Search PubMed⌕ Search

Biomedical subjects

J T Coyle

Publications and source records attributed to J T Coyle.

At least 361 records · Page 20Linked to original sources

Inhibitors of GABA metabolism: implications for Huntington's disease.

Stereotaxic injection of kainic acid into rat striatum produces neuronal degeneration and neurochemical alterations resembling Huntington's disease (HD). Since correction of the deficiency in gamma-aminobutyric acid (GABA) in HD may be of therapeutic value, the efficacy of drugs that inhibit the GABA-degrading enzyme (GABA-T) in elevating the levels of GABA has been examined in the animal model for HD. High doses of di-N-propylacetic acid only partially correct the GABA deficiency in the striatum, whereas low doses of gamma-acetylenic GABA, a specific irreversible inhibitor of GABA-T, completely restore the levels of GABA in striatum and substantia nigra.

4-Aminobutyrate Transaminase↗

Tangent screen perimetry using twin test objects.

A T-shaped carrier with twin test objects is an inexpensive efficient visual field screening device which facilitated identification of a nasal steppe, a paracentral scotoma, an enlarged blind spot, an arcuate scotoma, macular sparing, or hemianopic defects.

Brain Diseases↗

Kainic acid: neurotoxic effects after intraocular injection.

Intraocular injection of 120 nmol. of kainic acid, a powerful glutamate receptor agonist, induces a marked degeneration of cells in the inner nuclear layer of the retina. Within 2 hours after injection there is a significant decrement in the specific activities of tyrosine hydroxylase, choline acetyltransferase, and glutamic acid decarboxylase; by 48 hours after injection there is nearly a complete loss in the presynaptic neurochemical markers for the cholinergic and GABAergic neurons. The dopaminergic neurons, as assessed by activity of tyrosine hydroxylase and concentration of endogenous dopamine, are reduced only 50% by the kainic acid treatment. Although basal adenylate cyclase activity is unaffected by kainic acid, there is a 90 percent reduction in the activating effects of dopamine on adenylate cyclase in the kainic acid-treated retina.

Acetylcholine↗

Neurochemical aspects of the ontogenesis of cholinergic neurons in the rat brain.

Ontogenic development of central cholinergic neurons in rat brain was examined by measuring the activity of choline acetyltransferase (CAT), concentration of acetylcholine (ACh) after focused microwave irradiation, the activity of the high affinity uptake process for choline and the apparent muscarinic receptor as quantified by specific binding of [3H]3-quinuclidinyl benzilate (QNB). For whole brain, the specific activity of CAT increases from 1 to 8% of adult between 15 days gestation and 7 days postpartum and then increases linearly to 83% by 4 weeks postpartum. The concentration of ACh is 22% of adult at 15 days gestation, rises to 29% by birth and attains adult levels by 4 weeks postpartum. The developmental rise in specific binding of [3H]QNB is intermediate between CAT and ACh with 10% of adult concentration of receptor at birth and a linear increase to 90% by 4 weeks postpartum. The development of the uptake of [3H]choline parallels that of CAT. In all regions of the neonatal rat brain, the relative level (% adult) of ACh is higher than [3H]QNB binding, which is higher than CAT. The neonatal medulla-pons has higher levels of [3H]QNB binding and activity of CAT (% adult) and develops more rapidly than the parietal cortex and corpus striatum; the hypothalamus and midbrain-thalamus exhibit intermediate rates of development.

Acetylcholine↗

Neurochemical aspects of the ontogenesis of GABAnergic neurons in the rat brain.

Examination of various biochemical characteristics of the GABAnergic nervous system in the rat brain was made between 15 days of gestation and adulthood. At birth, the concentration of GABA in whole brain and most regions is approximately 50% of adult levels, whereas the medulla-pons has achieved adult levels by this time. Compared to GABA levels, there is a marked lag in the development of the activity of glutamic acid decarboxylase in all areas studied; however, the activity of the enzyme increases in a linear fashion from birth to adulthood. The development of the uptake of GABA into particulate fractions prepared from whole brain and regions differs markedly from that of GABA and glutamic acid decarboxylase, with uptake near adult levels by birth, peaking considerably above that of the adult between one to two weeks after birth and then declining toward adult activity by 4 weeks after birth. Examination of the kinetics of GABA uptake into resuspended P2 fractions demonstrates that the developmental changes in the uptake reflects differences in the Vmax whereas the Kt remains constant; Studies on the development of the apparent postsynaptic receptor for GABA reveals that in all regions binding is approximately 25% of adult up to 8 days after birth, at which time it increases dramatically, approximating adult levels by 4 weeks after birth. The rise in the density of the apparent postsynaptic GABA receptor after 8 days postpartum correlates best with the increase in the activity of glutamic acid decarboxylase, a presynaptic marker.

Age Factors↗

Rat adrenal dopamine-beta-hydroxylase: purification and immunologic characteristics.

Dopamine-beta-hydroxylase (DBH) was purified from rat adrenal medulla by a series of steps including sedimentation of membranes, extraction with n-butanol, ammonium sulfate fractionation, gel chromatography and ion-exchange chromatography. Disk gel electrophoresis revealed two protein bands, both of which were active. Antiserum was prepared against homogeneously purified bovine adrenal and rat adrenal DBH; Ouchterlony immunodiffusion, enzyme neutralization and complement fixation tests demonstrated that the respective homologous antisera were monospecific and of high titer. Antiserum to bovine DBH was only 2- to 3-fold more potent than pre-immune serum in inhibition of rat DBH activity. Complement fixation tests demonstrate that antiserum to bovine DBH has a 25,000-fold lower immunoreactivity with rat DBH than with bovine DBH.

Adrenal Glands↗