Search PubMed⌕ Search

Biomedical subjects

J M Fletcher

Publications and source records attributed to J M Fletcher.

At least 163 records · Page 9Linked to original sources
PubMed1987

Estrone sulfate sulfohydrolase in the developing brain and pituitary of rat, mouse and guinea pig.

The pattern of estrone sulfate sulfohydrolase (estrogen sulfatase) development in the brain of rat, mouse and guinea pig has been established by assaying whole homogenates. Activity was measurable in each species from the fetal state to adulthood. Maximum brain content was reached at about 20 days of age in rat, 14 days in mouse and 15 days in guinea pig. A considerable decrease occurred between 14 days and adulthood in mouse and lesser decreases were seen in rat and guinea pig. The subcellular distribution of enzyme in rat and mouse brain appeared to change from the immature to the adult state. No major differences in enzyme activity occurred between the sexes at any age. Tissue concentration of enzyme in the hypothalamic-preoptic area of rat and mouse was similar to that in the remainder of the brain. In guinea pig the brain concentration was slightly lower than that of the hypothalamic-preoptic region. Sulfatase content of the pituitary was low in all 3 species but the tissue concentration was considerably higher than that of brain, particularly in rat and mouse. Apparent Km values for brain sulfatase were in the range 6-17 microM, with no striking sex difference. Apparent Km's for pituitary sulfatase of immature rat and guinea pig were similar to those for brain in the same animals but that for mouse pituitary (0.9 microM) was much lower. It is unlikely that brain or pituitary sulfatase is by itself, a major factor in making available potentially active estrogen for use during differential sex development in these species.

Aging↗
PubMed1987

HRAS1-selected chromosome transfer generates markers that colocalize aniridia- and genitourinary dysplasia-associated translocation breakpoints and the Wilms tumor gene within band 11p13.

We show that chromosome-mediated gene transfer can provide an enriched source of DNA markers for predetermined, subchromosomal regions of the human genome. Forty-four human DNA recombinants isolated from a HRAS1-selected chromosome-mediated gene transformant map exclusively to chromosome 11, with several sublocalizing to the Wilms tumor region at 11p13. We present a detailed molecular map of the deletion chromosomes 11 from five WAGR (Wilms tumor/aniridia/genitourinary abnormalities/mental retardation) syndrome patients, three of which are at the limits of cytogenetic resolution but shown here to be molecularly distinguishable and overlapping. We can define ten distinct regions of the short arm of chromosome 11, five of which subdivide band 11p13. We also map two independent 11p13 translocation breakpoints to within the smallest region of overlap defined by the WAGR deletions. The first comes from a patient with familial aniridia, and the second from a patient with Potter facies and genitourinary dysplasia. The close similarities in map location and affected cell lineage for Wilms tumor and genitourinary dysplasia suggest that they may be alternative manifestations of mutation at the same locus.

Animals↗
PubMed1987

Language functions following closed-head injury in children and adolescents.

Fifty-six children and adolescents who sustained a closed-head injury were divided into two groups based on neurological criteria. Language performance was assessed using the Neurosensory Center Comprehensive Examination for Aphasia during the subacute stage of recovery. Naming, expressive, and written language were more impaired than receptive-language functions. At least 20% of the sample exhibited deficits on measures of describing the function of objects, sentence repetition, verbal associative fluency, writing to dictation, and copying sentences. No sparing of function was observed in children relative to adolescents. Moreover, written-language performance was more depressed in children than adolescents. Results were discussed in terms of acquired aphasia in children and posttraumatic linguistic deficits in adults.

Adolescent↗
PubMed1987

Administration of testosterone to wether lambs: effects on protein and energy metabolism and growth hormone status.

