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D A Price

Publications and source records attributed to D A Price.

At least 163 records · Page 9Linked to original sources
PubMed1992

Dynamics of atrial natriuretic factor-guanylate cyclase receptors and receptor-ligand complexes in cultured glomerular mesangial and renomedullary interstitial cells.

The dynamics of the guanylate cyclase receptor of atrial natriuretic factor (GCA-ANF receptor) were investigated in cultured glomerular mesangial and renomedullary interstitial cells from the rat. In these cells, the GCA-ANF receptor did not mediate internalization and lysosomal hydrolysis of 125I-ANF1-28 and did not undergo ligand-induced endocytosis. Glomerular mesangial cells were able, however, to mediate internalization and lysosomal hydrolysis of 125I-ANF1-28 via clearance ANF (C-ANF) receptors and to promote rapid receptor-mediated internalization and lysosomal hydrolysis of 125I-(Sar1) angiotensin II. Radioligand specifically bound to surface GCA-ANF receptors was rapidly dissociated at 37 degrees C (k(off) greater than 0.8 min-1), with a Q10(30-37 degrees C) greater than 6. The dissociation was markedly slower at subphysiological temperatures (Q10(4-30 degrees C), 2-3) or in the presence of 0.5 mM amiloride. The results demonstrate that the GCA-ANF receptor, contrary to C-ANF receptors and most other polypeptide hormone receptors, is a membrane resident protein that does not mediate internalization and lysosomal hydrolysis of ligand. The termination of the interaction of ANF with GCA-ANF receptors results from a physiological process that leads to rapid dissociation of receptor-ligand complexes. The unique dynamics of GCA-ANF receptor-ligand complexes are likely to contribute importantly to stimulus-response homeostasis of ANF.

Amiloride↗
PubMed1992

Fundulus heteroclitus gonadotropins. 3. Cloning and sequencing of gonadotropic hormone (GTH) I and II beta-subunits using the polymerase chain reaction.

mRNA was isolated from Fundulus heteroclitus pituitaries and used to construct a cDNA library in lambda gt22A. A series of synthetic oligonucleotides, based on conserved regions of teleost gonadotropic hormone (GTH) beta-subunits, were constructed and used as primers in the polymerase chain reaction (PCR) to amplify GTH cDNAs. Appropriate length PCR products were subcloned and sequenced. Eight clones were eventually identified as cDNAs encoding two distinct beta-subunits of F. heteroclitus, GTH I and GTH II. By comparison with known GTH sequences, putative signal sequences of 19 end 21 amino acids and mature beta-subunits of 95 and 115 amino acids were found for GTH I and GTH II, respectively. Both beta-subunits had well conserved cysteine positions when aligned with other members of the glycoprotein family. The elucidation of the complete nucleotide sequences of two types of F. heteroclitus GTH provides definitive proof that in this species there are at least two distinct forms of pituitary GTH analogous to the classical luteinizing hormone-follicle stimulating hormone family.

Amino Acid Sequence↗
PubMed1992

Relationships among the FMRFamide-like peptides.

The nuclear family of FaRPs (comprising those peptides that are, on compelling evidence, homologous) appears to be restricted to the protostome invertebrate phyla: i.e. Mollusca, Arthropoda, Annelida and Nematoda. Neither the origin nor the range of the family has been definitively established. That is, no genuine homologs have been demonstrated yet in the flatworms (though not for lack of trying), and neither the pseudocoelomate phyla related to the nematodes, nor the coelomate relatives of the annelids have been examined. The extended family of FaRPs (including peptides with little consistent sequence similarity beyond a penultimate Arg and an amidated hydrophobic residue at the C-terminal) exists in all phyla. Such a superfamily was probably first proposed by Morris et al. (1982), whose sequencing of SCPB suggested to them a class of peptides, "... the key unit for biological activity being Phe-A-Arg-B-amide (where A and B are also hydrophobic amino acids)." The ubiquity of the convergent FaRPs could reflect a conserved family of complementary heptahelical receptors requiring the arginyl residue for binding (Price and Greenberg, 1989). But another selective advantage would be the protection provided by a penultimate Arg against certain deamidating peptidases, found so far in yeast and mammals (Jackman et al., 1990).

