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Biomedical subjects

N Roberts

Publications and source records attributed to N Roberts.

At least 37 records · Page 2Linked to original sources
PubMed2001

A proton magnetic resonance spectroscopy study of age-related changes in frontal lobe metabolite concentrations.

Ageing is associated with reduction of grey matter volume and it is reported that the frontal lobes are preferentially affected. We have applied quantitative magnetic resonance spectroscopy (MRS), incorporating measurement of brain tissue water content and metabolite T(2) relaxation times, to determine absolute concentrations of the putative neuronal marker N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) compounds in the frontal lobe of 50 male subjects aged between 20 and 70 years (10 per decade). The fractional brain water content (beta(MR)) did not change significantly as a function of age (r = 0.07, P = 0.65) and had a mean value of 81% (CV = 2%). The concentration (in millimoles per litre brain tissue) of NAA decreased significantly with age (r = -0.42, P = 0.003), with an overall decrease of 12% between the third and seventh decades. The concentrations of Cr and Cho did not change significantly with age. The interpretation of the age-dependent decrease in NAA concentration as reflecting either a reduction in neuronal volume, number or function is discussed.

Adult↗
PubMed2000

Failure of cidofovir therapy in progressive multifocal leukoencephalopathy unrelated to human immunodeficiency virus.

We describe the first reported human immunodeficiency virus (HIV)-seronegative patient treated with cidofovir for progressive multifocal leukoencephalopathy (PML). Marked clinical and radiological progression of PML occurred during cidofovir therapy. The improvement observed during cidofovir therapy of HIV-infected patients may be due to the effect of concomitant antiretroviral therapy rather than cidofovir.

Anti-HIV Agents↗
PubMed2000

Convergent neuroanatomical and behavioural evidence of an amygdala hypothesis of autism.

In this study we report a convergence of behavioural and neuroanatomical evidence in support of an amygdala hypothesis of autism. We find that people with high-functioning autism (HFA) show neuropsychological profiles characteristic of the effects of amygdala damage, in particular selective impairment in the recognition of facial expressions of fear, perception of eye-gaze direction, and recognition memory for faces. Using quantitative magnetic resonance (MR) image analysis techniques, we find that the same individuals also show abnormalities of medial temporal lobe (MTL) brain structure, notably bilaterally enlarged amygdala volumes. These results combine to suggest that developmental malformation of the amygdala may underlie the social-cognitive impairments characteristic of HFA. This malformation may reflect incomplete neuronal pruning in early development.

Adolescent↗
PubMed2000

Quantitative analysis of gene amplification in insecticide-resistant Culex mosquitoes.

The amplification of carboxylesterase structural genes followed by their overexpression is the most common mechanism of resistance to organophosphorus insecticides in Culex mosquitoes. Most resistant Culex quinquefasciatus mosquitoes have co-amplified estalpha2(1) and estbeta2(1) genes. Recently, Southern, DNA dot-blot analysis and phosphorimaging technology were used to quantify the est gene copy number in aphids and mosquitoes. Although more accurate than autoradiography, this method relies on probe hybridization, which can be variable. We have directly measured gene and mRNA copy number by using real-time quantitative PCRs in mosquitoes. The acquisition of fluorescence from incorporation of the double-strand-specific dye SYBR GreenI into a PCR product once per cycle is used to provide an absolute quantification of the initial template copy number. Thus it has been possible to show that estalpha2(1) and estbeta2(1) are co-amplified approx. 80-fold in the genome of the resistant PelRR strain of C. quinquefasciatus. The two genes, although co-amplified in a 1:1 ratio, are differentially transcribed: the estbeta2(1) gene from this amplicon has greater transcription than estalpha2(1) in all individual mosquito larvae tested, with an average ratio of 10:1. Purified esterases from mosquito homogenates were found in a ratio of 3:1, which, combined with the quantitative mRNA data, suggests the operation of both transcriptional and translational control mechanisms to regulate the expression of the amplified genes in C. quinquefasciatus insecticide-resistant mosquitoes.

Animals↗
PubMed2000

Postprandial decrease in splenic volume demonstrated by magnetic resonance imaging and stereology.

The aim of this study was to determine if the volume of the spleen changes after food intake. We applied an unbiased and efficient method for splenic volume estimation using magnetic resonance imaging (MRI) in combination with modern design stereology. MR images of the spleen were obtained for 10 healthy volunteers (five men and five women; mean age 28.9 years [range 23-35 years]) without a history of splenomegaly. The initial scans were performed in the morning after overnight fasting. Each volunteer then consumed a standard balanced meal weighing 500 g [2,460 kJ (627 kcal) energy] with 500 ml of still mineral water. Second identical MR scans were performed approximately 1 hr later. Postprandially, splenic volume decreased by an average of 6.6% (P = 0.005), probably due to increased splanchnic blood flow after food intake.

