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Biomedical subjects

A Richardson

Publications and source records attributed to A Richardson.

At least 163 records · Page 9Linked to original sources
PubMed1995

The age-related decline in the induction of IL-2 transcription is correlated to changes in the transcription factor NFAT.

The effect of aging on the induction of IL-2 transcription by concanavalin A was studied in spleen lymphocytes isolated from young (4-6 months) and old (24 months) male Fischer 344 rats. The induction of IL-2 mRNA levels and IL-2 transcription were 40 to 50% lower for spleen lymphocytes isolated from old rats compared to spleen lymphocytes isolated from young rats. Because the transcription factor NFAT (nuclear factor activating IL-2 transcription) plays a major role in the regulation of IL-2 transcription, the DNA binding activity of NFAT in nuclear extracts of concanavalin A-stimulated lymphocytes was measured using a gel shift assay. The ability of nuclear extracts isolated from either total spleen lymphocytes or T cells to bind the NFAT oligonucleotide decreased 50 to 60% with age. Therefore, the age-related decrease in the expression of IL-2 appears to occur at the level of transcription and involves the transcription factor NFAT.

Aging↗
PubMed1995

Signal transduction through integrins: a central role for focal adhesion kinase?

The integrins are receptors for proteins of the extracellular matrix, both providing a physical link to the cytoskeleton and transducing signals from the extracellular matrix. Activation of integrins leads to tyrosine and serine phosphorylation of a number of proteins, elevation of cytosolic calcium levels, cytoplasmic alkalinization, changes in phospholipid metabolism and, ultimately, changes in gene expression. The recently discovered focal adhesion kinase localizes to focal contacts, which are sites of integrin clustering, and focal adhesion kinase can physically associate with integrins in vitro. As integrins lack intrinsic catalytic activity, focal adhesion kinase is a candidate for a signaling molecule that is recruited by integrins in order to trigger the generation of intracellular second messengers. Thus, focal adhesion kinase may play a central role in signal transduction through integrins.

Cell Adhesion↗
PubMed1995

The expression of heat shock protein 70 decreases with age in lymphocytes from rats and rhesus monkeys.

The ability of cells to express heat shock proteins in response to a stress such as heat is universal to all organisms and is believed to play a critical protective role. Therefore, it was of interest to determine the influence of aging on the ability of lymphocytes to express the heat shock protein hsp70 in response to a heat shock (42.5 degrees C for 1 h). Splenic lymphocytes isolated from old (24-26 months) rats showed a marked decrease in the induction of hsp70 protein levels or hsp70 synthesis when compared to lymphocytes isolated from young (4-5 months) rats. An age-related decrease in the induction of hsp70 levels by heat also was observed in peripheral lymphocytes isolated from rhesus monkeys. The decline with age in the induction of hsp70 by lymphocytes from rats was paralleled by a decrease in the induction of hsp70 mRNA and the nuclear transcription of hsp70. In addition, it was found that the ability of extracts from heat-shocked lymphocytes to bind the heat shock element (HSE) decreased approximately 50% with age. Therefore, it appears that the reduced ability of lymphocytes from old rats to express hsp70 in response to a heat shock occurs at the level of transcription because of an alteration in the ability of the heat shock transcription factor to bind the HSE on the promoter of the hsp70 gene. The age-related decrease in the induction of hsp70 appears to be physiologically important because the viability of spleen lymphocytes exposed to high temperatures decreases significantly with age.

Aging↗
PubMed1995

Contrast sensitivity and coherent motion detection measured at photopic luminance levels in dyslexics and controls.

Development dyslexics perform differently from controls on a number of low level visual tasks. We carried out three experiments to explore some of these differences. Dyslexics have been found to have reduced luminance contrast sensitivity at mesopic luminance levels. We failed to replicate this finding at photopic luminance levels. We also compared the (photopic) coherent motion detection thresholds of groups of child and adult dyslexics with those of age matched controls. Dyslexics were significantly less sensitive to motion. The results are discussed in relation to a recent suggestion that developmental dyslexia may be associated with a magnocellular visual deficit.

Adolescent↗
PubMed1995

Outcome prediction in open bite cases.

