinucleotide (phosphate) in Geobacter sulfurreducens in response to electron acceptor and anode potential variation

KAUST Repository

Rose, Nicholas D.; Regan, John M.

2015-01-01

© 2015 Elsevier B.V. Geobacter sulfurreducens is one of the dominant bacterial species found in biofilms growing on anodes in bioelectrochemical systems. The intracellular concentrations of reduced and oxidized forms of nicotinamide-adenine dinucleotide (NADH and NAD⁺, respectively) and nicotinamide-adenine dinucleotide phosphate (NADPH and NADP⁺, respectively) as well as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were measured in G. sulfurreducens using fumarate, Fe(III)-citrate, or anodes poised at different potentials (110, 10, -90, and -190mV (vs. SHE)) as the electron acceptor. The ratios of CNADH/CNAD+ (0.088±0.022) and CNADPH/CNADP+ (0.268±0.098) were similar under all anode potentials tested and with Fe(III)-citrate (reduced extracellularly). Both ratios significantly increased with fumarate as the electron acceptor (0.331±0.094 for NAD and 1.96±0.37 for NADP). The adenylate energy charge (the fraction of phosphorylation in intracellular adenosine phosphates) was maintained near 0.47 under almost all conditions. Anode-growing biofilms demonstrated a significantly higher molar ratio of ATP/ADP relative to suspended cultures grown on fumarate or Fe(III)-citrate. These results provide evidence that the cellular location of reduction and not the redox potential of the electron acceptor controls the intracellular redox potential in G. sulfurreducens and that biofilm growth alters adenylate phosphorylation.

Changes in phosphorylation of adenosine phosphate and redox state of nicotinamide-adenine dinucleotide (phosphate) in Geobacter sulfurreducens in response to electron acceptor and anode potential variation

KAUST Repository

Rose, Nicholas D.

2015-12-01

© 2015 Elsevier B.V. Geobacter sulfurreducens is one of the dominant bacterial species found in biofilms growing on anodes in bioelectrochemical systems. The intracellular concentrations of reduced and oxidized forms of nicotinamide-adenine dinucleotide (NADH and NAD⁺, respectively) and nicotinamide-adenine dinucleotide phosphate (NADPH and NADP⁺, respectively) as well as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were measured in G. sulfurreducens using fumarate, Fe(III)-citrate, or anodes poised at different potentials (110, 10, -90, and -190mV (vs. SHE)) as the electron acceptor. The ratios of CNADH/CNAD+ (0.088±0.022) and CNADPH/CNADP+ (0.268±0.098) were similar under all anode potentials tested and with Fe(III)-citrate (reduced extracellularly). Both ratios significantly increased with fumarate as the electron acceptor (0.331±0.094 for NAD and 1.96±0.37 for NADP). The adenylate energy charge (the fraction of phosphorylation in intracellular adenosine phosphates) was maintained near 0.47 under almost all conditions. Anode-growing biofilms demonstrated a significantly higher molar ratio of ATP/ADP relative to suspended cultures grown on fumarate or Fe(III)-citrate. These results provide evidence that the cellular location of reduction and not the redox potential of the electron acceptor controls the intracellular redox potential in G. sulfurreducens and that biofilm growth alters adenylate phosphorylation.

Stroke Lesions in a Large Upper Limb Rehabilitation Trial Cohort Rarely Match Lesions in Common Preclinical Models

Science.gov (United States)

Edwardson, Matthew A.; Wang, Ximing; Liu, Brent; Ding, Li; Lane, Christianne J.; Park, Caron; Nelsen, Monica A.; Jones, Theresa A; Wolf, Steven L; Winstein, Carolee J; Dromerick, Alexander W.

2017-01-01

Background Stroke patients with mild-moderate upper extremity (UE) motor impairments and minimal sensory and cognitive deficits provide a useful model to study recovery and improve rehabilitation. Laboratory-based investigators use lesioning techniques for similar goals. Objective Determine whether stroke lesions in an UE rehabilitation trial cohort match lesions from the preclinical stroke recovery models used to drive translational research. Methods Clinical neuroimages from 297 participants enrolled in the Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) study were reviewed. Images were characterized based on lesion type (ischemic or hemorrhagic), volume, vascular territory, depth (cortical gray matter, cortical white matter, subcortical), old strokes, and leukoaraiosis. Lesions were compared with those of preclinical stroke models commonly used to study upper limb recovery. Results Among the ischemic stroke participants, median infarct volume was 1.8 mL, with most lesions confined to subcortical structures (61%) including the anterior choroidal artery territory (30%) and the pons (23%). Of ICARE participants, stroke patients, but they represent a clinically and scientifically important subgroup. Compared to lesions in general stroke populations and widely-studied animal models of recovery, ICARE participants had smaller, more subcortically-based strokes. Improved preclinical-clinical translational efforts may require better alignment of lesions between preclinical and human stroke recovery models. PMID:28337932

Radiologic appearance of primary jaw lesions in children

Energy Technology Data Exchange (ETDEWEB)

Gupta, Malini; Kaste, Sue C. [Department of Diagnostic Imaging, St. Jude Children' s Research Hospital, Memphis, TN (United States); Hopkins, Kenneth P. [Department of Surgery, Division of Dentistry, St. Jude Children' s Research Hospital, Memphis, TN (United States)

2002-03-01

Background: The jaw (an unusual site of primary tumors in children and adolescents) has lesions often found incidentally by dentists on routine panoramic radiographs or during examination of a child who has swelling or tooth pain. Objective: This pictorial seeks to familiarize pediatric radiologists with the radiographic appearance of a variety of primary jaw lesions. Materials and methods: We retrospectively searched institutional records for cases of primary jaw lesions in children and adolescents. Jaw lesions were characterized as: I, well-circumscribed radiolucent lesions; II, lesions with mixed or variable appearance; III, poorly circumscribed radiolucent lesions; and IV, radiopaque lesions. Results: Although most oral and maxillofacial lesions in children are benign, a broad spectrum of tumors was identified; lesions may occur in patients with unrelated prior malignancy. Conclusion: Because radiologic studies may identify jaw lesions and direct further care, familiarity with the appearance of these entities is prudent. (orig.)

Celiac lesion T cells recognize epitopes that cluster in regions of gliadins rich in proline residues

DEFF Research Database (Denmark)

Arentz-Hansen, Helene; McAdam, Stephen N; Molberg, Øyvind

2002-01-01

BACKGROUND & AIMS: Celiac disease is a gluten-induced enteropathy that shows a strong association with HLA-DQ2 and -DQ8. Gluten-specific T cells, invariably restricted by DQ2 or DQ8, can be isolated from celiac lesions. Such gut-derived T cells have a preference for recognition of gluten that has...

