PubMed Health⌕ Search

Biomedical subjects

R C Pearson

Publications and source records attributed to R C Pearson.

At least 19 recordsLinked to original sources
PubMed1998

Metabolic and inflammatory responses after laparoscopic and open inguinal hernia repair.

A prospective comparison of metabolic and inflammatory responses after laparoscopic and open inguinal hernia operations was undertaken. There were 10 patients in each group. Plasma levels of cortisol, growth hormone, prolactin, C-reactive protein (CRP) and interleukin-6 (IL-6) were measured preoperatively and at fixed intervals up to 120 h postoperatively. In vitro, endotoxin stimulated whole blood tumour necrosis factor alpha (TNF alpha) was measured in preoperative and 24 h postoperative blood samples. Changes in the plasma levels of cortisol, growth hormone and prolactin showed no statistically significant difference between the groups. No significant change in IL-6 levels were recorded in any group. Changes in CRP levels were significantly higher (P < 0.006) in open hernia patients. Endotoxin stimulated TNF alpha production was suppressed in both groups. The degree of suppression in open hernia patients was significantly higher (P < 0.005). This study has shown that both these operations produce similar stress responses. However, open hernia operation results in a higher acute phase response and induces a greater endotoxin tolerance.

Acute-Phase Reaction↗
PubMed1997

Mitochondrial DNA mutations in Alzheimer's disease.

Several reports have indicated that point mutations of the mitochondrial DNA (mtDNA) contribute to the pathogenesis of Alzheimer's disease (AD). However, other groups have failed to find similar associations between these mutations and AD. A recent report described a set of mutations in the mtDNA encoded cytochrome oxidase genes which may account for 20% of all AD cases. We screened brain tissue from 65 AD patients for each of these previously reported mtDNA mutations but were unable to find an increased incidence of any of them in our AD sample. However, one patient with a mutation in the APP gene did harbour a novel mtDNA mutation (G to C at position 5705 in the tRNAAsn gene) that might have contributed to the very early onset of dementia in this individual. The role of mtDNA mutations in the pathogenesis of AD remains unclear, but they do not appear to be primary causes but may contribute to the onset of the disease.

Aged↗
PubMed1997

Neuronal degeneration by suicide transport following injection of volkensin into rat cerebral cortex.

We have examined the time course of neurodegeneration in subcortical nuclei and other cortical areas known to project to the rat parietal cortex, following unilateral injection of the suicide transport agent, volkensin, into the cortex of one side. Degenerating neurons, visualized by Gallyas silver staining were most prominent 21 days after injection. At this time darkly staining neurons were present in nuclei and areas known to project to the injected cortical area but not in other sites. Affected subcortical nuclei included the ipsilateral ventral thalamus and intralaminar nuclei, the basal nucleus of Meynert and claustrum of the same side, and the dorsal median raphé nucleus of both sides. Within the cortex degenerating pyramidal neurons were visible in the contralateral parietal cortex and in the frontal cortex of the same side. The distribution of degenerating cells is in agreement with the conclusion that only neurons projecting to the injection site were affected. The time course of the appearance of the degeneration and its distribution are in keeping with axonal transport rather than spread by diffusion of the toxin. Neuronal counts in Nissl-stained sections of the contralateral SMI confirmed significant neuronal loss 28 days after injection. In situ hybridization studies using an oligonucleotide probe directed against GAD mRNA and counts of GAD mRNA-positive neurons in the contralateral cortex confirmed that this population of cortical interneurons, which do not project to the injection site, were unaffected.

Animals↗
PubMed1997

Selective loss of cholinergic receptors following unilateral intracortical injection of volkensin.

Experimental lesions and quantitative autoradiography were used to investigate the cellular distribution of neurotransmitter receptors in rats. Lesions were produced by intracortical injections of either volkensin or ricin. However, only the former is retrogradely transported and volkensin treatment causes significant loss of contralateral cortical pyramidal neurones. Binding of [3H]pirenzepine (muscarinic M1 receptors) and [3H]nicotine was reduced in contralateral cortex in volkensin compared with ricin and/or control (uninjected) animals. However, binding of [3H]8-hydroxy-2-(n-dipropylamino)tetralin (5-HT1A receptors), [3H]ketanserin (5-HT2A receptors), and [3H]1,3-dipropylcyclopentylxanthine (adenosine A1 receptors) was unchanged. The most likely explanation for these results is that M1 and nicotinic receptors are present in large numbers on those pyramidal neurones that are lost. The results are discussed in terms of the biology of cortical pyramidal neurones, drugs for Alzheimer's disease, and novel ligands for improving human brain scanning techniques.

