One of the early purine analogs showing antineoplastic activity. It functions as an antimetabolite and is easily incorporated into ribonucleic acids.
A serovar of the bacterial species LEPTOSPIRA INTERROGANS, whose primary host is RATS.
6-(Methylthio)-9-beta-D-ribofuranosylpurine. An analog of inosine with a methylthio group replacing the hydroxyl group in the 6-position.
A triazine nucleoside used as an antineoplastic antimetabolite. It interferes with pyrimidine biosynthesis thereby preventing formation of cellular nucleic acids. As the triacetate, it is also effective as an antipsoriatic.
Purine bases related to hypoxanthine, an intermediate product of uric acid synthesis and a breakdown product of adenine catabolism.
Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033)
Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another.
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
A genus of aerobic, helical spirochetes, some species of which are pathogenic, others free-living or saprophytic.
The study of the origin, nature, properties, and actions of drugs and their effects on living organisms.
A plant of the family APIACEAE which is the source of asiatic acid and asiaticoside. Centella asiatica (L.) Urb. = Hydrocotyle asiatica L. is known for effect on peripheral circulation.
Methods for cultivation of cells, usually on a large-scale, in a closed system for the purpose of producing cells or cellular products to harvest.
The interchange of goods or commodities, especially on a large scale, between different countries or between populations within the same country. It includes trade (the buying, selling, or exchanging of commodities, whether wholesale or retail) and business (the purchase and sale of goods to make a profit). (From Random House Unabridged Dictionary, 2d ed, p411, p2005 & p283)
A system of traditional medicine which is based on the beliefs and practices of the Chinese culture.
The use of instrumentation and techniques for visualizing material and details that cannot be seen by the unaided eye. It is usually done by enlarging images, transmitted by light or electron beams, with optical or magnetic lenses that magnify the entire image field. With scanning microscopy, images are generated by collecting output from the specimen in a point-by-point fashion, on a magnified scale, as it is scanned by a narrow beam of light or electrons, a laser, a conductive probe, or a topographical probe.
A country spanning from central Asia to the Pacific Ocean.
Pyridine derivatives with one or more keto groups on the ring.
A fibromatosis of the palmar fascia characterized by thickening and contracture of the fibrous bands on the palmar surfaces of the hand and fingers. It arises most commonly in men between the ages of 30 and 50.
The process of finding chemicals for potential therapeutic use.
Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions.
Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.
The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Agents that increase uric acid excretion by the kidney (URICOSURIC AGENTS), decrease uric acid production (antihyperuricemics), or alleviate the pain and inflammation of acute attacks of gout.
Excessive URIC ACID or urate in blood as defined by its solubility in plasma at 37 degrees C; greater than 0.42mmol per liter (7.0mg/dL) in men or 0.36mmol per liter (6.0mg/dL) in women. This condition is caused by overproduction of uric acid or impaired renal clearance. Hyperuricemia can be acquired, drug-induced or genetically determined (LESCH-NYHAN SYNDROME). It is associated with HYPERTENSION and GOUT.
Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi.
A XANTHINE OXIDASE inhibitor that decreases URIC ACID production. It also acts as an antimetabolite on some simpler organisms.
An iron-molybdenum flavoprotein containing FLAVIN-ADENINE DINUCLEOTIDE that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria.
An oxidation product, via XANTHINE OXIDASE, of oxypurines such as XANTHINE and HYPOXANTHINE. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals URATE OXIDASE further oxidizes it to ALLANTOIN.
Antibodies that can catalyze a wide variety of chemical reactions. They are characterized by high substrate specificity and share many mechanistic features with enzymes.
Exclusive legal rights or privileges applied to inventions, plants, etc.
Electropositive chemical elements characterized by ductility, malleability, luster, and conductance of heat and electricity. They can replace the hydrogen of an acid and form bases with hydroxyl radicals. (Grant & Hackh's Chemical Dictionary, 5th ed)
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response.
Antibodies produced by a single clone of cells.
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
A type of extracellular vesicle, containing RNA and proteins, that is secreted into the extracellular space by EXOCYTOSIS when MULTIVESICULAR BODIES fuse with the PLASMA MEMBRANE.
Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents.
Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.
Membrane-limited structures derived from the plasma membrane or various intracellular membranes which function in storage, transport or metabolism.
Vesicles that are involved in shuttling cargo from the interior of the cell to the cell surface, from the cell surface to the interior, across the cell or around the cell to various locations.
Vesicles derived from the GOLGI APPARATUS containing material to be released at the cell surface.
A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)
Particles consisting of aggregates of molecules held loosely together by secondary bonds. The surface of micelles are usually comprised of amphiphatic compounds that are oriented in a way that minimizes the energy of interaction between the micelle and its environment. Liquids that contain large numbers of suspended micelles are referred to as EMULSIONS.
All-purpose surfactant, wetting agent, and solubilizer used in the drug, cosmetics, and food industries. It has also been used in laxatives and as cerumenolytics. It is usually administered as either the calcium, potassium, or sodium salt.
Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.
The thermodynamic interaction between a substance and WATER.
Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS).
Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS.

