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At least 73 records · Page 4Linked to original sources
PubMed1994

Incomplete excision of CIN in conization: further excision or conservative management?

The aim of this study was to investigate the experience of the further management in 112 cases with histological diagnosis of incomplete excision of CIN in cone biopsy. Two groups of women were studied. The women in the first group (n = 78) had a second excision while the women in the second group (n = 34) underwent conservative management with cytology and colposcopy. The histologic, cytologic and colposcopic findings in the women of both groups were compared. From the first group 38% had a second cone, 62% an hysterectomy; in 5 cases the second cone was followed by hysterectomy and the histology was negative in 75% and 65%, respectively. No indication of residual disease was found within 2-10 years of follow-up in any of the women in the second group. According to our study and being aware of the natural history of CIN, we can conclude that the decision for further excision should not be based exclusively on the histology report of involved margins, but should only be taken after careful cytological and colposcopic selection of the cases.

Adult↗
PubMed2004

[Extrafascial excision of the rectum or total meso-rectal excision?].

Total mesorectal excision is a valuable technique in preventing local recurrences cancer. However the use of the word "mesorectum" is inaccurate anatomically, and the implication that total excision of all the perirectal fat contained within the perirectal fascia in all patients with rectal cancer will minimize local recurrences remains contentious. The term extrafascial excision of the rectum is more accurate. He may contribute as well to a better understanding of the surgical technique allowing all surgeons to improve their own results.

Fasciotomy↗
PubMed2004

Nucleotide excision repair defect influences lethality and mutagenicity induced by Me-lex, a sequence-selective N3-adenine methylating agent in the absence of base excision repair.

Using a yeast shuttle vector system, we have previously reported on the toxicity and mutagenicity of Me-lex, [1-methyl-4-[1-methyl-4-[3-(methoxysulfonyl)propanamido]pyrrole-2-carboxamido]pyrrole-2-carboxamido]propane, a compound that selectively generates 3-methyladenine (3-MeA). We observed that a mutant strain defective in Mag1, the glycosylase that excises 3-MeA in the initial step of base excision repair (BER) to generate an abasic site, is significantly more sensitive to the toxicity of Me-lex with respect to wild type but shows only a marginal increase in mutagenicity. A strain defective in AP endonuclease activity (Deltaapn1apn2), also required for functional BER, is equally sensitive to the toxicity as the Deltamag1 mutant but showed a significantly higher mutation frequency. In the present work, we have explored the role of nucleotide excision repair (NER) in Me-lex-induced toxicity and mutagenicity since it is known that NER acts on abasic sites in vivo in yeast and in vitro assays. To accomplish this, we have deleted one of the genes essential for NER in yeast, namely, RAD14, both in the context of an otherwise DNA repair-proficient strain (Deltarad14) and in a BER-defective isogenic derivative lacking the MAG1 gene (Deltamag1rad14). Interestingly, no sensitivity to the treatment with Me-lex was conferred by the simple deletion of RAD14. However, a significant enhancement in toxicity and mutagenicity was observed when cells lacked both Rad14 and Mag1. The mutation spectrum induced by Me-lex in the Deltamag1rad14 strain is indistinguishable from that observed in the Deltaapn1/Deltaapn2 or in the Deltamag1 strains. The results indicate that in yeast NER can play a protective role against 3-MeA-mediated toxicity and mutagenicity; however, the role of NER is appreciable only in a BER-defective background.

Adenine↗
PubMed1994

Excision of DNA fragments corresponding to the unit-length a sequence of herpes simplex virus type 1 and terminus variation predominate on one side of the excised fragment.

