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Biomedical subjects

D Scott

Publications and source records attributed to D Scott.

At least 325 records · Page 18Linked to original sources

Relationships between chromosome damage, cell cycle delay and cell killing induced by bleomycin or X-rays.

The extent of mitotic delay and chromosome aberration induction by X-rays and bleomycin has been compared in normal human foetal fibroblasts at doses giving approximately equal levels of cell killing, assayed as colony-forming ability. Bleomycin induced much less G2 delay and chromosome damage than X-rays. We conclude that the major mechanism of cell killing by bleomycin does not involve chromosome damage but the cells pass through a number of division cycles before dying and a common DNA lesion is involved in G2 delay and chromosome damage.

Bleomycin↗

The response of normal and ataxia-telangiectasia cells to bleomycin: relationships between chromosome damage, cell cycle delay and cell killing.

In agreement with our earlier observation (Scott and Zampetti-Bosseler, 1982) on X-irradiated normal and ataxia-telangiectasia (A-T) fibroblasts, we now report that after bleomycin or neocarzinostatin treatment also, A-T cells exhibit less G2 delay than normal cells. We confirm that A-T cells sustain more chromosome damage and lethality than normal cells after bleomycin. These observations support the hypothesis (Painter and Young, 1980) that A-T cells are defective in the recognition of certain lesions which normally lead to delays in progression through the cell cycle, during which they are repaired, and which, if unrepaired, lead to cell-lethal chromosome damage. However, we find that after bleomycin, as opposed to X-rays, the contribution of this type of lesion to cell death is minimal. The predominant lesions leading to cell death after bleomycin are not manifested at chromosome aberrations and do not lead to G2 delay or DNA-synthesis inhibition. A-T cells are defective in the recognition and/or repair of both types of lesion.

Ataxia Telangiectasia↗

Cystitis with ureteral reflux caused by ureaplasma urealyticum.

The authors present a case of a fifteen-year-old boy with urgency, suprapubic pain, hematuria, and pyuria with negative routine urine cultures. Cystoscopy revealed gross cystitis, and VCUG showed bilateral reflux and ureteral dilatation. Renal arteriograms, percutaneous renal biopsy, and bladder biopsy also were performed. After finding a positive culture for Ureaplasma, therapy with doxycycline rendered the patient asymptomatic and reflux improved on follow-up VCUG. Ureaplasma urealyticum should be considered in patients with symptomatic pyuria and negative routine cultures. Ureteral reflux, reversible with appropriate therapy, may be part of the infectious process.

Adolescent↗

Changes in spontaneous SCE frequencies as a function of sampling time in lymphocytes from normal donors and cancer patients.

Spontaneous SCE frequencies were measured in cells undergoing their second mitosis at 54, 68, 72, 78 or 90 h after PHA stimulation of whole blood cultures from 7 normal donors. A consistent pattern of fluctuation of SCE levels was observed between 54 and 78 h. The magnitude of change in SCE frequency between consecutive fixation times was as high as 80% for some donors. These observations support the hypothesis of Snope and Rary (1979) that there are subpopulations of lymphocytes with different spontaneous SCE levels and different proliferation rates. In untreated cancer patients the patterns of change in SCE frequency with time were different from that seen in normal donors. This may be because of quantitative changes in T-lymphocyte sub-populations which have been observed in cancer patients. Changes in SCE frequency of less than about a factor of two, observed at a single sampling time may not be indicative of genotoxic events or genetic instability but simply represent changes in the composition of lymphocyte sub-populations and/or in their rates of proliferation in vitro.

Age Factors↗

The effect of caffeine on X-ray-induced mitotic delay in normal human and ataxia-telangiectasia fibroblasts.

We previously showed that radiation-sensitive fibroblasts from ataxia-telangiectasia (A-T) patients sustain less G2 delay after X-irradiation than normal fibroblasts (Scott and Zampetti-Bosseler, 1982). Caffeine is known to reduce the amount of X-ray-induced delay in various mammalian cell types. Painter and Young (1980) proposed that A-T cells have an altered chromatin structure, similar to that of caffeine-treated normal cells and that this results in a failure of A-T cells to delay their progression through the cell cycle to allow time for DNA repair. We now show that caffeine treatment after X-irradiation reduces G2 delay in both A-T and normal cells. We confirm the results previously obtained on lymphocytes that caffeine potentiates the chromosome-damaging effects of X-rays in both A-T and normal fibroblasts. These and other data suggest that the radiation responses of A-T cells and of caffeine-treated normal cells are caused by different mechanisms.

Ataxia Telangiectasia↗

The effect of potassium and magnesium infusion on plasma Mg concentration and Mg balance in ewes.

1. Concentrations of magnesium in plasma, the ionic concentration in rumen digesta supernatant fractions, Mg balance and electropotential differences were measured in three ewes which were fed on grass and supplemented with potassium and Mg by intraruminal infusion. 2. Mean plasma Mg concentrations were unaltered by combined K and Mg treatments, but fell (P less than 0.001) when K alone was infused. 3. The mean concentrations, in rumen digesta, of sodium and K varied reciprocally (P less than 0.001) with each other when K was infused, but were unaffected by Mg infusion. The mean Mg concentrations in rumen digesta fell (P less than 0.01) with K infusion but rose (P less than 0.001) with Mg infusion. 4. Absorption and excretion of Mg rose (P less than 0.001) when Mg intake was increased but was unaffected by K intake.

Absorption↗

Pseudo-precocious puberty caused by bilateral idiopathic testicular hyperplasia.

