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Biomedical subjects

R C Pearson

Publications and source records attributed to R C Pearson.

At least 55 records · Page 3Linked to original sources
PubMed1991

Transient increase in glutamic acid decarboxylase mRNA in the cerebral cortex following focal cortical lesion in the rat.

In situ hybridization histochemistry (ISHH) was used to study the expression of glutamic acid decarboxylase (GAD) mRNA changes in the rat cerebral cortex following unilateral frontal and somatosensory cortical lesion by devascularisation. 4 days after the lesion, a significant transient increase in GAD mRNA level in the ipsilateral cortex was observed when compared with contralateral, ipsi-sham operated and ipsi-normal control cortices. The change occurred throughout the ipsilateral neocortex, with no significant difference between the magnitude of increase in frontal, parieto-occipital, parieto-temporal, cingulate or retrosplenial areas; no obvious change was seen in pyriform, entorhinal or hippocampal cortices. This unexpected GAD mRNA increase in neocortex may be part of a long term adaptive functional alteration and changes in the gene expression of the cerebral cortex following focal cortical injury.

Animals↗
PubMed1991

Destruction of a sub-population of cortical neurones by suicide transport of volkensin, a lectin from Adenia volkensii.

A method for the destruction of a sub-population of neocortical pyramidal neurones is described. The technique uses unilateral striatal injections of volkensin, a toxic lectin from Adenia volkensii, which undergoes retrograde axonal transport from the site of injection to destroy subcortically projecting pyramidal cells within the neocortex. Striatal volkensin injections produce a significant reduction in the number of large pyramidal neurones of the infragranular layer. The selectivity of the lesion was demonstrated by the preservation of glutamic acid decarboxylase mRNA positive cells, considered to be cortical interneurones within ipsilateral cortex. The binding of the serotonin 1A receptor agonist [3H]-8-hydroxy-2-(n-dipropylamino)tetralin, visualised by autoradiography, was reduced in areas showing loss of large cells, indicating that these receptors may be present on subcortically projecting pyramidal cells. Ricin, another toxin lectin, but effective as a suicide transport agent in only the peripheral nervous system, produced local striatal damage but no cortical cell loss. The selective destruction by volkensin of neocortical pyramidal neurones with subcortical projection targets should aid the neurobiological investigation of such cells. Additionally, data obtained using this technique may provide insights into the interpretation of biochemical findings in neurodegenerative disease in which pyramidal cell loss is a significant feature.

Animals↗
PubMed1991

Alzheimer's disease: specific increases in a G protein subunit (Gs alpha) mRNA in hippocampal and cortical neurons.

The GTP binding protein, Gs, activates adenyl cyclase in direct response to stimulation of several neurotransmitter receptors. In situ hybridization histochemistry (ISHH) with a 35S-labelled oligonucleotide has been used to detect the mRNA encoding the alpha subunit of Gs (Gs alpha) in human hippocampus, temporal and visual cortices and cerebellum, and its level has been compared between Alzheimer's disease (AD) and control brains. A marked regional increase was found in the hippocampus of AD cases. Analysis of levels of Gs alpha mRNA in individual constituent pyramidal cells confirmed this increase (3 to 4-fold in densitometric units) in hippocampal fields CA1, CA3 and CA4, as well as in temporal cortex. Levels of Gs alpha mRNA were also determined relative to total poly(A)+ mRNA in the same cell populations in each case. Gene-specific elevation of Gs alpha mRNA was thereby confirmed in hippocampal fields, and also in temporal cortex. No changes were seen in visual cortex. The increase in Gs alpha mRNA may represent a response by AD neurons in affected areas to receptor alterations, or to an abnormality in receptor-G protein coupling. Alternatively, altered G protein gene expression might be a pathogenic event underlying changes in linked receptor populations.

Aged↗
PubMed1991

Increased muscarinic receptor messenger RNA in Alzheimer's disease temporal cortex demonstrated by in situ hybridization histochemistry.

