Coformycin: A ribonucleoside antibiotic synergist and adenosine deaminase inhibitor isolated from Nocardia interforma and Streptomyces kaniharaensis. It is proposed as an antineoplastic synergist and immunosuppressant.Adenosine Deaminase Inhibitors: Drugs that inhibit ADENOSINE DEAMINASE activity.AMP Deaminase: An enzyme that catalyzes the deamination of AMP to IMP. EC 3.5.4.6.Ribonucleosides: Nucleosides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)Nucleotide Deaminases: Catalyze the hydrolysis of nucleotides with the elimination of ammonia.Nucleoside Deaminases: Catalyze the hydrolysis of nucleosides with the elimination of ammonia.Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.Adenosine: A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.Hypothalamic Area, Lateral: Area in the hypothalamus bounded medially by the mammillothalamic tract and the anterior column of the FORNIX (BRAIN). The medial edge of the INTERNAL CAPSULE and the subthalamic region form its lateral boundary. It contains the lateral hypothalamic nucleus, tuberomammillary nucleus, lateral tuberal nuclei, and fibers of the MEDIAL FOREBRAIN BUNDLE.Preoptic Area: Region of hypothalamus between the ANTERIOR COMMISSURE and OPTIC CHIASM.Sleep: A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility.Arousal: Cortical vigilance or readiness of tone, presumed to be in response to sensory stimulation via the reticular activating system.Histamine: An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.Histidine Decarboxylase: An enzyme that catalyzes the decarboxylation of histidine to histamine and carbon dioxide. It requires pyridoxal phosphate in animal tissues, but not in microorganisms. EC 4.1.1.22.Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli.Nucleosides: Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Annonaceae: The custard-apple plant family of the order Magnoliales, subclass Magnoliidae, class Magnoliopsida. Some members provide large pulpy fruits and commercial timber. Leaves and wood are often fragrant. Leaves are simple, with smooth margins, and alternately arranged in two rows along the stems.Ethers, Cyclic: Compounds of the general formula R-O-R arranged in a ring or crown formation.Purine Nucleosides: Purines with a RIBOSE attached that can be phosphorylated to PURINE NUCLEOTIDES.Pyrimidine Nucleosides: Pyrimidines with a RIBOSE attached that can be phosphorylated to PYRIMIDINE NUCLEOTIDES.Nucleoside Transport Proteins: Proteins involved in the transport of NUCLEOSIDES across cellular membranes.Sodium Channels: Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.Voltage-Gated Sodium Channel beta-4 Subunit: A voltage-gated sodium channel beta subunit subtype that covalently associates with voltage-gated alpha subunits. Defects in the SCN4B gene, which codes for this beta subunit, are associated with long QT syndrome-10.Los AngelesSodium Channel Blockers: A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.Ion Channel Gating: The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.Voltage-Gated Sodium Channels: A family of membrane proteins that selectively conduct SODIUM ions due to changes in the TRANSMEMBRANE POTENTIAL DIFFERENCE. They typically have a multimeric structure with a core alpha subunit that defines the sodium channel subtype and several beta subunits that modulate sodium channel activity.United States National Aeronautics and Space Administration: An independent Federal agency established in 1958. It conducts research for the solution of problems of flight within and outside the Earth's atmosphere and develops, constructs, tests, and operates aeronautical and space vehicles. (From U.S. Government Manual, 1993)National Library of Medicine (U.S.): An agency of the NATIONAL INSTITUTES OF HEALTH concerned with overall planning, promoting, and administering programs pertaining to advancement of medical and related sciences. Major activities of this institute include the collection, dissemination, and exchange of information important to the progress of medicine and health, research in medical informatics and support for medical library development.Surgical Mesh: Any woven or knit material of open texture used in surgery for the repair, reconstruction, or substitution of tissue. The mesh is usually a synthetic fabric made of various polymers. It is occasionally made of metal.United StatesNational Health Insurance, United StatesPolypropylenes: Propylene or propene polymers. Thermoplastics that can be extruded into fibers, films or solid forms. They are used as a copolymer in plastics, especially polyethylene. The fibers are used for fabrics, filters and surgical sutures.MEDLARS: A computerized biomedical bibliographic storage and retrieval system operated by the NATIONAL LIBRARY OF MEDICINE. MEDLARS stands for Medical Literature Analysis and Retrieval System, which was first introduced in 1964 and evolved into an online system in 1971 called MEDLINE (MEDLARS Online). As other online databases were developed, MEDLARS became the name of the entire NLM information system while MEDLINE became the name of the premier database. MEDLARS was used to produce the former printed Cumulated Index Medicus, and the printed monthly Index Medicus, until that publication ceased in December 2004.

5'-Nucleotidase as a marker of both general and local inflammation in rheumatoid arthritis patients. (1/126)

OBJECTIVES: To evaluate measurements of serum and synovial fluid 5'-nucleotidase (5'N) activity as a marker of general and local inflammation in arthritis, and to resolve a contradiction in the literature as to whether or not the activity of 5'N in the synovial fluids of rheumatoid arthritis (RA) patients is raised in comparison with that in the synovial fluids of other arthritis patients. METHODS: Assays for 5'N were carried out in the presence of inhibitors of other phosphatases, AMP deaminase and of 5'N itself. RESULTS: The 5'N activity in the synovial fluid of RA patients was both significantly higher (mean 1.7-fold) and had a greater variance than that in the synovial fluids of other arthritis patients, and the contradiction in the literature was resolved. There was a strong correlation between the 5'N activity in the sera of RA patients and their erythrocyte sedimentation rate. There was no significant correlation between the 5'N in the serum and synovial fluid for the RA patients, in marked contrast to the strong correlation between the two 5'N activities shown by the osteoarthritis patients. The 5'N activity was greater in the synovial fluid than in the serum for virtually all the patients, showing that it was being made locally. CONCLUSIONS: The 5'N activity in the serum (which came mostly from the liver) could be used as a marker of general inflammation, whereas the 5'N in the synovial fluid was mostly produced locally, and could be used as a marker of joint inflammation, particularly for the RA patients.  (+info)

