Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of two closely related peroxidase isogenes, Shpx6a and Shpx6b, of the legume Stylosanthes humilis was studied using isogene-specific reverse transcriptase PCR techniques. Results indicated that transcripts of both genes were rapidly induced following inoculation with the fungal pathogen Colletotrichum gloeosporioides, wounding and treatment with the defense regulator methyl jasmonate (MeJA). In contrast treatment of leaves of S. humilis with abscisic acid (ABA) and salicylic acid (SA) did not induce transcripts of either isogene. A genomic clone containing the Shpx6b gene was isolated and 594 bp of 5' sequence upstream of the translation start was fused in frame to the coding region of the uidA reporter gene and introduced into tobacco. Expression from the Shpx6b promoter in transgenic plants was determined by histochemical staining and quantitative assays of beta-glucuronidase (GUS). In transgenic tobacco, GUS expression was detected in cotyledons, vascular cells of young leaves, anthers, pollen, and the stigma and style. Wounding of the tobacco plants produced very localized GUS staining. Much more extensive staining for GUS was observed following inoculation of tobacco leaves with conidia of the fungal pathogen Cercospora nicotianae and the inoculation of wound sites with mycelium of the Oomycete pathogen Phytophthora parasitica var. nicotianae. Treatment of mature leaves with methyl jasmonate induced GUS activity while treatment with ABA, SA, and H2O2 had no effect. A similar strong induction of GUS activity was measured in young transgenic seedlings germinated on MeJA while some, but much weaker, induction of GUS activity was observed in seedlings treated with SA. The sequence of the promoter contained motifs homologous to putative cis elements in other plant genes responsive to MeJA. The Shpx6b gene is the first plant peroxidase gene shown to be induced by both microbial pathogens and MeJA and its promoter will be useful for investigations of signaling processes during fungal infection and for the expression of foreign gene products at infection sites.
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PMID:A peroxidase gene promoter induced by phytopathogens and methyl jasmonate in transgenic plants. 910 Mar 78

In plants, the pollen coat covers the exine wall of the pollen and is the outermost layer that makes the initial contact with the stigma surface during sexual reproduction. Little is known about the constituents of the pollen coat, especially in wind-pollinated species. The pollen coat was extracted with diethyl ether from the pollen of maize (Zea mays L.), and a predominant protein of 35 kDa was identified. On the basis of the N-terminal sequence of this protein, a cDNA clone of the Xyl gene was obtained by reverse transcriptase-polymerase chain reaction. The deduced amino acid sequence of the 35-kDa protein shared similarities with the sequences of many microbial xylanases and a barley aleurone-layer xylanase. The 35-kDa protein in the pollen-coat extract was purified to homogeneity by fast protein liquid chromatography and determined to be an acidic endoxylanase that was most active on oat spelt xylan. Northern and in situ hybridization showed that Xyl was specifically expressed in the tapetum of the anther after the tetrad microspores had become individual microspores. Southern hybridization and gene-copy reconstruction studies showed only one copy of the Xyl gene per haploid genome. Analyses of the genomic DNA sequence of Xyl and RNase protection studies with the transcript revealed many regulatory motifs at the promoter region and an intron at the 5' leader region of the transcript. The Xyl transcript had a 562-nucleotide (nt) 5' leader, a 54-nt sequence encoding a putative signal peptide, a 933-nt coding sequence, and a 420-nt 3'-untranslated sequence. The unusually long 5' leader had an open reading frame encoding a putative 175-residue protein whose sequence was most similar to that of a microbial arabinosidase. The maize xylanase is the first enzyme documented to be present in the pollen coat. Its possible role in the hydrolysis of the maize type II primary cell wall (having xylose, glucose, and arabinose as the major moieties) of the tapetum cells and the stigma surface is discussed.
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PMID:The predominant protein on the surface of maize pollen is an endoxylanase synthesized by a tapetum mRNA with a long 5' leader. 1042 75

Applying 10 pmol of okadaic acid (OA), a specific inhibitor of type 1 or type 2A serine/threonine protein phosphatases, to the orchid (Phalaenopsis species) stigma induced a dramatic increase in ethylene production and an accelerated senescence of the whole flower. Aminoethoxyvinylglycine or silver thiosulfate, inhibitors of ethylene biosynthesis or action, respectively, effectively inhibited the OA-induced ethylene production and retarded flower senescence, suggesting that the protein phosphatase inhibitor induced orchid flower senescence through an ethylene-mediated signaling pathway. OA treatment induced a differential expression pattern for the 1-aminocyclopropane-1-carboxylic acid synthase multigene family. Accumulation of Phal-ACS1 transcript in the stigma, labelum, and ovary induced by OA were higher than those induced by pollination as determined by "semiquantitative" reverse transcriptase-polymerase chain reaction. In contrast, the transcript levels of Phal-ACS2 and Phal-ACS3 induced by OA were much lower than those induced by pollination. Staurosporine, a protein kinase inhibitor, on the other hand, inhibited the OA-induced Phal-ACS1 expression in the stigma and delayed flower senescence. Our results suggest that a hyper-phosphorylation status of an unidentified protein(s) is involved in up-regulating the expression of Phal-ACS1 gene resulting in increased ethylene production and accelerated the senescence process of orchid flower.
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PMID:Differential expression of 1-aminocyclopropane-1-carboxylate synthase genes during orchid flower senescence induced by the protein phosphatase inhibitor okadaic acid. 1135 Oct 88

