Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The t(2;5) generates a chimeric NPM-ALK transcript encoded by the nucleophosmin NPM gene fused to the anaplastic lymphoma kinase gene ALK. Using a reverse transcriptase nested polymerase chain reaction assay we have detected NPM-ALK transcripts within CD30+ primary cutaneous lymphoma and lymphomatoid papulosis (LP). The t(2;5) was identified in 4 out of 9 CD30+ anaplastic lymphomas and in 1 out of 4 CD30+ pleomorphic lymphomas. Moreover, the t(2;5) was detected in 3 out of 10 LPs. All NPM-ALK-positive lymphomas and 1 NPM-ALK-positive LP exhibited a clonal rearrangement of the T cell receptor gamma-chain gene. The t(2;5) was detected in 2 cases of LP without other evidence for a clonal lymphoid population. To identify cells carrying the t(2;5) translocation, we used immunohistochemistry to detect the ALK-encoded p80 protein and in situ hybridization for the specific detection of NPM-ALK transcripts. Both p80 protein and NPM-ALK transcripts were expressed by anaplastic or large CD30+ lymphoma cells with positive NPM-ALK amplification. The presence of t(2;5) in a subset of CD30+ cutaneous lymphoma and LP may indicate a common pathogenesis with a subset of anaplastic nodal lymphoma.
...
PMID:Detection of t(2;5)(p23;q35) translocation by reverse transcriptase polymerase chain reaction and in situ hybridization in CD30-positive primary cutaneous lymphoma and lymphomatoid papulosis. 870 87

Two novel classes of pyrrolobenzothiazepinones and pyrrolobenzoxazepinones were investigated as potential anti-AIDS drugs. These compounds were found to inhibit HIV-1 reverse transcriptase (RT) enzyme in vitro and to prevent HIV-1 cytopathogenicity in T4 lymphocytes, without appreciable activity on HIV-2 cytopathic effects, and against HBV as well as calfthymus DNA alpha-polymerase. Their potency is influenced by substituents at position 6 and on the fused aromatic ring. Specifically, small lipophilic substituents at C-6 were preferred, whereas substitutions on the benzo-fused ring were found to be detrimental to activity, with respect to the unsubstituted compounds. Modification of the pie-system at C-6 is well tolerated, although the replacement of the benzo-fused with a [2,3]naphtho-fused ring leads to a less active compound. Maximum potency and specificity is achieved with a phenyl and an ethyl group at position 6 of the pyrrolobenzoxazepinone system. In the enzymatic assay the oxazepinone derivative (+/-)-6-ethyl-6-phenylpyrrolo[2,1-d][1,5] benzoxazepin-7(6H)-one 16e (IC50 = 0.25 microM) was found to be more potent than nevirapine (IC50 = 0.5 microM), tested in the same experimental conditions using rC.dG as a template-primer. In cell culture assay benzoxazepine 16e was active against HIV-1, both wild type and AZT-sensitive, and HIV-1 (IIIB) strains, but not against HIV-2. In enzyme assay although 16e inhibited HIV-1 RT, it was inactive against the nevirapine-resistant recombinant RT Y181C at 50 microM. Molecular modeling studies suggest that these derivatives present a 3D pharmacophoric arrangement similar to that of other non-nucleoside inhibitors such as nevirapine.
...
PMID:Pyrrolobenzothiazepinones and pyrrolobenzoxazepinones: novel and specific non-nucleoside HIV-1 reverse transcriptase inhibitors with antiviral activity. 870 96

