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Biomedical subjects

A Richardson

Publications and source records attributed to A Richardson.

At least 145 records · Page 8Linked to original sources
PubMed1996

Molecular cloning of higher plant homologues of the high-affinity nitrate transporters of Chlamydomonas reinhardtii and Aspergillus nidulans.

The crnA nitrate transporter from Aspergillus nidulans was identified as belonging to the major facilitator superfamily (MFS) of membrane transporters. Degenerate oligonucleotides corresponding to the crnA sequences at the locations of two conserved sequence motifs were designed and used in the polymerase chain reaction (PCR) to amplify related sequences from barley root poly(A)+ RNA. A 130 bp cDNA fragment with sequence similarities to crnA was amplified and used as a probe to screen a barley root cDNA library. Two full-length clones (pBCH1 and pBCH2) were isolated. The nt sequences of pBHC1 and pBCH2 are closely related (80% identical) and potentially encode hydrophobic polypeptides of 54.7 and 55.0 kDa respectively, with twelve predicted transmembrane domains. The encoded polypeptides are 41-43% identical to the A. nidulans CRNA protein and 56-57% identical to NAR-3, a high-affinity nitrate transporter from the eukaryotic alga Chlamydomonas reinhardtii. Phylogenetic analysis indicated that crnA, nar-3 and the barley homologues belong to a new family within the MFS, a family that also includes narK, the gene for a nitrite efflux pump in Escherichia coli. In northern blots, BCH1 hybridised to a mRNA species of 1.9 kb which is rapidly induced in barley roots by NO3-, but not by NH4+, and genomic Southern blots indicated that there may be seven to ten BCH1-related genes in the barley genome.

Amino Acid Sequence↗
PubMed1996

The effect of age on the expression of interleukin-2.

Interleukin-2 (IL-2) is a growth promoting cytokine that has received a great deal of attention over the past decade with respect to aging and cancer. It is produced primarily by helper T cells and regulates the growth and function of various cells that are involved in cellular and humoral immunity. The expression of IL-2 has been found to decrease with age in humans and rodents. The decline in IL-2 production has been shown to parallel the age-related decrease in immunologic function. Several studies indicate that treatment of lymphocytes from old subjects with exogenous IL-2 or infusion of IL-2 into old animals partially or completely restores some of the immune functions that decline with age. The age-related decline in IL-2 production has been shown to arise from a decline in IL-2 transcription, and a recent study suggests that the transcription factor NFAT (nuclear factor of activated T cells) may play a role in the decline in IL-2 transcription.

Aging↗
PubMed1996

The identification of p130cas-binding proteins and their role in cellular transformation.

Adaptor proteins play an important role in signal transduction by regulating the establishment and maintenance of functionally important protein complexes. A recently described member of this group of proteins is p130cas (CAS), which contains numerous sequence motifs predicted to be involved in mediating protein-protein interactions. We propose that adaptor molecules like CAS may help determine the response of a cell to a particular signal by interacting with specific subsets of cellular proteins. To test this hypothesis, we have identified potential binding partners of CAS that may play a rote in cellular transformation by the oncoproteins v-SRC and/or v-CRK. We show that individual domains of CAS associate with specific subsets of proteins in vitro, and that many of these interactions are dependent on the state of tyrosine-phosphorylation of CAS. Sequences necessary for interacting with the focal adhesion kinase pp125FAK (FAK), v-SRC and v-CRK have been mapped to distinct regions of CAS. In addition, the identification of a number of putative CAS-binding partners that are present in crk-transformed cell extracts but undetectable in normal and src-transformed cell extracts supports a model in which unique protein complexes are formed in response to different signals.

Carrier Proteins↗
PubMed1996

A mechanism for regulation of the adhesion-associated proteintyrosine kinase pp125FAK.

Focal adhesion kinase (pp125FAK) is a member of a growing family of structurally distinct protein tyrosine kinases that includes the recently identified FakB and PYK2/CAKbeta/RAFTK. Activation of pp125FAK has been functionally linked to the formation of focal adhesions, integrin-mediated sites of contact between the cell and the extracellular matrix. The carboxy-terminal domain of pp125FAK is also expressed as a separate protein called pp41/43FRNK (where FRNK represents pp125FAK-related non-kinase). Here we show that pp41/43FRNK acts as an inhibitor of pp125FAK by transiently blocking the formation of focal adhesions on fibronectin and constitutively reducing tyrosine phosphorylation of both pp125FAK and two focal adhesion proteins, tensin and paxillin. These inhibitory effects of pp41/43FRNK are reversed by co-expression of pp125FAK, suggesting that pp125FAK and pp41/43 FRNK compete for a common binding protein(s) whose association with pp125FAK is necessary for signalling by pp125FAK. We propose that pp41/43FRNK functions as an endogenous regulator of pp125FAK, thus providing an unusual means to regulate both tyrosine kinase activity and cellular adhesion to the extracellular matrix.

