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Biomedical subjects

A Parker

Publications and source records attributed to A Parker.

At least 19 recordsLinked to original sources
PubMed1998

Pathogenic mechanisms in the rheumatoid nodule: comparison of proinflammatory cytokine production and cell adhesion molecule expression in rheumatoid nodules and synovial membranes from the same patient.

OBJECTIVE: To investigate the production of proinflammatory cytokines and expression of cell adhesion molecules in the rheumatoid nodule. METHODS: Cytokine content (tumor necrosis factor alpha [TNFalpha], interleukin-1beta [IL-1beta], and IL-1 receptor antagonist [IL-1Ra]), at the messenger RNA (mRNA) and protein levels, and cell adhesion molecule expression were studied in 16 rheumatoid nodules and 6 synovial membranes. RESULTS: Macrophages in the rheumatoid nodules contained TNFalpha, IL-1beta, and IL-1Ra mRNA and protein, particularly in perivascular cells of the stroma and in the palisading layer. All cell adhesion molecules studied were expressed in both the rheumatoid nodules and synovial membranes, with increased expression of E-selectin in the rheumatoid nodule compared with the synovial membrane, and with the absence of vascular cell adhesion molecule 1 expression on cells of the palisading layer in the rheumatoid nodule. CONCLUSION: The presence of similar proinflammatory cytokines and cell adhesion molecules in the rheumatoid nodule and synovial membrane suggests that similar pathogenic processes result in the chronic inflammation and tissue destruction in these lesions.

Adult↗
PubMed1998

Memory after frontal/temporal disconnection in monkeys: conditional and non-conditional tasks, unilateral and bilateral frontal lesions.

Seven Cynomolgus monkeys (Macaca fascicularis) learned a series of reward-visual conditional discrimination problems, in which the arrival or non-arrival of a food pellet at the beginning of each trial acted as an instruction cue, signalling which of two visually distinct stimulus objects the animal should choose on that trial in order to obtain a further food pellet reward. Following surgical removal of the ventrolateral prefrontal cortex in one hemisphere and the inferior temporal cortex in the contralateral hemisphere, combined with forebrain commissurotomy, the four operated animals were severely impaired at relearning this task. They were not impaired, however, in non-conditional visual discrimination learning. Extending the unilateral frontal lesion to include the ventromedial prefrontal cortex had no detrimental effect, nor did complete unilateral removal of the frontal cortex. In a third experiment, the operated animals underwent a further surgery to remove either ventrolateral, ventral or complete frontal cortex similar to that in the opposite hemisphere. Compared to their previous level of performance, the animals with bilateral ventrolateral prefrontal lesions were now mildly impaired and the animals with the bilateral lesion extended to the ventromedial cortex more severely impaired on the non-conditional visual discrimination task. The bilaterally lobectomized animals were unable to relearn the task. We suggest that behaviour in visual learning tasks is controlled by cortical convergence upon subcortical structures, possibly by striatal efferents from both the visual cortex and frontal cortex, and that intrahemispheric convergence of these two efferents within the corpus striatum of one hemisphere could allow detailed control of visual choices by non-visual information, while subcortical interhemispheric transfer allows only less detailed, more general control.

Animals↗
PubMed1998

Lesions of the primate rhinal cortex cause deficits in flavour-visual associative memory.

Three Cynomolgus monkeys (Macaca fascicularis) learned a flavour-visual conditional discrimination problem, in which one of two possible food items was presented at the beginning of each trial, and acted as an instruction cue to signal which of two visually distinct stimulus objects the animal must displace on that trial in order to obtain a further food reward. The task was learned first in light then in dark conditions. Following rhinal cortex ablation the animals were unable to use the flavour properties of the food items to guide visual choices, performing at close to chance levels. Postoperative performance on a food preference test showed that their problem in associating a flavour cue with a visual object in the conditional learning task also extended to aberrant choice of foods based on their visual appearance.

Animals↗
PubMed1998

Intensive care services; a crisis of increasing expressed demand.

Critical care services appear to face increasing demand. To attempt to identify factors which may predispose to such increases in demand, the patients and their treatment were reviewed. The patients' ages, referring specialty and their risk of hospital mortality were recorded on admission. The durations of respiratory and renal support (if required) were recorded. Pulmonary artery catheter insertion and the number of vasoactive drugs infused were also noted. During the study, the capacity of the intensive care unit was initially increased by one bed (from six to seven) and later by a six-bedded high-dependency unit. This capacity increase was not matched by a proportionate decrease in occupancy. The patients' mean ages increased by 1 year per year. The number of patients referred from general surgery consistently increased. The proportion of patients receiving vasoactive drugs and pulmonary artery catheters declined as did the duration of respiratory and renal support.