We investigated TEL/AML1 fusion mRNA in 108 children with acute lymphoblastic leukemia (ALL) (86 B-lineage ALL, 15 T-ALL, two mixed lineage ALL, and five other phenotypes) using reverse transcriptase-polymerase chain reaction (RT-PCR). TEL/AML1 transcripts were found in 14 patients (13%) including three relapsed patients, and were unexceptionally limited to B-lineage ALL patients. The incidence of TEL/AML1 transcripts among B-lineage ALL was 16% (14/86). The reciprocal AML1/TEL transcripts were detected in 12 (86%) of the 14 cases expressing a TEL/AML1 transcript. In three cases, the TEL gene was fused to exon 3 of the AML1 gene, and to exon 2 in the remaining cases. To evaluate the amount of TEL/AML1 molecules for the quantification of a minimal residual disease (MRD), a plasmid vector which contained either a long TEL/AML1 PCR product (464 bp) or a short one (425 bp) was used as a competitor. We amplified RNAs obtained from bone marrow (BM) at complete remission or from peripheral blood stem cell (PBSC) harvests in two representative cases. For one PBSC harvest showing a positive result, a competitive PCR was carried out to quantify the amount of MRD. A 1:4 dilution series of competitor vectors was constructed, and each vector was added to a PCR reaction which contain a constant amount of cDNA obtained from the PBSC harvest. An equivalent point was compared to that of corresponding samples at diagnosis. Using this method, MRD in the PBSC harvest was 3.9:10(3). Our results elucidated the incidence, lineage-specificity, and variant forms of TEL/AML1 fusion transcripts in childhood ALL. Since the percentage of other chromosomal translocations in childhood ALL is not more than 5%, TEL/AML1 transcript would be the most feasible clone-specific marker for these patients. In addition, our method could be a powerful tool for quantification of the TEL/AML1 transcript and for the detection of MRD.
...
PMID:Detection and quantification of TEL/AML1 fusion transcripts by polymerase chain reaction in childhood acute lymphoblastic leukemia. 875 64

Plants contain complex actin gene families composed of several diverse and ancient subclasses of genes. One Arabidopsis actin gene subclass represented by the ACT4 and ACT12 genes has been isolated and characterized. Both actin genes have typical plant actin gene structures, including three small introns interrupting the coding region and an intron within the mRNA leader. Their encoded proteins differ from each other in only one amino acid, whereas they differ in 3-10% of their amino acids from the other five Arabidopsis actin subclasses. They also share a few small blocks of DNA sequence homology in the 5' flanking region near their TATA boxs, but not in their introns, 3' flanking regions, or degenerate positions within codons. Southern analysis with gene-specific probes from 5' flanking sequences showed that both were single copy genes in the genome. Both RNA gel blot analysis with 3' gene-specific probes and reverse transcriptase-mediated polymerase chain reactions (RT-PCR) with gene-specific primers detected low levels of ACT4 and ACT12 mRNAs in flowers and very high levels in pollen. The RT-PCR detected very low levels of these mRNAs in the vegetative organs. The 5' region from both genes, including the promoter region, TATA box, the sequence for the mRNA leader and its intron, and the first 19 actin codons, was fused to a beta-glucuronidase (GUS) reporter gene. Expression of the GUS fusions were examined histochemically in 40 independent transgenic Arabidopsis plants. Expression of the ACT4/GUS fusion was restricted to young vascular tissues, tapetum, and developing and mature pollen. Similar expression patterns in these tissues and cell types were observed for ACT12/GUS fusion, yet unlike ACT4, ACT12 was also strongly expressed in the root cap and in a ring of pericycle tissues during lateral root initiation and early development. The unique expression patterns of the ACT4/ACT12 actin gene subclass are discussed in light of recent data on the other expressed members of the Arabidopsis actin gene family.
...
PMID:The Arabidopsis thaliana ACT4/ACT12 actin gene subclass is strongly expressed throughout pollen development. 877 77

