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A Benson

Publications and source records attributed to A Benson.

45 records · Page 3Linked to original sources

Partition of porphyrins between cyclohexanone and aqueous sodium acetate as a function of pH. Determination of uroporphyrin and of hydrophilic porphyrin conjugates.

1. The partition of uroporphyrins I and III, coproporphyrins I and III, haematoporphyrin IX, porphyrin c and a hydrophilic porphyrin-peptide fraction from variegate-porphyria faeces has been studied in systems of equal volumes of cyclohexanone and sodium acetate buffers of varying pH and concentration. 2. The concentration of acetate in the aqueous phase has little effect on the partition of porphyrin c, but markedly influences that of uroporphyrin. At 50% acetate saturation and pH4.5, only 5% enters the cyclohexanone phase whereas 60% of porphyrin c is extracted under similar conditions. 3. This circumstance forms the basis of a method for the determination of hydrophilic porphyrin-peptides in variegate-porphyria urine. Its reliability has been checked in model experiments. 4. At pH1.5 and an aqueous phase half-saturated with sodium acetate, an equal volume of cyclohexanone removes 95-97% of uroporphyrin and about 55% of porphyrin c. Uroporphyrin may therefore be determined as a second step in the method. 5. For the routine determination of uroporphyrin in systems free from other hydrophilic porphyrins, cyclohexanone extraction may be performed at any pH in the range 1.0-3.0.

Journal Article↗

Purification and properties of coproporphyrinogenase.

1. Coproporphyrinogenase has been prepared from rat-liver mitochondria and its properties have been studied. The isoelectric point was found to be around pH5.0 and the molecular weight to be 80000+/-8000. The pH optimum of the enzymic reaction was 7.4 and the apparent K(m) was of the order 0.03mm. The enzyme was destroyed by boiling and irreversible inactivation occurred below pH3.5. It could be stored at -10 degrees without loss of activity. The enzyme acts specifically on coproporphyrinogen III and does not form protoporphyrinogen from trans-2,4-diacrylicdeuteroporphyrin or its porphyrinogen. It was unaffected by prolonged dialysis and no cofactor requirement could be demonstrated. 2. Column chromatography of a partially purified enzyme preparation on Sephadex G-200 was found to be an improved method of purification, which gave a coproporphyrinogenase 58-fold purified. The purified enzyme was studied electrophoretically but no evidence was obtained to suggest that more than one enzyme was involved in the reaction. 3. The action was studied of various compounds added to the system. The presence of monothiol groups in the enzyme system was indicated, whereas vicinal dithiol groups were not involved in the reaction. Metal-chelating agents did not inhibit the reaction and no requirement for the presence of any essential metal has been found. All attempts to demonstrate the presence of a prosthetic group, in particular flavines, failed. Neither pyridoxal phosphate nor ATP was involved in the reaction, nor was a mitochondrial electron-transport chain required for the activity of the enzyme. Some circumstantial evidence was obtained to suggest that cis-2,4-diacrylicdeuteroporphyrin is an intermediate in the reaction.

Animals↗

Sphincter-sparing treatment for distal rectal adenocarcinoma.

BACKGROUND: Studies suggest that the anal sphincter can be preserved in some patients with distal rectal adenocarcinoma (DRA), but this has not been validated in any prospective multi-institutional trial. METHODS: To test the hypothesis that the anal sphincter can be preserved in some patients with DRA, the Cancer and Leukemia Group B and collaborators reviewed 177 patients who had T1/T2 adenocarcinomas < or = 4 cm in diameter, which encompassed < or = 40% of bowel wall circumference, and were < or = 10 cm from the dentate line. Of the 177 patients, 59 patients who were eligible for the study had T1 adenocarcinomas and received no further treatment; 51 eligible T2 patients received external beam irradiation (5400 cGY/30 fractions 5 days/week) and 5-fluorouracil (500 mg/m2 IV d1-3, d29-31) after local excision. RESULTS: At 48 months median follow-up, 6-year survival and failure-free survival rates of the eligible patients are 85% and 78% respectively. Three patients died of unrelated disease. Two patients were treated for second primary colorectal tumors; both remain disease free (NED). Another eight patients died of disease, four with distant recurrence only. One T1 patient is alive with distant disease. Two T1 and seven T2 patients experienced isolated local recurrences; all underwent salvage abdominoperineal resection (APR). After APR, one T1 and four of seven T2 patients were NED at the time of last visit (2-7 years). One T1 patient died of local and distant disease. Three of seven T2 patients died with distant disease. CONCLUSIONS: We conclude that sphincter preservation can be achieved with excellent cancer control without initial sacrifice of anal function in most patients. After local recurrence, salvage resection appears effective, but longer follow-up time of local and distant disease-free survival is advised before extrapolation to patients with T3 primaries.

Adenocarcinoma↗

Molecular markers and prediction of response to chemoradiation in rectal cancer.

Preoperative chemotherapy and radiation (chemoradiation) are increasingly used in the treatment of advanced rectal carcinoma to downstage the tumor so that a sphincter sparing procedure is used. This treatment modality has also resulted in not only local disease control but also decreased metastasis and increased survival. It is well known that with standard chemoradiation some tumors show marked pathologic response, while others remain non-responsive. Identification of tumor markers that can predict responsiveness to chemoradiation is extremely useful to avoid unnecessary preoperative treatment. To understand the role of thymidylate synthase (TS), p53 and Bcl-2 proteins, if any, in tumor response/resistance to chemoradiation, we examined pretreatment biopsy material obtained from 12 responsive and 13 non-responsive patients by immunohistochemistry. TS was undetectable in 11 of 12 (92%) responsive tumors and overexpressed in only 1 tumor (8%); whereas, p53 or Bcl-2 was overexpressed in 8 tumors (66%). In the non-responsive group of 13 tumors, overexpression of TS, p53 and Bcl-2 was observed in 7, 5 and 6 tumors, respectively. In 6 non-responsive tumors in which TS was undetectable, 5 tumors contained high levels of p53 or Bcl-2. These results indicate that level of TS in tumors is the best predictor of sensitivity or resistance to chemoradiation. No such correlation between overexpression of p53 and Bcl-2 and response to chemoradiation is observed.

Adult↗