Disease relevance of AMT

• Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic hyperglycinemia [1].
• Radiolabeled membrane proteins were solubilized with either sodium deoxycholate (DOC) or NP-40 detergents, precipitated with AMT, and Staphylococcus aureus Cowan strain I, and analyzed by sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis (SDS-PAGE) [2].
• The formation of 3'-amino-3'-deoxythymidine (AMT) in patients receiving 3'-azido-3'-deoxythymidine (zidovudine) and the potential role of this metabolite in zidovudine-induced toxicity was recently demonstrated by our laboratory [3].
• The substantial levels of AMT in the plasma of patients after zidovudine administration suggests that this catabolite may affect the pharmacodynamic properties of zidovudine in relation to its activity against human immunodeficiency virus replication and cytotoxicity to host cells [4].
• Given the diverse chemical nature of the scavengers and their wide range of concentrations utilized, these findings are evidence for the involvement of a Type I photosensitization in the induction of DNA single-strand breaks by photoactivated AMT [5].

Psychiatry related information on AMT

• There was a highly significant (P less than .001; slope = 1.2) linear correlation between the AMT-inhibiting potencies of AMPH analogs and their potencies in stimulating locomotor activity in rodents [6].
• We used a novel EEG-based measure (the Awake Maintenance Task, AMT) to determine objectively whether patients on chronic, stable AED therapy had impaired ability to maintain wakefulness [7].
• 3. Compared with patients not taking diuretics, diuretic-users were older (mean +/- s.d., 70 years +/- 14 vs 54 +/- 20, P < 0.001), had lower abbreviated mental test scores (AMT scores seven or less, 21% vs 9%, chi 2 = 3.48, P = 0.06) and were prescribed more drugs (5.0 +/- 2.4 vs 3.2 +/- 2.0, P < 0.001) [8].
• Comparison of these results with those of a previous study in which the AMT and PMT regions were removed jointly (Aggleton and Mishkin 1983) suggests that damage in either region can induce a memory loss but that combined damage to both is required to produce a full-blown amnesia [9].
• Resting (RMT) and active (AMT) motor threshold, cortical and peripheral silent period, evaluation of motor imagery, reaction time and premovement facilitation of motor evoked potential (MEP) were tested bilaterally using TMS [10].

High impact information on AMT

• Intact HeLa cells were treated with AMT, and high molecular weight RNA was isolated under denaturing conditions from nuclei or from subnuclear fractions [11].
• Brief intrapulmonary infusions of AG (140 mg), AMT (0.12 mg), and EIT (0.12 mg) increased basal PVR by 82, 69, and 77%, respectively (P < 0.05) [12].
• RNA blot analysis using polyacrylamide gels demonstrated that RNA from AMT-treated virus had a slowed migration, consistent with it being a single-stranded circle [13].
• Using 1.0 Joule/cm2 UVA, the lowest dose of S-59, AMT and 8-MOP required to reduce the number of T cells to the limit of detection was 0.05 micromol/L, 1.0 micromol/L, and 10.0 micromol/L, respectively [14].
• (2) Cytokine synthesis: Treatment with 1.9 Joules/cm2 UVA and 150 micromol/L S-59 or AMT completely inhibited synthesis of the cytokine IL-8 by contaminating leukocytes during 5 days of platelet storage [14].

Chemical compound and disease context of AMT

• AMT catalepsy and hypokinesia: interaction with morphine and cocaine [15].
• AMT was soon superseded by its 10-methyl congener, methotrexate (MTX), based on toxicity considerations; MTX remains, with one limited exception, the only antifolate anticancer agent in clinical use to this date [16].
• In addition, beta-D-uridine also protected human CFU-GM against toxicity of the in vivo AZT metabolite, 3'-amino-3'-deoxythymidine (AMT) [17].
• Fourteen patients with TD, all but one also having tardive akathisia, were evaluated on presynaptically acting dopamine-depleting drugs, reserpine, TBZ, and AMT [18].
• Amiodarone-induced thyrotoxicosis (AMT) is a life-threatening condition, the appropriate management of which is achieved by identifying its different subtypes [19].

Biological context of AMT

• Mutation analysis was performed by sequencing all GLDC, GCSH and AMT exons [20].
• In plants, the AMT gene family can be subdivided according to their amino-acid sequences into three subfamilies: a large subfamily of AMT1 genes and two additional subfamilies each with single members (LeAMT1;3 from tomato and AtAMT2;1 from Arabidopsis thaliana) [21].
• 4'-aminomethyl-4,5',8--trimethyl-psoralen (AMT) has a high affinity for both RNA and DNA and can be shown to cause mitotic abortion when centriolar regions of prophase PTK2 cells and reacted with AMT and 365-nm laser light [22].
• These large variations of AMT levels as a function of P450 suggest that major interindividual differences may be observed in the pharmacokinetics and formation of this metabolite that may affect the pharmacodynamic properties of zidovudine [3].
• Globin mRNA stability was not affected by either 100 microM AZT or AMT, as measured after blockage of transcription with actinomycin D [23].

