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A Richardson

Publications and source records attributed to A Richardson.

At least 91 records · Page 5Linked to original sources
PubMed1999

Application of exogenously regulatable promoter systems to transgenic models for the study of aging.

Transgenic mouse and gene knockout technologies offer powerful tools for dissecting the roles of specific genes in the process of aging. Tke interpretation of the results of such studies is limited, however, by the fact that the gene of interest of over- or underexpressed throughout the life span of the animal model. Among other problems, this situation makes it difficult to separate the effects that a specific gene has an embryological development from those that it may exert on the subsequent maturation and aging of the animal. It is also not possible with these methods alone to alter the expression of genes in an age-dependent fashion and to assess the effects of these alterations on the aging process. This capacity would be of particular interest in studying genes which are thought to have a role in regulating physiological homeostasis. Because they offer the opportunity to activate or render inactive the expression of genes at will, exogenously regulatable promoter systems, particularly when used in combination with traditional transgenic or gene knockout approaches, provide a new and potentially very powerful tool for studying the effect of selected genes on aging. This review discusses the merits and limitations of the application of either the tetracycline-regulatable promoter system, the RU 486-inducible promoter system, or the ecdysone-inducible promoter system to exogenously regulate the expression of a transcriptionally linked gene and to thus assess the effect of that gene on aging.

Aging↗
PubMed1999

From theory to practice: designing interventions to reduce fatigue in patients with cancer.

PURPOSE/OBJECTIVES: To review the evidence available to guide the development of interventions to alleviate cancer-related fatigue. DATA SOURCES: Published fatigue theories and research describing patients' self-care strategies and the efficacy of interventions for the management of fatigue. DATA SYNTHESIS: Fatigue is a pervasive problem for patients with cancer. Without guidance, patients adopt common-sense strategies that generally prove unsuccessful in alleviating fatigue. Theories that identify self-care actions that can reduce fatigue are becoming increasingly sophisticated. A small number of strategies, most notably exercise, has been evaluated. Other interventions--educational, attention-restoring, and psychosocial--have been tested to a lesser extent. The theoretical foundations of these experimental studies frequently are unclear. However, primary evidence is favorable and supports further evaluation. CONCLUSIONS: Passive approaches frequently fail to reduce fatigue in patients with cancer. Alternative approaches based on the growing body of theoretical and research evidence should be adopted. IMPLICATIONS FOR NURSING PRACTICE: Patients require guidance in managing cancer-related fatigue. Nurses need to develop and evaluate relief interventions. Systematic research programs based on sound theoretical premises and previous research will contribute to the growing body of evidence to aid future management of this troublesome symptom.

Attention↗
PubMed1998

Nucleotide excision repair of actively transcribed versus nontranscribed DNA in rat hepatocytes: effect of age and dietary restriction.

The ability of primary cultures of rat hepatocytes to remove cyclobutane pyrimidine dimers (CPDs) from DNA fragments containing the transcriptionally active albumin gene and the transcriptionally inactive embryonic myosin heavy chain (MHCemb) and H-ras fragments as well as the genome overall was measured. At all UV doses studied, more CPDs were observed in the three DNA fragments and the genome overall in hepatocytes isolated from old (24-month-old) rats fed ad libitum than in young (6-month-old) rats fed ad libitum or old rats fed a calorie-restricted diet. The cultured hepatocytes preferentially removed CPDs from the albumin fragment compared to the genome overall or the MHCemb and H-ras fragments. The rate of repair (12 h after UV irradiation) of the albumin fragment was approximately 40% less in hepatocytes isolated from old rats than from young rats; this was due to a decrease in repair of the transcribed strand of this fragment, and dietary restriction prevented this decrease. The extent of repair (24 h after UV irradiation) of the MHCemb and H-ras fragments as well as the genome overall was reduced approximately 40% with age, and this decrease was reversed by dietary restriction.

Aging↗
PubMed1998

Increased oxidative damage is correlated to altered mitochondrial function in heterozygous manganese superoxide dismutase knockout mice.

