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A Segal

Publications and source records attributed to A Segal.

At least 127 records · Page 7Linked to original sources

Carcinogen specificity in the activation of transforming genes by direct-acting alkylating agents.

DNAs from rat nasal and mouse skin carcinomas and fibrosarcomas induced by the alkylating agents methylmethane sulfonate (MMS), beta-propiolactone (BPL), and dimethylcarbamyl chloride (DMCC) were tested for their ability to transform NIH3T3 cells by DNA transfection. Each of eight MMS-induced rat nasal carcinomas and two of five BPL-induced mouse skin tumors were positive in the transfection assay while all of four fibrosarcomas and six carcinomas induced by DMCC were negative. Anchorage independent growth, tumorigenicity in nude mice, and secondary transfection confirmed the transformed phenotype of the positive transfectants. The transfectants from MMS-induced tumor DNAs did not contain restriction fragments homologous to rat H-, K- or N-ras oncogenes although exogenous (rat) tumor-derived DNA sequences were detected in transfectant genomes by Southern analysis. In contrast a BPL-induced mouse skin tumor showed evidence of containing activated H-ras. These results suggest specificity among causal chemical carcinogens for activation of transforming genes in experimental tumors.

Alkylating Agents↗

Evaluation of argon laser photocoagulation of the posterior pole in oedematous diabetic retinopathy.

The authors present the results obtained in the treatment of oedematous diabetic retinopathy of 70 patients, i.e. 129 eyes. Follow-up was from 6 months to 6 years. Argon laser photocoagulation of the posterior pole is simple and without risk at the early stages of oedematous retinopathy, and has also proved to be effective in the later stages. Out of 115 eyes exhibiting oedemas of the posterior pole, 84% were stabilized or improved. The same encouraging results were obtained in the case of macular oedemas. Ideally, regular follow-up and treatment as required should prevent cystoid degeneration of the macula.

Diabetes Mellitus, Type 1↗

Direct alkylation of calf thymus DNA by acrylonitrile. Isolation of cyanoethyl adducts of guanine and thymine and carboxyethyl adducts of adenine and cytosine.

Reaction of the rodent carcinogen acrylonitrile (AN) at pH 7.0 for 10 and/or 40 days with 2'-deoxyadenosine (dAdo), 2'-deoxycytidine (dCyd), 2'-deoxyguanosine (dGuo), 2'-deoxyinosine (dIno), and thymidine (dThd) resulted in the formation of cyanoethyl and carboxyethyl adducts. The adducts isolated were 1-(2-carboxyethyl)-dAdo (1-CE-dAdo), N6-CE-dAdo, 3-CE-dCyd, 7-(2-cyanoethyl)-Gua (7-CNE-Gua), 7,9-bis-CNE-Gua, imidazole ring-opened 7,9-bis-CNE-Gua, 1-CNE-dIno, and 3-CNE-dThd. Structures were assigned on the basis of UV spectra and electron impact (EI), desorption chemical ionization (DCI) and Californium-252 fission fragment ionization mass spectra. The carboxyethyl adducts resulted from initial cyanoethylation at a ring nitrogen adjacent to an exocyclic nitrogen followed by rapid hydrolysis of the nitrile moiety to a carboxylic acid. It was postulated that the facile hydrolysis is the result of an intramolecular-catalyzed reaction resulting from the formation of a transient cyclic intermediate between nitrile carbon and exocyclic nitrogen. AN was reacted with calf thymus DNA (pH 7.0, 37 degrees C, 40 days) and the relative amounts of adducts isolated was 1-CE-Ade (25.8%), N6-CE-Ade (7.6%), 3-CE-Cyt (1.3%), 7-CNE-Gua (25.8%), 7,9-bis-CNE-Gua (4.3%), imidazole ring-opened 7,9-bis-CNE-Gua (18.9%) and 3-CNE-Thy (16.3%). Thus a carcinogen once adducted to a base in DNA was shown to be subsequently modified resulting in a mixed pattern of cyanoethylated and carboxyethylated AN-DNA adducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylonitrile↗

Direct alkylation of 2'-deoxynucleosides and DNA following in vitro reaction with acrylamide.

Reaction of the rodent carcinogen acrylamide (AM) at pH 7.0 and 37 degrees C for 10 and 40 days with 2'-deoxyadenosine (dAdo), 2'-deoxycytidine (dCyd), 2'-deoxyguanosine (dGuo), and thymidine (dThd) resulted in the formation of 2-formamidoethyl and 2-carboxyethyl adducts via Michael addition. The alkylated 2'-deoxynucleoside adducts isolated (% yield after 40 days) were 1-(2-carboxyethyl)-dAdo (1-CE-dAdo) (8%), N6-CE-dAdo (21%) (via Dimroth rearrangement of 1-CE-dAdo), 1-CE-dGuo (4%), 7-(2-formamidoethyl)-Gua (7-FAE-Gua) (6%), 7, 9-bis-FAE-Gua (1%) (formed by reaction of AM with depurinated 7-FAE-Gua during the course of the reaction), and 3-FAE-dThd (4%). The products isolated following in vitro reaction of AM with calf thymus DNA at pH 7.0 and 37 degrees C for 40 days were (nmol/mg DNA) 1-CE-dAdo (5.5), N6-CE-dAdo (1.4), 3-CE-dCyd (2.8), 1-CE-dGuo (0.3), and 7-FAe-Gua (1.6). Compound 3-FAE-dThd was not detected. Structures were assigned on the basis of chemical properties, UV spectra, and electron impact, chemical ionization, desorption chemical ionization, Californium-252 fission fragment ionization, and fast atom bombardment mass spectra. A facile hydrolysis of the amide group to a carboxylic acid was observed when AM alkylated a ring nitrogen adjacent to an exocyclic nitrogen atom. In previous studies, we had observed an analogous phenomenon when studying the in vitro reactions of acrylonitrile with DNA, i.e., a facile hydrolysis of nitrile to carboxylic acid when acrylonitrile alkylated (via Michael addition) a ring nitrogen adjacent to an exocyclic nitrogen. Since the nitrile group hydrolyzes to a carboxylic acid via an amide intermediate, we had hypothesized in the present study that the same facile hydrolysis of amide to carboxylic acid would occur under identical stereochemical conditions as had occurred with the nitrile group. Thus, in vitro alkylation of calf thymus DNA by both acrylonitrile and, in the present study, AM, resulted in mixed adduct formation.

