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Biomedical subjects

D A Price

Publications and source records attributed to D A Price.

At least 145 records · Page 8Linked to original sources
PubMed1994

N-terminally extended FMRFamide-related peptides of Helix aspersa: processing of the precursor protein and distribution of the released peptides.

Sequencing of cDNA clones reveals a precursor protein that can be processed into 10 different hepta-FaRPs. Two of the peptides are previously undescribed and are N-terminally extended forms of-YMRFamide, making them the only methionine-containing peptides in the precursor. They are separated from the main cluster of hepta-FaRPs by a recognition site (RQKR) for the Golgi-resident proteolytic enzyme furin. Antisera raised against the synthetic peptide KQDPFLRFGK specifically stain the clusters of neurons in the parietal ganglia that have been shown to contain hepta-FaRP mRNA. These antisera recognize two major protein bands of 35 and 23 kDa on immunoblots. Evidence is presented to identify the larger band as the precursor protein and the smaller band as the fragment containing the main cluster of hepta-FaRPs produced after furin cleavage. A series of immunostaining bands of 22-13 kDa suggests sequential and non-preferential N- or C-terminal cleavage at the mainly monobasic (K and R) sites that link all of the peptide sequences throughout the 23-kDa fragment, to yield the preamidated hepta-FaRPs. Immunostaining of sections shows punctate staining in the perikarya of the parietal cluster neurons commensurate with label within the endoplasmic reticulum and Golgi apparatus. Staining is followed through the axons to many fibers in the nerve trunks and is picked up as fine processes within the skin. These observations indicate that the antiserum used here recognizes one or more of the processed hepta-FaRPs, a view confirmed by radioimmunoassay. The abundance of immunoreactive fibers within the skin suggests a major role for the peptides in this tissue.

Amino Acid Sequence↗
PubMed1994

FMRFamide-related peptides from the kidney of the snail, Helisoma trivolvis.

Three FMRFamide-related peptides (FaRPs) were purified and characterized from the kidney of the snail, Helisoma trivolvis, by HPLC and detected using two radioimmunoassays (RIA) for FaRPs. Automated sequencing and mass spectrometry of the isolated peptides suggest the following sequences: Phe-Met-Arg-Phe-NH2 (FMRFamide), Phe-Leu-Arg-Phe-NH2 (FMRFamide), and Gly-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (GDPFLRFamide). The FaRPs, predominantly the heptapeptides, were also detected by HPLC and RIA in other osmoregulatory tissues such as the skin, mantle, and the hemolymph. The level of FaRPs, detected by radioimmunoassay, appears to be lower in snails kept under hyposmotic stress than in snails kept under isosmotic stress. The FaRPs appear to be involved in osmoregulation in H. trivolvis.

Amino Acid Sequence↗
PubMed1994

The quality of medical teaching and learning in rural settings: the learner's perspective.

During 1992-93, the authors produced a video-based teacher development resource kit for rural and isolated general practitioners and hospital medical personnel who are involved in medical teaching. As part of the development process, we surveyed 240 medical undergraduate students of the University of Queensland about their experiences and perceptions of teaching and learning in rural settings in Queensland. For approximately 90% of undergraduate learners, the experience with a rural medical practitioner was extremely positive. The major positive features identified by students were: being treated as a colleague; being allowed/encouraged to work independently; receiving feedback on their work; and being given ample 'hands-on' minor procedural experience and/or teaching. The 10% of students who reported unfavourably on their rural terms identified lack of opportunities to carry out solo consultations/work independently, lack of structure in teaching/learning experiences, and lack of hands-on experience as the major disappointments. The results demonstrate clearly how and why the majority of rural medical teachers in Queensland are effective facilitators of undergraduate learning.

Attitude↗
PubMed1994

FRF peptides in the ARC neuromuscular system of Aplysia: purification and physiological actions.

