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Biomedical subjects

A Henderson

Publications and source records attributed to A Henderson.

At least 19 recordsLinked to original sources

The beta-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors.

The lymphatic vessels (lymphatics) play an important role in channeling fluid and leukocytes from the tissues to the secondary lymphoid organs. In addition to driving leukocyte egress from blood, chemokines have been suggested to contribute to leukocyte recirculation via the lymphatics. Previously, we have demonstrated that binding sites for several pro-inflammatory beta-chemokines are found on the endothelial cells (ECs) of lymphatics in human dermis. Here, using the MIP-1alpha isoform MIP-1alphaP, we have extended these studies to further support the contention that the in situ chemokine binding to afferent lymphatics exhibits specificity akin to that observed in vitro with the promiscuous beta-chemokine receptor D6. We have generated monoclonal antibodies to human D6 and showed D6 immunoreactivity on the ECs lining afferent lymphatics, confirmed as such by staining serial skin sections with antibodies against podoplanin, a known lymphatic EC marker. In parallel, in situ hybridization on skin with antisense D6 probes demonstrated the expression of D6 mRNA by lymphatic ECs. D6-immunoreactive lymphatics were also abundant in mucosa and submucosa of small and large intestine and appendix, but not observed in several other organs tested. In lymph nodes, D6 immunoreactivity was present on the afferent lymphatics and also in subcapsular and medullary sinuses. Tonsilar lymphatic sinuses were also D6-positive. Peripheral blood cells and the ECs of blood vessels and high endothelial venules were consistently nonreactive with anti-D6 antibodies. Additionally, we have demonstrated that D6 immunoreactivity is detectable in some malignant vascular tumors suggesting they may be derived from, or phenotypically similar to, lymphatic ECs. This is the first demonstration of chemokine receptor expression by lymphatic ECs, and suggests that D6 may influence the chemokine-driven recirculation of leukocytes through the lymphatics and modify the putative chemokine effects on the development and growth of vascular tumors.

Adult↗

A study of the impact of discharge information for surgical patients.

AIM OF THE STUDY: To establish whether the routine information surgical patients receive about the management of pain and wound care during their hospitalization is sufficient for them to care for themselves without seeking assistance from a health professional or health care agency. BACKGROUND: While there has been considerable evidence suggesting cost benefits of discharge information the health care environment is constantly changing. Contemporary issues such as increased patient participation, extensive use of technology, reduction in health care expenditure, and greater awareness of consumer rights necessitate further inquiry into the appropriateness of discharge information. METHOD: One hundred and fifty-eight adult patients discharged within a week of their operation participated in the study. A written questionnaire was distributed within 24 hours prior to discharge and a telephone interview conducted 1 to 2 weeks after discharge. At the time of discharge the majority of patients had received information. FINDINGS: Those patients who had received information were less likely to access a health facility than those who had not received information. However, the telephone interview, revealed that there was no evidence that patients who believed they were well informed within 24 hours of discharge about the management of their wound, still felt well informed 1 to 2 weeks later. CONCLUSION: Nurses need to be aware that patients who leave the hospital with little or no discharge information may not be confident in the management of their health condition and therefore may access a health facility, if even just for reassurance.

Adolescent↗

Emotional labor and nursing: an under-appreciated aspect of caring work.

This paper describes one component of the findings of a larger research study entitled 'Nurses' social construction of self: Implications for work with abused women'. One of the most consistent themes arising from that study involved nurses' views regarding the relevance of emotional engagement/detachment in pursuit of excellence in their practice. In this article this theme is examined in the light of work on emotional labor and the emotional work of nursing. Nurses' high degree of satisfaction in the emotional rewards of their work with clients is described and contrasted with their dissatisfaction in relation to nursing education and their views of the lack of valuing of nurses' work by others within the healthcare system. The importance of supporting them in relation to the emotional aspects of their work is explored.

Attitude of Health Personnel↗

Postpartum positioning and attachment education for increasing breastfeeding: a randomized trial.