Anatomical context of AMT

• These cells were labeled with the N-hydroxysuccinimide ester of [3H]aminopterin (AMT), the isolated plasma membrane alkaline washed to remove nonintegral membrane proteins, detergent-solubilized, and RFT-separated on an anti-AMT antibody-protein G-Sepharose column followed by preparative SDS-polyacrylamide gel electrophoresis [24].
• A cross-adsorption analysis demonstrated that each of the three cell lines differed in their adsorbing efficiency to remove AMT antibodies reactive with the reciprocal cell lines [2].
• The conserved family of AMT/Rh proteins facilitates ammonium transport across animal, plant, and microbial membranes [25].
• These differences include transport at the blood-brain barrier and the presence of a large unmetabolized pool of AMT, precluding the method from providing the absolute serotonin synthesis rate [26].
• Studies using human hematopoietic progenitor cells demonstrated that AMT was 5- to 7-fold more toxic to human colony-forming units granulocyte-macrophage and burst-forming units erythroid than was AZT [27].

Associations of AMT with chemical compounds

• Using functional complementation of yeast mutants, it has been possible to identify a new class of membrane proteins, the ammonium transporter/methylammonium permease (AMT/MEP) family, that mediate secondary active ammonium uptake in eukaryotic and prokaryotic organisms [21].
• The zidovudine/AMT plasma peak concentration and area under the concentration-time curve ratios were approximately 8 and 5, respectively [4].
• In addition to unchanged drug and its 5'-O-glucuronide (zidovudine glucuronide), two novel catabolites of zidovudine were detected as 3'-amino-3'-deoxythymidine (AMT), and its 5'-O-glucuronide (GAMT) [4].
• AMT glucuronide was not detected in urine or plasma, and only low levels of this catabolite were detected in bile [4].
• However, although AMT is similar to 2-deoxyglucose with regard to an irreversible pool of tracer uptake, there are important differences between the two tracers and how the model can be applied [26].

Regulatory relationships of AMT

• The enhanced NO production by IL-15 was inhibited by AMT, an iNOS-specific inhibitor [28].
• AMT (100 microM) did not affect L-arginine transport studied by electrophysiological techniques in Xenopus laevis oocytes expressing either the human cationic amino acid transporter hCAT-1 or hCAT-2B [29].

Other interactions of AMT

• Our results indicate that AZT reduction to AMT by human liver microsomes involves both b5 and P450 enzymes plus their corresponding reductases [30].
• Pre-treatment of rats with beta-naphthoflavone and ethanol (CYP1A and CYP2E1 inducers, respectively) had no effect on AMT formation [31].
• Aminoguanidine (AG), 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), NG-monomethyl-L-arginine (L-NMMA), and Nomega-nitro-L-arginine (L-NNA) inhibited NOS activity in tumor tissues by 18, 14, 11 and 13%, respectively [32].
• We suggest that the GP assay supplemented with AMT is the method of choice for detection of MPO deficiency, particularly partial deficiency [33].
• In addition to the CYP3A4 inhibitors ketoconazole, fluconazole, indinavir, ritonavir, and saquinavir, metyrapone strongly inhibited AMT formation [34].

Analytical, diagnostic and therapeutic context of AMT

• Electron microscopy of purified RNA following treatment of virus with the psoralen reagent 4'-aminomethyltrioxsalen (AMT) revealed circles with lengths corresponding to the individual segments [13].
• The degree of PCR amplification inhibition correlated with the level of adduct formation (S-59 > AMT > 8-MOP) [14].
• Alpha[C-11]methyl-L-tryptophan (AMT) is an analog of tryptophan used with positron emission tomography for the measurement of serotonin synthesis in humans [26].
• These catabolites were identified as 3'-amino-3'-deoxythymidine (AMT) by fast atom bombardment mass spectrometry and 3'-amino-3'-deoxythymidine glucuronide (GAMT) through specific enzymatic hydrolysis [27].
• High-performance liquid chromatography analyses of the extracellular medium and cell extracts revealed the presence of unchanged dimer, AZT, 3'-azido-3'-deoxy-5'-beta-D-glucopyranosylthymidine (GAZT), 3'-amino-3'-deoxythymidine (AMT), ddI, and a previously unrecognized derivative of the dideoxyribose moiety of ddI, designated ddI-M [35].

References