Animals↗
PubMed1996

Expression of genes coding for antioxidant enzymes and heat shock proteins is altered in primary cultures of rat hepatocytes.

The expression of genes for heat shock proteins in the HSP70 family and genes for antioxidant enzymes was studied in rat hepatocytes cultured in either L-15 or Williams E media on a collagen matrix for up to 48 hours. The mRNA transcripts for the heat shock proteins hsp70, hsc70, and grp78 were induced dramatically when hepatocytes were cultured in L-15, and to a lesser extent when cultured in Williams E. The increase in hsp70 and hsc70 mRNA levels in the cultured hepatocytes was correlated with an increase in the nuclear transcription of these two genes and the binding activity of the heat shock transcription factor to the heat shock element. Culturing rat hepatocytes in either L-15 or Williams E resulted in a decrease in the levels of the mRNA transcripts for catalase and glutathione peroxidase and the activities of these two enzymes. However, the expression of Cu/Zn-superoxide dismutase, i.e., the level of the mRNA transcript or the enzymatic activity, did not change appreciably when hepatocytes were cultured for up to 48 hours. The decline in catalase and glutathione peroxidase expression in the cultured hepatocytes was correlated with a decrease in the GSH/GSSG ratio and an increase in lipid peroxidation. These data show that the expression of several genes involved in cellular protection change when hepatocytes are placed in primary cultures. Therefore, one must be careful in extrapolating from primary cultures to the liver in vivo, especially when studying processes that might be affected by heat shock proteins or antioxidant enzymes.

Animals↗
PubMed1996

Effect of caloric restriction on the expression of heat shock protein 70 and the activation of heat shock transcription factor 1.

The regulation of heat shock protein 70 (hsp70) expression is an excellent example of a cellular mechanism that has evolved to protect all living organisms from various types of physiological stresses; therefore, the reported age-related alterations in the ability of cells to express hsp70 in response to stress could seriously compromise the ability of a senescent organism in respond to changes in its environment. Because caloric restriction (CR) is the only experimental manipulation known to retard aging and increase the survival of rodents, it was of interest to analyze the effect of CR on the age-related alteration in the induction of hsp70 expression in rat hepatocytes. The effect of CR on the nuclear transcription of hsp70 gene in rat hepatocytes in response to various levels of heat shock was determined, and it was found that the age-related decline in the transcription of hsp70 at all temperatures studied was reversed by CR. Because the heat shock transcription factor (HSF) mediates the heat-induced transcription of hsp70, the effect of CR on the induction of HSF binding activity by heat shock was studied and found to arise from HSF1, which has been shown to be involved in the induction of HSF binding activity in other cell types. The age-related decrease in the induction of HSF1 binding activity in rat hepatocytes was reversed by CR, and did not appear to be due to an accumulation of inhibitory molecules with age. Interestingly, the level of HSF1 protein was significantly higher in hepatocytes isolated from old rats fed ad libitum compared to hepatocytes obtained from rats fed the CR diet even though the levels of HSF1 binding activity were lower for hepatocytes isolated from the old rats fed ad libitum. The levels of the mRNA transcript for HSF1 was not significantly altered by age or CR. Thus, the changes in HSF1 binding activity with age and CR do not arise from changes in the level of HSF1 protein available for activation.

Age Factors↗
PubMed1996

Fatigue: a concept analysis.

Fatigue is probably the most common symptom of illness affecting sufferers of both acute and chronic conditions. However, confusion surrounds the definition and use of the term fatigue. As with many other nursing concepts, it is a word that is commonly used in colloquial language. This concept analysis aims to identify the attributes that are essential to the concept of fatigue, and to distinguish between its colloquial and its nursing usage by following the strategy suggested by Walker and Avant (1995, Strategies for Theory Construction in Nursing, Appleton Lange, London). A review of the literature identifies nursing uses of the term fatigue which reflect and conflict with colloquial uses. Defining attributes, demonstration cases, antecedents, consequences and empirical referents are identified before a definition of fatigue is developed and proposed for nursing. This clarification of the phenomenon has particular relevance for clinical nursing, future research and the development of fatigue theories.

Chronic Disease↗
PubMed1996

Evaluation of 1-(9-anthracenylmethyl) piperazine for the analysis of isocyanates in spray-painting operations.

