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Biomedical subjects

P J Barker

Publications and source records attributed to P J Barker.

At least 19 recordsLinked to original sources
PubMed2001

Truncation of the mu heavy chain alters BCR signalling and allows recruitment of CD5+ B cells.

Ig are multifunctional molecules with distinct properties assigned to individual domains. To assess the importance of IgM domain assembly in B cell development we generated two transgenic mouse lines with truncated muH chains by homologous integration of the neomycin resistance gene (neo(r)) into exons C(mu)1 and C(mu)2. Upon DNA rearrangement shortened muH chain transcripts, V(H)-D-J(H)-C(mu)3-C(mu)4, are produced independent of the transcriptional orientation and termination signals provided by neo(r). The truncated muH chain of approximately 52 kDa associates non-covalently with the L chain to form a monovalent HL heterodimer. Surface IgM is assembled into a defective BCR complex which has lost important signalling capacity. In immunizations with T-dependent and T-independent antigens, specific IgM antibodies cannot be detected, whilst IgG responses remain normal. B cell development in the bone marrow is characterized by an increase in early B cells, but a decrease of B220(+) cells from the stage when muH chain rearrangement is completed. The peritoneal lymphocyte population has elevated levels of CD5(+) B cells and their expansion may be the result of a negative feedback mechanism. The results show that antigenic stimulation is compromised by truncated monovalent IgM and that this deficit in stimulation leads to reduced levels of conventional B-2 lymphocytes, but dramatically increased levels of B-1 cells.

Alternative Splicing↗
PubMed2001

The teaching of health care ethics to students of nursing in the UK: a pilot study.

Senior lecturers/lecturers in mental health nursing (11 in round one, nine in round two, and eight in the final round) participated in a three-round Delphi study into the teaching of health care ethics (HCE) to students of nursing. The participants were drawn from six (round one) and four (round three) UK universities. Information was gathered on the organization, methods used and content of HCE modules. Questionnaire responses were transcribed and the content analysed for patterns of interest and areas of convergence or divergence. Findings include: the majority (72.8%) of the sample believed that insufficient time was allocated to the teaching of HCE; case studies were considered a popular, although problematic, teaching method; the 'four principles' approach was less than dominant in the teaching of HCE; and virtue ethics was taught by only 36.4% of the participants. The Delphi technique proved adequate and worth while for the purposes of this study. Further empirical research could aim to replicate or contradict these findings, using a larger sample and recruiting more university departments. Reflection is required on several issues, including the depth and breadth to which ethics theory and, more controversially, meta-ethics, are taught to nursing students.

Adult↗
PubMed2001

Impact of gemifloxacin on the normal human intestinal microflora.

Gemifloxacin is a new fluoroquinolone that has been shown to possess a broad spectrum of antimicrobial activity against gram-positive and gram-negative microorganisms including methicillin-susceptible and methicillin-resistant staphylococci, Streptococcus pneumoniae, Haemophilus influenzae and most members of the family Enterobacteriaceae. The aim of the present study was to investigate the effect of gemifloxacin on the human intestinal microflora. Gemifloxacin was given in oral doses of 320 mg for 7 days to 10 healthy subjects and 5 subjects received a once-daily dose of matched placebo for 7 days. Faecal samples were collected prior to administration (days -8 and -6), during the administration period (days 2 and 4) and after withdrawal of administration (days 8, 11, 21, 28 and 56). In the aerobic intestinal microflora the numbers of enterobacteria were suppressed during the gemifloxacin administration and the numbers of enterococci and streptococci were also decreased. No other aerobic microorganisms were affected. In the anaerobic microflora the numbers of anaerobic cocci and lactobacilli were suppressed during the gemifloxacin administration while no other changes occurred. The microflora was normalized 49 days after the administration of gemifloxacin had stopped. No selection or overgrowth of resistant bacterial strains or yeasts occurred. The ecological impact of gemifloxacin was shown to be selective and similar to that of ciprofloxacin, levofloxacin and ofloxacin.