Adult↗
PubMed2000

Estimation of body composition in muscular dystrophy by MRI and stereology.

We have applied the Cavalieri method of modern design stereology with magnetic resonance imaging for estimating the volume of whole-body muscle and fat compartments in four patients with muscular dystrophy, a patient with myopathy, five controls, an anorexic subject, and a body builder. Detailed systematic series (ie, 50) of axial MR images (T1-weighted, TR/TE 400/10 msec) were obtained throughout the whole body of each subject. The results showed that 15, 20, and 35 axial sections through the body are sufficient to secure coefficients of error (CEs) on the estimates of total muscle and fat volume of around 10%, 5%, and 3% respectively in muscular dystrophy patients and controls. The mean normalized volumes of muscle in four muscular dystrophy patients were decreased by 27% (t-test: P < 0.05), and those of total fat were increased by 12% (t-test: P > 0.05) relative to controls. The Cavalieri method provides a direct, efficient, and mathematically unbiased approach for studying human body compartments and may have application in assessing treatment efficacy in patients with muscular dystrophy. J. Magn. Reson. Imaging 2000;12:467-475.

Adipose Tissue↗
PubMed2000

A comparison of egocentric and allocentric spatial memory in a patient with selective hippocampal damage.

The spatial memory of a single patient (YR) was investigated. This patient, who had relatively selective bilateral hippocampal damage, showed the pattern of impaired recall but preserved item recognition on standardised memory tests that has been suggested by Aggleton and Shaw [Aggleton JP, Shaw C. Amnesia and recognition memory: a reanalysis of psychometric data. Neuropsychologia 1996;34:51-62] to be a consequence of Papez circuit lesions. YR was tested on three recall tests and one recognition test for visuospatial information. The initial recall test assessed visuospatial memory over very short unfilled delays and YR was not significantly impaired. This test was then modified to test recall of allocentric and egocentric spatial information separately after filled delays of between 5 and 60 s. YR was found to be more impaired at recalling allocentric than egocentric information after a 60 s interval with a tendency for the impairment to increase up to this delay. Recognition of allocentric spatial information was also assessed after delays of 5 and 60 s. YR was impaired after the 60 s delay. The results suggest that the human hippocampus has a greater involvement in allocentric than egocentric spatial memory, and that this most likely concerns the consolidation of allocentric information into long-term memory rather than the initial encoding of allocentric spatial information. The findings also suggest that YR's item recognition/free recall deficit pattern reflects a problem retrieving or storing certain kinds of associative information.

Brain Mapping↗
PubMed2000

The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses.

In 1997, an H5N1 avian influenza A/Hong Kong/156/97 virus transmitted directly to humans and killed six of the 18 people infected. In 1999, another avian A/Hong/1074/99 (H9N2) virus caused influenza in two children. In such cases in which vaccines are unavailable, antiviral drugs are crucial for prophylaxis and therapy. Here we demonstrate the efficacy of the neuraminidase inhibitor GS4104 (oseltamivir phosphate) against these H5N1 and H9N2 viruses. GS4071 (the active metabolite of oseltamivir) inhibited viral replication in MDCK cells (EC(50) values, 7.5-12 microM) and neuraminidase activity (IC(50) values, 7.0-15 nM). When orally administered at doses of 1 and 10 mg/kg per day, GS4104 prevented death of mice infected with A/Hong Kong/156/97 (H5N1), mouse-adapted A/Quail/Hong Kong/G1/97 (H9N2), or human A/Hong Kong/1074/99 (H9N2) viruses and reduced virus titers in the lungs and prevented the spread of virus to the brain of mice infected with A/Hong Kong/156/97 (H5N1) and mouse-adapted A/Quail/Hong Kong/G1/97 (H9N2) viruses. When therapy was delayed until 36 h after exposure to the H5N1 virus, GS4104 was still effective and significantly increased the number of survivors as compared with control. Oral administration of GS4104 (0.1 mg/kg per day) in combination with rimantadine (1 mg/kg per day) reduced the number of deaths of mice infected with 100 MLD(50) of H9N2 virus and prevented the deaths of mice infected with 5 MLD(50) of virus. Thus, GS4104 is efficacious in treating infections caused by H5N1 and H9N2 influenza viruses in mice.