Lesion localization in aphasia without hemiparesis

International Nuclear Information System (INIS)

Komatsu, Midori; Senoh, Yoko; Okamoto, Koichi; Morimatsu, Mitsunori; Hirai, Shunsaku

1983-01-01

The distribution of the lesions responsible for aphasia unassociated with right-sided hemiparesis was evaluated by cranial computed tomography (CT) among stroke patients. In the Broca aphasia group were observed atypical aphasic symptoms, and the lesions were far more localized than in ordinary Broca one. In the Wernicke aphasia group showed relatively large lesions in the left superior temporal gyrus, sometimes extending to supramarginal and angular gyri, which caused such additional symptoms as apraxia without motor paresis in some cases. In the Transcortical motor aphasia group showed the occlusion of the left internal carotid artery, though without obvious abnormality at CT. In another patient a circumscribed low density lesion was disclosed in the area anterior and superior to so-called Broca's area. In the Transcortical sensory aphasia group, the lesion involved the borderzone supplied by the left middle and posterior cerebral arteries. In the Amnestic aphasia group showed a lesion in the left parietal lobe, while in another no remarkable change was demonstrated. In the Global aphasia group, one had multiple isolated lesions in both anterior and posterior speech areas. Another showed a large lesion involving the whole territory of the left middle cerebral artery. In the remaining one a high density area was observed in the left superior temporal, supramarginal and angular gyri, not extending to the frontal lobe beyond with sylvian fissure. Therefore, in interpreting CTs of such aphasic patients we must take account of not only the extent of the lesion but also the severity of destruction. (J.P.N.)

Lesion localization in aphasia without hemiparesis

Energy Technology Data Exchange (ETDEWEB)

Komatsu, Midori; Senoh, Yoko; Okamoto, Koichi; Morimatsu, Mitsunori; Hirai, Shunsaku (Gunma Univ., Maebashi (Japan). School of Medicine)

1983-06-01

The distribution of the lesions responsible for aphasia unassociated with right-sided hemiparesis was evaluated by cranial computed tomography (CT) among stroke patients. In the Broca aphasia group were observed atypical aphasic symptoms, and the lesions were far more localized than in ordinary Broca one. In the Wernicke aphasia group showed relatively large lesions in the left superior temporal gyrus, sometimes extending to supramarginal and angular gyri, which caused such additional symptoms as apraxia without motor paresis in some cases. In the Transcortical motor aphasia group showed the occlusion of the left internal carotid artery, though without obvious abnormality at CT. In another patient a circumscribed low density lesion was disclosed in the area anterior and superior to so-called Broca's area. In the Transcortical sensory aphasia group, the lesion involved the borderzone supplied by the left middle and posterior cerebral arteries. In the Amnestic aphasia group showed a lesion in the left parietal lobe, while in another no remarkable change was demonstrated. In the Global aphasia group, one had multiple isolated lesions in both anterior and posterior speech areas. Another showed a large lesion involving the whole territory of the left middle cerebral artery. In the remaining one a high density area was observed in the left superior temporal, supramarginal and angular gyri, not extending to the frontal lobe beyond with sylvian fissure. Therefore, in interpreting CTs of such aphasic patients we must take account of not only the extent of the lesion but also the severity of destruction.

Brain lesions in neurofibromatosis: clinical and MRI findings

International Nuclear Information System (INIS)

Magnaldi, S.

1990-01-01

Neurofibromatosis is the commonest neuroectodermal disease. It is characterized by dysplasias and/or tumors of organs and tissues derived from the embryonic ectoderm, and most frequently presents with nervous system and cutaneous lesions. It can be classified as neurofibromatosis type 2 (NF-2 or bilateral acoustic neurofibromatosis). In order to assess clinical presentation of the disease and diagnostic value of Magnetic Resonance Imaging (MRI), the authors retrospectively evaluated the clinical records and the cranial MR studies of 21 patients with neurofibromatosis (18 with NF-1 and 3 with NF-2). Distinctive abnormalities between the two types were found in both clinical presentation and MR studies. Clinically, NF-1 patients presented most often with blindness, while NF-2 patients were deaf and had fewer cutaneous lesions. The evaluation of MR studies showed that NF-1 patients were more likely to be affected with intracranial gliomas, predominantly of the optic pathways. Moreover, foci of prolonged T2 relaxation were frequently observed, primarily in the globus pallidus of the basal ganglia and in the dentate nucleus of the cerebellum. Some of the foci in the globi pallidi exhibited increased signal intensity on T1-weighted images as well. NF-2 patients more frequently presented with bilateral acoustic schwannomas, meningiomas and cerebral white matter foci of prolonged T2 relaxation, but they did not have dentate and basal ganglia lesions. The authors conclude that as a rule the manifestations of NF-1 and NF-2 on cranial MRI are separate and distinct; they do not overlap. MRI is an useful clinical tool for the diagnosis and the follow-up of patients with neurofibromatosis

Non-invasive optical estimate of tissue composition to differentiate malignant from benign breast lesions: A pilot study

Science.gov (United States)

Taroni, Paola; Paganoni, Anna Maria; Ieva, Francesca; Pifferi, Antonio; Quarto, Giovanna; Abbate, Francesca; Cassano, Enrico; Cubeddu, Rinaldo

2017-01-01

Several techniques are being investigated as a complement to screening mammography, to reduce its false-positive rate, but results are still insufficient to draw conclusions. This initial study explores time domain diffuse optical imaging as an adjunct method to classify non-invasively malignant vs benign breast lesions. We estimated differences in tissue composition (oxy- and deoxyhemoglobin, lipid, water, collagen) and absorption properties between lesion and average healthy tissue in the same breast applying a perturbative approach to optical images collected at 7 red-near infrared wavelengths (635-1060 nm) from subjects bearing breast lesions. The Discrete AdaBoost procedure, a machine-learning algorithm, was then exploited to classify lesions based on optically derived information (either tissue composition or absorption) and risk factors obtained from patient’s anamnesis (age, body mass index, familiarity, parity, use of oral contraceptives, and use of Tamoxifen). Collagen content, in particular, turned out to be the most important parameter for discrimination. Based on the initial results of this study the proposed method deserves further investigation.

Comparative evaluation of carcinogenesis risk in case of radiation effect and pollution of atmospheric air with coal ashes and benzo(a)pyrene

International Nuclear Information System (INIS)

Knizhnikov, V.A.; Shandala, N.K.; Komleva, V.A.; Likhovajdo, N.V.; Shvetsov, A.I.

