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G W Roberts

Publications and source records attributed to G W Roberts.

At least 55 records · Page 3Linked to original sources
PubMed1995

Distribution of beta-amyloid protein in the brain following severe head injury.

Deposits of beta-amyloid protein (beta AP) can be found in the brains of 30% of fatally head-injured patients; they have been found in children and after survival times of only 4 h. The principal aims of this study were to map the distribution of beta AP in 14 patients aged 65 years or less in whom it was known that the protein had been deposited, and to correlate its distribution with the pathologies of traumatic brain injury. The results show that beta AP is widely distributed, and that there is no correlation between its presence and cerebral contusions, intracranial haematoma, axonal injury, ischaemic brain damage, brain swelling or the pathology of raised intracranial pressure. These findings suggest that the deposition of beta AP is a consequence of the acute phase response of nerve cells to stress in susceptible individuals. Further studies will be required to establish the possible relationship between the deposition of beta AP following head injury and the molecular neuropathology of Alzheimer's disease.

Adolescent↗
PubMed1994

Increased numbers of beta APP-immunoreactive neurones in the entorhinal cortex after head injury.

In a previous publication we hypothesized that Alzheimer's disease (AD) can be induced by the age-related increase in expression of beta-amyloid precursor protein (beta APP) in the medial temporal lobe. Head injury has also been identified as a risk factor for AD and as such, similarities should exist between the pathology found after head injury and the earliest stages of pathology in AD. In this study, we have quantified the number of beta APP-immunoreactive neurones in the medial temporal cortex (pre-alpha cells, layer II) of 13 head injured and 17 control patients. Significantly more beta APP immunoreactive neurones were observed in head injury cases (mean 18.4 per cluster) compared with controls (mean 13.4 per cluster, p < 0.05). These data provide a mechanism to explain how an environmental event such as head injury can generate the same molecular pathology (increased neuronal beta APP) as is found in the earliest stages of AD.

Adolescent↗
PubMed1994

Microglial interleukin-1 alpha expression in human head injury: correlations with neuronal and neuritic beta-amyloid precursor protein expression.

Activated microglia containing IL-1 alpha-immunoreactive (IL-1 alpha +) product were increased 3-fold in number in the acute phase following head injury, a risk factor for later development of Alzheimer's disease, and this increase was correlated with a 7-fold increase in the number of neurons with elevated beta-amyloid precursor protein (beta-APP) levels (R = 0.78; P < 0.05). Furthermore, clusters of beta-APP+ dystrophic neurites present in these patients were invariably associated with activated IL-1 alpha + microglia. These findings suggest that early overexpression of IL-1 alpha and beta-APP is a priming event for later neuropathological changes evident at end stages of Alzheimer's disease.

Adult↗
PubMed1994

Differential synaptic loss in the cortex in Alzheimer's disease: a study using archival material.

We have developed techniques to utilize immunocytochemical localization of synaptic protein (SNAP-25) in conjunction with image analysis to investigate synaptic loss in readily available archival material. Sections from 5 cortical regions were examined in cases of Alzheimer's disease (n = 7) and controls (n = 5). Image analysis was used to determine a relative synaptic index (RSI) and probe for changes in synaptic integrity. RSI value for cortical regions did not differ in controls. RSIs from sulci and gyri were significantly correlated in Brodmann areas 6, 9 and 18 (40 and 52 approached significance). Cases with Alzheimer's disease showed decreases in sulcal and gyral RSI values of between 60% (Brodmann area 6 < 0.01) and 10% (Brodmann area 18 > 0.4) and a lack of correlation in sulco-gyral values except in Brodmann area 18. We have demonstrated that synaptic pathology is heterogeneous with frontal cortex most and occipital cortex least affected. Sulci and gyri are affected to different degrees. The underlying cytoarchitecture of the cortex and its pattern of connectivity appears to have a considerable influence on the degree and extent of synaptic pathology.

Aged↗
PubMed1994

Reduced concentrations of the alpha-subunit of GTP-binding protein Go in schizophrenic brain.

Concentrations of the alpha-subunits of GTP-binding protein, Go (Go alpha) and of Gi2 (Gi2 alpha) in 6 areas (the hippocampus, parahippocampus, putamen, caudate head, orbital frontal cortex, and lateral temporal cortex) of control and schizophrenic postmortem brains were investigated using the highly sensitive enzyme immunoassay method. There was a significant decrease in Go alpha in the hippocampus and caudate head of the right hemisphere in schizophrenic patients compared to controls; the ANOVA (a general linear model; SAS Type II) demonstrated a significant diagnosis x side interaction only in the hippocampus. In other areas of the brain, analysis by grouping under diagnosis, side, age, gender, and postmortem delay showed no significant deviations in Go alpha between controls and schizophrenics. The concentrations of Gi2 alpha did not differ significantly in any area. These findings contrasted with the results yielded by ADP-ribosylation, which showed decreased pertussis toxin ADP-ribosylated amounts in the hippocampus and putamen of the contralateral (left) hemisphere. Some abnormal receptor-Go or Gi 1 signalling in hippocampus, putamen or caudate head may be involved in the pathogenesis of schizophrenia.

