Biomedical subjects
E Murphy
Publications and source records attributed to E Murphy.
Magnesium homeostasis in cardiac cells.
Several aspects of Mg2+ homeostasis were investigated in cultured chicken heart cells using the fluorescent Mg2+ indicator, FURAPTRA. The concentration of cytosolic Mg2+ ([Mg2+]i) is 0.48 +/- 0.03 mM (n = 31). To test whether a putative Na/Mg exchange mechanism controls [Mg2+]i below electrochemical equilibrium, we manipulated the Na+ gradient and assessed the effects on [Mg2+]i. When extracellular Na+ was removed, [Mg2+]i increased; this increase was not altered in Mg-free solutions, but was attenuated in Ca-free solutions. A similar increase in [Mg2+]i, which was dependent upon extracellular Ca2+, was observed when intracellular Na+ was raised by inhibiting the Na/K pump with ouabain. These results do not provide evidence for Na/Mg exchange in heart cells, but they suggest that Ca2+ can modulate [Mg2+]i. In addition, removing extracellular Na+ caused a decrease in intracellular pH (pHi), as measured by pH-sensitive microelectrodes, and this acidification was attenuated when Ca2+ was also removed from the solution. These results suggest that Ca2+ and H+ interact intracellularly. Since changes in the Na+ gradient can also alter pHi, we questioned whether pH can modulate [Mg2+]i. pHi was manipulated by the NH4Cl prepulse method. NH4(+)-evoked changes in pHi, as measured by the fluorescent indicator BCECF, were accompanied by opposite changes in [Mg2+]i; [Mg2+]i changed by -0.16 mM/unit pH. These NH4(+)-evoked changes in [Mg2+]i were not caused by movements of Mg2+ or Ca2+ across the sarcolemma or by changes in cytosolic Ca2+. Additionally, pHi was manipulated by changing extracellular pH (pHo).(ABSTRACT TRUNCATED AT 250 WORDS)
Adhesion to vascular cell adhesion molecule 1 and fibronectin. Comparison of alpha 4 beta 1 (VLA-4) and alpha 4 beta 7 on the human B cell line JY.
Most mononuclear leukocytes and cell lines express the integrin alpha 4 beta 1 (VLA-4) heterodimer. In this study we have used Northern blotting and immunoprecipitation experiments to demonstrate that a B lymphoblastoid cell line (JY) expressed the integrin beta 7 subunit in association with alpha 4. These alpha 4 beta 7-positive JY cells bound poorly or not at all to VLA-4 ligands (soluble form of vascular cell adhesion molecule 1 (sVCAM-1) and the CS1 region of fibronectin). In contrast, a beta 1-positive variant of JY cells (selected to express a mixture of alpha 4 beta 1 and alpha 4 beta 7) bound avidly to VLA-4 ligands, and this binding was completely inhibitable by anti-alpha 4 and anti-beta 1 monoclonal antibodies. Thus, beta 1 expression appears to be a critically important component of VLA-4-mediated binding to its ligands. After either JY or JY-beta 1 cells were stimulated for 15 min with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, the majority of adhesion to VCAM or fibronectin remained alpha 4- and beta 1-dependent, but a low amount of adhesion to sVCAM-1 or fibronectin became alpha 4-dependent, beta 1-independent, thus suggesting a role for alpha 4 beta 7. In summary, we have found (i) that alpha 4 beta 7 makes little or no contribution to fibronectin or VCAM-1 binding on unstimulated JY cells, (ii) that alpha 4 beta 7 perhaps makes a minor contribution to ligand binding on 12-O-tetradecanoyl-phorbol-13-acetate-stimulated cells, and (iii) that alpha 4 beta 1 is the functionally dominant VCAM-1 and fibronectin receptor even when expressed in relatively low amounts compared to alpha 4 beta 7.
Community care: "the cascade of change".
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Managing change in general practice: a step by step guide.
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Qualitative research and family practice: a marriage made in heaven?
Recent years have seen the development of interest in the usefulness of qualitative methods in family practice research. This paper shows how the underlying concerns of family practice medicine parallel those of the qualitative research tradition. After contrasting the philosophical underpinnings of both quantitative and qualitative methods, we go on to describe the methodological commitments of qualitative research. We relate this emerging debate within family practice to that which has taken place in other disciplines, particularly that of education. We discuss the relative strengths of qualitative and quantitative methods, and argue that these two traditions have complementary contributions to make to the discipline of family practice medicine.
Sexual transmission of HTLV infections in southern India.