1993-01-01

Assessment of the risk of lung carcinogenesis under the effect of benzo(a)pyrene (BP) and volatil coal ash in the atmospheric air was performed as well as comparison of this risk with the risk due to ionizing radiation effect from natural and technogenic sources. White mice were used as experimental animals. It was shown that BP was rather more carcinogenic than volatile coal ash. BP inhalation at a maximum permissible concentration level (0.1 μg/100 m 3 of air) corresponds to the equivalent risk of whole-body gamma exposure at bout 2 Sv. Coal ash inhalation at the concentration of 0.05 mg/m 3 corresponds to the same equivalent risk as for radiation dose 0.05 Sv. Conclusion is made that safety standards for coal ash and BP contents in the air do not remove carcinogenesis risk for the population. Whereas carcinogenesis risk due to irradiation at the level of radiation safety standards is considerably lower

Juxtacortical Lesions and Cortical Thinning in Multiple Sclerosis.

Science.gov (United States)

Pareto, D; Sastre-Garriga, J; Auger, C; Vives-Gilabert, Y; Delgado, J; Tintoré, M; Montalban, X; Rovira, A

2015-12-01

The role of juxtacortical lesions in brain volume loss in multiple sclerosis has not been fully clarified. The aim of this study was to explore the role of juxtacortical lesions on cortical atrophy and to investigate whether the presence of juxtacortical lesions is related to local cortical thinning in the early stages of MS. A total of 131 patients with clinically isolated syndrome or with relapsing-remitting MS were scanned on a 3T system. Patients with clinically isolated syndrome were classified into 3 groups based on the presence and topography of brain lesions: no lesions (n = 24), only non-juxtacortical lesions (n = 33), and juxtacortical lesions and non-juxtacortical lesions (n = 34). Patients with relapsing-remitting MS were classified into 2 groups: only non-juxtacortical lesions (n = 10) and with non-juxtacortical lesions and juxtacortical lesions (n = 30). A juxtacortical lesion probability map was generated, and cortical thickness was measured by using FreeSurfer. Juxtacortical lesion volume in relapsing-remitting MS was double that of patients with clinically isolated syndrome. The insula showed the highest density of juxtacortical lesions, followed by the temporal, parietal, frontal, and occipital lobes. Patients with relapsing-remitting MS with juxtacortical lesions showed significantly thinner cortices overall and in the parietal and temporal lobes compared with those with clinically isolated syndrome with normal brain MR imaging. The volume of subcortical structures (thalamus, pallidum, putamen, and accumbens) was significantly decreased in relapsing-remitting MS with juxtacortical lesions compared with clinically isolated syndrome with normal brain MR imaging. The spatial distribution of juxtacortical lesions was not found to overlap with areas of cortical thinning. Cortical thinning and subcortical gray matter volume loss in patients with a clinically isolated syndrome or relapsing-remitting MS was related to the presence of juxtacortical

DW-MRI of liver lesions: Can a single ADC-value represent the entire lesion?

International Nuclear Information System (INIS)

Schmid-Tannwald, C.; Dahi, F.; Jiang, Y.; Ivancevic, M.K.; Rist, C.; Sethi, I.; Oommen, J.; Oto, A.

2014-01-01

Aim: To evaluate whether focal liver lesions (FLLs) exhibit a homogeneous appearance on apparent diffusion coefficient (ADC) maps and whether there is inter-section variation in the calculated ADC values of FLLs (inter-section range). Materials and methods: Eighty-eight patients with 128 FLLs (70 benign, 58 malignant) who underwent abdominal magnetic resonance imaging (MRI) including diffusion-weighted (DW)-MRI were included. Two observers evaluated variation of signal intensity of each FLL within each ADC map image (intra-section) and among different ADC map images through the lesion (inter-section). ADC values of each FLL and neighbouring liver parenchyma were measured on all sections. The inter-section range of FLLs was compared with the neighbouring liver parenchyma. Results: Intra-section inhomogeneity was noted in 39.8% (97/244 sections) and 38.9% (95/244) of benign lesions, and 61% (114/187 sections) and 61.5% (115/187) of malignant lesions, by observer 1 and observer 2, respectively. Inter-section inhomogeneity was noted in 25.7% (18/70) and 27.1% (19/70) of benign lesions, and 51.7% (30/58) and 50% (29/58) of malignant lesions, by observer 1 and observer 2, respectively. The inter-section range for both benign (0.28 × 10 −3  mm²/s) and malignant (0.25 × 10 −3  mm²/s) FLLs were significantly greater than that of liver parenchyma surrounding benign (0.16 × 10 −3  mm²/s, p < 0.001) and malignant (0.14 × 10 −3  mm²/s, p = 0.01) FLLs. Conclusion: Due to intra-/inter-section variations in ADC values of benign and malignant FLLs, a single ADC value may not reliably represent the entire lesion

Tratamiento no quirúrgico de lesiones periapicales Non-surgical treatment of periapical lesions

Directory of Open Access Journals (Sweden)

Pedro Pablo Ferro Benítez

2005-08-01

Full Text Available El tratamiento de dientes con lesiones periapicales crónicas ha sido estudiado por diferentes autores en el campo endodóntico. Basados en los resultados obtenidos en diferentes trabajos experimentales, nos propusimos realizar la presente investigación, tomando 30 dientes humanos que al momento de realizar el tratamiento pulpo-radicular mostraban presencia de lesiones periapicales con diámetros variables, por encima de los 5 mm . Se tuvieron en cuenta 2 grupos: en uno de ellos se les realizaron a los conductos radiculares rellenos temporales de pasta de hidróxido de calcio y agua destilada; en el otro grupo a estos conductos se les realizaron rellenos temporales con pasta de hidróxido de calcio, agua destilada y paramonoclorofenol alcanforado. Se evaluó la disminución de las lesiones periapicales en ambos grupos a los 3 y 6 meses de iniciado el tratamiento, sin que se observaran diferencias estadísticamente significativas. Igual ocurrió en la evaluación de la reparación ósea periapical a los 9 meses de iniciado el tratamiento. Con ambas técnicas los resultados fueron satisfactorios, lo que demuestra una participación activa del hidróxido de calcio en la reparación de las lesiones periapicales, independientemente de su asociación con el paramonoclorofenol alcanforado.The treatment of teeth with chronic periapical lesions has been studied by different authors in the endodontics field. Based on the results attained in different experimental works, we proposed ourselves to make the present research taking 30 human teeth that at the time of applying the pulpar radicular treatment presented periapical lesions with variable diameters over 5 mm. Two groups were taken into account: in one of them, the radicular ducts were temporarily filled up with calcium hydroxide paste and distilled water, whereas in the other one these ducts were filled up with calcium hydroxide paste, distilled water and camphorated paramonochlorophenol. The

A new method for automated high-dimensional lesion segmentation evaluated in vascular injury and applied to the human occipital lobe.