This study characterizes mitochondria isolated from livers of Sod2(-/+) and Sod2(+/+) mice. A 50% decrease in manganese superoxide dismutase (MnSOD) activity was observed in mitochondria isolated from Sod2(-/+) mice compared with Sod2(+/+) mice, with no change in the activities of either glutathione peroxidase or copper/zinc superoxide dismutase. However, the level of total glutathione was 30% less in liver mitochondria of the Sod2(-/+) mice. The reduction in MnSOD activity in Sod2(-/+) mice was correlated to an increase in oxidative damage to mitochondria: decreased activities of the Fe-S proteins (aconitase and NADH oxidoreductase), increased carbonyl groups in proteins, and increased levels of 8-hydroxydeoxyguanosine in mitochondrial DNA. In contrast, there were no significant changes in oxidative damage in the cytosolic proteins or nuclear DNA. The increase in oxidative damage in mitochondria was correlated to altered mitochondrial function. A significant decrease in the respiratory control ratio was observed in mitochondria isolated from Sod2(-/+) mice compared with Sod2(+/+) mice for substrates metabolized by complexes I, II, and III. In addition, mitochondria isolated from Sod2(-/+) mice showed an increased rate of induction of the permeability transition. Therefore, this study provides direct evidence correlating reduced MnSOD activity in vivo to increased oxidative damage in mitochondria and alterations in mitochondrial function.

Aconitate Hydratase↗
PubMed1998

Effect of cAMP-induced transcription on the repair of the phosphoenolpyruvate carboxykinase gene by hepatocytes isolated from young and old rats.

The repair of UV-induced DNA damage in the phosphoenolpyruvate carboxykinase (PEPCK) gene was studied in primary cultures of hepatocytes isolated from young (6-month-old) and old (24-month-old) rats fed ad libitum and old rats fed a calorie-restricted diet. Incubation of the hepatocytes with cAMP rapidly induced PEPCK transcription and mRNA levels 4- to 5-fold. In absence of cAMP, the repair of the PEPCK fragment was similar in cultured hepatocytes isolated from young and old rats fed ad libitum. However, cAMP significantly increased the percentage of cyclobutane pyrimidine dimers (CPDs) removed from the PEPCK fragment 12 h after UV-irradiation in cultured hepatocytes isolated from young rats fed ad libitum. This increase was due to an increase in the repair of the transcribed strand of the PEPCK fragment. In contrast, cAMP did not increase the repair of the PEPCK fragment in cultured hepatocytes isolated from old rats fed ad libitum in spite of an increase in PEPCK transcription. Thus, it appears that the coupling of transcription and DNA repair is compromised in cultured hepatocytes isolated from old rats fed ad libitum. However, cultured hepatocytes isolated from old rats fed a calorie-restricted diet showed an induction in the rate of repair of the transcribed strand of the PEPCK fragment by cAMP that was similar to hepatocytes isolated from young rats fed ad libitum.

Aging↗
PubMed1998

Effect of age and dietary restriction on expression of heat shock protein 70 in rat alveolar macrophages.

Dietary restriction (DR) is the only effective experimental manipulation known to retard aging in rodents, and this manipulation has been shown to alter a variety of processes that change with age. However, there is no information on the effect of DR on macrophage Function. In the present study, the effect of aging and DR on the ability of alveolar macrophages (AMs) to express the heat shock gene, hsp70 was studied. AMs were isolated by lavage from the lungs of young (4-6 months) and old (24-26 months) rats fed either ad libitum (AL) or a restricted diet (60% of AL). There was no age-related change in the number of cells recovered from young and old rats fed AL. However, the number of cells recovered from the lungs of the DR rats was reduced, and this decrease was statistically significant in young rats. The expression of heat shock protein 70 (hsp70) was measured by the level of the hsp70 mRNA transcript in total RNA isolated from AMs cultured under two conditions: in suspension and after adherence to plastic. When AMs were incubated at 37 degrees C in suspension, no detectable hsp70 expression was observed; however, hsp70 expression was induced at 37 degrees C when the AMs adhered to the plastic culture dishes. Hsp70 mRNA levels were rapidly induced by heat shock (43 degrees C, 1 h) in AMs cultured both in suspension and on plastic. The induction of hsp70 expression did not change significantly with either age or DR in AMs cultured in suspension. In contrast, the induction of hsp70 mRNA levels by AMs adherent to plastic culture plates decreased approximately 70% with age, and hsp70 induction was greater in AMs isolated from DR rats; this difference was statistically significant in young rats. The induction of hsp70 by heat shock (43 degrees C, 1 h) also decreased with age in the adherent AMs, and DR increased the induction of hsp70 expression three- to fourfold in adherent AMs from both young and old rats.