Aged↗
PubMed1994

The distribution of nitric oxide synthase immunoreactivity in the human brain.

Nitric oxide is a free radical which is produced in the brain and is thought to be the first of a new class of neural messenger molecules. It is postulated to act by inducing an increase in cyclic guanosine monophosphate levels in target cells. The neuronal isoform of nitric oxide synthase, the enzyme responsible for the calcium-dependent synthesis of nitric oxide from L-arginine, has been purified from brain homogenate. Using a specific polyclonal antibody, we have localized brain nitric oxide synthase to the cytosol of discrete neuronal subpopulations and glial elements. These include non-pyramidal cells in the cerebral cortex, pyramidal and non-pyramidal cells of the hippocampus, aspiny neurons of the corpus striatum, basket, Purkinje and granule cells in the cerebellum and neurons of various brain stem nuclei. The localization of nitric oxide-producing neurons in morphologically different and neurochemically diverse cell types suggests a widespread neuromodulatory role for nitric oxide in the central nervous system of man.

Adult↗
PubMed1994

Beta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer's disease.

In a recent preliminary study it was reported that a severe head injury resulted in the deposition of beta amyloid protein (beta AP) in the cortical ribbon of 30% of patients who survived for less than two weeks. Multiple cortical areas have now been examined from 152 patients (age range 8 weeks-81 years) after a severe head injury with a survival time of between four hours and 2.5 years. This series was compared with a group of 44 neurologically normal controls (age range 51 to 80 years). Immunostaining with an antibody to beta AP confirmed the original findings that 30% of cases of head injury have beta AP deposits in one or more cortical areas. Increasing age seemed to accentuate the extent of beta AP deposition and potential correlations with other pathological changes associated with head injury were also investigated. In addition, beta amyloid precursor protein (beta APP) immunoreactivity was increased in the perikarya of neurons in the vicinity of beta AP deposits. The data from this study support proposals that increased expression of beta APP is part of an acute phase response to neuronal injury in the human brain, that extensive overexpression of beta APP can lead to deposition of beta AP and the initiation of an Alzheimer disease-type process within days, and that head injury may be an important aetiological factor in Alzheimer's disease.

Adolescent↗
PubMed1994

Peripheral intravenous line survival and phlebitis prevention in patients receiving intravenous antibiotics: heparin/hydrocortisone versus in-line filters.

OBJECTIVE: To compare the use of in-line filtration with the addition of heparin/hydrocortisone (hep/hc) to the infusate for both phlebitis prevention and intravenous (i.v.) line survival in peripheral i.v. catheters. This study was specific for a patient group receiving prolonged courses of i.v. antibiotics. Analysis of the two endpoints for conventional short i.v. catheters (short lines) versus long (30 cm) i.v. catheters (long lines) was also performed. METHODS: Patients with cystic fibrosis receiving intermittent i.v. antibiotics were randomly allocated to receive their drugs either through an in-line filter using a drug-free infusate or with no filter and an infusate containing heparin 500 units and hydrocortisone 10 mg/L. Infusion sites were assessed daily. RESULTS: Both the hep/hc and filter groups were similar in terms of phlebitis incidence and i.v. line survival when analyzed separately for both short and long lines. Long lines displayed markedly prolonged survival times and reduced phlebitis compared with short lines. CONCLUSIONS: The effectiveness of i.v. filters in excluding the large particle load introduced by i.v. antibiotics and hence in reducing the subsequent phlebitis makes them a useful alternative to the use of hep/hc. The use of filters in this patient group may offer advantages in terms of ease of use and a possible decrease in hep/hc-related problems. Long lines offer practical advantages over short lines for patients requiring longer term i.v. access.

Anti-Bacterial Agents↗
PubMed1993

Frontal lobe dementia is not a variant of prion disease.

Frontal lobe dementia (FLD) is a syndromal diagnosis with a variable pathology. It has been argued that FLD is a dementing disorder which should be nosologically and etiologically distinguished from other types of dementia. However, similarities with prior disease and Alzheimer's disease have led to the suggestion that FLD is a variant of one or other of these dementias. We have tested this line of argument by examining the frontal cortex and cerebellum of 14 FLD cases and probing the molecular pathology using well characterized antibodies to prion protein and beta-amyloid protein. No prion protein deposits or significant levels of beta-amyloid protein were detected. FLD is a dementing disorder whose molecular pathology, whilst as yet uncharacterised, can be distinguished from those of other dementing disorders.