The effects of episodic infusion of testosterone into the vascular system on energy expenditure, nitrogen retention and whole body protein synthesis (determined from [1-14C]leucine kinetics) were studied in castrated male lambs under conditions of controlled food intake. Comparisons were made between a 10-day control period and a 10-day treatment period for each lamb. Infusion of testosterone produced a significant increase in heat production, but the magnitude (198 kJ/day, +2.5%) was less than the differences in energy expenditure expected between entire and castrated male ruminants. The retention of nitrogen improved by 1.24 g/day (+22%) in response to the administration of androgen, and this was accompanied by a decrease in amino acid oxidation. Total protein synthesis also declined, and the anabolic nature of testosterone supply must, therefore, be effected through a reduction in the breakdown of protein, the mechanism being similar to that proposed for certain anabolic steroids and the beta-agonist, clenbuterol. Contrary to other reports, the presence of testosterone had no effect on the plasma concentration of GH.

Animals↗
PubMed1987

Whole body fatty acid synthesis and fatty acid intake in young rats of the Zucker strain (Fa/- and fa/fa).

The rate of whole body fatty acid synthesis was measured in immature (18- and 25-day-old) lean and obese male Zucker rats. The effect of stress and diurnal variation on the rate of fatty acid synthesis was also determined in 25-day-old animals. In addition, the intake of fatty acid from the diet was also determined. At 16 and 18 days the carcase of the obese rat contained significantly more lipid than its lean counterpart. In neither phenotype was there any significant lipid deposition from 18 to 23 days. Over the period 23 to 27 days the obese rat deposited approximately six times more lipid than its lean counterpart. Consistent with this finding is the observation that at 25 days the obese rat synthesized at least four to five times more fatty acid than its lean littermate. There was no phenotypic difference in the rate of fatty acid synthesis at 18 days. It is suggested that the young obese rat becomes obese before weaning because of a reduced oxidation, and hence increased storage, of dietary fatty acid. After weaning, although this unusual partition persists, hyperlipogenesis is the main cause of the further development of obesity.

Age Factors↗
PubMed1986

Effects of adrenalectomy before weaning and short- or long-term glucocorticoid administration on the genetically obese Zucker rat.

Intact obese rats were hyperinsulinaemic, had higher rates of whole-body fatty acid synthesis, higher activities of hepatic acetyl-CoA carboxylase and tyrosine aminotransferase and a higher hepatic glycogen concentration than intact lean animals. Adrenalectomy abolished all these factors of the obese phenotype. Treatment of adrenalectomized rats with corticosterone for 24 h increased the rate of whole-body fatty acid synthesis to the same extent in both phenotypes, but caused a larger increase in glycogen concentration, tyrosine aminotransferase activity and plasma insulin concentration in obese rats.

Acetyl-CoA Carboxylase↗
PubMed1986

The fate of 14C derived from radioactively labelled dietary precursors in young rats of the Zucker strain (Fa/- and fa/fa).

The metabolic fate of 14C derived from radioactively labelled dietary precursors was determined in immature (18- and 25-day-old) lean and obese Zucker rats. This included measurement of 14C incorporated into body lipid, non-essential amino acids and expired CO2. Before weaning (18 days) there was no phenotypic difference between the fates of [14C]palmitate and [14C]-glucose. However, after weaning (25 days) all the precursors studied exhibited an increase in the fraction incorporated into lipid in the obese rat as compared with the lean animal. This was reflected in the fate of acetyl-CoA in the tricarboxylic acid cycle. There was little phenotypic difference in the fraction of leucine or valine catabolized. The results presented here suggest that the high rate of lipogenesis found in the obese rat is supported by carbon from all the dietary precursors studied. It is also argued that the decreased protein deposition found in the obese rat is not caused by the high rate of lipogenesis removing precursors for protein synthesis, as has been suggested elsewhere [Cleary, Vasselli & Greenwood (1980) Am. J. Physiol. 238, E284-E292].

Animals↗
PubMed1986

Effects on growth and endocrine status of maintaining obese and lean Zucker rats at 22 degrees C and 30 degrees C from weaning.