Acetamides↗
PubMed2000

Quantitative magnetic resonance imaging in consecutive patients evaluated for surgical treatment of temporal lobe epilepsy.

We present the results of quantitative Magnetic Resonance Imaging (MRI) in 55 consecutively referred patients with clinical evidence of temporal lobe epilepsy (TLE). The Cavalieri method was used in combination with point counting to provide unbiased estimates of the volume of the left and right hippocampus, amygdala, temporal lobe, lateral ventricles and cerebral hemisphere, and pixel by pixel maps of the T2 relaxation time were computed for both central and anterior sections of the hippocampus. The 99th centiles of hippocampal volume, hippocampal volume asymmetry and T2 relaxation times in 20 control subjects provided limits which identified the presence of MTS. The results of the quantitative MRI were compared with the results of conventional diagnostic MRI, foramen ovale (FO) recording and the WADA test. Thirty-one patients were found to have unilateral MTS (17 left and 14 right) and 7 bilateral MTS. No evidence of MTS was detected in 16 patients. Of the 31 patients diagnosed with unilateral MTS on the basis of hippocampal volume and T2 measurement, 74% and 77% would respectively have received the same diagnosis on the basis of hippocampal volume and T2 measurements alone. In comparison to FO recording, quantitative MRI has a sensitivity of 55% and a specificity of 86%, while conventional diagnostic MRI has a sensitivity of 42% and a specificity of 80% for detection of MTS. Unilateral abnormalities were detected by FO recording in 30% cent of patients who appeared normal on quantitative MRI. WADA test results were available for 40 patients. The findings were consistent with quantitative MRI showing reduced memory function ipsilateral to unilateral MTS in 18 patients, but reduced memory function contralateral to unilateral MTS in two patients, and reduced memory function without MR abnormality in seven patients. WADA testing revealed unilateral memory impairments where MRI found bilateral pathology in 4 patients and in 4 patients in whom quantitative MRI detected unilateral MTS there was no evidence of reduced memory during WADA testing of the corresponding cerebral hemisphere. In the patients with unilateral right MTS a highly significant negative correlation (p = 0.0003) was observed between age of onset and the volume of the contralateral temporal lobe. Quantitative MR imaging of the hippocampus (i.e. volume and T2 measurement) is preferable to conventional radiological reporting for providing objective evidence of the presence of MTS on which to base the referral of patients for surgery, and since it has associated morbidity FO recording is now only being used in selected patients. Furthermore, stereology provides a convenient method for estimating the volume of other brain structures, which is relevant to obtaining a better understanding of the effects of laterality and age of onset of TLE.

Adolescent↗
PubMed2000

Automatic measurement of changes in brain volume on consecutive 3D MR images by segmentation propagation.

This article presents a technique to automatically measure changes in the volume of a structure of interest in successive 3D magnetic resonance (MR) images and its application in the study of the brain and lateral cerebral ventricles. The only manual step is a segmentation of the structure of interest in the first image. The analysis comprises, first, precise rigid co-registration of the time series of images; second, computation of residual deformations between pairs of images; third, automatic quantification of the volume change, obtained by propagation of the segmentation of the structure of interest through the series of MR images. This approach has been applied to monitor changes in the volume of the brain and lateral cerebral ventricles in a healthy subject and a patient with primary progressive aphasia (PPA). Results are consistent with those obtained by application of the boundary shift integral (BSI) and by stereology in the same subjects.

Aged↗
PubMed2000

Statistical analysis of normal and abnormal dissymmetry in volumetric medical images.

We present a general method to study the dissymmetry of anatomical structures such as those found in the human brain. Our method relies on the estimate of 3D dissymmetry fields, the use of 3D vector field operators, and T2 statistics to compute significance maps. We also present a fully automated implementation of this method which relies mainly on the intensive use of a 3D non-rigid inter-patient matching tool. Such a tool is applied successively between the images and their symmetric versions with respect to an arbitrary plane, both to realign the images with respect to the mid-plane of the subject and to compute a dense 3D dissymmetry map. Inter-patient matching is also used to fuse the data of a population of subjects. We then describe three main application fields: the study of the normal dissymmetry within a given population, the comparison of the dissymmetry between two populations, and the detection of the significant abnormal dissymmetries of a patient with respect to a reference population. Finally, we present preliminary results illustrating these three applications for the case of the human brain.

Aphasia↗
PubMed2000

Short-term ventricular volume changes on serial MRI in multiple sclerosis.