Aged↗
PubMed1993

Beta-amyloid precursor protein (beta APP) as a marker for axonal injury after head injury.

It has been demonstrated recently that beta-amyloid protein (beta AP), generally associated with the plaques of Alzheimer's disease, can also be found in the brains of survivors of head injury. In this study the distribution of the beta AP precursor protein (beta APP) was examined immunohistochemically to determine if it is colocalized with beta AP in such cases. beta APP immunoreactivity was observed in neuronal perikarya in the neocortex and in dystrophic neurites surrounding beta AP immunoreactive plaques i.e. in a distribution similar to that seen in Alzheimer's disease. In addition, beta APP immunoreactivity was noted within white matter tracts where it marked damaged axons. However, no colocalisation of beta APP with beta AP was observed in any white matter region. These results indicate that processing of beta APP to produce beta AP occurs in the synaptic terminal field of axons and illustrate the utility of beta APP immunoreactivity as a general marker for axonal injury.

Adult↗
PubMed1993

Ubiquitination as a probe for neurodegeneration in the brain in schizophrenia: the prefrontal cortex.

Abnormalities in brain structure and brain function have been described in schizophrenia. It is not yet known whether these are caused by an abnormality of brain development, some form of birth injury, or a neurodegenerative process. Using immunocytochemical methods and a marker for neurodegeneration (ubiquitin), we examined an area of prefrontal cortex from elderly schizophrenic and control subjects for the presence of ubiquitin-positive degeneration products. There was no statistical difference in the degree of ubiquitination between the control and the patient samples. The findings provide no evidence to support a neurodegenerative process.

Aged↗
PubMed1993

On the origin of Alzheimer's disease: a hypothesis.

There is no unifying hypothesis to account for the anatomical distribution of neuropathology, the involvement of beta-amyloid precursor protein (beta APP) and the role of increasing age in triggering the Alzheimer disease process. We report here that layer II pre-alpha neurones in transentorhinal and entorhinal cortex contain more beta APP immunoreactivity than other cortical neurones in normal individuals. This immunoreactivity increased in the early stages of Alzheimer's disease and was lost as the disease progressed. These neurones are known to undergo genetically programmed re-sprouting and synaptogenesis during the fifth and sixth decades of life. We hypothesize that these phenomena are related and that the Alzheimer's disease process originates in entorhinal cortex neurones due to the enhancement of their normally high content of beta APP during age-related resprouting.

Adult↗
PubMed1993

Synaptic degeneration is the primary neuropathological feature in prion disease: a preliminary study.

The range of neuropathology found in cases of prion disease is considerable. The pathology present in dendrites and axons is associated with a marked loss of spines and synaptic contacts. It is probable that this loss underlies the functional and neurological deficits in the disease. Immunocytochemical re-examination of 2 cases of inherited disease with a 144 bp prion gene insertion with no characteristic pathology (i.e. spongiform change, astrocytosis and gliosis), together with 3 typical cases of prion disease (CJD), with antibodies to synaptophysin and synaptic protein demonstrated the presence of synaptic "plaque-like" lesions throughout the temporal cortex and cerebellum. In addition, examining the tissue by image analysis demonstrated a greater than 30% reduction in the relative synaptic index in all the prior disease cases when compared with controls. Synaptic disorganization and/or loss is a fundamental and constant feature of prion disease, irrespective of the presence or absence of spongiform change, neuronal loss and severe gliosis. Assessment of the extent and location of synaptic deficits might produce a more accurate documentation of the degree of neuronal disorganisation occurring during the course of prion disease.

Adult↗
PubMed1993

An in vivo assessment of the tobramycin/ticarcillin interaction in cystic fibrosis patients.

A non-blinded, randomized, cross-over investigation of the pharmacokinetic interaction between tobramycin and ticarcillin was performed in 18 healthy cystic fibrosis (CF) patients with normal renal function. On consecutive mornings the patients were given either tobramycin intravenously (i.v.) over 3-5 min (TOB phase), or tobramycin i.v. over 3-5 min followed immediately by ticarcillin infused i.v. over 20-30 min (TOB+TIC phase). Capillary blood samples were taken 30 min and 330 min after administration of the tobramycin dose in each phase. Tobramycin was measured in serum by fluorescence polarization immunoassay (TDx). There were decreases in serum tobramycin concentrations of 11% at 30 min (P < 0.001) and 330 min (P = 0.012) when measured in the presence of ticarcillin. No difference in elimination half-life was found (TOB phase 95 +/- 13 min, TOB+TIC phase 95 +/- 13 min, P = 0.86). The volume of distribution and clearance of tobramycin increased by 14% (P < 0.001) and 13% (P < 0.001), respectively, in the presence of ticarcillin. This interaction appears to be of minor clinical importance but pharmacokinetic studies of tobramycin should exclude concurrent use of ticarcillin.

Adolescent↗