Weighing the evidence for vitamin supplementation and CVD prevention.
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Ascorbic Acid↗
Biomedical subjects
A Adams
Publications and source records attributed to A Adams.
Intersectin, an adaptor protein involved in clathrin-mediated endocytosis, activates mitogenic signaling pathways.
Intersectin is a member of a growing family of adaptor proteins that possess conserved Eps15 homology (EH) domains as well as additional protein recognition motifs. In general, EH domain-containing proteins play an integral role in clathrin-mediated endocytosis. Indeed, intersectin functions in the intermediate stages of clathrin-coated vesicle assembly. However, recent evidence suggests that components of the endocytic machinery also regulate mitogenic signaling pathways. In this report, we provide several lines of evidence that intersectin has the capacity to activate mitogenic signaling pathways. First, intersectin overexpression activated the Elk-1 transcription factor in an MAPK-independent manner. This ability resides within the EH domains, as expression of the tandem EH domains was sufficient to activate Elk-1. Second, intersectin cooperated with epidermal growth factor to potentiate Elk-1 activation; however, a similar level of Elk-1 activation was obtained by expression of the tandem EH domains suggesting that the coiled-coil region and SH3 domains act to regulate the EH domains. Third, intersectin expression was sufficient to induce oncogenic transformation of rodent fibroblasts. And finally, intersectin cooperated with progesterone to accelerate maturation of Xenopus laevis oocytes. Together, these data suggest that intersectin links endocytosis with regulation of pathways important for cell growth and differentiation.
3T3 Cells↗
Observations on the electron-dense bodies of the PKX parasite, agent of proliferative kidney disease in salmonids.
Ultrastructural observations on structures associated with the 'haplosporosome'-like electron-dense bodies (EDBs) of the primary cell of the extrasporogonic stage of PKX are described. Observations made include formation of EDBs by the trans-Golgi network, an additional membrane associated with EDB structure, confronting cisternae, engulfment and presence of EDBs in multivesicular bodies, fusion of EDBs with the plasmalemma, degeneration of EDBs in disintegrating primary cells and endocytosis of PKX cytoplasm by adherent macrophages. Immunogold localisation of a PKX-specific monoclonal antibody (MAb A3) suggests that the EDBs contain periodate-sensitive carbohydrates on their membranes. Tissues prepared for immunogold electron microscopy further suggest that some contain a lipid-rich core. An interpretation is made on their possible function and their relationship with the haplosporosomes and sporoplasmasomes found in members of the Haplosporidea and Myxosporea respectively.
Animals↗
Bovine adrenal cells secrete interleukin-6 and tumor necrosis factor in vitro.
Interleukin-6 (IL-6) and tumor necrosis factor (TNF) are secreted and/or synthesized by the rat and human adrenal cortex. In this study, the release of IL-6 and TNF from bovine adrenal cells was determined. Bovine adrenal glands were collected from an abattoir and dissected into the zona glomerulosa (ZG), zona fasciculata (ZF), zona reticularis (ZR), and medulla. The tissues were enzymatically dispersed to single cells and cultured for 4-6 days. The cells were then exposed (4 h) to angiotensin II (AII), adrenocorticotrophic hormone (ACTH), phorbol dibutyrate (PDB), interleukin-1beta (IL-1beta), interleukin-1alpha (IL-1alpha), and endotoxin (LPS). The IL-6 and TNF content of the incubation medium was determined by bioassays. The release of IL-6 and TNF from the ZG, ZF, ZR, and medulla was increased by PDB, IL-1alpha, IL-1beta, and LPS. In contrast, ACTH and AII increased IL-6 release from the ZG, ZF, and ZR but had no effect on IL-6 release from the medulla. ACTH decreased TNF release from all adrenal cortical zones but had no effect on TNF release from the medulla. Immunohistochemistry utilizing antibodies against TNFalpha demonstrated TNFalpha-containing cells throughout the adrenal gland. The majority of the cells of the ZG, ZF, and ZR contained TNFalpha. However, the cells of the ZG contained more TNFalpha than the cells of the ZR or ZF. Small patches of TNFalpha-containing cells were also found in the adrenal medulla and capsule. These findings support the hypothesis that IL-6 and TNF may have autocrine/paracrine effects on the adrenal gland.
