Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skin from acute and healed herpes simplex virus or herpes simplex virus-associated erythema multiforme (HAEM) lesions was examined by polymerase chain reaction with primers for DNA polymerase, ICP8, thymidine kinase (5' end of herpes simplex virus genome), and ICP27 (3' end of herpes simplex virus genome). The primers were herpes simplex virus specific and equally sensitive. The four herpes simplex virus genes were seen in acute herpes simplex virus lesions, but except for one patient, only polymerase (or polymerase and ICP8) were seen in 7-d healed lesional skin. Herpes simplex virus DNA was not seen 1-1.5 mo after healing. HAEM skins from 18 of 24 patients (75%) were positive for polymerase DNA and four of 24 (17%) were also positive for ICP8 or thymidine kinase DNA. Only one tissue (4%) was positive for polymerase, ICP8, and ICP27 DNA. Skin from healed HAEM lesions was still polymerase DNA positive 1-3 mo after lesion resolution. The polymerase DNA signal was in the basal and spinous cell layers of the epidermis and in the outer root sheath of the hair follicle. Polymerase RNA was identified by reverse transcriptase polymerase chain reaction in skin from acute, but not healed polymerase DNA positive HAEM lesions, suggesting that polymerase expression is associated with HAEM lesion development.
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PMID:Expression of herpes simplex virus DNA fragments located in epidermal keratinocytes and germinative cells is associated with the development of erythema multiforme lesions. 932 89

A common form of erythema multiforme, herpes-associated erythema multiforme (HAEM), occurs following infection with herpes simplex virus (HSV). Here we report that HSV gene expression and the qualitative nature of the virus-specific T-cell responses are related to HAEM lesion development. Skin from HAEM lesions and 1-3 months healed HAEM lesional skin were positive for the viral DNA polymerase gene (Pol) by polymerase chain reaction. However, gene expression as determined by immunohistochemistry with Pol-specific antibody was seen only in HAEM lesions, suggesting that lesion development is associated with Pol gene expression. Similar HSV-specific T-cell lymphoproliferative responses were seen in peripheral blood mononuclear cells (PBMCs) from patients with acute or healed HAEM lesions or HSV lesions and from HSV-seropositive patients with unrelated inflammatory diseases. However, the T-cell receptor variable (V beta) chain repertoire of HSV-stimulated PBMCs obtained from HAEM lesions was altered; the prevalence of some families of variable chain (namely V beta 16 and V beta 19) was reduced, whereas the prevalence of others was increased (namely V beta 2 and V beta 7). V beta 2 cells were found in HAEM lesional skin positive for Pol antigen, suggesting that these cells home to viral antigen-positive skin.
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PMID:Erythema multiforme lesions are associated with expression of a herpes simplex virus (HSV) gene and qualitative alterations in the HSV-specific T-cell response. 974 55

Erythema multiforme (EM) is a polymorphic, often recurring eruption caused by exposure to medication or various infections, notably herpes simplex virus (HSV). Understanding the pathogenesis of HSV-associated EM (HAEM) is essential for patient management. We suggest that HAEM results from the combination of viropathic effects mediated by HSV proteins, notably DNA polymerase (Pol), and an immunological reaction to viral antigens. Presumably, viral DNA and proteins ingested by macrophages at HSV lesion sites undergo fragmentation and processing for presentation to T cells with HSV memory. HSV DNA is deposited on the skin, where it is expressed. Activated T cells are recruited to the skin site of Pol expression, directly or indirectly resulting in the generation of an inflammatory cascade. Factors potentially involved in the incidence of recurrences, lesion severity and anatomical localization include the identity of the deposited HSV genes, cutaneous capillary size, degree of vasoconstriction and ambient temperature. Evidence in support of this interpretation is reviewed.
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PMID:Understanding the pathogenesis of HSV-associated erythema multiforme. 981 24

Erythema multiforme follows administration of several drugs or infection with various agents, including herpes simplex virus, a syndrome designated herpes simplex virus associated erythema multiforme. Lesional skin from 21 of 26 (81%) herpes simplex virus associated erythema multiforme patients was positive for herpes simplex virus gene expression as evidenced by reverse transcriptase-polymerase chain reaction with primers for DNA polymerase and/or immunohistochemistry with DNA polymerase antibody. Reverse transcriptase-polymerase chain reaction and immunohistochemistry studies indicated that herpes simplex virus associated erythema multiforme lesional skin from 16 of 21 (76%) DNA polymerase positive herpes simplex virus associated erythema multiforme patients was also positive for interferon-gamma, a product of T cells involved in delayed-type hypersensitivity (p < 0. 0001 by Pearson correlation coefficient). Interferon-gamma signals were in infiltrating mononuclear cells and in intercellular spaces within inflammatory sites in the epidermis and at the epidermis/dermis junction. Herpes simplex virus lesional skin was also positive for DNA polymerase [five of five (100%)] and interferon-gamma [four of five (80%)], but lesional skin from drug-induced erythema multiforme patients was negative. Lesional herpes simplex virus associated erythema multiforme keratinocytes also stained with antibody to transforming growth factor-beta [14 of 23 (61%)] and cyclin-dependent kinase inhibitor waf [12 of 18 (67%)]. Staining was also seen in keratinocytes from herpes simplex virus lesions [five of five (100%)], but not in normal skin. By contrast, staining with antibody to tumor necrosis factor-alpha, another pro-inflammatory cytokine, was seen in seven of 11 (64%) drug-induced erythema multiforme patients, but not in herpes simplex virus or herpes simplex virus associated erythema multiforme patients, and lesional keratinocytes from drug-induced erythema multiforme patients were negative for transforming growth factor-beta and cyclin-dependent kinase inhibitor waf. We interpret the data to indicate that herpes simplex virus associated erythema multiforme pathology includes a delayed-type hypersensitivity component and is mechanistically distinct from drug-induced erythema multiforme.
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PMID:Herpes simplex virus associated erythema multiforme (HAEM) is mechanistically distinct from drug-induced erythema multiforme: interferon-gamma is expressed in HAEM lesions and tumor necrosis factor-alpha in drug-induced erythema multiforme lesions. 1057 38

