Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several papillomas from a single patient who exhibited an unusual immune deficiency syndrome were analyzed for the presence of specific human papillomavirus (HPV) types. Preliminary analysis indicated that the HPV DNA species present in each of these tissues was quite unlike any of the previously characterized HPV types. In order to more rigorously analyze the HPV from this patient we have isolated the HPV DNA by molecularly cloning it into a bacteriophage lambda vector and have constructed a detailed restriction endonuclease map. Comparative hybridization studies using S1 nuclease analyses showed 6% or less nucleotide sequence homology of this viral DNA with HPV types 1, 2, 3, 4, 5, 6, or an HPV-11, molecularly cloned in this laboratory. Moreover, Southern blot analyses under stringent hybridization conditions revealed little, if any, hybridization to HPV types 1, 2, 4, 5, 7, 8, 10, 11, HPV-EV isolated from a patient with epidermodysplasia verruciformis (EV), or 2 previously described HPVs (HPV-P and HPV-PW) related to HPV-3. There was, however, a very weak sequence homology detected with HPV-6 and an extremely weak homology to HPV-3. No filter hybridization was observed with the recently characterized HPVs 9 or -12 to -24. These data accumulatively indicate that the HPV species from this immunosuppressed patient represents a new, hitherto unidentified HPV type.
J Invest Dermatol 1984 Apr
PMID:Molecular cloning and characterization of a unique type of human papillomavirus from an immune deficient patient. 632 88

We have studied 11 patients with the papillomavirus-induced disease epidermodysplasia verruciformis (EV). Clinical diagnostic features are widespread, long-lasting, pityriasis versicolor-like macules and flat, wart-like papules, both usually occurring in early childhood, with the subsequent development in the third decade of multiple skin cancers of the Bowenoid in situ and squamous cell types, primarily in sun-exposed skin. Virologic studies using the methods of immunofluorescence microscopy, restriction endonuclease analysis, and DNA blot hybridization have shown benign lesions to be associated with one or several types of the human papillomaviruses (HPVs) specifically associated with EV (at least 15 types recognized on the basis of sequence homology studies of molecularly cloned genomes). Skin cancers in these patients were associated with the genomes of either HPV-5, HPV-8 or HPV-14, suggesting that these three viruses are potentially oncogenic. A genetic factor appears to play a role in the pathogenesis of EV, since 5 of our patients were children of consanguineous parents and 2 had siblings also suffering with EV, suggesting a recessive inheritance pattern. Treatment of 4 EV patients with an oral retinoid resulted in partial temporary improvement of benign lesions, and the treatment of 2 patients with intralesional interferon injections into multiple Bowenoid cancers in situ has resulted in the disappearance of these lesions. Finally, EV serves as a model for studying the interplay of oncogenic viruses, genetic and immunologic factors, and sunlight in the production of skin cancer in humans.
J Invest Dermatol 1984 Jul
PMID:Clinical observations, virologic studies, and treatment trials in patients with epidermodysplasia verruciformis, a disease induced by specific human papillomaviruses. 633 Feb 17

The in vivo repair of pyrimidine dimers induced in the DNA of skin of 9 patients diagnosed as systemic or discoid lupus erythematosus (LE) was measured. A small area of the buttock was exposed to radiation emitted from a Burdick UV-800 sunlamp. The number of pyrimidine dimers was measured by incubating the epidermal skin DNA with UV-specific endonuclease and sedimenting the DNA through alkaline sucrose gradients. The initial number of dimers induced following sunlamp exposure was 7.6 +/- 1.8 per 10(8) daltons DNA. The level of photorepair was measured by illuminating an area of the skin with greater than 450-nm radiation immediately following sunlamp exposure. We found that 56.5 +/- 9.5% of the dimers are photorepaired with 5 min of illumination. Excision repair was measured in an area of the skin covered for 2 and 24 h postirradiation. Approximately 44 and 81% of the dimers induced immediately following sunlamp exposure were removed at these respective times. These observations in LE are similar to those observed in the skin of normal individuals.
J Invest Dermatol 1983 Nov
PMID:DNA repair in skin of lupus erythematosus following in vivo exposure to ultraviolet radiation. 663 Oct 57

