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Biomedical subjects

P D Lewis

Publications and source records attributed to P D Lewis.

At least 19 recordsLinked to original sources
PubMed1979

Effects of thyroxine on postnatal cell acquisition in the rat brain.

The effects of treatment with L-thyroxine (3 micrograms by subcutaneous injection daily from birth) on cell acquisition in the rat brain were studied during the first 3 postnatal weeks. In the forebrain, thyroxine has no effect on cell proliferation in the first 6 days, but it causes decreased cell acquisition from 12 to 21 days so that cell number becomes significantly reduced. Estimates of cell proliferation kinetics and of cell death in the lateral ventricular subependymal layer show no apparent abnormality. In the cerebellum, treatment from birth leads to increased cell proliferation during the first week: in comparison with controls, the rate of [3H]thymidine incorporation into DNA, thymidine kinase activity, and the number of cells both in the major germinal site (external granular layer: EGL) and in the whole cerebellum are elevated. This initial effect of thyroxine appears by day 3 and is short-lived, being no longer evident after day 6. The build-up of cell numbers in the EGL at day 6 seems to be related to a preceding, transient retardation of cell migration from this layer rather than to an acceleration of cell replication, since cell cycle parameters are normal. From day 12 the rate of [3H]thymidine incorporation into DNA is severely reduced in treated rats. Advancement of cellular differentiation rather than increased cell death in the EGL appears to be involved in this phenomenon.

Aging↗
PubMed1979

A quantitative study of cell proliferation in ependyma and choroid plexus in the postnatal rat brain.

Profliferative activity in forebrain ependyma aand choroid plexus epithelium was studied in rats aged up to 42 days by means of autoradiography after injection of [3H]-thymidine. Labelling indices were higher in the lateral than in the third ventricle, while values for choroid plexus epithelium were lower than those for ependyma. In all areas examined, labelling indices showed a similar pattern of decline in the first two postnatal weeks reaching by day 12 a level about 20-30% of that on day 1. This low level, corresponding to a turnover time of 130 days for ependyma, was maintained tereafter up to day 42, indicating the persistence of proliferation in the young adult.

Age Factors↗
PubMed1977

Effect of undernutrition on cell generation in the adult rat brain.

Cell proliferation and cell death in the lateral ventricular subependymal layer were studied in acutely food-deprived and chronically undernourished 6-week-old rats. The length of the cell cycle was increased by 40-75%, while the DNA synthesis phase of the cycle was prolonged by 70-85%. The rate of cell acquisition was reduced to approximately half the control level, and the proportion of degenerating cells was significantly increased. The response to undernutrition of proliferating cells in the subependymal layer of adult rats differs from that in animals in the first two weeks of life, and resembles that seen in other tissues.

Animals↗
PubMed1977

Effect of reserpine on cell proliferation in the developing rat bran: a biochemical study.

Reserpine, a well-known CNS depressant which depletes central monoamine stores, was found to produce in the brains of 11-day-old rats a severe depression in cell proliferation in terms of the rate of [3H]thymidine incorporation into DNA. The effect was studied in detail 12 h after ther administration of the drug (2.5 mg/kg, s.c.) when the rate of in vivo DNA synthesis in the forebrain was about one-third of control: the decrease was less marked in the cerebellum (rate about two-thirds of control). It was possible to exclude side effects of the drug, such as restricted food intake, hypothermia and an elevation of the level of blood corticosteroids being responsible for the reduction of [3H]thymidine incorporation into DNA. Kinetic studies showed that reserpine had no marked effect on the entry of [3H]thymidine from blood to brain, but it caused some retardation in the rate of [3H]thymidine conversion into [3H]thymidine nucleotides. Nevertheless, the severe depression of DNA labelling was evident even after correcting the values on the basis of [3H]thymidine nucleotide concentrations. In contrast to these effects, thymidine kinase activity was normal in the brain of reserpine-treated animals.

Animals↗
PubMed1977

Effect of reserpine on cell proliferation in the developing rat brain: a quantivative histological study.

Rats aged 11 days were injected with reserpine (2.5 mg/kg body wt.) and the rate of [3H]thymidine incorporation into brain DNA was followed over a period of 36h. In the forebrain this was significantly depressed by 2h, and it reached a nadir of about 30% of the control level at 4h, at which it remained for another 26h. A partial recovery occurred by 36h. The effect was less pronounced in the cerebellum. On the basis of this information brains of rats were examined histologically and by autoradiography between 7 and 36 h after reserpine to obtain estimates of cell cycle parameters and of rates of cell proliferation and cell loss. In the forebrain lateral ventricular subependymal layer the labelling index was markedly reduced in comparison withe controls. Cell cycle time was prolonged by 50% and turnover time increased by 60%. In the cerebellar external granular layer, the mitotic index was reduced and increased numbers of degenerate postmitotic nuclei were found, notably in the latter part of the experimental period. These effects are potentially of functional and clinical significance.

Animals↗
PubMed1977

The effects of fast neutrons and X rays on the subependymal layer of the rat brain.

