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P element excision in Drosophila melanogaster and related drosophilids.

The frequency of P element excision and the structure of the resulting excision products were determined in three drosophilid species. Drosophila melanogaster, D. virilis, and Chymomyza procnemis. A transient P element mobility assay was conducted in the cells of developing insect embryos, but unlike previous assays, this mobility assay permitted the recovery of excision products from plasmids regardless of whether the excision event was precise or imprecise. Both quantitative and qualitative differences between the products of excision in the various species studied were observed. The frequency with which P element excision products were recovered from D. melanogaster was 10-fold greater than from D. virilis and C. procnemis; however, the proportion of all excision events resulting in the reversion of a P-induced mutant phenotype was the same. Virtually all excision products recovered, including those resulting in a reversion of the mutant phenotype, did not result in the exact restoration of the original target sequence. Sequence analysis suggested that duplex cleavage at the 3' and 5' termini of the P element, or their subsequent modification, occurred asymmetrically and interdependently. P element-encoded transposase was not absolutely required for P element excision.

Animals↗

The hobo transposable element has transposase-dependent and -independent excision activity in drosophilid species.

Mobility of the hobo transposable element was determined for several strains of Drosophila melanogaster and several Drosophila species. Mobility was assessed by use of an in vivo transient assay in the soma of developing embryos, which monitored hobo excision from injected indicator plasmids. Excision was detected in a D. melanogaster strain (cn; ry42) devoid of endogenous hobo elements only after co-injection of a helper plasmid containing functional hobo transposase under either heat shock or normal promoter regulation. Excision was also detected in D. melanogaster without helper in strains known to contain genomic copies of hobo. In Drosophila species confirmed not to contain hobo, hobo excision occurred at significant rates both in the presence and absence of co-injected helper plasmid. In four of the seven species tested, excision frequencies were two- to fivefold lower in the presence of plasmid-borne hobo, hobo excision donor sites were sequenced in indicator plasmids extracted from D. melanogaster cn; ry42 and D. virilis embryos. In the presence of hobo transposase, the predominant excision sites were identical in both species, having breakpoints at the hobo termini with an inverted duplication of proximal insertion site DNA. However, in the absence of hobo transposase in D. virilis, excision breakpoints were apparently random and occurred distal to the hobo termini. The data indicate that hobo is capable of functioning in the soma during embryogenesis, and that its mobility is unrestricted in drosophilids. Furthermore, drosophilids not containing hobo are able to mobilize hobo, presumably by a hobo-related cross-mobilizing system. The cross-mobilizing system in D. virilis is not functionally identical to hobo with respect to excision sequence specificity.

Animals↗

Local excision of carcinoma of the rectum: indications.

To discuss indications for local excision of adenocarcinoma of the low rectum, two different series of patients were analysed. Series I consisted of 60 patients treated by local excision from 1969 to 1985 in whom local recurrence developed. Series II consisted of 59 patients who underwent resection for non high grade tumors less than or equal to 3.5 cm from 1980 to 1990 in whom lymph node spread was studied. A distinction is made between tumors which are obvious cancers and malignant polyps, and the discussion of indications for local excision is orientated to the former. The results of local excision have been disappointing but a number of compromise selections for local excision have been necessary. Endorectal ultrasound has emerged as the most important method of assessing the depth of invasion of the tumor. Stratifying the depth of the tumor is at present the most important prognostic indicator for lymph node metastasis and local recurrence in non high grade tumors. If the muscle layer is invaded by tumor, local metastasis will occur in 17% of patients. It is likely that only tumors involving superficial layers of muscle are suitable for local excision, but this needs further study. Mucinous carcinomas and the presence of lymphatic invasion are contra-indications to local excision. The shape and size of tumors are not independent prognostic indicators. The techniques available for local excision alter the indications. Salvage operations for recurrence after local excision have proved disappointing.

Adenocarcinoma↗

Scar area and cosmetic outcome after circular and elliptical excision of small skin lesions.