The gene responsible for xeroderma pigmentosum (XP) group A has recently been cloned and designated XPA gene. Previous studies have shown that most Japanese XPA patients have homozygous mutations for the splicing site of intron 3 of the XPA gene, which was recognized by restriction endonuclease (RE) AlwNI (AlwNI mutation). Other mutations found to date have been the nonsense mutation at codon 228 in exon 6, recognized by RE HphI (HphI mutation), and at codon 116 in exon 3, recognized by RE MseI (MseI mutation). Using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis, we examined the point mutations of the XPA gene in 16 XPA patients, their parents, and their four asymptomatic siblings. We found that eight patients were homozygous for the AlwNI mutation, two were compound heterozygotes for the AlwNI mutation and the HphI mutation, one was a compound heterozygote for the AlwNI mutation and the MseI mutation, three were compound heterozygotes for the AlwNI mutation and an unidentified mutation, and two were compound heterozygotes for the HphI mutation and an unidentified mutation. Investigation of their clinical features suggested that the four patients who were heterozygous for the HphI mutation and the AlwNI or an unidentified mutation had milder clinical manifestations such as later development of skin cancers and milder neurological deterioration, than those patients who were either homozygous for the AlwNI mutation or heterozygous for the AlwNI mutation and MseI mutation.(ABSTRACT TRUNCATED AT 250 WORDS)
Br J Dermatol 1995 Oct
PMID:Correlation of the clinical manifestations and gene mutations of Japanese xeroderma pigmentosum group A patients. 757 88

The ability of heat shock to induce functional protection against ultraviolet B (UVB) light was examined in keratinocytes cultured from human skin. Cell death, measured with fluorescent vital dyes, increased in a UVB dose-dependent manner (LD50 approximately 20-60 mJ/cm2). However, a 60-min heat shock at 40 degrees C or 42 degrees C, administered several hours before UVB irradiation, reduced cell death by 2.0-2.5 times. Inducible protection took time to develop, with an optimal interval of approximately 6 h between heat and UVB exposures. Heat-inducible protection was completely blocked if either cordycepin (3'-deoxyadenosine), to inhibit mRNA synthesis, or cycloheximide, to inhibit protein synthesis, were present during the heating period. To determine whether apoptosis might be involved in UVB-induced keratinocyte death in this system, evidence for endonuclease activity was sought via in situ enzymatic labeling with terminal deoxynucleotidyl transferase and biotinylated-dUTP. Labeled nuclei were detected in UVB-irradiated cultures, and heat pretreatment at 6 h prior to UVB exposure (< 60 mJ/cm2) resulted in a 50% reduction in labeled nuclei. Overall, the data show that UVB-induced cell death in human keratinocyte cultures is attenuated by a heat-inducible mechanism that requires ongoing synthesis of mRNA and protein.
J Invest Dermatol 1994 Oct
PMID:Heat shock modulates UVB-induced cell death in human epidermal keratinocytes: evidence for a hyperthermia-inducible protective response. 793 Jun 80

All the reported Japanese patients with group A xeroderma pigmentosum (XP) have two or three mutations at codon 116 in exon 3, codon 228 in exon 6, and the splicing acceptor site of intron 3 of XP group A complementing (XPAC) gene. A homozygote (XP39OS) with a nonsense mutation at codon 228 has less severe neurological abnormalities than patients with the splicing mutation at the acceptor site of intron 3. As homozygotes for the nonsense mutation at codon 116, which truncates a carboxyl-terminal site of XPAC protein at an early part of its zinc-finger domain, have not been reported previously, the possible severity of associated neurological abnormalities was not known. We report a group A XP patient, XP18OS, who had neurological abnormalities which were more severe than those in patients homozygous for the splicing mutation. The polymerase chain reaction product from exon 3 of the patient's XPAC gene was digested completely into three fragments by MseI restriction endonuclease. Thus, the patient was homozygous for the mutation at codon 116.
Br J Dermatol 1994 Oct
PMID:Severe neurological abnormalities associated with a mutation in the zinc-finger domain in a group A xeroderma pigmentosum patient. 794 12

A 26-year-old man had a primary infection or reinfection of genital herpes due to herpes simplex virus (HSV) type 2 complicated with herpetic urethritis. By analysis of the restriction endonuclease digestion pattern of the viral DNA, two isolates, one from the penile lesion and one from the urethra, were identified as the same strain.
J Dermatol 1994 Aug
PMID:Male genital herpes complicated with urethral infection. 796 59