Adult↗
PubMed2000

Nurses' perceptions of multidisciplinary teamwork in acute psychiatric settings.

The findings of a pilot telephone survey of senior nurses' views of multidisciplinary teamwork (MDT) practice in 26 acute psychiatric admission wards within the ambit of one English health authority are reported. The survey was conducted in two stages. The first stage focused on obtaining the senior nurse's general perceptions of the organization of the work of the multidisciplinary team, and in the second stage more detailed responses to the original questions were obtained. The findings suggest that the composition and operations of the acute ward team are limited, and the relationship between the MDT and patients and their families do not entirely support the concept of increased collaboration with patients and their families. The findings are discussed within the context of the perceived crisis in acute psychiatric care in England and the ambitions for more egalitarian 'mental health' services.

Acute Disease↗
PubMed2000

Nov gene encodes adhesion factor for vascular smooth muscle cells and is dynamically regulated in response to vascular injury.

Nephroblastoma overexpressed (NOV) is a member of the CCN family (connective tissue growth factor, CYR61, and NOV) of proteins that are involved in regulating the proliferation, differentiation, and adhesion of a variety of cell types. We have examined the expression of the NOV: gene and NOV protein by vascular smooth muscle cells (VSMCs), in vitro and in vivo, and the effects of recombinant NOV on VSMCs. Rat aortic VSMCs were found to express NOV: mRNA and NOV protein in vitro and in vivo. NOV: expression in adult rat tissues was very high in the aorta and was detected only weakly in the brain and lung by Northern analysis (relative levels 33:3:1). During postnatal development (3 days to 12 weeks), the expression of NOV: was correlated with markers of the differentiated smooth muscle cell phenotype (smooth muscle myosin heavy chain and SM22 alpha). In the rat carotid artery balloon injury model, NOV: was detectable by in situ hybridization and was downregulated in the media of the injured artery compared with the uninjured artery at 7 and 14 days after injury. Expression in the developing intima was barely detectable at 7 days after injury except for strong expression at the luminal surface. At 14 days after injury, NOV: expression was substantially increased throughout the intima. In vitro studies of the function of NOV protein showed that it promoted VSMC adhesion via a mechanism that was divalent cation and Arg-Gly-Asp independent but that it did not modulate VSMC proliferation or phenotype. The strong expression and dynamic regulation of NOV: in the arterial wall, together with its ability to promote VSMC adhesion, suggest that it may be involved in homeostasis and repair.

Animals↗
PubMed2000

An inquiry into moral virtues, especially compassion, in psychiatric nurses: findings from a Delphi study.

A three-round Delphi study was conducted to gather data on ethical reasoning among psychiatric nurses (N = 26 in round one (R1), decreasing to N = 14 in the final round (R3)). Transcripts of questionnaires were carefully read and compared. Responses were manually sorted into categories, themes and patterns of interest. Eight debates emerged from the data. This article discusses two in detail: the nature of moral virtues and the meaning of compassion in psychiatric nursing. A sympathetic overview of virtue ethics is also provided. The nurses' responses included a lot of virtue terms, such as, 'honest', 'fair', and 'care". However, 'nurses' moral virtues' was ranked low in importance as a notion invoked in ethical decision making in the round-one ranking exercise. Only half of the sample believed that the moral character of a psychiatric nurse is important in ethical decision-making. Further, most of the round-one sample thought the virtues could not be acquired. Compassion was identified as crucial to psychiatric nursing and the nurse-client relationship, though, as expected, many diverse meanings were attributed to this notion. While the Delphi method proved adequate for our purposes, problems with regard to accurately understanding the respondents' intended meanings highlighted a major weakness of this technique, in common with other methods relying on questionnaires. Further inquiry is needed regarding the role of moral virtues and virtue ethics in both psychiatric nursing and nurse education.

Delphi Technique↗
PubMed1999

Attachments of the posterior layer of lumbar fascia.