BACKGROUND: Cutaneous surgery for removal of small skin tumors is usually performed as elliptical excision. There is some indication that circular excisions could result in cosmetically more favorable scars and should therefore be considered as an alternative method. OBJECTIVE: The aim of this study was to compare circular and elliptical excisions with respect to scar area and cosmetic result. METHODS: Fifty-six operations were performed, 27 elliptical and 29 circular. The cosmetic results were determined as patient's opinion by questionnaire and assessment of photo slides by three independent observers. Also, scar areas were measured by computer program. RESULTS: The scar area was significantly smaller after circular excisions compared with elliptical excisions after 6 and 12 months of observation (p = 0.005 and p = 0.001, respectively). The assessment of cosmetic results by the patients did not differ between the two groups (p = 0.44), while the independent observers slightly favored the cosmetic outcome of elliptical scars (p = 0.03). When analyzing only excisions without complications, there was no difference in cosmetic results between the two groups. CONCLUSION: Circular excisions seemed to cause smaller scars and equal cosmetic results compared with traditional elliptical excisions and could therefore be an alternative method for small skin excisions on the trunk and extremities.

Adult↗

Immediate radical resection after local excision of rectal cancer: an oncologic compromise?

PURPOSE: Local excision for early-staged rectal cancers is controversial. Preoperative understaging is not uncommon and radical resection after local resection may be needed for a curative treatment. The aim of this study was to determine the frequency and outcome of radical resection (within 30 days) after local excision for rectal adenocarcinoma. METHODS: All locally excised rectal cancers (curative intent) that required radical surgery within 30 days were reviewed (1980-2000). T2-3N0-1 stage cancers were each matched to three primary radical surgery controls for stage, age (+/- 5 years), gender, date (+/- 1 years), and type (abdominoperineal resection or low anterior resection) of operation. T1N0-1 cancers were compared with stage-matched rectal cancers treated by either primary radical surgery (n = 78) or local excision alone (n = 77). RESULTS: Fifty-two locally excised rectal adenocarcinomas (29 transanal and 23 polypectomies) were followed by radical surgery (24 abdominoperineal resection and 28 low anterior resection) within 7 (range, 1-29) days. Radical surgery was performed because of a cancerous polyp (n = 42), positive margins (5), lymphovascular invasion (3), and T3-staged cancer (2). Twelve of 52 cancers (23 percent) were found to have nodal involvement and 15 of 52 (29 percent) showed residual cancer in the resected specimen. The T2-3N0-1 stage controls were well matched. No significant difference in tumor location, size, adjuvant therapy, or length of follow-up was noted. Local and distant recurrence occurred in 2 of 4 T2-3N1 tumors and in 2 of 11 T2-3N0 cancers and were comparable to the matched controls, as was survival, with the exception of shorter survival in T3N1 cases, but numbers were too small for a definitive conclusion. Length of follow-up was not different. For T1 cancers, the controls were also comparable regarding patient and tumor demographics and adjuvant therapy. Nodal involvement was 21 percent in T1 study cases and 15 percent in T1 primary radical-surgery controls, with a trend toward location in the lower third of the rectum in both groups (58 percent and 50 percent, respectively). Local recurrence rates were 3 percent in the study group, 5 percent for patients undergoing primary radical surgery, and 8 percent for local excision alone. Distant metastasis (11 percent, 12 percent, and 13 percent, respectively) and overall five-year survival were also not significantly different (78 percent, 89 percent, and 73 percent, respectively). CONCLUSIONS: Nodal involvement in attempted locally excised rectal cancers is not uncommon. Local excision of rectal tumors followed by radical surgery within 30 days in cancer patients does not compromise outcome compared with primary radical surgery. Even after radical surgery for superficial T1 rectal cancers, recurrence rates are not insignificant. Future improvements in preoperative staging may be helpful in selecting tumors for local excision only.

Adenocarcinoma↗

Loop electrosurgical excision procedures for cervical dysplasia: experience in a community hospital.

OBJECTIVE: The study was undertaken to evaluate the use of the loop electrosurgical excision procedure as an outpatient hospital or surgicenter procedure. STUDY DESIGN: The records of 358 patients treated for cervical intraepithelial neoplasia at a large community hospital over a 1-year period were reviewed. RESULTS: The specimens obtained by loop electrosurgical excision procedure and laser cone excision were comparable in size but smaller than those by means of cold-knife conization. Seventy-two percent of loop electrosurgical excision procedure specimens consisted of two to eight tissue fragments (mean 3.4). In addition, 48% of the loop electrosurgical excision procedure specimens and 38% of laser cones had moderate or severe thermal artifacts. Fragmentation and cautery damage precluded orientation of tissue and evaluation of margins in 19% of the cases. CONCLUSIONS: The advent of the loop electrosurgical excision procedure has shifted the management of cervical intraepithelial neoplasia from the office to the outpatient surgery centers. This negates and, in fact, reverses the advantage of loop electrosurgical excision procedure over other methods in regard to cost and convenience through evaluating and treating a patient with cervical intraepithelial neoplasia in one office visit. Loop electrosurgical excision procedures provide specimens that are inferior compared with cold-knife cones; therefore the role of loop electrosurgical excision procedure for the management of cervical intraepithelial neoplasia outside the office appears limited.