Hammerhead ribozymes have been shown to specifically suppress the expression of target genes in various cells, but their in vivo cleavage products have seldom been directly detected. A hammerhead ribozyme sequence was designed to cleave the phosphodiester bond just 3' to the GUC of SalI site of M13mp 18. The ribozyme was inserted some base pairs upstream of the target region without disrupting the reading frame of the lacZ' gene and without introducing any translational stop codons. More than 90% RNAs synthesized in vitro were cleaved at the expected site after 1-h incubation in the presence of 10 mM magnesium ion at 37 and 50 degrees C. Inclusion of the designed ribozyme sequence was also shown to suppress the expression of the fused lacZ' gene in E. coli cells. When the cells were infected by the ribozyme-containing phage, they remained colourless in the presence of X-gal, and the cellular beta-galactosidase activity was reduced by more than 90%. Insertion of the same ribozyme sequence in reverse orientation showed little effect on beta-galactosidase activity. Furthermore, a primer extension by reverse transcriptase revealed a cleavage product that resulted from cleavage of LacZ' mRNA at the targeted site as designed. Thus, our data demonstrated that the designed hammerhead ribozyme cleaves and reduces the expression of a fused LacZ' mRNA in E. coli cells.
...
PMID:Detection of hammerhead ribozyme-mediated cleavage and reduced expression of LacZ' mRNA in E. coli. 878 57

Ten physicochemical variables have been calculated for each of 100 different aromatic rings. These variables were selected because of their potential involvement in the molecular recognition of drug-receptor binding interactions, and they include size, lipophilicity, dipole magnitude and orientation, HOMO and LUMO energies, and electronic point charges. A total of 59 different aromatic ring systems were studied including monocyclics and [5.5]-, [6.5]- and [6.6]-fused bicyclics. A principal components analysis of b1ese results generated four principal components which account for 84% of the total variance in the data. These principal components provide a quantitative measure of molecular diversity, and their relevance for structure-activity relationships is discussed. The principal components correlate with the in vitro biological activity of heterocyclic aromatic fragments within a series of previously reported HIV-1 reverse transcriptase inhibitors.
...
PMID:Principal components describing biological activities and molecular diversity of heterocyclic aromatic ring fragments. 883 72

Poly-2'-O-(2,4-dinitrophenyl)poly[A] (DNP-poly[A] is a potent inhibitor of reverse transcriptases from a variety of sources (I. Kang and J. H. Wang, J. Biol. Chem. 269:12024-12031, 1994). In the present study, its inhibitory effect on the reverse transcriptase (RT) from Moloney murine leukemia virus (MuLV) was investigated. DNP-poly[A] was found to enter the virus spontaneously and to completely inhibit the RT within 30 min at 0 degree C. The inhibitor was also spontaneously transported into isolated human lymphocytes and leukocytes at 37 degrees C. Animal studies have demonstrated the effectiveness of DNP-poly[A] as an antiviral drug when administered intraperitoneally at various doses from 1 to 100 mg/kg of body weight. MuLV-infected mice show the presence of RT in their blood as well as increased numbers of leukocytes. After the administration of DNP-poly[A] at a dosage of 100 mg/kg of body weight three times a week over a 3-week period, RT could no longer be detected by an ultrasensitive RT-PCR assay. Autopsy showed that the spleens of infected but untreated mice were enlarged 2- to 10-fold, with fused nodules and the proliferation of large abnormal lymphocytes, whereas the spleens of infected but treated mice resembled the normal spleens of uninfected control mice. These observations indicate that further study of DNP-poly[A] as a general antiretroviral agent is desirable.
...
PMID:Inhibition of murine leukemia virus with poly-2'-O-(2,4-dinitrophenyl)poly[A]. 889 Nov 36

Based on homologies between the yeast DMC1 and the lily LIM15 meiosis-specific genes, degenerate PCR primers were designed that amplified the Arabidopsis DMC1 gene (AtDMC1). AtDMC1 genomic DNA (8 kb) was sequenced, and the transcript was characterized by reverse transcriptase-polymerase chain reaction (RT-PCR) and by 5' and 3' RACE (rapid amplification of cDNA ends). The AtDMC1 gene contains 15 exons and 14 introns. RNA in situ hybridization analysis showed that expression of the AtDMC1 is restricted to pollen mother cells in anthers and to megaspore mother cells in ovules. The AtDMC1 promoter was fused to the GUS reporter gene, and conferred meiosis-associated expression in both male and female floral lineages. Comparison of AtDMC1 isolated from Landsberg erecta ecotype to its Columbia allele ArLIM15, revealed the presence of a 1874 bp transposon-like element within the promoter region of ArLIM15. RT-PCR analysis showed that the expression levels of AtDMC1 and ArLIM15 are similar. Possible uses for the AtDMC1 promoter are discussed.
...
PMID:AtDMC1, the Arabidopsis homologue of the yeast DMC1 gene: characterization, transposon-induced allelic variation and meiosis-associated expression. 902 99