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Chronic otitis media: a new extra-articular manifestation in ankylosing spondylitis?
Following a study reporting a fourfold increase in the occurrence of chronic otitis media in patients with ankylosing spondylitis, this prospective study examines this association with respect to severity, duration of disease, and acute phase in ankylosing spondylitis. Forty two consecutive patients with classical ankylosing spondylitis seen at the rheumatology clinic of a teaching hospital where the features of ankylosing spondylitis were recorded had an otological examination by an otolaryngologist. The occurrence of chronic otitis media (all categories) was 12/42 (29%). The acute phase serum markers (C reactive protein and IgG) were increased in patients with active or inactive chronic otitis media. Extra-articular manifestations were significantly more common in the chronic otitis media group than in those with no history of chronic otitis media. The results of this study suggest that chronic otitis media may be another extra-articular manifestation of ankylosing spondylitis. Alternative explanations, however, include similar aetiological factors for the two conditions or a previously unrecognised increased occurrence of HLA-B27 in patients with chronic otitis media.
Intracellular pH modulates cytosolic free magnesium in cultured chicken heart cells.
To assess the role of pH in cellular Mg homeostasis, cytosolic pH (pHi) was manipulated by the NH4Cl prepulse technique; pHi, cytosolic Mg2+ (Mgi), and cytosolic Ca2+ (Cai) were measured fluorometrically in single cultured embryonic chicken heart cells loaded with 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF), FURAPTRA, and fura-2, respectively. The basal values obtained were as follows: pHi = 7.21 +/- 0.10 (n = 7), [Mg]i = 0.51 +/- 0.08 mM (n = 9), [Ca]i = 126 +/- 15 nM (n = 7). When cells were perfused with 10 mM NH4Cl solution for 5 min, a transient alkalinization (0.53 U) of the cytosol was accompanied by a transient decrease (0.12 mM) in [Mg]i and a transient increase (59 nM) in [Ca]i; these changes approached control levels within 5 min. Upon removal of NH4Cl, a transient acidification (0.89 U) of the cytosol was accompanied by a transient increase (0.10 mM) in [Mg]i and a transient increase (125 nM) in [Ca]i; again, these changes returned toward control levels within 5 min. No significant changes in total cell Mg or Ca were observed during these manipulations. NH4Cl-evoked changes in [Mg]i were not altered significantly by either Mg-free or Ca-free conditions. Changes in [Mg]i were inversely correlated with changes in pHi and were not secondary to changes in [Ca]i. The results suggest that pHi modulates Mgi, probably by affecting cytosolic Mg binding and/or the transport of Mg across subcellular organelles.
Metabolic substrates can alter postischemic recovery in preconditioned ischemic heart.
The mechanisms that contribute to myocardial cell injury are not well understood. Furthermore, the ability of reperfusion conditions to modify ischemic injury is unclear. Recent studies have indicated that glucose utilization may improve ionic homeostasis. Because considerable derangement of ion concentrations occurs during ischemia, glucose utilization may be beneficial when stimulated during the reperfusion period. The effects of glycolytic vs. mitochondrial substrates on postischemic contractile function, high-energy phosphates and ion balance (intracellular Ca2+ and pH) were determined. Reperfusion conditions were compared in the "preconditioned ischemic" heart where baseline contractile recovery during reperfusion with glucose as the sole exogenous substrate was 74 +/- 5% (n = 10). Contractile recovery was determined for reperfusion with pyruvate (14 +/- 2%, n = 10), pyruvate+glucose (23 +/- 4%, n = 10), deoxyglucose+acetate (25 +/- 4%, n = 10), and lactate+glucose (60 +/- 11%, n = 10). Contractile dysfunction could not be attributed to differences in high-energy phosphate contents. Elevated levels of intracellular Ca2+ during reperfusion were, however, correlated with poor contractile function. After 20 min of reperfusion, the mean time-averaged intracellular Ca2+ values, measured with 19F-nuclear magnetic resonance of 5-fluoro-1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-loaded hearts, were 994 +/- 110 nM (glucose, n = 5), 2,270 +/- 494 nM (pyruvate, n = 5), 2,671 +/- 419 nM (pyruvate+glucose, n = 5), 2,382 +/- 480 nM (deoxyglucose+acetate, n = 5), and 1,019 +/- 33 nM (lactate+glucose, n = 5). These results are consistent with a beneficial role for glucose utilization during reperfusion, where enhanced recovery of contractile function and ionic homeostasis were observed.
General practice based diabetes surveillance: the views of patients.
