Search PubMed⌕ Search

Biomedical subjects

K Barnes

Publications and source records attributed to K Barnes.

At least 91 records · Page 5Linked to original sources
PubMed1988

Endopeptidase-24.11 is striosomally ordered in pig brain and, in contrast to aminopeptidase N and peptidyl dipeptidase A ('angiotensin converting enzyme'), is a marker for a set of striatal efferent fibres.

Endopeptidase-24.11 (sometimes referred to as 'enkephalinase') is a key cell-surface enzyme in the metabolism of neuropeptides. A previous immunohistochemical study mapped the enzyme in pig brain and indicated a striosomal ordering of the enzyme within the striatum. This point has now been confirmed by staining adjacent sections for acetylcholinesterase (by histochemistry) and endopeptidase-24.11 (by an immunoperoxidase method). While there were some general similarities in the mapping of these two hydrolases, e.g. in the caudate-putamen, globus pallidus, olfactory tubercle, substantia nigra and striatonigral tract, there were differences in intensity and in the microscopic distribution, e.g. as in striosomes for which acetylcholinesterase was diminished. Two other membrane peptidases, peptidyl dipeptidase A ('angiotensin converting enzyme') and aminopeptidase N, were also mapped by the same immunohistochemical method. Peptidyl dipeptidase A had some similarities with endopeptidase-24.11, e.g. in its concentration within the striatal nuclei, but clear differences were also apparent, in particular the absence of staining of the former in the globus pallidus and olfactory tubercle. Immunostaining for aminopeptidase N, in contrast to the other peptidases, was observed as a diffuse staining throughout the gray matter. At the microscopic level, two important differences were that staining for aminopeptidase N and peptidyl dipeptidase A was very intense throughout the vasculature of the brain and that striatal efferent bundles of unmyelinated fibres staining positively for endopeptidase-24.11 were depleted of the other two peptidases. All three peptidases were identified in the pia mater. Thus, endopeptidase-24.11, unlike peptidyl dipeptidase A and aminopeptidase N, is a marker for a set of striatal efferent fibres in pig brain.

Aminopeptidases↗
PubMed1988

Abnormal growth hormone secretory dynamics in children with familial hypercholesterolemia.

Growth hormone secretory dynamics and plasma somatomedin C concentrations were assessed in four prepubertal patients with defects in the low-density lipoprotein (LDL) receptor pathway before and after 2 months of treatment with mevinolin, an HMG-CoA reductase inhibitor that reduces intracellular cholesterol. Pre- and posttreatment mean 24-hour growth hormone levels and pulse amplitude were similar and tended to be higher than in age-matched prepubertal controls. Pre- and posttreatment somatomedin C levels were also similar and lower than in age-matched prepubertal controls. All patients responded to growth hormone provocative testing with a peak response of greater than 7 ng/ml, independent of treatment status. Growth velocity was not significantly altered in any patient following 2 months of treatment with mevinolin, and was within the normal range for age. Thus, children with defects in the LDL receptor pathway express abnormalities in growth hormone secretion and somatomedin C generation comparable to those seen in other chronic diseases. Treatment with mevinolin has no apparent effect on these biochemical abnormalities, suggesting that it may not have long-term effects on growth. Regardless of mevinolin therapy, children with defects in the LDL receptor pathway may manifest a degree of growth retardation and, hence, growth rate and skeletal maturation should be closely monitored.

Child↗
PubMed1988

The antiglucocorticoid and antiprogestin steroid RU 486 suppresses the adrenocorticotropin response to ovine corticotropin releasing hormone in man.

