Spiritual retrieval: bringing spirituality to work.
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Canada↗
Biomedical subjects
S Cowley
Publications and source records attributed to S Cowley.
The mitogen-activated protein kinase kinase MEK1 stimulates a pattern of gene expression typical of the hypertrophic phenotype in rat ventricular cardiomyocytes.
Adult mammalian ventricular cardiomyocytes are terminally differentiated cells that enlarge adaptively by hypertrophy. In this situation, genes normally expressed in the fetal ventricular cardiomyocyte (e.g. atrial natriuretic factor (ANF), beta-myosin heavy chain (beta-MHC), and skeletal muscle (SkM) alpha-actin) are re-expressed, and there is transient expression of immediate early genes (e.g. c-fos). Using appropriate reporter plasmids, we studied the effects of transfection of the constitutively active or dominant negative mitogen-activated protein kinase kinase MEK1 on ANF, beta-MHC, and SkM alpha-actin promoter activities in cultured ventricular cardiomyocytes. ANF expression was stimulated (maximally 75-fold) by the hypertrophic agonist phenylephrine in a dose-dependent manner (EC50, 10 microM), and this stimulation was inhibited by dominant negative MEK1. Cotransfection of dominant negative MEK1 with a dominant negative mitogen-activated protein kinase (extracellular signal-regulated protein kinase (ERK2)) increased this inhibition. Transfection with constitutively active MEK1 constructs doubled ANF promoter activity. The additional cotransfection of wild-type ERK2 stimulated ANF promoter activity by about 5-fold. Expression of beta-MHC and SkM alpha-actin was also stimulated. Promoter activity regulated by activator protein-1 or c-fos serum response element consensus sequences was also increased. We conclude that the MEK1/ERK2 cascade may play a role in regulating gene expression during hypertrophy.
Amino Acid Sequence↗
Regulation of GATA-2 phosphorylation by mitogen-activated protein kinase and interleukin-3.
GATA-2 is a member of a family of transcription factors which bind a common DNA sequence motif (WGA-TAR) through an evolutionarily conserved zinc finger domain. An essential role for GATA-2 in the development of hematopoietic stem cells has recently been shown in gene targeting experiments in mice. Here we show that GATA-2 exists in hematopoietic progenitor cells as a phosphoprotein. Stimulation of progenitors with interleukin-3 (IL-3) results in enhanced phosphorylation of GATA-2 which occurs within 5 min. IL-3 is known to signal in part through mitogen-activated protein (MAP) kinase, and evidence for MAP kinase signaling in the control of GATA-2 phosphorylation was obtained by genetically manipulating the MAP kinase pathway in COS cells using either constitutively activating or interfering mutants of MAP kinase kinase. Furthermore, using an interfering mutant of MAP kinase kinase, we directly demonstrated a critical role for the MAP kinase pathway in the IL-3-dependent phosphorylation of GATA-2 in hematopoietic progenitor cells. Finally, in vitro phosphorylation experiments using recombinant GATA-2 raise the possibility that MAP kinase itself may phosphorylate GATA-2. Our results provide evidence for phosphorylation via the MAP kinase pathway constituting a cytoplasmic link between GATA-2 and growth factor receptors and are consistent with the hypothesis that GATA-2 is involved in the growth factor responsiveness and proliferation control of hematopoietic progenitor cells.
Animals↗
Assay and expression of mitogen-activated protein kinase, MAP kinase kinase, and Raf.
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Amino Acid Sequence↗
Professional development and change in a learning organization.
There is a growing tendency for learning in the workplace to be seen as a managerial function rather than as the responsibility of educationalists. As managers prepare to take a more active role in facilitating professional education, they need to consider the extent to which their organizational arrangements help or hinder the learning of professional skills. There is a potential risk that the development of important clinical practice skills may be inadvertently overlooked, because of the kind of organizational arrangements in force. This paper outlines alternative approaches to organizational development, explaining the basis for implementing 'holographic principles' when planning a system. A situational analysis carried out in an inner-city community provider unit revealed an alternative, more directive and fragmented arrangement. The analysis is used to illustrate how a focus on developing the organization as a learning environment during periods of rapid and multiple change can also help to promote clinical nursing skills.