Adolescent↗

Splicing of the E2A premessenger RNA of adenovirus serotype 2. Multiple pathways in spite of excision of the entire large intron.

During the early period of infection, the 4.9 kb (kb = 10(3) bases) E2A premRNA of adenovirus serotype 2 is matured mainly into a 2.0 kb mRNA by excision of introns of 2233 and 626 nucleotides. In order to define all the possible steps of splicing occurring in vivo, we characterized splicing intermediates present after a limiting treatment of cells with cycloheximide. Three complementary methods of analysis were used: RNA transfer analysis, S1 nuclease mapping and complementary DNA-RNase assay. Our principal conclusions concerning the poly(A)+ species are as follows. The RNA intermediate family detected is more complex than expected, since two major RNA intermediates of 4.6 kb and 4.3 kb, two minor intermediates of 2.9 kb and 2.6 kb, and a 2.3 kb RNA, which represents a minor alternative mRNA form, are revealed. Despite its large size and the presence of multiple internal donor and acceptor signals, intron 1 is exclusively excised as a whole. Intron 2 is either primarily excised as a whole, removing the standard 626-nucleotide sequence, or a smaller sequence of 337 nucleotides is removed, generating the 2.3 kb alternative mRNA. Kinetics of the ligation reaction demonstrate that the minimal time for excision of intron 2 is no more than two minutes, indicating a high level of co-ordination of the multiple individual reactions occurring during excision of an intron. Besides the major pathway for E2A premRNA splicing, namely the excision first of intron 2, followed by the excision of intron 1 after a lag time of five minutes, a minor pathway (used with a frequency of 10%) can be detected where the order of intron excision was inverted. With the alternative variant of excision of intron 2, at least three different pathways are therefore used to mature the E2A premRNA. RNA intermediates resulting from the cleavage at the 5' end of introns and branching can be detected by S1 mapping experiments, but their low accumulative level (1% relatively to the initial premRNA) precluded their direction by RNA transfer experiments and their complete characterization.

Adenoviridae↗

Surgical management of incompletely excised basal cell carcinomas of the head and neck.

We made a retrospective audit of all basal cell carcinomas excised in the Maxillofacial Units at St. Richard's Hospital, Chichester and the Worthing and Southlands NHS Trust between 1990 and 1999. A total of 3795 BCCs were excised. Of these, 3560 were completely excised (93.8%) and 235 were incompletely excised (6.2%), which compares favourably with other series. Of these, 84 patients had further excision, 11 had radiotherapy, and 140 were kept under review. Residual tumour was present in 45% of the re-excised specimens. Of the 140 cases managed by observation, 21% recurred. Notably, 31% of patients in the observation cohort died of other causes without recurrence. Incomplete excision was significantly more likely (P < 0.001) if multiple lesions were excised at the time of operation. Involvement of multiple margins was not a significant risk factor for recurrence in the 'observed' cohort. This study shows that a flexible strategy, which balances observation, further excision and radiotherapy, is superior to any single approach.

Basal Cell Carcinoma↗

Do basal cell carcinomas recur after complete conventional surgical excision?

