WorldWideScience
 
 
1

ras gene alterations in invasive and non-invasive rat bladder carcinomas induced by N-methyl-N-nitrosourea.  

UK PubMed Central (United Kingdom)

We have established a reliable method to induce invasive and non-invasive carcinomas in the heterotopically transplanted urinary bladder of rats by repeated injection of N-methyl-N-nitrosourea (MNU),...Full Text Available

1991-07-01

2

Induction of bladder cancer in rats by fractionated intravesicular doses of N-methyl-N-nitrosourea.  

UK PubMed Central (United Kingdom)

Experiments were conducted to determine the dose response of rat bladder urothelium to a range of different single and fractionated intravesicular doses of the carcinogen, N-methyl-N-nitrosourea (MNU)....Full Text Available

1982-03-01

3

Interaction of N-methyl-2-alkenyl-4-quinolones with ATP-dependent MurE ligase of Mycobacterium tuberculosis: antibacterial activity, molecular docking and inhibition kinetics  

UK PubMed Central (United Kingdom)

ObjectivesThe aim of this study was to comprehensively evaluate the antibacterial activity and MurE inhibition of a set of N-methyl-2-alkenyl-4-quinolones found...Full Text Available

2011-08-01

4

Stable Isotope-Coded Quaternization for Comparative Quantification of Estrogen Metabolites by High-Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry  

UK PubMed Central (United Kingdom)

A fast and sensitive LC-ESI-MS method is described for the comparative quantification of 16 estrogen metabolites based on the derivatization of estrogens with a novel derivatizing reagent, N-methyl-nicotinic...Full Text Available

2008-07-15

5

Influence of murine leukemia proviral integrations on development of N-methyl-N-nitrosourea-induced thymic lymphomas in AKR mice.  

UK PubMed Central (United Kingdom)

The AKR mouse strain is characterized by a high incidence of spontaneous thymic lymphoma that appears in older animals (greater than 6 months of age) and is associated with novel provirus integrations...Full Text Available

1991-11-01

6

Dynamin-dependent NMDAR endocytosis during LTD and its dependence on synaptic state  

UK PubMed Central (United Kingdom)

BackgroundThe N-methyl-D-aspartate (NMDA)-type glutamate receptor expressed at excitatory glutamatergic synapses is required for learning and memory and is critical for normal brain...Full Text Available

7

Relationship between O6-alkylguanine-DNA alkyltransferase activity and N-methyl-N'-nitro-N-nitrosoguanidine-induced mutation, transformation, and cytotoxicity in C3H/10T1/2 cells expressing exogenous alkyltransferase genes.  

UK PubMed Central (United Kingdom)

While a great deal of evidence has directly implicated the importance of O6-alkylation of guanine in the mutagenicity of alkylating agents, evidence demonstrating the oncogenic potential of this lesion...Full Text Available

1992-12-01

8

Analysis of forward mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine in the bacteriophage P22 mnt repressor gene  

Energy Technology Data Exchange (ETDEWEB)

We describe the isolation and genetic characterization of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced mutations in the phage P22 mnt repressor gene cloned in plasmid pBR322. Mutations in the mnt repressor gene or its operator on this plasmid, pPY98, confer a tetracycline resistance phenotype, whereas the wild-type plasmid confers tetracycline sensitivity. Cells carrying pPY98 were briefly exposed to MNNG to give 20 to 40% survival and a 50- to 100-fold increase in tetracycline-resistant cells. DNA sequence analysis showed that 29 to 30 MNNG-induced mutations were GC-to-AT transitions and one was an AT-to-GC transition. About 80% of the mutations are in three hotspots. This mutation spectrum is consistent with the proposed mechanism of mutagenic action of MNNG, which involves mispairing of an alkylated base, O/sup 6/-methylguanine. The mnt gene may be a useful target for determining mutagenic specificity at the nucleotide level because (i) forward ...

1986-04-01

9

Targeting the kynurenine pathway as a potential strategy to prevent and treat Alzheimer's disease  

British Library Electronic Table of Contents (United Kingdom)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly accounting for the vast majority of dementia. Recently, many studies have implicated the role of inflammatory response, especially neuroinflammatory response in the development and progression of AD. However, the underlying mechanism of how inflammatory response induces AD is unknown. Kynurenine pathway is a major route of the amino acid tryptophan catabolism, resulting in the production of nicotine adenine dinucleotide and other neuroactive intermediates: quinolinic acid (QA) and kynurenic acid (KA). QA exerts different toxic effects, including over-activation of N-methyl-d-aspartate (NMDA) receptor and excitotoxicity, synaptic dysfunction and neuronal death. On the other hand, KA is identified as the only...