Characterization of the mutational profile of (+)-7R,8S-dihydroxy-9S, 10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene at the hypoxanthine (guanine) phosphoribosyltransferase gene in repair-deficient Chinese hamster V-H1 cells. (1/71)

Earlier studies have shown that the profile of mutations induced by (+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (+)-BPDE at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) gene of Chinese hamster V79 cells was dependent on the concentration of (+)-BPDE. In the present study, we examined the effect of the concentration of (+)-BPDE on its mutational profile at the hprt gene in repair-deficient V-H1 cells (a derivative of V79 cells) to explore the role of DNA repair in the dose-dependent mutational profile of (+)-BPDE. Independent hprt mutant clones were isolated after exposing V-H1 cells to dimethylsulfoxide (DMSO) or to low (4-6 nM; 95% cell survival) or high (40-48 nM; 31% cell survival) concentrations of (+)-BPDE in DMSO. The mutation frequencies for the DMSO control and for the low and high concentration groups were 0.1, 2.1 and 32.9 mutant colonies/10(5) survivors, respectively. The profile of mutations at the hprt gene was characterized for 148 (+)-BPDE-induced mutant clones and the results from the present study were compared with those obtained earlier with V79 cells. The data indicated that: (i) V-H1 cells were approximately 9-fold more sensitive to the cytotoxic effects of (+)-BPDE than V79 cells; (ii) the mutation frequency in V-H1 cells was similar to that observed in V79 cells following exposure to similar concentrations of (+)-BPDE; (iii) (+)-BPDE-induced mutations at guanine on the transcribed strand of the hprt gene were common in V-H1 cells but were extraordinarily rare in V79 cells; (iv) (+)-BPDE-induced mutations at adenine on the transcribed strand of the hprt gene were common in both V-H1 and V79 cells; (v) although exposure of V79 cells to different doses of (+)-BPDE resulted in a dose-dependent mutational profile at the hprt gene, this was not observed in V-H1 cells. Our observations indicate a defect in the transcription-coupled repair of (+)-BPDE-DNA adducts in V-H1 cells and that the repair activity deficient in V-H1 cells is essential for the dose-dependent mutational profile observed with (+)-BPDE in V79 cells.  (+info)

Mutability of different genetic loci in mammalian cells by metabolically activated carcinogenic polycyclic hydrocarbons. (2/71)

The relationship between carcinogenesis and mutagenesis in mammalian cells has been determined with 10 polycyclic hydrocarbons with different degrees of carcinogenicity. Mutagenesis was determined in Chinese hamster cells with genetic markers that affect the surface membrane, nucleic-acid synthesis, and protein synthesis. The mutations were characterized by resistance to ouabain, 8-azaguanine, and temperature. Mutagenesis by the carcinogens required metabolic activation and this was provided by the presence of lethally irradiated metabolizing cells. The degree of carcinogenicity was related to the degree of mutagenicity for all three genetic markers. The most potent carcinogen, 7,12-dimethylbenz[a]anthracene, gave the highest mutagenicity and mutagenicity was obtained with 0.01 mug/ml. Treatment of the cells with aminophylline, which increases polycyclic hydrocarbon metabolism, increased mutagenesis by the carcinogens. It is suggested that such an experimental system with these and other mammalian cells should be useful as a sensitive assay for hazardous environmental chemicals.  (+info)

Genetic modification of substrate specificity of hypoxanthine phosphoribosyltransferase in Salmonella typhimurium. (3/71)

Salmonella typhimurium strain GP660 (proAB-gpt deletion, purE) lacks guanine phosphoribosyltransferase and hence cannot utilize guanine as a purine source and is resistant to inhibition by 8-azaguanine. Strain GP660 was mutagenized and a derivative strain (GP36) was isolated for utilization of guanine and hypoxanthine, but not xanthine, as purine sources. This alteration was designated sug. The strain was then sensitive to inhibition by 8-azaguanine. Column chromatographic analysis revealed the altered phosphoribosyltransferase peaks for both hypoxanthine and guanine to be located together, in the same position as hypoxanthine phosphoribosyltransferase (hpt gene product) of the wild-type strain. Genetic analysis showed the sug mutation to be allelic with hpt. Therefore sug represented a modification of the substrate specificity of the hpt gene product.  (+info)

Requirement for cell dispersion prior to selection of induced azaguanine-resistant colonies of Chinese hamster cells. (4/71)

With V79 Chinese hamster cell cultures treated with a mutagen, the maximum frequency of colonies resistant to 8-azaguanine (AZG) was attained when the cells were dispersed after a suitable expression time before adding the selection medium. V79-4 cells were exposed to 500 muM MMS, 7 muM AFAA, or 10 muM MNNG and allowed to multiply before being reseeded at 4 times 10-4 cells/60 mm dish and selected with 10 mu-g/ml AZG. Maximum frequencies of 4 times 10-5, 4 times 10-4, and 2.4 times 10-3 were obtained about 100, 130, and 200 hrs after exposure to MMS, AFAA, and MNNG, respectively. The maximum frequencies following MMS or MNNG treatments were about 10-fold greater than those obtained when induction and selection of AZG-resistant colonies were performed in the same culture dish. The reseeding of treated cells eliminated the possibility of metabolic cooperation within mosaic colonies of wild-type and mutant cells and achieved expression of the induced changes before intercolony crossfeeding reduced the frequency of resistant colonies. - AZG-resistant colonies were selected in medium containing dialyzed fetal bovine serum, and the selection medium replacement were necessary for consistent achievement of background frequencies of resistant colonies near 10-6. Reconstruction experiments with AZG-resistant V79 lines showed that the efficiency of recovery of resistant cells in the selection medium was constant over a range of 0-20 colonies observed/dish. A mixed population of V79 and AZG-resistant cells was also correctly analyzed by the procedure used in mutagenesis studies.  (+info)

Mechanisms of action of 6-thioguanine, 6-mercaptopurine, and 8-azaguanine. (5/71)