BACKGROUND: Although lactation experts suggest that a correct positioning and attachment technique reduces breastfeeding problems and enhances long-term breastfeeding, evidence from randomized trials is lacking. The objective of this study was to evaluate the effect of postpartum positioning and attachment education on breastfeeding outcomes in first-time mothers. METHOD: A randomized trial was performed in a public hospital in Adelaide, South Australia, where 160 first-time mothers were randomly allocated to receive either structured one-to-one education (experimental group) or usual postpartum care (control group) within 24 hours of birth. The primary outcome was breastfeeding at 6 weeks and 3 and 6 months postpartum; other outcomes were nipple pain and trauma in hospital and at 6 weeks and 3 and 6 months, and satisfaction with breastfeeding. RESULTS: No significant differences occurred in breastfeeding rates between the groups at each endpoint, although a trend in the direction of lower rates was seen at each endpoint in the experimental group. This group reported less nipple pain on days 2 (p = 0.004) and 3 (p = 0.04), but this was not sustained on follow-up. No differences were observed in nipple trauma in hospital or in self-reported nipple pain and/or trauma at the three endpoints. Experimental group women were less satisfied with breastfeeding at 3 and 6 months postpartum when using a one-item measure; however, a multiple-item measure showed no significant differences at the three endpoints. CONCLUSIONS: The intervention did not increase breastfeeding duration at any assessment time or demonstrate any differences between the groups on secondary outcomes. The trend toward lower breastfeeding rates in the experimental group suggests a need for a larger trial to evaluate whether or nor postpartum positioning and attachment education may negatively affect breastfeeding.

Adult↗

Interaction between CCAAT/enhancer binding protein and cyclic AMP response element binding protein 1 regulates human immunodeficiency virus type 1 transcription in cells of the monocyte/macrophage lineage.

Recent observations have shown two CCAAT/enhancer binding protein (C/EBP) binding sites to be critically important for efficient human immunodeficiency virus type 1 (HIV-1) replication within cells of the monocyte/macrophage lineage, a cell type likely involved in transport of the virus to the brain. Additionally, sequence variation at C/EBP site I, which lies immediately upstream of the distal nuclear factor kappa B site and immediately downstream of a binding site for activating transcription factor (ATF)/cyclic AMP response element binding protein (CREB), has been shown to affect HIV-1 long terminal repeat (LTR) activity. Given that C/EBP proteins have been shown to interact with many other transcription factors including members of the ATF/CREB family, we proceeded to determine whether an adjacent ATF/CREB binding site could affect C/EBP protein binding to C/EBP site I. Electrophoretic mobility shift analyses indicated that selected ATF/CREB site variants assisted in the recruitment of C/EBP proteins to an adjacent, naturally occurring, low-affinity C/EBP site. This biophysical interaction appears to occur via at least two mechanisms. First, low amounts of CREB-1 and C/EBP appear to heterodimerize and bind to a site consisting of a half site from both the ATF/CREB and C/EBP binding sites. In addition, CREB-1 homodimers bind to the ATF/CREB site and recruit C/EBP dimers to their cognate weak binding sites. This interaction is reciprocal, since C/EBP dimer binding to a strong C/EBP site leads to enhanced CREB-1 recruitment to ATF/CREB sites that are weakly bound by CREB. Sequence variation at both C/EBP and ATF/CREB sites affects the molecular interactions involved in mediating both of these mechanisms. Most importantly, sequence variation at the ATF/CREB binding site affected basal LTR activity as well as LTR function following interleukin-6 stimulation, a treatment that leads to increases in C/EBP activation. Thus, HIV-1 LTR ATF/CREB binding site sequence variation may modulate cellular signaling at the viral promoter through the C/EBP pathway.

Binding Sites↗

Inhibition of insulin-like growth factor-I signaling by ethanol in neuronal cells.