Adult↗
PubMed1998

Interaction of frontal and perirhinal cortices in visual object recognition memory in monkeys.

Monkeys were trained preoperatively in visual object recognition memory. The task was delayed matching-to-sample with lists of trial-unique randomly generated visual stimuli in an automated apparatus, and the stimuli were 2D visual objects made from randomly generated coloured shapes. We then examined the effect of either: (i) disconnecting the frontal cortex in one hemisphere from the perirhinal cortex in the contralateral hemisphere by crossed unilateral ablations; (ii) disconnecting the magnocellular portion of the mediodorsal (MDmc) thalamic nucleus in one hemisphere from the perirhinal cortex in the contralateral hemisphere; or (iii) bilaterally ablating first the amygdala, then adding fornix transection, then finally perirhinal cortex ablation. We found that both frontal/perirhinal and MDmc/perirhinal disconnection had a large effect on visual object recognition memory, whereas both amygdalectomy and the addition of fornix transection had only a mild effect. We conclude that the frontal lobe needs to interact with the perirhinal cortex within the same hemisphere for visual object recognition memory, but that routes through the amygdala and hippocampus are not of primary importance.

Amygdala↗
PubMed1998

Quantitation of left ventricular volumes and ejection fraction in post-infarction patients from biplane and single plane two-dimensional echocardiograms. A prospective longitudinal study of 371 patients.

AIMS: To determine whether left ventricular volumes and ejection fractions calculated from single plane two-dimensional echocardiograms using the algorithm (0.85A2L) correlate with those calculated using the biplane Simpson's method, and whether small changes in volumes and ejection fraction occurring post-infarction could be detected from single-plane as well as from biplane two-dimensional echocardiograms. METHODS AND RESULTS: Serial two-dimensional echocardiograms were obtained in 371 patients from the DEFIANT II trial a mean of 2 days, 1 week and 6 months post-infarction. Single plane volumes from the apical four chamber and apical long axis correlated closely with biplane Simpson's left ventricular volumes. Both single-plane left ventricular volumes significantly over-estimated biplane Simpson's volumes. Biplane Simpson's ejection fractions were consistently slightly under-estimated from the single-plane images. Differences between biplane Simpson's and single-plane volumes increased independently with increasing left ventricular size and distortion. The small changes in left ventricular volumes and ejection fraction over time were as reliably detected from single plane as from biplane images. CONCLUSION: Single-plane left ventricular volumes over-estimate biplane Simpson's volumes and under-estimate ejection fraction, and these discrepancies are amplified in dilated hearts with abnormal shape.

Adult↗
PubMed1998

Binding of insulin-like growth factor (IGF)-binding protein-5 to smooth-muscle cell extracellular matrix is a major determinant of the cellular response to IGF-I.

Insulin-like growth factor-binding protein-5 (IGFBP-5) has been shown to bind to fibroblast extracellular matrix (ECM). Extracellular matrix binding of IGFBP-5 leads to a decrease in its affinity for insulin-like growth factor-I (IGF-I), which allows IGF-I to better equilibrate with IGF receptors. When the amount of IGFBP-5 that is bound to ECM is increased by exogenous addition, IGF-I's effect on fibroblast growth is enhanced. In this study we identified the specific basic residues in IGFBP-5 that mediate its binding to porcine smooth-muscle cell (pSMC) ECM. An IGFBP-5 mutant containing alterations of basic residues at positions 211, 214, 217, and 218 had the greatest reduction in ECM binding, although three other mutants, R214A, R207A/K211N, and K202A/R206N/R207A, also had major decreases. In contrast, three other mutants, R201A/K202N/R206N/R208A, and K217N/R218A and K211N, had only minimal reductions in ECM binding. This suggested that residues R207 and R214 were the most important for binding, whereas alterations in K211 and R218, which align near them, had minimal effects. To determine the effect of a reduction in ECM binding on the cellular replication response to IGF-I, pSMCs were transfected with the mutant cDNAs that encoded the forms of IGFBPs with the greatest changes in ECM binding. The ECM content of IGFBP-5 from cultures expressing the K211N, R214A, R217A/R218A, and K202A/R206N/R207A mutants was reduced by 79.6 and 71.7%, respectively, compared with cells expressing the wild-type protein. In contrast, abundance of the R201A/K202N/R206N/R208A mutant was reduced by only 14%. Cells expressing the two mutants with reduced ECM binding had decreased DNA synthesis responses to IGF-I, but the cells expressing the R201A/K202N/R206N/R208A mutant responded well to IGF-I. The findings suggest that specific basic amino acids at positions 207 and 214 mediate the binding of IGFBP-5 to pSMC/ECM. Smooth-muscle cells that constitutively express the mutants that bind weakly to ECM are less responsive to IGF-I, suggesting that ECM binding of IGFBP-5 is an important variable that determines cellular responsiveness.