Amino Acid Sequence↗
PubMed1992

Renal receptors and effects of atrial natriuretic factor in compensatory renal hypertrophy.

In the present study we investigated the in vivo and in vitro renal responsiveness to ANF, and the adaptation of ANF receptors in compensatory renal hypertrophy in the rat. One week after left nephrectomy (UNx), plasma levels of immunoreactive ANF, blood pressure (MAP), hematocrit (Hct), and urine flow rate (V) were unaltered compared to control (C) rats. Baseline GFR and potassium excretion (UKV) were significantly higher, and sodium excretion (UNaV) tended to be elevated in UNx rats. Administered ANF led to similar dose-related decreases in MAP and increases in Hct in UNx and C rats. However, at each dose of infused ANF, absolute values and the increase in GFR and UNaV were higher in UNx than in C rats. Hypertrophied (H) kidneys were removed from UNx and perfused in vitro to determine distribution and density of ANF receptors, responsiveness to ANF, and receptor-mediated organ clearance of 125I-ANF1-28. The density of ANF receptors in cortex, outer medulla, and papilla of H kidneys was not significantly different from that in C kidneys. In H isolated kidneys, ANF led to dose-related increases in GFR, V, UNaV, and UKV that were indistinguishable (P greater than 0.05) from those in C kidneys. Receptor-mediated organ clearance of 125I-ANF1-28 in isolated H kidneys was 2.8 +/- .02 ml/min, a value not significantly different (P greater than 0.05) from that in C kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A YAC contig in Xp21 containing the adrenal hypoplasia congenita and glycerol kinase deficiency genes.

The gene loci for adrenal hypoplasia congenita (AHC) and glycerol kinase deficiency (GK) map in Xp21 distal to Duchenne muscular dystrophy (DMD), and proximal to DXS28 (C7), by analysis of patient deletions. We have constructed a yeast artificial chromosome (YAC) contig encompassing a 1.2 Mb region extending distally from DMD, and containing DXS708 (JC-1), the distal junction clone of a patient with GK and DMD. A pulsed-field gel electrophoresis map of the YAC contig identified 3 potential CpG islands. Whole YAC hybridization identified cosmids both for construction of cosmid contigs, and isolation of single copy probes. Thirteen new single copy probes and DXS28 and DXS708 were hybridized on a panel of patients; the deletion mapping indicates that the YAC contig contains both GK and at least part of AHC, and together with the physical map defines a GK critical region of 50-250 kb. In one AHC patient with a cytogenetically detectable deletion we used the new probes to characterize a complex double deletion. Non-overlapping deletions observed in other unrelated AHC patients indicate that the AHC gene is large, extending over at least 200-500 kb. This mapping provides the basis for the identification of the AHC and GK genes.

Adrenal Gland Diseases↗
PubMed1992

Sustaining and rewarding clinical teaching.

High standards of clinical teaching are essential in the training of medical students but greater prominence needs to be given to its importance. Strategies are described by which one medical school has raised the awareness of clinical teaching and supported those who deliver it.

Clinical Clerkship↗
PubMed1992

FMRFamide-related peptides potentiate transmission at the squid giant synapse.

The stellate ganglion of the squid Loligo pealli contains the neuropeptides Phe-Met-Arg-Phe-NH2 (FMRFamide), Phe-Leu-Arg-Phe-NH2 (FLRFamide) and at least one N-terminally extended FMRFamide-related peptide that is yet to be fully characterized. Both local application and arterial perfusion of FLRFamide potentiate transmission at the giant synapse. The N-terminally related peptide Ser-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (SDPFLRFamide) produced a similar effect. The threshold for both the tetra- and the hepta-peptides was less than 10 microM. Potentiation could be detected as an increase in rate of rise of the EPSPs, as an increase in amplitude of the EPSP in the absence of spikes, or under voltage clamp as an increase in the EPSC. The effect was most pronounced when the synapse was fatigued by high frequency stimulation. Another molluscan peptide, eledoisin and also leucine enkephalin were without effect. In the absence of any detectable effects of FLRFamide on the resting membrane potential of either pre- or postsynaptic terminals or on the presynaptic spike, it is suggested that the peptide influences transmitter mobilization. However, the peptide could also exert small changes in preterminal calcium currents, which so far we have been unable to detect.

