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Biomedical subjects

J A Darling

Publications and source records attributed to J A Darling.

At least 19 recordsLinked to original sources
PubMed2004

Regional population structure of a widely introduced estuarine invertebrate: Nematostella vectensis Stephenson in New England.

Nematostella vectensis is an infaunal anemone occurring in salt marshes, lagoons and other estuarine habitats in North America and the United Kingdom. Although it is considered rare and receives protection in England, it is widely distributed and abundant in the United States, particularly along the Atlantic coast. Recent studies suggest that both anthropogenic dispersal and reproductive plasticity may significantly influence the genetic structure of N. vectensis populations. Amplified fragment length polymorphism (AFLP) fingerprinting of individuals from nine populations in the northeastern United States indicates that stable populations are maintained by both asexual and sexual reproduction; in some cases asexually reproducing lineages exist within sexually reproducing populations. F statistics reveal extraordinarily high degrees of genetic differentiation between populations, even those separated by very short distances (less than 100 m). Genetic distances show little to no correlation with geographical distances, consistent with a role for sporadic, geographically discontinuous dispersal coupled with limited gene flow. No single genotype was found at more than one site, despite apparent homogeneity of habitat. In contrast with reported genotypic distributions for Nematostella in the United Kingdom, where a single clonal genotype dominates at multiple sites through southern England, our data thus fail to support the hypothesis of a general-purpose genotype in the northeastern United States. However, they are consistent with important roles for reproductive plasticity, sporadic introductions and complex local population dynamics in determining the global and regional distribution of this species.

Analysis of Variance↗
PubMed1999

Recombinant expression, purification, and characterization of Toxoplasma gondii adenosine kinase.

Toxoplasma gondii lacks the capacity to synthesize purines de novo, and adenosine kinase (AK)-mediated phosphorylation of salvaged adenosine provides the major route of purine acquisition by this parasite. T. gondii AK thus represents a promising target for rational design of antiparasitic compounds. In order to further our understanding of this therapeutically relevant enzyme, an AK cDNA from T. gondii was overexpressed in E. coli using the pBAce expression system, and the recombinant protein was purified to apparent homogeneity using conventional protein purification techniques. Kinetic analysis of TgAK revealed Km values of 1.9 microM for adenosine and 54.4 microM for ATP, with a k(cat) of 26.1 min(-1). Other naturally occurring purine nucleosides, nucleobases, and ribose did not significantly inhibit adenosine phosphorylation, but inhibition was observed using certain purine nucleoside analogs. Adenine arabinoside (AraA), 4-nitrobenzylthioinosine (NBMPR), and 7-deazaadenosine (tubercidin) were all shown to be substrates of T. gondii AK. Transgenic AK knock-out parasites were resistant to these compounds in cell culture assays, consistent with their proposed action as subversive substrates in vivo.

Adenosine Kinase↗
PubMed1994

Sweet's syndrome and hypothyroidism.

Hypothyroidism and Sweet's syndrome occurring together were diagnosed in a 33 year old woman. This association is uncommon, but may be underdiagnosed and underreported.

Adult↗
PubMed1994

Evolution of pseudohypoparathyroidism: an informative family study.

An adult woman with pseudopseudohypoparathyroidism had a child with normal calcium and parathyroid hormone concentrations and cyclic AMP response to injected parathyroid hormone in infancy. By 2.5 years he had features of pseudohypoparathyroidism with raised parathyroid hormone and 'flat' cyclic AMP response. This is the first documented case of a change in parathyroid hormone responsiveness. The abnormal cyclic AMP response to parathyroid hormone in pseudohypoparathyroidism can evolve during childhood.

Adult↗
PubMed1991

Plasma cyclic AMP response to intravenous parathyroid hormone in pseudohypoparathyroidism.

Highly purified bovine parathyroid hormone (PTH) was given by intravenous bolus injection to patients being investigated for disorders of mineral metabolism, and to adult volunteer controls. Plasma cyclic AMP measured basally and at 10 min gave reliable discrimination between the normal response and cases of pseudohypoparathyroidism. Infants under 3 months of age tended to have higher basal levels of cAMP and a flatter pattern of response to the dose of PTH used. This simplified test procedure in children offers considerable advantages over previous tests of PTH responsiveness which involve urine collections and multiple blood sampling. It is suitable for selective screening of individuals suspected of pseudohypoparathyroidism on the basis of their family history or physical abnormalities.

