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Biomedical subjects

C Hunter

Publications and source records attributed to C Hunter.

At least 55 records · Page 3Linked to original sources

Neurotransmission in the auditory system.

Neurotransmitters and neuromodulators thought to be active on neurons in the cochlea, CN, and SOC have been reviewed. The variety of neurotransmitters and neuromodulators present and likely colocalized in these neurons are the chemical substrates that link morphologically and physiologically diverse neurons to process sound information. The impact of the limited number of neurotransmitters and neuromodulators in the auditory system is magnified by their interaction with structurally diverse receptors; thus great functional diversity is possible. Moreover, the effects of neurotransmitters and neuromodulators are not limited to synaptic transmission but serve as trophic agents for the establishment of neuronal circuitry during development and the rearrangement of synapses as a result of sensory experience or injury. An understanding of the neurochemical aspects of sensory processing at these diverse synapses then is of fundamental importance in understanding the organization of the auditory system.

Auditory Pathways↗

Health policy and the distribution of lifetime income.

A number of health policies have implications for, and in turn can be influenced by, the distribution of income. However, current discussions define the distribution in current, not lifetime, income. This study describes a method of estimating gender and race differences in the distribution of lifetime incomes that account for mortality differences. When cohort lifetime incomes of living and deceased persons are compared, black men are found to be much worse off, whereas white women are found to be better off than existing estimates using annual income suggest. The mortality and lifetime income advantage of white women, however, is offset if, as some argue, white women have higher morbidity rates than white men of the same age. The authors use the concept of lifetime income to draw implications for health policy debates on cigarette and beer taxes, occupational safety and health, Medicaid versus Medicare spending, educational health promotion programs, and general investments in education.

Adult↗

Current issues in occupational health nursing. A Canadian perspective.

The National Association of Occupational Health Nurses is still in its infancy and is striving to become an interest group under the umbrella of the Canadian Nurses Association. This will bring together the provincial associations in a common goal of promoting worker health and safety. The diversity of the country and the sheer magnitude of the various occupations of Canadians reflect the need for the occupational health nurse to be well educated and kept abreast of new developments. Changes in the worksite echo changes in health and safety legislation that will help to improve conditions in the workplace. Future challenges arise from changes in the work force and the nature of work and include: ergonomic issues, job stress, older workers, EAPs, and increased competition.

Canada↗

Antibodies to a C-terminal peptide of the rat brain glutamate receptor subunit, GluR-A, recognize a subpopulation of AMPA binding sites but not kainate sites.

Antibodies were made to a thirteen amino acid synthetic peptide corresponding to the C-terminal portion of the glutamate (glu) receptor, GluR-A. The immunoprecipitation of kainic acid (KA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) binding sites by the anti-peptide antibodies was studied using a detergent-solubilized preparation of rat brain membranes. Under these conditions a subpopulation of AMPA binding sites was recognized by the antibodies, but no KA binding sites were recognized. Scatchard analysis of this subpopulation of AMPA binding sites yields a curvilinear plot which fits a two-site model with dissociation constants of 4.6 and 323 nM. These studies show that the glu receptor complex, GluR-A, binds AMPA but not KA and suggest that (i) the binding sites for these two ligands reside on different proteins, and (ii) the KA receptor identified physiologically is not equivalent to the KA binding sites identified with 3H-labelled KA.

Amino Acid Sequence↗

Solubilization and partial purification of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid binding sites from rat brain.

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) binding sites were solubilized from rat brain membranes using 1% Triton X-100 in 0.5 M potassium phosphate buffer containing 20% glycerol. The solubilized binding sites were stable, permitting biochemical and pharmacological characterization as well as partial purification. Pharmacological and binding analyses indicated that the solubilized binding sites were similar to the membrane-bound sites. Both the solubilized and the membrane-bound preparations contained high- and low-affinity AMPA binding sites in the presence of potassium thiocyanate. A similar rank order for inhibition of [3H]AMPA binding by several excitatory amino acid analogs was obtained for the soluble and membrane-bound preparations. [3H]AMPA binding to both soluble and membrane-bound preparations was increased in the presence of potassium thiocyanate. The solubilized AMPA binding sites migrated as a single peak with gel filtration chromatography, with an Mr of 425,000. Beginning with the solubilized preparation, AMPA binding sites were purified 54-fold with ion-exchange chromatography and gel filtration. The characterization and purification of these soluble binding sites is potentially useful for the molecular characterization of this putative excitatory amino acid receptor subtype.

Animals↗

Isolation, localization, and cloning of a kainic acid binding protein from frog brain.