Animals↗
PubMed1992

Relationship between urinary and serum growth hormone and pubertal status.

Urinary growth hormone (uGH) excretion and serum growth hormone concentrations have been compared in three groups of children. Group 1 consisted of 21 children who had had cranial irradiation as part of their treatment for acute lymphoblastic leukaemia; group 2, 18 normal children; and group 3, 12 boys with constitutional delay in growth and puberty who were in early puberty. Children in groups 1 and 2 each had a 24 hour serum growth hormone profile (sampling every 20 minutes) and concurrent urine collection. The 12 boys in group 3 had a total of 21 profiles (sampling every 15 minutes for 12 hours) and concurrent urine collections. In the prepubertal children (n = 17), in both groups 1 and 2, there was a significant correlation between mean serum growth hormone and total uGHng/g creatinine. There were also significant correlations between total uGHng/g creatinine and both peak serum growth hormone and mean amplitude of the pulses in the growth hormone profile. In the pubertal children (n = 22), in groups 1 and 2, whether combined or in separate groups, there was no significant correlation between total uGHng/g creatinine and mean serum growth hormone, peak serum growth hormone, or mean amplitude of the pulses in the growth hormone profile. In group 3 there were significant correlations between total uGHng/g creatinine and both the mean serum growth hormone and mean amplitude of the pulses in the profile. Therefore uGH estimations appear to correlate well with serum growth hormone profiles in children who are prepubertal or in early puberty, but not in those further advanced in pubertal development. These results may reflect a variation in the renal handling of growth hormone during pubertal development. uGH estimation may be an unreliable screening investigation for growth hormone sufficiency in mid to late puberty.

Adolescent↗
PubMed1992

The influence of age, size, pubertal status and renal factors on urinary growth hormone excretion in normal children and adolescents.

Overnight urinary growth hormone (GH) excretion was measured in 528 schoolchildren (aged 4-16 years) whose heights and weights were between the third and 97th centiles. Urinary GH increased significantly with age, reaching a maximum in boys at 15-years-old and in girls at 13-years-old. Peak levels were five and three times higher in boys and girls respectively than in 4-year-olds. Maximum urinary GH excretion was seen at breast stages 3 and 4 in girls and at genital stage 4 in boys followed by a decline in both sexes at stage 5. Boys excreted more GH than girls during prepubertal and pubertal years. During prepubertal years there were fluctuations of urinary excretion of GH with age. Height, weight and pubertal status predicted 31% of the variability of urinary excretion of GH, and urinary excretion of creatinine, albumin and N-acetylglucosaminidase (NAG) predicted 52% of the variability. The importance of establishing sound age and sex-related reference ranges for urinary growth hormone is stressed before application of this test to children with growth disorders.

Adolescent↗
PubMed1991

The SALMFamides: a new family of neuropeptides isolated from an echinoderm.

We have isolated two novel related neuropeptides from the radial nerve cords of the starfishes Asterias rubens and Asterias forbesi. One is an octapeptide with the amino acid sequence Gly-Phe-Asn-Ser-Ala-Leu-Met-Phe-NH2 and the other is a dodecapeptide with the amino acid sequence Ser-Gly-Pro-Tyr-Ser-Phe-Asn-Ser-Gly-Leu-Thr-Phe-NH2. The peptides were purified using high performance liquid chromatography (HPLC) and a radioimmunoassay for the molluscan FMRFamide-related neuropeptide, pQDPFLRFamide. Both peptides share minimal sequence identity with members of the family of FMRFamide-like peptides so we have designated them as founder members of a new family, the SALMFamides. We refer to the octapeptide as SALMFamide 1 (S1) and the dodecapeptide as SALMFamide 2 (S2). S1 and S2 are the first neuropeptides identified in species belonging to the phylum Echinodermata.

Amino Acid Sequence↗
PubMed1991

Final height in girls with untreated constitutional delay in growth and puberty.