Lean and genetically obese Zucker rats were maintained from 21 to 34 days of age at an ambient temperature of 22 degrees C or 30 degrees C. Maintenance at 30 degrees C normalised the lower rectal temperature of obese rats. At 30 degrees C obese rats reduced their food intake compared with obese animals at 22 degrees C but they were still hyperphagic compared with non-obese animals at 30 degrees C. At 30 degrees C obese rats accumulated as much lipid in their carcase, but deposited less protein than obese animals at 22 degrees C. Obese rats were hyperinsulinemic compared with non-obese animals at either temperature. Plasma T3 and T4 levels did not differ between phenotypes and T4 levels were lower in both phenotypes at 30 degrees C. Plasma corticosterone levels were higher in obese rats at both temperatures and this phenotypic difference was larger at 30 degrees C. In a second experiment rats were maintained at 22 degrees C from 21-34 days of age and obese rats pair-fed to the ad lib intake of non-obese animals. Obese rats still became more obese than non-obese animals and deposited less protein than either non-obese or ad lib fed obese animals. Pair-fed obese rats were hyperinsulinemic and had higher plasma corticosterone concentrations than non-obese animals. These findings suggest that the raised plasma corticosterone concentrations of obese rats kept at 30 degrees C, or not allowed to express their greater appetite, may cause reduced protein deposition.

Animals↗
PubMed1986

Hormonal studies of young lean and obese Zucker rats.

Plasma concentrations of insulin, corticosterone, T3, T4 and glucose were measured at 6 hour intervals throughout 24 hours in undisturbed, 34-day-old lean (Fa/?) and genetically obese (fa/fa) Zucker rats. fa/fa rats had higher plasma concentrations of insulin at all sampling times and higher plasma concentrations of corticosterone at 0300 and 0900 hours. Neither T3 nor T4 levels differed between phenotypes at any sampling time. Fasting for 24 hours at 34 days abolished the hyperinsulinaemia of fa/fa rats and raised the plasma corticosterone concentrations of both phenotypes. Before weaning there were no phenotypic differences in the plasma insulin or corticosterone concentrations measured at two sampling times in undisturbed rats. Following an intra-gastric glucose load however, fa/fa rats became hyper-insulinaemic compared with similarly treated Fa/? animals. Pancreatic insulin contents were higher in fa/fa rats at 34 days of age, but not before weaning. Somatostatin contents of the pancreas, hypothalamus and cerebral cortex did not differ between phenotypes at either 18 or 34 days of age. In conclusion, the elevated plasma concentrations of insulin and corticosterone in young fa/fa rats may contribute to their greater lipid deposition and lower protein deposition.

Animals↗
PubMed1986

Increased placental growth and raised plasma glucocorticoid concentrations in fetal rabbits injected with insulin in utero.

Individual rabbit fetuses in utero were injected intramuscularly with either 2.0 Units protamine zinc insulin or saline at 23 days gestation after surgical reduction of litter size to 4 fetuses at 9 days gestation. Insulin-treated fetuses were still hyperinsulinaemic compared with littermate controls at 28 days gestation. Neither fetal body weight nor carcase composition were affected by insulin injection, but placental weight and RNA content were increased. Placental weight was highly correlated with plasma insulin concentration in control fetuses, but not in insulin-injected fetuses. Twenty-four hours after injection of insulin into individual fetal rabbits from normal litters at 23 or 27 days gestation insulin-injected fetuses were hyperinsulinaemic and euglycaemic, but had significantly higher plasma glucocorticoid concentrations than saline-injected littermates. Stimulation of placental growth by fetal insulin may be an important component of the fetal growth stimulatory effect of endogenous insulin. Growth stimulatory effects of exogenous insulin may be antagonised by raised plasma glucocorticoid concentrations.

Animals↗
PubMed1986

Effects of adrenalectomy before weaning in the genetically obese Zucker rat (fa/fa).