A 35S-labelled synthetic oligonucleotide directed against part of the mRNA coding for the M1 subtype muscarinic receptor was used for in situ hybridization histochemistry in sections of human temporal cortex. M1 receptor mRNA was found in cell populations throughout the grey matter, especially in pyramidal cells. Quantitative densitometric analysis of autoradiograms was used to compare levels of this mRNA between Alzheimer's disease and controls. A significant (2.7-fold) increase in hybridization signal was found in Alzheimer's disease cases, both in absolute terms and relative to total polyadenylated mRNA as determined by hybridization with an oligodeoxythymidine probe. Elevated levels of muscarinic receptor mRNA may reflect up-regulation of transcription of this gene in response to the cholinergic deficits occurring in the disease.

Alzheimer Disease↗
PubMed1991

Terminal coma affects messenger RNA detection in post mortem human temporal cortex.

In situ hybridization histochemistry has been used to study the amount of M1 muscarinic receptor mRNA in temporal cortex from subjects with Alzheimer's disease and other neurodegenerative disorders, where the duration of terminal coma was known. Total polyadenylated mRNA and glutamate decarboxylase activity were also measured. Both muscarinic receptor mRNA and enzyme activity showed a significant decline with increasing duration of terminal coma, but were not related to diagnosis. Polyadenylated mRNA signal did not show an association with coma. These data indicate the need to consider the nature of the terminal illness in post mortem studies of mRNA as well as for neurochemical research.

Alzheimer Disease↗
PubMed1991

Regional and neuronal reductions of polyadenylated messenger RNA in Alzheimer's disease.

Messenger RNA (mRNA) is the key intermediate in the gene expression pathway. The amount of mRNA in Alzheimer's disease (AD) brains has been determined using in situ hybridization histochemistry (ISHH) to detect the poly(A) tails of polyadenylated mRNA (poly(A) + mRNA). On a regional basis, AD cases had significantly less poly(A) + mRNA than controls in hippocampus (field CA3) and cerebellum (granule cell layer). Analysis of constituent pyramidal neurons showed mean reductions per cell within AD hippocampus (field CA3) and temporal cortex, but not in visual cortex. Similar changes were seen in a small group of non-AD dementias. The finding of reduced poly(A) + mRNA content is another indication of the altered brain gene expression occurring in AD. It is proposed that measurement of poly(A) + mRNA may be valuable in identifying functionally impaired neuronal populations. The methodology also provides a means by which changes in the quantitative distribution of individual mRNAs can be determined relative to that of poly(A) + mRNA as a whole.

Adult↗
PubMed1991

Expression of amyloid beta-protein precursor mRNAs in familial Alzheimer's disease.

The amyloid beta-protein precursor (APP) gene and its products are implicated in the pathogenesis of Alzheimer's disease. The differential expression of APP transcripts may contribute to this process. In the present study, the distribution of mRNAs encoding APP variants has been determined in the brain of three cases of familial Alzheimer's disease (FAD) using in-situ hybridization histochemistry. One FAD case was associated with a mutation in the APP gene. No differences in distribution or quantity of APP transcripts were observed between FAD cases and controls. Overexpression of APP mRNAs is therefore an unlikely explanation for the deposition of the beta-amyloid (beta/A4) peptide in FAD brains.

Adult↗
PubMed1991

A comparison of the frequency of stress ulceration and secondary pneumonia in sucralfate- or ranitidine-treated intensive care unit patients.