Excitatory amino acids (EAA) are major neurotransmitters in the vertebrate central nervous system. EAA receptors have been divided into three major subtypes on the basis of electrophysiological and ligand binding studies: N-methyl-D-aspartate, kainate, and quisqualate receptors. To understand their molecular properties, we undertook a project aimed at isolation and cloning of these receptor subtypes. We purified a kainate binding protein (KBP) from frog brain, in which kainate binding sites are about fortyfold more abundant than in rat brain, using domoic acid affinity chromatography, and made monoclonal and polyclonal antibodies to the purified protein. These antibodies immunoprecipitate the frog KBP but not KBPs from other species. Immunocytochemical analyses show that KBP has a synaptic and extrasynaptic localization in frog optic tectum, with most labeling being extrasynaptic. The cDNA encoding frog brain KBP was isolated by screening a frog brain cDNA library with oligonucleotide probes that were based on the amino acid sequence of the purified protein. The deduced amino acid sequence of the KBP has a hydrophobic profile similar to those of other ligand-gated ion channel subunits, such as the nicotinic acetylcholine receptor, the GABAA receptor, and the glycine receptor. Frog brain KBP is very similar (36% amino acid identity to the carboxyl half) to rat brain kainate receptor, suggesting that these two proteins evolved from a common ancestor. The function of KBP in frog brain remains a major question. Preliminary results showed that Xenopus laevis oocytes injected with KBP RNA did not produce a detectable electrophysiological response when perfused with kainate. These results suggest that additional subunits may be required to form a functional receptor or that KBP is not functionally related to a neurotransmitter receptor.

Amino Acid Sequence↗

Age-dependent changes in brain glycine concentration and strychnine-induced seizures in the rat.

Glycine levels and receptor binding were measured in the medulla and spinal cord of 2-month, 10-month, and 24-month-old Fischer 344 rats. The behavioral response to the administration of the glycine antagonist, strychnine, was also evaluated in 2- and 24-month-old animals to investigate the relevance of these parameters to the susceptibility to seizures. Significant reductions in glycine in both the spinal cord and medulla occurred from 2 to 24 months of age. The glycine precursors, serine and threonine, were decreased only in the spinal cord. [3H]Strychnine binding was also decreased by 38% and 34% in the medulla and spinal cord, respectively, of 24-month-old rats compared to 2-month-olds. [3H]GABA binding was similarly reduced while no age-related changes in [3H]diazepam binding in the spinal cord were detected. Comparison of 2- and 24-month-old animals after systemic injection of 1.75 mg/kg strychnine showed that senescent animals have a higher incidence of seizures and mortality compared to young animals. Decreases in glycinergic neurotransmission may lower strychnine seizure threshold in the aged animal.

Aging↗

The incidence and notification of measles in Australia.

The incidence of measles in Australia in 1986 was estimated as 43 per 100,000 population, high by the standards of countries where immunization levels are high, low by the standards of countries where immunization levels are low. It is estimated that only 5 per cent of cases are notified in New South Wales, one of only 2 States which require notification. The reasons for this, its significance and a possible remedy are discussed.

Australia↗

A highly sensitive and specific radioimmunoassay for quantitation of plasma fluphenazine.

Antisera of high sensitivity and selectivity were obtained from rabbits immunized with conjugates of hemisuccinylated fluphenazine and porcine thyroglobulin. The antiserum selected (titer 1:6000) for the development of the RIA was obtained after a priming dose and a single iv booster injection three months later. This antiserum had negligible crossreactivity with known available metabolites of fluphenazine (FPZ) and an affinity constant of 2 X 10(10) L/mol. Tritiated FPZ was further purified by HPLC and used as a ligand. The method detects as little as 20 pg/mL of plasma (4 pg/RIA tube) after 1 mL of plasma is extracted. The extraction was performed at a basic pH with heptane: isoamyl alcohol (99:1); the solvent was then back extracted using an acetic phosphate buffer. Recoveries were uniformly high (88.6 +/- 2.1%), and this aqueous buffer extract was used directly in the RIA procedure. The assay has intra- and interassay coefficients of variation of 5.8 and 8.2%, respectively, in a plasma concentration of 95 pg/mL. Results using this procedure have been cross validated against an HPLC procedure (r = 0.952, slope = 1.032, intercept = 0.009, n = 18). In a single-dose FPZ study (10 mg, po), plasma FPZ levels in 25 normal volunteers could be monitored greater than 48 h post dose. Single plasma level profiles, after an initial injection of 12.5 mg of FPZ decanoate, could be measured greater than 36 d, and, in some cases, up to 100 d post dose.

Administration, Oral↗

Erythrocyte catechol O-methyltransferase activity in schizophrenia: analysis of family data.

The authors determined the erythrocyte catechol O-methyltransferase (COMT) activity of 38 chronic schizophrenic patients, 69 of their first-degree relatives, and 39 normal controls. COMT activity did not distinguish patients from controls. Within families, COMT activity was not associated with schizophrenia spectrum disorders. The data suggest that COMT activity is not an indicator of vulnerability to schizophrenia.

Adolescent↗

Assay of human erythrocyte catechol-o-methyltransferase activity with naturally occurring catecholamines as substrates.

This report describes a simple and sensitive radiometric assay for catechol-o-methyltransferase activity in human erythrocytes and other tissues. Saturating concentrations of the endogenous catecholamines and S-adenosylmethionine are used under optimum assay conditions. Erythrocyte catechol-o-methyltransferase activity is also dependent on storage conditions, as activity was lost at -20 degrees C but not at -80 degrees C.

Catechol O-Methyltransferase↗

Complete remission of idiopathic pure red cell aplasia. Case reports.

Two patients with pure red cell aplasia of undetermined aetiology are in sustained, complete remission after immunosuppressive therapy. In the first, short-term supplementary plasmapheresis was used during initial chemotherapy, and in the second, anabolic androgens were administered. In both patients haematopoietic recovery was temporally related to the withdrawal of the cyclophosphamide used to cause immunosuppression in the patients over a 4- and 6-month period respectively.

Adolescent↗