DNA fragments corresponding to the unit-length a sequence of herpes simplex virus type 1 (HSV-1) were identified in HSV-1 DNA preparations extracted by the method of Hirt. The DNA fragments were molecularly cloned, and nucleotide sequences were determined. Most termini of the fragments were at sites on DR1 corresponding to the termini of linear HSV-1 DNA generated by the cleavage-packaging system. In one-step growth experiments, DNA fragments of the unit-length a sequence appeared simultaneously with the termini of linear HSV-1 DNAs produced by cleavage of circular and concatemeric DNAs. Therefore, excision of the unit-length a sequence appeared closely related to the cleavage-packaging system. Termini of the excised DNA fragments of the variant a sequence with two DR2 arrays varied on the L-component side, while termini on the S-component side were at the site on DR1 corresponding to the authentic cleavage site. It is thus assumed that the cleavage-packaging system functions adequately on the DR1 second distal from the S component, and cleavages of other DR1 are rare and less accurate. If this notion is tenable, then most termini on the S-component side of the excised DNA fragments are derived from the second DR1 properly cleaved and should be constant, while termini on the L-component side are from regions on and around the DR1 third distal from the S component and may be variable. Cleavage of DR1 is likely to be affected by the topological relationship with the S component.

Animals↗
PubMed1979

Excisional biopsy and delayed wide excision versus primary wide excision of malignant melanoma.

In a retrospective study of 269 cutaneous malignant melanomas in stage I the influence of biopsy on survival was studied. Sixty patients were treated with primary wide excision and 209 patients with excisional biopsy followed by wide excision. The 5-year survival rates for the two groups were 75.0% and 82.8% respectively. There was an equal distribution of prognostic factors such as thickness, level of invasion, presence of ulceration, location and maximal size of the tumours in the two groups. As excisional biopsy with subsequent wide excision gives an accurate histopathologic diagnosis and permits a more rational treatment of thin melanomas, this form of treatment is recommended.

Biopsy↗
PubMed2000

Excision of tamoxifen-DNA adducts by the human nucleotide excision repair system.

The antiestrogen tamoxifen is used in the treatment of breast cancer and has recently been recommended as a chemopreventive drug for women at high risk for breast cancer. However, women treated with the drug have an increased incidence of endometrial cancer. It has been suggested that this endometrial cancer might result from mutagenic DNA adducts, which are formed by electrophilic tamoxifen species generated by metabolic activation of the drug. Because the frequency of damage-induced mutations is strongly dependent on the repairability of the lesion, we investigated the repair of the major tamoxifen-DNA adducts by the human nucleotide excision repair system. Using the reconstituted human excision repair system and synthetic DNA substrates, we found that the four types of tamoxifen-DNA adducts detected in the endometrium were repaired with moderate to poor efficiency by nucleotide excision repair. It is concluded that individual variations in repair capacity may play a role in the development of tamoxifen-induced endometrial cancer.

Antineoplastic Agents, Hormonal↗
PubMed1988

Results of L4-L5 disc excision alone versus disc excision and fusion.

We evaluated the results of 85 patients having L4-L5 disc excision (52 having disc excision alone, and 33 having disc excision and fusion) using the Smiley-Webster scale at an average follow-up of 7.3 years. Both groups (fusion and nonfusion) were comparable except that the nonfusion group had a significantly higher percentage of patients with a history of chronic back pain and degenerative changes on their initial radiographs. The fusion group had significantly better results compared with the nonfusion group (85% satisfactory results versus 39% satisfactory results). The most common cause of unsatisfactory results in the fusion group was pseudarthrosis (two) while progressive degenerative disc disease (18) and recurrent disc prolapse (eight) were the most common cause of unsatisfactory results in the nonfusion group. The overall reoperation rate was 9.4% (13.5% in the nonfusion group, and 3% in the fusion group.

Adult↗
PubMed1995

Human papillomavirus detection in cervical smears and cervical tissue excised by the Loop Electrosurgical Excision Procedure (LEEP). Diagnostic value of cytology, colposcopy and histology.