The glucocorticoid and progesterone antagonist RU 486 normalizes the clinical and biochemical features of hypercortisolism in patients with nonpituitary Cushing's syndrome, presumably by antagonizing the action(s) of cortisol. Since RU 486 has progesterone agonist activity in addition to its progesterone antagonist action, the possibility that it might have some glucocorticoid agonist action did not seem unreasonable. To test this hypothesis we examined the effects of RU 486 on pituitary ACTH secretion in 10 patients with primary adrenal insufficiency in whom glucocorticoid replacement was withheld for 36 h. Each patient received, in randomized sequence 3-7 days apart, an oral dose of placebo, RU 486 (20 mg/kg), cortisol (0.1 mg/kg), or a combination of RU 486 and cortisol at 1800 h. Two hours later, an iv bolus dose of ovine CRH (1 microgram/kg) was administered, and plasma ACTH levels were measured serially for 3 h. RU 486 suppressed ovine CRH-stimulated ACTH secretion, albeit less than cortisol. Its glucocorticoid agonist effect was calculated to be approximately 1/250th that of cortisol on a weight basis. Additionally, RU 486 partially antagonized cortisol-induced suppression of ACTH secretion. These findings suggest that RU 486 is a partial glucocorticoid agonist and offer some insight as to its action in patients with Cushing's syndrome. Whether this degree of glucocorticoid agonist activity is adequate to support life, however, is not known.

Addison Disease↗
PubMed1988

Absence of dawn phenomenon in normal children and adolescents.

The dawn phenomenon consists of a rise in plasma glucose levels or insulin requirements in the early morning. This phenomenon has been observed in normal adults and in patients with diabetes mellitus. To determine whether this phenomenon also occurs in normal children and adolescents, we evaluated plasma glucose, insulin, C-peptide, and growth hormone levels during the early morning in 31 normal children between the ages of 8 and 18 yr. Blood samples were obtained through an indwelling catheter every 20 min for growth hormone and hourly for glucose, insulin, and C-peptide from 2100 to 0900 h. Glucose levels decreased slowly overnight from 2100 to 0900 h, despite increases in growth hormone levels. No significant rise in insulin or C-peptide levels was detected in the early morning in these normal subjects. There were no significant differences between prepubertal and pubertal children. We conclude that glucose, insulin, and C-peptide levels remain stable overnight, suggesting that the dawn phenomenon is not observed in normal children.

Adolescent↗
PubMed1987

Growth hormone secretory dynamics in children with precocious puberty.

We investigated whether an increase in growth hormone secretion contributed to the growth spurt in children with precocious puberty by measuring the 24-hour profile of serum growth hormone in 51 patients with central precocious puberty. Girls with central precocious puberty had significantly greater mean 24-hour levels of growth hormone in comparison with normal prepubertal girls (5.1 +/- 0.5 SEM vs 3.4 +/- 0.3 ng/mL, P less than 0.005). Mean 24-hour growth hormone levels did not differ significantly between boys with central precocious puberty and normal prepubertal boys (4.4 +/- 1.2 vs 3.0 +/- 0.4 ng/mL). Serum somatomedin C levels were significantly correlated with mean 24-hour growth hormone levels in the girls only. Height age advancement (expressed as height age/chronologic age) was significantly correlated with mean 24-hour growth hormone levels in both boys and girls with central precocious puberty. We conclude that spontaneous 24-hour growth hormone secretion in girls with precocious puberty is greater than that of normal prepubertal girls and may mediate at least in part the increased growth rate in this disorder.

Body Height↗
PubMed1987

The effect of mevinolin on steroidogenesis in patients with defects in the low density lipoprotein receptor pathway.

Adrenal steroidogenesis is dependent upon cholesterol derived from both de novo biosynthesis and uptake of plasma lipoproteins through the low density lipoprotein (LDL) receptor pathway. Recent studies have demonstrated that patients homozygous for familial hypercholesterolemia have a mild impairment in cortisol secretion during maximal ACTH stimulation. Mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, has been used clinically to inhibit de novo cholesterol synthesis in patients with familial hypercholesterolemia. In this study we examined hypothalamic-pituitary-adrenal function in seven patients with defects in the LDL receptor pathway, both before and during treatment with oral mevinolin (20 mg, twice a day), to assess whether inhibition of cholesterol synthesis influences steroidogenesis under basal conditions and in response to ovine CRH and exogenous ACTH. Two months after initiation of therapy, high density lipoprotein cholesterol levels were significantly elevated, and LDL cholesterol levels were reduced, although not normalized. Basal and ovine CRH-stimulated adrenocortical function were normal in all patients both before and during therapy. Plateau plasma cortisol concentrations achieved during maximal ACTH stimulation were lower than those in control subjects in all patients both before and during therapy. All patients, however, had an approximately 3-fold increase over basal values. These results suggest that treatment of patients with defects in the LDL receptor pathway with mevinolin improves the plasma lipid profile and does not result in adrenal dysfunction or further exacerbation of the mild impairment of adrenal function during maximal ACTH stimulation.