BACKGROUND: Ethanol inhibits insulin-like growth factor-I receptor (IGF-IR) activation. However, the potency of ethanol for inhibition of the IGF-IR and other receptor tyrosine kinases varies considerably among different cell types. We investigated the effect of ethanol on IGF-I signaling in several neuronal cell types. METHODS: IGF-I signaling was examined in SH-SY5Y neuroblastoma cells, primary cultured rat cerebellar granule neurons, and rat NG-108 neuroblastoma x glioma hybrids. The tyrosine phosphorylation of IGF-IR, IRS-2, Shc, and p42/p44 MAP kinase (MAPK), and the association of Grb-2 with Shc, were examined by immunoprecipitations and Western blotting. RESULTS: IGF-I-mediated tyrosine phosphorylation of MAPK was inhibited by ethanol in all cell lines. IGF-IR autophosphorylation was markedly inhibited by ethanol in SH-SY5Y cells, was only mildly inhibited in cerebellar granule neurons, and was unaffected in rat NG-108 cells. In vitro tyrosine autophosphorylation of immunopurified IGF-IR obtained from all cell lines was inhibited by ethanol. There was also differential ethanol sensitivity of IRS-2 and Shc phosphorylation, and the association of Shc with IRS-2, among the different cell types. CONCLUSIONS: The findings demonstrate that IGF-I-mediated MAPK activation is a sensitive target of ethanol in diverse neuronal cell types. The data are consistent with ethanol-induced inhibition of IGF-IR activity, although the extent of IGF-IR tyrosine autophosphorylation per se is a poor marker of the inhibitory action of ethanol on this receptor. Furthermore, despite uniform inhibition of MAPK in the different neuronal cell types, tyrosine phosphorylation of proximal mediators of the IGF-IR are differentially inhibited by ethanol.

Blotting, Western↗

Effects of the protein tyrosine phosphatase CD45 on FcgammaRIIa signaling and neutrophil function.

OBJECTIVE: Neutrophil receptors for the Fc portion of IgG (FcgammaR) trigger immune responses following cross-linking by IgG-coated foreign particles or immune complexes. Membrane-associated CD45, a protein tyrosine phosphatase termed leukocyte common antigen, has been shown to be essential for antigen receptor kinase mediated signaling in lymphocytes, and we hypothesized that CD45 may play a similar role in FcgammaR-mediated signaling and immune function in human neutrophils. METHODS: The experimental approach was that of cell surface molecule ligation via cross-linking with specific antibodies. Antibody dependent cellular cytotoxicity (ADCC) was assessed using a single-cell plaque assay and IL-6 production measured using ELISA. Tyrosine phosphorylation levels were assessed with anti-phospho-tyrosine blots and F-actin polymerization by flow cytometry and confocal microscopy. RESULTS: Neutrophils pretreated with anti-CD45 had a reduced ability to perform ADCC compared to untreated neutrophils. FcgammaRIIa cross-linking resulted in significantly increased concentrations of secreted IL-6 compared to untreated neutrophils, and IL-6 production was further enhanced by cocross-linking CD45 with FcgammaRIIa. Cross-linking CD45 alone also induced IL-6 production. FcgammaRIIa cross-linking resulted in increased protein tyrosine phosphorylation and F-actin polymerization in neutrophils. Cocross-linking CD45 with FcgammaRIIa resulted in abrogation of FcgammaRIIa mediated tyrosine phosphorylation and F-actin polymerization. CONCLUSIONS: These data provide evidence that CD45 can regulate or enhance the stimulation and function of human neutrophils mediated through FcgammaR(s). In addition, CD45 ligation may play an essential role in cytokine induction pathways that lead to inflammatory reactions in vivo.

Actins↗

High-mobility-group protein I can modulate binding of transcription factors to the U5 region of the human immunodeficiency virus type 1 proviral promoter.

HMG I/Y appears to be a multifunctional protein that relies on in its ability to interact with DNA in a structure-specific manner and with DNA, binding transcriptional activators via distinct protein-protein interaction surfaces. To investigate the hypothesis that HMG I/Y may have a role in human immunodeficiency virus type 1 (HIV-1) expression, we have analyzed whether HMG I/Y interacts with the 5' long terminal repeat and whether this interaction can modulate transcription factor binding. Using purified recombinant HMG I, we have identified several high-affinity binding sites which overlap important transcription factor binding sites. One of these HMG I binding sites coincides with an important binding site for AP-1 located downstream of the transcriptional start site, in the 5' untranslated region at the boundary of a positioned nucleosome. HMG I binding to this composite site inhibits the binding of recombinant AP-1. Consistent with this observation, using nuclear extracts prepared from Jurkat T cells, we show that HMG I (but not HMG Y) is strongly induced upon phorbol myristate acetate stimulation and this induced HMG I appears to both selectively inhibit the binding of basal DNA-binding proteins and enhance the binding of an inducible AP-1 transcription factor to this AP-1 binding site. We also report the novel finding that a component present in this inducible AP-1 complex is ATF-3. Taken together, these results argue that HMG I may play a fundamental role in HIV-1 expression by determining the nature of transcription factor-promoter interactions.