2011-01-01

10

Polymeric nanosponges as an alternative carrier for improved retention of econazole nitrate onto the skin through topical hydrogel formulation  

British Library Electronic Table of Contents (United Kingdom)

The present study was carried out to exploit the feasibility of using polymeric nanosponges as an alternative carrier for targeting econazole nitrate (EN) to the skin through topical hydrogel formulation. Nanosponges prepared by emulsion solvent diffusion method were evaluated for various physicochemical parameters and in vitro drug release. The nanosponges of EN were discrete free flowing nanosized particles with perforated orange peel like morphology as visualized by SEM. The nanosponge formulated using PVA:EC (3:2) displayed highest in vitro release after 12 ?h in phosphate buffer (pH 6.8) that fitted matrix model. Selected nanosponge was formulated as Carbopol 934 NF hydrogel using varying concentrations of permeation enhancers propylene glycol and N-methyl-2-pyrrolidone. The EN nanosp...

2011-01-01

11

Imaging hypoxia in vivo by controlling the electrochemistry of copper radionuclide complexes  

British Library Electronic Table of Contents (United Kingdom)

Tissue hypoxia is a feature of cancer, heart disease and stroke, and imaging it may become clinically important. Copper-ATSM (ATSMH2 = 2,3-butanedione bis(N-methyl)thiosemicarb-azone), labelled with 60Cu, 62Cu or 64Cu, is selectively taken up in hypoxic cells in vitro and in vivo by a bioreductive mechanism, and is a prototype hypoxia imaging agent amenable to improvement. In vitro studies with several differently alkylated analogues of CuATSM show that hypoxia selectivity is a general property of complexes with two alkyl groups at the diketone backbone, offering a range of pharmacokinetic properties while retaining hypoxia selectivity. This pharmacokinetic control affords a route to development of second-generation hypoxia imaging agents with optimized properties for different clinical ap...

2007-01-01

12

Facilitated Proton Transfer by a Novel 2-Aminothiazole Derivative Across the Water/1,2-Dichloroethane Interface  

British Library Electronic Table of Contents (United Kingdom)

The behavior of proton transfer facilitated by a novel thiazole derivative, N-methyl-4-(4-phenoxyphenyl)thiazol-2-amine (MPPT), across the water/1,2-dichloroethane (1,2-DCE) interface was investigated electrochemically. The ionic partition diagram for MPPT was obtained from interpretation of the cyclic voltammograms. The apparent partition coefficient of MPPT was evaluated by the shaking-flask method under experimental conditions, while that for the protonated form of MPPT was calculated from its transfer potential obtained from the ionic partition diagram. It was suggested that the mechanism for transfer of MPPT across the water/1,2-DCE) interface depends on the pH of the aqueous phase. The parameters of the facilitated proton transfer across the water/1,2-DCE interface were evaluated as ...

2011-01-01

13

Synthesis and PET imaging of the benzodiazepine receptor tracer [N-methyl-"1"1C]iomazenil  

International Nuclear Information System (INIS)

The central benzodiazepine receptor tracer [N-methyl-"1"1C]iomazenil (Ro 16-0154) was synthesized by alkylation of the desmethyl precursor noriomazenil with ["1"1C]methyl iodide. The ["1"1C]CH_3I (prepared by reduction of ["1"1C]CO_2 with LiAlH_4 followed by reaction with HI) was reacted with noriomazenil inN,N -dimethylformamide and Bu_4N"+OH"- for 1 min at 80 deg. C and purified by HPLC (C_1_8, 34% CH_3CN/H_2O, 7 mL/min). The product was obtained with synthesis time 35 #+-# 5 min (mean #+-# SD, n = 7), radiochemical yield (EOB) 36 #+-# 16%, radiochemical purity 99 #+-# 1%, and specific activity 5100 #+-# 2800 mCi/#mu#mol. Absorbed radiation doses were calculated from previously acquired human biodistribution data. The urinary bladder wall received the highest dose (0.099 mGy/MBq) for 4.8 h voiding interval and the effective dose equivalent was 0.015 mSv/MBq. After i.v. injection of ["1"1C]iomazenil in an adult baboon or healthy human volunteer, radioactivity ...