Clinical Competence↗
In health visiting, a routine visit is one that has passed.
Pressure on British health workers to be more explicit in articulating the function, purpose and outcome of their role has increased with the introduction of general management and shift to a market-place orientation, since implementation of the NHS and Community Care Act (1990). However, a recurring theme in the history of health visiting has been the difficulty which practitioners experience in trying to explain exactly what it is that they do. This has often been portrayed as a major failing, and possibly even a reason to discontinue the service. This paper will offer a potential explanation for this difficulty, and suggest that the management of uncertainty and ambiguity are central to the role. It will draw on a grounded theory study which explored how health visitors choose which approach to use in any particular situation encountered in their work. The analysis suggested that health visiting's central focus is on situations which are unpredictable, ambiguous or anomalous. The study revealed an approach to health promotion which requires a highly developed ability to cope in a safe and therapeutic way with shifting, uncertain and ill-defined health needs, and to recognize and respond to complex, potentially risk-filled situations. Drawing on examples which illustrate the implications of these concepts in practice, the paper suggests that, much as midwives have long claimed that a 'normal delivery is one that is over', so in health visiting a 'routine visit' can only be recognized as such once it has taken place.(ABSTRACT TRUNCATED AT 250 WORDS)
Child↗
Health-as-process: a health visiting perspective.
Health visitors are community nurses who define their role specifically in terms of health promotion, although they have often found difficulty in explaining how their seemingly diffuse and unfocused practice achieves this. The grounded theory study reported here set out to uncover some of the hidden processes and features embedded within health visiting, so the practice might be more clearly articulated. This paper reports one aspect of that study, which suggests that health visitors treat health as a lifelong process, involving the accumulation and use of 'resources for health'. The relevance of approaches which appeared both caring and educational will be set in the context of therapeutic nursing and adult education theories. Historically, health visitors have links with both nursing and health education; the analysis presented here helps to clarify the relationships between these different areas of work. The paper will explain how treating health as a process allows multiple competing views and ideas about health and health promotion to be integrated into a manageable form, thus allowing positive health to be promoted within a broad, acceptable socio-cultural context. However, the analysis also highlighted various points at which treating health as a process contradicts the firmly measurable requirements of the market-orientated health service. Nevertheless, where health visitors are sufficiently skilled, and are permitted by their employing authorities to use this approach, it may serve to protect clients from intrusive and accusing interventions, made in the name of health promotion.
Community Health Nursing↗
Approaches to community needs assessment: a literature review.
In the light of the growing awareness of professionals in the community of the need to undertake health needs assessments of the population, this literature review sets out to explore, delineate and critically analyse the various approaches to community needs assessment, to facilitate a greater understanding of their strengths and weaknesses. The review commences by highlighting its complex nature, and attempting to define what is meant by 'needs assessment' from the differing perspectives of three dominant approaches, namely sociology, epidemiology and health economics. It continues by putting forward an argument for the use of the community health profile, being a multi-focal approach to needs assessment, combining quantitative with qualitative data, and proceeds with a discussion of strengths and weaknesses related to its compilation, in particular factors relating to reliability and validity of data sources. The consumer perspective is also reviewed, as are issues surrounding the ethics of data collection and problems concerning aggregation of the numerous data sources into meaningful policy. Throughout the review, issues are discussed with reference to the current political context in the United Kingdom. Equally important is the community nurse perspective, which is integrated into the arguments where appropriate.
Community Health Nursing↗
Caring with technology: relationship as the key to promoting dignity.
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Canada↗
Health promotion in the general practice setting.