Adenosine-mediated killing of cultured epithelial cancer cells. (2/126)

Because micromolar concentrations of adenosine (Ado) have been documented recently in the interstitial fluid of carcinomas growing in animals, we examined the effects of low concentrations of Ado on the growth of cultured human carcinoma cells. Ado alone had little effect upon cell growth. In the presence of one of a number of Ado deaminase (ADA) inhibitors, Ado led to significant growth inhibition of all cell lines tested. Similar effects were found when ATP, ADP, or AMP was substituted for Ado. Surprisingly, the ADA inhibitor coformycin (CF) had a much greater potentiating effect than did 2'-deoxycoformycin (DCF), although DCF is a more potent ADA inhibitor. The growth inhibition of the Ado/CF combination was not abrogated by pyrimidines or caffeine, a nonspecific Ado receptor blocker. Toxicity was prevented by the addition of the Ado transport inhibitor dipyridamole or the Ado kinase inhibitor 5'-amino 5'-deoxyadenosine. S-Adenosylhomocysteine hydrolase is not involved because neither homocysteine thiolactone nor an S-adenosylhomocysteine hydrolase inhibitor (adenosine dialdehyde) potentiated toxicity of the Ado/CF combination. Unexpectedly, substitution of 2'-deoxyadenosine (the toxic moiety in congenital ADA deficiency) for Ado, did not lead to equivalent toxicity. The Ado/CF combination inhibited DNA synthesis and brought about morphological changes consistent with apoptosis. Together, these findings indicate that the Ado-mediated killing proceeds via an intracellular route that requires the action of Ado kinase. The enhanced cofactor activity of CF may be attributable to its being a more potent inhibitor of AMP deaminase than is DCF.  (+info)

Direct measurement of adenosine release during hypoxia in the CA1 region of the rat hippocampal slice. (3/126)

We have used an enzyme-based, twin-barrelled sensor to measure adenosine release during hypoxia in the CA1 region of rat hippocampal slices in conjunction with simultaneous extracellular field recordings of excitatory synaptic transmission. When loaded with a combination of adenosine deaminase, nucleoside phosphorylase and xanthine oxidase, the sensor responded linearly to exogenous adenosine over the concentration range 10 nM to 20 microM. Without enzymes, the sensor when placed on the surface of hippocampal slices recorded a very small net signal during hypoxia of 40 +/- 43 pA (mean +/- s.e.m.; n = 7). Only when one barrel was loaded with the complete sequence of enzymes and the other with the last two in the cascade did the sensor record a large net difference signal during hypoxia (1226 +/- 423 pA; n = 7). This signal increased progressively during the hypoxic episode, scaled with the hypoxic depression of the simultaneously recorded field excitatory postsynaptic potential and was greatly reduced (67 +/- 6.5 %; n = 9) by coformycin (0.5-2 microM), a selective inhibitor of adenosine deaminase, the first enzyme in the enzymic cascade within the sensor. For 5 min hypoxic episodes, the sensor recorded a peak concentration of adenosine of 5.6 +/- 1.2 microM (n = 16) with an IC(50) for the depression of transmission of approximately 3 microM. In slices pre-incubated for 3-6 h in nominally Ca(2+)-free artificial cerebrospinal fluid, 5 min of hypoxia resulted in an approximately 9-fold greater release of adenosine (48.9 +/- 17.7 microM; n = 6). High extracellular Ca(2+) (4 mM) both reduced the adenosine signal recorded by the sensor during hypoxia (3.5 +/- 0.6 microM; n = 4) and delayed the hypoxic depression of excitatory synaptic transmission.  (+info)

Enhancement of cellular adenosine triphosphate levels in PC12 cells by extracellular adenosine. (4/126)

To elucidate the biological significance of extracellular adenine compounds, the effects of adenosine (Ado) on cellular levels of adenine compounds, especially adenosine triphosphate (ATP), in PC12 cells were studied. Ado and inosine but not adenosine 5'-monophosphate, adenosine 5'-diphosphate, ATP, guanosine, cytosine, thymidine, and uridine, significantly enhanced cellular ATP levels in PC12 cells in time- and dose-dependent manners. Various P1 receptor agonists of Ado did not enhance the ATP level. In addition, theophylline, an antagonist of P1 receptors, did not inhibit the Ado-evoked ATP enhancement. These results suggest that the Ado receptor is not involved in the augmentation of the cellular ATP level induced by Ado in PC12 cells. The ATP-enhancing effect of Ado was potentiated by dipyridamole, an inhibitor of Ado uptake, or coformycin, an inhibitor of Ado deaminase. The effect of Ado on the ATP level was also observed when PC12 cells were incubated in glucose-free medium. Together these results suggest that enhancement of cellular ATP levels in PC12 cells by extracellular Ado might be acceleration of ATP synthesis through the Ado salvage system using hypoxanthine-guanine phosphoribosyltransferase rather than Ado kinase since 5'-iodotubercidin, an inhibitor of Ado kinase, had no effect on the enhancement elicited by Ado.  (+info)

Extracellular ATP and adenosine induce cell apoptosis of human hepatoma Li-7A cells via the A3 adenosine receptor. (5/126)