1. One preparation that has proven to be advantageous for the study of neuromuscular modulation is the accessory radula closer (ARC) muscle of Aplysia californica and its motor neurons B15 and B16. In this study three members of a new peptide family have been purified from this well-characterized preparation. Because these peptides terminate in Phe-Arg-Phe-amide, we have named them FRFA, FRFB, and FRFC. The FRFs are thus RFamide peptides and are related to the widely studied neuropeptide FMRFamide. 2. The FRFs are present in the ARC motor neuron B15 in small quantities. 3. When they are exogenously applied, the FRFs decrease the size of ARC muscle contractions elicited by stimulation of either motor neuron B15 or B16. They appear to do this by a combination of presynaptic and postsynaptic actions. 4. Presynaptically, the FRFs appear to act like the buccalins, another family of inhibitory ARC neuropeptides. Both families of peptides reduce the size of motor neuron-elicited excitatory junction potentials (EJPs) presumably by decreasing presynaptic acetylcholine (ACh) release. 5. Postsynaptically, the FRFs appear to depress contractions because they activate a characteristic voltage-dependent, 4-amino-pyridine-sensitive K current in the ARC muscle. The same current is activated by a second class of ARC modulators: those that exert potentiating actions at low doses and inhibitory actions at high doses, i.e., serotonin, the small cardioactive peptides (SCPs), and particularly the myomodulins. Receptors mediating activation of the K current by the FRFs and the other modulators do, however, appear to be different. 6. We hypothesize that the inhibitory actions of the FRFs prevent excessively large muscle contractions. If contraction size is limited, then contraction duration is also limited. This may allow faster and more energetically favorable switching between contractions of antagonistic muscles.

Acetylcholine↗
PubMed1994

Characterization and solubilization of the FMRFamide receptor of squid.

The optic lobe of squid (Loligo pealei) contains FMRFamide receptors that can bind an iodinated FMRFamide analog: [125I]-desaminoTyr-Phe- norLeu-Arg-Phe-amide ([125I]-daYFnLRFa). Radioligand binding assays revealed that squid FMRFamide receptors are specific, saturable, high affinity sites (Kd = 0.15 nM) densely concentrated in optic lobe membranes (Bmax = 237 fmole/mg protein). The receptors appeared to be coupled to Gs because guanine nucleotides inhibit receptor binding and the stimulation of adenylate cyclase by FMRFamide is GTP-dependent. Both the binding and cyclase data showed that FMRFamide, but not FMRF-OH, interacts at FMRFamide receptors; thus the C-terminal Arg-Phe-amide is critical for binding. The high binding affinity of FMRFamide (0.4 nM IC50) was specific for FMRFamide-like peptides. The structure-activity relations of many FMRFamide analogs were defined in detail and were nearly identical for both the membrane-bound and detergent-solubilized receptors. We also found that squid optic lobe contains FMRFamide-like reactivity as measured with both a radioimmunoassay and a radioreceptor assay. Moreover, we have sequenced a fragment of genomic DNA that encodes a FMRFamide precursor. Our findings in sum suggest that FMRFamide is a neurotransmitter in squid optic lobe, and that this tissue is a good source from which to purify FMRFamide receptors.

Adenylyl Cyclases↗
PubMed1994

The influence of body mass index on growth hormone secretion in normal and short statured children.

Obesity is one of the factors which limits the value of growth hormone (GH) provocation tests in the diagnosis of GH deficiency. We have therefore examined (1) the relationship between urinary GH (uGH), a physiological parameter of GH secretion, and percent ideal body mass index (BMI%), an indirect estimate of body fat, in 528 schoolchildren; and (2) the extent to which peak arginine stimulated (0.5 g/kg i.v.) GH concentrations were influenced by BMI% in 176 short normal (SN) children and 48 girls with Turner syndrome (TS). The mean BMI% (SD) for each group was 102.9 (10.8) in schoolboys, 102.7 (13.4) in schoolgirls, 95.8 (13.9) in SN boys, 98.2 (21.4) in SN girls and 105.9 (18.0) in TS. BMI% correlated inversely with log uGH in school-children (boys r = -0.16, P = 0.01; girls r = -0.25, P < 0.001). However, if each sex was subdivided by pubertal status, the inverse relationship only persisted in pubertal (boys r = -0.18, P = 0.04; girls r = -0.39, P < 0.001) but not prepubertal children (boys r = -0.1, P = 0.3; girls r = -0.11, P = 0.3). BMI% was also inversely related to log peak stimulated GH concentration in SN girls (r = -0.49, P < 0.001) but not SN boys (r = -0.14, P = 0.2) or girls with TS (r = 0.19, P = 0.2). The inverse relationship between normal body fat and physiological GH secretion becomes significant during puberty; in girls it accounts for 15% of the variability in uGH excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1993

Opsins from the lateral eyes and ocelli of the horseshoe crab, Limulus polyphemus.

cDNA clones encoding opsins from the lateral eyes and median ocelli of the horseshoe crab, Limulus polyphemus, were isolated from cDNA libraries. The opsin cDNAs obtained from the lateral eye and ocellar libraries code for deduced proteins with 376 amino acids. The two cDNAs are 96% identical at the nucleic acid level, differing primarily at the 3' untranslated region, and are apparently the products of two separate genes. The deduced opsin proteins are 99% identical to each other, differing at only 5 amino acids. The opsins encoded by these cDNAs are most likely the protein moiety of the visible-wavelength rhodopsins in this animal. In the lateral eye, expression of the opsin gene is restricted to the photoreceptor cells of the ommatidia. Comparisons with opsins of other species show that the Limulus opsin proteins are most similar (53% identity) to the opsin from the R1-6 photoreceptors of flies.