Adrenal Glands↗
In situ hybridisation identifies the gill as a portal of entry for PKX (Phylum Myxozoa), the causative agent of proliferative kidney disease in salmonids.
PKX (Phylum Myxozoa) is an important pathogen affecting salmonid culture in Western Europe and North America. All of the available oligonucleotide probes developed for the PCR amplification of PKX DNA were examined for their ability to detect PKX in fixed tissue sections using in situ hybridisation. Out of the 12 probes examined, only four stained PKX in tissue sections. The specificity of these probes to PKX was examined by testing them individually against a range of myxosporean infections. One of the probes (1032) cross-reacted with Sphaerospora truttae infecting brown trout kidney and stained this parasite in tissue sections, while probe 6R stained stickleback DNA. The results from these studies allowed for an optimised, relatively rapid, in situ hybridisation protocol to be developed for PKX detection. Using this protocol, a preliminary study was conducted on the life history of the parasite in the rainbow trout Oncorhynchus mykiss. This demonstrated the presence of PKX in the gill arch 3 days after initial exposure in an enzootic river. It is suggested that a portal of entry for PKX is the gill. From here. it migrates to the kidney where the disease progresses as previously described.
Animals↗
Production of high-titer stocks of the English strain of rat cytomegalovirus.
A simple technique to increase dramatically the yield of rat cytomegalovirus (RCMV) from infected monolayers of a rat embryo fibroblast-derived cell line is described. The method, which involves daily changes of the cell culture medium, can result in a 50000-fold amplification of virus from cell monolayers inoculated with only a few RCMV particles. This modification of the standard in vitro culture technique to amplify viral yield can be used to increase the sensitivity of the plaque assay for detecting very small amounts of infectious virus in organ homogenates of RCMV infected animals.
Animals↗
Hospital nurses' job satisfaction, individual and organizational characteristics.
Hospital nurses' job satisfaction, individual and organizational characteristics Using the Ward Organizational Features Scales (WOFS), relationships between aspects of the organization of acute hospital wards, nurses' personal characteristics and nurses' job satisfaction are examined among a nationally representative sample of 834 nurses in England. The analysis contributes to a growing body of evidence demonstrating the importance of interpersonal relationships to nurses' job satisfaction. In particular, the positive contribution of the cohesiveness of ward nursing staff is highlighted, but the potential for many current NHS staffing strategies and work environments to undermine the development of cohesive working relationships is also noted. Other influential factors are nurses' relationships with medical staff, perceptions of their workload and their evaluation of the appropriateness of the system of nursing being practised. The importance of measuring nurses' subjective assessments of their work environment is emphasized. A weak association was found between grade and job satisfaction. Individual nurse characteristics were found not to be associated with job satisfaction.
Adult↗
Surgical site infections. Another look at banishing bugs.
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Humans↗
Possible function of IL-6 and TNF as intraadrenal factors in the regulation of adrenal steroid secretion.
Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) and their mRNAs are present in the human, rat, and bovine adrenal cortex. The release of these cytokines from adrenal cells is regulated by factors that alter adrenal function (e.g., ACTH, angiotensin II, interleukin-1). IL-6 and TNF type 1 receptors are also present on adrenocortical cells. Exposure to IL-6 increases cortisol or corticosterone release from human, bovine, and rat adrenal cells. IL-6 increases basal and ACTH-stimulated aldosterone release, but inhibits angiotensin II-stimulated aldosterone secretion from bovine adrenal cells. IL-6 increases dehydroepiandrosterone (DHEA) release from human cells, but decreases DHEA secretion from bovine cells. TNF alpha inhibits corticosterone release from normal rat adrenal cells or fragments, but increases corticosterone release from cholestatic rat adrenal slices. TNF alpha decreases cortisol release from bovine and fetal human adrenal cells, but increases cortisol release from adult human adrenal cells. TNF alpha inhibits aldosterone secretion from rat and bovine adrenocortical cells. TNF alpha does not affect DHEA secretion from fetal human adrenocortical cells, but inhibits basal and ACTH-stimulated DHEA release from bovine adrenal cell. Because IL-6 and TNF alpha are produced in the adrenal gland and modify adrenal steroid secretion, these cytokines may function as intraadrenal factors in the regulation of adrenal steroid secretion.
