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Biomedical subjects

A Francis

Publications and source records attributed to A Francis.

At least 73 records · Page 4Linked to original sources
PubMed1985

Cellular localization of MAO A and B in brain: evidence from kainic acid lesions in striatum.

The cellular localization of the two forms of monoamine oxidase (MAO A and MAO B) was studied by measuring their activities in rat striatum following unilateral stereotaxic injection of kainic acid to produce selective degeneration of striatal neurons and subsequent proliferation of astrocytes. The results demonstrated a persistent loss of 15-20% in MAO A activity, whereas MAO B activity decreased initially by 25% and then increased to more than twice the control value by 54 days after lesions. The changes in activity were compared to parallel estimates of the postsynaptic neuronal enzyme markers glutamic acid decarboxylase (GAD) and neuron-specific enolase (NSE), astroglial enzyme markers glutamine synthetase (GS) and non-neuronal enolase (NNE), and the presynaptic enzyme marker DOPA decarboxylase (DDC). The results suggest that a small amount of striatal MAO A is present in kainic acid-sensitive postsynaptic striatal neurons and that MAO B is probably localized in both neurons and astrocytes.

Animals↗
PubMed1984

Psychiatric abnormality and brain calcification over four generations.

An association between basal ganglia calcification and psychiatric abnormality, mainly schizophrenia, is described in three generations of a family; schizophrenia is also recorded in the previous generation. The mode of inheritance appears to be an X-linked dominant one. Unusual sensitivity to neuroleptics also occurred in four members of the family. No comparable family study is believed by the authors to have been reported previously.

Adolescent↗
PubMed1984

Sulfate conjugation of dopamine in rat brain: regional distribution of activity and evidence for neuronal localization.

Brain tissue contains at least two forms of phenolsulfotransferase that are involved in the sulfate conjugation of biogenic amines and their metabolites. Two apparent Km values were obtained for p-nitrophenol at pH 7.4 (0.6 microM and 0.3 mM) but only one enzyme had the capacity to conjugate dopamine (Km = 130 microM). Dopamine sulfotransferase activity was found to vary 17-fold in different brain regions, with the highest levels in diencephalon, hippocampus, and striatum. To determine the cellular localization of the enzymes, phenolsulfotransferase activity was measured in striatum following selective destruction of striatal neurons by stereotaxic injection of 2 micrograms kainic acid. Fourteen days after injection the catecholamine sulfotransferase activity in the lesioned striatum was reduced to approximately 40-50% of that in the control contralateral striatum. There was a statistically significant correlation between the ratio of lesioned to control activity for the sulfotransferase and the neuronal marker enzymes glutamate decarboxylase and neuron-specific enolase. p-Nitrophenol sulfotransferase activity was also decreased in the lesioned striatum. These results suggest that PST activity is present within the kainic acid-sensitive neurons of the striatum. The regional variation in activity, together with the results of the kainic acid studies, suggest that sulfate conjugation of biogenic amines and their metabolites in brain may take place within specific types of neurons.

Animals↗
PubMed1983

Activity of neuron-specific enolase in normal and lesioned rat brain.

Rat brain contains 3 forms of enolase, a neuron-specific form (NSE), a hybrid form, and a non-neuronal form (NNE) which were separated by DEAE-cellulose column chromatography. The enolase activity corresponding to each form of the enzyme eluted from the columns was determined spectrophotometrically. Using this assay procedure, an activity ratio (%NNE/%NSE) was calculated for cerebellum, brainstem, sciatic nerve, adrenals and liver. The results indicated excellent agreement between this enzymatically determined ratio and published values of a similar ratio (NNE/NSE) determined by radioimmunoassay for enzyme protein. Following in vivo destruction of neurons by intracerebral injection of the selective neurotoxin, kainic acid, there was a significant decrease in the activity of NSE and hybrid enolase (neuronal forms) and no change in the activity of NNE (glial form). These data indicate that separation and measurement of enolase species is useful to determine levels of these species in normal tissue and to estimate neuronal damage biochemically in brain lesions.