For 1378 patients treated in the 11 years 1988-1998 by conventional excision of 1635 basal cell carcinomas, 1516 first index lesions were histologically completely excised. All patients having more than one BCC excised were identified from the data base from 1988 to 2003 to give minimum 5 years follow for last treated primary lesions in 1998. Measured clearance margins around the initial lesions at or near sites of presumptive recurrent lesions were noted and the lesions recorded photographically. All incompletely excised lesions whether or not re-excised were excluded. The median age for all patients was 70 years. Over minimum 5 years follow up, six patients developed nine subsequent lesions contiguous with the scar or graft repair of primary index lesion excision site (probable recurrences). The median interval to recurrence was 41 months (4 months-8 years 10 months), with median lateral clearance margin around the primary tumour of 2 mm (0.3-6.8 mm). A further nine patients developed 11 new lesions near (within 1cm of) the scar or graft of primary index lesion excision site (possible recurrences). The median interval to recurrence was 59 months (1 year-8 years 6 months). The median lateral clearance margin around the primary tumour was 4.1 mm (0.8-5.8 mm). For the two groups combined the maximum recurrence rate expressed as a percentage of index lesions was 1.3% (20/1516). Two thirds of possible and probable recurrences occurred in the temple and forehead, although these sites represented only 22% of all lesions, which may rather suggest new lesions in an area of field change as opposed to residual disease. The measured clearance margins reported here perhaps suggest that some original lesions may well have been completely excised primarily and many 'recurrences' were new primaries. These figures indicate there is a low order of probability for the incidence of recurrent basal cell carcinoma during minimum 5 years follow period after conventional surgical excision and conventional histological assessment of tumour resection margins.

Aged↗

Imbrication versus excision for fascial healing.

BACKGROUND: The purpose of this study was to determine whether imbrication of native fascia versus excision and closure of new raw fascia forms a stronger union. METHODS: We utilized the anterior rectus sheath fascia of Sprague-Dawley rats as the model. Sixty rats underwent fascial tightening procedures. Each rat had the anterior rectus sheath shortened by 1 cm, 30 by imbrication and 30 by excision and closure. Ten of each group were harvested at 7 days' healing, 10 at 14 days, and 10 of each group at 28 days' healing. The anterior rectus sheath was removed, a "dumbbell" shape constructed, and the cross sectional area at the point of interest determined. The fascia was placed on an Instron tensiometer to determine the breaking strength. Tensile strength was calculated and the data analyzed by ANOVA and the Kruskall-Wallis test. Tissue samples of the closures were histologically analyzed for fibroblast counts, degree of inflammation, and presence of dense fibrous connective tissue. Tissue samples were also analyzed for enzymatic collagen crosslinking. RESULTS: There was a statistically significant difference in tensile strength between the two groups at 7, 14, and 28 days. Results show that at 7 days the mean tensile strength of excision was 0.133 kg/mm2 +/- 0.056 and the mean tensile strength of imbrication was 0.083 kg/mm2 +/- .048 (P < 0.05); at 14 days the mean tensile strength of excision was 0.105 kg/mm2 +/- 0.033 and the mean tensile strength of imbrication was 0.057 kg/mm2 +/- 0.014 (P < 0.002), and at 28 days the mean tensile strength of excision was 0.279 kg/mm2 +/- 0.143 and the mean tensile strength of imbrication was 0.145 kg/mm2 +/- 0.061 (P < 0.03). Histologic findings showed no statistical significance between the two closure methods when comparing degree of inflammation or the number of fibroblasts present. However, at 7 and 14 days there is a significantly greater presence of dense fibrous connective tissue in the excision group (P < 0.03 at 7 days and P < 0.044 at 14 days by ANOVA). Collagen crosslink analysis showed that by day 28 there is a significantly greater amount (P < 0.05 by ANOVA) of the difunctional crosslink dihydroxylysinonorleucine (DHLNL) and a greater ratio between DHLNL and the difunctional crosslink hydroxylysinonorleucine (HLNL) in the excision and closure group. CONCLUSION: We conclude that at 7, 14, and 28 days healing, excision provides a significantly stronger closure than imbrication. According to the crosslinking analysis, it is likely that this strength advantage may continue to increase over time. These findings suggest that excision and closure may be the preferred method for fascial tightening procedures.

Animals↗

Rhegmatogenous retinal detachment after block excision of epithelial implantation cysts and tumors of the anterior uvea.