During a 10-year period, 23 girls compared to 118 boys presented with constitutional delay in growth and puberty. Of these girls, 15 were followed to final height to determine the outcome of the untreated condition in terms of both growth and psychological well-being. At presentation chronological age was 13.2 (1.7) years [mean (S.D.)], bone age delay 2.7 (0.9) years, standing height standard deviation score (SDS) -3.4 (0.9), and predicted adult height (PAH) SDS -1.3 (0.7) (Tanner-Whitehouse II method). Final height SDS was -1.5 (0.8) measured at 18.9 (2.6) years of age. Mean age at menarche was 15.6 (0.9) years. There was no significant difference between final adult height (FH) and PAH but there was a significant difference between FH and target height (P less than 0.001). Psychological questionnaires revealed no significant difference in self-esteem, marital or employment status between the patient and control groups. There was no significant correlation between self-esteem and FH but 80% felt their growth delay had affected success either at school, work or socially. Of the patients, 50% would have preferred treatment to advance their growth spurt. This study demonstrates that girls with constitutional delay in growth and puberty reached their PAH, although this was lower than the midparental heights. The girls also experienced significant distress due to delayed growth and puberty and treatment to advance growth should be considered more frequently.

Adolescent↗
PubMed1991

Puberty in children with idiopathic growth hormone deficiency on growth hormone treatment: preliminary analysis of the data from the Kabi Pharmacia International Growth Study.

In total, 524 children (335 boys, 189 girls) with idiopathic growth hormone deficiency (GHD) who had entered puberty after at least 1 year of growth hormone (GH) treatment were studied. Spontaneous onset of puberty occurred in 319 boys and 174 girls, and puberty was induced in 16 boys and 15 girls. Median chronological and bone ages at onset of spontaneous puberty were 14.8 and 13.4 years in boys, and 13.3 and 11.8 years in girls, respectively. Age at onset of spontaneous puberty was correlated to age at start of GH treatment. Puberty was induced at a median chronological age of 16.0 years in boys and 14.4 years in girls. Height velocity increased in the year before spontaneous puberty in boys and girls, and rose further to a maximum (median, 8.3 cm/year) in the first year of puberty in boys. In girls, the maximum height velocity occurred in the year before puberty (median, 6.5 cm/year). Height velocity increased in the year before spontaneous puberty in boys and girls, and rose further to a maximum (median, 8.3 cm/year) in the first year of puberty in boys. In girls, the maximum height velocity occurred in the year before puberty (median, 6.5 cm/year). Height velocity during the first year of puberty was inversely correlated to age at puberty onset (r = -0.56, p = 0.0001). After medical induction of puberty, height velocities in the first year of puberty were 5.4 and 3.4 cm/year for boys and girls, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Subcutaneous or intramuscular insulin injections.

To find out whether diabetic children may inject their insulin intramuscularly rather than subcutaneously, a random sample of 32 patients aged 4.3-17.9 (median 11.3) years was studied. Distance from skin to muscle fascia was measured by ultrasonography at standard injection sites on the outer arm, anterior and lateral thigh, abdomen, buttock, and calf. Distances were greater in girls (n = 15) than in boys (n = 17). Whereas in most boys the distances were less than the length of the needle (12.5 mm) at all sites except the buttock, in most girls, the distances were greater than 12.5 mm except over the calf. Over the fascial plane just lateral to the rectus muscle the distance from skin to peritoneum was less than 12.5 mm in 14 of the 17 boys and one of the 15 girls. Twenty five of the 32 children injected at an angle of 90 degrees, and 24 children raised a skinfold before injecting. By raising a skinfold over the anterior thigh, the distance from skin to muscle fascia was increased by 19% (range 0-38%). We conclude that most boys and some girls who use the perpendicular injection technique may often inject insulin into muscle, and perhaps on occasions into the peritoneal cavity.

Adolescent↗
PubMed1991

Activation of a peptidergic synapse locally modulates postsynaptic calcium influx.