1. Extracellular ATP is a potent signaling molecule that modulates a myriad of cellular functions through the activation of P2 purinergic receptors and is cytotoxic to a variety of cells at higher concentrations. The mechanism of ATP-elicited cytotoxicity is not fully understood. In this study, we investigated the effect of extracellular ATP on the human hepatoma Li-7A cells. 2. We observed a time- and dose-dependent growth inhibition of Li-7A cells by ATP, which is accompanied by an increase in the active form of caspase-3 as well as increased cleavage of its substrate, poly (ADP-ribose) polymerase. The cytotoxic effect of extracellular ATP was not mediated by the P2X7 receptor, since (1).the effect was not abolished by the P2X7 receptor antagonists oxidized ATP and KN-62, and (2).extracellular ADP, AMP, and adenosine were also cytotoxic. 3. We found that ATP and ADP were degraded to adenosine by Li-7A cells and that treatment of Li-7A cells by adenosine resulted in growth inhibition and caspase-3 activation, indicating that adenosine is the apoptotic agent. Using adenosine receptor agonists and antagonists, as well as inhibitors of adenosine transport and deamination, we showed that the cytotoxic effect of adenosine is specifically mediated by the A3 receptor even though transcripts of A1, A2A, A2B, and a splice variant of the P2X7 receptors were detected in Li-7A cells by RT-PCR. 4. Cytotoxicity caused by exogenous ATP and adenosine was completely abolished by the caspase-3 inhibitor Z-DEVD-FMK, demonstrating the central role of caspase-3 in apoptosis of Li-7A cells.  (+info)

Relatively small increases in the steady-state levels of nucleobase deamination products in DNA from human TK6 cells exposed to toxic levels of nitric oxide. (6/126)

Nitric oxide (NO) is a physiologically important molecule that has been implicated in the pathophysiology of diseases associated with chronic inflammation, such as cancer. While the complicated chemistry of NO-mediated genotoxicity has been extensively study in vitro, neither the spectrum of DNA lesions nor their consequences in vivo have been rigorously defined. We have approached this problem by exposing human TK6 lymphoblastoid cells to controlled steady-state concentrations of 1.75 or 0.65 microM NO along with 186 microM O2 in a recently developed reactor that avoids the anomalous gas-phase chemistry of NO and approximates the conditions at sites of inflammation in tissues. The resulting spectrum of nucleobase deamination products was defined using a recently developed liquid chromatography/mass spectrometry (LC/MS) method, and the results were correlated with cytotoxicity and apoptosis. A series of control experiments revealed the necessity of using dC and dA deaminase inhibitors to avoid adventitious formation of 2'-deoxyuridine (dU) and 2'-deoxyinosine (dI), respectively, during DNA isolation and processing. Exposure of TK6 cells to 1.75 microM NO and 186 microM O2 for 12 h (1260 microM x min dose) resulted in 32% loss of cell viability measured immediately after exposure and 87% cytotoxicity after a 24 h recovery period. The same exposure resulted in 3.5-, 3.8-, and 4.1-fold increases in dX, dI, and dU, respectively, to reach the following levels: dX, 7 (+/- 1) per 10(6) nt; dI, 25 (+/- 2.1) per 10(6) nt; and dU, 40 (+/- 3.8) per 10(6) nt. dO was not detected above the limit of detection of 6 lesions per 10(7) nt in 50 microg of DNA. A 12 h exposure to 0.65 microM NO and 190 microM O2 (468 microM x min dose) caused 1.7-, 1.8-, and 2.0-fold increases in dX, dI, and dU, respectively, accompanied by a approximately 15% (+/- 3.6) reduction in cell viability immediately after exposure. Again, dO was not detected. These results reveal modest increases in the steady-state levels of DNA deamination products in cells exposed to relatively cytotoxic levels of NO. This could result from limited nitrosative chemistry in nuclear DNA in cells exposed to NO or high levels of formation balanced by rapid repair of nucleobase deamination lesions in DNA.  (+info)

Crystallization and preliminary X-ray crystallographic analysis of adenosine 5'-monophosphate deaminase (AMPD) from Arabidopsis thaliana in complex with coformycin 5'-phosphate. (7/126)

Adenosine 5'-monophosphate deaminase (AMPD) is a eukaryotic enzyme that converts adenosine 5'-monophosphate (AMP) to inosine 5'-monophosphate (IMP) and ammonia. AMPD from Arabidopsis thaliana (AtAMPD) was cloned into the baculoviral transfer vector p2Bac and co-transfected along with a modified baculoviral genome into Spodoptera frugiperda (Sf9) cells. The resulting recombinant baculovirus were plaque-purified, amplified and used to overexpress recombinant AtAMPD. Crystals of purified AtAMPD have been obtained to which coformycin 5'-phosphate, a transition-state inhibitor, is bound. Crystals belong to space group P6(2)22, with unit-cell parameters a = b = 131.325, c = 208.254 A, alpha = beta = 90, gamma = 120 degrees. Diffraction data were collected to 3.34 A resolution from a crystal in complex with coformycin 5'-phosphate and to 4.05 A resolution from a crystal of a mercury derivative.  (+info)

AMP-activated protein kinase-independent inhibition of hepatic mitochondrial oxidative phosphorylation by AICA riboside. (8/126)