Aging↗
PubMed1998

Regenerating livers of old rats contain high levels of C/EBPalpha that correlate with altered expression of cell cycle associated proteins.

The nuclear transcription factor, CCAAT/enhancer binding protein alpha (C/EBPalpha) is expressed at high levels in the liver and inhibits growth in cultured cells. We have tested the correlation between C/EBPalpha levels, cell cycle proteins and hepatocyte proliferation in old and young animals as an in vivo model system in which the proliferative response to partial hepatectomy (PH) has been shown to be reduced and delayed in old animals. Here we present evidence that the expression of C/EBPalpha in old rats (24 months) differs from its expression in young animals (6-10 months) during liver regeneration. Induction of proliferating cell nuclear antigen (PCNA), a marker of DNA synthesis, occurs at 24 h after PH in young rats but is delayed and reduced in old animals. Induction of the mitotic-specific protein, cdc2 p34, is 3-4-fold less in regenerating liver of old rats than in the liver of young animals, confirming the reduced proliferative response in old animals. In young rats, the normal regenerative response involves a reduction of 3-4-fold in the levels of C/EBPalpha protein at 3-24 h. In old animals, C/EBPalpha is not reduced within 24 h after PH, but a decrease of C/EBPalpha protein levels can be detected at 72 h after PH. Induction of C/EBPbeta, another member of the C/EBP family, is delayed in old animals. Changes in the expression of C/EBP proteins are accompanied by alteration of the CDK inhibitor, p21, which is also decreased in young rats after PH, but in old animals remains unchanged. High levels of p21 protein in older animals correlate with the lack of cdk2 activation. We suggest that the failure to reduce the amount of C/EBPalpha and p21 is a critical event in the dysregulation of hepatocyte proliferation in old animals following PH.

Aging↗
PubMed1998

Failed appointments in an academic orthodontic clinic.

OBJECTIVE: To investigate the reasons for patients failing to keep appointments in the orthodontic department of a dental school and related circumstances. DESIGN: Retrospective single centre postal questionnaire. SETTING: University orthodontic department in Belfast, Northern Ireland, 1994. SUBJECTS: All 1995 patients failing to keep appointments during the first six months of 1994 (13.6% of total appointments). MAIN OUTCOME MEASURES: The responses expressed as frequencies. RESULTS: Responses were received from 758 patients (37% male, 55% female). The most frequent reasons for failure to keep appointments were illness, other commitments and forgetfulness. Only half of the patients attempted to cancel the appointment. The majority of failures occurred when appointments were made for the preferred time of attendance. Keenness for treatment exceeded perception of the severity of malocclusion. Seven in ten patients were satisfied with their treatment, more than half thought that they were nearing the end of treatment and 21.2% would not be upset if their appliances were withdrawn. CONCLUSIONS: Parents and patients should be aware of school commitments in advance of making appointments and an automated telephone reminder system should be introduced. The importance of cancelling appointments which cannot be fulfilled should be emphasised. Patients wearing retainers should be overbooked in a special clinical session.

Academic Medical Centers↗
PubMed1998

The expression of heat shock protein 70 decreases with cellular senescence in vitro and in cells derived from young and old human subjects.