Science.gov (United States)

Mah, Yee-Haur; Jager, Rolf; Kennard, Christopher; Husain, Masud; Nachev, Parashkev

2014-07-01

Making robust inferences about the functional neuroanatomy of the brain is critically dependent on experimental techniques that examine the consequences of focal loss of brain function. Unfortunately, the use of the most comprehensive such technique-lesion-function mapping-is complicated by the need for time-consuming and subjective manual delineation of the lesions, greatly limiting the practicability of the approach. Here we exploit a recently-described general measure of statistical anomaly, zeta, to devise a fully-automated, high-dimensional algorithm for identifying the parameters of lesions within a brain image given a reference set of normal brain images. We proceed to evaluate such an algorithm in the context of diffusion-weighted imaging of the commonest type of lesion used in neuroanatomical research: ischaemic damage. Summary performance metrics exceed those previously published for diffusion-weighted imaging and approach the current gold standard-manual segmentation-sufficiently closely for fully-automated lesion-mapping studies to become a possibility. We apply the new method to 435 unselected images of patients with ischaemic stroke to derive a probabilistic map of the pattern of damage in lesions involving the occipital lobe, demonstrating the variation of anatomical resolvability of occipital areas so as to guide future lesion-function studies of the region. Copyright © 2012 Elsevier Ltd. All rights reserved.

Atypical idiopathic inflammatory demyelinating lesions

DEFF Research Database (Denmark)

Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo

2013-01-01

Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be class......Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can...... be classified according to previously suggested radiologic characteristics and how this classification relates to prognosis. Searching the databases of eight tertiary referral centres we identified 90 adult patients (61 women, 29 men; mean age 34 years) with ≥1 AIIDL. We collected their demographic, clinical...

Measuring Cutaneous Lesions: Trends in Clinical Practice.

Science.gov (United States)

Zhang, Shali; Blalock, Travis W

2018-03-01

Knowing the size of a cutaneous lesion can be important for tracking its progression over time, selecting the proper treatment modality, surgical planning, determining prognosis, and accurate billing. However, providers vary in their consistency, accuracy, and methods of measuring cutaneous lesions. To investigate the clinical practices of US dermatologists and dermatologic surgeons regarding how they determine the size of cutaneous lesions. A survey was electronically distributed to members of the American Society for Dermatologic Surgery. Four hundred twenty-six dermatologists completed the online survey. When a lesion is suspected to be malignant, 85% of respondents obtained exact measurements most, if not all, of the time; however, only 8% did for benign lesions. Most providers determined lesion sizes themselves rather than delegating to staff. When performing visual estimation, approximately three-quarters believed that they were accurate to within 1 to 2 mm. The top reasons for obtaining exact measurements were for tracking atypical pigmented lesions, determining treatment pathways, and accurate billing. The majority of respondents believed that lesion size affected management decisions; however, the need for exact measurement remains controversial, particularly for benign lesions. Future studies may investigate whether taking exact versus estimated measurements has an effect on outcomes.

Male breast lesions

International Nuclear Information System (INIS)

Matushita, J.P.K.; Andrade, L.G. de; Carregal, E.; Marimatsu, R.I.; Matushita, J.S.

1989-01-01

Roentgenographic examination of the male breast is an important aspect of the continued, intensive investigation of the radiologic morphology of the normal and diseased breast conducted in 17 cases examined at the Instituto Nacional do Cancer - RJ. It is purpose of this report to present the Roentgen appearance of various lesions of the male breast as they have been found in our practice and also to stress some of the difficulties in the differential diagnosis of these lesions. (author) [pt

Effect of gamma radiation on levels of adenine nucleotides in erythrocytes of healthy individuals after submaximum physical exertion

International Nuclear Information System (INIS)

Zagorski, T.; Dudek, I.; Mazurek, M.; Berkan, L.; Chmielewski, H.; Kedziora, J.

1994-01-01

The authors studied the effect of gamma radiation and submaximum physical exercise on adenosine-5'-triphosphate (ATP), adenosine-5'-diphosphate (ADP) and adenosine-5'-monophosphate (AMP) contents in erythrocytes of healthy males. Twenty one men aged 20-22 years were examined. They underwent physical exercise at doses of 2 w/kg body weight for 15 min. Erythrocytes were exposed to gamma radiation (500 Gy doses) from 60 Co source. The concentration of adenine nucleotides in erythrocytes was measured by the Boehringer Mannheim tests. The submaximum physical exercise was found to decrease ATP content and to increase ADP and AMP in erythrocytes. Gamma radiation at 500 Gy dose was found to decrease ATP concentration in erythrocytes both at rest and after submaximum exercise and to increase AD content. It was revealed that AMP content increased at rest and decreased after submaximum exercise in irradiated erythrocytes. (author). 20 refs, 1 tab

Thermophysical lesions caused by HZE particles

International Nuclear Information System (INIS)

Tobias, C.A.; Malachowski, M.; Nelson, A.; Philpott, D.E.

1980-01-01

This paper deals with a type of damage caused by heavy particles that may occur in subcellular structures. These lesions are called thermophysical radiation injury and are similar to damage produced in solids by HZE particles. This chapter summarizes some of the experimental evidence for the presence of these lesions in certain mammalian tissues including the retina, brain, cornea, lens of mice and seeds of corn. Of all tissues examined, only the cornea exhibited a type of lesion which would fulfill the criteria of thermophysical lesions

Humic acid-bonded silica as a novel sorbent for solid-phase extraction of benzo[a]pyrene in edible oils

International Nuclear Information System (INIS)

Luo Dan; Yu Qiongwei; Yin Hongrui; Feng Yuqi

2007-01-01

A novel solid-phase extraction (SPE) sorbent, humic acid-bonded silica (HAS), was prepared. Humic acids (HAs) were grafted onto silica matrices via an amide linkage between humyl chloride and the amido terminus of 3-aminopropyltrimethoxysilane (APTS)-silica gel. The resulting material was characterized by Fourier transform infrared spectrometer, elemental analysis, and nitrogen adsorption analysis. This sorbent exhibits an excellent adsorption capacity for some electron-abundant analytes owing to its peculiar structure. In this paper, we choose benzo[a]pyrene (BaP) in oil as a probe to validate the adsorption capacity of the material. Thus a fast, cheap and simple SPE method with humic acid-bonded silica cartridge for edible oil clean-up, followed by high-performance liquid chromatography (HPLC) with fluorescence detection was established. The effects of experimental variables, such as washing and elution solvents, and the amount of sorbents have been studied. The recoveries of BaP in edible oils spiked at 0.2-100 μg kg -1 were in the range of 78.8-102.7% with relative standard deviations ranging between 1.3 and 9.3%; the limit of detection was -0.06 μg kg -1

Molecular characterization of ABC transporters in marine ciliate, Euplotes crassus: Identification and response to cadmium and benzo[a]pyrene.