AICA riboside (5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside) has been extensively used in cells to activate the AMPK (AMP-activated protein kinase), a metabolic sensor involved in cell energy homoeostasis. In the present study, we investigated the effects of AICA riboside on mitochondrial oxidative; phosphorylation. AICA riboside was found to dose-dependently inhibit the oligomycin-sensitive JO2 (oxygen consumption rate) of isolated rat hepatocytes. A decrease in P(i) (inorganic phosphate), ATP, AMP and total adenine nucleotide contents was also observed with AICA riboside concentrations >0.1 mM. Interestingly, in hepatocytes from mice lacking both alpha1 and alpha2 AMPK catalytic subunits, basal JO2 and expression of several mitochondrial proteins were significantly reduced compared with wild-type mice, suggesting that mitochondrial biogenesis was perturbed. However, inhibition of JO2 by AICA riboside was still present in the mutant mice and thus was clearly not mediated by AMPK. In permeabilized hepatocytes, this inhibition was no longer evident, suggesting that it could be due to intracellular accumulation of Z nucleotides and/or loss of adenine nucleotides and P(i). ZMP did indeed inhibit respiration in isolated rat mitochondria through a direct effect on the respiratory-chain complex I. In addition, inhibition of JO2 by AICA riboside was also potentiated in cells incubated with fructose to deplete adenine nucleotides and P(i). We conclude that AICA riboside inhibits cellular respiration by an AMPK-independent mechanism that likely results from the combined intracellular P(i) depletion and ZMP accumulation. Our data also demonstrate that the cellular effects of AICA riboside are not necessarily caused by AMPK activation and that their interpretation should be taken with caution.  (+info)