STUDY DESIGN: Superficial and deep laminae of the posterior layer of lumbar fascia were dissected. The lumbar portion was measured for evidence of segmental thickenings. Superior attachments were dissected, documented, and photographed. OBJECTIVES: To verify the existence of posterior accessory ligaments and establish the superior attachments and fiber angles of the posterior layer of lumbar fascia. SUMMARY OF BACKGROUND DATA: There have been two small dissection studies on the posterior layer. Their findings are conflicting in several areas of clinical significance. Thickenings in the lumbar region were described in one study, but have not been verified. The superior attachments of the posterior layer have not been formally documented. METHODS: Study 1: In 21 embalmed cadavers, the lumbar region of the posterior layer was dissected. The lumbar spinous processes and adjacent fascia were marked. The fascia was removed and examined, and its thickness measured with a manual micrometer. Results were statistically analyzed. Study 2: Superior attachments of the posterior layer in 20 cadavers were dissected and photographed. Capacity to transmit tension was estimated and documented photographically, and fiber angles measured in situ. RESULTS: Study 1: There was no evidence of macroscopic segmental thickening in the posterior layer. Study 2: The superficial lamina was continuous superiorly with the rhomboids, and the deep lamina with the tendons of splenius cervices and capitis. These previously undocumented attachments were of variable thickness and fibrosity, and capable of transmitting tension. CONCLUSIONS: Both superficial and deep laminae of the posterior layer are more extensive superiorly than previously thought. This may have implications for certain tests used in assessment and management of low back pain such as the slump and "nonorganic" tests. The thickness of the superior attachments is variable. Their capacity for load bearing is yet to be quantified.

Aged↗
PubMed1999

Position-dependent processing of peptides presented on the surface of cowpea mosaic virus.

The plant virus cowpea mosaic virus (CPMV) has been developed as an epitope-presentation system. Numerous epitopes have been expressed in the betaB-betaC loop of the CPMV small coat protein, all of which undergo a cleavage reaction between their two carboxy-terminal residues. Although many peptides presented in this manner give an authentic immune response, this was not the case for the NIm-1A epitope from human rhinovirus-14. Crystallography revealed significant differences between the structure of NIm-1A on CPMV compared with its native configuration. The 3D structure of C PMV expressing NIm-1A was used to design alterations to the context of the NIm-1A graft.

Amino Acid Sequence↗
PubMed1998

Efficient generation of major histocompatibility complex class I-peptide complexes using synthetic peptide libraries.

The use of synthetic random peptide libraries is a powerful technology for the study of many aspects of antigen presentation and peptide selection by major histocompatibility complex (MHC) molecules. Here we have used them in conjunction with a recombinant system to determine the peptide binding motifs of three classical class I MHC molecules of the laboratory rat: RT1-Aa, RT1-Au, and RT1-A1c. Described is a method for producing large amounts of soluble class I heavy and light chains in bacteria. Refolding RT1-Aa heavy chain (HC) with rat beta2-microglobulin (beta2m) in the presence of a specific peptide and the subsequent purification of the complex yielded conformationally correct material. This was assessed by gel chromatography, SDS-polyacrylamide gel electrophoresis, isoelectric focussing gel electrophoresis, enzyme-linked immunosorbent assay, and fluorescence-activated cell sorter analysis employing a previously unreported method utilizing a His-Tag affinity silica. By refolding RT1-Aa HC and rat beta2m around a random nonapeptide library and subjecting the resulting complex to acid elution of the bound peptides and pool sequencing, the peptide binding motif for this MHC class I molecule was determined. Results corresponded well with those previously determined from naturally bound peptides and in addition gave a clear and unambiguous signal for the C-terminal anchor residue. This method was then applied to determine the previously undescribed binding motifs for RT1-Au and RT1-A1c. For both molecules, the whole motif was confirmed from naturally bound peptides. We propose this method as an alternative way to obtain the whole class I MHC peptide motif, particularly when a specific antibody is unavailable and/or natural expression of the class I molecule of interest is low.

Animals↗
PubMed1998

The concept of serious mental illness: modern myths and grim realities.