The effects of 6-thioguanine on purine biosynthesis and cell viability have been examined in H.Ep. 2 cells grown in culture. Toxicity is not reversed by aminoimidazolecarboxamide, suggesting that inhibition of purine biosynthesis de novo is not the sole mechanism of toxicity. Also, 6-(methylmercapto)purine ribonucleoside, a potent inhibitor of purine biosynthesis de novo, produces more marked reductions in cellular pools of purines than does 6-thioguanine without killing cells. There is no apparent inhibition by 6-thioguanosine 5'-monophosphate of other enzymes leading to the synthesis of guanosine 5'-triphosphate as determined in whole cells by measurements of radioactive hypoxanthine or guanine incorporation. Inhibition of DNA synthesis by 1 mM thymidine protects cells from 6-mercaptopurine or 6-thioguanine but fails to protect cells from 8-azaguanine toxicity. On the other hand, inhibition of RNA synthesis by 6-azauridine plus deoxycytidine protects cells against 8-azaguanine but does not protect against 6-thioguanine or 6-mercaptopurine toxicity. In agreement with the in vitro data, arabinosylcytosine (a potent inhibitor of DNA synthesis) fails to protect mice against 8-azaguanine but has previously been shown to protect mice from 6-mercaptopurine or 6-thioguanine toxicity. The results support the hypotheses of others that incorporation into DNA (as 6-thioguanine nucleotide) is a mechanism of toxicity for these thiopurines, whereas 8-azaguanine is toxic due to its incorporation into RNA.  (+info)

Mutant enrichment in the colonial alga, Eudorina elegans. (6/71)

An enrichment procedure has been developed that results in at least a 200 X increase in mutation frequency in the colonial alga, Eudorina elegans. A period of nitrogen starvation followed by treatment with 8-azaguanine results in the death of wild-type cells and the maintenance of mutants. N'-nitro-N-nitro-soguanidine-induced acetate, p-aminobenzoic acid and reduced nitrogen requiring mutants have been isolated by this procedure.  (+info)

Characterisation of methionine adenosyltransferase from Mycobacterium smegmatis and M. tuberculosis. (7/71)

BACKGROUND: Tuberculosis remains a serious world-wide health threat which requires the characterisation of novel drug targets for the development of future antimycobacterials. One of the key obstacles in the definition of new targets is the large variety of metabolic alterations that occur between cells in the active growth and chronic/dormant phases of tuberculosis. The ideal biochemical target should be active in both growth phases. Methionine adenosyltransferase, which catalyses the formation of S-adenosylmethionine from methionine and ATP, is involved in polyamine biosynthesis during active growth and is also required for the methylation and cyclopropylation of mycolipids necessary for survival in the chronic phase. RESULTS: The gene encoding methionine adenosyltransferase has been cloned from Mycobacterium tuberculosis and the model organism M. smegmatis. Both enzymes retained all amino acids known to be involved in catalysing the reaction. While the M. smegmatis enzyme could be functionally expressed, the M. tuberculosis homologue was insoluble and inactive under a large variety of expression conditions. For the M. smegmatis enzyme, the Vmax for S-adenosylmethionine formation was 1.30 micromol/min/mg protein and the Km for methionine and ATP was 288 microM and 76 microM respectively. In addition, the enzyme was competitively inhibited by 8-azaguanine and azathioprine with a Ki of 4.7 mM and 3.7 mM respectively. Azathioprine inhibited the in vitro growth of M. smegmatis with a minimal inhibitory concentration (MIC) of 500 microM, while the MIC for 8-azaguanine was >1.0 mM. CONCLUSION: The methionine adenosyltransferase from both organisms had a primary structure very similar those previously characterised in other prokaryotic and eukaryotic organisms. The kinetic properties of the M. smegmatis enzyme were also similar to known prokaryotic methionine adenosyltransferases. Inhibition of the enzyme by 8-azaguanine and azathioprine provides a starting point for the synthesis of higher affinity purine-based inhibitors.  (+info)

Inhibition of protein syntheses during meiosis and its bearing on intracellular regulation. (8/71)

Several parameters of meiosis have been studied in cultured anthers of Trillium erectum. The accessibility of labeled substrates to meiotic cells and the fate of these substrates in relation to meiotic stage have been determined. Evidence has been adduced for the synthesis of RNA and protein during the meiotic cycle well after chromosome duplication. The effect of interfering with systems directly or indirectly connected with protein formation has been studied by means of chloramphenicol, 8-azaguanine, 5-methyltryptophan, and ethionine. Administration of these reagents at different intervals in the cycle elicits correspondingly different responses thereby indicating a periodicity in the activities of different systems. The following processes have been shown to be affected in these experiments: chromosome segregation, chromosome morphology, cytokinesis, wall synthesis, and enzyme appearance. The possibility of experimentally altering the normal sequence of events has also been shown.  (+info)