Animals↗
PubMed1997

MAL mRNA is induced during the differentiation of human embryonal carcinoma cells into neurons and is also localised within specific regions of the human brain.

We have found that the MAL gene, which encodes a membrane proteolipid expressed during the late stages of T-lymphocyte maturation, is also activated during neuronal differentiation of NTERA2 human embryonal carcinoma cells following induction with retinoic acid. An RT-PCR fragment with a sequence identical to MAL was found amongst 30 cloned DNA fragments corresponding to genes putatively activated during NTERA2 differentiation and isolated using a differential display PCR screen. PCR and Northern blot analysis with a cloned MAL cDNA as a probe confirmed that MAL is not expressed by undifferentiated NTERA2 EC cells, but is expressed, predominantly as a 1.1 kb transcript, within 7 days of retinoic acid-induced differentiation and later in the post-mitotic neurons arising in such cultures. MAL was not expressed in the non-neuronal lineages induced by treatment of NTERA2 cells with the gratuitous inducer hexamethylene bisacetamide. Analysis of cDNA libraries constructed from EC cells, purified neurons and a sub-population of non-neuronal cells (ME311+), confirmed that expression of the MAL gene is activated in the neural lineage of NTERA2 differentiation. Using in situ hybridisation we found that MAL is expressed in the human CNS and especially in grey matter of the cerebral cortex, with less in the cerebellum and the amygdala and little or none in subcortical white matter. In contrast to reports concerning the expression pattern of a rat MAL homologue, MAL was expressed in the human brain predominantly in cell bodies which include neurons, correlating with in vitro data from the NTERA2 line.

Brain↗
PubMed1996

Allelic variations of the human histamine H2 receptor gene.

The gene encoding the human histamine H2 receptor (H2R) has previously been cloned and sequenced from gastric cDNA. Following PCR amplification of a fragment of the H2R gene from total human DNA, three single nucleotide base substitutions were observed and confirmed when compared with the previously published sequence. One of these base changes introduces an additional TaqI restriction endonuclease site in the coding portion of the gene. PCR amplification of human H2R gene fragments followed by cleavage with TaqI demonstrated the existence of allelic variation of the human H2R gene.

Alleles↗
PubMed1996

Importance of minimizing HLA-DR mismatch and cold preservation time in cadaveric renal transplantation.

Univariate and multivariate analyses have been performed on donor an d recipient variables to determine possible effects on the outcome of 516 primary cadaveric renal transplants performed in our single center from 1989 until 1993. The overall actuarial patient survival at 1 year and 5 years was 94.4% and 87.4%, respectively; the 1 year and 5 year graft survival rates were 88.3% and 77.8%, respectively. A total of 95 grafts were lost; death with function (35%) and chronic rejection (22%) were the major causes. Three variables (HLA-DR mismatch, delayed graft function, and prolonged cold ischemia time) had a significant detrimental effect on both short- and long-term graft survival. Zero HLA-DR mismatched grafts showed significantly enhanced survival over those with 1 HLA-DR mismatch both at 1 year (92.8% vs. 84.5%) and at 5 years (88.3% vs. 73.9%) only if cold ischemia time was less than 26 hours (P=0.0009). Occurrence of delayed graft function significantly lowered graft survival at both 1 year and 5 years (P=0.002), and the incidence was significantly associated with prolonged cold ischemia time (P<0.0001). HLA-A or HLA-B matching, percentage panel reactive antibodies (PRA), and anastomosis time showed no independent effect on long-term survival. The small number of 2 HLA-DR mismatched grafts (n=6) precluded separate analysis of this group. Acute rejection accounted for 12% of losses but had no statistically significant effect on graft survival, even though an increased frequency of rejection episodes was significantly associated with HLA-DR mismatch (P<0.0001). These results would suggest that significant survival benefits may be achieved by prospective HLA matching if cold ischemia times are limited. The efficiency of organ sharing must he improved to make optimal use of a limited resource.

Adolescent↗
PubMed1996

Alteration in brain presenilin 1 mRNA expression in early onset familial Alzheimer's disease.

The expression of the presenilin 1 (PS-1) gene has been investigated by in situ hybridization in early onset familial Alzheimer's disease (FAD), late onset Alzheimer's disease (AD) and normal control brain. Mutations in this gene are responsible for chromosome 14-linked FAD. We have found that presenilin 1 mRNA is present throughout the human brain with a distribution consistent with both a glial and neuronal localization. The in situ hybridization pattern was similar for the controls, the early onset FAD cases and the late onset AD cases. However, one of the two forms of the mRNA for PS-1, the long form (which contains a sequence encoding a four amino acid (VRSQ) insert at its 5' end) was significantly reduced in early onset FAD brain compared with late onset AD. We suggest that this long transcript may alter the normal pathway for processing of amyloid precursor protein, the protein which appears to be central in the pathogenesis of AD.