We examined the synaptic connection between Phe-Met-Arg-Phe-NH2 (FMRFamide)-immunoreactive neurone VD4 and its target neurone P1, both found in the central nervous system of the pond snail Helisoma trivolvis. The major FMRFamide-like peak in neurone VD4 appears to be FMRFamide itself, based on its high performance liquid chromatography (HPLC) elution time and immunoreactivity before and after oxidation, but small peaks are also present at the elution times of Phe-Leu-Arg-Phe-NH2 (FLRFamide) and Gly-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (GDPFLRFamide). The modulatory actions of the neuropeptides found in neurone VD4 were tested on the postsynaptic target cell P1. Bath application of both the tetrapeptides FMRFamide and FLRFamide at a concentration of 10(-5) mol l-1 reduced the macroscopic voltage-sensitive calcium current of neurone P1 in culture; FMRFamide by 45% and FLRFamide by 51%. Bath application of the heptapeptide GDPFLRFamide (10(-5) mol l-1) reduced the calcium current by only 8%. We reconstructed the synaptic connection between VD4 and P1 in culture. Action-potential-evoked calcium transients in neurites growing from P1 cells in culture were monitored using Fura-2. Addition of FMRFamide, FLRFamide or GDPFLRFamide reduced the magnitude of the calcium transient in P1. Stimulation of VD4 mimicked the effects of peptide application and caused localized reductions in the action-potential-evoked calcium transients in P1 at the points of contact between the neurites of neurones VD4 and P1. These results suggest that neurone VD4 modulates the calcium influx of neurone P1 through the release of endogenous FMRFamide-related peptides and that this modulatory action is restricted to sites of synaptic interaction.

Animals↗
PubMed1990

Growth response in the first year of growth hormone treatment in prepubertal children with organic growth hormone deficiency: a comparison with idiopathic growth hormone deficiency. The Executive Scientific Committee of the Kabi International Growth Study.

Patients in the Kabi International Growth Study (KIGS) up to 1st January 1990 who had organic growth hormone deficiency (OGHD) were identified. They accounted for 21% of all patients with growth hormone deficiency (GHD). Diagnostic categories within the OGHD group included septo-optic dysplasia, postnatal trauma, craniopharyngioma, other cranial tumours, and following acute leukaemia. Features at presentation and during the first year of hGH treatment were compared with those of children with idiopathic growth hormone deficiency (IGHD). Ninety prepubertal children with OGHD were selected for comparison of observed first-year height velocity (HV) with predicted values based on those observed in 257 children with IGHD. Those with septo-optic dysplasia, postnatal trauma and craniopharyngioma responded as predicted, whereas those with other cranial tumours appeared to grow less well than predicted. Glucocorticoid treatment did not affect response, but previous cranial or craniospinal irradiation was found to be associated with an observed HV which was significantly less than predicted.

Adolescent↗
PubMed1990

Final height in boys with untreated constitutional delay in growth and puberty.

To determine the natural history and psychological impact of the growth pattern in boys with constitutional delay in growth and puberty (CDGP), 43 boys presenting with short stature due to CDGP were followed up to final height. At presentation mean (SD) chronological age was 14.0 (1.9) years, bone age delay 2.7 (1.0) years, standing height standard deviation score (SDS) -3.4 (0.6), and predicted adult height SDS -1.3 (0.7). Final adult height SDS was -1.6 (0.9), measured at 21.2 (2.6) years. There was no significant difference between final height and predicted adult height, but there was a significant difference between final height and measured mid-parental height. Psychological questionnaires showed no significant difference in self esteem, marital, or employment state between the CDGP group and a control group. There was no correlation between self esteem and final height, but 25 felt their growth delay had affected their success either at school, work, or socially and 20 would rather have had treatment to advance their growth spurt. This study supports the more frequent use of active medical treatment to advance growth in boys with CDGP, and shows that although boys with CDGP reach their predicted heights, this is short for their families.

Adolescent↗
PubMed1990

Increase in urinary growth hormone excretion in puberty.

During the pubertal years the overnight urinary excretion rate of growth hormone (hGHu) increases to three to four times the prepubertal rate, reaching a peak in girls at 13 years and in boys at 15 years. After puberty the mean rate of overnight hGHu is twice that before puberty.

Adolescent↗