This cell line was a T lymphoblastoid line obtained from the peripheral blood of a 4 year old Caucasian female with acute lymphoblastoid leukaemia. These may be grown to a high density in a spinner type suspension culture. Cells are reported to be free of virus particles as determined by electron microscopy ...
TY - JOUR. T1 - Conversion of a stem cell leukemia from a T-lymphoid to a myeloid phenotype induced by the adenosine deaminase inhibitor 2-deoxycoformycin. AU - Hershfield, M. S.. AU - Kurtzberg, J.. AU - Harden, E.. AU - Moore, J. O.. AU - Whang-Peng, J.. AU - Haynes, B. F.. PY - 1984/3/22. Y1 - 1984/3/22. N2 - Selective failure of lymphoid development occurs in genetic deficiency of adenosine deaminase (ADA). We examined the in vivo effects of a potent inhibitor of ADA, 2-deoxycoformycin, which was used to treat a patient with refractory acute leukemia. Unexpectedly, within 7 days of starting treatment, the leukemic phenotype underwent complete conversion from T lymphoblastic to promyelocytic, with kinetics that suggested a precursor-product relationship between the two cell populations. Pretreatment of T lymphoblasts and posttreatment of promyelocytes had the same abnormal karyotype. Upon culture in vitro, the former transformed spontaneously over several weeks into mature myeloid cells. We ...
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TY - JOUR. T1 - Preparation of tRNAs Terminating in 2′- and 3′-Deoxyadenosine. AU - Alford, Bernadette L.. AU - Craig Chinault, A.. AU - Jolly, Setsuko O.. AU - Hecht, Sidney M.. PY - 1979/1/1. Y1 - 1979/1/1. N2 - The chapter describes the preparation of isomeric tRNAs terminating in 2- and 3-deoxyadenosine. The modification procedure is illustrated both for unfractionated Escherichia coli tRNA and for E. coli tRNA Trp. The principle states that by limited digestion of tRNAs with purified venom exonuclease, it is possible to effect partial removal of the cytidine and adenosine moieties from the 3 terminus without significant hydrolysis of nucleotides from the adjacent double-stranded portion of the accepter stem. While hydrolysis does not proceed uniformly over the entire population of treated tRNAs, especially where unfractionated material is utilized, the average extent of hydrolysis can be monitored conveniently. Reconstitution to afford tRNA-C-COH is subsequently achieved by ...
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Adenosine deaminase (ADA) is an enzyme involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues. Present in virtually all mammalian cells, its primary function in humans is the development and maintenance of the immune system. Adenosine deaminase is considered one of the key enzymes of purine metabolism. Adenosine deaminase in humans is involved in the development and maintenance of the immune system. However, Adenosine deaminase association has also been observed with epithelial cell differentiation, neurotransmission, and gestation maintenance. It has also been proposed that Adenosine deaminase, in addition to adenosine breakdown, stimulates release of excitatory amino acids and is necessary to the coupling of A1 adenosine receptors and heterotrimeric G proteins.. ...
1. Cawley JC, Burns GF, Hayhoe FG. A chronic lymphoproliferative disorder with distinctive features: a distinct variant of hairy-cell leukaemia. Leuk Res. 1980;4(6):547-59 2. Matutes E, Wotherspoon A, Catovsky D. The variant form of hairy-cell leukaemia. Best Pract Res Clin Haematol. 2003;16(1):41-56 3. Robak T. Hairy-cell leukemia variant: recent view on diagnosis, biology and treatment. Cancer Treat Rev. 2011;37(1):3-10 4. Matutes E, Martínez-Trillos A, Campo E. Hairy cell leukaemia-variant: Disease features and treatment. Best Pract Res Clin Haematol. 2015;28(4):253-63 5. Jain P, Pemmaraju N, Ravandi F. Update on the biology and treatment options for hairy cell leukemia. Curr Treat Options Oncol. 2014;15(2):187-209 6. Swerdlow S, Campo E, Harris NL. et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (4th ed.). Lyon: International Agency for Research on Cancer (IARC). 2008:188-90 7. Tiacci E, Trifonov V, Schiavoni G, Holmes A, Kern W, Martelli MP. et al. BRAF ...
The aminopyrimidopyrimidine nucleoside 4-amino-8-(beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (APP), which was previously shown to possess experimental antitumor and antiviral activity, was metabolized within WI-L2 human lymphoblastoid cells to a derivative identified as the beta-D-ribonucleotide (APP-MP). In a subline of WI-L2 cells deficient in adenosine kinase, this metabolite was not formed and APP was not cytotoxic, suggesting that APP is converted by adenosine kinase to its 5-monophosphate. Because no evidence of di- or triphosphates was seen, the monophosphate appeared to be the active species. Treatment of WI-L2 or L1210 cells with APP (10 microM) for 30 min caused extensive depletion of both purine and pyrimidine ribonucleotides. Purine and pyrimidine deoxyribonucleotides were also depleted. Cells were not protected from the cytotoxicity of APP by hypoxanthine plus uridine, but uridine plus adenosine plus 2-deoxycoformycin gave considerable protection. This result was ...
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The targeted agent, Zelboraf® (vemurafenib), which is approved for the treatment of melanoma, provided high anti-cancer activity among patients with hairy-cell leukemia that had stopped responding to prior therapies. These results were recently published in the New England Journal of Medicine.. Hairy-cell leukemia is a type of cancer in which too many abnormal immune cells are produced. It is considered a slow-growing type of leukemia that occurs more commonly in older men. The cancer cells have a "hairy" appearance under the microscope.. A genetic mutation referred to as the BRAF V600E mutation is thought to be an involved the excessive replication of hairy cell leukemia, as it is a common mutation in this type of cancer. Zelboraf binds to a specific site in cells that blocks the excessive replication caused by the BRAF V600E mutation.. Researchers from Italy and the United States conducted clinical trials to evaluate Zelboraf among patients with hairy cell leukemia that had stopped responding ...
Hereditary deficiency of the enzyme adenosie deaminase (adenosine aminohydrolase, EC 3.5.4.4) results in an immunodeficiency syndrome characterized by a marked reduction in circulating lymphocytes. We have administered 2-deoxycoformycin, a potent inhibitor of adenosine deaminase, to a patient with a lymphoproliferative malignancy. The clinical consequences of pharmacologic inhibition of adenosine deaminase activity included an abrupt decrease in the lymphocyte count, abnormalities of renal and hepatic function, and hemolytic anemia. The plasma concentrations of adenosine and deoxyadenosine rose to peak values of 13 microM and 5 microM, respectively, and erythrocyte dATP levels increased to 110 pmol/10(6) cells over 9 days. There was a corresponding decrease in erythrocyte ATP levels from 128 to , 6 pmol/10(6) cells. A similar profound reductin in ATP occurred in the erythrocytes of a second patient. The rapid and unexpected depletion of ATP associated with dATP accumulation may account, at ...