Adrenal Cortex↗
Acridinecarboxamide topoisomerase poisons: structural and kinetic studies of the DNA complexes of 5-substituted 9-amino-(N-(2-dimethylamino)ethyl)acridine-4-carboxamides.
For a series of antitumor-active 5-substituted 9-aminoacridine-4-carboxamide topoisomerase II poisons, we have used X-ray crystallography and stopped-flow spectrophotometry to explore relationships between DNA binding kinetics, biological activity, and the structures of their DNA complexes. The structure of 5-F-9-amino-[N-(2-dimethylamino)ethyl]-acridine-4-carboxamide bound to d(CGTACG)(2) has been solved to a resolution of 1.55 A in space group P6(4). A drug molecule intercalates between each of the CpG dinucleotide steps, its protonated dimethylamino group partially occupying positions close to the N7 and O6 atoms of guanine G2 in the major groove. A water molecule forms bridging hydrogen bonds between the 4-carboxamide NH and the phosphate group of the same guanine. Intercalation unwinds steps 1 and 2 by 12 degrees and 8 degrees, respectively compared with B-DNA, whereas the central TpA step is overwound by 10 degrees. Nonphenyl 5-substituents, on average, decrease mean DNA dissociation rates by a factor of three, regardless of their steric, hydrophobic, H-bonding, or electronic properties. Cytotoxicity is enhanced on average 4-fold and binding affinities rise by 3-fold, thus there is an apparent association between kinetics, affinity, and cytotoxicity. Taken together, the structural and kinetic studies imply that the main origin of this association is enhanced stacking interactions between the 5-substituent and cytosine in the CpG binding site. Ligand-dependent perturbations in base pair twist angles and their consequent effects on base pair-base pair stacking interactions may also contribute to the stability of the intercalated complex. 5-Phenyl substituents modify dissociation rates without affecting affinities, and variations in their biological activity are not correlated with DNA binding properties, which suggests that they interact directly with the topoisomerase protein.
Aminacrine↗
Oxygenation response to a recruitment maneuver during supine and prone positions in an oleic acid-induced lung injury model.
Prone position and recruitment maneuvers (RM) are proposed as adjuncts to mechanical ventilation to open up the lung and keep it open. We studied the oxygenation response to a RM (composed of a 30-s sustained inflation at 60 cm H(2)O airway pressure) performed in prone and supine positions in dogs after oleic acid- induced lung injury using an inspired O(2) fraction of 0.60. In one group (n = 6) first supine then prone positions were examined after a RM at 8 cm H(2)O and 15 cm H(2)O of positive end-expiratory pressure (PEEP). In the second group (n = 6) the sequence of positions was reversed. Prone positioning after supine position always improved oxygenation, whereas the decrement in Pa(O(2)) was relatively small when dogs were returned to the supine position. Oxygenation improved in both groups after a RM, and the improvement was sustained (after 15 min) in the prone position at 8 cm H(2)O of PEEP, but 15 cm H(2)O of PEEP was required in supine position. Our results suggest that a RM improves oxygenation more effectively with a decreased PEEP requirement for the preservation of the oxygenation response in prone compared with supine position.
Animals↗
Stimulation by interleukin-6 and inhibition by tumor necrosis factor of cortisol release from bovine adrenal zona fasciculata cells through their receptors.
Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are synthesized and released from adrenal cells. Therefore, the effects of TNF-alpha and IL-6 on cortisol release from bovine zona fasciculata (ZF) cells were investigated. IL-6 (10-1000 pg/mL) significantly increased basal and adrenocorticotropic hormone (ACTH)-stimulated cortisol release in a concentration-dependent manner. This stimulatory effect of IL-6 became apparent at intervals as short as 4 h and continued through 24 h. IL-6 also potentiated the cortisol release stimulated by the adenylyl cyclase activator forskolin. By contrast, TNF-alpha (0.1-10 ng) inhibited basal and ACTH-stimulated cortisol release in a concentration-dependent manner. The inhibitory effects of TNF-alpha on cortisol release were significant at time intervals as short as 4 h and continued through 24 h. TNF-alpha inhibited forskolin-stimulated cortisol release. Binding studies demonstrated that ZF cells have IL-6 receptors (100 receptors/cell, Kd of 7.5 x 10(-11)) and TNF receptors (200 receptors/cell, Kd of 2.4 x 10(-9) M). Immunohistochemical analysis provided evidence that the majority of ZF cells have IL-6 receptors, TNF type 1 receptors, and TNF type 2 receptors. Because IL-6 and TNF-alpha are released from the adrenal cortex and these cytokines modify the release of cortisol from the ZF, IL-6 and TNF-alpha may play a paracrine or autocrine role in the regulation of adrenal function.