5' Untranslated Regions↗

Ethanol inhibits insulin receptor tyrosine kinase.

BACKGROUND: Ethanol inhibits insulin-like growth factor-I (IGF-I) and insulin signaling in various cell types. The tyrosine autophosphorylation of the IGF-I and insulin receptors appears to be a target for ethanol, as well as other receptor tyrosine kinases. METHODS AND RESULTS: The effect of ethanol on purified recombinant insulin receptor kinase activity was examined. A noncompetitive inhibition was observed at pharmacologically relevant concentrations of ethanol. Both peptide substrate tyrosine phosphorylation and kinase autophosphorylation are inhibited by ethanol. Near equivalent inhibition of kinase activity was noted for 300 mM methanol, 150 mM ethanol, 20 mM 1-propanol, and 10 mM 1-butanol. CONCLUSION: The findings identify a direct protein interaction site of ethanol, and provide insight into the mechanism by which ethanol inhibits receptor tyrosine kinase activity.

Dose-Response Relationship, Drug↗

EMF induces differentiation in HL-60 cells.

This investigation provides evidence that a 60-Hz electromagnetic field (EMF) at 1 gauss (G) can drive differentiation of cultured hematopoietic progenitor cells. HL-60 cells are known to differentiate from a nonphagocytic suspension culture to an attached fibroblast-like culture with high phagocytic activity in the presence of the tumor-promoting phorbol ester 12-O-tetradecanoylphorbal-13-acetate (TPA). The effect of 60-Hz EMF at 1 G on differentiation is approximately equivalent to treatment of the cells with 250-500 pg/ml TPA. Furthermore, the effect of both EMF and TPA treatment on differentiation is additive at low TPA concentrations. The results strongly suggest similarities between the effects of TPA treatment and EMF exposure and thus provide an approach for tracing the origins of the molecular effects of EMF exposure, as many transduction pathways in the differentiative process are defined.

Cell Differentiation↗

Abused women and child custody: the ongoing exposure to abusive ex-partners.

Abuse of women in domestic relationships has become an epidemic. Research studies have documented that abuse does not end when a woman with children leaves the abuser but, in fact, the danger increases. A father's legal right to custody of and access to his children and the children's bond with their father prevent a woman from truly breaking free of her abuser. Theoretical literature has addressed how custody and access can serve as a means for an abuser to continue his abuse and expose his children to ongoing abuse and discord. Research on how custody and access issues are affecting abused women is limited. Key details about this phenomenon are not known. Hence, a research study using the qualitative methodology of phenomenology was conducted on abused women's experiences with custody and access and the ongoing exposure to abusive ex-partners. Six single mothers who had left abusive relationships and were at the time sharing custody of and/or access to their children with their abusive ex-partners participated in the study. Unstructured, non-directive interviews were conducted. Direction for analysis was taken from the specific steps outlined by Giorgi. Data analysis revealed that all of the women were living in great fear for their safety and that of their children. The ongoing danger and stress of living with the restrictions of the law took its toll on the women and ultimately affected their physical health and psychological well-being. The women described their experiences as having four components: (1) safety--living with ongoing danger; (2) stress--living with the restrictions of the law and the legal system; (3) coping--social support systems; and (4) to heal and move forward in life.

Adolescent↗

Evaluation of a constipation risk assessment scale.

This project was undertaken in order to evaluate the utility of a constipation risk assessment scale and the accompanying bowel management protocol. The risk assessment scale was primarily introduced to teach and guide staff in managing constipation when caring for patients. The intention of the project was to reduce the incidence of constipation in patients during their admission to hospital.