A study was performed on 176 patients with benign cervical lesions. Human papillomavirus (HPV) structural antigens which were stained with the immunoperoxidase staining were sought for in cervical smears and in cervical tissues excised by the loop electrosurgical excision procedure (LEEP). HPV infection was found in 16.4% of the patients. Furthermore, cytologic screening on Papanicolaou (PAP) smears, colposcopy, and histologic examinations of whole transformation zones excised by the LEEP were performed. The diagnosis of HPV was based on the positive immunoperoxidase staining of either the exfoliated cells or the cervical tissue. HPV was detected on 5.6% of the PAP smears. The reliability of cytologic colposcopic, and histologic diagnosis of HPV was investigated.

Antigens, Viral↗
PubMed1996

Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein.

The human basal transcription factor TFIIH plays a central role in two distinct processes. TFIIH is an obligatory component of the RNA polymerase II (RNAP II) transcription initiation complex. Additionally, it is believed to be the core structure around which some if not all the components of the nucleotide excision repair (NER) machinery assemble to constitute a nucleotide excision repairosome. At least two of the subunits of TFIIH (XPB and XPD proteins) are implicated in the disease xeroderma pigmentosum (XP). We have exploited the availability of the cloned XPB, XPD, p62, p44, and p34 genes (all of which encode polypeptide subunits of TFIIH) to examine interactions between in vitro-translated polypeptides by co-immunoprecipitation. Additionally we have examined interactions between TFIIH components, the human NER protein XPG, and the CSB protein which is implicated in Cockayne syndrome (CS). Our analyses demonstrate that the XPB, XPD, p44, and p62 proteins interact with each other. XPG protein interacts with multiple subunits of TFIIH and with CSB protein.

Base Sequence↗
PubMed2003

Histopathologic recognition of involved margins of lentigo maligna excised by staged excision: an interobserver comparison study.

OBJECTIVES: To assess interobserver and intraobserver concordance for identifying positive and negative margins in staged excisions of lentigo maligna and lentigo maligna melanoma and to determine if control biopsy specimens are useful to improve concordance. DESIGN: Retrospective, randomized interobserver and intraobserver comparison study of archived pathologic specimens. The study was conducted in 3 phases, and slides were evaluated blindly and independently by 5 pathologists: in phase 1, all slides were randomized and diagnosed as positive or negative. In phase 2, every third slide was evaluated again and diagnosed as positive or negative. In phase 3, slides were organized into cases, allowing evaluation of each margin in the context of the positive control (tumor from the center of the lesion) and negative control (control biopsy specimen), if available. SETTING: University referral center. STUDY MATERIAL: A total of 301 glass microscopic slides from 27 patients who underwent staged excision for lentigo maligna or lentigo maligna melanoma from March 1997 to April 2001. MAIN OUTCOME MEASURES: Interobserver and intraobserver concordance between original diagnoses and study diagnoses rendered on all slides by 5 pathologists. RESULTS: Phase 1 and 3 agreement was moderate (kappa range, 0.4-0.5). Phase 2 (intraobserver) agreement was moderate to good for all pathologists (kappa range, 0.6-0.9). Subset analysis revealed a statistically significant increase in agreement with the use of a control strip biopsy specimen for difficult slides. CONCLUSIONS: Interobserver concordance for margin analysis in lentigo maligna and lentigo maligna melanoma is moderate, and intraobserver concordance is moderate to good. A control strip biopsy specimen may improve concordance in some cases.