Science.gov (United States)

Kim, Hokyun; Yim, Bora; Kim, Jisoo; Kim, Haeyeon; Lee, Young-Mi

2017-11-30

ATP-binding cassette (ABC) transporters participate in transporting various substances, including xenobiotics, in or out of cells. However, their genetic information and function in ciliates remain still unclear. In this study, we sequenced and characterized two ABC transporter genes (EcABCB and EcABCC), and investigated the effect of cadmium (Cd) and benzo[a]pyrene (B[a]P) on their function and gene expression, using efflux assay and real-time reverse transcription-polymerase chain reaction (qRT-PCR), respectively, in the marine ciliate, Euplotes crassus. Sequencing analysis and efflux assay showed that EcABCB and EcABCC are typical ABC transporters, possessing conserved function. Exposure to Cd (≥5mg/L) and B[a]P (≥50.5μg/L) enhanced accumulation of a substrate. A significant increase in the expression of EcABCB and EcABC mRNA was observed at lower concentration in response to Cd and B[a]P. Our findings indicate that Cd and B[a]P could inhibit the efflux function of ABC transporters, leading to cellular toxicity in the ciliate. Copyright © 2017 Elsevier Ltd. All rights reserved.

DNA adenine methylation is required to replicate both Vibrio cholerae chromosomes once per cell cycle.

Science.gov (United States)

Demarre, Gaëlle; Chattoraj, Dhruba K

2010-05-06

DNA adenine methylation is widely used to control many DNA transactions, including replication. In Escherichia coli, methylation serves to silence newly synthesized (hemimethylated) sister origins. SeqA, a protein that binds to hemimethylated DNA, mediates the silencing, and this is necessary to restrict replication to once per cell cycle. The methylation, however, is not essential for replication initiation per se but appeared so when the origins (oriI and oriII) of the two Vibrio cholerae chromosomes were used to drive plasmid replication in E. coli. Here we show that, as in the case of E. coli, methylation is not essential for oriI when it drives chromosomal replication and is needed for once-per-cell-cycle replication in a SeqA-dependent fashion. We found that oriII also needs SeqA for once-per-cell-cycle replication and, additionally, full methylation for efficient initiator binding. The requirement for initiator binding might suffice to make methylation an essential function in V. cholerae. The structure of oriII suggests that it originated from a plasmid, but unlike plasmids, oriII makes use of methylation for once-per-cell-cycle replication, the norm for chromosomal but not plasmid replication.

Disseminated paracoccidioidomycosis diagnosis based on oral lesions

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Liana Preto Webber

2014-01-01

Full Text Available Paracoccidioidomycosis (PCM is a deep mycosis with primary lung manifestations that may present cutaneous and oral lesions. Oral lesions mimic other infectious diseases or even squamous cell carcinoma, clinically and microscopically. Sometimes, the dentist is the first to detect the disease, because lung lesions are asymptomatic, or even misdiagnosed. An unusual case of PCM with 5 months of evolution presenting pulmonary, oral, and cutaneous lesions that was diagnosed by the dentist based on oral lesions is presented and discussed.

Lesiones periapicales agudas en pacientes adultos Acute periapical lesions in adult patients

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María Elena Fernández Collazo

2012-06-01

Full Text Available Se realizó un estudio analítico de corte transversal en el área de salud del Policlínico "27 de Noviembre" del municipio Marianao, La Habana, en el periodo correspondiente de enero a diciembre de 2009. Se incluyeron todos los pacientes que acudieron al servicio de urgencia y que presentaron lesiones periapicales agudas. Se recogió información de las variables edad, sexo, grupo dentario, causa de la enfermedad, características clínicas e higiene bucal. Esta última se clasificó en las categorías eficiente y deficiente según el índice simplificado de higiene bucal. Se utilizó el X² para estimar la relación entre las variables, y la comparación de proporciones para contrastar la hipótesis de que existieran diferencias entre las lesiones periapicales para las categorías de las variables grupo dentario, causa de la enfermedad y características clínicas. Se encontró un predominio del absceso periapical agudo en un 84,7 % del grupo de edad de 35 a 59 años y del sexo masculino, aunque no se encontraron diferencias significativas para estas variables, ni en los grupos dentarios con respecto a la enfermedad. La higiene bucal resultó estar relacionada con las lesiones periapicales. Se encontraron diferencias significativas en las lesiones periapicales respecto a todas las causas estudiadas, con excepción de las enfermedades periodontales. Respecto a las características clínicas hubo significación en cuanto al aumento de volumen del fondo del surco vestibular y la movilidad dentaria.A cross-sectional and analytical study was conducted in the health area of the "27 de Noviembre" of Marianao municipality, La Habana, from January to December, 2009 including all patients came to emergency service presenting with acute periapical lesions. Information on following variables was available: age, sex, dental group, cause of disease, clinical features and oral hygiene. This latter was classified in the efficient and deficient categories

Overexpression of Catalase Enhances Benzo(a)pyrene Detoxification in Endothelial Microsomes.

Science.gov (United States)

Yang, Fang; Yang, Hong; Ramesh, Aramandla; Goodwin, J Shawn; Okoro, Emmanuel U; Guo, ZhongMao

2016-01-01

We previously reported that overexpression of catalase upregulated xenobiotic- metabolizing enzyme (XME) expression and diminished benzo(a)pyrene (BaP) intermediate accumulation in mouse aortic endothelial cells (MAECs). Endoplasmic reticulum (ER) is the most active organelle involved in BaP metabolism. To examine the involvement of ER in catalase-induced BaP detoxification, we compared the level and distribution of XMEs, and the profile of BaP intermediates in the microsomes of wild-type and catalase transgenic endothelial cells. Our data showed that endothelial microsomes were enriched in cytochrome P450 (CYP) 1A1, CYP1B1 and epoxide hydrolase 1 (EH1), and contained considerable levels of quinone oxidoreductase-1 (NQO1) and glutathione S-transferase-pi (GSTP). Treatment of wild-type MAECs with 1μM BaP for 2 h increased the expression of microsomal CYP1A1, 1B1 and NQO1 by ~300, 64 and 116%, respectively. However, the same treatment did not significantly alter the expression of EH1 and GSTP. Overexpression of catalase did not significantly increase EH1, but upregulated BaP-induced expression of microsomal CYP1A1, 1B1, NQO1 and GSTP in the following order: 1A1>NQO1>GSTP>1B1. Overexpression of catalase did not alter the distribution of each of these enzymes in the microsomes. In contrast to our previous report showing lower level of BaP phenols versus BaP diols/diones in the whole-cell, this report demonstrated that the sum of microsomal BaP phenolic metabolites were ~60% greater than that of the BaP diols/diones after exposure of microsomes to BaP. Overexpression of catalase reduced the concentrations of microsomal BaP phenols and diols/diones by ~45 and 95%, respectively. This process enhanced the ratio of BaP phenol versus diol/dione metabolites in a potent manner. Taken together, upregulation of phase II XMEs and CYP1 proteins, but not EH1 in the ER might be the mechanism by which overexpression of catalase reduces the levels of all the BaP metabolites, and

Compartmental analysis of the disposition of benzo[a]pyrene in rats.