Current mental health practice and legislation is influenced significantly by the ill-defined concept of serious mental illness (SMI). Although the concept of SMI originally appeared to include a consideration of a range of forms of mental illness, including dementias, by custom and practice the term has come to mean, often, only people with a psychotic diagnosis. This paper reviews the influence of the term SMI, considering the way older people, younger people and other subgroups within the 'adult' population have been marginalized by the narrow definition of the concept. The paper concludes with a consideration of some of the ethical implications of mental health nurses focusing on an ill-defined 'illness' grouping, and the impact that such a narrow focus might have on the ambition to establish 'health for all by the year 2000'.

Adolescent↗
PubMed1998

Characterization of site-directed antisera against endothelin-converting enzymes.

Site-directed antisera have been developed against the two endothelin-converting enzyme-1 (ECE-1) isoforms cloned to date in humans, ECE-1 alpha and ECE-1 beta. Antisera were raised in rabbits against synthetic peptides corresponding to the deduced amino acid sequences that differ between ECE-1 alpha and ECE-1 beta. Antisera were highly selective for their corresponding antigen (titer 1 x 10(4)) and did not detect ET-1 or big ET-1. Furthermore, no detectable crossreactivity was observed between the different site-specific antisera and the other immunizing peptides, suggesting that the antisera would be selective for ECE-1 alpha and ECE-1 beta. Standard displacement curves have been developed to determine the levels of immunoreactive ECE-1 alpha and ECE-1 beta in solubilized microsomal fractions of human tissue. In conclusion, we have described the first production and characterization of site-directed antisera raised against ECE-1 alpha and ECE-1 beta capable of discriminating between the two ECE-1 isoforms. Furthermore, using these antisera, we have found that ECE-1 alpha appears to be the predominant isoform in human tissue.

Amino Acid Sequence↗
PubMed1997

PRS1 is a key member of the gene family encoding phosphoribosylpyrophosphate synthetase in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae the metabolite phosphoribosyl-pyrophosphate (PRPP) is required for purine, pyrimidine, tryptophan and histidine biosynthesis. Enzymes that can synthesize PRPP can be encoded by at least four genes. We have studied 5-phospho-ribosyl-1(alpha)-pyrophosphate synthetases (PRS) genetically and biochemically. Each of the four genes, all of which are transcribed, has been disrupted in haploid yeast strains of each mating type and although all disruptants are able to grow on complete medium, differences in growth rate and enzyme activity suggest that disruption of PRS1 or PRS3 has a significant effect on cell metabolism, whereas disruption of PRS2 or PRS4 has little measurable effect. Using Western blot analysis with antisera raised against peptides derived from the non-homology region (NHR) and the N-terminal half of the PRS1 gene product it has been shown that the NHR is not removed by protein splicing. However, the fact that disruption of this gene causes the most dramatic decrease in cell growth rate and enzyme activity suggests that Prs1p may have a key structural or regulatory role in the production of PRPP in the cell.

Amino Acid Sequence↗
PubMed1997

Nutrient regulation of the intestinal Na+/glucose co-transporter (SGLT1) gene expression.

It is known that dietary carbohydrates regulate the activity of the intestinal SGLT1. We have demonstrated that modifications in SGLT1 activity are due to alterations in SGLT1 expression in response to the sugar content of the diet. To assess the correlation between changes in the activity of SGLT1 and the abundance of SGLT1 protein, we have employed a method for the quantitative measurement of immunoreactive proteins. A calibration curve has been constructed using either a nonadecapeptide (amino acids 402-420), or a recombinant protein corresponding to amino acids 554-640 of the SGLT1 sequence. Immunoblotting the protein samples concurrently with specific quantities of either the peptide or recombinant standard, using antibodies raised against these antigens, enabled accurate quantification of the absolute amounts of immunoreactive protein in the samples. The amount of SGLT1 protein correlates well with measurements of SGLT1 activity. The modulation of the activity of SGLT1 in response to lumenal sugars is due to corresponding changes in the absolute levels of SGLT1 protein.