Acrylamide↗

[Participation of the external carotid artery in orbital vascularization].

The authors present the result of 70 dissections of the arterial vascular system of the orbit. The craniofacial junction is an important location because of possible anastomosis between the two carotid systems. These anastomosis can be situated at the meningeal level, palpebral and also inside the orbit cavity. The embryology of the encephalic vascular supply allows one to explain the possible dual origin of the orbital blood supply. This work shows the frequent participation of the external carotid artery to the orbital vascularisation by mean of three collateral branches: the infraorbital artery, a branch of the maxillary artery, partakes in the arterial supply of the inferior oblique muscle in 85,7% of cases. Usually, the inferior muscular artery which is a branch of the ophthalmic artery also partakes in this supply. In very exceptional cases (2 of 70) the infraorbital artery alone supplies the muscle. the lacrimal artery which can come from the external carotid system either from the middle meningeal artery or from the anterior deep temporal artery. This meningolacrimal artery can be either a solo lacrimal artery (17,14% of cases) or be associated with another classical lacrimal artery, from the ophthalmic artery (11,43%). These lacrimal arteries coming from the external carotid system have the following characteristics: they are thinner than classical arteries, they penetrate the orbit by their own orifice, the Hyrtl canal, and they can participate in the muscular vascularisation, especially of the lateral rectus. When these arteries are unique, most often they are encountered when the ophthalmic artery has undercrossed the optic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗

In vitro alkylation of calf thymus DNA by acrylonitrile. Isolation of cyanoethyl-adducts of guanine and thymine and carboxyethyl-adducts of adenine and cytosine.

Reaction of the rodent carcinogen acrylonitrile (AN) at pH 5.0 and/or pH 7.0 for 10 and/or 40 days with 2'-deoxyadenosine (dAdo), 2'-deoxycytidine (dCyd), 2'-deoxyguanosine (dGuo), 2'-deoxyinosine (dIno), N6-methyl-2'-deoxyadenosine (N6-Me-dAdo) and thymidine (dThd) resulted in the formation of cyanoethyl and carboxyethyl adducts. Adducts were not detected after 4 h. The adducts isolated were 1-(2-carboxyethyl)-dAdo (1-CE-dAdo), N6-CE-dAdo, 3-CE-dCyd, 7-(2-cyanoethyl)-Gua (7-CNE-Gua), 7,9-bis-CNE-Gua, imidazole ring-opened 7,9-bis-CNE-Gua, 1-CNE-dIno, 1-CE-N6-Me-dAdo and 3-CNE-dThd. Structures were assigned on the basis of UV spectra and electron impact (EI), chemical ionization (CI), desorption chemical ionization (DCI) and Californium-252 fission fragment ionization mass spectra. Evidence is presented which strongly suggests that N6-CE-dAdo was formed by Dimroth rearrangement of 1-CE-dAdo during the reaction between AN and dAdo. The carboxyethyl adducts resulted from initial cyanoethylation (by Michael addition) at a ring nitrogen adjacent to an exocyclic nitrogen atom followed by rapid hydrolysis of the nitrile moiety to a carboxylic acid. It was postulated that the facile hydrolysis is an autocatalyzed reaction resulting from the formation of a cyclic intermediate between nitrile carbon and exocyclic nitrogen. AN was reacted with calf thymus DNA (pH 7.0, 37 degrees C, 40 days) and the relative amounts of adducts isolated were 1-CE-Ade (26%), N6-CE-Ade (8%), 3-CE-Cyt (1%), 7-CNE-Gua (26%), 7,9-bis-CNE-Gua (4%), imidazole ring-opened 7,9-bis-CNE-Gua (19%) and 3-CNE-Thy (16%). Thus a carcinogen once adducted to a base in DNA was shown to be subsequently modified resulting in a mixed pattern of cyanoethylated and carboxyethylated AN-DNA adducts. Three of the adducts (1-CE-Ade, N6-CE-Ade and 3-CE-Cyt) were identical to adducts previously reported by us to be formed following in vitro reaction of the carcinogen beta-propiolactone (BPL) and calf thymus DNA. The results demonstrate that AN can directly alkylate DNA in vitro at a physiological pH and temperature.

Acrylonitrile↗

[Struma ovarii].

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Adult↗

Liquid nitrogen therapy.

Benign skin lesions such as solar and seborrhoeic keratoses, viral warts, and skin tags can be treated successfully by cutaneous cryotherapy. Complications are infrequent if the correct technique is used and local anaesthetic usually is unnecessary. Liquid nitrogen (boiling point -196 degrees C) is the usual freezing agent but carbon dioxide snow (-79 degrees C) is an adequate substitute.

Cryosurgery↗