A new reagent, 1-(9-anthracenylmethyl)piperzine (MAP), was used for the derivatization of airborne 1,6-hexamethylene diisocyanate (HDI) and polyisocyanates generated during spray-painting operations. The new reagent, which offers enhanced sensitivity and uniformity of response to both the monomeric and oligomeric forms of HDI, was compared directly with 1-(2-methoxyphenyl)piperazine (MOP), the currently employed derivatizing reagent used in the National Institute for Occupational Safety and Health Method 5521. Both the validity of the side-by-side sampling protocol and the efficacy of two derivatizing reagents were evaluated in field studies. The analytical results indicate that there is no significant difference at the 95% confidence level in the concentration of polyisocyanate in the aerosol as determined by two impingers containing MAP and a third containing MOP when these are positioned in a side-by-side-by-side arrangement.

Air Pollutants, Occupational↗
PubMed1996

Expression of heat shock protein 70 in rat spleen lymphocytes is affected by age but not by food restriction.

The purpose of this study was to determine if food restriction alters the age-related decline in heat shock protein 70 (hsp70) expression in lymphocytes from male Fischer 344 rats. Spleen lymphocytes were isolated from young (6 mo) and old (24 mo) rats that had free access to food (control group) and from food-restricted old (24 mo) rats that, beginning at 6 wk of age, were fed 60% (40% food restriction) of the diet consumed by the control rats. Lymphocytes were either heat shocked (42.5 degrees C for 1 h) or maintained at 37 degrees C (control). The levels of hsp70 protein and mRNA and the induction of interleukin-2 (IL-2) mRNA by concanavalin A (conA) were measured in these rats. In addition, the percentage of viability (as an index of thermosensitivity) of the lymphocytes from these rats was also measured after exposure of cells to different temperatures (first at 42.5 degrees C and then 45 degrees C). We found that the induction of hsp70 protein and mRNA in lymphocytes isolated from control old rats and food-restricted old rats was lower (P < 0.001) than that in control young rats. However, the levels of hsp70 and mRNA in lymphocytes isolated from food-restricted old rats were similar to the levels in age-matched control rats. Lymphocytes from both control old rats and food-restricted old rats were more thermosensitive than lymphocytes from control young rats; however, thermosensitivity of lymphocytes from food-restricted old rats was similar to that of age-matched control rats. The induction of IL-2 mRNA levels by conA was significantly (P < 0.001) lower in old than in young control rats. In contrast to hsp70, which was not affected by food restriction, the induction of IL-2 mRNA was higher (P < 0.05) in food-restricted old rats than in age-matched control rats. Therefore, food restriction has a differential effect on gene expression.

Aging↗
PubMed1996

Fatigue in cancer: a phenomenological perspective.

Fatigue is a frequently encountered symptom in cancer populations. This study aimed to describe the experience of fatigue from the perspective of cancer patients who had recently completed a course of chemotherapy. A phenomenological method was used. The themes which emerged from the data indicated both a shared and individual experience of fatigue. These incorporated: the nature of fatigue; the causes, consequences, strategies for coping with fatigue; and the trajectory of the fatigue experience. Issues arising from the nature of phenomenological inquiry and the research were also elicited from this study. An understanding of the fatigue experience for this population and the use of phenomenology have implications for the nursing profession's knowledge base and for clinical practice.

Adaptation, Psychological↗
PubMed1996

The role of information in patients' adaptation to chemotherapy and radiotherapy: a review of the literature.

This paper reviews the literature concerning the role of information in facilitating patients' adaptation to chemotherapy and radiotherapy. The relationship between information and patient self-efficacy is examined, and the information requirements of cancer patients receiving treatment are reviewed. Finally, studies evaluating informational interventions for patients receiving either chemotherapy or radiotherapy are critiqued before recommendations for practice are formulated.

Adaptation, Psychological↗
PubMed1996

A study to explore the role of a community oncology nurse specialist.

Cancer patients are increasingly being cared for in the community. However, the role of the community oncology nurse specialist (CONS) remains a rare appointment in the United Kingdom. There is little research evidence to substantiate the view that this is a worthwhile and effective role. This study aimed to explore the role of one CONS using a qualitative case study approach. The sample consisted of the CONS, seven patients, no relatives and five community nurses. Semi-structured interviews were used to elicit the view of these participants. In addition, documents containing details of the CONS's work to date were reviewed. A number of the CONS's role components were identified by the different respondent groups. Five themes were identified within the data collected: functions of the CONS, communication between the CONS and other health care professionals, structural and organizational factors, characteristics of the service and benefits to patients and their families. Furthermore, all respondent groups were positive about the service offered by the CONS, and felt that the role was valuable. Some negative features were identified and these were concerned with organizational aspects of the service. The findings suggest the need for further research and evaluation in this area.