Some anterior open bites close spontaneously, others do not. It would be advantageous if the orthodontist had some means of predicting the spontaneous outcome in open bite patients. One-hundred-and-twenty-seven patients having open bite were recorded longitudinally for a minimum period of 3 years using cephalometric radiographs. The open bite closed spontaneously in 50 per cent of a prepuberal group aged between 7 and 10 years, in 49 per cent of a puberal group aged 11-14 years, and in 44 per cent of a post-puberal group aged between 14 and 21 years when first seen. Data from cephalometric analysis of the first film in each case was analysed using discriminant function analysis. The analysis correctly predicted the outcome in 88 per cent of the prepuberal group, in 74 per cent of the puberal group, and in 94 per cent of the post-puberal group. The accuracy of the prediction equation was checked in a new sample of 35 subjects with open bite observed over at least 2 years so that the spontaneous outcome was known. The equation correctly predicted the outcome in 79 per cent of prepuberal, in 80 per cent of puberal, and in 100 per cent of post-puberal patients in the second sample.

Adolescent↗
PubMed1995

Activities of antioxidant enzymes in various tissues of male Fischer 344 rats are altered by food restriction.

The objective of this study was to determine how food restriction (40% restriction of food intake) altered the age-related changes in the activities of Cu,Zn superoxide dismutase, catalase and glutathione peroxidase in liver, brain cortex, heart, kidney and intestinal mucosa obtained from 6-, 16- and 26-mo-old male Fischer 344 rats. Food restriction increased the activity of one or more of the antioxidant enzymes in the liver, brain cortex, heart and kidney of the rats. However, the magnitude of the effect and the antioxidant enzyme(s) affected by food restriction varied from tissue to tissue, and food restriction had no significant effect on the activities of these enzymes in intestinal mucosa. Interestingly, the four tissues in which food restriction increased the activity of one or more of the antioxidant enzymes showed reduced lipid peroxidation as measured by thiobarbituric acid-reactive material. These data suggest that food restriction might enhance the survival of rodents by altering the levels of the antioxidant enzymes and hence reducing free radical damage.

Aging↗
PubMed1995

Expression of heat shock genes in hepatocytes is affected by age and food restriction in rats.

The objective of this study was to determine how food restriction altered the age-related changes in the basal and heat-induced expression of heat shock genes (hsc70, grp78, and ubiquitin) by hepatocytes isolated from young (4 to 6 mo old) and old (26 to 28 mo old) male Fischer 344 rats. The basal levels of the mRNA transcripts for hsc70 and ubiquitin were similar for hepatocytes isolated from young and old rats fed with free access to the diet (control) or from rats fed a restricted diet (40% restriction of food intake). However, the induction of the mRNA transcripts for hsc70 and ubiquitin by a heat shock (42.5 degrees C for 30 min) was significantly higher for hepatocytes isolated from old rats fed the restricted diet compared with old rats fed with free access to the diet. The changes in hsc70 mRNA levels were paralleled by similar changes in hsc70 transcription by isolated nuclei; therefore, the greater induction of hsc70 expression by food restriction results from changes in the transcription of hsc70 gene. In contrast with hsc70 and ubiquitin, the basal levels of grp78 were reduced with age and by food restriction. Therefore, the effect of aging and food restriction on the basal and heat-induced expression of heat shock genes varies considerably from gene to gene.

Aging↗
PubMed1995

Fatigue in cancer patients: a review of the literature.

This paper reviews the research literature concerning fatigue in cancer patients, evaluating the quality of the evidence, thus helping to focus the direction and methodological rigour required in future investigations. Since fatigue in this population has been attributed to several mechanisms these will be discussed. The prevalence of fatigue in cancer patients will then be documented. An overview of what is currently understood about fatigue in cancer will follow. Based on the literature, conceptual and methodological difficulties will be described. Finally, gaps in understanding will be identified. Suggestions for future research will be formulated and potential interventions to decrease feelings of fatigue explored.

Adaptation, Psychological↗
PubMed1995

Mixed dentition analysis: a review of methods and their accuracy.

Methods that have been proposed for mixed dentition analysis are reviewed. Prediction of the space required in the dental arch for unerupted permanent canines and premolars has been based either on the correlation between the mesio-distal widths of these teeth and of erupted mandibular incisors, or on measurements of the unerupted teeth on radiographs. Studies comparing the different methods have shown that the method of Hixon & Oldfather (1958), as refined by Staley & Kerber (1980), is the most accurate.