Two major studies of health promotion interventions in the general practice setting appear to show that nurses are less effective than doctors in influencing people to make necessary lifestyle changes. But, as this briefing argues, both studies were heavily dominated by the medical model. Such an approach, focusing on ill-health, not health, fails to take into account the wider social and economic factors influencing individuals' behaviours. Far from indicating the need for greater input from doctors, the studies serve to reinforce arguments against the medical model in health. promotion, and underline the need for the health-oriented approach which now underpins all nursing education and training.
Family Practice↗
Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27.
An IL-1-stimulated protein kinase cascade resulting in phosphorylation of the small heat shock protein hsp27 has been identified in KB cells. It is distinct from the p42 MAP kinase cascade. An upstream activator kinase phosphorylated a 40 kDa kinase (p40) upon threonine and tyrosine residues, which in turn phosphorylated a 50 kDa kinase (p50) upon threonine (and some serine) residues. p50 phosphorylated hsp27 upon serine. p40 and p50 were purified to near homogeneity. All three components were inactivated by protein phosphatase 2A, and p40 was inactivated by protein tyrosine phosphatase 1B. The substrate specificity of p40 differed from that of p42 and p54 MAP kinases. The upstream activator was not a MAP kinase kinase. p50 resembled MAPKAPK-2 and may be identical.
Amino Acid Sequence↗
Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells.
The MAP kinase pathway is activated by a wide variety of external signals leading to cell proliferation or differentiation. However, it is not clear whether activation of this pathway is required for cellular responses or whether it is only one branch point in signal transduction. To investigate these questions, we generated constitutively activated and interfering mutants of MAP kinase kinase 1. The activated mutants stimulated PC12 cell neuronal differentiation and transformed NIH 3T3 cells. The interfering mutants inhibited growth factor-induced PC12 differentiation, growth factor stimulation of proliferation, and reverted v-src- and ras-transformed cells. These results therefore show that, depending on cellular context, activation of MAP kinase kinase is necessary and sufficient for cell differentiation or proliferation.
3T3 Cells↗
Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1.
Many growth factors whose receptors are protein tyrosine kinases stimulate the MAP kinase pathway by activating first the GTP-binding protein Ras and then the protein kinase p74raf-1. p74raf-1 phosphorylates and activates MAP kinase kinase (MAPKK). To understand the mechanism of activation of MAPKK, we have identified Ser217 and Ser221 of MAPKK1 as the sites phosphorylated by p74raf-1. This represents the first characterization of sites phosphorylated by this proto-oncogene product. Ser217 and Ser221 lie in a region of the catalytic domain where the activating phosphorylation sites of several other protein kinases are located. Among MAPKK family members, this region is the most conserved, suggesting that all members of the family are activated by the phosphorylation of these sites. A 'kinase-dead' MAPKK1 mutant was phosphorylated at the same residues as the wild-type enzyme, establishing that both sites are phosphorylated directly by p74raf-1, and not by autophosphorylation. Only the diphosphorylated form of MAPKK1 (phosphorylated at both Ser217 and Ser221) was detected, even when the stoichiometry of phosphorylation by p74raf-1 was low, indicating that phosphorylation of one of these sites is rate limiting, phosphorylation of the second then occurring extremely rapidly. Ser217 and Ser221 were both phosphorylated in vivo within minutes when PC12 cells were stimulated with nerve growth factor. Analysis of MAPKK1 mutants in which either Ser217 or Ser221 were changed to glutamic acid, and the finding that inactivation of maximally activated MAPKK1 required the dephosphorylation of both serines, shows that phosphorylation of either residue is sufficient for maximal activation.
Amino Acid Sequence↗
Identification and characterization of a novel tyrosine kinase from megakaryocytes.