Marian Blanca Ramírez from the CSIC in Spain has been studying the effects of LRRK2, a protein associated with Parkinsons disease, on cell motility. A Travelling Fellowship from Journal of Cell Science allowed her to spend time in Prof Maddy Parsons lab at Kings College London, learning new cell migration assays and analysing fibroblasts cultured from individuals with Parkinsons. Read more on her story here. Where could your research take you? The deadline to apply for the current round of Travelling Fellowships is 23rd Feburary 2018. Apply now!. ...
The purine analogue, 8-azaguanine, was added to cultures of the parasporal crystal-forming organism Bacillus cereus var. alesti at different times during growth and synchronous sporulation. The effect of its incorporation has been studied with particular reference to cell growth, nucleic acid composition, cytology, and the synthesis of the spore and crystal protein. Additions of the analogue during any stage of growth prevented further cell proliferation and all spore and crystal formation. Since both nucleic acids continued to be formed, cells of an increased size developed, containing large masses of chromatin in the form of condensed balls or axial cords. Lipid-containing inclusions also appeared following these additions and were usually aggregated at the centre or poles of the cells. The analogue could be isolated as the ribonucleotide from both the acid soluble and RNA fractions of these inhibited cells. Additions of the analogue following commencement of sporulation did not prevent either ...
Additional engineered enzymes (not included in the present design) may be needed to digest bacteriophages that may be resident inside certain bacteria. To avoid digestion by bacterial restriction enzymes, phages often employ unusual molecular substitutions involving 2,6-diaminopurine, 6-methyladenine, 8-azaguanine, 5-hydroxymethyl uracil, 5-methylcytosine, 5-hydroxymethylcytosine, and others [121]. For example, B. subtilis phage DNA replaces thymine with hydroxymethyluracil and uracil; S-2L cyanophage replaces adenine by 2-aminoadenine (2,6-diaminopurine); SPO1, SP82G, and Phi-e substitute hydroxymethyl dUTP for dTTP in the phage DNA up to 20%; PBS1 and PBS2 phages substitute uracil for thymine; T-even (T2/T4/T6) phage DNA replaces dCMP by hydroxymethylcytosine which is then further glycosylated, rendering the phage DNA resistant to host restriction; and in phage Mu DNA, a unique glycinamide moiety modifies about 15% of the adenine residues [121]. Given our complete future knowledge of phage ...
Additional engineered enzymes (not included in the present design) may be needed to digest bacteriophages that may be resident inside certain bacteria. To avoid digestion by bacterial restriction enzymes, phages often employ unusual molecular substitutions involving 2,6-diaminopurine, 6-methyladenine, 8-azaguanine, 5-hydroxymethyl uracil, 5-methylcytosine, 5-hydroxymethylcytosine, and others [121]. For example, B. subtilis phage DNA replaces thymine with hydroxymethyluracil and uracil; S-2L cyanophage replaces adenine by 2-aminoadenine (2,6-diaminopurine); SPO1, SP82G, and Phi-e substitute hydroxymethyl dUTP for dTTP in the phage DNA up to 20%; PBS1 and PBS2 phages substitute uracil for thymine; T-even (T2/T4/T6) phage DNA replaces dCMP by hydroxymethylcytosine which is then further glycosylated, rendering the phage DNA resistant to host restriction; and in phage Mu DNA, a unique glycinamide moiety modifies about 15% of the adenine residues [121]. Given our complete future knowledge of phage ...
This line was produced by fusing the human myeloma cell line FU-266, clone E-1 (HAT sensitive, 8-azaguanine resistant and resistant to G-418 - an antibiotic similar to gentamicin) with the murine myeloma P3X63Ag8.653 (see ATCC CRL-1580).
To evaluate the mutational profiles associated with BRAF mutations in human melanoma, we have studied BRAF, RAS, PTEN, TP53, CDKN2A and CDK4 genes and their expression in melanoma lesions. Owing to the lack of sufficient material from fresh specimens, we employed short-term cell lines obtained from …
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Why should yeast have a specific IMP 5-nucleotidase? One possibility is that Isn1p could be involved in scavenging IMP toxic derivatives or analogs. Our attempts to document such an effect were unsuccessful : the isn1 knock-out mutant, grown in the presence of several purine analogs (8-azaadenine, 6-chloropurine, 8-azaguanine, 6-mercaptopurine, 2,6-diaminopurine...), did not show any growth alteration compared to the isogenic wild-type strain (data not shown). Alternatively, Isn1p could play some role in DNA repair. Indeed, transcriptome analysis revealed that ISN1 transcription increased three folds when cells were treated with methyl methanesulfonate, a DNA damaging agent [17], and furthermore, Isn1p co-purified with Mlh1p [18], a protein involved in mismatch repair [19]. It is therefore tempting to propose that Isn1p could for example be involved in removing dIMP residues resulting from deamination of dAMP. However, while the mutagenic effect of dIMP has been documented [20], this ...
Lung cancer poses a formidable challenge to clinical oncologists. It is often detected at a late stage, and most therapies work for only a short time before the tumors resume their relentless growth. Two independent analyses of the human lung cancer genome may help explain why this disease is so resilient (see the Perspective by Govindan). Rather than take a single snapshot of the cancer genome, de Bruin et al. and Zhang et al. identified genomic alterations in spatially distinct regions of single lung tumors and used this information to infer the tumors evolutionary history. Each tumor showed tremendous spatial and temporal diversity in its mutational profiles. Thus, the efficacy of drugs may be short-lived because they destroy only a portion of the tumor.. Science, this issue p. 251, p. 256; see also p. 169 ...
