More on centralisation.
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Diagnosis, Differential↗
Biomedical subjects
A Long
Publications and source records attributed to A Long.
Inside the crawling T cell: leukocyte function-associated antigen-1 cross-linking is associated with microtubule-directed translocation of protein kinase C isoenzymes beta(I) and delta.
T cells activated via integrin receptors can polarize and start crawling locomotion with repeated cycles of cytoskeletal reassembly processes, many of which depend on phosphorylation. We demonstrate that protein kinase C (PKC) activation represents an essential event in induction of active T cell motility. We find that in crawling T cells triggered via cross-linking of integrin LFA-1 two PKC isoenzymes, beta(I) and delta, are targeted to the cytoskeleton with specific localization corresponding to the microtubule-organizing center (MTOC) and microtubules, as detected by immunocytochemistry and immunoblotting. Clustering of LFA-1 associated with its signaling function also occurs at the membrane sites adjacent to the MTOC. We further show that cells of a PKC-beta-deficient clone derived from parental PKC-beta-expressing T cell line can neither crawl nor develop a polarized microtubule array upon integrin cross-linking. However, their adhesion and formation of actin-based pseudopodia remain unaffected. Our data demonstrate the critical importance of the microtubule cytoskeleton in T cell locomotion and suggest a novel microtubule-directed intracellular signaling pathway mediated by integrins and involving two distinctive PKC isoforms.
Biological Transport↗
Getting prepared for rural practice.
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Canada↗
Neuropeptide immunoreactivity in ligature-induced neuromas of the inferior alveolar nerve in the ferret.
Injury to branches of the trigeminal nerve can sometimes result in persistent dysaesthesia. In an attempt to understand the aetiology of this condition we are currently investigating changes which occur at the injury site. In the present study we have examined the expression of seven neuropeptides, all of which have been implicated in nociceptive transmission, or have previously been shown to have altered expression following nerve injury. In 20 adult ferrets the inferior alveolar nerve was sectioned and ligated, and recovery permitted for 3 days, 8 days, 3 weeks, 6 weeks or 12 weeks. Longitudinal sections of the neuromas were processed using immunohistochemical techniques to quantify the expression of substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, galanin, somatostatin, enkephalin and neuropeptide Y. After 3 days, all of the neuropeptides were expressed at the injury site. In the neuromas examined after longer recovery periods these levels of expression had declined and were similar to those found in the contralateral controls. This initial high level, followed by a decline, parallels the incidence of ectopic neural activity recorded electrophysiologically in the same model. It is, therefore, possible that the accumulation of neuropeptides at the injury site may play a role in the initiation or modulation of ectopic neural activity.
Animals↗
The conception of community children's nursing services in Northern Ireland.
This report is an exploration of the implications of establishing a community children's nursing service in Northern Ireland. It provides a description of the backdrop to the development of the service in the United Kingdom, and the experiences of children's nurses in attempting to upgrade the quality of care offered to sick children in this province. The frustrations that have characterized this development are explored in detail within the context of broader changes in health care on the national scene. The article ends with recommendations for implementing an effective service, following our experiences in Northern Ireland.
Adolescent↗
Are altered pharmacokinetics of non-steroidal anti-inflammatory drugs (NSAIDs) a risk factor for gastrointestinal bleeding?
AIMS: We hypothesised that pharmacokinetic factors might go some way to explaining the risk of major gastrointestinal haemorrhage with non-steroidal anti-inflammatory drugs (NSAIDs), with bleeders exhibiting a reduced clearance of NSAIDs compared with non-bleeders and set out to investigate this. METHODS: Fifty patients presenting to hospital with acute gastrointestinal bleeding while taking piroxicam, indomethacin, diclofenac or naproxen and age, sex, musculoskeletal disease and drug matched community dwelling controls, up to two for each index case, who had not bled were recruited. Clinical details including duration of therapy were recorded. Bleeders discontinued the implicated NSAID at presentation, controls at least five half-lives before the study. Bleeders were contacted by letter 1 month after discharge and invited to take part and were studied after a median delay of 5 months. Subjects received an oral dose of their respective NSAID and venous blood was sampled, over a period determined by the half-life of the NSAID. Plasma concentrations were determined by high performance liquid chromatography. RESULTS: The median length of treatment for the index patients was 1 year (range 2 weeks--28 years) and for the control patients 2 years (1 month--25 years), P<0.0005. There were no significant differences in peak plasma concentration, time to peak plasma concentration or area under the plasma concentration-time curve between bleeders or controls for any of the NSAIDs studied, apart from piroxicam Cmax being lower in bleeders at 2.07 mg l(-1) than in controls at 3.21 mg l(-1), mean difference (95% CI) -1.14 (-1.83 - -0.48), P<0.005. CONCLUSIONS: The data failed to support the hypothesis that reduced clearance of NSAIDs, which results in higher plasma concentrations, is a risk factor for acute gastrointestinal haemorrhage.
Anti-Inflammatory Agents, Non-Steroidal↗
The role of mental health nursing in the prevention of child sexual abuse and the therapeutic care of survivors.
