Biomedical subjects
Publications and source records attributed to R A Lloyd.
Relative survival rates in the National Cancer Institute (NCI) 'SEER' review of cancer in the USA are fitted by a model which can be used to estimate median survival time in any calendar year. It is argued that median survival times (MSTs) are better indicators of survival than 5-year relative survival rates (RSRs), especially when survival times are short.
Paediatric cancer of the retinae arises from a transient population of stem cells whose growth and decay are responsible for the development of the fully differentiated photo-receptors and nerve cells. A model is described which fits the data on the incidence of bilateral retinoblastoma and gives the somatic mutation rate without using an estimate of the size of the population at risk. It also gives the shape of the retinoblast growth/decay curve. The model has been tested on two independent sets of data from the USA, and given that both sets are representative of the USA as a whole, there seems to have been little change in the somatic mutation rate over the last 30 or so years. For a total retinoblast formation of 4 x 10(6) cells, the average mutation rate is 2.94 x 10(-7) per cell per year.
An assay for alpha-tubulin acetyltransferase (TAT) activity based on affinity isolation of labeled acetylated alpha-tubulin was developed for use with crude subcellular fractions. Microtubules were polymerized and immobilized on an anti-alpha-tubulin-agarose and then incubated with the subcellular fraction and [3H]acetyl-coenzyme A (CoA). The labeled product was eluted from the antibody-agarose and the tritiated acetate incorporation determined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot of the eluate verified the presence of acetyl-alpha-tubulin. Analysis of bovine retinal fractions showed the highest specific activity of tubulin acetyltransferase activity in the 27,000g pellet fraction (P2) of retinal homogenates. This transferase activity was proportional to the concentration of microtubule protein immobilized under polymerizing conditions and had an apparent Km of 3 microM for acetyl-CoA. The activity was solubilized from the P2 pellet by a high ionic strength buffer. The properties of the retinal TAT determined by this assay are very similar to those reported for a more purified enzyme preparation from Chlamydomonas flagella using the conventional trichloroacetic acid precipitation assay and support the use of this method for samples in which high backgrounds prohibit use of the conventional assay.
Etretinate, a synthetic retinoid, is a potent teratogen. It has previously been shown that acute exposure of gestational day 8 (equivalent to human week 4 post-fertilization) C57BL/6J mouse embryos to this retinoid results in a spectrum of abnormalities that are recognized as constituting caudal regression (dysgenesis). These defects, which include spina bifida, imperforate anus, genitourinary anomalies, omphalocele and limb anomalies, result from a major insult to the primitive streak, that is the gastrulation process. Developmental stages present early on gestational day 9 in mice represent the final stages during which the primitive streak contributes to the trunk of the embryo and, therefore, the last opportunity for abnormalities within the realm of caudal regression to be induced. In fact, acute etretinate exposure on gestational day 9 resulted in anal and urethral atresia, bladder and ureteral dilatation, and tail deficiencies as observed in 251 near-term fetuses in this study. To examine in further detail the gestational day 9 etretinate induced urogenital and anal abnormalities and their pathogenetic basis, analyses were conducted using scanning electron microscopy, light microscopy, antegrade cystourethrograms and a vital staining technique as early as 6 hours following maternal drug administration. It appears that diminution of the caudal cell populations, including those of and those surrounding the cloaca, at this critical stage of embryogenesis accounts for the observed phenotype. We propose that anal and urethral atresia temporally represents the end of the caudal regression (dysgenesis) syndrome.
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