Adult↗
PubMed2001

Synergism between base excision repair, mediated by the DNA glycosylases Ntg1 and Ntg2, and nucleotide excision repair in the removal of oxidatively damaged DNA bases in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, inactivation of the two DNA N-glycosylases Ntg1p and Ntg2p does not result in a spontaneous mutator phenotype, whereas simultaneous inactivation of Ntglp, Ntg2p and Radlp or Rad14p, both of which are involved in nucleotide excision repair (NER), does. The triple mutants rad1 ntg1 ntg2 and rad14 ntg1 ntg2 show 15- and 22-fold increases, respectively, in spontaneous forward mutation to canavanine resistance (CanR) relative to the wild-type strain (WT). In contrast, neither of these triple mutants shows an increase in the incidence of Lys+ revertants of the lys1-1 ochre allele. Furthermore, the rad1 ntg1 ntg2 mutant is hypersensitive to the lethal effect of H2O2 relative to WT, rad1 and ntg1 ntg2 mutant strains. Moreover, the rad1 ntg1 ntg2 strain is hypermutable (CanR and Lys+) upon exposure to H2O2, relative to WT, rad1 and ntg1 ntg2 strains. Mutagen sensitivity and enhanced mutagenesis in the rad1 ntg1 ntg2 triple mutant, relative to the other strains tested, were also observed upon exposure to oxidizing agents such as tertbutylhydroperoxide and menadione. In contrast, the sensitivity of the rad1 ntg1 ntg2 triple mutant to gamma-irradiation does not differ from that of the WT. However, the triple mutant shows an increase in the frequency of Lys+ revertants recovered after gamma-irradiation. The results reported in this study demonstrate that base excision repair (BER) mediated by Ntglp and Ntg2p acts synergistically with NER to repair endogenous or induced lethal and mutagenic oxidative DNA damage in yeast. The substrate specificity of Ntg1 p and Ntg2p, and the spectrum of lesions induced by the DNA-damaging agents used, strongly suggest that oxidized DNA bases, presumably oxidized pyrimidines, represent the major targets of this repair pathway.

Alleles↗
PubMed1984

Quantitative characterization of pyrimidine dimer excision from UV-irradiated DNA (excision capacity) by cell-free extracts of the yeast Saccharomyces cerevisiae.

Cell-free extracts from wild-type yeast (RAD+) and from rad mutants belonging to the RAD3 epistatic group (rad1-1, rad2-1, rad3-1, rad4 -1) contain activities catalyzing the excision of pyrimidine dimers (PD) from purified ultraviolet-irradiated DNA which was not pre-treated with exogenous UV-endonuclease. The level of these activities in cell-free extracts from rad mutants did not differ from that in wild-type extract and was close to the in vivo excision capacity of the latter calculated from the LD37 (about 10(4) PD per haploid genome).

DNA, Fungal↗
PubMed1975

The influence of caffeine on cell survival in excision-proficient and excision-deficient xeroderma pigmentosum and normal human cell strains following ultraviolet-light irradiation.

A uniform response to UV of four normal cell strains was demonstrated. One excision-proficient xeroderma pigmentosum variant strain (XP7TA) had a wild-type UV response but a second (XP30RO) was more sensitive. An excision-deficient xeroderma pigmentosum strain XP4L0 was substantially more sensitive than wild-type cell strains. A continuous post-irradiation treatment with non-toxic levels of caffeine enhanced the lethal effect of UV light in both xeroderma pigmentosum variant cell strains but not in cells from normal individuals. There was no detectable effect on cells from a xeroderma pigmentosum individual from complementation group A. These results correlate well with observations on the influence of caffeine on post-replication repair in the three classes of cells.

Caffeine↗
PubMed1979

Enhancement of excision-repair efficiency by conditioned medium from density-inhibited cultures in V79 Chinese hamster cells: evidence for excision repair as an error-free repair process.

Conditioned medium from density-inhibited V79 Chinese hamster cell cultures, given as a post-treatment to UV-irradiated homologous cells, was demonstrated to reduce the lethal action of ultraviolet light by temporarily blocking DNA replication. Since the increased survival was not affected by various non-toxic concentrations of caffeine, such protective effect would be attributable to the prolonged intervention of excision repair before DNA replication during the post-treatment period. The influence of conditioned medium on the UV-induced mutation at the ouabain-resistance locus was also examined and a significant decrease in mutation frequency was noted. The observed reduction in killing and mutation as a result of post-incubation in conditioned medium, which delays DNA replication, would be interpreted as evidence that conditioned medium provides a longer period of time for an error-free excision-repair process, leaving lesion in DNA available for error-prone post-replication repair.