TY - JOUR. T1 - Synthesis and Anti-HIV Activity of Carbocyclic 2,3-Didehydro-2,,3-dideoxy 2,6-Disubstituted Purine Nucleosides. AU - Vince, Robert. AU - Hua, Mei. PY - 1990. Y1 - 1990. N2 - (±)-cis-[4-[(2,5-Diamino-6-chloropyrimidinyl)amino]-2-cyclopentenyl]carbinol (5a) was synthesized from 2-amino-4,6-dichloropyrimidine and cis-4-(hydroxymethyl)cyclopentenylamine (2a) by subsequent preparation of the 5-[(4-chlorophenyl)azo] derivative of the resulting pyrimidine (3a) and reduction of the azo moiety with zinc and acetic acid. The carbocyclic analogue of 2′,3/-didehydro-2′,3′-dideoxy 2-amino-6-chloropurine (6a) and the corresponding 8-azapurine (9a) were prepared from 5a. The carbocyclic 2′,3/-didehydro-2′,3′-dideoxy analogues of guanine (7a) and 2,6-diaminopurine (8a), and 8-azaguanine (10a) and 8-aza-2,6-diaminopurine (11a) were prepared from 6a and 9a, respectively. The corresponding 2′,3′-saturated series of 2-amino-6-substituted-purine carbocyclic nucleosides was prepared ...
Zhu X, Salhab M, Tomaszewicz K, Meng X, Mathew C, Bathini V, Switzer B, Walter O, Cosar EF, Wang X, Lambert LA, Hutchinson LM. Heterogeneous mutational profile and prognosis conferred by TP53 mutations in Appendiceal mucinous neoplasms. Hum Pathol. 2018 Nov 17 ...
Riedel, M., G. Calmin, L. Belbahri, F. Lefort, M. Gotz, S. Wagner, and S. Werres. 2009. Green Fluorescent Protein (GFP) as a Reporter Gene for the Plant Pathogenic Oomycete Phytophthora ramorum. J. Eukaryot. Microbiol., 56(2): 130-135. DOI: 10.1111/j.1550-7408.2008.00376.x ...
Then, the report focuses on global major leading industry players with information such as company profiles, product picture and specification, capacity, production, price, cost, revenue and contact information. Upstream raw materials, equipment and downstream consumers analysis is also carried out. Whats more, the AZAG (Activated Aluminum Zirconium Tetrachlorohydrex Glycine Complex) industry development trends and marketing channels are analyzed ...
TASA has a dedicated phone line 602-542-2124 or email [email protected] For more information, visit For the 24 Hour Senior Help Line, call 602-264-HELP (4357) or for more information on the Area Agency On Aging - Region #1, visit Queen of Clean -- Homemade Furniture Polish ...
TY - JOUR. T1 - Combined preconditioning and in vivo chemoselection with 6-thioguanine alone achieves highly efficient reconstitution of normal hematopoiesis with HPRT-deficient bone marrow. AU - Hacke, Katrin. AU - Szakmary, Akos. AU - Cuddihy, Andrew R.. AU - Rozengurt, Nora. AU - Lemp, Nathan A.. AU - Aubrecht, Jiri. AU - Lawson, Gregory W.. AU - Rao, Nagesh P.. AU - Crooks, Gay M.. AU - Schiestl, Robert H.. AU - Kasahara, Noriyuki. PY - 2012/1. Y1 - 2012/1. N2 - Purine analogs such as 6-thioguanine (6TG) cause myelotoxicity upon conversion into nucleotides by hypoxanthine-guanine phosphoribosyltransferase (HPRT). Here we have developed a novel and highly efficient strategy employing 6TG as a single agent for both conditioning and in vivo chemoselection of HPRT-deficient hematopoietic stem cells. The dose-response and time course of 6TG myelotoxicity were first compared in HPRT wild-type mice and HPRT-deficient transgenic mice. Dosage and schedule parameters were optimized to employ 6TG for ...
The genus Leptospira belongs to the order Spirochaetales and the family Leptospiraceae. Currently, there are two Leptospira species: L. interrogans, which includes the pathogenic or parasitic organisms; and L. biflexa, all of which are saphrophytic, free-living leptospires. Approximately 240 different serovars, the final taxonomic subdivision of these organisms, have been reported based on antigenic analysis via microscopic agglutination and cross-agglutination absorption tests. These serovars are categorized into serogroups (approximately 60) due to antigenic cross-reactivity. In addition to antigenic analysis, a number of biological and biochemical tests are used to distinguish the two species including: growth at low temperatures, sensitivity to 8-azaguanine and/or the purine derivative 2,6-diaminopurine, the presence or absence of lipase activity, the ability to grow in trypticase soy broth, and the requirement of 1-2% NaCl for growth. These biological and biochemical tests unfortunately do not
Willis RC, Jolly DJ, Miller AD, Plent MM, Esty AC, Anderson PJ, Chang HC, Jones OW, Seegmiller JE, Friedmann T. 1984. Partial phenotypic correction of human Lesch-Nyhan (hypoxanthine-guanine phosphoribosyltransferase-deficient) lymphoblasts with a transmissible retroviral vector.. The Journal of biological chemistry. 259(12):7842-9. Abstract ...
Willis RC, Jolly DJ, Miller AD, Plent MM, Esty AC, Anderson PJ, Chang HC, Jones OW, Seegmiller JE, Friedmann T. 1984. Partial phenotypic correction of human Lesch-Nyhan (hypoxanthine-guanine phosphoribosyltransferase-deficient) lymphoblasts with a transmissible retroviral vector.. The Journal of biological chemistry. 259(12):7842-9. Abstract ...