This paper is primarily designed to stimulate discussion and debate on the role of the mental health nurse dealing with survivors of sexual abuse. The authors contend that, in reality, all nurses should be prepared through education and training to treat the sufferers of emotional and spiritual pain, regardless of from where the hurting stems. The need for nurses to open their eyes and acknowledge the agony and distress caused to children as a result of abuse by adults is highlighted. So too is the necessity for nurses to enhance their own unique and specific practice. Nurses (and particularly mental health nurses) have a role in promoting a healthy generation of children--children who are looked after and protected by caregivers and not by caretakers. As the result of nurses advocating healthy caregiving and healthy relationships children may never need to suffer from inhumane and denigrating acts against their very beings. Nurses have no excuse for being unable to imagine child sexual abuse. Therefore they have no excuse for not being prepared to deal with the resulting, excruciating pain. It is both uncaring and inhumane for nurses not to be prepared to accept the sharing of such emotionally painful and disturbing experiences. Mental health nurses have a genuine role in offering therapeutic care to victims and survivors. This paper concludes by exploring and examining the nurse's role in counselling survivors of child sexual abuse.
Adult↗
The healing process, the road to recovery and positive mental health.
This paper is designed to explore and examine the experience of loss following a hysterectomy. The painful aftermath of the ordeal and the work involved in the healing process are outlined and discussed from both a personal and professional perspective. The manuscript highlights a number of inner struggles that had to negotiated before an equilibrium in mental health and wellbeing was successfully achieved. The forces that move the dialogue forward from one theme to the other are complex in their simplicity. The enigmatic dimensions of physical pain and emotional torment are expressed and worked through in a sensitive and intimate manner. The mysteries of internalized, conflicting messages on socialization issues, such as gender roles and living in and identifying with only one culture are discussed and debated. In addition, the disharmony between spiritual ideals, the meaning and purpose of life, the process of self-actualizing and the physical realities involved in living are identified and elaborated upon. Embroidered within the tapestry of the text is the need to revisit the curriculum for the education and training of mental health nurses to enhance the quality and provision of effective, humane and therapeutic nursing care.
Adaptation, Psychological↗
Linking injection drug users to medical services: role of street outreach referrals.
Street outreach workers in HIV prevention have expanded their role to include referring injection drug users to medical services. However, little is known about whether drug users act on these referrals. The study discussed in this article examined the level of exposure to street outreach reported by injection drug users, the most common medical referrals acted on as a result of such contacts, and the predictors of acting on these referrals. Findings indicate that injection drug users with four or more contacts with street outreach workers during the preceding six months were more likely to report acting on referrals. To maximize the relevance of outreach for encouraging medical treatment, both street outreach workers and social workers in health care could benefit from cross training that focuses on strengthening the referral process.
Adult↗
New needle and syringe use, and use of needle exchange programmes by street recruited injection drug users in 1993.
BACKGROUND: Needle exchange programmes (NEP) provide injection drug users (IDU) with sterile injection equipment and receive used needles in exchange. In this paper we describe the use of new syringes and NEP by IDU and characteristics associated with using NEP in 1993. METHODS: Street-recruited IDU were interviewed in five US locations: Atlanta, Philadelphia, Chicago, New York City, and Los Angeles (LA) county. RESULTS: Most (75-95%) reported it was easy to get a new syringe and for their last injection, 45-77% used a new syringe and 2-18% used a syringe previously used by another IDU. Use of NEP ranged from 8% to 16% in Chicago, Philadelphia, and LA County. In LA County not having injected 'speedball' in the last 30 days, last injection with a new syringe, and reporting it was very easy to get a new syringe were associated with NEP use. In Philadelphia, NEP use was associated with 'speedball' injection in the last 30 days, and in Chicago, not injecting with 'speedball' and injecting with cocaine were associated with NEP use. CONCLUSIONS: In 1993, most street-recruited IDU in Chicago, Philadelphia, and LA County had not used NEP. Factors associated with NEP use were not consistent across sites. Dispersion of NEP and removal of legal barriers restricting access to sterile syringes may be more important in increasing the use of sterile syringes and NEP than client characteristics.
Adult↗
Suicide: a statement of suffering.
This article is designed to focus on the provision of nursing care in general medical wards following the admission of persons who have attempted suicide or who have a previous history of attempting suicide. The authors explore, analyse and synthesize how nurses, as key players in the health care team, may begin by recognizing the uniqueness of the individual, and by cotravelling therapeutically with the person on part of his or her journey towards recovery and healing. Efforts are made to demonstrate how nurses can influence the health gain of this group of people and their families. Professional attitudes and related ethical aspects, such as autonomy, respect for autonomy and paternalism, are also examined within the context of the nursing care of people who have attempted suicide. The need to enhance sensitive and caring communication skills for nurses who work with this group of people is tentatively considered. Some reasoning about why there may be difficulties in specific areas of communication such as empathy are contested and explored.
Attitude of Health Personnel↗
The legal and ethical status of children in health care in the UK.