Forty three patients with non-insulin dependent diabetes registered at two suburban practices were interviewed at least one year after the introduction of an organized general practice based system of diabetic surveillance and the results compared with data gathered from interviews administered before the introduction of the system. Structured data from the two interviews were compared in relation to the importance which patients attached to diabetes and its medical review, patients' preference for place of future review and the health professionals from whom they wished to receive diabetes care. Patients' ratings of the performance of health professionals on various aspects of care were compared with the ratings given before the introduction of the new service. At the follow-up interviews the reasons behind patients' responses to the structured questions were explored using a qualitative method. The introduction of a general practice based diabetes service was marked by an improvement in attendance for diabetes monitoring (56% before introduction, 98% in the year following introduction). This was associated with an increase in the importance which patients attached to diabetes and its medical review. After experience of diabetes care in general practice, patients remained enthusiastic about general practice involvement and confident in their general practitioners' knowledge about diabetes management. In spite of an improvement in the patients' ratings of hospital doctors' communication skills, they continued to rate general practitioners significantly more highly in these skills (P < 0.01) and in terms of convenience and accessibility (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Iron and nutritional status of toddlers.
The iron and nutritional status of 22 clinically well and normal toddlers, aged from one to four years inclusive was determined. Mean energy intake was normal. Protein, fibre and ascorbic acid intakes were high. Total iron intake was low in 73%, and available iron was low in 96%. The percentage availability of the total iron intake was 6.98 +/- 1.2, which is below the 10% assumption of iron availability based on consumption of the recommended daily allowances. Mean haemoglobin was with in the normal range. Low normal serum ferritin suggested poor iron stores. Anthropometric measurements were normal. Although the toddlers; intake of most dietary parameters was normal, the finding of poor iron intake and stores is of concern given recent reports of the role of iron in weight gain and psychomotor development.
'Will you help me with my research?' Gaining access to primary care settings and subjects.
This paper is concerned with the negotiation of agreement to carry out research in primary care settings. It is argued that this is a key part of any research project, and that careful handling of this process will not only improve response rates, but will also often enhance the quality of the data obtained. A number of strategies for negotiating access are proposed which have been developed and applied in primary care settings. These strategies depend on creating a sense of collective ownership of projects between researchers and participants which contributes to the successful completion of the projects and provides a positive atmosphere for further collaboration.
Alzheimer's disease: beta-amyloid precursor protein expression in plaques varies among cytoarchitectonic areas of the medial temporal lobe.
The anatomic distributions of beta-amyloid peptide (beta AP) and beta-amyloid precursor protein (beta APP) in the medial temporal lobe were examined with immunocytochemistry in Alzheimer's disease. beta AP-containing plaques were found most frequently in the cortical and basal regions of the amygdala, and in the hippocampal CA1, subiculum, and dentate molecular layer. beta APP expression in plaques was found in a similar distribution, with some, but not all beta AP plaques also showing beta APP. In the cortical and basal amygdala, some cases showed beta APP in the centers of plaques, whereas in the hippocampus, all cases displayed beta APP mainly in plaque neurites. The lateral regions of the amygdala contained mainly diffuse beta AP plaques which had little beta APP. These findings suggest that although beta APP expression and beta AP deposition generally colocalize, processing of beta APP may vary among closely interconnected anatomic regions.
Community mental health services: a vision for the future.
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Good records provide defense against malpractice suits.
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Delaying community care.
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Mutational analysis of att554, the target of the site-specific transposon Tn554.
Tn554 is a high-frequency, site-specific transposable element of Staphylococcus aureus which has integrative properties resembling those of temperate bacteriophages. Tn554 inserts at a unique chromosomal location, designated att554. att554 contains a core hexanucleotide sequence, 5'-GATGTA-3' (nucleotides numbered -3 to +3). Most of the time (greater than 99%) insertion occurs immediately 3' to this sequence; the resulting orientation of Tn554 to att554 is designated as the (+) orientation. Infrequent insertions immediately 5' to the core sequence result in the opposite, or (-) orientation. Mutational analysis of a cloned att554 site indicates that deletions extending from the left and ending at -15 or from the right ending between +8 and +12 reduced attachment site efficiency. Plasmids with deletions extending closer to the insertion site, although still retaining the core sequence from -3 to +3, were totally inactive. Tn554 insertions into partially active att554 sites retained normal site- and orientation-specificity with respect to att554, but they frequently contained abnormal sequences at the junction of att554 and the 3' end of Tn554. These data indicate that att554 contains a short nucleotide sequence essential for transposition and flanking sequences that greatly increase the frequency of recombination.