A boy aged two years presenting with advanced development of the genitalia, but with prepubertal testes, and accelerated growth is described. Investigation indicated pseudo-precocious puberty, due to idiopathic interstitial cell hyperplasia. Difficulties in interpretation of the hormonal studies were encountered due to an aberrant left testicular vein. This rare condition which has been called Testotoxicosis is probably due to an inborn error of metabolism not yet identified.

Child, Preschool↗

The effects of feeding either roughage or concentrate diets on salivary phosphorus secretion, net intestinal phosphorus absorption and urinary phosphorus excretion in the sheep.

Mature sheep fitted with rumen and duodenal cannulae were fed either a hay or a concentrate diet and the effects on salivary phosphorus secretion, net intestinal phosphorous absorption and pathway for phosphorous excretion were examined. Route of excretion was markedly affected by diet with urine phosphorus levels being much higher and faecal levels lower when the concentrate diet was fed. This difference was not due to differences in phosphorus intake nor could it be related to differences in either plasma phosphorus levels or net intestinal phosphorus absorption. Salivary phosphorus secretion and renal tubular reabsorptive efficiency for phosphorus were, however, both lower when the concentrate diet was fed. The significance of these effects of diet in relation to the control of phosphorus balance in ruminants is discussed.

Animal Feed↗

Spontaneous sparsely-granulated prolactin-producing pituitary adenomas in aging rats. A prospective study of the effect of bromocriptine.

The effect of bromocriptine (BEC) treatment on spontaneous, sparsely granulated, prolactin-producing pituitary adenomas was studied in aging female Long-Evans rats of at least 23 months of age. Rats treated with BEC for 1-44 days showed a marked decrease in serum prolactin (PRL) concentrations at the end of the treatment period (9.1-34 ng/ml) when compared to the serum PRL levels of age-matched control animals (94.6-233 ng/ml). No significant differences in serum PRL levels (ng/ml; mean +/- SEM) were noted in rats withdrawn for 14 days from BEC treatment (132.9 +/- 18.8) when compared to age-matched controls (181.5 +/- 70.9). The mean pituitary weight (mg) was significantly reduced in the rats treated for 44 days with BEC (23.4 +/- 1.4) compared to untreated controls (43.4 +/- 8.3). At the time of sacrifice, PRL-producing adenomas were found in 16 of 33 control rats, 5 of 10 rats treated for 1 day with BEC, 5 of 20 rats treated with BEC for 44 days, and 12 of 28 rats in the animals withdrawn from BEC treatment for 14 days. Morphometric analysis of sparsely granulated PRL-containing adenomas revealed that, although the nuclear area was reduced after 1 day of BEC treatment, the cytoplasmic area was reduced only after 44 days. Forming granule diameters were significantly increased after 44 days of BEC treatment and markedly decreased in the withdrawal group. Storage granule diameters were increased in both the 1-day and 44-day groups and were decreased in rats withdrawn from BEC for 14 days. Rough endoplasmic reticulum, forming granule, storage granule, and lysosome volume densities were increased after 1 day of BEC treatment. The Golgi region volume density decreased only after 44 days of BEC treatment. We conclude that aging female Long-Evans rats harboring PRL-producing pituitary adenomas can respond to BEC administration with a decrease in serum PRL levels and morphologic changes in adenoma cells. However, the structural alterations in PRL cells of the rat adenomas are less conspicuous than those of human tumors. In the rat, like in human patients, a direct toxic effect of BEC on PRL-producing adenoma cells has not been demonstrated.

Adenoma↗

Intravenous histamine administration in ponies with recurrent airway obstruction (heaves).

Pulmonary function and airway reactivity to IV histamine were measured in a group of ponies with a history of recurrent airway obstruction (heaves) and their age-, weight-, and gender-matched controls. Ponies were studied during a period of clinical remission (period A), after exposure to a barn environment (period B), and twice during a 2-week recovery phase (periods C and D). At periods A, C, and D, PaO2, dynamic compliance (Cdyn), pulmonary resistance, tidal volume, respiratory frequency, and the log dose of histamine required to reduce Cdyn to 65% of base-line value (log ED65Cdyn) of principals and controls did not differ. Barn exposure (period B) decreased Cdyn, PaO2, and ED65Cdyn and increased pulmonary resistance in principals but not controls. The slope of the histamine dose-Cdyn response curves was not different between principal and control groups of ponies and was unaffected by barn exposure or return to pasture. There was a poor correlation between ED65Cdyn and indices of airway caliber. During acute airway obstruction, ponies with a history of heaves were hyperreactive to IV histamine, but during disease remission, airway response to histamine was not different from that of control ponies. Seemingly, hyperreactivity in principal ponies after exposure to a barn environment cannot be explained solely by alterations in base-line airway caliber.

Airway Obstruction↗

Outcome of fetal ventriculomegaly.

Ventriculomegaly was diagnosed in 50 fetuses in the perinatal ultrasound unit of Yale-New Haven Medical Center. The outcomes were elective abortion, 13 (26%); antepartum death, 0 (0%); intrapartum death, 7 (14%); neonatal death within 24 h, 11 (22%); neonatal death after 24 h and within 28 days, 3 (6%); death after 28 days, 2 (4%); survival, 14 (28%). 70% of the deaths were associated with severe congenital anomalies or intrapartum cephalocentesis. Of the 14 survivors, 6 (43%) had Bayley mental or Stanford-Binet scores of over 80, 2 (14%) had scores from 65 to 80, and 6 (43%) had scores of less than 65. The differences in outcome between this antenatal population and previously described neonatal populations with ventriculomegaly may result from the high rate (84%) of abnormalities in association with ventriculomegaly in this study and selection biases in neonatal studies.

Abnormalities, Multiple↗