Ethical issues about children's rights in respect of matters concerning resource allocation or treatment opportunities are now a matter for public consumption and concern. Alongside this exists a long-frustrated desire by children's nurses to promote children's health. Long-held assumptions about the legal and moral status of children within the health care system in this country are now rightly scrutinized and challenged. Those of us who claim to represent children now possess an opportunity to exploit public attention for the benefit of these children. This article will explore selected major relevant legal and moral concepts that relate to children with the aim of making transparent some of the important and often confusing information available. It is anticipated that debates about the legal and ethical status of children may be stimulated and fuelled from the following discussion. It is strongly recommended that entering into dialogue with families and children about their perceived needs will go a long way towards advancing thoughtful nursing care of individual children, their families and the general population.
Child↗
[Medical recommendations and references 1997. Stenosis of the origin of the cervical internal carotid and the carotid bifurcation: surgery, angioplasty. ANAES. National Agency for Accreditation and Evaluation in Health].
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Angioplasty↗
Protein kinase C and T cell function.
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Animals↗
Characterization of murine Flt4 ligand/VEGF-C.
Flt4 is a receptor protein tyrosine kinase that is expressed in the adult lymphatic endothelium and high endothelial venules. We have used a BIAcore assay to identify rodent and human cell conditioned media containing the ligand of Flt4 (Flt4-L). Receptor-based affinity chromatography was used to purify this growth factor, followed by amino acid sequencing and molecular cloning of the murine cDNA, the orthologue of human vascular endothelial growth factor-C and vascular endothelial growth factor related protein. The murine flt4-L gene was localized to chromosome 8 and demonstrated to be widely expressed. Flt4-L was found to have a hydrophobic signal sequence and a pro-peptide-like sequence that is removed to generate the mature N-terminus. In addition, the C-terminal region of Flt4-L has four repeats of a cysteine-rich motif that is presumably also proteolytically processed to generate the 21000 Mr polypeptide subunit of the Flt4-L homodimer. Recombinant Flt4-L activated Flt4 as judged by induction of tyrosyl phosphorylation, and induced mitogenesis in vitro of lymphatic endothelial cells.
Amino Acid Sequence↗
Vegetarians and vegans may be most at risk from low selenium intakes.
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Diet, Vegetarian↗
TNF-mediated cytotoxicity of L929 cells: role of staurosporine in enhancement of cytotoxicity and translocation of protein kinase C isozymes.
The role of protein kinase C (PKC) in tumour necrosis factor (TNF)-mediated cytotoxicity was investigated, using the L929 cell line. The PKC activator phorbol-12-myristate 13-acetate (PMA) increased proliferation and inhibited TNF-induced cytotoxicity of L929 cells. A range of specific PKC inhibitors had no effect on TNF-mediated killing, suggesting that PKC does not play a direct role in this response. However, staurosporine enhanced cytotoxicity by TNF in the presence of actinomycin D, a protein synthesis inhibitor. In view of this finding, the authors investigated the role of specific PKC isozymes in both TNF-mediated cytotoxicity and staurosporine-induced sensitization to killing. PKC-alpha, beta, epsilon and zeta were detected in L929 cells. PKC-beta was only weakly detected in the cytoplasm, PKC alpha, epsilon and zeta were all found in resting cytoplasm and membrane. Stimulation with PMA caused a strong translocation of PKC-alpha but not zeta to the membrane. TNF had no effect on these isozymes but interestingly caused a translocation of PKC-epsilon, which also occurred in response to PMA. Staurosporine caused a translocation of PKC-zeta to the plasma membrane and a loss of PKC-epsilon from the cytosol. Although TNF induced PKC-epsilon translocation, this is unlikely to be involved in cytotoxicity as this effect was also induced by PMA which protected against TNF-mediated cytotoxicity. Staurosporine also induced translocation of PKC-zeta, an isozyme whose activity was previously found to be resistant to inhibition by staurosporine. These findings suggest the possibility that the mechanism by which staurosporine potentiates TNF action does not involve inhibition of PKC, but in contrast may involve modulation of PKC-zeta.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Protein kinase C isotypes theta, delta and eta in human lymphocytes: differential responses to signalling through the T-cell receptor and phorbol esters.
The repertoire of novel and atypical protein kinase C (PKC) isotypes present in human T cells and their subcellular localization have not been fully characterized. We detected calcium-independent PKC activity in whole cell fractions from unstimulated peripheral blood lymphocytes (PBL). Towards an understanding of the role of PKC isoforms in lymphocyte activation we have studied the expression of calcium-independent PKC isoforms theta, delta and eta in PBL. With isoformspecific antibodies we detected the presence of PKC theta and delta in whole cell fractions from unstimulated human PBL by Western blot analysis. In addition, immunocytochemical analysis confirmed the presence of the novel PKC isoform PKC eta in PBL. Using immunocytochemistry, PKC theta, delta and eta had distinct patterns of redistribution following activation by phorbol myristate acetate (PMA). However, signalling through the T-cell receptor (TCR) did not appear to induce such changes in isoenzyme redistribution. These findings indicate that activation of lymphocytes either through the TCR-CD3 complex or with PMA induces different signalling pathways with respect to calcium-independent isoenzymes. Signalling through receptors other than the CD3 complex may be involved in activation of these isotypes.
Blotting, Western↗