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Biomedical subjects

G Hayes

Publications and source records attributed to G Hayes.

At least 19 recordsLinked to original sources
PubMed1992

Cloned human neuropeptide Y receptor couples to two different second messenger systems.

Neuropeptide Y (NPY) is one of the most abundant neuropeptides in the mammalian nervous system and exhibits a diverse range of important physiological activities, including effects on psychomotor activity, food intake, regulation of central endocrine secretion, and potent vasoactive effects on the cardiovascular system. Two major subtypes of NPY receptor (Y1 and Y2) have been defined by pharmacological criteria. We report here the molecular cloning of a cDNA sequence encoding a human NPY receptor and the corrected sequence for a rat homologue. Analysis of this sequence confirms that the receptor is a member of the G protein-coupled receptor superfamily. When expressed in Chinese hamster ovary (CHO) or human embryonic kidney (293) cells, the receptor exhibits the characteristic ligand specificity of a Y1 type of NPY receptor. In the 293 cell line, the receptor is coupled to a pertussis toxin-sensitive G protein that mediates the inhibition of cyclic AMP accumulation. In the CHO cell line, the receptor is coupled not to the inhibition of adenylate cyclase but rather to the elevation of intracellular calcium. These results demonstrate that second messenger coupling of the NPY-Y1 receptor is cell type specific, depending on the specific repertoire of G proteins and effector systems present in any cell type.

Adenylyl Cyclases↗
PubMed1992

Structural subtypes of the dopamine D2 receptor are functionally distinct: expression of the cloned D2A and D2B subtypes in a heterologous cell line.

Dopamine, a major neurotransmitter in the mammalian nervous system, exerts its physiological effects through receptors of the G-protein-coupled receptor superfamily. Two major classes of dopamine receptor, D1 and D2, are distinguishable by both biochemical and pharmacological criteria. D1 receptors activate adenylyl cyclase, whereas the D2 class of receptors inhibits this second messenger system. Two subtypes of the human dopamine D2 receptor are generated by alternate splicing of the RNA transcript of a single gene. These two forms, termed D2A (long) and D2B (short), differ by the insertion of 29 amino acids within the putative third cytoplasmic loop, an intracellular domain thought to have a role in coupling this class of receptors to particular second messenger systems. We report here that the D2A and D2B structural subtypes are also functionally distinct. Expression of the two subtypes in a fibroblast cell line revealed that while occupation of both receptors leads to an increase in cytosolic free calcium concentration, they differ in their capacity to inhibit cAMP production. At physiological dopamine concentrations, the D2B-mediated inhibition of calcitonin gene-related peptide-stimulated cAMP accumulation is almost double the response mediated by the D2A subtype. Furthermore, the D2B subtype can maximally attenuate cAMP accumulation by up to 85%, whereas the D2A subtype is less effective, maximally inhibiting cAMP accumulation by only 64%. The D2A and D2B subtypes, thus, constitute functionally distinct forms of the dopamine receptor that can couple to multiple intracellular signalling pathways.

Animals↗
PubMed1991

Inflight anxiety conditions presenting with "break-off" symptoms.

The psychological dimension of disorientation is explored through two experienced pilots who developed inflight anxiety conditions. These were associated with "break-off" symptoms, which are inflight sensations of separation from the ground, the environment, and the aircraft. Following extensive psychiatric and medical evaluations, one aviator was diagnosed as having agoraphobia without panic disorder, and the other as having an otherwise unspecified anxiety disorder. These patient reports demonstrate the need for the clinical aerospace medicine specialist to investigate inflight anxiety conditions for underlying neuropsychiatric disorders. The reports also contrast some of the historical aeromedical concepts with modern psychiatric diagnostic nomenclature.

Adult↗
PubMed1990

The role of extracellular calcium in ischemia/reperfusion injury in skeletal muscle.