ACT11 represents a unique and ancient actin subclass in the complex Arabidopsis actin gene family. We have isolated and characterized the Arabidopsis ACT11 actin gene and examined its expression. Southern blotting with a 5' gene-specific probe showed that ACT11 was a single-copy gene in the genome. Northern analysis with a 3' gene-specific probe and reverse transcriptase-mediated PCR (RT-PCR) using gene-specific primers detected ACT11 mRNA at low levels in seedling, root, leaf, and silique tissue; at moderate levels in the inflorescence stem and flower; and at very high levels in pollen. The 5' region of the ACT11 gene, including the promoter region, the 5'-untranslated leader, the intron within the leader, and the first 19 actin codons, was fused to a beta-glucuronidase (GUS) reporter gene. The expression of the ACT11/GUS fusion was examined histochemically in numerous independent transgenic Arabidopsis plants. Strong ACT11/GUS activity was detected in rapidly elongating tissues and organs (e.g., etiolated hypocotyls, expanding leaves, stems) and in floral organ primordia. As the floral buds developed into mature flowers, strong GUS activity was gradually restricted to mature pollen and developing ovules. ACT11 appears to be the only Arabidopsis actin gene expressed at significant levels in ovule, embryo, and endosperm. The unique expression patterns in reproductive organs and the sequence divergence of the ACT11 actin gene suggest that the ACT11 isovariant plays distinct and required roles during Arabidopsis development.
...
PMID:The Arabidopsis ACT11 actin gene is strongly expressed in tissues of the emerging inflorescence, pollen, and developing ovules. 903 65

We used a catecholaminergic neuron-like cell line (CATH.a cells) as a model system to investigate the likelihood that pituitary adenylate cyclase-activating polypeptide (PACAP) may participate in the regulation of specific gene expression in catecholaminergic neurons. Analysis by reverse transcriptase-PCR amplification revealed the presence in these cells of type I PACAP receptors, with a short isoform, together with a heavier so-called Hop splice variant. PACAP38 and PACAP27 enhanced, in a dose-dependent manner, both cyclic AMP formation and phosphoinositide breakdown, with EC50 values of, respectively, 0.6 x 10(-10) and 2 x 10(-9) M. These peptides, in addition, also elevated [Ca2+]i by mobilizing intracellular calcium pools. Vasoactive intestinal peptide (VIP) was approximately 1,000-fold less potent in stimulating cyclic AMP (with EC50 = 2 x 10(-7) M) and failed to change the turnover of phosphoinositides and to alter [Ca2+]i. Both forms of PACAP, as well as forskolin, stimulated transcriptional induction of tyrosine hydroxylase (TH) and c-fos promoters fused to a chloramphenicol acetyltransferase (CAT) reporter gene in transiently transfected cells (p < 0.01 vs. controls). Induction of CAT activity linked to both TH and c-fos promoters was obliterated upon coexpression of a dominant inhibitory mutant (Mt-RAB) of cyclic AMP-dependent protein kinase. We conclude that CATH.a cells do express functional PACAP type I receptors, the activation of which impinges on TH and c-fos transcription according to a process that is primarily dependent on the cyclic AMP-PKA pathway.
...
PMID:Pituitary adenylate cyclase-activating polypeptide triggers dual transduction signaling in CATH.a cells and transcriptionally activates tyrosine hydroxylase and c-fos expression. 908 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---