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

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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)

Vascular endothellal growth factor (VEGF) increases vascular permeability and acts as a mitogen for endothelial cells in vivo and in vitro. We and others recently demonstrated that cultured human keratinocytes constitutively secrete VEGF. In the present study, we examined the expression of this growth factor in various epithelial skin tumors and in normal skin. Using in situ hybridization, we detected strong VEGF mRNA expression in all of 10 squamous cell carcinomas, 13 common warts, 11 seborrheic keratoses, and in 7 of 8 keratoacanthomas studied. By contrast, we found no VEGF mRNA in 9 of 14 basal cell carcinomas. VEGF mRNA was readily detectable within the epidermis adjacent to the tumors as well as in tumor cells and in the epidermis of normal human skin. Northern hybridization of RNA derived from normal human epidermis identified VEGF transcripts of 3.7 and 1.8 kb, and reverse transcriptase polymerase chain reaction confirmed that epidermal cells, like keratinocytes in vitro, express the three major splice forms of VEGF. Immunohistochemical staining with monoclonal antibodies confirmed that expression of VEGF mRNA was accompanied by the presence of VEGF protein. Our data demonstrate that VEGF production by tumor cells in situ does not distinguish malignant from benign epithelial tumors of the skin because it is present in both. The constitutive expression of VEGF by normal keratinocytes in situ suggests that this angiotropic cytokine is important for the regulation of vessel function under physiologic conditions.
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PMID:Vascular endothelial growth factor production in normal epidermis and in benign and malignant epithelial skin tumors. 894 Dec 11

The persistence of human papillomavirus at cutaneous sites may be due to impaired trafficking of immune effector cells to the epidermis. We investigated whether HPV infection modulates cytokine mRNA expression in skin, thereby influencing local immunity. The mRNA expression of tumour necrosis factor-alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist (IL-1ra), IL-4, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor, transforming growth factor-beta, interferon-gamma and amphiregulin were assayed in cutaneous warts and normal skin by semiquantitative reverse transcriptase-polymerase chain reaction. The expression of the cytokines was heterogeneous in the specimens but, of the 12 mRNA species investigated, only IL-10 mRNA was significantly downregulated in warts compared with normal skin (P = 0.002). IL-1 alpha mRNA expression was significantly upregulated in common warts (P = 0.019) and plantar warts (P = 0.003) compared with normal skin. The expression of IL-1 alpha and IL-1ra mRNAs were significantly correlated in plantar warts (P < 0.05). Warts expressing IL-1 alpha also expressed amphiregulin, and there was a significant correlation between the expression of these two genes (P < 0.05). It is possible that IL-1 alpha expression in cutaneous warts may modulate the growth of papillomavirus-infected keratinocytes, mediated by amphiregulin, thus ensuring viral persistence.
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PMID:Cytokine mRNA expression in cutaneous warts: induction of interleukin-1 alpha. 901 32

The mechanism of action of imiquimod 5% cream applied topically to patients with genital warts was evaluated in a double-blind, placebo-controlled study. Imiquimod (16 patients) or placebo (three patients) was applied three times per week for up to 16 weeks. All imiquimod-treated patients had a > or =75% reduction in total wart area while only one of three placebo-treated patients had a similar reduction. Wart biopsies were taken at prestudy, week 6, and end of treatment. Polymerase chain reaction (PCR) for human papillomavirus (HPV) DNA and reverse transcriptase (RT)-PCR for messenger (m)RNAs were used to identify cytokines, cellular markers, viral gene products, and cell cycle markers in these biopsies. Treatment with imiquimod, an immune response modifier, stimulated significant increases in mRNA for interferon (IFN)-alpha, IFN-gamma and 2',5' oligoadenylate synthetase (2',5'-AS) as well as a tendency towards increases in tumor necrosis factor (TNF)-alpha and interleukin-12 p40. Significant increases in mRNA for CD4 and a trend toward increases in CD8 were also observed in imiquimod-treated patients, suggesting activation of a cell mediated immune response. Imiquimod administration was also associated with a significant decrease in viral load as measured by HPV DNA and L1 mRNA. The effects on HPV markers were accompanied by an apparent decrease in mRNA expression for markers of cell proliferation and an increase in mRNA for markers of keratinocyte differentiation and tumor suppressors.
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PMID:Enhancement of the innate and cellular immune response in patients with genital warts treated with topical imiquimod cream 5%. 1048 Feb 63