Because heat shock proteins have been shown to play a critical role in protecting cells from hyperthermia and other types of stresses, it was of interest to determine what effect cellular senescence in vitro and cells cultured in vitro from young and old human donors have on the ability of cells to regulate the expression of heat shock protein 70 (hsp70), the most prominent and most evolutionary conserved of the heat shock proteins. The ability of early and late passage IMR-90 lung fibroblasts and epidermal melanocytes and skin fibroblasts obtained from young and old human donors to express hsp70 was determined after a brief heat shock. We found that the levels of hsp70 protein and mRNA were lower in late passage cells and cells from old donors than in early passage cells and cells from young donors. The binding activity of the heat shock transcription factor HSF1, as measured by a gel shift assay, was significantly higher in early passage cells and cells from young donors in comparison to late passage cells and cells from old donors. In addition, the levels of HSF1 decreased significantly in late passage cells and cells from old donors in comparison to early passage cells and cells from young donors. Thus, our study demonstrates that the induction of hsp70 by hyperthermia in fibroblasts is significantly lower in late passage fibroblasts and in fibroblasts from old donors. In addition, our study shows that the decline in hsp70 expression during cellular senescence in vitro and in cells derived from old human subjects is paralleled by a decrease in the levels of HSF1.

Adult↗
PubMed1998

Activation of p21ras/MAPK signal transduction molecules decreases with age in mitogen-stimulated T cells from rats.

Signal transduction is ubiquitously involved in the initiation of physiological signals that lead to growth and proliferation of cells. The signaling cascade mediated by the mitogen-activated protein kinase (MAPK) is considered essential for T cell growth and function. Therefore, it was of interest to determine the influence of age on the induction of MAPK in mitogen-activated T cells. T cells from young (4-6 months) and old (24-26 months) rats responded to concanavalin A (Con A) stimulation by increasing MAPK, c-jun amino terminal kinase (JNK), and p21ras activities. The time course of induction of MAPK/JNK and p21ras activities was similar in T cells isolated from young and old rats. The induction of JNK activity did not change significantly with age; however, the induction of MAPK and p21ras activities was significantly less (50 to 65%) in T cells from old rats than in T cells from young rats. Although the relative protein levels of p42 and p44 MAPK did not change with age, the proportion of the phosphorylated p44 MAPK decreased with age. In addition, it was found that the in vitro kinase activities of the T cell receptor-associated protein tyrosine kinase Lck (p56Lck) and ZAP-70 but not Fyn (p59Fyn) were lower in T cells from old rats than in T cells from young rats. The decline in activities of these signaling molecules with age was not associated with changes in their corresponding protein levels. Thus, our results demonstrate that aging alters the activation of the signal transduction cascade that leads to T cell activation.

Aging↗
PubMed1998

Analysis of the transcriptional activity of the 5'-flanking region of the rat catalase gene in transiently transfected cells and in transgenic mice.

Transiently transfected cell lines and transgenic mice were used to study the transcriptional activity of the 5'-flanking region of the catalase gene. Fragments of the 5'-flanking region of the rat catalase gene ranging in length from 3,421 base pairs (bp) to 69 bp were fused to the chloramphenicol acetyltransferase (CAT) reporter gene, and the transcriptional activity of the reporter gene was measured following transient transfection in three cell lines: a human hepatoma cell line (HepG2), a porcine kidney epithelial cell line (LLCPK1), and a human glioma cell line (U-138 MG). The 3,421-bp fragment of the 5'-flanking region resulted in a high level of expression of the reporter gene in all three cell lines. Shorter fragments of the 5'-flanking region resulted in a decrease in the level of CAT reporter expression that varied among the three cell lines, implying the presence of tissue-specific regulatory sites. To study the tissue-specific regulation of the catalase promoter, transgenic mice containing the 3,421-bp 5'-flanking sequence attached to the CAT reporter gene were produced, and CAT expression was measured in various tissues of three independent transgenic lines. CAT activity was consistently high in muscle tissue (heart, skeletal muscle, and diaphragm) and low in most other tissues studied, particularly in liver and kidney. In contrast, the endogenous expression of catalase is low in muscle and high in liver and kidney; thus, the tissue-specific expression of the reporter gene driven by the 3,421-bp fragment of the 5'-flanking region of the catalase gene was not similar to the expression of the endogenous catalase gene.