Ischemia-reperfusion injury to skeletal muscle, following an acute arterial occlusion is a significant cause of morbidity and mortality. The purpose of this study is to examine the role of extracellular calcium in the production of cellular necrosis following a prolonged period of normothermic ischemia. Bilateral canine gracilis muscles were made ischemic for 4.5 to 5 hr. The control muscle had normal blood reperfusion (ionized Ca2+ 1.2 mM). The treated muscle was perfused for 30 min with an oxygenated solution (ionized Ca2+ 0.11 mM) containing free radical scavengers followed by normal blood perfusion. Necrosis was determined by nitroblue tetrazolium staining after 48 hr of reperfusion. Total muscle Ca2+ was measured by atomic absorption spectrometry. Pre- and postischemic muscle Ca2+ levels were similar (2.8 +/- 0.4 vs 3.2 +/- 0.8 nmole/mg protein, n = 13, P greater than 0.1). After 30 min of reperfusion the treated muscle Ca2+ was 2.4 +/- 0.4 compared to control levels of 8.6 +/- 0.8 nmole/mg protein (P less than 0.001). Total tissue calcium returned to normal at 60 min in viable muscle, but continued to accumulate in necrotic tissue. However, the delay in initial muscle Ca2+ influx was not associated with increased overall salvage of muscle 78 +/- 9% vs 77 +/- 8% necrosis, (P greater than 0.1). In conclusion we could not demonstrate a protective effect of reduced extracellular Ca2+ during early reperfusion, and it negated our previously demonstrated beneficial effects of free radical scavengers. It was shown however that the early ability to extrude intracellular calcium was associated with significant salvage of muscle tissue.

Animals↗
PubMed1990

Quantitation of skeletal muscle necrosis using 99Tcm-pyrophosphate with SPECT in a canine model.

Patients with acute arterial occlusion may suffer from significant muscle necrosis. It is important to determine the amount of regional muscle necrosis for prognostic purposes and evaluation of therapy. We have used technetium-99m-pyrophosphate (PPi) with single photon emission computed tomography (SPECT) to quantitate muscle necrosis. A canine gracilis muscle ischaemia model was used. PPi was injected 1.5 h before the muscle preparation was removed from the dog. SPECT was performed on the muscle preparations. An automatic edge detection program using the threshold technique determined the number of pixels with significant PPi activity in each transaxial section. Volume was calculated by summing the number of pixels with significant PPi activity and multiplying by the voxel size. The results were compared with quantitation using computerized planimetry with nitroblue tetrazolium staining (correlation coefficient = 0.93). PPi with SPECT is an accurate method for quantiating muscle necrosis.

Animals↗
PubMed1990

Efficacy and tolerability of controlled-release trazodone in depression: a large multicentre study in general practice.

A double-blind, parallel-group study was carried out to compare the efficacy and tolerability of a controlled-release tablet formulation of trazodone with the standard trazodone tablet. Three hundred and forty-seven general practice patients with depressive symptoms were recruited into the trial. Patients were randomly allocated to receive either 1 controlled-release trazodone (150 mg) tablet at night or 1 standard trazodone (150 mg) tablet at night for a period of 6 weeks. Assessments of efficacy, tolerability and compliance were made at study entry and after 1, 2, 4 and 6 weeks of study medication. Seventy-seven patients withdrew from the study of whom 44 were in the standard trazodone tablet group and 33 were in the controlled-release trazodone tablet group. There were no statistically significant differences between treatment groups in any of the measures of efficacy (global severity, global improvement and Hamilton Depression Rating Scales 17- and 21-item). Major improvements in patients' condition were shown in all efficacy measures by the end of the study in comparison with study entry. Treatment differences were small but were numerically in favour of the controlled-release tablet formulation. As expected, a greater proportion of side-effects were reported during the first 2 weeks of treatment in both groups. Treatment differences, revealed in a five symptom adverse event checklist used throughout the study, were small, although in favour of the controlled-release tablet in the majority of cases, but not statistically significant.

Adolescent↗
PubMed1990

Somatosensory evoked potentials in schizophrenia. A lateralisation study.

The SSEPs obtained from 19 schizophrenics defined by RDC, DSM-III and PSE criteria were compared with those from a control group of healthy volunteers. Previous findings of an abnormal lack of lateralising response in schizophrenic patients were not replicated. No significant difference in either amplitude or morphology between the traces obtained from the two groups were recorded. Ipsilateral and contralateral latencies for stimulation of the left and right index finger showed no significant difference in peak latency for any component between patient and control group. When mean peak-to-peak amplitudes were plotted the contralateral component was always greater in amplitude than the ipsilateral one. An objective measure of the degree of lateralisation, the percentage lateralisation quotient, showed no lateralisation differences between the patient and control groups. A case of myogenic contamination of ipsilateral components was observed calling into doubt findings where no temporal region monitoring has been performed.

Adult↗
PubMed1990

Role of a pharmacist in a seizure clinic.