Despite the decrease in opportunistic infections associated with HIV in the highly active antiretroviral treatment (HAART) era, a significant number of patients still present with skin pathology, some of which can be attributed directly or indirectly to antiretroviral therapy. The non-nucleoside reverse transcriptase inhibitors exhibit a class effect with regard to skin adverse manifestations, and the spectrum of disease can vary from a mild morbilliform rash to Stevens-Johnson syndrome. Certain protease inhibitors are associated with rash, and indinavir causes retinoid-like manifestations such as paronychia, alopecia, ingrown toe-nails, and curling of straight hair. Abacavir, a nucleoside reverse transcriptase inhibitor, is notorious for causing a hypersensitivity reaction in select patients. The fusion inhibitor enfuvirtide causes injection-site reactions in the overwhelming majority of patients, although a new method of delivery has decreased the rate and severity of these reactions. A syndrome of lipoatrophy with or without lipohypertrophy, often termed lipodystrophy, has been described in patients receiving HAART. Potential management of lipoatrophy includes switching antiretrovirals and surgical treatment with facial fillers. Lastly, skin manifestations of the immune reconstitution inflammatory syndrome, including herpes zoster and warts, must be recognized and treated accordingly. In the evaluation of the individual HIV-infected patient receiving antiretroviral therapy who presents with a skin disorder, clinicians should consider the CD4 cell count as a marker of the degree of immunodeficiency, the specific antiretrovirals used, and the timing of the initiation of antiretroviral therapy in order to formulate a rational differential diagnosis. Management should be individualized based on the specific drug that is implicated and the severity of the reaction.
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PMID:Dermatologic adverse effects of antiretroviral therapy: recognition and management. 1764 77

CD70 (CD27L) has been shown to be preferentially expressed on Th1, but not Th2, CD4+ lymphocytes in murine contact sensitivity. The CD70-CD27 co-stimulatory pathway as well as the Th17 subset of lymphocytes have also been identified in human contact sensitivity reactions. The authors have previously reported increased expression of CD70 and the Th17-specific transcription factor retinoid orphan receptor gamma T in the elicitation phase of allergic contact dermatitis by reverse transcriptase-polymerase chain reaction. The manipulation of these pathways has potential for ameliorating autoimmune and inflammatory disorders such as allergic contact dermatitis, psoriasis and rheumatoid arthritis. Also, upregulation of the CD70-CD27 and Th17 pathways has been associated with the remarkable ability of topical sensitizers to treat warts and skin cancers including melanoma. As natural killer and natural killer T cells are also involved in contact sensitivity, future studies investigating the function of these cells are necessary to elucidate the transition between innate and acquired immune responses in the context of the Th1/Th2/Th17 and regulatory T cell paradigm.
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PMID:CD70 and Th17 are involved in human contact sensitivity. 2196 71

Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2'-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2'-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide.
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PMID:Approved Antiviral Drugs over the Past 50 Years. 2728 42

Papaya ringspot virus (PRSV, genus Potyvirus, family Potyviridae) is economically important due to its worldwide distribution and because it can cause serious losses in both cucurbit crops and papaya (3). PRSV has been previously reported from cucurbit crops in Iran (2). In Khuzestan Province, southwest Iran, cucurbit crops, including cucumber, melon, squash, pumpkin, and watermelon, are grown on about 30,000 ha with 720,000 t production annually. To identify possible alternative hosts that may serve as PRSV reservoirs, samples of 36 different common weed species (17 symptomatic and 19 asymptomatic) including Amaranthus sp. (slim amaranth), Carthamus sp. (safflower), Chenopodium album L. (lamb squarters), Citrullus colocynthis (L.) Schrad (colocynth), Convolvulus arvensis L. (field bindweed), Datura stramonium L. (jimson weed), Euphorbia sp. (wart weed), Malva sylvestirs L. (common malva), Solanum nigrum L. (black nightshade), and Sonchus asper (L.) Hill (prickly sow-thistle) were collected in cucurbit open fields during 2012 to 2013 in Khuzestan Province, where PRSV symptoms were observed. Symptoms on weed samples included mottling, mosaic, blistering, cholorosis, vein clearing, interveinal yellowing, yellows, necrosis, leaf distortion, and curling. Samples were tested by DAS-ELISA with specific antisera against PRSV using reagents from Bioreba (Switzerland). Three of the 36 weed samples belonging to C. colocynthis (Cucurbitaceae) with mottling and chlorosis symptoms were positive for PRSV by ELISA. Leaf extracts from PRSV ELISA-positive samples were mechanically inoculated onto indicator host plants, causing local lesions on Chenopodium amaranticolor and systemic symptoms on Cucumis melo, Cucumis sativus, and Cucurbita pepo, but could not produce symptoms on Nicotiana glutinosa, N. tabacum cv. White Burley, or N. tabacum cv. Xanthi. Total RNA was extracted from infected leaves using Tri-reagent (Sigma) and first-strand cDNA synthesis was performed using M-MuLV reverse transcriptase (Fermentas, Lithuania), according to the manufacturer's instructions. The presence of PRSV was confirmed by RT-PCR using primers for the complete coat protein (CP) gene of PRSV-W (forward 5'-GCAGCAATGATAGAGTCATG-3' and reverse 5'-AACACACAAGCGCGAGTATTCA-3') (1). The complete CP nucleotide sequence of three Iranian PRSV isolates consisted of 864 nt, coding for a 288 amino acid (aa) protein. Subsequent analysis showed that the CP nucleotide sequences of Iranian isolates (GenBank Accession Nos. KM047884 to KM047886) from C. colocynthis samples were identical. Furthermore, BLAST analysis of the nucleotide sequence comparisons revealed that the Iranian isolates shared the highest identity (96%) with the Chinese PRSV isolate (DQ449533). PRSV-W has been previously reported from different cucurbits using serological and biological detection (2); however, this result provides the first molecular demonstration, to our knowledge, of PRSV-W on C. colocynthis. C. colocynthis is a perennial weed in West and South Iran. This information on the natural infection of C. colocynthis with PSRV-W will help to better understand PRSV epidemiology and to develop a successful management program for reducing the impact of this disease. References: (1) A. Ali et al. Plant Dis. 96:243, 2012. (2) K. Bananej and A. Vahdat. Phytopathol. Mediterr. 47:247, 2008. (3) D. J. Purcifull et al. CMI/AAB Descriptions of Plant Viruses. No. 292, 1984.
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PMID:Natural Infection of Citrullus colocynthis by Papaya ringspot virus-W in Iran. 3070 9