Adenylyl Cyclases↗
HMO liability.
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Employee Retirement Income Security Act↗
Phase I pharmacokinetic trial of perillyl alcohol (NSC 641066) in patients with refractory solid malignancies.
Perillyl alcohol (POH) is a monoterpene with anticarcinogenic and antitumor activity in murine tumor models. Putative mechanisms of action include activation of the transforming growth factor beta pathway and/or inhibition of p21ras signaling, leading to differentiation or apoptosis. In this Phase I trial, 17 patients took POH p.o. three times daily for 14 days of each 28-day cycle. The starting dose of POH was 1600 mg/m2/dose, with escalations to 2100 and 2800 mg/m2/dose in subsequent cohorts. Chronic nausea and fatigue were dose-limiting toxic effects at 2800 mg/m2. Grade 1-2 hypokalemia was common at 2100 and 2800 mg/m2. Although POH could not be detected in plasma, two of its metabolites, dihydroperillic acid (DHPA) and perillic acid (PA), were measured in plasma and urine on days 1 and 15 after the first and last doses of POH, respectively. Both area under the concentration versus time curve and peak plasma concentration (Cmax) values increased with dose and exhibited high intersubject variability. Day 15 DHPA Cmax values ranged from a mean +/- SD of 22.6+/-12 microM at 1600 mg/m2/dose to 42.4+/-15.24 microM at 2800 mg/m2/dose. Corresponding mean +/- SD Cmax values for PA were 433.2+/-245.8 and 774.1+/-439.6 microM. One patient treated at the 2800 mg/m2/dose had markedly prolonged plasma levels of both PA and DHPA and developed grade 3 mucositis. POH treatment did not consistently alter the expression of p21ras, rap1, or rhoA in peripheral blood mononuclear cells obtained from patients treated at the highest dose level. The metabolites PA and DHPA did not change expression or isoprenylation of p21ras in MCF-7 breast or DU145 prostate carcinoma cells at concentrations that exceeded those achieved in patient plasma after POH treatment. We conclude that POH at 1600-2100 mg/m2 p.o. three times daily is well tolerated on a 14-day on/14-day off dosing schedule. Inhibition of p21ras function in humans is not likely to occur after POH administration at safe doses of the present oral formulation.
Administration, Oral↗
Los Angeles College of Chiropractic practice model.
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Chiropractic↗
Classifying clinical decision making: a unifying approach.
This is the first of two linked papers exploring decision making in nursing which integrate research evidence from different clinical and academic disciplines. Currently there are many decision-making theories, each with their own distinctive concepts and terminology, and there is a tendency for separate disciplines to view their own decision-making processes as unique. Identifying good nursing decisions and where improvements can be made is therefore problematic, and this can undermine clinical and organizational effectiveness, as well as nurses' professional status. Within the unifying framework of psychological classification, the overall aim of the two papers is to clarify and compare terms, concepts and processes identified in a diversity of decision-making theories, and to demonstrate their underlying similarities. It is argued that the range of explanations used across disciplines can usefully be re-conceptualized as classification behaviour. This paper explores problems arising from multiple theories of decision making being applied to separate clinical disciplines. Attention is given to detrimental effects on nursing practice within the context of multidisciplinary health-care organizations and the changing role of nurses. The different theories are outlined and difficulties in applying them to nursing decisions highlighted. An alternative approach based on a general model of classification is then presented in detail to introduce its terminology and the unifying framework for interpreting all types of decisions. The classification model is used to provide the context for relating alternative philosophical approaches and to define decision-making activities common to all clinical domains. This may benefit nurses by improving multidisciplinary collaboration and weakening clinical elitism.
Clinical Competence↗