OBJECTIVE: To compare the frequency of acute stress ulceration and secondary pneumonia caused by aerobic Gram-negative bacilli in ICU patients treated with either sucralfate or ranitidine. DESIGN: Prospective, randomized study. SETTING: ICU, university hospital. PATIENTS: Sixty adult patients who were mechanically ventilated and at risk of developing stress ulceration. INTERVENTION: The patients were randomized to receive either sucralfate (1 g every 6 hrs) via the nasogastric tube or iv ranitidine (50 mg every 6 hrs). If the gastric pH was less than 3.5 in the latter group, 30 mL of 0.3M sodium citrate was given via the nasogastric tube. MEASUREMENTS AND MAIN RESULTS: On admission, the frequency rate of erosion/ulceration (assessed with the endoscope) was 13.5%. After 4 days, this rate had increased to 18% in sucralfate-treated patients and 36% in ranitidine-treated patients (NS). Mean gastric pH was more alkaline in the ranitidine-treated patients (5.50) compared with the sucralfate-treated patients (4.26) (p less than .01). This pH permitted a higher occurrence rate of gastric colonization by aerobic Gram-negative bacilli in ranitidine-treated patients (64.3%) compared with sucralfate-treated patients (23.8%) (p less than .01). Retrograde bacterial colonization from the stomach to oropharynx and trachea occurred more frequently in ranitidine-treated patients compared with sucralfate-treated patients. Ultimately, the occurrence rate of pneumonia was greater in the ranitidine-treated (35.7%) than in the sucralfate-treated patients (10.3%) (p less than .05). CONCLUSION: Based on our findings, we recommend the adoption of sucralfate for routine prophylaxis against stress ulceration.

Administration, Oral↗
PubMed1991

Neuronal hypertrophy in the pars reticulata of the substantia nigra in Parkinson's disease.

The size of neurons in the pars reticulata of the substantia nigra in patients dying with Parkinson's disease has been compared with that in non-parkinsonian control cases. Parkinson's disease is accompanied by a significant (+53%) hypertrophy of reticulata neurons. This is similar to changes seen in experimental rats with ipsilateral damage of the striatum. It is suggested that the enlargement seen in Parkinson's disease, similar to that in the rat, is indicative of plasticity in the GABA-ergic reticulata neurons, and may be associated with increased inhibitory flux in pathways arising from the pars reticulata to the superior colliculus and thalamus.

Adult↗
PubMed1991

Lesions of the Cerebral Cortex and Caudate-Putamen Enhance GABA Function in the Rat Superior Colliculus.

Unilateral lesions of the rat frontal cortex were made either alone or in combination with the caudate-putamen in order to examine (a) their morphological influence on the substantia nigra and (b) their neurochemical influence on GABA function in the superior colliculus. One to two months following the combined lesion, neuronal somata in the ipsilateral pars reticulata of the substantia nigra were clearly hypertrophied (+ 30%). Morphological changes in the substantia nigra were not evident contralaterally or in animals bearing only cortical lesions. One to two months following cortex-only lesions, no significant alterations in tectal GABA concentration were observed. However, the combined lesion induced elevations of GABA within both the medial and lateral sectors of the intermediate and deep layers of the superior colliculus. This effect was restricted to the ipsilateral side and was most pronounced in lateral sectors. The vast majority of GABA released from superfused control tectal slices by a depolarizing stimulus (35 mM KCl) was calcium-dependent. Such evoked GABA release from ipsilateral tectal slices was significantly reduced (- 25%) by unilateral lesions of the substantia nigra, a structure that is known to provide GABA-containing inputs to the tectum. In contrast, cortical lesions alone significantly enhanced the evoked tectal GABA release (+ 66%), although their influence was again confined to the ipsilateral side. Combined lesions of the cerebral cortex and caudate-putamen significantly enhanced the evoked GABA release from tectal slices in both hemispheres but the changes were most marked ipsilaterally (+ 147%). It is suggested that the hypertrophy of GABA-containing nigrotectal somata seen after removal of corticostriatal, corticotectal and in particular GABA-containing striatonigral fibres may reflect concomitant increases in GABA synthesis within and/or sprouting of nigrotectal terminals.

Journal Article↗
PubMed1990

The connections of area PG, 7a, with cortex in the parietal, occipital and temporal lobes of the monkey.