Science.gov (United States)

Bevan, D R; Weyand, E H

1988-11-01

We have previously reported the disposition of benzo[a]pyrene (B[a]P) and its metabolites in male Sprague-Dawley rats following intratracheal instillation of [3H]B[a]P [Weyand, E.H. and Bevan, D.R. (1986) Cancer Res., 46, 5655-5661]. In some experiments, cannulas were implanted in the bile duct of the animals prior to administration of [3H]B[a]P [Weyand, E.H. and Bevan, D.R. (1987) Drug Metab. Disposition, 15, 442-448]. Based on these data, we have developed a compartmental model of the distribution of radioactivity to provide a quantitative description of the fate of B[a]P and its metabolites in rats. Modeling of the distribution of radioactivity was performed using the Simulation, Analysis and Modeling (SAAM) and conversational SAAM (CONSAM) computer programs. Compartments in the model included organs into which the largest amounts of radioactivity were distributed as well as pathways for excretion of radioactivity from the animals. Data from animals with and without cannulas implanted in the bile duct were considered simultaneously during modeling. Radioactivity was so rapidly absorbed from the lungs that an absorption phase into blood was not apparent at the earliest sampling times. Using the model of extrapolate to shorter times, it was predicted that the maximum amount of radioactivity was present in blood within 2 min after administration. In addition, considerable recycling of radioactivity back to lungs from blood was predicted by the model. Transfer of radioactivity from blood to liver and carcass (skin, muscle, bones, fat and associated blood) also was extensive. Carcass was modeled as the sum of two compartments to obtain agreement between the model and experimental data. The model accounted for enterohepatic circulation of B[a]P metabolites; data also required that intestinal secretion be included in the model. Quantitative data obtained from compartmental analysis included rate constants for transfer of radioactivity among compartments as well as

Temporal evolution of ischemic lesions in nonhuman primates: a diffusion and perfusion MRI study.

Directory of Open Access Journals (Sweden)

Xiaodong Zhang

Full Text Available Diffusion-weighted imaging (DWI and perfusion MRI were used to examine the spatiotemporal evolution of stroke lesions in adult macaques with ischemic occlusion.Permanent MCA occlusion was induced with silk sutures through an interventional approach via the femoral artery in adult rhesus monkeys (n = 8, 10-21 years old. The stroke lesions were examined with high-resolution DWI and perfusion MRI, and T2-weighted imaging (T2W on a clinical 3T scanner at 1-6, 48, and 96 hours post occlusion and validated with H&E staining.The stroke infarct evolved via a natural logarithmic pattern with the mean infarct growth rate = 1.38 ± 1.32 ml per logarithmic time scale (hours (n = 7 in the hyperacute phase (1-6 hours. The mean infarct volume after 6 hours post occlusion was 3.6±2.8 ml (n = 7, by DWI and increased to 3.9±2.9 ml (n = 5, by T2W after 48 hours, and to 4.7±2.2ml (n = 3, by T2W after 96 hours post occlusion. The infarct volumes predicted by the natural logarithmic function were correlated significantly with the T2W-derived lesion volumes (n = 5, r = 0.92, p = 0.01 at 48 hours post occlusion. The final infarct volumes derived from T2W were correlated significantly with those from H&E staining (r = 0.999, p < 0.0001, n = 4. In addition, the diffusion-perfusion mismatch was visible generally at 6 hours but nearly diminished at 48 hours post occlusion.The infarct evolution follows a natural logarithmic pattern in the hyperacute phase of stroke. The logarithmic pattern of evolution could last up to 48 hours after stroke onset and may be used to predict the infarct volume growth during the acute phase of ischemic stroke. The nonhuman primate model, MRI protocols, and post data processing strategy may provide an excellent platform for characterizing the evolution of acute stroke lesion in mechanistic studies and therapeutic interventions of stroke disease.

Benign clavicular lesions that may mimic malignancy

International Nuclear Information System (INIS)

Gerscovich, E.G.; Greenspan, A.; Szabo, R.M.

1991-01-01

Nontraumatic lesions of the clavicle are infrequent. Of these, malignant tumors are more common than benign lesions. From January 1988 to January 1990, we examined 17 patients with benign lesions of the clavicle; in 8, the morphologic appearance of the lesion raised the possibility of malignancy in the differential diagnosis. The radiologic findings in these patients are presented. We propose that the unique shape and embryologic development of the clavicle may contribute to the atypical, aggressive presentation of some benign lesions in that bone. (orig.)

Topical photosan-mediated photodynamic therapy for DMBA-induced hamster buccal pouch early cancer lesions: an in vivo study

Science.gov (United States)

Hsu, Yih-Chih; Chang, Walter Hong-Shong; Chang, Junn-Liang; Liu, Kuang-Ting; Chiang, Chun-Pin; Liu, Chung-Ji; Chen, Chih-Ping

2011-03-01

Oral cancer has becomes the most prominent cancer disease in recent years in Taiwan. The reason is the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people results in oral cancer becomes the fastest growth incident cancer amongst other major cancer diseases. In previous studies showed that photosan, haematoporphyrin derivative (HPD), has demonstrated effective PDT results on human head and neck disease studies. To avoid the systemic phototoxic effect of photosan, this study was designed to use a topical photosan-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical photosan-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when photosan reached its peak level in the lesional epithelial cells after topical application of photosan gel. We found that photosan reached its peak level in cancerous lesions about 13.5 min after topical application of photosan gel. The cancerous lesions in hamsters were then treated with topical photosan-mediated PDT (fluence rate: 600 mW/cm2; light exposure dose 200 J/cm2) using the portable Lumacare 635 nm fiber-guided light device. Visual examination demonstrated that topical photosan-mediated PDT was an applicable treatment modality for DMBA-induced hamster buccal pouch cancerous lesions.