Animals↗
PubMed1995

Visuo-spatial short-term recognition memory and learning after temporal lobe excisions, frontal lobe excisions or amygdalo-hippocampectomy in man.

Three groups of neurosurgical patients with temporal lobe excisions, frontal lobe excisions or unilateral amygdalo-hippocampectomy were assessed on a computerized battery of tasks designed to investigate visuo-spatial short-term recognition memory and learning. A double dissociation is reported between deficits of pattern recognition memory and spatial recognition memory which were observed in the two posterior groups and frontal lobe patients, respectively. In addition, both the temporal lobe and amygdalo-hippocampectomy patients were also impaired on a delayed matching-to-sample paradigm whilst frontal lobe patients performed at an equivalent level to controls. Finally, whilst the impaired performance of the three groups was indistinguishable on a test of paired-associate learning, quite different patterns of deficit were observed on a test of spatial working memory. These results are discussed with reference to recent suggestions that visual recognition memory is mediated by a neural system which includes, as major components, the inferotemporal cortex, the medial temporal lobe structures and particular sectors of the frontal lobe, and are compared to previous findings from patients with idiopathic Parkinson's disease and dementia of the Alzheimer type.

Adult↗
PubMed2003

Substrate specificities and excision kinetics of DNA glycosylases involved in base-excision repair of oxidative DNA damage.

Reactive oxygen-derived species such as free radicals are formed in living cells by normal metabolism and exogenous sources, and cause a variety of types of DNA damage such as base and sugar damage, strand breaks and DNA-protein cross-links. Living organisms possess repair systems that repair DNA damage. Oxidative DNA damage caused by free radicals and other oxidizing agents is mainly repaired by base-excision repair (BER), which involves DNA glycosylases in the first step of the repair process. These enzymes remove modified bases from DNA by hydrolyzing the glycosidic bond between the modified base and the sugar moiety, generating an apurinic/apyrimidinic (AP) site. Some also possess AP lyase activity that subsequently cleaves DNA at AP sites. Many DNA glycosylases have been discovered and isolated, and their reaction mechanisms and substrate specificities have been elucidated. Most of the known products of oxidative damage to DNA are substrates of DNA glycosylases with broad or narrow substrate specificities. Some possess cross-activity and remove both pyrimidine- and purine-derived lesions. Overlapping activities between enzymes also exist. Studies of substrate specificities have been performed using either oligodeoxynucleotides with a single modified base embedded at a specific position or damaged DNA substrates containing a multiplicity of pyrimidine- and purine-derived lesions. This paper reviews the substrate specificities and excision kinetics of DNA glycosylases that have been investigated with the use of gas chromatography/mass spectrometry and DNA substrates with multiple lesions.

Animals↗
PubMed1989

Discontinuous DNA replication in a lig-7 strain of Escherichia coli is not the result of mismatch repair, nucleotide-excision repair, or the base-excision repair of DNA uracil.

After pulse-labeling with 3H-thymidine for 30 s at 42 degrees C, the newly-synthesized DNA from uvrB5 lig-7, uvrB5 lig-7 ung-1 (or ung152), uvrB5 lig-7 mutL218 (or mutS215), and uvrB5 lig-7 ung-1 mutL218 (or mutS215) cells sedimented very slowly in alkaline sucrose gradients. The bulk of these DNA molecules were smaller than 2,000 nucleotides long (i.e., about the size of Okazaki fragments), and none of the 3H-radioactivity was found to sediment as high-molecular-weight DNA. These results indicate that the apparent discontinuous DNA replication observed in lig-7 strains is not the result of mismatch repair, nucleotide-excision repair, or the base-excision repair of DNA uracil.

DNA Repair↗