Animals↗
PubMed1983

Distinct cellular localization of membrane-bound and soluble forms of catechol-O-methyltransferase in brain.

The cellular localization of the two forms of catechol-O-methyltransferase (COMT) was investigated by measuring their activities in rat striatum following unilateral stereotaxic injection of kainic acid, which causes degeneration of striatal neurons followed by proliferation of astroglial cells. Membrane-bound COMT activity was decreased in the lesioned striatum, while soluble COMT activity was increased. There was a statistically significant correlation between the ratio of lesioned to control activity for membrane-bond COMT and the neuronal marker enzyme glutamate decarboxylase. Similarly the increase in soluble COMT activity paralleled that of the astroglial marker enzyme, glutamine synthetase. These results indicate that the low-Km membrane-bound catechol-O-methyltransferase may be localized predominantly in neurons, whereas the high-Km soluble enzyme is found in glial cells.

Animals↗
PubMed1983

Localization of membrane-bound catechol-O-methyltransferase.

Previous studies of the distribution of catechol-O-methyltransferase (COMT) have concentrated on the soluble enzyme activity. In this study the activity of the membrane-bound enzyme was determined in different brain regions and peripheral tissues of the rat. Membrane-bound COMT, like the soluble enzyme, has a general distribution with high levels in liver, kidney, and vas deferens. However, the ratio of membrane-bound to soluble activity varies almost 30-fold in different tissues, with the highest ratio in brain. Membrane-bound activity varies twofold within brain. In view of their different localization and kinetic properties, it seems likely that the two forms of COMT have different functions in vivo.

Animals↗
PubMed1983

Increased binding of [3H]GABA to striatal membranes following ischemia.

Sodium-independent binding of [3H]gamma-aminobutyric acid ([3H]GABA) to membranes prepared from ischemic-damaged rat striatum was studied by kinetic and time-course analysis. Three days after 40 min of ischemia, [3H]GABA binding increased fourfold over control values. Scatchard analysis of the binding showed that ischemia significantly increased the affinity (KD) and the total number of binding sites (Bmax) for the high-affinity GABA receptor. These results support the conclusion that transient forebrain ischemia damages striatal GABAergic neurons.

Animals↗
PubMed1982

The response of GABAergic and cholinergic neurons to transient cerebral ischemia.

The vulnerability of striatal and hippocampal neurons to ischemia was studied by measuring the activity of neurotransmitter-related enzymes after transient forebrain ischemia in rats. Activities of glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) were measured 6 h to 8 days after 20, 30 or 40 min of forebrain ischemia, as markers for GABAergic and cholinergic neurons respectively. Transient forebrain ischemia resulted in depression of striatal GAD activity while striatal CAT and hippocampal GAD activities were unaffected. Striatal GAD activity progressively decreased during the first 24 h postischemia and remained depressed 5--8 days later, suggesting irreversible damage to this population of neurons. The stability of striatal CAT and hippocampal GAD activity indicates that these cells were resistant to the present ischemic conditions.

Acetylcholine↗
PubMed1982

Comparative commissure function: interocular transfer of successive visual discriminations in cats.

Intact and chiasm-sectioned cats were tested for interocular transfer after monocular training of a successive two-choice discrimination task. Similar tasks were previously employed to demonstrate complete failure of interocular transfer in both commissure-intact pigeons and goldfish. In contrast, both groups of cats showed clear interocular transfer. The results provide evidence for differing functional capacity in analogous interhemispheric pathways among vertebrates, and suggest that interocular transfer of successive visual discriminations may be a suitable paradigm for study of phyletic differences in behavioral ability.

Animals↗
PubMed1982

Optic nerve regeneration in goldfish under light deprivation.