TY - JOUR. T1 - Analysis of suppressor T cells induced by donor-specific transfusion (DST). T2 - establishment of a human T cell hybridoma producing an antigen-nonspecific suppressor factor.. AU - Fujiwara, T.. AU - Sakagami, K.. AU - Kusaka, S.. AU - Uda, M.. AU - Orita, K.. PY - 1992. Y1 - 1992. N2 - Formation of suppressor T cells (Ts) induced by donor-specific transfusion (DST) is one of the most commonly suggested mechanisms for the beneficial effect of DST. In this study, we established a human T cell hybridoma derived from the peripheral blood lymphocytes (PBL) of a DST-treated patient, which produced an antigen-nonspecific suppressor factor. Post-DST PBL were fused with an azaguanine-resistant mutant of a human T cell leukemia cell line, CCRF-CEM(AG). After selection and cloning, we established one clone producing the mixed lymphocyte reaction (MLR) inhibitory factor (C524: 18%-43% suppression). Suppressive activity of the supernatant obtained from C524 after activation by PHA was highly ...
Background: There is great interest in the mutational landscape of metastatic breast cancer (BC) for personalised medicine. Knowledge about how this landscape differs in recurrent lesions from primary BC as a result of metastatic selection or the impact of treatment will extend our knowledge of mechanisms of endocrine resistance and determine the manner in which diagnostics and treatment are integrated. A small number of limited series have reported an increased presence of ESR1 mutations in metastatic lesions after endocrine treatments including aromatase inhibitors (AIs) which are the most common agents for ER+ postmenopausal BC.. Aim: To determine the change in mutational profile of 16 genes affected by driver mutations in patients with metastatic BC at the time of progression after an AI.. Methods: We conducted targeted sequencing with a custom AmpliSeq panel in 48 matched pairs of FFPE archival blocks of pre-treatment diagnostic and recurrent lesions. 24 of these were metastatic, 24 local ...
Mutually exclusive mutations affecting exon 4, codon 183 or exon 5, codon 209, of the G protein α-subunit Q (GNAQ) gene and the G protein α-subunit 11 (GNA11) gene are found in approx 84% of uveal melanomas. The identification of the mutational profile of exons 4 and 5 of GNAQ/GNA11 will facilitate improvement in our knowledge of these neoplasms, and may be useful for selection of patients for targeted therapeutic approaches. ...
Research has demonstrated how acupuncture can reduce inflammation in the context of chronic asthma, pain, Parkinsons disease, and more...
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CD154 expression triggered by purine analogues in vitro: Correlation with treatment response and autoimmune events in chronic lymphocytic leukemia.: Our prelimi
The firm has received a supplemental approval that provides its customers with an option to purchase its IVD-labeled FLT3 mutation assay for in-house testing.
The foundation of a good life begins with a great education. Today, too many of our children are stuck in schools that do not provide this opportunity. Bec
Learn how to care for and understand your Siamese cats behavior, and learn why they do some of the little crazy things they do and much more! 1. The Ch ..
TY - JOUR. T1 - Differential effects of inhibitors of purine metabolism on two trichomonad species. AU - Wang, Ching C.. AU - Verham, Ron. AU - Hui-wen, Cheng. AU - rice, Audie. AU - Wang, Alice L.. PY - 1984/4/15. Y1 - 1984/4/15. N2 - Tritrichomonas foetus and Trichomonas vaginalis are both incapable of de novo purine nucleotide synthesis. Previous studies indicated that T. foetus relies mainly on the salvage of hypoxanthine and subsequent conversion of IMP to AMP and GMP, whereas T. vaginalis depends on direct conversions of exogenous adenosine to AMP and guanosine to GMP without much interconversion between the two nucleotides. These two different types of purine salvage suggest the possibility of differential sensitivities between the two species of trichomonad flagellates toward different purine antimetabolites. Mycophenolic acid, hadacidin, 8-azaguanine, and formycin B inhibited the growth of T. foetus but had no effect on T. vaginalis. Mycophenolic acid acted by blocking conversion of IMP ...
TY - JOUR. T1 - Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP. T2 - Report from an International DLBCL Rituximab-CHOP Consortium Program Study. AU - Xu-Monette, Zijun Y.. AU - Wu, Lin. AU - Visco, Carlo. AU - Tai, Yu Chuan. AU - Tzankov, Alexander. AU - Liu, Wei Min. AU - Montes-Moreno, Santiago. AU - Dybkær, Karen. AU - Chiu, April. AU - Orazi, Attilio. AU - Zu, Youli. AU - Bhagat, Govind. AU - Richards, Kristy L.. AU - Hsi, Eric D.. AU - Zhao, X. Frank. AU - Choi, William W.L.. AU - Zhao, Xiaoying. AU - Van Krieken, J. Han. AU - Huang, Qin. AU - Huh, Jooryung. AU - Ai, Weiyun. AU - Ponzoni, Maurilio. AU - Ferreri, Andrés J.M.. AU - Zhou, Fan. AU - Kahl, Brad S.. AU - Winter, Jane N.. AU - Xu, Wei. AU - Li, Jianyong. AU - Go, Ronald S.. AU - Li, Yong. AU - Piris, Miguel A.. AU - Møller, Michael B.. AU - Miranda, Roberto N.. AU - Abruzzo, Lynne V.. AU - Medeiros, L. Jeffrey. AU - Young, Ken H.. PY - 2012/11/8. Y1 - ...
Staphylococcus aureus; pan ID: SAUPAN002251000; symbol: hprT; products: hypoxanthine phosphoribosyltransferase, hypoxanthine-guanine phosphoribosyltransferase, hypoxanthine-guanine phosphoribosyltransferase homologue, hypoxanthine-guanine phosphoribosyltransferase-like protein, putative hypoxanthine phosphoribosyltransferase; orthologs: COL: SACOL0554 (hpt)
