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J D Harvey-White

Publications and source records attributed to J D Harvey-White.

8 recordsLinked to original sources
PubMed2000

Estimation of striatal dopamine spillover and metabolism in vivo.

A microdialysis probe with an attached microinjection cannula was inserted into rat striatum. [3H]dopamine (or [14C]sucrose as a reference substance for diffusion) was infused via the cannula, with microdialysate sampled for concentrations of endogenous and [3H]-labeled dopamine and its metabolites. The calculated specific activities of the [3H]-labeled metabolites led to the conclusions that striatal extracellular dopamine undergoes inactivation mainly by extraneuronal but also by neuronal uptake and intracellular metabolism. Some of the dopamine taken up into nerve terminals slowly re-enters (spillover) the extracellular fluid unchanged. This spillover was calculated to be about 5 pmol/min. Destruction of dopaminergic terminals increases the turnover of vesicular stores in the surviving terminals, both by increased vesicular leakage and by increased release into the extracellular fluid.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Determination of submicromolar concentrations of neurotransmitter amino acids by fluorescence detection using a modification of the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate method for amino acid analysis.

A sensitive method for quantitatively determining submicromolar levels of neurotransmitter amino acids (e.g. Asp, Glu and gamma-aminobutyric acid) in microdialysates from brain and cerebrospinal fluids is reported. 6-Aminoquinolyl-N-hydroxy-succinimidyl carbamate (AQC) was employed as the derivatization reagent, followed by HPLC separation and fluorescence detection of the derivatives. The derivatization was conducted simply by mixing the AQC directly with the microdialysis samples. The reaction was complete within seconds after mixing at room temperature. Separation development optimizing the gradient profile, eluent pH and column temperature resulted in an excellent separation of the required amino acids in less than 30 min. Other resolved amino acids in the same profile include Gly, taurine, and Pro. Recoveries for the amino acids of interest spiked into high salt containing perfusion buffers were greater than 97%. The sensitivity of the method was increased by employing a 16-microliter flow cell in the detector and analyzing 20-microliter aliquots of the derivatization mixtures. With the optimized conditions, the detection limits were 3-7 nM (fmol/microliter). Typical reproducibility (%R.S.D.) for quantitation of these amino acids at submicromolar levels was approximately 2%. Excellent linearity (r2 > 0.999) was achieved over the range 0.2-20 microM. The low detection limits permitted the analysis of a number of different microdialysate samples including those from cerebrospinal fluid, as well as substantia nigra and hypothalamus from brain samples, even at basal levels where gamma-aminobutyric acid concentration may be < 50 nM. The excellent sensitivity made it easy to distinguish basal from stimulated levels of neurotransmitter amino acids, even from sample sizes as small as 10 microliters.

Aminoquinolines↗
PubMed1996

Brain MRI, lumbar CSF monoamine concentrations, and clinical descriptors of patients with spinocerebellar ataxia mutations.

OBJECTIVES: To serially assess changes in lumbar CSF biogenic amines, radiographic characteristics, and neurological signs in 34 patients with dominantly inherited ataxia. METHODS: Mutational analysis was used to identify genetic subgroups. Annual assessment of lumbar CSF monoamine metabolites using a gas chromatographic/mass spectrometric method and morphometric measurements of the cerebellum, pons, and the cervical spinal cord on MRI were analysed for each patient and compared with normal controls. RESULTS: Patients with CAG trinucleotide repeat expansions on chromosome 6p (mutSCA1) and chromosome 14q (mutSCA3) had only about one half the normal concentrations of lumbar CSF homovanillic acid (HVA) whereas, 5-hydroxyindoleacetic acid (5-HIAA) concentrations were similar to those in age matched normal subjects. The HVA and 5-HIAA concentrations in clinically similar patients without mutSCA1 or mutSCA3 were normal. One year after the first study, HVA concentrations were reduced by a mean of 22% regardless of the patient's SCA mutation. Abnormalities on MRI were consistent with a spinopontine atrophy in patients with mutSCA3, spinopontocerebellar atrophy in patients with mutSCA1, and "pure" cerebellar atrophy in patients without these mutations. CONCLUSIONS: Quantitative MRI measurements were not useful in monitoring progression of disease but lumbar CSF HVA concentrations and total scores on a revised version of the ataxia clinical rating scale seemed to progress in parallel.

Biogenic Monoamines↗
PubMed1993

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) effects on enkephalinergic neurons in various regions of mouse brain.