Amino Acid Sequence↗
PubMed1993

Synapse loss in the temporal lobe in Alzheimer's disease.

The temporal lobe is a well-documented area showing neuropathological and neurochemical changes in Alzheimer's disease (AD). Autopsy tissue was obtained from the superior temporal (Brodmann area 22) and the middle temporal (Brodmann area 21) regions of the cortex from patients with AD (n = 10; postmortem time < 13 hr) and age-matched control subjects (n = 10; postmortem time < 13 hr). Ultrastructural examination of the tissue revealed a highly significant AD-related decline in synaptic numbers in lamina III and V in both the superior and the middle temporal gyrus. Both normal control and AD tissue samples demonstrated a significant negative correlation between the number of synapses and the synapse size, as indexed by the length of the postsynaptic density. This change in synaptic size appears to compensate for the loss of synaptic numbers when viewed in terms of total synaptic contact area. Although the AD tissue showed an average 30% decline in synaptic numbers, the total synaptic contact area remained largely unchanged in both regions of the cortex. There were no significant correlations with age, postmortem time, or number of plaques observed in these areas. The loss of synaptic contacts in AD does not appear to be isolated to a particular cortical region or lamina.

Aged↗
PubMed1993

Quantitative assessment of synaptic density in the entorhinal cortex in Alzheimer's disease.

We quantified the synaptic density in the entorhinal cortex (Brodmann area 28) in autopsy material from 10 individuals with Alzheimer's disease and compared them to 11 age-matched, postmortem-matched control subjects without dementia, using standard electron microscopy. The statistical data showed no change in synaptic density between control and Alzheimer subjects, in either lamina III or V of the cortex. There were no correlations between synaptic density and synaptic apposition length or density of senile plaques. The entorhinal cortex stands in marked contrast to other cortical areas that show a significant decline in synaptic numbers with Alzheimer's disease. This preservation of synaptic numbers may be related to a plasticity response that is greater in the entorhinal area than in other areas of the cortex.

Aged↗
PubMed1993

Urinary growth hormone excretion in the assessment of children with disorders of growth.

OBJECTIVE: We wished to evaluate the use of urinary GH measurements when compared to conventional GH provocation tests in the assessment of short children. DESIGN: Children presenting for the first time to a regional growth clinic were assessed clinically by one observer. Investigations comprising standard GH provocation tests and measurement of urinary GH were undertaken to exclude GH deficiency. PATIENTS: Fifty-eight children aged 5.8-16 years were enrolled. Ten were diagnosed on clinical assessment as GH deficient, 43 had delayed growth and/or familial short stature, and five had idiopathic short stature; the 48 children in the last two groups were defined as short normal. MEASUREMENTS: GH secretion was evaluated by two standard provocation tests and by the measurement of GH in five overnight urine collections. A normal peak GH concentration was defined as > 16 mU/l. The values for urinary GH excretion were compared to normal ranges (+/- 2 standard deviations from the mean), established in healthy schoolchildren of normal stature. RESULTS: All children considered GH deficient on clinical grounds had low peak GH concentrations on provocation tests, while 8/10 had low values of urinary GH excretion. All short normal children with normal peak GH concentrations (n = 36) on provocation tests and 11/12 children with low peak GH concentrations had urinary GH excretion within the normal range. There was therefore a significant difference in the classification of 'normal' GH secretion in the two tests. If the clinical diagnosis was used as the standard by which GH tests were judged, the predictive value of a positive urinary GH test in the diagnosis of GH deficiency was 89% compared with 45% for GH provocation tests.

Adolescent↗
PubMed1993

A model for clinical teaching and learning.

A set of criteria to observe clinical teaching was developed and used to describe and evaluate the teaching behaviour of 24 tutors of medical students in their initial clinical skill term. The tutors had no previous instruction in teaching techniques, nor had their teaching been previously evaluated. The criteria used focus on six basic dimensions: the teaching/learning environment; the degree of intellectual challenge; the degree of interaction; the logical structure of teaching sessions; the quality of teaching skills; and the modelling of professional skills and attitudes. A continuum of teaching behaviour was observed in each dimension, with most tutors demonstrating adequate levels of performance in each. The tutors all strongly supported the evaluation and the feedback they received. Their subsequent teaching behaviour will be reviewed to assess the impact of this feedback.