TY - JOUR. T1 - Structural basis for the growth factor activity of human adenosine deaminase ADA2. AU - Zavialov, Anton V.. AU - Yu, Xiaodi. AU - Spillmann, Dorothe. AU - Lauvau, Grégoire. AU - Zavialo, Andrey V.. PY - 2010/4/16. Y1 - 2010/4/16. N2 - Two distinct adenosine deaminases, ADA1 and ADA2, are found in humans. ADA1 has an important role in lymphocyte function and inherited mutations in ADA1 result in severe combined immunodeficiency. The recently isolated ADA2 belongs to the novel family of adenosine deaminase growth factors (ADGFs), which play an important role in tissue development. The crystal structures of ADA2 and ADA2 bound to a transition state analogue presented here reveal the structural basis of the catalytic/signaling activity of ADGF/ADA2 proteins. In addition to the catalytic domain, the structures discovered two ADGF/ADA2-specific domains of novel folds that mediate the protein dimerization and binding to the cell surface receptors. This complex architecture is in sharp ...
Making cancer remission a reality. A new drug designed using an innovative technique called molecular modeling --2-chlorodeoxyadenosine--is long on syllables but succinct in its effectiveness. A recent study shows it may trounce a rare form of cancer in only one treatment.. The cancer is known as hairy-cell leukemia. It causes smooth infection-fighting white blood cells in the bone marrow to be replaced with abnormal cells sprouting hairlike projections. It is often fatal.. In the study, 12 patients admitted to the Scripps Clinic in California, were given week-long infusions of very small amounts of the new drug. Eleven had complete remissions, meaning total disappearance of the disease. At present, the average remission continues at 18 months, with one patient going on four years leukemia-free. None of the patients have had relapses (New England Journal of Medicine, April 19, 1990).. "The response so far has been promising. Very rarely do you hear of long-lasting cancer remissions following one ...
Dynamics of the metallo-beta-lactamase from Bacteroides fragilis in the presence and absence of a tight-binding inhibitor.: A significant determinant for the br
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The objective of this exercise is to start with the simple Kronig-Penney model and understand formations of bands and gaps in the dispersion relation that describes the motion of carriers in 1D periodic potentials. The second exercise examines the behavior of the bands at the Brillouin zone boundaries. Finally, a simplified tight-binding approach for 1D lattice has to be derived as part of the third exercise..
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PEMBROKE, ONTARIO--(Marketwired - March 18, 2016) - After just 4 years, Trillium Health Partners, with 850 hospital beds and many operating suites, ended their 10 year contract with SteriPro and brought sterilization of instruments back in house. This is the same private company that the Pembroke Regional Hospital has signed...
Looking for online definition of adenosine deaminase in the Medical Dictionary? adenosine deaminase explanation free. What is adenosine deaminase? Meaning of adenosine deaminase medical term. What does adenosine deaminase mean?
... (ADA) is a protein produced by cells throughout the body and is associated with the activation of lymphocytes, a type of white blood cell that plays a role in the immune response to infections. The adenosine deaminase test may be used to help determine whether a person has a Mycobacterium tuberculosis infection (TB) of the lining of the lungs (pleurae).
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This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions ...
Contact Us. Tel:732-484-9848. Fax:888-484-5008. Email:[email protected]. Add:1 Deer Park Dr, Suite Q,. Monmouth Junction, NJ 08852, USA. ...
Contact Us. Tel:732-484-9848. Fax:888-484-5008. Email:[email protected]. Add:1 Deer Park Dr, Suite Q,. Monmouth Junction, NJ 08852, USA. ...
(2-5)-3-deoxyadenosine triphosphate-3-deoxyadenosine monophosphate: dimers & trimers of the (p3dA) part of above cpd were also synthesized in first source
Pegademase bovine is a man-made form of an enzyme called adenosine deaminase (ADA). ADA is important in the body for preventing the buildup of certain proteins harmful to the white blood cells that help your body fight infections. Pegademase bovine is used to replace ADA in people with severe combined immunodeficiency...
This event should not be confused with the Powder River Expedition (1865). The Big Horn Expedition, or Bighorn Expedition, was a military operation of the United States Army against the Sioux, and Cheyenne Indians in Wyoming Territory and Montana Territory. Although soldiers destroyed one Cheyenne and Oglala Sioux village, the expedition solidified Lakota Sioux and northern Cheyenne resistance against the United States attempt to force them to sell the Black Hills and live on a reservation, beginning the Great Sioux War of 1876. The Treaty of Fort Laramie (1868) granted the Lakota Sioux and their northern Cheyenne allies a reservation, including the Black Hills, in Dakota Territory and a large area of "unceded territory" in what became Montana and Wyoming. Both areas were for the exclusive use of the Indians, and whites except for government officials, were forbidden to trespass. In August, 1874, soldiers of the Black Hills Expedition under Lieutenant Colonel George A. Custer confirmed the ...
Synonyms for adenosine deaminase conjugated with polyethylene glycol in Free Thesaurus. Antonyms for adenosine deaminase conjugated with polyethylene glycol. 2 words related to adenosine: biochemistry, nucleoside. What are synonyms for adenosine deaminase conjugated with polyethylene glycol?
ADAR - ADAR (Myc-DDK-tagged)-Human adenosine deaminase, RNA-specific (ADAR), transcript variant 4 available for purchase from OriGene - Your Gene Company.
Pulmonology Advisor offers the latest asthma, COPD, lung cancer, pneumonia news articles for pulmonologists and the healthcare community. Download the FREE app now.
this is a serious disease that happens when your bodys defenses stop working because of a problem with your genes. you get ada-scid only if both your parents pass on a copy of a faulty gene to you.
The IUPHAR/BPS Guide to Pharmacology. pentostatin ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs.