Adolescent↗
PubMed1986

Onset of the release of spermatozoa (spermarche) in boys in relation to age, testicular growth, pubic hair, and height.

The onset of production of spermatozoa (spermarche) is the basis for achievement of reproductive capacity in men. We collected 24-h urine samples every 3 months in a 7-yr longitudinal study of 40 normal boys initially aged 8.6-11.7 yr. After centrifugation, the urine was analyzed for the presence of spermatozoa by microscopic examination, and spermarche was estimated on the basis of age at first observed spermaturia. The results were corrected for the intermittent occurrence of spermatozoa in the urine after first observed spermaturia and the fact that the urine samples were collected quarterly. In addition, physical examination, including determination of testicular size by orchidometer measurement, pubic hair distribution (Tanner stage), and height, was carried out every 6 months. Spermarche occurred at a median age of 13.4 yr (range, 11.7-15.3 yr), at a time when testicular size was 4.7-19.6 ml (median, 11.5 ml), and pubic hair distribution was 1-5 (median, 2.5). In most boys, spermarche preceded the age of peak height velocity (median, 13.8 yr; range, 12.2-15.2 yr); at the time of spermarche, median peak height growth velocity was 9.9 cm/yr (range, 7.5-13.4 cm/yr), and median height was 160.4 cm (range, 151.7-175.9 cm). We conclude that spermarche is an early pubertal event and that a wide variation in testicular size and secondary sex characteristics is found at that time. In particular, spermarche may occur when little or no pubic hair has developed, and the testes have grown only slightly.

Adolescent↗
PubMed1986

Longitudinal study of testosterone and luteinizing hormone (LH) in relation to spermarche, pubic hair, height and sitting height in normal boys.

In a 7-year longitudinal study of 40 normal boys, initially aged 8.6-11.7 years, 24-h urine samples were collected every 3 months and analysed for LH and testosterone as well as for the presence of spermatozoa (spermaturia). Spermarche (onset of the release of spermatozoa) was estimated on the basis of age at the first observed spermaturia. Physical examination, including measurements of height and sitting height and staging of pubic hair (Tanner stage) was performed every 6 months. Spermarche occurred early in puberty when the median pubic hair stage was 2.5. Urinary testosterone did not reach maximum levels until approximately 2 years after spermarche. Peak height velocity occurred when urinary testosterone levels were low, 1-2 years before adult levels of testosterone were attained. Our results support the proposition that low levels of testosterone have a predominantly growth-promoting effect, whilst higher concentrations have an inhibitory effect on height spurt.

Body Height↗
PubMed1980

Neutral 17beta-hydroxysteroid oxidoreductase deficiency in testes causing male pseudohermaphroditism in an infant.

A deficiency of neutral 17beta-hydroxysteroid oxidoreductase activity in testes has been diagnosed in a n infant with male pseudohermaphroditism. In vivo stimulation tests of testicular endocrine function with human chorionic gonadotrophin provided an accurate diagnosis in contrast to estimates of enzymic activity in vitro in testes and other tissues. The discrepancy in testes may be due to the absence of gonadotrophin stimulation in the latter studies. The in vitro studies show that there are at least two forms of 17beta-hydroxysteroid oxidoreductase under independent genetic control and that only one form is localized to the testes. The diagnosis before puberty has allowed early treatment by removal of the abnormal testes which should prevent the usual presenting clinical signs of marked masculinizatin and hirsutism at puberty.

17-Hydroxysteroid Dehydrogenases↗
PubMed1975

Familial glucocorticoid deficiency. Studies of diagnosis and pathogenesis.

The clinical and biochemical findings are described in 2 brothers who had intermittent hypoglycaemia generally precipitated by the "stress" of infection. Both were tall and pigmented. Both boys showed a failure of adrenocortical response to ACTH which was progressive in the eldest boy. The diagnosis of familial glucocorticoid deficiency (hereditary adrenocortical unresponsiveness) was confirmed by the absence of electrolyte imbalance even on a low sodium diet, and by very high levels of ACTH in plasma. High levels of deoxycorticosterone (DOC) were found in both children with normal levels of other plasma corticosteroids. It is suggested that the high levels of DOC may be in some way related to the apparent persistence of a "fetal" type of adrenocortical steroid biosynthesis for 18 months or more in these boys. After the diagnosis, established by relatively simple methods, treatment with cortisone acetate has 0een highly effective.

17-Hydroxycorticosteroids↗