Adrenal Cortex↗
PubMed1986

Treatment of precocious puberty in the McCune-Albright syndrome with the aromatase inhibitor testolactone.

The McCune-Albright syndrome is characterized by café au lait spots, fibrous dysplasia of bones, and sexual precocity. Girls with precocious puberty due to this syndrome have episodic increases in serum estrogen levels together with the formation of large ovarian cysts. The serum gonadotropin levels are typically suppressed, and the precocious puberty has not responded to treatment with long-acting analogues of luteinizing hormone-releasing hormone (LHRH). Encouraged by our initial success in a pilot study of one patient, we have now treated five girls with the McCune-Albright syndrome with the aromatase inhibitor testolactone, which blocks the synthesis of estrogens. Testolactone decreased the levels of circulating estradiol (P less than 0.05) and the ovarian volume (P less than 0.05), and there was a return to pretreatment levels after testolactone was stopped. During treatment, the peak responses of luteinizing hormone and follicle-stimulating hormone to stimulation by LHRH rose above suppressed pretreatment levels--significantly above pretreatment levels for follicle-stimulating hormone (P less than 0.02)--and then returned to pretreatment levels after testolactone was discontinued. Growth rates fell in three patients during treatment but could not be assessed in the other two because of bone deformities. The mean rate of bone maturation decreased and menses stopped in three of the four girls who were menstruating regularly. We conclude that testolactone is an effective treatment of precocious puberty in the McCune-Albright syndrome.

Aromatase Inhibitors↗
PubMed1986

The NIH experience with precocious puberty: diagnostic subgroups and response to short-term luteinizing hormone releasing hormone analogue therapy.

Between 1979 and 1983, 129 children (95 girls) with precocious puberty were referred to the National Institutes of Health and received treatment for at least 6 months with the long-acting LHRH analogue D-Trp6-Pro9-NEt-LHRH. The majority (107 of 129) of the children had central precocious puberty mediated by activation of the hypothalamic-pituitary-gonadal axis in association with hypothalamic hamartomas (24 of 107) or other central nervous system lesions (21 of 107), or idiopathic precocious puberty (62 of 107). Hypothalamic hamartomas or other central nervous system lesions were a frequent cause of central precocious puberty in girls (27 of 87), but idiopathic precocious puberty was still the most frequent diagnosis (63%). Idiopathic precocious puberty was uncommon in boys (6%). The patients with peripheral precocious puberty included six girls with McCune-Albright syndrome and six boys with familial male precocious puberty. These children had peripheral sex steroid secretion in the absence of hypothalamic-pituitary-gonadal axis maturation. The children with combined peripheral and central precocious puberty included nine children with congenital adrenal hyperplasia and one girl with a virilizing adrenal tumor. In the patients with central precocious puberty or combined peripheral and central precocious puberty, LHRHa therapy caused suppression of gonadotropin and sex steroid levels (P less than 0.001), stabilization or regression of secondary sexual characteristics, and decreases in growth rate and in the rate of bone age maturation (P less than 0.005). Patients with peripheral precocious puberty, however, had no significant change in gonadotropin or sex steroid levels, growth rate, or the rate of bone age maturation, and no improvement in secondary sexual characteristics. Thus, LHRHa is an effective treatment of central precocious puberty and combined peripheral and central precocious puberty, but is ineffective in the therapy of peripheral precocious puberty.

Adrenal Hyperplasia, Congenital↗
PubMed1985

Somatomedin-C in accelerated growth of children with precocious puberty.