The cortico-cortical connections of area PG, 7a, in the parietal, occipital and temporal lobes have been studied after injections of HRP in this area and in certain of the areas connected with it. After such injections in PG there are labelled cells in architectonic areas OA and PE (visual area PO), the cingulate and retrosplenial areas situated medial to PG; posteriorly labelled cells are present in OA, visual areas MST, MT, V2, V3, V4 and in the walls and floor of the lower part of the superior temporal sulcus. Injections in PE and V4 show that these connections are reciprocal. Small injections in PG result in cell labelling in different parts of the areas connected to PG, suggesting that the connections are well organized and that there may be an ordered representation of the visual field in PG. In the lower wall of the lower part of the superior temporal sulcus there is overlap of the two visual pathways in the cortex, that to the temporal lobe with that to the parietal lobe; and in a restricted part of this sulcus there is convergence and overlap of the sequences of cortico-cortical connections related to the visual, somatic and auditory sensory systems. There may be certain common principles in the sequences of cortical connections to the parietal and temporal lobes from the primary visual and somatic sensory areas; in both there are well organized hierarchical and parallel pathways, and both are related to the superior temporal sulcus and to the cingulate cortex.

Animals↗
PubMed1990

The ipsilateral cortico-cortical connections of area 7b, PF, in the parietal and temporal lobes of the monkey.

The cortico-cortical connections of area 7b (or PF) in the parietal and temporal lobes of the monkey have been studied with the method of axoplasmic transport of horseradish peroxidase (HRP). Area 7b is reciprocally and precisely connected with area 5, the second somatic sensory area (SII), the retroinsular area, the granular insular area (Ig), area 23 of the cingulate cortex and with the cortex in the walls of the superior temporal sulcus. Area 7b is not interconnected with area 7a (PG) nor with any of the prestriate visual areas. After injections of HRP into area PF the labelled cells in all these areas, except the granular insular area, are mainly in layer III and these cells are considered to be the origin of 'feed-forward' type connections; in the granular insular area most of the cell labelling is in layer V, interpreted to be the origin of 'feed-back' connections. Between SI and area PF there are two sequences of connections in parallel with each other, one through area 5 and the other through SII. In all areas the labelled cells are in clusters of 500-2000 microns width on individual sections and in bands of these widths on planar reconstructions.

Animals↗
PubMed1990

The ipsilateral corticocortical connections of area 7 with the frontal lobe in the monkey.

The corticocortical connections between area 7 and the frontal lobe have been studied in the monkey. Injections of HRP were made into area 7 of the parietal lobe or into area 46 in the walls of the principal sulcus. The two subdivisions of area 7, 7a or PG and 7b or PF, are connected with different parts of the frontal lobe, and each subdivision is connected with two distinct areas. Area 7b, PF, is connected in a well organized and somatotopic manner with the lower premotor area and with the lower part of area 46, below the fundus of the principal sulcus. Area 7a, PG, is connected with area 8a and with the upper part of area 46, above the fundus of the principal sulcus; it is suggested that the lower part of area 8a and the posterior part of area 46 are related to the central visual field, while the medial part of area 8a and the anterior part of area 46 are related to the periphery of the visual field. The corticocortical connections between area 7 and the frontal lobe are reciprocal and those passing from area 7 to the frontal lobe are 'feed-forward' and those to area 7 are 'feed-back'.

Animals↗
PubMed1990

Distribution of messenger RNAs encoding the enzymes glutaminase, aspartate aminotransferase and glutamic acid decarboxylase in rat brain.