1995-07-01

14

Viscoelasticity of various gel films prepared from solvent-soluble constituents in coal; Sekitanchu no yobai kayoseibun kara sakuseishita shushu no gel maku no nendansei  

Energy Technology Data Exchange (ETDEWEB)

Viscoelasticity of gel films prepared from solvent-soluble constituents without ash of coal using the mixed solvent of carbon disulfide and N-methyl-2-pyrrolidinone (CS2-NMP) was measured to study the network structure of the constituents. In experiment, Upper Freeport coal and Zao Zhuang coal were used as specimens. Viscoelasticity of various gels with different weight fractions of solvent was measured by creep measurement under a fixed load and stress-strain analysis under variable loads. In the 2nd and 3rd creep measurements, although no large changes in elastic strain and viscoelastic strain were found, viscous strain gradually decreased with an increase in viscosity. In the case of small weight fraction of solvent, small viscous strain and viscoelastic strain were found, while slightly large elastic strain was found. It was thus suggested that this elastic strain is derived from not only physical cross-linked networks by coal-solvent interaction but also those ...

1996-10-28

15

Synthesis, structural activity-relationships, and biological evaluation of novel amide-based allosteric binding site antagonists in NR1A/NR2B N-methyl-d-aspartate receptors  

British Library Electronic Table of Contents (United Kingdom)

The synthesis and structure-activity relationship analysis of a novel class of amide-based biaryl NR2B-selective NMDA receptor antagonists are presented. Some of the studied compounds are potent, selective, non-competitive, and voltage-independent antagonists of NR2B-containing NMDA receptors. Like the founding member of this class of antagonists (ifenprodil), several interesting compounds of the series bind to the amino terminal domain of the NR2B subunit to inhibit function. Analogue potency is modulated by linker length, flexibility, and hydrogen bonding opportunities. However, unlike previously described classes of NR2B-selective NMDA antagonists that exhibit off-target activity at a variety of monoamine receptors, the compounds described herein show much diminished effects against the...

2009-01-01

16

Surface tension of a coal extract in an organic solvent; Sekitan chushutsu seibun no kaigo to hyomen choryoku  

Energy Technology Data Exchange (ETDEWEB)

The behavior and properties of associated bodies were studied through measurement of surface tension considering acetone-soluble fraction relatively light among various solvent extracts of coal. In experiment, the acetone-soluble fraction was extracted from the substances extracted from Upper Freeport coal as standard specimen using the mixed solvent of carbon disulfide (CS2) and N-methyl-2-pyrrolidinone (NMP), and it was dissolved into NMP after drying. Surface tension was measured by Wilhelmy method. The experimental results are as follows. Equilibrium surface tension is equal to the surface tension of pure solvent in a low concentration range of solution, and decreases with an increase in concentration approaching a fixed value at 0 in log concentration, nearly showing an S curve. Adsorption of species with non-polar aromatic ring of the acetone-soluble fraction on a solution surface probably decreases surface tension. Change with time in surface tension is ...

1996-10-28

17

Nitroimidazole conjugates of bis(thiosemicarbazonato)64Cu(II) - Potential combination agents for the PET imaging of hypoxia  

British Library Electronic Table of Contents (United Kingdom)

Combination agents comprising two different pharmacophores with the same biological target have the potential to show additive or synergistic activity. Bis(thiosemicarbazonato)copper(II) complexes (e.g. 64Cu-ATSM) and nitroimidazoles (e.g. 18F-MISO) are classes of tracer used for the delineation of tumor hypoxia by positron emission tomography (PET). Three nitroimidazole-bis(thiosemicarbazonato)copper(II) conjugates were produced in order to investigate their potential as combination hypoxia imaging agents. Two were derived from the known bifunctional bis(thiosemicarbazone) H2ATSM/A and the third from the new precursor diacetyl-2-(4-N-methyl-3-thiosemicarbazone)-3-(4-N-ethylamino-3-thiosem icarbazone) - H2ATSM/en. Oxygen-dependent uptake studies were performed using the 64Cu radiolabelled ...