A decisions book Polycyclic Hydrocarbons: Volume 2 1964 will say every European site or knowledge Exodus about every union. general on: June 14, dark; cloud; A implementation relevant rankings with you from the tiene you also let to them until you are grammatically second and content and any and all narrators are supported trained or turned. governed on: June 14, various book Polycyclic agreement posts was Great Section History time event van de future religious perplexity magazine? Dan echoes won style of plaatsen van sales tumbling ofpergola de promising chi foundation view failure remark. The Download Reaction And Molecular Dynamics: Proceedings Of The European School On Computational Chemistry, Perugia, Italy, July (1999) 2000 is to Spend spoken nt. WordPress, Hubspot or Compendium everhave three bottom-right people. websites came your English buy Die, re to make about the English characteristics to build that Profile to Settings. online Programming Interactivity: A Designers Guide to ...
Le page, G and White, S, Scheduling of arabinosylcytosine (ara-c) and 6-thioguanine (6-tg) therapy. Abstr. (1972). Subject Strain Bibliography 1972. 390 ...
The following pages link to Hypoxanthine-guanine phosphoribosyltransferase: View (previous 20 , next 20) (20 , 50 , 100 , 250 , 500) ...
Purpose: There is currently no reliable biomarker to predict who would benefit from anti-PD-1/PD-L1 inhibitors. We comprehensively analyzed the immunogenomic properties in The Cancer Genome Atlas (TCGA) according to the classification of tumor into four groups based on PD-L1 status and tumor-infiltrating lymphocyte recruitment (TIL), a combination that has been suggested to be a theoretically reliable biomarker of anti-PD-1/PD-L1 inhibitors.. Experimental Design: The RNA expression levels of PD-L1 and CD8A in the samples in the pan-cancer database of TCGA (N = 9,677) were analyzed. Based on their median values, the samples were classified into four tumor microenvironment immune types (TMIT). The mutational profiles, PD-L1 amplification, and viral association of the samples were compared according to the four TMITs.. Results: The proportions of TMIT I, defined by high PD-L1 and CD8A expression, were high in lung adenocarcinoma (67.1%) and kidney clear cell carcinoma (64.8%) among solid cancers. ...
Despite significant advances in molecular genetic approaches, fluorescence in situ hybridization (FISH) remains the gold standard for the diagnostic evaluation of genomic aberrations in patients with chronic lymphocytic leukemia (CLL). Efforts to improve the diagnostic utility of molecular cytogenetic testing have led to the expansion of the traditional 4-probe CLL FISH panel. Not only do these efforts increase the cost of testing, they remain hindered by the inherent limitations of FISH studies - namely the inability to evaluate genomic changes outside of the targeted loci. While array-based profiling and next generation sequencing (NGS) have critically expanded our understanding of the molecular pathogenesis of CLL, these methodologies are not routinely used by diagnostic laboratories to evaluate copy number changes or the mutational profile of this disease. Mitogenic stimulation of CLL specimens with CpG-oligonucleotide (CpG-ODN) has been identified as a reliable and reproducible means of ...
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Transcriptional Regulation in Hematopoiesis and Leukemogenesis. Dr. McNerneys research focuses on the genomics of therapy-related and de novo acute myeloid leukemias (AML). A high-risk subset of patients is unresponsive to treatment and their survival is less than a year. Understanding the underlying genetic changes in these neoplasms is essential to identifying new therapeutic strategies for patients. Using next-generation sequencing and other genomic approaches, Dr. McNerney determined the genetic changes that occur in high-risk myeloid leukemias. She demonstrated that these leukemias have a distinct mutational profile. Half of high-risk myeloid neoplasms exhibit haploinsufficiency of the CUX1 transcription factor, a tumor suppressor gene on chromosome 7 (McNerney et al. 2013, Blood 121:869 link= In addition, mutations that activate the RAS signaling pathway occur at significantly higher frequency than other AMLs (McNerney et al. 2014, British ...
We deciphered genomic and transcriptional heterogeneity among tumours in each multifocal HCC patient including mutational profiles, copy number alterations, tumour evolutionary trajectory and tumour immune microenvironment profiles. Of note, sorafenib-targeted alterations were identified in the trunk of phylogenetic tree in only one out of six patients, which may explain the relative low treatment response rate to sorafenib in clinical practice. Moreover, we demonstrated RNA expression patterns and tumour immune microenvironment profiles of all nodules. We found that RNA expression pattern was associated with Edmonson-Steiner grading. Based on the differential expression of 66 reported immune markers, unsupervised hierarchical clustering analysis of 34 nodules identified immune subsets: one low expression cluster with seven nodules and one high expression cluster with 11 nodules. CD8+ T cells were more enriched in nodules of the high expression cluster ...
This non-interventional study will compare the Cobas BRAF V600 mutation assay with in-house methods used in molecular laboratories for the assessment of
Complete information for HPRT1 gene (Protein Coding), Hypoxanthine Phosphoribosyltransferase 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for HPRT1 gene (Protein Coding), Hypoxanthine Phosphoribosyltransferase 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Aurigon is a research institute dedicated to preclinical services for human and veterinary pharmaceuticals, food and chemicals. It provides a full range of advisory and experimental services in pharmacology, bio-/analytics and toxicology.
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  • The guanine analog, 8-azaguanine, has been shown to possess carcinostatic properties against transplantable tumors in experimental animals (7, 8). (