0034] Risk Adjusted Discount Cash Flow (DCF) module 44 employs a modification of the industry accepted discounted cash flow (DCF) analysis which values an investable entity (e.g., company) based on current transparent operating performance. Generally, analysis of an investable entity under existing DCF focuses on operating performance by identifying cash flow and estimated growth potential. However as a modification to the existing DCF process, the risk adjusted DCF analysis of the present application emphasizes analysis of the volatility of the investable entity. Particularly the present system and methodology views an investable entity as not only having operating functions (i.e. manufacturing and selling products and/or services) which are used to generate the cash flow and growth estimates, but also as having a banking operation aspect (i.e. providing capital to suppliers, buying debt or issuing debt, determining a dividend rate, buying equity and issuing equity, acquiring assets such as ...
3099-52-3 - JVWOCHRRAWHKLT-UHFFFAOYSA-N - Nicametate [INN:BAN:DCF] - Similar structures search, synonyms, formulas, resource links, and other chemical information.
La organización de FIB Heineken 2010, ha dado a conocer los horarios y la distribución por escenarios de su decimosexta edición.. Jueves 15 ...
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Major histocompatibility (MHC)-restricted, human immunodeficiency virus type one (HIV-1)-specific, cytotoxic T lymphocytes (CTLs) were detected in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected individuals. Using a system of autologous B and T lymphoblastoid cell lines infected with recombinant vaccinia vectors (VVs) expressing HIV-1 gene products, we were able to detect HIV-1-specific cytolytic responses in the PBMCs of 88% of HIV-1-seropositive hemophiliac patients in the absence of in vitro stimulation. These cytolytic responses were directed against both HIV-1 envelope and gag gene products. The responses were resistant to natural killer (NK) cell depletion and were inhibited by monoclonal antibodies (MoAbs) to the T cell receptor, CD8 surface antigens, and MHC class I antigens, suggesting a classical MHC class I restricted, virus-specific CTL response.
Iodotubercidin is an adenosine kinase inhibitor that through its ability to increase levels of endogenous adenosine can enhance adenosines receptor-mediated effects. We investigated whether iodotubercidin can inhibit [3H]adenosine accumulation by inhibiting transport processes in addition to inhibition of intracellular trapping of labeled adenine nucleotides. Under conditions in which extensive metabolism of intracellular adenosine was present, [3H]adenosine accumulation by DDT1 MF-2 cells was almost completely inhibited by iodotubercidin and the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)-adenine or by the nucleoside transport inhibitor nitrobenzylthioinosine. By using similar conditions, [3H]adenosine accumulation was significantly greater in Na+ buffer than in buffer containing N-methyl-D-glucamine in place of Na+; however, this effect may be explained by an observed 40% inhibition of adenosine kinase activity by N-methyl-D-glucamine. By using uptake intervals of 14 sec to ...
Introduction: Adenosine deaminase (ADA) is one of the major enzymes in purine metabolism. There are 2 isoforms of ADA: ADA1 and ADA2. The principal action of this enzyme is in immune system cells, the level of ADA in T-cell is 5-20 fold more than B-cell. The level of ADA elevates as the lymphocyte (T-cell) activity increase. Tuberculosis has been studied extensively with relevance of ADA levels and apart from serum, various body fluids as pleural, peritoneal, cerebrospinal fluids of patients of Pleural effusion, Ascitis and Tubercular Meningitis, has also its raised levels. Measurement of the level of (ADA) enzyme in body fluids is a helpful diagnostic tool. Aim: To study the serum Adenosine Deaminase Activity in patients of Pulmonary Tuberculosis and to evaluate the diagnostic significance of ADA activity in serum in these patients. Material and Methods: Present study was carried out in fifty patients of both the sexes with different ages suffering from Pulmonary Tuberculosis attending OPD and ...
A Continuous Method for the Estimation of Adenosine Deaminase Catalytic Concentration in Pleural Effusions with a Hitachi 705 Discrete ...
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During 2 years, we enrolled 25 patients diagnosed with typewriter tinnitus and evaluated the types of AICA loops in the IAC and CPA and the types of neurovascular contact by using 3T 3D T2-VISTA imaging in 15 patients. When we compared the symptomatic sides of patients with typewriter tinnitus (group 1) with the asymptomatic sides of those with typewriter tinnitus (group 2) and healthy controls (group 3), the difference was not statistically significant (Table). However, considering that in a previous study, type II and type III AICA loops were observed in 38.0% of 332 patients with ipsilateral auditory symptoms,13 our results, which demonstrated that 56.3% of group 1 and 18.8% of group 3 had type II and III AICA loops, showed a definite tendency toward type II and III AICA loops on the symptomatic sides of subjects with typewriter tinnitus. Moreover, the 3 groups in this study had significantly different (Table) neurovascular contact types. In group 1, 68.8% of the subjects showed type II or ...
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Introduction: The use of biological markers in the diagnosis of tuberculous pleural effusion (TPE) is a breakthrough. Demonstration of elevated levels of Pleural fluid Adenosine deaminase (ADA), interferon-gamma (IFN-γ), tuberculous proteins/antibodies lysozme etc. have been proposed. Adenosine deaminase (ADA) estimation in pleural fluid has been shown as reliable biomarker specially when there is suspicion of tuberculosis. Detection of mycobacterium DNA by PCR is also a proposed test3,4. However India being a developing country with much of its people below poverty line cannot afford expensive tests like ELISA, PCR, IFN-γ. Hence, there is need for relatively cheaper and simple tests with feasibility and sensitivity going hand-in-hand5 TPE being proposed to be a delayed hypersensitive reaction and lymphocytes play a major role in the pathogenesis. With ,50% lymphocytes in the pleural fluid, combined criterion of lymphocyte to neutrophil ratio of ,0.75 with a raised ADA level increased the ...
Adenosine deaminase (ADA) is a purine catabolic enzyme ubiquitous in mammalian tissue which catalyzes deamination of both adenosine and 2-deoxyadenosine to inosine and 2-deoxyinosine respectively. ...