In order to elucidate the effects of MPTP on enkephalinergic neurons, dopamine (DA), norepinephrine (NE), proenkephalin (PE) mRNA and met-enkephalin (ME) were measured in striatum, olfactory tubercle, and prefrontal cortex of C57/B16 mice 1 day-2 weeks following treatment with 96 mg/kg MPTP HCl (24 mg/kg i.p., twice/day for 2 days). DA and its metabolites were depleted 70% in striatum and 40% in olfactory tubercle within 1 day. In cortex, DA was unchanged, whereas homovanillic acid and NE were depleted 50 and 40% respectively by 3 days. ME increased in all three brain regions at different times whereas PE mRNA showed a different pattern in each region, with an increase in olfactory tubercle, a decrease in cortex, and in striatum, a decrease at 1 day followed by an increase at 3 days. Thus enkephalinergic neurons in each region respond differently to MPTP treatment. In striatum and olfactory tubercle. DA is depleted sufficiently to release its tonic inhibition on the enkephalinergic neurons, thereby leading to increased enkephalin synthesis. In cortex, the change in NE metabolism appears to cause a decrease of ME release and thereby a depression of PE synthesis. The possible relationship between these results and the changes observed in Parkinson's disease are discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Glycine stimulates striatal dopamine release in conscious rats.

1. Glycine is an inhibitory neurotransmitter in the spinal cord and brainstem. The mechanism of this inhibition is via binding of glycine to specific receptors, increasing transmembrane Cl- conductance and hyperpolarizing neurones. Strychnine selectively antagonizes these effects. The role of glycinergic neurones in supraspinal regions is poorly understood. 2. Effects of glycine on release of catecholamines in the striatum were examined by microdialysis in freely-moving rats. Transcription of the genes encoding strychnine-sensitive glycine receptors was assessed in the striatum and substantia nigra, by use of reverse transcription followed by the polymerase chain reaction. 3. Glycine administered via the microdialysis probe dose-dependently increased concentrations of dopamine and its metabolites, dihydroxyphenylacetic acid and homovanillic acid, in the perfusate, indicating increased local release and metabolism of dopamine. Strychnine markedly attenuated these responses. Whereas striatal tissue did not contain mRNA for either the adult or neonatal form of strychnine-sensitive glycine receptor, nigral tissue contained a message for the adult form. 4. The results suggest that dopaminergic cells in the substantia nigra synthesize strychnine-sensitive glycine receptors and transport the receptors to terminals in the striatum. Occupation of the glycine receptors then exerts a net stimulatory effect on striatal dopamine release in vivo.

Animals↗
PubMed1983

Reference serum pepsinogen concentrations in dairy cattle.

Serum samples from 27 yearling heifers and 50 lactating cows were analyzed for pepsinogen concentration. Concentrations were 44 +/- 12 (SD) ng of pepsinogen/ml (2,200 mU of tyrosine/ml) of serum for the yearling heifers and 20 +/- 8 ng/ml (1,400 mU of tyrosine/ml) for the lactating cows. These initial data indicate that a yearling calf, grazing on pasture, with a serum pepsinogen concentration greater than 68 ng/ml (2,900 mU of tyrosine/ml) should be examined for ostertagiasis.

Animals↗
PubMed1982

Method for determining serum pepsinogen concentration, using pepsin standards and ultraviolet absorbance.

A simplification of the traditional hemoglobin methods for determining serum pepsinogen concentration was developed. In this method, 10% trichloroacetic acid solution was added to control samples, and hemoglobin substrate was added to controls and active enzyme samples; standards and samples were incubated for 18 hours, the proteins in the active tubes were precipitated with trichloroacetic acid and removed by filtration, and the absorbances of the supernatant of each standard and sample at 280 nm were measured. The major differences between this method and other methods for determining pepsinogen values are that the preacidification of serum with hydrochloric acid was eliminated, the incubation period was reduced to 18 hours (down from 24 hours), the relative pepsinogen concentration was determined by measuring the concentration of hydrolysis products, using ultraviolet, rather than visible absorbance, and a pepsin standard curve was used to determine the serum pepsinogen concentration. Comparison of freshly prepared pepsinogen and pepsin standard curves indicated that the pepsinogen preparations were slightly more active than the pepsin preparations (on a weight-to-weight basis) on the same substrate. Pepsin standards are used because they are more stable than pepsinogen standards. Three linear standard curve ranges were used: O 10 to 100, 50 to 300, and 100 to 500 ng of pepsinogen/ml of serum. The use of pepsin standard curves permits some variability of the incubation conditions without altering the results. For best results, the hemoglobin substrate solution should be prepared daily. This method may be useful in diagnosing ostertagiasis.

Animals↗