2010-01-01

18

Enhancement of N-nitrosamine formation on granular-activated carbon from N-methylaniline and nitrite  

Energy Technology Data Exchange (ETDEWEB)

Sterile aqueous N-methylaniline solutions were allowed to equilibrate at various nitrite, F-400 granular-activated carbon, and pH levels for 1 week. The aqueous and activated carbon phases were extracted and analyzed for nitrosamines relative to an added internal standard. Selected ion monitoring GC/MS, utilizing continuous monitoring of the NO/sup +/ ion (m/z 29.9980) characteristic of nitrosamines, at medium resolution (R = 2500-3000) was applied to quantitatively measure nitrosamines at picograms per microliter concentrations. This method selected for nitrosamine products only and eliminated interferences from non-nitrosamine reaction products. Results indicate that the pressure of granular-activated carbon significantly enhanced the formation of nitrosamine from N-methyl-aniline (F = 145, P< 0.0001). The amount of N-nitrosomethylaniline formed in the presence of activated carbon was 75 times more than that formed in the absence of activated carbon under the ...

1986-10-01

19

6-Methyl-1,2,4-benzenetriol, a new intermediate in penicillic acid biosynthesis in Penicillium cyclopium  

International Nuclear Information System (INIS)

Penicillic acid-negative mutants were obtained from a color mutant derived from Penicillium cyclopium NRRL 1888 through N-methyl-N'-nitro-N-nitrosoguanidine treatment. One mutant (SK2N6) accumulated 6-methyl-1,2,4-benzenetriol, which was not previously known to be a metabolite of P. cyclopium, in addition to orsellinic acid and orcinol. The radioactivity of [1-"1"4C]acetic acid was rapidly incorporated into 6-methyl-1,2,4-benzenetriol in a culture of P. cyclopium SK2N6. Moreover, the radioactivity of ["1"4C]6-methyl-1,2,4-benzenetriol was efficiently incorporated into penicillic acid in a culture of P. cyclopium NRRL 1888. These data indicate that 6-methyl-1,2,4-benzenetriol is a precursor for penicillic acid biosynthesis. The results on the addition of 1,4-dihydroxy-6-methoxy-2-methylbenzene, 6-methoxy-2-methylbenzoquinone (1,4), and 1-O-methylorcinol to a culture of P. cyclopium SK2N6 indicated that only the former two compounds are converted to penicillic acid. ...

20

Involvement of a glutamergic mechanism in gamma-dendrotoxin-induced hippocampal neuronal cell loss in the rat.  

Science.gov (United States)

The epileptogenic and neurodegenerative effects of gamma-dendrotoxin, from Dendroaspis angusticeps, a specific blocker of a non-inactivating, voltage-sensitive K+ channel, were studied after focal injection into one dorsal hippocampus in rats pretreated with CGP040116, a N-methyl-D-aspartate (NMDA) receptor antagonist, and in rats bearing a monolateral surgical lesion of the Schaffer collaterals whose terminals originate from CA3 pyramids and release glutamate in the CA1 hippocampal area. Administration of 35 pmol gamma-dendrotoxin elicited in all of the treated animals (n=8) bilateral EEG discharges and damage to the hippocampal formation. Quantitation of the damage revealed significant bilateral neuronal cell loss in the CA1, CA3 and CA4 pyramidal cell layers. The lowest dose (0.35 pmol; n=4) of the toxin used did not affect EEG activity and failed to cause significant hippocampal cell loss whereas the 3.5 pmol (n=6) dose caused EEG seizures and hippocampal cell ...

2004-03-01

 
 
 
 
21

Developments of PET radioligands for NMDA receptors  

International Nuclear Information System (INIS)

Aim: There has been a great demand for developments of the radioligands to visualize the N-methyl-D-aspartate (NMDA) receptors by PET/SPECT. We have recently synthesized two C-11 labeled antagonists for the glycine-binding site on NMDA receptors. The aim of this work is to examine for their in vitro and in vivo binding characteristics, and to evaluate their potentials as PET radioligands for the NMDA receptors. Materials and methods: Two C-11 labeled 4-hydroxy-2-quinolones (1 and 2) were synthesized by conventional methylation of the corresponding phenols with ["1"1C]methyl iodide. In vitro and ex vivo quantitative autoradiographs with imaging plate, as well as animal PET, were employed in order to evaluate their in vitro and in vivo binding to the NMDA receptors. Results: The compound 1 showed the specific binding to rat brain slices with higher localization in the hippocampus and cerebral cortex than in the cerebellum. Both glycine antagonists and agonists ...

2002-09-01