1. Lean (Fa/?) and obese (fa/fa) Zucker rats were adrenalectomized or sham-operated at 19 d of age (3 d before weaning). Injection of corticosterone for 3 d after weaning (1.0 mg/d) was necessary to ensure survival of adrenalectomized fa/fa but not Fa/? rats. Intact and adrenalectomized fa/fa rats had a lower rectal temperature than Fa/? animals before and 3 d after adrenalectomy. The post-weaning survival of adrenalectomized fa/fa rats was enhanced by maintenance at an ambient temperature of 30 degrees rather than 22 degrees. 2. Adrenalectomized and sham-operated rats were therefore kept at 30 degrees, fed ad-lib. and killed at 34 d. Adrenalectomy had only small effects on the growth, body composition and appetite of Fa/? rats. The hyperphagia, greater lipid content, reduced protein content and hyperinsulinaemia of fa/fa rats were completely abolished by adrenalectomy. 3. Intact fa/fa rats had higher liver glycogen contents and higher activities of the hepatic enzymes tyrosine aminotransferase (EC 2.6.1.5) and acetyl CoA carboxylase (EC 6.4.1.2) than intact Fa/? animals. Adrenalectomy abolished these phenotypic differences. 4. Injection of adrenalectomized rats with 1.0 mg corticosterone-21-acetate daily from weaning to 34 d restored the abnormal body composition, hyperphagia, hyperinsulinaemia, higher hepatic glycogen and enzyme activities of fa/fa rats. 5. In a second experiment adrenalectomized rats were injected with 1.0 mg corticosterone-21-acetate daily from weaning to 34 d and kept at 22 degrees. fa/fa rats adrenalectomized and injected with corticosterone had a reduced body lipid content compared with intact fa/fa rats but still contained more lipid than intact or similarly treated Fa/? animals. 6. In both experiments adrenalectomized Fa/? and fa/fa rats injected daily with corticosterone had the same plasma concentrations of this hormone when killed 3 h after the last injection at 34 d. It is concluded that corticosterone is required for expression of the abnormal appetite, hyperinsulinaemia and body composition of the fa/fa rat.

Adrenalectomy↗
PubMed1986

Molecular and physical arrangements of human DNA in HRAS1-selected, chromosome-mediated transfectants.

We used mitotic chromosomes isolated from a human EJ bladder carcinoma cell line for morphological transformation of mouse C127 cells. These chromosome-mediated transformants were analyzed for cotransfer of markers syntenic with c-Ha-ras-1 on human chromosome 11. We also used cloned, dispersed human DNA repeats, in a general mapping strategy, to quantitate the amounts and molecular state of human DNA transferred along with the activated c-Ha-ras-1 gene. In situ hybridization was used to visualize the physical state of the transfected human chromatin. The combined use of these various techniques revealed the occurrence of both chromosomal and DNA rearrangements. However, our analysis also demonstrated that, in general, very substantial lengths of DNA are transferred intact. Closely linked markers are likely to cosegregate. Therefore, these transformants should be invaluable sources for the complete molecular cloning of isolated fragments of the short arm of human chromosome 11.

Cell Line↗
PubMed1986

Effects of streptozotocin injection into fetal rabbits on their subsequent growth in utero.

To investigate the effect of hypoinsulinaemia on prenatal growth, individual fetal rabbits were injected intramuscularly with streptozotocin (STZ) at 23 days of gestation following surgical reduction of litter number to 4 at 9 days' gestation. Two days after giving STZ (300 micrograms/g), plasma insulin levels were decreased, but by 30 days' gestation in either insulin nor glucose levels differed significantly from values in control fetuses. Despite only temporary hypoinsulinaemia, severe growth retardation was caused by STZ (300 micrograms/g estimated fetal weight), fetuses at 30 days' gestation weighing only 58% of the mean value obtained in saline-injected controls. At 250 micrograms/g STZ caused growth retardation in 3 out of 8 fetuses. A higher rate (500 micrograms/g) caused fetal death. The extent of growth retardation caused by STZ varied amongst tissues in the conceptus. Placenta and brain were not significantly altered, but relative to the size of the placenta the kidneys and empty carcass were severely retarded. The relationship between carcass and kidney weights did not differ from that in naturally small fetuses of the same age. Protein and RNA concentrations in the carcass were not altered by STZ, but that of DNA was reduced. In the placenta, DNA concentration was increased and RNA decreased. These observations are consistent with a major effect of hypoinsulinaemia on the growth of carcass and renal tissues, though loss of a renal growth factor cannot be ruled out.