OBJECTIVE: To report on frequency, time of occurrence, treatment, and final outcome of rhegmatogenous retinal detachment after block excision, combined with corneoscleral tectonic grafts, of intraocular epithelial implantation cysts and tumors of the anterior uvea involving the anterior chamber angle. DESIGN: Noncomparative case series. PARTICIPANTS: The study included 144 patients who had consecutively undergone scleral full-thickness block excision of tumors of the anterior uvea (n = 87) or intraocular epithelial implantation cysts (n = 57). Diameter of the block excision ranged between 5.5 and 20 mm. In 39 patients, the tumor extended posterior to the ora serrata. INTERVENTIONS: Retinal detachment surgery. MAIN OUTCOME MEASURES: Retinal detachment rate, visual acuity, risk factors. RESULTS: Retinal detachment occurred in 10 (6.9%) of 144 patients (2 of 57, or 3.5% of patients with cysts; 8 of 87 or 9.2% of patients with tumors) 3 to 12 months after block excision. Six patients underwent primary pars plana vitrectomy with temporary endotamponade by silicone oil, which was removed 3 to 9 months later. In four patients, a scleral buckling procedure only was performed. After a mean follow-up of 31 months after silicone oil removal or the buckling procedure (median, 30 months; range, 13-42 months), the retina has remained attached in all patients operated on. Visual acuity increased from 2/20 (median; range, light perception-6/20) to 8/20 (median; range, 2/20-12/20). In the eyes with retinal detachment compared to the eyes without retinal detachment, the block excision was significantly larger (13.75+/-4.86 mm vs. 9.41+/-3.02; P = 0.01) and was located significantly more posteriorly (limbus distance of posterior excision margin: 6.75+/-2.87 vs. 4.35+/-3.24 mm; P = 0.01). CONCLUSIONS: Scleral buckling procedures and primary pars plana vitrectomy with temporary ocular endotamponade can give acceptable results in eyes with rhegmatogenous retinal detachment occurring after block excision of epithelial implantation cysts or tumors of the anterior uvea. Despite intraoperative vitreous prolapse or tumor extension posterior to the ciliary body, rhegmatogenous retinal detachment occurs in fewer than 10% of patients undergoing block excision of cysts or tumors of the anterior uvea. Size and posterior location of the block excision are the main risk factors for rhegmatogenous retinal detachment, which becomes unlikely later than 12 months after surgery.

Adolescent↗

Repair of DNA damage in mammalian cells after treatment with UV and dimethyl sulphate: discrimination between nucleotide and base excision repair by their temperature dependence.

Alkylating agents have been reported to give rise to both short and long patches of repair. The reason for the different patch sizes is not known. One possibility is that alkylating agents can trigger both base and nucleotide excision repair. Another possibility is that base excision repair itself can result in different patch sizes. Recognition and incision at lesions is the rate limiting step in excision repair. In order to discriminate between base and nucleotide excision repair it would be desirable to be able to distinguish between different incision activities. In order to accurately measure incision rates, the rejoining of the strand-breaks formed must be inhibited. We have used two inhibitors, aphidicolin and 3-aminobenzamide. Aphidicolin, an inhibitor of DNA polymerases alpha/delta/epsilon. caused accumulation of single-strand breaks both after UV and dimethylsulphate. 3-Aminobenzamide, an inhibitor of poly(ADP-ribose)-polymerase caused accumulation of single-strand breaks only after alkylating agents and is thus specific for base excision repair. Enzymatic activities can be characterised by their activation energy. In order to discriminate between base and nucleotide excision repair the temperature dependence of incision activities was determined. When the temperature is decreased, the incision rate is reduced to a larger extent for UV than for DMS-induced repair. Incisions in UV-irradiated cells are practically cut off at temperatures of 15 degrees C and below, whereas DMS-exposed cells still are actively repairing at this temperature. In DMS treated cells the temperature dependence was the same whether aphidicolin or 3-aminobenzamide was used, speaking against an involvement of nucleotide excision repair. In addition, cell lines deficient in nucleotide excision repair responded in the same way to aphidicolin after DMS treatment as normal cells and were able to make incisions at 15 degrees C. This indicates that nucleotide excision repair is not to any significant amount involved in repair of DNA damage induced by a methylating agent.

Aphidicolin↗

Intraoperative ultrasound localization to guide surgical excision of nonpalpable breast carcinoma.

BACKGROUND: This report describes a technique of intraoperative tumor localization by ultrasound without the use of a needle or wire to guide the excision of nonpalpable breast cancers. The results of our experience with pathologic margin status are reviewed. STUDY DESIGN: From 1994 to 1998, 65 breast cancers in 62 patients with biopsy-proved nonpalpable breast cancer were excised using intraoperative ultrasound localization. The pathologic status of the margins from the initial surgical excision specimen and any further excisions, either at the first operation or later procedures, was recorded. The distance from the tumor to the closest margin of excision was also determined. RESULTS: The overall success in achieving pathologically negative excision margins at first operation was 97% (63 of 65 cancers). Three patients underwent a second operative procedure, two for positive margins and one for a margin less than 1 mm (second operation = 4.8% of patients). After completion of the first operative procedure, the mean distance to the closest margin of excision was 0.8 cm. CONCLUSIONS: Intraoperative ultrasound localization for excision of nonpalpable breast cancers is feasible and gives results, in terms of pathologic margins, that are comparable with those achieved by standard needle-wire-guided excisions.

