Proliferation dependence of topoisomerase II mediated drug action

Topoisomerase II mediated DNA scission induced by both a nonintercalating agent [4'-demethylepipodophyllotoxin 4-(4,6-O-ethylidene-beta-D-glucopyranoside) (VP-16)] and an intercalator [4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA)] was studied as a function of proliferation in Chinese hamster ovary (CHO), HeLa, and mouse leukemia L1210 cell lines. Log-phase CHO cells exhibited dose-dependent drug-induced DNA breaks, while plateau cells were found to be resistant to the effects of VP-16 and m-AMSA. Neither decreased viability nor altered drug uptake accounted for the drug resistance of these confluent cells. In contrast to CHO cells, plateau-phase HeLa and L1210 cells remained sensitive to VP-16 and m-AMSA. Recovery of drug sensitivity by plateau-phase CHO cells was found to reach a maximum approximately 18 h after these cells regained exponential growth and was independent of DNA synthesis. DNA strand break frequency correlated with cytotoxicity in CHO cells; log cells demonstrated an inverse log linear relationship between drug dose (or DNA damage) and colony survival, whereas plateau-derived colony survival was virtually unaffected by increasing drug dose. Topoisomerase II activity, whether determined by decatenation of kinetoplast DNA, by cleavage of pBR322 DNA, or by precipitation of the DNA-topoisomerase II complex, was uniformly severalfold greater in log-phase CHO cells compared to plateau-phase cells.     

Evolutionary Divergence in the Structure of Myelin Basic Protein: Comparison of Chondrichthye Basic Proteins with Those from Higher Vertebrates

Abstract: A basic protein has been purified from the CNS myelin of the gummy shark (Mustelus antarticus). Electroblotting was used to examine the capacity of rabbit antisera raised against this electrophoretically pure protein to recognize myelin basic protein from higher vertebrates. The antisera bound to two shark proteins including the original polypeptide antigen and to chicken, bovine, and human myelin basic proteins. Thus, the shark protein appeared to possess antigenic determinants that have been retained through evolutionary divergence of these proteins. Whereas bovine basic protein caused experimental allergic encephalomyelitis in guinea pigs, animals that received injections of the shark protein showed neither clinical nor histological signs of this disease. However, tests for delayed-type hypersensitivity and for Arthus reaction following injection with the shark protein revealed a T-cell-mediated response to this antigen and substantial cross-reactivity with higher vertebrate basic proteins. Analysis of the amino acid composition of the shark protein, and comparison of its tryptic peptide map with that of the bovine protein, revealed substantial changes in the amino acid sequence. Although the shark protein has some antigenic determinants in common with the proteins from higher vertebrates, it appears that much of the structure differs.     

Characteristics of the relative maximum in the decay of delayed light emission from Pothos leaf following far-red excitation

Following illumination with wavelengths longer than 700 nm, the intensity of light emission from Pothos aurea leaf falls for 1 min and then increases to a maximum after 2 min in the dark. The spectrum of this minute-range liminescence matches that of prompt fluorescence excited at the same wavelength, but differs from that of prompt or minute-range delayed emission excited by wavelengths shorter than 700 nm. This emission is less sensitive to heat damage than millisecond delayed emission, and may originate from photosystem I.     

The 131I Ortho-iodohippurate Photoscan in Human Renal Allografts

Nine examples, in seven patients, from a large cadaver renal allograft program, illustrate the value of radio-hippuran photoscans in differentiating causes of post-implant oliguria. Hippuran scans are shown to be more valuable than chlormerodrin scans when renal function is acutely depressed. Hippuran scans aided in the decision to remove kidneys in four cases of severe oliguria and to retain kidneys in two others. In two further examples, extravasation of urine was detected by scanning after radio-hippuran injection when other tests had failed to do so.The technique of radio-hippuran scanning has a place in the differentiation of acute and subacute renal dysfunction and has proved particularly valuable in the early oliguric complications of a cadaver renal transplant program.     

Natural History of Isolated Patent Ductus Arteriosus and the Effect of Surgical Correction: Twenty Years' Experience at The Hospital for Sick Children,Toronto

Seven hundred and forty-four cases of patent ductus arteriosus were diagnosed at The Hospital for Sick Children, Toronto, in the 20-year period from 1947 to 1966. Of these 705 have been treated surgically. It is concluded that operation is best performed between 6 and 12 months of age. Isolated ductus arteriosus is rarely a cause of congestive heart failure, and is more likely to be so in the presence of the rubella syndrome. Failure associated with the anomaly in the neonatal period can usually be successfully managed by medical treatment. Spontaneous closure after one month of age is not to be expected. Surgical treatment at the appropriate time prevents the subsequent development of Eisenmenger''s complex.