Protein-tyrosine kinases play pivotal roles in cell signal transduction. We have isolated a cDNA clone encoding a novel human intracytoplasmic tyrosine kinase, termed matk (megakaryocyte-associated tyrosine kinase). Expression of matk mRNA was predominantly found in cells of megakaryocytic lineage. The matk cDNA clone encodes a polypeptide of 527 amino acids and has closest sequence similarity to the csk tyrosine kinase. Sequence comparisons also indicate that matk contains src homology region 2 and 3 domains but lacks the NH2-terminal myristylation signal, the negative regulatory tyrosine (Tyr-527), and the autophosphorylation site (Tyr-416) corresponding to those found in src. Antibodies raised against the NH2 terminus of matk immunoprecipitated a 60-kDa protein from the CMK human megakaryocyte cell line. Expression of matk mRNA was up-regulated in megakaryocytic cells induced to differentiate by the phorbol ester. Based on its restriction in expression and its modulation during in vitro differentiation, it is likely that matk participates in signal transduction during megakaryocytopoiesis.
Base Sequence↗
Connecting values and program development. A Canadian hospital's experience with mission integration.
Catholic values distinguish Catholic healthcare facilities, their staff members like to say. But those values can remain merely rhetorical unless they are integrated into the facility's actual programs. The staff of St. Joseph's Hospital, Hamilton, Ontario, has been encouraged to express the facility's values in everyday language. More important, the staff has had an opportunity to employ those values--a belief in the sacredness of life and the dignity of the person; a special obligation to the poor and vulnerable; and a commitment to treat the "whole person"--in two new programs. One is for women who have miscarriages. The hospital's Obstetrics Department, realizing that society often fails to recognize the deep grief involved, developed a program for women experiencing early pregnancy loss (EPL). The EPL protocol stresses the uniqueness of each patient and the importance of support, continuity, appropriateness of care, and postdischarge follow-up for her. The hospital has also emphasized Catholic values in developing a set of guidelines for the examination of patients. St. Joseph's found that publicity about sexual abuse was making both patients and medical practitioners wary of physical examinations. The guidelines, called "Culture and Sensitivity," remind care givers that patients feel vulnerable and should be treated with respect and care, on one hand. On the other hand, the guidelines say, appropriate reassuring touch remains part of the healing process.
Catholicism↗
Collaboration in health care: the education link.
Collaboration is high on the current policy agenda. It is often suggested that 'shared learning' within multi-disciplinary teams, across sectors and different service agencies, will help to improve collaboration. But education has a wider role than one of simply teaching different groups together, writes Sarah Cowley. Improved inter-disciplinary working can be achieved by ensuring that each professional feels valued for their particular role and skills.
Community Health Nursing↗
Characterization of adhesive interactions between human endothelial cells and megakaryocytes.
Cell-cell adhesion is essential for many immunological functions and is believed to be important in the regulation of hematopoiesis. Adhesive interactions between human endothelial cells and megakaryocytes were characterized in vitro using the CMK megakaryocytic cell line as well as marrow megakaryocytes. Although there was no adhesion between unactivated human umbilical vein endothelial cells (HUVEC) and megakaryocytes, treatment of HUVEC with inflammatory cytokines such as IL-1 beta, tumor necrosis factor alpha, INF-gamma, or the phorbol ester phorbol myristate acetate (PMA) resulted in a time- and dose-dependent increase in adhesion. Stimulation of marrow megakaryocytes or CMK cells with the cytokines IL-1 beta, GM-CSF, IL-6, IL-3, or PMA augmented their adhesion to endothelium. Monoclonal antibodies against the LFA-1 subunit of the leukocyte adherence complex CD18 inhibited the binding of marrow megakaryocytes or CMK cells to HUVEC. Adhesion blocking experiments also demonstrated that the VLA-4/VCAM-1 pathway was important for megakaryocyte attachment to HUVEC. Adhesion promoted maturation of megakaryocytic cells as measured by increased expression of glycoproteins GpIb and GpIIb/IIIa and by increased DNA content. These observations suggest that alterations in megakaryocyte adhesion may occur during inflammatory conditions, mediated by certain cytokines, resulting in augmented megakaryocyte maturation.
Bone Marrow↗
Skill mix: value for whom?
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Clinical Competence↗