Erythema multiforme (EM) is a clinical conundrum the name of which reflects the broad morphological spectrum of the lesions. Molecular and immunologic evidence that herpes simplex virus (HSV) causes a subset of EM lesions [herpes-associated EM (HAEM)] is reviewed, and new data are presented which suggest that autoreactive T-cells triggered by virus infection play an important role in HAEM pathogenesis. Disease development begins with viral DNA fragmentation and the transport of the DNA fragments to distant skin sites by peripheral blood mononuclear cells (PBMCs). HSV genes within DNA fragments deposited on the skin [notably DNA polymerase (Pol)] are expressed, leading to recruitment of HSV-specific CD4+ Th1 cells that respond to viral antigens with production of interferon-gamma (IFN-gamma). This step initiates an inflammatory cascade that includes expression of IFN-gamma induced genes, increased sequestration of circulating leukocytes, monocytes and natural killer (NK) cells, and the recruitment of autoreactive T-cells generated by molecular mimicry or the release of cellular antigens from lysed cells. The PBMCs that pick up the HSV DNA [viz. macrophages or CD34+ Langerhans cells (LC) precursors], their ability to process it, the viral proteins expressed in the skin and the presence of epitopes shared with cellular proteins may determine whether a specific HSV episode is followed by HAEM development. Drug-associated EM (DIEM) is a mechanistically distinct EM subset that involves expression of tumor necrosis factor alpha (TNF-alpha) in lesional skin. It is our thesis that the polymerase chain reaction (PCR) assay for HSV DNA detection in lesional skin and staining with antibodies to IFN-gamma and TNF-alpha, are important criteria for the diagnosis of skin eruptions and improved patient management.
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PMID:Herpes simplex virus (HSV)-associated erythema multiforme (HAEM): a viral disease with an autoimmune component. 1263 59

A subset of erythema multiforme (erythema multiforme) is associated with herpes simplex virus (HSV) infection; viral cultures of erythema multiforme lesions are, however, usually negative and viral antigens difficult to identify. Polymerase chain reaction (PCR) has been used to demonstrate the association, hence, is currently the only available sensitive diagnostic means for HSV-associated erythema multiforme. A nested PCR, which could simultaneously detect and genotype HSV in erythema multiforme lesions and in clinical swab specimen was developed using the DNA polymerase gene of HSV as target gene because it is the only detectable HSV gene in a high proportion of erythema multiforme lesions. The PCR has demonstrated its robust sensitivity on swab samples by being able to detect further 45.3% HSV cases in comparison with virus isolation with 100% specificity in both detection and genotyping confirmed by virus isolation and DNA sequencing. This study represents the first investigation of typing HSV virus in HSV-associated erythema multiforme patients, and the finding that 66.7% of the patients was attributed to HSV1, 27.8% to HSV2, and 5.6% to HSV1 and 2 co-infection may reflect the distribution of HSV1 and 2 in local general population.
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PMID:Detection and genotyping of human herpes simplex viruses in cutaneous lesions of erythema multiforme by nested PCR. 1296 49

A 1-day-old male newborn was born with respiratory distress, low birth weight, hepatosplenomegaly, and bullous targetoid skin lesions over the face, back, buttocks, and extremities. A diagnosis of early congenital syphilis was made based on a treponemal serologic test. Pathologic examination of the skin lesion showed scattered dyskeratotic cells in the epidermis and interface dermatitis consistent with erythema multiforme. No spirochete could be found in the skin sections staining with Warthin-Starry stain. Using nested polymerase chain reaction, treponemal genomic DNA fragments encoding DNA polymerase I were detected.
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PMID:Early congenital syphilis and erythema multiforme-like bullous targetoid lesions in a 1-day-old newborn: detection of Treponema pallidum genomic DNA from the targetoid plaque using nested polymerase chain reaction. 1684 16

Erythema multiforme (EM) is an uncommon, immune-mediated disorder that presents with cutaneous or mucosal lesions or both. In herpes simplex virus (HSV)-associated EM, the findings are thought to result from cell-mediated immune reaction against viral antigen-positive cells that contain the HSV DNA polymerase gene (pol). The target lesion, with concentric zones of color change, represents the characteristic cutaneous finding seen in this disorder. Although EM can be induced by various factors, HSV infection continues to be the most common inciting factor. Histopathologic testing and other laboratory investigations may be used to confirm the diagnosis of EM and to differentiate it from other clinical imitators. Imitators of EM include urticaria, Stevens-Johnson syndrome, fixed drug eruption, bullous pemphigoid, paraneoplastic pemphigus, Sweet's syndrome, Rowell's syndrome, polymorphus light eruption, and cutaneous small-vessel vasculitis. Because disease severity and mucosal involvement differ among patients, treatment should be tailored to each patient, with careful consideration of treatment risk vs benefit. Mild cutaneous involvement of EM can be managed primarily with a goal of achieving symptomatic improvement; however, patients with HSV-associated recurrent EM and idiopathic recurrent EM require treatment with antiviral prophylaxis. Inpatient hospitalization may be required for patients with severe mucosal involvement that causes poor oral intake and subsequent fluid and electrolyte imbalance. With this review, we strive to provide guidance to the practicing dermatologist in the evaluation and treatment of a patient with EM.
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PMID:Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. 2278 3