Synonyms for -a in Free Thesaurus. Antonyms for -a. 11 synonyms for A: angstrom, angstrom unit, antiophthalmic factor, axerophthol, vitamin A, deoxyadenosine monophosphate, adenine, amp, ampere, group A, type A. What are synonyms for -a?
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Kepareng matur dhumateng …….. [bapak/ibu/simbah/kang mas/dll], kulo ngaturaken sugeng riyadi, ngaturaken sedaya lepat nyuwun pangapunten, kaping tiga nyuwun donga pangestunipun supados kula saged dados putra ingkang sholeh, migunani dhateng agami, nusa, bangsa, lan nagari, lancar anggenipun pados ilmu ingkang manfaat, gampil anggenipun pados rejeki ingkang halal lan thayyib, saha sukses nglampahi gesang ing donya lan akhirat ...
In enzymology, a 8-oxocoformycin reductase (EC 1.1.1.235) is an enzyme that catalyzes the chemical reaction coformycin + NADP+ ... The systematic name of this enzyme class is coformycin:NADP+ 8-oxidoreductase. This enzyme is also called 8-ketodeoxycoformycin ... deoxycoformycin and coformycin". Biochemistry. 27 (15): 5790-5. doi:10.1021/bi00415a059. PMID 3052586. Molecular and Cellular ... displaystyle \rightleftharpoons } 8-oxocoformycin + NADPH + H+ Thus, the two substrates of this enzyme are coformycin and NADP+ ...
Coformycin was also described as a adenosine deaminase inhibitor but is alleged to be an antibiotic. Adenosine deaminase ...
... coformycin MeSH D13.570.800.453 --- guanosine MeSH D13.570.800.453.500 --- nucleoside q MeSH D13.570.800.573 --- inosine MeSH ... coformycin MeSH D13.570.685.350.200.700 --- pentostatin MeSH D13.570.685.705 --- thymidine MeSH D13.570.685.705.875 --- ...
Coordinated Biosynthesis of the Purine Nucleoside Antibiotics Aristeromycin and Coformycin in Actinomycetes. Gudan Xu, Liyuan ... Coordinated Biosynthesis of the Purine Nucleoside Antibiotics Aristeromycin and Coformycin in Actinomycetes ... Coordinated Biosynthesis of the Purine Nucleoside Antibiotics Aristeromycin and Coformycin in Actinomycetes ... Coordinated Biosynthesis of the Purine Nucleoside Antibiotics Aristeromycin and Coformycin in Actinomycetes ...
The injection of coformycin (1.3 or 4 nmol/side) also decreased the histamine release for 1 h from 1 h after the injection (Fig ... Coformycin at 4 nmol/side also induced a significant increase in NREM sleep, by 2.0- and 1.8-fold during the third and fourth ... A-B) Time courses of NREM and REM sleep in rats administered adenosine (Ado) at 4.5 nmol/side (A) or coformycin (CF) at 4 nmol/ ... On the other hand, coformycin increased the total amount of NREM sleep weakly at a dose of 1.3 nmol/side and 1.9- and 1.7-fold ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Coformycin. A ribonucleoside antibiotic synergist and adenosine deaminase inhibitor isolated from Nocardia interforma and ...
... coformycin (5 μg/ml), desferrioxamine (0.6 μg/ml), and butylated hydroxytoluene (100 μM). εA, εC, 8oxoG, and Hx were quantified ...
3. SAR of 3-(Carboxyarylalkyl)coformycin Aglycon Analogues"; J. Med. Chem.;2000; 43; pp. 1508-1518. cited by other.. Kato, ... 4. Further N3-Substituted Coformycin Aglycon Analogues: N3-Alkylmalonates as Ribose 5-Monophosphate Mimetics; J. Med. Chem.; ...
Purine Catabolism in Isolated Hepatocytes : Influence of Coformycin Georges Van den Berghe, Françoise Bontemps, Henri-Géry Hers ...
In enzymology, a 8-oxocoformycin reductase (EC 1.1.1.235) is an enzyme that catalyzes the chemical reaction coformycin + NADP+ ... The systematic name of this enzyme class is coformycin:NADP+ 8-oxidoreductase. This enzyme is also called 8-ketodeoxycoformycin ... deoxycoformycin and coformycin". Biochemistry. 27 (15): 5790-5. doi:10.1021/bi00415a059. PMID 3052586. Molecular and Cellular ... displaystyle \rightleftharpoons } 8-oxocoformycin + NADPH + H+ Thus, the two substrates of this enzyme are coformycin and NADP+ ...
ANALOGUES OF COFORMYCIN AND THEIR USE FOR TREATING PROTOZOAN PARASITE INFECTIONS. This invention relates to compounds that are ... analogues of coformycin, pharmaceutical compositions containing the compounds, and methods of using the compounds for treating ...
Coformycin was also described as a adenosine deaminase inhibitor but is alleged to be an antibiotic. Adenosine deaminase ...
... plus coformycin to inhibit endogenous adenosine deaminase). Antigen-specific T-cell proliferation was similarly inhibited by ...
... coformycin, and pyrazomycin. These agents had too much toxicity to be clinically useful (and the antiviral activity of them may ...
Inhibited by Cu(2+) and Hg(2+), coformycin, deoxycoformycin (dCF), 2-deoxyadenosine, 6-methylaminopurine riboside, 2-3-iso- ...
Synonyms: coformycin, CHEBI:16213, CHEBI:141697, AIDS031186, C11H16N4O6, NSC 277817, AIDS-031186, CID25447, NSC277817, LS-77849 ... Coformycin), Coformycin2-(8-Hydroxy-7,8-dihydro-6H-imidazo[4,5-d][1,3]diazepin-3-yl)-5-hydroxymethyl-tetrahydro-furan-3,4-diol ...
Coformycin. 21. + 19. Antigens, CD56. 20. + 20. Piperazines. 18. + 21. GATA1 Transcription Factor. 18. + ...
TY - JOUR. T1 - Modulation of arabinosyladenine metabolism by 2-deoxycoformycin in the therapy of human acute leukemia.. AU - Plunkett, W.. AU - Nowak, B.. AU - Feun, Lynn G. AU - Benjamin, R. S.. AU - Keating, M.. AU - Freirich, E. J.. PY - 1984/1/1. Y1 - 1984/1/1. UR - http://www.scopus.com/inward/record.url?scp=0021305169&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0021305169&partnerID=8YFLogxK. M3 - Article. C2 - 6372382. AN - SCOPUS:0021305169. VL - 165 Pt B. SP - 345. EP - 350. JO - Advances in Experimental Medicine and Biology. JF - Advances in Experimental Medicine and Biology. SN - 0065-2598. ER - ...
PubMed comprises more than 29 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
... coformycin, PALA, hydroxyurea (HU), vincristine (VCR). colcemid (COL) and actinomycin D (AMD). Recently, we have studied SEWA ...
... coformycin, PALA, hydroxyurea (HU), vincristine (VCR). colcemid (COL) and actinomycin D (AMD). Recently, we have studied SEWA ...
Characterization of the coformycin biosynthetic gene cluster Edited by Squire J. Booker, The Pennsylvania State University, ...
Characterization of the coformycin biosynthetic gene cluster Edited by Squire J. Booker, The Pennsylvania State University, ...
Coformycin: 6*Pentostatin: 403*adechlorin: 1. *2-deoxycoformycin 5-phosphate. *8-ketodeoxycoformycin ...
Adenosine Deaminase Inhibitors, Child, Coformycin, adverse effects, analogs & derivatives, Humans, Leukemia, Lymphoid, drug ...
Adult, Aged, Aged, 80 and over, Antineoplastic Agents, adverse effects, therapeutic use, Bone Marrow, pathology, Coformycin, ... Antineoplastic Agents, adverse effects, therapeutic use, Coformycin, analogs & derivatives, Combined Modality Therapy, Humans, ...
... deoxy coformycin alone and in combination with 9 beta d arabinofuranosyl adenine ... ec 3.3.1.1 activity deoxy atp accumulation and competence of thymocyte and spleen leukocyte response to mitogens in coformycin ...