Adult↗
PubMed1996

Amyloid precursor protein mRNAs in Alzheimer's disease.

Hybridization studies of mRNA link genetic with neurochemical and neuropathological approaches to Alzheimer's disease (AD). Here we review the distribution and abundance of amyloid precursor protein mRNAs in normal and AD-afflicted brains. The expression of apolipoprotein E and presenilin mRNAs are also discussed.

Alzheimer Disease↗
PubMed1996

Cortical connections and the pathology of Alzheimer's disease.

The hypothesis that the distribution of neurodegeneration in Alzheimer's disease results from the spread of the pathology via anatomical connections is reviewed in the light of recent advances in knowledge of the connectivity of the cerebral cortex. Current understanding of cortical connections allows a more detailed examination of the distribution of pathology, particularly neurofibrillary tangles, in relation to this hypothesis. In particular, quantitative assessment of corticocortical pathways opens up the possibility of specific testing of the hypothesis. Theoretical considerations are discussed, and a predicted spread of pathology beginning in the olfactory centres of the medial temporal lobe and spreading retrogradely via known pathways is presented.

Afferent Pathways↗
PubMed1996

Repeated ECS induces GluR1 mRNA but not NMDAR1A-G mRNA in the rat hippocampus.

The neural basis underlying the cognitive side effects of ECT is unknown. Recent studies suggest that the memory dysfunction may be caused by alterations in hippocampal synaptic efficacy [20]. In situ hybridisation was used to examine the possible receptor mechanisms responsible for this effect. Repeated ECS markedly increased mRNA expression for the GluR1 subunit of the AMPA receptor, but not the NMDAR1A-G subtypes of the NMDA receptor, relative to control treatments. This effect was present 24 h after the last seizure and may be responsible for the expression of the ECS-induced increase in synaptic efficacy.

Animals↗
PubMed1996

Individuals with schizophrenia have an increased incidence of the H2R649G allele for the histamine H2 receptor gene.

We have previously described an allelic variant of the human H2R, nominated the H2R649G allele. This allele contains an adenine-->guanidine substitution at base 649, which introduces an additional TaqI restriction endonuclease site into the gene. With this in mind, we have investigated allelic polymorphism of this receptor and its association with schizophrenia. H2R DNA from 47 schizophrenic patients and 46 control subjects was amplified by the polymerase chain reaction (PCR). These PCR products were analyzed by observing TaqI cleavage patterns and single-stranded conformational polymorphisms. It was found that the H2R649G allele was 1.8 times more frequent in the schizophrenic population (chi 2 test P < 0.01). In addition, schizophrenic individuals were 2.8 times more likely to be homozygous for the H2R649G allele than the control population, (chi 2 test P < 0.05). These data place the attributable fraction for possession of the H2R649G allele at 28.4%.

Alleles↗
PubMed1995

The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: selective mRNA vulnerability and comparison with their encoded proteins.

To help account for the variable quality and quantity of RNA in human brain, we have studied the effect of premortem (agonal state) and postmortem factors on the detection of poly(A)+mRNA and eight mRNAs. For comparison, the influence of the same factors upon gene products encoded by the mRNAs was studied immunocytochemically or by receptor autoradiography. Brain pH declined with increasing age at death and was related to agonal state severity, but was independent of postmortem interval and the histological presence of hypoxic changes. By linear regression, pH was significantly associated with the abundance of several of the RNAs, but not with poly(A)+mRNA, immunoreactivities, or binding site densities. Postmortem interval had a limited influence upon mRNA and protein products. Freezer storage time showed no effect. Parallel rat brain studies showed no relationship between postmortem interval (0-48 h) and amounts of total RNA, poly(A)+RNA, or two individual mRNAs; however, RNA content was reduced by 40% at 96 h after death. pH is superior to clinical assessments of agonal state or mode of death in predicting mRNA preservation. It provides a simple means to improve human brain gene expression studies. pH is stable after death and during freezer storage and can be measured either in cerebrospinal fluid or in homogenised tissue.

Acidosis↗
PubMed1994

An aspect of Alzheimer neuropathology after suicide transport damage.