The involvement of a clinical pharmacist in a Department of Veterans Affairs seizure clinic is described. A pharmacist who had served a residency in ambulatory care began working in a seizure clinic in 1988 after obtaining the cooperation of a neurologist interested in a multidisciplinary approach to patient care. A clinical protocol was developed to guide the pharmacist's participation. The seizure clinic is staffed by the clinical pharmacist, a pharmacy resident, and a neurologist and is currently treating 162 adult male veterans. Of the 162 patients, 159 are receiving anti-convulsant therapy. The role of the pharmacist is to assist the neurologist in providing patient-care services. The pharmacist interviews each patient, performs a neurological assessment and mental status evaluation, and orders laboratory tests. Information is recorded by the pharmacist on a history form and a subjective and objective assessment and planning form. The pharmacist presents the findings to the neurologist, and the patient is then interviewed jointly by the pharmacist and the neurologist. Between appointments, the pharmacist follows up on abnormal laboratory test values and informs patients of any necessary dosage adjustments. More time is available for patient care, there has been an increase in the detection of adverse drug reactions and disease states, and record keeping has improved. A pharmacist assumed a primary-care role in a seizure clinic by interviewing and assessing patients, ordering laboratory tests, and participating in the selection and adjustment of anticonvulsant therapy.

Ambulatory Care Facilities↗
PubMed1989

Structure and properties of a human non-pancreatic phospholipase A2.

We have purified a human non-pancreatic phospholipase A2 that is present in platelets and is enriched in rheumatoid synovial fluid. The enzyme is calcium-dependent, has a pH optimum of 8-10, and shows a striking preference for substrate presented in the form of Escherichia coli membranes. In the E. coli phospholipase A2 assay the phospholipase exhibits an apparent specific activity of 300 mumol/mg/min. Using oligonucleotide probes based on amino-terminal sequence data, we cloned the corresponding human gene from a genomic DNA library and expressed the gene in animal cells. The protein was secreted from the cells in an active form. The deduced amino acid sequence of the human protein consists of 124 amino acids, contains structural features common to all known phospholipase A2s, and has a half-cystine pattern that is characteristic of the snake venom group II enzymes.

Amino Acid Sequence↗
PubMed1989

Spectral diagnosis of atherosclerosis using an optical fiber laser catheter.

This communication demonstrates that fluorescence spectra of human aorta with good S/N ratios can be collected using an optical fiber laser catheter. The performance of this catheter is compared to a non-fiber optic collection system with an equivalent delivery/collection geometry. For a given sample, fluorescence lineshapes obtained using the two systems are identical; differences in peak fluorescence intensity are related to the different collection efficiencies of the two systems. It is shown that the fluorescence lineshape of arterial tissue depends on the delivery/collection geometry of the detection system, and that this is due to the interaction of absorption and fluorescence within the artery wall. This effect is investigated systematically using a specially designed collection system. Results are analyzed qualitatively using a simple, one-dimensional model of tissue fluorescence. With this analysis, we present design requirements for a collection system in which such geometric effects are eliminated, and show that our optical fiber laser catheter satisfies these requirements.

Aortic Diseases↗
PubMed1989

The major dopamine D2 receptor: molecular analysis of the human D2A subtype.

The structural diversity of the human D2 dopamine receptor was examined at the nucleic acid level. Sequence analysis of receptor cDNA clones isolated from human brain and pituitary libraries and polymerase chain reaction (PCR) analysis of rat brain RNA and human genomic DNA demonstrate the presence of a predominant D2 subtype, D2A. The D2A subtype differs from the D2B subtype, previously described in rat brain RNA, in that an additional 29 amino acids are present in the putative third cytoplasmic domain, a region thought to be important for coupling to different G-proteins. The demonstration of intron sequences flanking the DNA encoding the 29-amino-acid insertion suggests that the generation of two distinct D2 dopamine receptor subtypes may arise from alternative splicing of a common genomic sequence.

Amino Acid Sequence↗
PubMed1989

Identification of clinically significant skeletal muscle necrosis by single photon emission computed tomography.

Ischemia-reperfusion damage to skeletal muscle may cause serious local as well as systemic complications, its impact predominantly related to the quantity of ischemic muscle in the lower extremity. To date, there has been no noninvasive method of estimating that quantity. The authors used single photon emission computed tomography (SPECT) to quantify the volume of muscle that takes up technetium-99 pyrophosphate above a baseline threshold. Compared with the standard technique of staining slices of the muscle with nitroblue tetrazolium they found a close correlation using SPECT (r = 0.88, p less than 0.01, n = 19) in the canine model. In humans, this clinically applicable noninvasive technique may allow the surgeon to document accurately the extent of muscle necrosis in the lower extremity, to anticipate the impact of an ischemia-reperfusion injury and evaluate methods of reducing the extent of post-ischemic skeletal muscle necrosis.

Animals↗