Animals↗
PubMed1998

Characterization of gene-specific DNA repair by primary cultures of rat hepatocytes.

At present, almost all the information on gene-specific DNA repair in mammals comes from studies with transformed cell lines and proliferating primary cells obtained from rodents and humans. In the present study, we measured the repair of specific DNA regions in primary cultures of nondividing rat hepatocytes (parenchymal cells). DNA damage was induced by irradiating the primary cultures of hepatocytes with ultraviolet (UV) light, and the presence of cyclobutane pyrimidine dimers (CPDs) was measured by using T4 endonuclease V in the following: a 21-kb BamHI fragment containing the albumin gene, a 14-kb BamHI fragment containing the H-ras gene, and the genome overall. The frequency of CPDs in the two BamHI fragments and the genome overall were similar and ranged from 0.5 to 1.3 CPDs per 10 kb for UV doses of 5-30 J/m2. However, the removal of CPDs from the DNA fragment containing the albumin gene was significantly higher than from that of the genome overall and the DNA fragment containing the H-ras gene. Within 24 hr, approximately 67% of the CPDs was removed from the DNA fragment containing the albumin gene versus less than 40% for the genome overall and the DNA fragment containing the H-ras gene. The lower repair observed for the 14-kb fragment containing the H-ras gene is probably indicative of repair of the nontranscribed region of this fragment because the H-ras gene makes up only 2.4 kb of the 14-kb fragment. Primary cultures of hepatocytes removed CPDs from the transcribed strand of albumin fragment more efficiently than from the nontranscribed strand; however, no differences were observed in the repair of the two strands of the fragment containing the H-ras gene. These results demonstrate that primary cultures of nondividing rat hepatocytes show differential repair of UV-induced DNA damage that is comparable to what has been reported for transformed, proliferating mammalian cell lines.

Albumins↗
PubMed1998

Measuring fatigue in patients with cancer.

Our current state of knowledge of the fatigue experienced by patients with cancer is limited, and further development is hampered by the definitions of fatigue, which remain numerous, inconsistent, and varied according to the discipline of the author and the nature of the research. It is fairly well established within the healthcare literature that it is multidimensional in nature. This has implications for the reliable and valid assessment of this phenomenon. There are a number of instruments currently available with which to measure cancer-related fatigue. These include instruments developed for use initially with healthy populations, such as airmen and workers engaged in manual and clerical work. However, cancer-specific fatigue assessment instruments are now available, and are preferable to those instruments developed without reference to this patient group. Fatigue is often found as a single item or scale in self-report measures of symptoms, mood and functional status reflecting the effect of fatigue and the interaction of fatigue with other symptoms or concepts related to quality of life. Factors to be considered in selecting a measure of fatigue for research will be outlined, and recommendations for the future development and validation of useful and scientifically credible measures of fatigue made.

Fatigue↗
PubMed1998

The ins and outs of a molecular chaperone machine.

Genetic and biochemical work has highlighted the biological importance of the GroEL/GroES (Hsp60/Hsp10; cpn60/cpn10) chaperone machine in protein folding. GroEL's donut-shaped structure has attracted the attention of structural biologists because of its elegance as well as the secrets (substrates) it can hide. The recent determination of the GroES and GroEL/GroES structures provides a glimpse of their plasticity, revealing dramatic conformational changes that point to an elaborate mechanism, coupling ATP hydrolysis to substrate release by GroEL.

Bacteriophage T4↗
PubMed1998

Multi-site samples of injecting drug users in Edinburgh: prevalence and correlates of risky injecting practices.