Pyrimidine dimers were induced in duplicates of cultured human skin fibroblasts by irradiation with various doses of UVB radiation. Subsequently, one set of cells was further exposed to either 5 or 10 J/cm2 of UVA radiation to assess the photoreactivating activity of this spectral range in a human cell system. Following irradiation, pyrimidine dimers were quantified in all cells by determining the number of endonuclease-sensitive sites (ESS). No difference in the yield of ESS was observed between cells which had been irradiated with UVB only as compared to cells which subsequently had been exposed to 5 or 10 J/cm2 UVA. In contrast, subsequent exposure of UVB-irradiated cells of Monodelphis domestica to 10 J/cm2 UVA resulted in an almost 50% reduction of UVB-induced pyrimidine dimers. These data indicate that UVA does not induce photoenzymatic repair in human fibroblasts.
Exp Dermatol 1993 Aug
PMID:UVA does not photoreactivate pyrimidine dimers in cultured human fibroblasts. 816 34

Exposure of skin to ultraviolet (UV) radiation inhibits the induction of delayed-type hypersensitivity (DTH) responses initiated at a distant, unirradiated site. Recent studies attributed this form of immune suppression to DNA damage in the form of cyclobutane pyrimidine dimers (CPD). In the present study, we investigated the protective defects of sunscreens on UV-induced systemic suppression of DTH to Candida albicans, inflammation, and DNA damage. The photoprotective effects of sunscreen preparations containing 8% octyl-N-dimethyl-p-aminobenzoate, 7.5% 2-ethylhexyl-p-methoxycinnamate, or 6% benzophenone-3 were studied in C3H mice exposed to a single dose of 500 mJ/cm2 UVB radiation from FS40 sunlamps. Inflammation was determined by the amount of skin edema at the site of UV irradiation, and DNA damage was assessed by measuring the frequency of endonuclease-sensitive sites in the epidermis. Application of the sunscreens before UV irradiation gave 75-97% protection against UV-induced edema, 67-91% protection against formation of CPD, but only 30-54% protection against suppression of DTH. In contrast, the topical application of liposomes containing a CPD-specific DNA repair enzyme immediately after UV irradiation resulted in 82% protection against suppression of DTH, but at best, 39% protection against skin edema. These findings demonstrate that sunscreens give less protection against UV-induced immune suppression than against skin edema and CPD formation. Furthermore, they suggest that less DNA damage is required to cause UV-induced immune suppression than to cause sunburn.
J Invest Dermatol 1993 Oct
PMID:Effects of sunscreens and a DNA excision repair enzyme on ultraviolet radiation-induced inflammation, immune suppression, and cyclobutane pyrimidine dimer formation in mice. 840 17

Mutations within the gene encoding the anchoring fibril protein type VII collagen (COL7A1) have recently been established as the pathogenetic basis for the inherited blistering skin disorder, dystrophic epidermolysis bullosa. We report a patient with a moderately severe phenotype of recessive dystrophic epidermolysis bullosa. We report a patient with a moderately severe phenotype of recessive dystrophic epidermolysis bullosa, in whom COL7A1 mutations have been identified on both alleles. The patient is a 5-y-old Japanese male of nonconsanguineous parents, with clinical features including generalized trauma-induced blistering since birth, complete loss of nails, and partial fusion of the fingers and toes. Immunofluorescence microscopy examination of the dermal-epidermal junction in the patient's skin revealed near-normal intensity staining with an antitype VII collagen antibody (LH7:2). Transmission electron microscopy showed a reduced number of thin, poorly-formed anchoring fibrils. PCR amplification of genomic DNA, followed by heteroduplex analysis, and nucleotide sequencing demonstrated that the patient was a compound heterozygote for a nonsense mutation (E2858X) within the NC-2 domain of type VII collagen and a missense mutation (G2576R) within the type VII collagen triple helix. Both mutations were verified by restriction endonuclease digestion. Information about these mutations advances our understanding of genotype-phenotype correlations in dystrophic epidermolysis bullosa, and further delineates the mechanisms involved in dermal-epidermal dysadhesion.
J Invest Dermatol 1996 Jan
PMID:Molecular basis of recessive dystrophic epidermolysis bullosa: genotype/phenotype correlation in a case of moderate clinical severity. 859 61


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