Animals↗
PubMed1986

Effects on growth and body composition of androgen deprivation by castration or autoimmunization to LH-releasing hormone in the male rat under conditions of controlled food intake.

The effects of endogenous gonadal hormones on the regulation of body composition and energy retention have been investigated under conditions of controlled food intake. Male and female rats were fed the same amount from weaning to 82 days of age. The carcases of males contained more protein, less lipid and yielded more ash than females, but they had the same amount of total energy in their carcases as females. In a second experiment, male rats were sham-operated or castrated at 19 days and then fed equal amounts from weaning. At 40 days, intact and castrated rats did not differ in total carcase energy content nor in carcase composition. At 82 days the carcases of intact rats had more protein but had retained the same amount of energy as castrated rats. By 131 days, the difference in protein content was larger and intact rats had less carcase lipid, less carcase energy and gave less ash than castrated rats. At the same age and with a similar food intake, the differences in carcase composition between intact males and females were considerably larger than between intact and castrated males. In a third experiment, male rats were sham-operated or castrated at 1 day post partum and fed the same amount as in the second experiment from weaning to 82 days. Both sham-castrated and castrated rats grew less well than rats operated on at 19 days. The differences in carcase composition between intact and castrated rats were in the same direction but of greater magnitude than in rats operated at the later age.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗
PubMed1985

Memory for verbal and nonverbal stimuli in learning disability subgroups: analysis by selective reminding.

Memory for verbal and nonverbal stimuli was evaluated using selective reminding procedures in normal achieving children and four groups of disabled learners: (1) reading-spelling disabled (R-S); (2) reading-spelling-arithmetic disabled (R-S-A); (3) spelling-arithmetic disabled (S-A); and (4) arithmetic disabled (A). Each child received two analogous free-list memory tasks, one for verbal material (animal names) and the other for nonverbal material (random dot patterns). These tasks were administered using selective reminding procedures that permit separation of storage and retrieval aspects of memory by reminding children only of those words not recalled on previous trials. Results revealed that relative to controls, the A and S-A children had significantly lower storage and retrieval scores on the nonverbal task, but did not differ on the verbal task; the R-S children differed only on retrieval scores from the verbal task; and the R-S-A children on retrieval scores on the verbal task and storage and retrieval scores on the nonverbal task. Thus, results indicate that the memory performance of disabled learners varies according to (1) the type of learning problem (arithmetic vs reading), (2) the nature of the stimuli (verbal vs nonverbal), and (3) the aspect of memory being assessed (storage vs retrieval). This study provides external validation for the classification of disabled learners according to patterns of academic achievement, demonstrating a useful procedure for dealing with the intrasubject variability characteristic of disabled learners.

Achievement↗
PubMed1985

Molecular analysis of chromosome 11 deletions in aniridia-Wilms tumor syndrome.

We describe five individuals who have constitutional deletions of the short arm of one chromosome 11, including all or part of the band p13. All of these individuals suffer from aniridia; two have had a Wilms tumor removed. We have established lymphoblastoid cell lines from these and in three cases constructed somatic cell hybrids containing the deleted chromosome 11. Analysis of DNA from the cell lines and hybrids with a cloned cDNA probe has shown that the catalase gene is deleted in four of five patients. The catalase locus must be proximal to the Wilms and aniridia-related loci. We have not detected a deletion of the beta-globin or calcitonin genes in any of these individuals; we conclude these genes are likely to be outside the region 11p12-11p15.4. In addition, we have used monoclonal antibodies in fluorescence-activated cell sorting analysis to measure expression in the hybrids of two cell surface markers encoded by genes that map to the short arm of chromosome 11. The genes for both of these are deleted in two individuals but are present in the individual with the smallest deletion.

Antigens, Surface↗