The radiology in the solitary bone lesions

International Nuclear Information System (INIS)

Veloso, G.A.; Cardoso, V.M.

1985-01-01

Three methods of radiologic analysis of the solitary bone lesions are reviewed. 1. Radiological analysis of the lesions with the objective to suppose the histologic type; 2. To appreciate the velocity of growth and aggressiveness of the lesions. 3. To appreciate the biological behaviour of the bone lesions, making the diagnosis necessary for the treatment. (M.A.C.) [pt

Peripheral Exophytic Oral Lesions: A Clinical Decision Tree

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Hamed Mortazavi

2017-01-01

Full Text Available Diagnosis of peripheral oral exophytic lesions might be quite challenging. This review article aimed to introduce a decision tree for oral exophytic lesions according to their clinical features. General search engines and specialized databases including PubMed, PubMed Central, Medline Plus, EBSCO, Science Direct, Scopus, Embase, and authenticated textbooks were used to find relevant topics by means of keywords such as “oral soft tissue lesion,” “oral tumor like lesion,” “oral mucosal enlargement,” and “oral exophytic lesion.” Related English-language articles published since 1988 to 2016 in both medical and dental journals were appraised. Upon compilation of data, peripheral oral exophytic lesions were categorized into two major groups according to their surface texture: smooth (mesenchymal or nonsquamous epithelium-originated and rough (squamous epithelium-originated. Lesions with smooth surface were also categorized into three subgroups according to their general frequency: reactive hyperplastic lesions/inflammatory hyperplasia, salivary gland lesions (nonneoplastic and neoplastic, and mesenchymal lesions (benign and malignant neoplasms. In addition, lesions with rough surface were summarized in six more common lesions. In total, 29 entities were organized in the form of a decision tree in order to help clinicians establish a logical diagnosis by a stepwise progression method.

Correlation of needle core biopsy with excision histology in screen-detected B3 lesions: the Merrion Breast Screening Unit experience.

LENUS (Irish Health Repository)

Hayes, B D

2012-02-01

AIMS: Needle core biopsy (NCB) is a widely-used technique for non-operative evaluation of screen-detected breast lesions. Although most NCBs are B2 (benign) or B5 (malignant), some fall into the B3 category of "uncertain malignant potential". This study aims to categorise the lesions prompting a B3 NCB in the Merrion Breast Screening Unit, and establish the incidence of malignancy on subsequent excision biopsy. METHODS: Patients attending the Merrion Breast Screening Unit in Dublin between 2000 and 2008 who had a B3 NCB were identified. The NCB pathology reports were reviewed and the diagnosis correlated with excision histology; the latter was classified as benign, atypical or malignant. Lesion-specific positive predictive values (PPVs) for malignancy were derived. RESULTS: 141 patients with a B3 NCB were identified. The most frequent lesions on NCB were radial scar (RS; n = 57), atypical intraductal epithelial proliferation (AIDEP; n = 25) and papillary lesion (n = 24). The final diagnosis was malignant in 22 patients (16%), atypical in 40 (28%) and benign in 79 (56%). Two of the patients with a malignant diagnosis had invasive carcinoma. The lesion-specific PPVs were: lobular neoplasia 50%, AIDEP 32%, columnar cell lesion with atypia 12.5%, RS 12.3%, papillary lesion 8.3%, suspected phyllodes tumour 7.7%, and spindle cell lesion 0%. Atypia on RS NCB predicted an atypical or malignant excision diagnosis, but atypia on papillary lesion NCB did not. CONCLUSIONS: One-sixth of B3 NCBs in this series proved to be malignant on excision. The PPV for malignancy varied according to lesion type.

Theoretical Analysis of Penalized Maximum-Likelihood Patlak Parametric Image Reconstruction in Dynamic PET for Lesion Detection.

Science.gov (United States)

Yang, Li; Wang, Guobao; Qi, Jinyi

2016-04-01

Detecting cancerous lesions is a major clinical application of emission tomography. In a previous work, we studied penalized maximum-likelihood (PML) image reconstruction for lesion detection in static PET. Here we extend our theoretical analysis of static PET reconstruction to dynamic PET. We study both the conventional indirect reconstruction and direct reconstruction for Patlak parametric image estimation. In indirect reconstruction, Patlak parametric images are generated by first reconstructing a sequence of dynamic PET images, and then performing Patlak analysis on the time activity curves (TACs) pixel-by-pixel. In direct reconstruction, Patlak parametric images are estimated directly from raw sinogram data by incorporating the Patlak model into the image reconstruction procedure. PML reconstruction is used in both the indirect and direct reconstruction methods. We use a channelized Hotelling observer (CHO) to assess lesion detectability in Patlak parametric images. Simplified expressions for evaluating the lesion detectability have been derived and applied to the selection of the regularization parameter value to maximize detection performance. The proposed method is validated using computer-based Monte Carlo simulations. Good agreements between the theoretical predictions and the Monte Carlo results are observed. Both theoretical predictions and Monte Carlo simulation results show the benefit of the indirect and direct methods under optimized regularization parameters in dynamic PET reconstruction for lesion detection, when compared with the conventional static PET reconstruction.

Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) blocks differentiation and maintains the expression of pluripotency markers in human embryonic stem cells.

Science.gov (United States)

Burton, Peter; Adams, David R; Abraham, Achamma; Allcock, Robert W; Jiang, Zhong; McCahill, Angela; Gilmour, Jane; McAbney, John; Kaupisch, Alexandra; Kane, Nicole M; Baillie, George S; Baker, Andrew H; Milligan, Graeme; Houslay, Miles D; Mountford, Joanne C

2010-12-15

hESCs (human embryonic stem cells) have enormous potential for use in pharmaceutical development and therapeutics; however, to realize this potential, there is a requirement for simple and reproducible cell culture methods that provide adequate numbers of cells of suitable quality. We have discovered a novel way of blocking the spontaneous differentiation of hESCs in the absence of exogenous cytokines by supplementing feeder-free conditions with EHNA [erythro-9-(2-hydroxy-3-nonyl)adenine], an established inhibitor of ADA (adenosine deaminase) and cyclic nucleotide PDE2 (phosphodiesterase 2). hESCs maintained in feeder-free conditions with EHNA for more than ten passages showed no reduction in hESC-associated markers including NANOG, POU5F1 (POU domain class 5 transcription factor 1, also known as Oct-4) and SSEA4 (stage-specific embryonic antigen 4) compared with cells maintained in feeder-free conditions containing bFGF (basic fibroblast growth factor). Spontaneous differentiation was reversibly suppressed by the addition of EHNA, but, upon removing EHNA, hESC populations underwent efficient spontaneous, multi-lineage and directed differentiation. EHNA also acts as a strong blocker of directed neuronal differentiation. Chemically distinct inhibitors of ADA and PDE2 lacked the capacity of EHNA to suppress hESC differentiation, suggesting that the effect is not driven by inhibition of either ADA or PDE2. Preliminary structure-activity relationship analysis found the differentiation-blocking properties of EHNA to reside in a pharmacophore comprising a close adenine mimetic with an extended hydrophobic substituent in the 8- or 9-position. We conclude that EHNA and simple 9-alkyladenines can block directed neuronal and spontaneous differentiation in the absence of exogenous cytokine addition, and may provide a useful replacement for bFGF in large-scale or cGMP-compliant processes.