Adolescent↗
PubMed1995

Damage to cerebellocortical pathways after closed head injury: a behavioural and magnetic resonance imaging study.

The objective was to investigate the anatomical substrate of ataxia seen after severe head injury. Five patients were recruited from present and former inpatients at Rivermead Rehabilitation Centre. All patients had had a closed head injury and all had cerebellar type ataxia. Four normal controls were also studied. Brain MRI, clinical examination, computer based recording, and analysis of visuomotor tracking were carried out. Focal damage was found in the superior cerebellar peduncle in all five ataxic patients. The patients' tracking movements showed profound tremor, and unusual reliance on visual feedback. Ataxia seen after severe head injury can arise from damage to the superior cerebellar peduncle, which may interfere with the cerebellocortical circuits involved in coordinated movement.

Adult↗
PubMed1995

The Edinburgh City Hospital cohort: analysis of enrollment, progression and mortality by baseline covariates.

We describe baseline characteristics, enrollment, progression and mortality of the Edinburgh City Hospital HIV cohort. There were 431 men and 191 (31%) women; 439 (71%) infected via injection drug use (IDU); 92 (15%) via homosexual intercourse; 84 (13%) via heterosexual intercourse and 7 from blood products. Median annual rate of CD4 cell loss was 49 (90% range: 15-146); Both homosexual men and patients aged > 40 years at enrollment lost CD4 cells significantly more quickly. In multifactorial analysis controlled for baseline CD4 count and IgA, there was no gender effect, but young patients (< 25 years) progressed significantly more slowly to AIDS (RR 0.4, p = 0.00). Homosexual men progressed significantly more quickly than IDUs, with adjusted relative risks (RR) of 2.9 (p = 0.00), 2.5 (p = 0.01) and 1.5 (p = 0.1) for progression to CDC stage IV, AIDS and death, respectively. The three-year survival rate post-AIDS was 25% (SE 4.3) and there was no gender effect on survival. There was, however, an age effect whereby individuals diagnosed with AIDS in their 40s or later showed poorer survival (RR 1.9, p = 0.04). Zidovudine treatment after an AIDS diagnosis significantly lengthened post-AIDS survival (RR 0.5, p = 0.08).

Acquired Immunodeficiency Syndrome↗
PubMed1994

Hsp70 and aging.

An alteration in the ability of cells to express heat shock proteins could be physiologically important in aging because all living organisms show a reduced ability to respond to stress with increasing age. Using hepatocytes freshly isolated from young adult and old rats, we have shown that the induction of hsp70 expression by heat shock is reduced approximately 50% with age. The decrease in hsp70 expression occurs at the level of transcription and appears to arise from a defect in the heat shock transcription factor. Other investigators have also shown that the induction of hsp70 expression by heat shock as well as other stresses declines significantly with age in a variety of tissues from rats as well as mononuclear cells from human subjects. In addition, a decrease in the inducibility of hsp70 is observed with cell senescence in cultured cells. Therefore, it appears that a reduced ability to express hsp70 in response to stress may be a common phenomenon underlying the aging process.

Aging↗
PubMed1994

The heat shock transcription factor in liver exists in a form that has DNA binding activity but no transcriptional activity.

The binding activity of the heat shock transcription factor (HSF) to the heat shock element (HSE) is observed in non-stressed liver and freshly isolated hepatocytes when the expression of hsp70 is undetectable. HSF binding activity in non-stressed liver/hepatocytes is specific for HSE and similar to the HSF binding activity observed in heat shocked hepatocytes that is associated with hsp70 transcription. However, the HSF binding activity in non-stressed and heat shock cells can be distinguished on the basis of the thermal stability in vitro. The HSE binding activity of cell extracts isolated from non-stressed liver/hepatocytes was lost rapidly when the extracts were incubated at 37 degrees C. In contrast, the HSF binding activity of cell extracts isolated from heat shocked hepatocytes was relatively stable at 37 degrees C. Based on our observations, we propose that the activation of HSF is a multistep process that involves a change in conformation after oligomerization and the acquisition of DNA binding to a form that is more thermostable and is associated with increased hsp70 transcription.

Animals↗