To assess the role of somatomedin-C as a possible mediator of the growth spurt in children with central precocious puberty, we compared Sm-C levels in 40 children with central precocious puberty, 87 age-matched normal children, and 110 normal pubertal controls. Somatomedin C levels were significantly elevated for age in the children with precocious puberty (P less than 0.01), and were similar to the levels observed during normal puberty. The patients with precocious puberty were given the luteinizing hormone releasing hormone analogue D-Trp6-Pro9-NEt-LHRH (LHRHa) for 6 months. Treatment caused a significant decrease in secondary sexual characteristics, growth rate, plasma gonadotropins, sex steroids (estradiol in the girls and testosterone in the boys), and Sm-C levels. Growth during LHRHa treatment returned to the age-appropriate rate, whereas plasma Sm-C levels, although lower than pretreatment levels, remained significantly elevated for age (P less than 0.002). In addition, growth rates before and during treatment did not correlate with the plasma somatomedin C levels, nor did the decreases in growth rate during LHRHa therapy correlate with the decreases in somatomedin C levels. Growth rates did correlate significantly, however, with plasma estradiol levels in the girls (P less than 0.0005) and with plasma testosterone levels in the boys (P less than 0.025). We conclude that the growth spurt in children with precocious puberty cannot be explained by the plasma level of somatomedin C.

Child↗
PubMed1985

Sideroblastic colonies in erythroid cultures grown from normal human marrow.

Normal human erythroid progenitor cells from bone marrow were grown in culture using a methyl cellulose clonal assay technique. Sideroblastic erythroid cells were found in the majority of colonies examined at 14-17 days, and a few sideroblasts were found in some of the colonies examined after shorter periods of culture. Electron microscopy confirmed the presence of both intramitochondrial iron deposits and cytoplasmic ferritin aggregates. These morphological appearances probably represent an abnormality induced by the in vitro culture conditions and cannot be used as evidence for an intrinsic defect in haem synthesis.

Cells, Cultured↗
PubMed1985

Survey of drug use by the elderly and possible impact of drugs on nutritional status.

The drug consumption of institutionalized and noninstitutionalized elderly in the central Kentucky area was surveyed. The 259 subjects above age 60 were randomly selected and consisted of 122 institutionalized and 137 noninstitutionalized subjects. Individual data on age, sex, drug intake, dosage, and health status were recorded. The drugs taken were categorized by their pharmacological action, and the number of subjects on each drug was recorded. Institutionalized elderly subjects had a significantly higher drug intake (average 5.2 drugs a day) than noninstitutionalized elderly subjects (average 1.6 drugs a day). A consistent increase was found in the average number of drugs used with increasing age. The results also showed that the medications most frequently used were drugs used for cardiovascular disease, for the central nervous system, and for constipation. Aspirin and Tylenol were also commonly used. Institutionalized elderly subjects had especially high intakes of these drugs. The possible impact of these drugs on the nutritional status of the elderly was discussed. Some medications for long-term use may exert serious adverse effects on the nutritional status.

Aged↗
PubMed1982

Erythroblast iron metabolism in sideroblastic marrows.

The uptake of iron by bone marrow erythroblasts and its intracellular distribution have been studied in 23 patients with primary sideroblastic anaemia (SA), five patients with secondary SA and one patient with only non-ringed sideroblasts. EM of erythroblasts from 18 cases showed both mitochondrial iron deposits and cytoplasmic ferritin aggregates in all cases except the patient with only non-ringed sideroblasts. Iron uptake by erythroblasts in whole bone marrow was normal but there was a decreased incorporation into haem and an increased incorporation into cell stroma. Age matching of erythroblasts using Percoll density gradient centrifugation indicated that stromal iron incorporation was high at all stages of erythroblast development even before haem synthesis had become a major metabolic activity and in intermediate and late erythroblasts a real decrease in haem synthesis appeared less certain. These observations, together with the inability to correct the abnormality in vitro with either pyridoxal phosphate or delta amino-laevulinic acid suggest that the primary defect in SA may be an abnormality of mitochondrial iron metabolism rather than an abnormality of haem synthesis.

Adult↗
PubMed1980

Demographic and social background characteristics of members of the Royal College of Obstetricians and Gynaecologists in Australia.

Demographic and social background characteristics of a random sample of 200 Australian members of the Royal College of Obstetricians and Gynaecologists were obtained in a questionnaire survey. Data are presented on age-sex distribution, marital status, period since graduation, length of College membership, type of practice, birthplace, education, religion, political orientation and social rank of family of origin.

Adult↗