Constipation↗

Ideological implications of paradigm discourse.

Whilst the notions of paradigm and paradigm shift have become popularized in nursing's scholarly literature, there has been relatively little critical analysis of their impact upon theoretical understanding. In this paper, the authors attempt to deconstruct the ways in which paradigm discourse has been applied in nursing scholarship, looking beyond the claims that are made in the name of paradigm shifts to the apparent motivation underlying those claims. Comparing discourse associated with the paradigm shifts that have emerged in nursing education, research and practice theory, they reveal an inherently divisive purpose to which paradigm language is commonly used, and examine the implications of the discourse for nursing knowledge development. On the basis of this analysis, the authors urge a cautious approach to the extremes of paradigm claims, and argue for a more thoughtful and lively dialogue regarding the interests served by locating ideological positions within paradigm language.

Education, Nursing↗

Nursing's metaparadigm concepts: disimpacting the debates.

Theoretical advances in nursing have been complicated by polarization and extreme positions regarding nursing's approach to its main metaparadigm concepts: person, health, environment and nursing. In this paper, the authors deconstruct some of the central arguments that are used to further this polarization. Using a critical interpretive approach, they explain some of the logical implications imposed by various extreme positions for the larger project of nursing's health and social mandate, and consider the effects of such polarization. On the basis of an appreciation of the serious difficulties inherent in certain philosophical and theoretical positions currently evident within nursing's literature, the authors argue for a less extreme and more integrated reference point for nursing's theory and practice.

Disease↗

Evaluating the effectiveness of two teaching strategies for patients diagnosed with hypertension.

This study investigated whether a structured patient-centred education programme was more effective than the normal ad hoc information that patients receive in improving their knowledge of hypertension whilst in hospital. Forty patients were assessed to determine their knowledge level regarding the management of risk factors related to hypertension. A pre-test was performed shortly after admission to hospital. Twenty patients in the test group received a structured education programme, and 20 patients in the control group received the usual ad hoc information. Two post-tests were performed, one at the time of discharge and the other approximately 8 weeks after discharge, to determine the change in knowledge levels. Comparison of the pre- and post-tests of the test group revealed a significant increase in knowledge level at the time of discharge from hospital. Patients were found to retain this new knowledge at 8 weeks and 1 year after discharge. No significant difference was found for the control group. This study has shown that a structured approach to health education is more effective in improving patients' knowledge about their condition than relying on the ad hoc information that patients traditionally receive during their hospitalization.

Adult↗

Aneuploidy in male Indian muntjac cells is limited to the Y2 chromosome.

In untreated cell cultures of Indian muntjac (Munticus muntiacus vaginalis; 2n = 6 female, 7 male) we observed that spontaneous aneuploidy is limited primarily to the Y2 chromosome. We therefore treated the cells with aneugenic agents to determine if induced aneuploidy follows the same pattern and, hence, if there are limitations on the generation of aneuploidy or survival of cells lacking certain chromosomes. Exposing the cells to benomyl (8-100 micrograms/ml for 1 h), caffeine (5 x 10(-5)-2 x 10(-4) M for 2, 24 and 72 h) and colchicine (2 x 10(-4) and 5 x 10(-5) M for 1, 24, 48 and 72 h) resulted in cells primarily aneuploid for the Y2 chromosome. The frequency of cells lacking Y2 was far higher than those having an extra Y2 chromosome. The frequency of cells aneuploid for all other chromosomes combined was much lower than that for Y2. The data imply that the Indian muntjac genome can tolerate loss of the Y2 chromosome only and that aneuploidy for other chromosomes might cause lethality. This might be because the small number of chromosomes in the genome predisposes aneuploid cells to an imbalance of genes carrying out the basic activities required for cell division and cell survival. Because of the small chromosome number, the large size of the chromosomes and the ease of distinguishing every chromosome without banding or any other special treatment, e.g. FISH, this system could be useful and convenient in the study of induction of aneuploidy. This simple and inexpensive system can be utilized as a screening system for preliminary studies dealing with induced aneuploidy.

Aneuploidy↗