Animals↗
PubMed1997

Isolation and N-terminal sequence determination of a novel gamma/delta T cell surface antigen.

An antigen complex unique for porcine gamma/delta T cells has previously been identified using the monoclonal antibodies MAC319 and MAC320. Here we use digestion with the proteolytic enzyme bromelain to selectively release the MAC319 antigen as a soluble fragment, for further characterisation. A cytofluorometric inhibition assay was developed to follow the purification of this fragment, as the conformation sensitivity of the MAC319 epitope prevented the use of immunoblotting techniques. The antigen has been purified using a combination of anion-exchange and hydrophobic-interaction columns, followed by separation on a size-exclusion column. Fractions from the size-exclusion column containing the antigen consisted of one major band at Mr 95,000. This species was shown to be specifically absorbed onto MAC319-coupled Sepharose, thereby identifying the MAC319 antigen. N-terminal amino acid sequencing of this band has revealed a previously unidentified sequence. This fragment was also shown to be glycosylated, most likely with a single sugar moiety. Enzymatic removal of the sugars showed that they did not appear to be necessary for binding of the polypeptide to the MAC319 antibody.

Animals↗
PubMed1997

The human science basis of psychiatric nursing: theory and practice.

Psychiatric nurses in the United Kingdom (UK) have begun to reattend to people with 'serious and enduring mental illness'. At the same time research in the USA and UK has refocused much of its attention on neuroscientific theories and models of serious mental illness. Psychiatric nurses are being encouraged to consider the value of biomedical explanations of serious illness, such as schizophrenia, and to accommodate these theories and models in the practice of nursing. This paper will examine the challenge of the biomedical approach for the continued development of psychiatric nursing theory and practice. It is proposed that psychiatric nursing needs to develop further its own 'proper focus', if it is to survive as a key player in the health care field on the 21st century.

Humans↗
PubMed1996

Stress signaling in plants: a mitogen-activated protein kinase pathway is activated by cold and drought.

Yeast and animals use mitogen-activated protein (MAP) kinase cascades to mediate stress and extracellular signals. We have tested whether MAP kinases are involved in mediating environmental stress responses in plants. Using specific peptide antibodies that were raised against different alfalfa MAP kinases, we found exclusive activation of p44MMK4 kinase in drought- and cold-treated plants. p44MMK4 kinase was transiently activated by these treatments and was correlated with a shift in the electrophoretic mobility of the p44MMK4 protein. Although transcript levels of the MMK4 gene accumulated after drought and cold treatment, no changes in p44MMK4 steady state protein levels were observed, indicating a posttranslational activation mechanism. Extreme temperatures, drought, and salt stress are considered to be different forms of osmotic stress. However, high salt concentrations or heat shock did not induce activation of p44MMK4, indicating the existence of distinct mechanisms to mediate different stresses in alfalfa. Stress adaptation in plants is mediated by abscisic acid (ABA)-dependent and ABA-independent processes. Although ABA rapidly induced the transcription of an ABA-inducible marker gene, MMK4 transcript levels did not increase and p44MMK4 kinase was not activated. These data indicate that the MMK4 kinase pathway mediates drought and cold signaling independently of ABA.

Base Sequence↗
PubMed1996

Immunocytochemical mapping of a C-terminus anti-peptide antibody to the GABA receptor subunit, RDL in the nervous system in Drosophila melanogaster.

An antibody raised against a peptide based on the C-terminal derived amino acid sequence from a cloned Drosophila melanogaster (fruit fly) gene, Rdl (resistant to dieldrin), was used to investigate localization of a GABA receptor subunit in adult male D. melanogaster. Many regions in the brain and thoracic ganglia were stained with this antibody. For example, staining was detected in the medulla, lobula and lobular plate optic neurpiles. Also stained were the antennal lobe glomeruli, the ellipsoid body of the central complex and the mushroom bodies. These results suggest possible roles for an RDL-like GABA receptor subunit in the processing of olfactory, visual and mechanosensory information in the nervous system of D. melanogaster.

Amino Acid Sequence↗