Effects of benzo(a)pyrene on the skeletal development of Sebastiscus marmoratus embryos and the molecular mechanism involved

International Nuclear Information System (INIS)

He Chengyong; Zuo Zhenghong; Shi Xiao; Li Ruixia; Chen Donglei; Huang Xin; Chen Yixin; Wang Chonggang

2011-01-01

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, which have been known to be carcinogenic and teratogenic. However, the skeletal development toxicity of PAHs and the mechanism involved remain unclear. In fishes, the neurocranial and craniofacial skeleton develop as cartilage. The signaling molecules of hedgehog (Hh) family play crucial roles in regulating skeletal development. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to benzo(a)pyrene (BaP) for 7 days at environmental levels (0.05, 0.5 and 5 nmol/L) which resulted in craniofacial skeleton deformities. BaP exposure reduced the cell proliferation activity in the craniofacial skeleton as detected by quantitative PCR and in situ hybridization. The expression of Sonic hedgehog (Shh), rather than Indian hedgehog (Ihh), was down-regulated in the craniofacial skeleton in the 0.5 and 5 nmol/L groups. Consistent with the Shh results, the expression of Ptch1 and Gli2 was decreased by BaP exposure and BMP4 was presented on changes in the 0.5 and 5 nmol/L groups. These results suggested that BaP could impair the expression and function of Shh signaling pathway, perturbing the proliferation of chondrocytes and so disturbing craniofacial skeletal development.

Effects of benzo(a)pyrene on the skeletal development of Sebastiscus marmoratus embryos and the molecular mechanism involved

Energy Technology Data Exchange (ETDEWEB)

He Chengyong [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); Zuo Zhenghong [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China); Shi Xiao; Li Ruixia; Chen Donglei; Huang Xin; Chen Yixin [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); Wang Chonggang, E-mail: cgwang@xmu.edu.cn [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China)

2011-01-25

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, which have been known to be carcinogenic and teratogenic. However, the skeletal development toxicity of PAHs and the mechanism involved remain unclear. In fishes, the neurocranial and craniofacial skeleton develop as cartilage. The signaling molecules of hedgehog (Hh) family play crucial roles in regulating skeletal development. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to benzo(a)pyrene (BaP) for 7 days at environmental levels (0.05, 0.5 and 5 nmol/L) which resulted in craniofacial skeleton deformities. BaP exposure reduced the cell proliferation activity in the craniofacial skeleton as detected by quantitative PCR and in situ hybridization. The expression of Sonic hedgehog (Shh), rather than Indian hedgehog (Ihh), was down-regulated in the craniofacial skeleton in the 0.5 and 5 nmol/L groups. Consistent with the Shh results, the expression of Ptch1 and Gli2 was decreased by BaP exposure and BMP4 was presented on changes in the 0.5 and 5 nmol/L groups. These results suggested that BaP could impair the expression and function of Shh signaling pathway, perturbing the proliferation of chondrocytes and so disturbing craniofacial skeletal development.

[Bile duct lesions in laparoscopic cholecystectomy].

Science.gov (United States)

Siewert, J R; Ungeheuer, A; Feussner, H

1994-09-01

Laparoscopic cholecystectomy is both resulting in a slightly higher incidence of biliary lesions and a change of prevalence of the type of lesions. Damage to the biliary system occurs in 4 different types: The most severe case is the lesion with a structural defect of the hepatic or common bile duct with (IVa) or without (IVb) vascular injury. Tangential lesions without structural loss of the duct should be denominated as type III (IIIa with additional lesion to the vessels, type IIIb without). Type II comprehends late strictures without obvious intraoperative trauma to the duct. Type I includes immediate biliary fistulae of usually good prognosis. The increasing prevalence of structural defects of the bile ducts appears to be a peculiarity of laparoscopic cholecystectomy necessitating highly demanding operative repair. In the majority of cases, hepatico-jejunostomy or even intraparenchymatous anastomoses are required. Adaptation of well proven principles of open surgery is the best prevention of biliary lesions in laparoscopic cholecystectomy as well as the readiness to convert early to the open procedure.

Contrast-enhanced magnetic resonance imaging of pulmonary lesions: Description of a technique aiming clinical practice

International Nuclear Information System (INIS)

Koenigkam-Santos, Marcel; Optazaite, Elzbieta; Sommer, Gregor; Safi, Seyer; Heussel, Claus Peter; Kauczor, Hans-Ulrich

2015-01-01

To propose a technique for evaluation of pulmonary lesions using contrast-enhanced MRI; to assess morphological patterns of enhancement and correlate quantitative analysis with histopathology. Material and methods: Thirty-six patients were prospectively studied. Volumetric-interpolated T1W images were obtained during consecutive breath holds after bolus triggered contrast injection. Volume coverage of first three acquisitions was limited (higher temporal resolution) and last acquisition obtained at 4th min. Two radiologists individually evaluated the patterns of enhancement. Region-of-interest-based signal intensity (SI)-time curves were created to assess quantitative parameters. Results: Readers agreed moderately to substantially concerning lesions’ enhancement pattern. SI-time curves could be created for all lesions. In comparison to benign, malignant lesions showed higher values of maximum enhancement, early peak, slope and 4th min enhancement. Early peak >15% showed 100% sensitivity to detect malignancy, maximum enhancement >40% showed 100% specificity. Conclusions: The proposed technique is robust, simple to perform and can be applied in clinical scenario. It allows visual evaluation of enhancement pattern/progression together with creation of SI-time curves and assessment of derived quantitative parameters. Perfusion analysis was highly sensitive to detect malignancy, in accordance to what is recommended by most recent guidelines on imaging evaluation of pulmonary lesions

Mucocele-like lesions of the breast: a clinical outcome and histologic analysis of 102 cases.

Science.gov (United States)

Meares, Annie L; Frank, Ryan D; Degnim, Amy C; Vierkant, Robert A; Frost, Marlene H; Hartmann, Lynn C; Winham, Stacey J; Visscher, Daniel W