Adult↗

Identification of genes required for excision of CTnDOT, a Bacteroides conjugative transposon.

Integrated self-transmissible elements called conjugative transposons have been found in many different bacteria, but little is known about how they excise from the chromosome to form the circular intermediate, which is then transferred by conjugation. We have now identified a gene, exc, which is required for the excision of the Bacteroides conjugative transposon, CTnDOT. The int gene of CTnDOT is a member of the lambda integrase family of recombinases, a family that also contains the integrase of the Gram-positive conjugative transposon Tn916. The exc gene was located 15 kbp from the int gene, which is located at one end of the 65 kbp element. The exc gene, together with the regulatory genes, rteA, rteB and rteC, were necessary to excise a miniature form of CTnDOT that contained only the ends of the element and the int gene. Another open reading frame (ORF) in the same operon and upstream of exc, orf3, was not essential for excision and had no significant amino acid sequence similarity to any proteins in the databases. The deduced amino acid sequence of the CTnDOT Exc protein has significant similarity to topoisomerases. A small ORF (orf2) that could encode a small, basic protein comparable with lambda and Tn916 excision proteins (Xis) was located immediately downstream of the CTnDOT int gene. Although Xis proteins are required for excision of lambda and Tn916, orf2 had no effect on excision of the element. Excision of the CTnDOT mini-element was not affected by the site in which it was integrated, another difference from Tn916. Our results demonstrate that the Bacteroides CTnDOT excision system is tightly regulated and appears to be different from that of any other known integrated transmissible element, including those of some Bacteroides mobilizable transposons that are mobilized by CTnDOT.

Amino Acid Sequence↗

The significance of tumor persistence after incomplete excision of basal cell carcinoma.

BACKGROUND: Physicians inevitably receive a pathology report after excision of a basal cell carcinoma that indicates that it is incompletely excised. The physician and patient are then left with the dilemma of whether immediate re-excision or close clinical follow-up is indicated. OBJECTIVE: Our purpose was to identify characteristics of incompletely excised basal cell carcinomas that are at low risk for recurrence. METHODS: We retrospectively reviewed the charts and pathology slides of all incompletely excised basal cell carcinomas from 1991 to 1994 in a university hospital tumor registry. RESULTS: Incompletely excised basal cell carcinomas of superficial or nodular subtype, less than 1 cm in diameter, located anywhere except the nose or ears, with less than 4% marginal involvement on the initial inadequate excision had no evidence of tumor persistence. CONCLUSION: When physicians receive a pathology report indicating the incomplete excision of a basal cell carcinoma, they face the dilemma of further management. The majority of patients should undergo immediate re-excision or Mohs micrographic surgery because tumor persistence was found in 28% of cases. Occasionally, for a small group of select patients, close clinical follow-up may be indicated if the risk of recurrence is very low.

Basal Cell Carcinoma↗

Risk factors for incomplete excision of basal cell carcinomas.

Incomplete excision of basal cell carcinomas (BCCs) may be followed by recurrence of the tumor. In order to detect risk factors for incomplete excision of BCCs we performed a cross-sectional study of 1278 patients who underwent a primary excision of BCCs, during a four-year period, within an ambulatory and hospital plastic surgery department setting. Incomplete excision occurred in 159 of 1478 primary excisions of BCCs (10.8%) and was significantly associated with location of the tumors in the eyelids (OR 3.64, 95% CI 1.96-6.71), ears (OR 2.51, 95% CI 1.25-4.94), naso-labial folds (OR 2.26, 95% CI 0.99-5.04) and nose (OR 1.88, 95% CI 1.30-2.71). There was an inverse association with location of the tumors in the upper limbs (OR 0.44, 95% CI 0.21-0.90), back (OR 0.12, 95% CI 0.02-0.48) or chest (OR 0.09, 95% CI 0.00-0.57). Baso-squamous differentiation was associated with incomplete excision of BCCs (p = 0.03). No association was observed between incomplete excision of BCCs and gender, age, setting of the operation (ambulatory vs. hospital), clinical appearance of the lesion (suspected BCCs vs. other diagnoses) or diameter of the lesions. In conclusion, incomplete excision of BCCs was associated with location of the tumors in the eyelids, ears, naso-labial folds and nose. We recommend that in patients with BCCs located in these sites, surgeons should commence particular surgical measures to avoid inadequate excisions of the tumors.