Animals↗
PubMed1998

Synovial mast cell responses during clinical improvement in early rheumatoid arthritis.

OBJECTIVES: To determine the synovial mast cell response in early rheumatoid arthritis (RA) during clinical improvement, and to examine for relations with clinical and histological parameters of disease activity. METHODS: Twenty two synovial samples were obtained from six patients with RA using needle arthroscopy. The mean disease duration at baseline was eight months, and two to three further samples were obtained over a mean follow up period of 15 months during which treatment initiated clinical improvement occurred. Sections were immunostained to detect MCT and MCTC mast cells and correlations were sought between clinical and histological data. RESULTS: The overall mean synovial mast cell density was 40.3 cells/mm2, with regional densities of 60.6 and 34.2 mast cells/mm2 in the superficial and deeper synovial layers respectively. The MCT subset predominated, outnumbering MCTC by 3:1. There was a significant correlation between the histological inflammation index and the MCT density, (r = 0.4, p < 0.05) but not the MCTC subset. The regional distribution and predominant subset of mast cells varied in individual patient's synovia over time, with a trend towards restriction of the mast cell response to the superficial synovium during clinical improvement. CONCLUSIONS: The mast cell response in early RA is characterised by substantial expansion of predominantly MCT mast cells that correlates with histological indices of inflammation. During clinical improvement, this expansion tended to become more superficial. Taken together with previous studies of long duration RA, which implicate MCTC cells in synovial damage and disease progression, these results suggest that MCT and MCTC mast cells may possess distinct functions in the spectrum of inflammatory events occurring during RA.

Arthritis, Rheumatoid↗
PubMed1998

The Von Restorff effect in visual object recognition memory in humans and monkeys. The role of frontal/perirhinal interaction.

This study reports the development of a new, modified delayed matching to sample (DMS) visual recognition memory task that controls the relative novelty of test stimuli and can be used in human and nonhuman primates. We report findings from normal humans and unoperated monkeys, as well as three groups of operated monkeys. In the study phase of this modified paradigm, subjects studied lists of two-dimensional visual object stimuli. In the test phase each studied object was presented again, now paired with a new stimulus (a foil), and the subject had to choose the studied item. In some lists one study item (the novel or isolate item) and its associated foil differed from the others (the homogenous items) along one stimulus dimension (color). The critical experimental measure was the comparison of the visual object recognition error rates for isolate and homogenous test items. This task was initially administered to human subjects and unoperated monkeys. Error rates for both groups were reliably lower for isolate than for homogenous stimuli in the same list position (the von Restorff effect). The task was then administered to three groups of monkeys who had selective brain lesions. Monkeys with bilateral lesions of the amygdata and fornix, two structures that have been proposed to play a role in novelty and memory encoding, were similar to normal monkeys in their performance on this task. Two further groups--with disconnection lesions of the perirhinal cortex and either the prefrontal cortex or the magnocellular mediodorsal thalamus--showed no evidence of a von Restorff effect. These findings are not consistent with previous proposals that the hippocampus and amygdala constitute a general novelty processing network. Instead, the results support an interaction between the perirhinal and frontal cortices in the processing of certain kinds of novel information that support visual object recognition memory.

Adolescent↗
PubMed1998

Theoretical and empirical scaling patterns and topological homology in bone trabeculae.

Trabecular or cancellous bone is a major element in the structural design of the vertebrate skeleton, but has received little attention from the perspective of the biology of scale. In this study, we investigated scaling patterns in the discrete bony elements of cancellous bone. First, we constructed two theoretical models, representative of the two extremes of realistic patterns of trabecular size changes associated with body size changes. In one, constant trabecular size (CTS), increases in cancellous bone volume with size arise through the addition of new elements of constant size. In the other model, constant trabecular geometry (CTG), the size of trabeculae increases isometrically. These models produce fundamentally different patterns of surface area and volume scaling. We then compared the models with empirical observations of scaling of trabecular dimensions in mammals ranging in mass from 4 to 40x10(6)g. Trabecular size showed little dependence on body size, approaching one of our theoretical models (CTS). This result suggests that some elements of trabecular architecture may be driven by the requirements of maintaining adequate surface area for calcium homeostasis. Additionally, we found two key consequences of this strongly negative allometry. First, the connectivity among trabecular elements is qualitatively different for small versus large animals; trabeculae connect primarily to cortical bone in very small animals and primarily to other trabeculae in larger animals. Second, small animals have very few trabeculae and, as a consequence, we were able to identify particular elements with a consistent position across individuals and, for some elements, across species. Finally, in order to infer the possible influence of gross differences in mechanical loading on trabecular size, we sampled trabecular dimensions extensively within Chiroptera and compared their trabecular dimensions with those of non-volant mammals. We found no systematic differences in trabecular size or scaling patterns related to locomotor mode.