Attitude of Health Personnel↗
PubMed1993

Demography, auxology and response to recombinant human growth hormone treatment in girls with Turner's syndrome in the Kabi Pharmacia International Growth Study. International Board of the Kabi Pharmacia International Growth Study.

Demographic and auxological data were analysed from 818 girls with Turner's syndrome treated with recombinant human growth hormone (GH) and entered into the Kabi Pharmacia International Growth Study. Size at birth was low and correlated with the heights of both parents. The median age at start of GH treatment was 11.4 years and the parents had a median height SDS of -2.9. Height SDS at the start of treatment correlated with parental heights. Height velocities conformed to Turner-specific standards. The weight-for-height index increased sharply above 9 years of age. The frequency of spontaneous appearance of Tanner breast stage 2 was high (34.1% of girls > 10 years of age). Bone age (Greulich and Pyle) data were described by the equation: bone age = 1.61(chronological age) - 0.04(chronological age)2 - 3.61. This equation was used to correct adult height predictions. The median initial dose of GH was 0.8 IU/kg/week and was maintained during the first 3 years of treatment. The median frequency of injections was six/week. Height velocity increased from 4.1 to 6.8 cm/year in the first year, and height velocity SDS for chronological age remained positive for 4 years. The height prediction corrected for bone age increased over the first 2 years only. Differences in demography and auxology were described according to karyotype and country of origin. A greater height velocity SDS was observed at higher GH doses and when oxandrolone was used concomitantly.

Age Determination by Skeleton↗
PubMed1993

Safety and efficacy of human growth hormone treatment in girls with Turner syndrome.

Six major adverse medical events (AMEs) and 44 minor AMEs were recorded in 6 and 23 patients, respectively, during human growth hormone (GH) treatment of Turner syndrome, equivalent to 118 treatment years. During the first year of GH treatment, there was no change in the SD score (SDS) for systolic or diastolic blood pressure. In a subgroup of 20 patients, there was no change in psychological tests, oral glucose tolerance, glycosylated haemoglobin or serum triglycerides over the first year of GH treatment. The mean total serum cholesterol level fell over this period. The low incidence of adverse medical problems during GH treatment complemented its efficacy. Height velocity in the first year was 7.7 +/- 1.8 cm/year (mean +/- SD) and was correlated with maternal height SDS, though not with paternal height SDS. Some 36% of first-year height velocity SDS could be predicted by the dose of GH and maternal height SDS.

Adolescent↗
PubMed1993

Decreased sweating in seven patients with Laron syndrome.

Previous studies have shown that sweat secretion was reduced in patients with GH deficiency and increased during GH treatment, indicating an influence of GH on sweat gland function. Thus, patients with GH deficiency have impaired thermoregulation. We report on sweat secretion rates (SSRs) in seven patients with Laron syndrome, measured by pilocarpine iontophoresis. The patients had significantly lower SSRs than healthy children matched for sex and pubertal stage (P < 0.00005) and moderately, but significantly, elevated sweat electrolyte concentrations (P < 0.00005 for potassium; P < 0.01 for sodium). These observations further supported the hypothesis that sweat gland function in humans is under the influence of the GH-insulin-like growth factor-I axis. It remains to be seen whether the decrease in SSR also leads to altered thermoregulation in patients with Laron syndrome.

Adolescent↗
PubMed1993

Variability in the urinary excretion of growth hormone in children: a comparison with other urinary proteins.

As a basis for assessment of the clinical validity of urinary GH (uGH) measurements in children, the day-to-day variability in renal handling of GH has been compared with that of albumin, N-acetylglucosaminidase (NAG) and creatinine. Five overnight urine specimens were collected over a 2-week period from 78 healthy children (aged 5-16 years), 20 of normal stature and 58 with growth disorders; ten children were classified as GH-deficient (GHD) and 48 were designated short normal (SN). The variability of excretion of each substance was expressed as a coefficient of variation (C.V.) which was not influenced by expressing the urine results as total mass excreted, concentration, excretion rate or as a ratio to creatinine. There was considerable night-to-night variability in the excretion of all substances (mean C.V. values for all groups: 56% for albumin, 41% for GH, 33% for NAG and 27% for creatinine). No differences were found in the variability of GH excretion between males and females, nor between prepubertal and pubertal subjects. The mean C.V. for uGH excretion ranged from 37% in normal and 35% in SN children to 52% in those with GHD (P < 0.05). Assay variation rather than a change in renal protein handling accounted for the large variations in uGH concentrations of < 5 pg/ml, thus contributing to the high uGH C.V. of the GHD group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