AIMS: To estimate the frequency of injecting and prevalence of equipment sharing and other risky injecting practices among intravenous drug users (IDUs) and to identify correlates of these behaviours. DESIGN: Three cross-sectional surveys of IDUs by face-to-face interview in the years 1992-94. SETTING: Multiple treatment and non-treatment sites throughout the city of Edinburgh, Scotland, UK. PARTICIPANTS: Six hundred and thirty-four interviews of 480 IDUs who reported having injected a drug in the previous six months. MEASUREMENTS: Self-reports of drug-taking behaviours, service contact, sexual behaviour and HIV knowledge, and anonymous testing of saliva for HIV antibodies. FINDINGS: Only 18% had injected at least daily. Thirty-five per cent had accepted or passed on used equipment. Eighty-five per cent of subjects recruited from non-treatment sites were receiving treatment for their drug taking. Multivariate analyses indicated that risky injecting was associated with a consistent history of sharing, polydrug injecting, injecting in prison, having recently started injecting, and recent experience of methadone detoxification. CONCLUSIONS: Injecting frequency and equipment sharing have declined substantially in Edinburgh during the past 10 years and are low compared to other cities in the United Kingdom and elsewhere. These improvements have occurred in the context of remarkably high levels of drug treatment service contact. Our findings support the international evidence indicating that IDUs have modified their injecting habits significantly without completely eliminating this form of HIV risk. High levels of service contact in Edinburgh provide ample opportunities to instigate further HIV prevention measures which target identifiable subgroups of IDUs who persist in risky injecting.

Adolescent↗
PubMed1998

Attitudes to LIS education and academic-practitioner liaison: results of a survey of members of the Library Association Health Libraries Group.

A questionnaire survey was conducted by the Library Association Health Libraries Group in October-December 1996. Information practitioners in the health care sector were asked what they considered were the education and research needs of the profession, their opinion of Library and Information Sciences education, and their views on practitioner input to education and research. They were also asked whether they would be prepared to give talks to students and to offer student placements. The results show that there is still a considerable gulf between academics and practitioners, and that although practitioners are enthusiastic about getting more involved in liaison, they are constrained by lack of time and resources. Practical solutions need to be found to encourage greater understanding and closer working relationships, to achieve the benefits of academic-practitioner liaison.

Adult↗
PubMed1998

The chronology and sequence of eruption of human permanent teeth in Northern Ireland.

OBJECTIVES: To ascertain the average and range of ages and sequence of eruption of human permanent teeth, taking into account the effect of premature loss of primary antecedents. DESIGN: Longitudinal study. SETTING: Caucasian subjects in Northern Ireland. SAMPLE AND METHODS: Study casts at 6-monthly intervals from age 5 to 15 years of 276 children (146 males and 130 females) enrolled in the Belfast Growth Study. The mean and range of ages of eruption of each individual tooth were computed. Comparisons were made between the mean ages of eruption with and without premature loss of primary antecedents, between upper and lower arches, between right and left sides and between males and females. The sequence of eruption was also investigated. RESULTS: The means and ranges of eruption ages are reported. Premature loss of primary antecedents delayed eruption of permanent successors except for the upper premolars which were accelerated. The differences relating to the upper first premolar and lower canine were not statistically significant. Each lower tooth erupted before its upper counterpart except for the premolars. There was no significant difference in age of eruption between right and left sides. Females tended to erupt teeth before males with the exception of the second molars in both arches; however, the only differences to reach statistical significance related to upper and lower canines and upper lateral incisors. The most frequent orders of eruption were unique to the subject. These occurred in 22% of upper and 33% of lower arches. The classic sequences: first molar-central incisor-lateral incisor-first premolar-canine-second premolar-second molar (M1-I1-I2-PM1-C-PM2-M2) in the upper arch and I1-M1-I2-C-PM1-PM2-M2 in the lower arch occurred in only 16% of upper arches and 13% of lower arches. Males adhered to the textbook sequence (20% upper, 17% lower) more than females (12% upper, 8% lower). In the upper arch of females, the order M1-I1-I2-PM1-PM2-C-M2 in 10% of subjects was almost as frequent as the classic sequence. CONCLUSION: The ages, ranges and orders of eruption found in this study are more reliable than many which are frequently quoted on account of its longitudinal nature and the fact that the effect of premature loss of primary antecedents is taken into account. The exclusively Caucasian sample makes the data quite precise but limits applicability to patients of this ethnic origin.

Adolescent↗