Some effects of irradiation of rat brain with single doses of X rays or fast neutrons have been measured. This was done by estimating the total number of cells in the subependymal layer at various times after irradiation. The gross response to X rays and neutrons was somewhat different, and the results suggest that the two histologically distinguishable cell types in the subependymal layer have different values of RBE.

Animals↗
PubMed1976

Treatment of Nelson's syndrome by pituitary implantation of yttrium-90 or gold-198.

Eight patients with Nelson's syndrome were treated with a pituitary implant of yttrium-90 or gold-198 four to 16 years after adrenal surgery. All had considerable pigmentation. One already had cranial nerve abnormalities and visual field defects and had had both a craniotomy and deep x-ray treatment. Radiographs showed that the pituitary fossa was abnormal in seven patients. A biopsy performed in six cases showed mucoid (or basophil) adenoma in all. In the four specimens examined ACTH was identified by electron microscopy or immunofluorescence, or both. Patients were followed up after pituitary implantation for three months to 12 years. All showed decreased pigmentation, and six became normal. Four patients regained normal ACTH levels and the other two studied had decreased levels. In no case did new cranial nerve disease or further sellar expansion develop since operation, and two patients showed remodelling of the sella. Complications were temporary leakage of cerebrospinal fluid and diabetes insipidus in one patient and gonadotrophin deficiency in another.

Adenoma↗
PubMed1976

Effect of thyroid deficiency on postnatal cell formation in the rat brain: a biochemical investigation.

In thyroid deficiency, interference with postnatal cell formation seems to be confined to those regions of the brain where postnatal neurogenesis is significant. In comparison with controls the increase in cell number in the cerebellum is retarded in the second week of life, but a normal number is reached by 35 days. In contrast the DNA content of the olfactory bulbs is apparently irreversibly depressed. Mitotic activity, in terms of incorporation of [2-14C]thymidine into DNA, is mainly affected in the cerebellum: in thyroid deficient rats, it is depressed below control levels at day 12, but it is about 4 times higher than in controls at day 21 when, under normal conditions, cell proliferation has virtually ceased. The time course (15-240 min) of [14C]thymidine metabolism at day 14 shows regional differences in control rats. The rate of conversion of [14C]thymidine to [14C]thymidine nucleotides, and of these in turn to [14C]DNA is slower in the forebrain - where cell proliferation occurs on a smaller scale - than in the cerebellum. Consequently, in the forebrain nearly linear DNA synthesis rate is maintained for a longer time than in the cerebellum (1 h vs. 0.5 h), and since less 14C is conserved in DNA a significant efflux of unconverted [14C]thymidine is evident during the experimental period. The effect of thyroid deficiency on [14C]thymidine metabolism in the brain is only slight, and is due to an abnormally large supply of [14C]thymidine consequent to depressed systemic utilization of this precursor.

Animals↗
PubMed1976

Effect of thyroid deficiency on cell acquistion in the postnatal rat brain: a quantitative histological study.

The mechanisms underlying transient reduction of cell number in the developing cerebellum of thyroid-deficient rats have been studied by quantitative histological methods. Thyroid deficiency has no significant effect on the generation cycle of dividing cells in either the subependymal layer of the lateral ventricular walls or the external granulay layer of the cerebellum: the length of the cell cycle and the duration of the different phases of the cycle, including the DNA synthesis time appears to be normal. However, the external granular layer of the cerebellum contains fewer cells than in control at 12 days. Pyknotic nuclei are prominent in the granule cell layer of the hypothyroid cerebellum at this age. These amount to an estimated loss of about 1% of the total cerebellar cell population in 24 h. It is suggested that death of granule cells is for the most part a consequence of reduced Purkinje cell dendritic arborization, with failure of parallel fibre/Purkinje cell synaptogenesis. In the second postnatal week, granule cell death and reduced numbers of cells in the germinal zone can account to a great extent for the observed shortfall in cerebellar DNA content. The eventual attainment of normal cell numbers in the cerebellum of hypothyroid rats is related to a persistent external granular layer in the forth and fifth postnatal weeks.

Animals↗
PubMed1975

Staining of sulphatides in metachromatic leukodystrophy with Alcian blue at high salt concentrations.

Alcian blue combines with purified sulphatide in 1.OM magnesium chloride. In tissue sections from patients with metachromatic leukodystrophy, sulphatide is stained by Alcian blue in 0.8 M magnesium chloride, and the staining can be abolished by prior treatment with chloroform and methanol. The simplicity of the technique, its specificity and ease of interpretation recommend Alcian blue staining at high salt concentrations as a routine method in the diagnosis of metachromatic leukodystrophy.

Alcian Blue↗
PubMed1975

The effect of undernutrition in early life on cell generation in the rat brain.

In undernourished rats aged up to 21 days, the DNA synthesis period in dividing cells of the subependymal and external granular layers is consistently and markedly prolonged, while rates of cell production from these layers are only slightly altered. Cell cycle times are unchanged up to the end of the first week of life and prolonged from day 12. The G1 phase is markedly shortened at 1, 6 and 12 days of age. It would appear that, in comparison with controls, disappearance of the external granular layer is delayed, and cell numbers in both germinal layers may be reduced.

Animals↗