Adult↗
PubMed1996

Development of nursing documentation for use in the outpatient oncology setting.

In response to the particular demands upon patients and nursing staff in the outpatient setting, and the identification of a need for nursing orientated documentation, a new nursing documentation system has been developed and implemented within an oncology day unit. The documentation is used by the nursing team engaged in the care of patients receiving outpatient chemotherapy treatment. The system consists of documents for the initial and ongoing assessment, planning, implementation and evaluation of nursing care. These include pretreatment patient self-assessment forms, flowsheets for the documentation of chemotherapy treatment and administration and a record for information and teaching given to patients and significant others. Referrals to other services and health care professionals are also documented. This tool is designed to ensure a high standard of nursing intervention and maximize quality of life in this group of patients. An audit is planned to evaluate the effectiveness of this tool and highlight any areas requiring improvement or modification. There are also plans to further develop this system for use in the inpatient and community setting.

Ambulatory Care↗
PubMed1996

The experience of fatigue and other symptoms in patients receiving chemotherapy.

Fatigue has been recognized as the most frequently reported symptom of cancer and cancer therapy. There is a lack of research on such aspects as the pattern of fatigue which accompanies treatment, its exacerbating and relieving factors, the different mechanisms of fatigue and its relationship with the factors purported to be related to the fatigue experience. It has been suggested that cancer patients may be those best placed to reveal the likely causes of fatigue. As part of a larger study examining the pattern of fatigue in cancer patients who were undergoing a course of chemotherapy treatment, patients' perceptions of fatigue and tiredness and the nature, pattern and causes of fatigue in relation to cancer and its treatment were obtained. In addition to a diary, interviews were conducted at two time points, at the beginning and end of a cycle of chemotherapy, with over 100 cancer patients. Just under 90% of the sample reported fatigue at some point during a cycle of chemotherapy. The majority of the sample did not consider tiredness and fatigue to constitute the same feelings. Subjects attributed their fatigue to a combination of factors but most frequently mentioned treatment, changes in sleep patterns and other symptoms. Implications for practice and research are outlined.

Adult↗
PubMed1996

Large scale synthesis of recombinant human thyrotropin using methotrexate amplification: chromatographic, immunological, and biological characterization.

Studies of human TSH (hTSH) structure and function have been limited by difficulties in producing large quantities of recombinant hormone. We describe a system for the stable expression of high levels of recombinant human TSH (rec hTSH) using a mutant form of dihydrofolate reductase (dhfr) as an amplifiable dominant selectable marker. A vector expressing both the hTSH alpha-subunit and the mutant dhfr was cotransfected with a hTSH beta-subunit expression vector into dhfr-deficient cells. Amplification of the transfected sequences by methotrexate selection, followed by cell culture in a hollow fiber perfusion system, yielded rec hTSH production as high as 100,000 microU/ mL. Immunoradiometric assays using five different antibodies revealed no differences in the immunological activities of rec hTSH and pituitary hTSH. Bioactivity was measured in a novel TSH bioassay coupling the generation of cAMP by a transfected hTSH receptor to the cAMP-dependent regulation of a luciferase reporter gene. The ED50 for bovine TSH in this bioassay was 1.4 ng/mL (3.5 x 10(-11) mol/L). The ratio of the ED50 values for rec hTSH and pituitary hTSH was 1.0:1.1 (P = NS), indicating that the two TSHs were of equivalent potency. In conclusion, we have developed techniques for the high level production of rec hTSH that is immunologically and biologically equivalent to pituitary hTSH. The ability to produce large quantities of rec hTSH using standard laboratory techniques should facilitate future studies, such as the development of clinically useful TSH analogs.

Animals↗
PubMed1995

Consulting the public about health service priorities.

Consulting the public is an important component of commissioning health services. Somerset Health Authority has devised a method of consultation using eight focus groups meeting three times a year. Each group consists of 12 people, and together the groups are demographically representative of Somerset's population. The groups are asked about issues that are concerning the health authority, and their views have influenced health authority decisions. Each group is given some background information before the meeting, together with more information at the meeting. The discussions are tape recorded and analysed for qualitative information, but the groups are also asked to score certain priorities. The groups have been found to be representative, valid, and focused on community rather than individual values. Health authorities wanting to know the values people attach to health services should adopt this qualitative approach to consultation.

Adolescent↗