Axonal loss is likely to be an important component of atrophy and the pathological substrate for the fixed disability of MS. To estimate the rate of central white matter reduction we investigated ventricular volume change and disease activity on monthly MRI in 19 patients over 6 months. At baseline, ventricular volumes were largest in primary progressive MS and smallest in relapsing-remitting MS. Over the study period ventricular volumes increased overall by 0.2% (F= 2.75, P = 0.02), but the percentage changes in relapsing-remitting MS were much larger (median increase 14.9%). Lesion volumes were also highest at baseline in relapsing-remitting MS, but serial changes in ventricular volumes were not correlated with serial changes in lesions. This study shows that ventricular enlargement in MS may occur over short epochs, particularly in relapsing-remitting cases. However, the loss of central white matter volume observed in any brief period may be related to inflammatory activity that occurred in a preceding or earlier epoch, a delayed post-inflammatory degenerative process, or most likely, a combination of both.

Adult↗
PubMed2000

A comparison in normal individuals and sickle cell patients of reduced glutathione precursors and their transport between plasma and red cells.

INTRODUCTION: Reduced glutathione is an important antioxidant in red cells whose depletion may contribute to the pathophysiology of sickle cell disease. The current study was designed to examine the availability of reduced glutathione precursors (glutamate, cysteine, glycine and possibly glutamine) together with the activity of the main transport pathways for their uptake (system ASC for cysteine and glycine; system gly for glycine). MATERIALS AND METHODS: Blood samples were obtained from normal (HbAA, HbA cells) and sickle cell disease patients (HbSS, HbS cells); amino acids were measured by HPLC; and transporter activity was measured by radioactive tracer fluxes (using serine and glycine for activity of system ASC; and glycine for that of system gly). RESULTS: Plasma concentrations of cysteine and glycine were increased and concentrations of all amino acids were elevated in HbS cells. The activity of system ASC was increased in HbS cells (both transport capacity and affinity were elevated for serine transport; transport capacity only for glycine). Activity of system gly was also increased (twofold increase in V(max) for glycine flux), though not significantly. Oxygenation also increased the activity of both transporters in normal and HbS cells. CO prevented deoxy-inhibition of glycine transport. Staurosporine (5 microM) inhibited O(2)-stimulated glycine transport through system ASC. It also inhibited the absolute magnitude of transport through system gly, but the O(2)-dependent flux was unaffected. CONCLUSION: Low reduced glutathione levels in HbS cells were not due to decreased substrate availability and O(2) stimulated transport of reduced glutathione precursors in both normal and HbS cells, through a mechanism that is likely to involve Hb and possibly protein phosphorylation.

Adult↗
PubMed2000

Single nucleotide polymorphisms in an intron of the ovine calpastatin gene.

Calpastatin is the specific inhibitor of the ubiquitous calcium-dependent proteases mu-calpain and m-calpain. Enzyme assay data from sheep and cattle inversely correlates post-mortem muscle calpastatin levels with ultimate meat tenderness. Genetic markers of meat quality may therefore be found linked to the calpastatin gene (CAST). A three-allele system detected by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) has been observed in the ovine CAST. The three allele amplimers have been fully nucleotide sequenced and their differences in terms of single nucleotide polymorphism (SNPs) in the intron region of the amplimer are reported and compared to a consensus sequence of the orthologous region of the cattle CAST. A PCR-RFLP for more rapid CAST genotyping of all three ovine alleles was also developed.

Alleles↗
PubMed2000

The benefit of stereology for quantitative radiology.

A knowledge of stereology (i.e. proper sampling), the opportunities provided by computers for image analysis (i.e. image segmentation, image registration, data base exploration, 3D reconstruction), and the strengths (i.e. non-invasive) and limitations (i.e. finite resolution, image artefacts) of medical imaging equipment must all be combined for reliable quantitative magnetic resonance imaging (MRI), the goal of which is to obtain a deeper understanding of the structure, function, life cycle and evolution of the human body, especially the brain, and a more objective diagnosis of disease and assessment of its response to treatment. In this article we illustrate the first of these requirements. We describe the application of proper sampling strategies and efficient computer-based counting procedures for obtaining unbiased estimates of volume by the Cavalieri method and of surface area from vertical sections. In particular, we estimate the volume of a brain tumour from Cavalieri sections, the volume of grey matter in the cerebral hemispheres from Cavalieri slices and the surface area of the cerebral cortex from vertical sections. The estimates obtained are mathematically unbiased. In each case, we assess the precision of the estimates empirically. Application of formulae available for predicting the precision of volume estimates obtained using the Cavalieri sections and slices methods is also described.

Algorithms↗