Aged↗

Melanoma of the face: the safety of narrow excision margins.

Recent studies have shown that narrower excision margins may be safe, but the optimal or minimum margin for melanoma is unknown. Wide margins of excision are possible on the trunk and limbs, but functional and cosmetic constraints often limit the extent of excision on the face. A collaborative study from two continents (Cape Town, South Africa and Northwood, England) investigated the outcome of different excision margins of 106 patients with stage I melanoma of the face. The margin of excision was measured from the records of the pathological specimen. Thirty patients had margins of less than 1 cm, 64 had margins of between 1 and 2 cm, and 12 had margins greater than 2 cm. Primary apposition or flap closure was possible in 85 patients. Seven patients developed local recurrences and these were not influenced by the excision margin. This study supports the contention that the primary treatment of cutaneous melanoma on the face should be histologically confirmed complete excision, and that this can be achieved with margins of excision less than 1 cm. Local recurrence is not related to the margin of excision or to tumour thickness.

Adult↗

Excision of oxidatively damaged DNA bases by the human alpha-hOgg1 protein and the polymorphic alpha-hOgg1(Ser326Cys) protein which is frequently found in human populations.

We have investigated the substrate specificity of the major nuclear form of the human Ogg1 protein, referred as alpha-hOgg1, for excision of damaged bases from DNA exposed to gamma-irradiation. Excision products were identified and quantified using gas chromatography/isotope dilution mass spectrometry (GC/IDMS). The GST-alpha-hOgg1 protein used in this study is a fusion of alpha-hOgg1 to the C-terminus of the GST protein. The results show that GST-alpha-hOgg1 protein excises 8-hydroxyguanine (8-OH-Gua) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) from DNA exposed to gamma-irradiation in a solution saturated with N(2)O or air. Fourteen other lesions, including oxidised purines and pyrimidines, were not excised from these substrates. Catalytic constants were measured for the excision of 8-OH-Gua and FapyGua from DNA gamma-irradiated under N(2)O. The k (cat)/ K (m)values for excision of 8-OH-Gua and FapyGua were 4.47 x 10(-5)and 8.97 x 10(-5)(min(-1)nM(-1)), respectively. The substrate specificity and the catalytic parameters of the wild-type GST-alpha-hOgg1 protein were compared to that of a polymorphic form of alpha-hOgg1 harbouring a Ser-->Cys mutation at codon 326. In the Japanese population, 47.6% of individuals possess both alleles coding for the wild-type alpha-hOgg1-Ser(326)and mutant alpha-hOgg1-Cys(326)proteins. The GST-alpha-hOgg1-Cys(326)protein was purified and its substrate specificity was determined by GC/IDMS analysis. The results show that the GST-alpha-hOgg1-Cys(326)protein efficiently excises 8-OH-Gua and FapyGua from gamma-irradiated DNA. The k (cat)/ K (m)values for excision of 8-OH-Gua and FapyGua were 2. 82 x 10(-5)and 4.43 x 10(-5)(min(-1)nM(-1)), respectively. Furthermore, we compared the capacity of these two forms of alpha-hOgg1 to act on substrates containing 2,6-diamino-4-hydroxy-5- N -methylformamidopyrimidine (Me-FapyGua). The k (cat)/ K (m)values for excision of Me-FapyGua were 278 x 10(-5)and 319 x 10(-5)(min(-1)nM(-1)), respectively. Cleavage of 34mer oligodeoxyribonucleotides containing 8-OH-Gua, 8-hydroxyadenine or an apurinic/apyrimidinic site paired with a cytosine was also investigated. The results show that both GST-alpha-hOgg1-Ser(326)and GST-alpha-hOgg1-Cys(326)catalyse the various cleavage reactions at very similar rates. Furthermore, both proteins efficiently complement the mutator phenotype of the fpg mutY mutant of Escherichia coli.

Amino Acid Substitution↗