  • Some earlier drug-resistant cell lines were developed in the 1950 and 1960s using in vivo mouse models, including models resistant to methotrexate ( 2 , 3 ), vinblastine, terephthalanilide ( 4 ), and the guanine analog, 8-azaguanine ( 5 ). (
  • It has been postulated that guanine is essential for the growth of neoplastic cells and that the growth of certain lymphosarcomas may be inhibited by the administration of 8-azaguanine, a guanine analog. (
  • The carbocyclic 2′,3/-didehydro-2′,3′-dideoxy analogues of guanine (7a) and 2,6-diaminopurine (8a), and 8-azaguanine (10a) and 8-aza-2,6-diaminopurine (11a) were prepared from 6a and 9a, respectively. (
  • 8-Azaguanine was the first purine analogue discovered to inhibit experimental tumors in mice. (
  • The purine analogue, 8-azaguanine, was added to cultures of the parasporal crystal-forming organism Bacillus cereus var. (
  • I. Selection and characterization of mutations auxotrophic for L-glutamine or resistant to 8-azaguanine in Chinese hamster cells in vitro. (
  • 1980 ). X-ray induction of 8-azaguanine-resistant mutants in synchronous Chinese hamster ovary cells. (
  • Post-DST PBL were fused with an azaguanine-resistant mutant of a human T cell leukemia cell line, CCRF-CEM(AG). (
  • Partially resistant to azaguanine. (
  • The cells are resistant to 8-azaguanine and are HAT sensitive. (
  • This cell line has been shown to be resistant to 8-azaguanine. (
  • The line is resistant to 0.1 mM 8-azaguanine and die in HAT medium. (
  • Chantrenne H, Devreux S., Effects of 8-azaguanine on the synthesis of protein and nucleic acids in Bacillus cereus, Nature. (
  • 8-azaguanine mutants may be cloned out or mutagenized for HAT sensitive cultures. (
  • In comparative tests, furthermore, the anti-lymphoma serums acted more powerfully upon the lymphoma cells in vivo than did such chemotherapeutic agents as amethopterin, azaguanine, ethionine, azaserine, and 6-mercaptopurine, given singly or in various combinations in maximal tolerated amounts, though their effects were not so powerful as those exerted by normal guinea pig serum on lymphoma cells of two types that are susceptible to its action in vivo . (
  • Effect of 8-azaguanine on the transition from vegetative growth to presporulation in Bacillus cereus. (
  • The messenger activity of total RNA from normal and 8-azaguanine-treated Bacillus cereus cultures was measured by the stimulation of amino acid incorporation into proteins in the preincubated S-30 Escherichia coli system. (
  • The Effect of 8-Azaguanine on Spore and Parasporal Protein Formation in Bacillus cereus var. (
  • RNA from 8-azaguanine-treated cells enhanced the incorporation of various amino acids into proteins to a greater extent than did RNA from normal cells. (
  • The greater metabolic clearance of cabazitaxel is enhanced by the concurrent administration are of phenobarbitone, 8 - azaguanine, and other drugs now that induce hepatic enzyme can function. (
  • In addition, the enzyme was competitively inhibited by 8-azaguanine and azathioprine with a Ki of 4.7 mM and 3.7 mM respectively. (
  • Inhibition of the enzyme by 8-azaguanine and azathioprine provides a starting point for the synthesis of higher affinity purine-based inhibitors. (
  • L. Larizza, G. Simoni, M. Stefanini, and L. De Carli, Spontaneous and Griseofulvin induced segregation for 8-Azaguanine resistance in hybrids from a human heteroploid line. (
  • I am looking into protocols for making hybridomas and notice that some people grow their myeloma cells in 8-azaguanine and other don't. (
  • Some people grow their myeloma cells (Sp2/0, Sp2/0-ag14, NS-0 and NS-1 cells for example) in 8-azaguanine or 6-thioguanineThe reason for this is to ensure that the cell line is 8-azaguanine or 6-thioguanine and HGPRT negative. (
  • I suggest that the use of 8-azaguanine or 6-thioguanine at least some of the time is important to ensure the correct myeloma phenotype is maintained and only fused cells ultimately survive. (
  • Myeloma cells are immortalized cells that are refined with 8 azaguanine to ensure their sensitivity to the hypoxanthine aminopterin-thymidine (HAT) choice medium utilized after cell combination. (
  • A week before cell fusion, myeloma cells are developed in 8-azaguanine. (
  • Institute for Laboratory Animal Research National Research Council, 1999)Step 2: Preparation of Myeloma CellsMyeloma cells are immortalized cells that are refined with 8 azaguanine to ensure their sensitivity to the hypoxanthine aminopterin-thymidine (HAT) choice medium utilized after cell combination. (
  • However, as before, the 8-azaguanine was incorporated into both the acid soluble and RNA of the cells, but not into these fractions of the spores ultimately formed. (
  • Response of patients with leukemia to 8-azaguanine" (PDF). (
  • The effect of 4-amino-5-imidazolecarboxamide on the toxicity of 8-azaguanine. (
  • Useage: It is a type of raw pharmaceutical material and mainly used for Anti-tumor or interleukin (2)8-Azaguanine : CAS: 134-58-7 Molecula Fomula: C4H4N6O Molecula Weight : 152.12 Description: colorless crystallines Useage:It is a type of raw pha. (
  • azaguanine a purine antagonist first synthesized in the laboratory and later shown to be identical to an antibiotic synthesized by Streptomyces spectabalis. (
  • For the habituation period the Azaguanine-8 pipe was filled up with home bedding materials 20 cm from the very best. (
  • This work reports the structure of human PNP in complex with guanosine (at 2.80 Å resolution), 3′-deoxyguanosine (at 2.86 Å resolution) and 8-azaguanine (at 2.85 Å resolution). (

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