Concentrations of APP-like immunoreactivity have been determined by western blotting in a soluble fraction and two membrane fractions of brain cortex from demented patients (14 with Alzheimer's disease and 8 with other diagnoses). The concentration of APP in the soluble fraction correlated with the number of pyramidal neurones but not astrocytes or indices of interneurones. Experimental lesions in rats and quantitative autoradiography were used to investigate the cellular localisation of receptors. Lesions were produced by intrastriatal or intracortical injections of volkensin to destroy corticofugal and corticortical pyramidal neurons respectively. Volkensin treatment caused significant loss of pyramidal neurones which was accompanied by reduced binding to muscarinic cholinergic m1 receptors. [3H] 8-OH-DPAT (serotonin 1A receptors) binding was reduced only following intrastriatal volkensin. Results from the human and rat investigations are discussed in terms of the biology of cortical pyramidal neurones and drugs for the treatment of Alzheimer's disease.

Alzheimer Disease↗
PubMed1994

beta-Amyloid precursor protein isoforms show correlations with neurones but not with glia of demented subjects.

Post-mortem cerebral cortex from 15 demented patients was specially collected to minimise autolysis and two membrane fractions and one soluble fraction were quantitatively examined for the major species of beta-amyloid precursor protein (APP) of high apparent molecular mass (> or = 80 kDa) together with the major mRNA species encoding APP isoforms. The number of pyramidal neurones and astrocytes, putative biochemical indices of interneurones and pyramidal neurones, and choline acetyl transferase activity were also determined. Multiple regression analysis has been used to investigate intercorrelations of APP species with biochemical and morphometric measures, free of any effects of confounding demographic variables. Subjects with Alzheimer's disease showed a loss of cholinergic activity and D-aspartate uptake compared with patients with other causes of dementia. The major finding of the study is that measures of neurones rather than astrocytes most closely correlate with the concentration of APP. Pyramidal cell numbers were positively correlated with mRNA for APP695. APP in the soluble fraction showed a negative correlation with pyramidal cell numbers and cholinergic activity. These results indicate that neurones within the cerebral cortex are the major source of APP, and that secretion of APP is dependent upon cortical pyramidal neuronal activity and cholinergic activity.

Aged↗
PubMed1994

The effects of Alzheimer's disease, other dementias, and premortem course on beta-amyloid precursor protein messenger RNA in frontal cortex.

There are conflicting data regarding alterations in beta-amyloid precursor protein (APP) mRNAs in Alzheimer's disease (AD). This may be due partly to variables such as agonal state and choice of control group. We have used in situ hybridization histochemistry to study expression of APP mRNAs, with and without the domain encoding the Kunitz protease inhibitor, in a way that overcomes some of the limitations of the current data. Tissue from frontal cortex was collected at rapid autopsy from patients with AD or other cognitive impairments whose terminal phase was prospectively assessed. There were three main findings. Firstly, the amount of APP mRNAs correlated strongly with glutamate decarboxylase activity and was reduced in association with terminal pyrexia. These correlations suggest that agonal state affects APP mRNA and, therefore, that differences in premortem course may contribute to the varying changes in APP transcript abundance reported in AD. Secondly, a reduction of both forms of APP mRNA, normalized to polyadenylated mRNA, was found in AD compared with normal controls and with non-AD dementias. This supports findings that the APP-related pathology of AD is not due to overexpression of APP mRNA or an altered proportion of Kunitz protease inhibitor-containing isoforms. Thirdly, the amount of APP mRNA correlated inversely with that of heat-shock protein (hsx70) mRNA. This relationship was unexpected given current theories that APP expression occurs as part of a stress response, and suggests that other factors predominate in determining neocortical APP mRNA content in neurodegenerative disorders.

Aged↗
PubMed1994

Prospective endoscopic study of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo.

OBJECTIVE: To compare the frequency of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo. DESIGN: Prospective, randomized study. SETTING: Intensive care unit in a university hospital. PATIENTS: Twenty-six adult patients. All patients were mechanically ventilated and were at risk of developing stress ulceration. INTERVENTIONS: Patients were randomized to receive either sucralfate (2 g every 8 hrs) (group 1) via the nasogastric tube (flushed with 10 mL of sterile water) or 20 mL of sterile water every 8 hrs (group 2) via the nasogastric tube. MEASUREMENTS AND MAIN RESULTS: At the time of intensive care unit admission, the frequency of stress (acute) erosions (as assessed with the endoscope) was 21.7%. No ulcers were detected. By day 3, the frequency had increased to 37.5% in group 1 and 88.9% in group 2. Mucosal deterioration was more likely in the patients treated with placebo (water) (p < .05). In total, seven patients developed acute ulceration in group 2 compared with only one patient in group 1 (p < .05). The frequency of gastric colonization with aerobic Gram-negative bacilli was 25.6% in group 1 and 28.6% in group 2. Only one retrograde nosocomial pneumonia developed (group 1). CONCLUSION: Based on our findings, we strongly recommend the adoption of sucralfate as opposed to no prophylaxis in the prevention of acute upper gastrointestinal ulceration.

Adult↗