An unprecedented international effort to expand high activity antiretroviral therapy (HAART) to resource-poor nations has been launched. The World Health Organization (WHO) has created antiretroviral (ARV) treatment guidelines adapted to resource-poor settings. The first-line regimen is two nucleoside reverse transcriptase inhibitors (NsRTIs) and one nonnucleoside reverse transcriptase inhibitor (NNRTI). Therapy is initiated by clinical staging and CD4 T-cell counts when available. Adherence is the responsibility of health care workers. The use of ARV therapy in resource-poor settings faces several challenges, including the poverty of patients, political and social upheavals and violence, social stigma associated with HIV/AIDS, unreliable pharmacy systems, tuberculosis, and lack of trained health care workers. Using our experience in Haiti, we describe how we have addressed these challenges with the goal of increasing access to care for the poor with HIV/AIDS.
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PMID:HIV antiretroviral therapy in resource-limited settings: experiences from Haiti. 1609 Dec 55

The huge improvement in the therapeutic arsenal for HIV infection has led to HIV becoming a chronic disease. Like us, our patients are aging and their life expectancy is close to that of the general population. Consequently, we need safe, easily administered drugs with interactions that can be controlled and the least possible impact on highly prevalent comorbidities such as atherosclerosis or coinfection with hepatotropic viruses. Drugs should fit the patient's lifestyle without affecting quality of life and, above all, be free of effects leading to stigma, such as lipoatrophy, a major concern for most recently diagnosed patients. The choice of the two nucleoside analogue reverse transcriptase inhibitors used at the start of antiretroviral therapy should be based on careful evaluation of the abundant data accumulated on all these determining factors which are heralding a new era in the control of HIV infection. Thus, in this scenario, thymidine analogues have been relegated to alternative use. Fixeddose combinations of tenofovir and emtricitabine (TDF/FTC) or abacavir and lamivudine (ABC/3TC) are the backbone of choice when initiating antiretroviral therapy. Direct comparative data are still scarce but suggest similar virological efficacy, with highly preliminary data suggesting some disadvantages associated with the use of ABC/3TC. After excluding patients at risk of hypersensitivity to ABC, both combinations are well tolerated, but TDF/FTC is associated with a better lipid profile. Recent data from the Data Collection on Adverse Events of Anti-HIV drugs (DAD) study show an unexpected association of ABC with increased cardiovascular risk and thus more detailed studies are required.
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PMID:[Are all analogue combinations equal?]. 1919 37

HIV-associated lipodystrophy syndrome affects approximately 50% of HIV-positive patients, particularly those receiving antiretroviral therapy based on nucleoside reverse transcriptase inhibitors and protease inhibitors. Growing evidence suggests that certain antiretroviral drugs may precipitate or exacerbate lipoatrophy and associated metabolic abnormalities, and this is an important consideration when selecting appropriate treatment regimens. However, because of problems of cross-resistance among antiretroviral drug classes and other treatment-related toxicities, it is likely that, at some stage, the HIV-infected patient will have to take drugs that confer a risk of development of lipodystrophy syndrome. Combination therapy for HIV, known as highly active antiretroviral therapy (HAART), has dramatically altered the prognosis for the HIV-infected individual. With optimal use of HAART, which includes regular monitoring of viral load, viral resistance, and compliance with medication, HIV infection has changed from being a fatal disease to a lifelong infection. However, HAART-related lipodystrophy syndrome, and especially facial lipoatrophy, is of great concern for patients and physicians involved in HIV care. For the patient, facial lipoatrophy is a major stigma that affects self-esteem and social interaction, and in some cases, it is a cause of noncompliance with HAART. Accordingly, many treatment-experienced HIV patients are requesting, and being treated with, various dermal fillers for cosmetic correction of facial lipoatrophy. Prior to the introduction of HAART, when life expectancy for the HIV-infected individual was severely limited, permanent fillers were widely used for this purpose. Because these products remain in situ indefinitely and the facial soft tissues change over time, the permanent fillers are no longer a satisfactory treatment option. Now that HIV infection has been transformed into a chronic but not necessarily life-threatening disease, there is an urgent need for a safe, biodegradable, and biocompatible alternative dermal filler for treating HIV-associated facial lipoatrophy.
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PMID:HIV-related lipodystrophy and facial lipoatrophy: the role of Restylane SubQ in reversing facial wasting. 1933 75

Long-acting and extended-release formulations represent one of the most important approaches to improving the treatment and prevention of chronic HIV infection. Long-acting small molecules and monoclonal antibodies have demonstrated potent anti-HIV activity in early- and late-stage clinical trials. Strategies to manage toxicity and falling drug concentrations after missed doses, as well as primary and secondary resistance to current drugs and monoclonal antibodies are important considerations. Long-acting injectable nanoformulations of the integrase inhibitor cabotegravir and the non-nucleoside reverse transcriptase inhibitor rilpivirine were safe, well tolerated and efficacious in large randomised phase 3 studies. Regulatory approval for this two-drug combination for HIV maintenance therapy was granted in Canada in 2020 and is expected in the USA during 2021. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (islatravir) is a novel nucleoside reverse transcriptase inhibitor in clinical development as a long-acting oral drug and as a long-acting subcutaneous polymer implant. GS-6207 is a novel HIV capsid inhibitor that is injected subcutaneously every 3 months. Broadly-neutralising monoclonal antibodies have potent antiviral activity in early human trials, however there is substantial baseline resistance and rapid development of resistance to these antibodies if used as monotherapy. Limitations of these antiretroviral approaches include management of toxicities and prevention of drug resistance when these drugs are discontinued and drug concentrations are slowly reduced over time. These approaches appear to be especially attractive for patients complaining of pill fatigue and for those experiencing HIV-associated stigma. As these formulations are shown to be safe, well tolerated and economical, they are likely to gain broader appeal.
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PMID:Long-acting drugs and formulations for the treatment and prevention of HIV infection. 3316 93