Regeneration following bilateral optic nerve crush was studied in groups of goldfish housed either on a standard diurnal cycle or under total light deprivation. Unoperated fish were included in each deprivation condition. Regeneration was only slightly delayed in the surgical group housed under light deprivation (68-81 days), compared to fish undergoing regeneration on the diurnal cycle (59-63 days). Visual capacity, as judged by days to meet criterion on a visual pattern discrimination task, was unrelated to deprivation condition, but significantly lessened in fish having regenerated optic nerves. These results are discussed in terms of visual acuity following optic nerve regeneration and mechanisms of axonal reconnection.

Animals↗
PubMed1982

Computed tomographic evaluation of carcinoma of the cervix.

To assess the accuracy of computed tomography (CT) in staging advanced carcinoma of the cervix, 18 staging evaluations were performed in 16 patients with locally advanced (FIGO Stage IB-IVA) cervical carcinoma. CT staging results were compared with the results of clinical staging and postoperative staging. CT was accurate in 12/18 (66%) cases, clinical staging was accurate in 10/18 (55%) cases, and clinical staging with cystoscopy was accurate in 14/18 (78%) cases. CT staging failed to detect microscopic pelvic sidewall involvement and bladder involvement when there was no contrast material in the bladder. In the detection of para-aortic lymph node involvement by tumor, there were 12 true-negative, 4 true-positive, 1 false-positive, and 1 false-negative study (sensitivity = 80%, specificity = 92%). It is concluded that CT is equal in accuracy to other clinical staging techniques and offers the advantage of visualizing the tumor, which allows for more accurate determination of radiation portals.

Carcinoma↗
PubMed1981

Glutamic acid binding in goldfish brain and denervated optic tectum.

The binding of L-glutamic acid to goldfish brain membranes and changes in tectal binding following optic nerve denervation and regeneration were investigated. Saturable, reversible, and specific binding occurred to sodium-free washed membranes from goldfish brain at a single population of sites having an apparent Kd of 3.4 microM and a capacity of 10 pM/mg original tissue. Binding was enriched in crude synaptosomal (P2) subcellular fractions. There was a 10-fold regional variation in the concentration of binding sites. In pharmacological studies protection constants (Kp) (the concentration which resulted in a 50% inhibition of binding) ranged from 4 microM for glutamate to greater than 10 mM for GABA. Following eye removal, the total number of tectal glutamic acid binding sites was stable for 4 days, followed by a rapid loss in binding, reaching 40% of control at 24 days. After optic nerve crush and optic nerve regeneration, the number and concentration of binding sites was not different from control. The relationship between glutamate, nicotinic, and muscarinic receptor sites in the retinotectal pathway is discussed.

Animals↗
PubMed1980

Electrophoretic analysis of specific proteins in the regenerating goldfish retinotectal pathway.

Proteins in the goldfish retinotectal pathway were analyzed by 2-D gel electrophoresis, under conditions of optic nerve crush or eye removal. A specific cluster of proteins was detected, consisting of 4 components, all of which are highly concentrated in the intact optic nerve. Two components were not detectable in non-visual areas of the goldfish brain. The total cluster was diminished by about 80% in the denervated optic tectum, and its level was restored during optic nerve regeneration. These data were interpreted as evidence for visual system-specific proteins in the goldfish retinotectal pathway.

Animals↗
PubMed1980

Stability of muscarinic-cholinergic receptor activity in the deafferented retinotectal pathway.

The high-affinity antagonist, 3-quinuclidinyl benzilidate (QNB), was used to analyze muscarinic-cholinergic receptor activity in the optic tectum of goldfish and optic lobe of developing chicks and adult pigeons after deafferentation. After deafferentation no significant loss of total or specific muscarinic receptor binding activity was observed in contrast to prior experiments where there was a marked and rapid loss of nictonic-cholinergic receptor binding activity, as measured by alphabungarotoxin binding. The relative stability of the muscarinic site as opposed to the instability of the nicotinic site in these experiments is discussed.

Animals↗