In situ hybridization histochemistry (ISHH) using synthetic oligonucleotide probes has been used to identify cells containing the mRNAs coding for glutaminase (GluT), aspartate aminotransferase (AspT) and glutamic acid decarboxylase (GAD). The distribution of GAD mRNA confirms previous descriptions and matches the distribution of GAD detected using specific antibodies. AspT mRNA is widely distributed in the brain, but is present at high levels in GABAergic neuronal populations, some that may be glutamatergic, and in a subset of neurons which do not contain significant levels of either GAD or GluT mRNA. Particularly prominent are the neurons of the magnocellular division of the red nucleus, the large cells in the deep cerebellar nuclei and the vestibular nuclei and neurons of the lateral superior olivary nucleus. GluT mRNA does not appear to be present at high levels in all GAD-containing neurons, but is seen prominently in many neuronal populations that may use glutamate as a neurotransmitter, such as neocortical and hippocampal pyramidal cells, the granule cells of the cerebellum and neurons of the dentate gyrus of the hippocampus. The heaviest labelling of GluT mRNA is seen in the lateral reticular nucleus of the medulla. ISHH using probes directed against the mRNAs encoding these enzymes may be an important technique for identifying glutamate and aspartate using neuronal populations and for examining their regulation in a variety of experimental and pathological circumstances.

Animals↗
PubMed1990

Distribution of a kainate/AMPA receptor mRNA in normal and Alzheimer brain.

In-situ hybridization (ISH) has been used to determine the distribution of the mRNA encoding a non-NMDA glutamatergic receptor subtype in rat and human brain. In the rat, signal is concentrated over neurons in hippocampus and cerebellum, with moderate labelling of neocortex and diencephalon. In human brain, a similar hippocampal and cerebellar distribution is seen, although with lower overall levels. Quantitative comparison between normal and Alzheimer's disease (AD) brain reveals a modest increase of this mRNA in AD subiculum and CA4 hippocampal field with no change in cerebellum. The significance of the increase is discussed in relation to other data suggesting glutamatergic involvement in AD.

Alzheimer Disease↗
PubMed1990

Midazolam and flumazenil in gastroenterology.

Flumazenil, a specific benzodiazepine antagonist, has been used to reverse sedation in a double-blind, controlled study of patients undergoing upper gastrointestinal (GI) endoscopy. Forty patients in each of two centres were given a standard dose of either flumazenil (n = 40) or placebo (n = 40) after gastroscopy under midazolam sedation. Assessments were made of degree of sedation, psychomotor ability and amnesia up to 24 h after endoscopy. In patients treated with flumazenil, sedation was effectively reversed within 5 min in 77.5% of cases compared to 27.5% of patients treated with placebo. The difference was both clinically and statistically significant at 5 and 30 min but not at 60 min after reversal. There was no evidence of resedation 18 to 24 h later. Times to complete Trieger dot-joining tests were significantly faster in the flumazenil group at 5, 30 and 60 min. Amnesia for the procedure was retained but did not occur for events after administration of flumazenil. The only adverse event was severe pain in the arm of one patient during the injection of flumazenil. Flumazenil rapidly and safely reverses midazolam-induced sedation while retaining amnesia for gastroscopy.

Adolescent↗
PubMed1990

A quantitative study of the neurofibrillary tangles and the choline acetyltransferase activity in the cerebral cortex and the amygdala in Alzheimer's disease.

A quantitative study has been made of the number of neurofibrillary tangles and of the choline acetyltransferase activity in several sites in the cerebral hemispheres of eight patients who had had Alzheimer's disease. The neurofibrillary tangles were maximal in structures in the medial temporal lobe (uncus, amygdala, hippocampus and parahippocampal gyrus), severe in the neocortex on the lateral surface of the temporal lobe, moderate in the "association cortex" of the parietal and frontal lobes and minimal in primary somatic and visual sensory areas. There was a significant decrease in choline acetyltransferase activity in almost all areas, and the means of the percentage decreases for the different groups of areas correlate well with the counts of the neurofibrillary tangles. These results support the hypothesis that the pathological process in Alzheimer's disease may spread along a sequence of corticocortical connections between the main sensory areas and the hippocampal formation. The disease process may also spread along the reciprocal connections between the amygdala and the neocortex because the numbers of tangles in different areas of the neocortex closely parallel the density of their connections and the amygdala.

Aged↗