Animals↗
PubMed1997

Effects of pulse methylprednisolone on inflammatory mediators in peripheral blood, synovial fluid, and synovial membrane in rheumatoid arthritis.

OBJECTIVE: To establish whether the clinical efficacy of pulse methylprednisolone (MP; 1,000 mg intravenously) is related to the modulation of proinflammatory cytokines within the peripheral blood, synovial membrane, or synovial fluid compartments. METHODS: Eighteen patients with active rheumatoid arthritis (RA) were studied. Peripheral blood (11 patients) and knee synovial fluid (9 patients, 10 knees) were obtained before and at 4 and 24 hours after MP therapy. Interleukin-1beta (IL-1beta), IL-8, and tumor necrosis factor alpha (TNFalpha) were measured by enzyme-linked immunosorbent assay and biologic assays; prostaglandin E2 (PGE2) was measured by competitive radioimmunoassay. In 10 patients, arthroscopically directed synovial biopsies were obtained before and at 24 hours after treatment, at disease relapse (4 patients), and after retreatment (1 patient). Membranes were stained by immunohistochemical techniques with monoclonal antibodies against TNFalpha, IL-8, IL-1beta, and the IL-1 receptor antagonist protein (IL-1Ra). RESULTS: MP therapy was associated with a rapid (within 24 hours) and substantial decrease in the expression of TNFalpha in the lining and sublining regions of the synovial membrane, as well as substantial decreases in the levels of TNFalpha in serum and synovial fluid. There was also reduced IL-8 expression in the synovial lining, as well as reduced synovial fluid IL-8 levels. No effect on synovial membrane IL-1beta and IL-1Ra or synovial fluid IL-1beta and PGE2 was found. CONCLUSION: MP therapy rapidly reduces IL-8 and TNFalpha levels in the synovial compartment, with cytokine changes in the serum and synovial fluid reflecting the changes in the synovial membrane. Alterations in TNFalpha expression in the synovial membrane correlated with clinical response to, and subsequent relapse after, MP therapy.

Aged↗
PubMed1997

Evolution of the mitochondrial DNA control region in the mbuna (Cichlidae) species flock of Lake Malawi, East Africa.

Considerable controversy has surrounded the application of mitochondrial DNA data to reconstruction of evolutionary relationships among the endemic cichlids of Lake Malawi. Central to this debate has been the issue of whether lineage sorting is complete, and thus whether these data actually reflect species phylogeny, or simply gene genealogy. Review of all mtDNA control region sequences available for members of one monophyletic subset of this species flock, the Malawi rockfishes, or mbuna, strongly indicates that lineage sorting is incomplete: Character-based analyses of these sequences reconstruct gene, not species, interrelationships. Analysis of the pattern of nucleotide substitutions differentiating these mtDNA alleles suggests that pyrimidine residues undergo transition substitutions more often than do purines. Estimation of the magnitude of derived sequence differentiation in light of the reconstructed gene genealogy suggests that the mbuna may be of considerably more recent vintage than previous molecular characterizations have indicated.

Africa↗
PubMed1997

The effect of anterior thalamic and cingulate cortex lesions on object-in-place memory in monkeys.

Six Macaque monkeys (Macaca mulatta) were trained in an object-in-place memory task, designed to capture the 'whole scene' nature of episodic memory. In this task the correct, rewarded, response in each scene was to a particular object of a pair, which always occupied a particular position in a unique background which had been generated using randomly chosen colours and shapes. In each session, the monkey learned a new list of these unique scenes. The animals then underwent surgical ablation of either the anterior thalamic nuclei or the cingulate cortex. It was found that the animals with anterior thalamic lesions showed a substantial impairment, whereas the monkeys with cingulate cortex ablations were not significantly impaired at the task. These results confirm the importance of the anterior thalamic nuclei in episodic memory, and suggest that the cingulate gyrus is not a region which is crucial in the type of episodic memory task used in the present experiment.

Animals↗