Cherry mottle leaf virus (CMLV) is a member of the genus Trichovirus (family Betaflexiviridae). CMLV infects several species of the genus Prunus including cherry (Prunus avium) and peach (P. persica) (2,3). It is spread via budding and grafting with infected wood and can be transmitted from infected bitter cherry (P. emarginata), or infected but symptomless peach trees to healthy sweet cherry trees by the bud mite (Eriophyes inaequalis) (1). On susceptible sweet cherry cultivars, CMLV causes symptoms such as chlorotic mottle-leaf pattern, distortion, puckering of younger leaves, and small fruits that ripen late (1), which may lead to severe economic losses in some cultivars. Cherry is one of the most important fruit tree species in North China, and Shandong Province is one of the major cherry production areas. In June 2013, a survey of possible CMLV presence was conducted in a cherry orchard planted in 1996 in Zoucheng city, Shandong. The sweet cherry cultivars in this orchard included Black Tartarian, Bing, Hongdeng (a hybrid between cvs. Napoleon and Huangyu), and others; the rootstock cultivar utilized to graft these cultivars was mountain cherry (P. tomentosa). During the survey, characteristic symptoms on leaves such as leaf mottling, distortion, and puckering similar to those caused by CMLV were observed on some trees of the cv. Hongdeng, and the symptomatic trees accounted for ~10% of the total trees of this cultivar. Five symptomatic cherry leaf samples and three healthy-looking cherry leaf samples of cv. Hongdeng were collected. Total RNA extracted from the leaf samples using RNeasy plant mini kit (Qiagen Inc., Valencia, CA) was subjected to first strand cDNA synthesis with the reverse primer CMLV-3R (5'-CTCGAGAACACAGAGATTTGTCGAGAC-3', sequence in italics indicates restriction site XhoI) and M-MLV reverse transcriptase (Promega, Madison, WI) according to the manufacturer's instruction. The cDNA was then used as template in the PCR assay using primers CMLV-5F (5'-GGATCCATGTCGGCGCGATTGAATC-3', sequence in italics indicates restriction site BamHI) and CMLV-3R, which amplify the genome fragment including the capsid protein gene of CMLV. The expected PCR product ~590 bp was amplified from all five symptomatic samples, while no such PCR product was amplified from the symptomless samples. The PCR products were cloned into pMD18-T vector (TaKaRa, Dalian, China). Three positive clones for each of the five amplicons were sequenced in both directions. Sequence alignment and nucleotide BLAST analysis of the sequences revealed that they were 99% to 100% identical to the corresponding capsid protein gene sequence of a cherry isolate of CMLV (GenBank Accession No. AF170028) and 85% identical with that of the peach wart strain of CMLV (KC207480). Our results confirm the infection of cherry trees by CMLV in Shandong. To our knowledge, this is the first report of CMLV on cherry in China. As the spread of CMLV by mite vector in the field is rare (1), and no bud mite outbreak had occurred in this orchard in the past years, so it is possible that virus-infected propagation materials are largely responsible for the spread of this virus. Considering the importance of cherry cultivation in China, this report prompts the need to survey the occurrence of this virus in Shandong and other provinces, and the need to develop more effective management strategies such as the use of certified virus-free nursery stocks to reduce the impact of CMLV. References: (1) J. E. Adaskaveg et al. Diseases. Page 61 in: UC IPM Pest Management Guidelines: Cherry. University of California ANR Publication 3444, 2014. (2) D. James et al. Arch. Virol. 145:995, 2000. (3) T. A. Mekuria et al. Arch. Virol. 158:2201, 2013.
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PMID:First Report of Cherry mottle leaf virus Infecting Cherry in China. 3070 33

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