Cell surface organization of stress-inducible proteins ULBP and MICA that stimulate human NK cells and T cells via NKG2D

Cell surface proteins major histocompatibility complex (MHC) class I-related chain A (MICA) and UL16-binding proteins (ULBP) 1, 2, and 3 are up-regulated upon infection or tumor transformation and can activate human natural killer (NK) cells. Patches of cross-linked raft resident ganglioside GM1 colocalized with ULBP1, 2, 3, or MICA, but not CD45. Thus, ULBPs and MICA are expressed in lipid rafts at the cell surface. Western blotting revealed that glycosylphosphatidylinositol (GPI)-anchored ULBP3 but not transmembrane MICA, MHC class I protein, or transferrin receptor, accumulated in detergent-resistant membranes containing GM1. Thus, MICA may have a weaker association with lipid rafts than ULBP3, yet both proteins accumulate at an activating human NK cell immune synapse. Target cell lipid rafts marked by green fluorescent protein-tagged GPI also accumulate with ULBP3 at some synapses. Electron microscopy reveals constitutive clusters of ULBP at the cell surface. Regarding a specific molecular basis for the organization of these proteins, ULBP1, 2, and 3 and MICA are lipid modified. ULBP1, 2, and 3 are GPI anchored, and we demonstrate here that MICA is S-acylated. Finally, expression of a truncated form of MICA that lacks the putative site for S-acylation and the cytoplasmic tail can be expressed at the cell surface, but is unable to activate NK cells.     

Music therapy's relevance in a cancer hospital researched through a constructivist lens

The constructivist research paradigm informed a research investigation on the relevance of music therapy in a cancer hospital, that is, what did the music therapy do and did it help? Over 3 months, criterion sampling was used to elicit interpretations in 5 studies from 5 sources: 128 patients who participated, 27 patients who overheard or witnessed music therapy, 41 visitors, 61 staff, and the music therapist-researcher. Fifty-seven percent of the patients who participated had advanced or end stage cancer. The music therapist's interpretations were recorded in a reflexive clinical journal and the respondents' interpretations were written on anonymous open-ended questionnaires. Thematic and content analyses were performed on the 5 groups of data with the support of qualitative data management software. Findings from the 5 data groups were contrasted and compared. Many patients', visitors' and staff members' affective, contemplative, and imagined moments in music therapy affirmed their "aliveness," resonating with an expanded consciousness, in a context where life's vulnerability is constantly apparent. Philosophical depictions about the relevance of music in human life, including theories by Addis and Winnicott, substantiated the therapeutic reactions.     

Ventilator-associated events in children: A review of literature

Background

The complexity and variation in ventilator associated pneumonia (VAP) definitions in paediatrics may pose threats to the reliable identification of VAP. The revision of the surveillance definition to ventilator-associated event (VAE) has been mandated in adult populations, to overcome these issues. However, the evidence for application of the definition is unknown in children.

Sonographic appearances of cervical lymph nodes: variations by age and sex.

PURPOSE: The purpose of this study was to evaluate the age- and sex-related variations in the numbers and sonographic appearances of normal cervical lymph nodes. METHODS: One hundred thirty-three healthy subjects (67 men and 66 women) underwent sonographic examinations of the neck, during which 1,299 lymph nodes were detected. The lymph nodes were assessed for their size, shape (short-to-long-axis ratio), and border sharpness, as well as for the presence of an echogenic hilum. The subjects were categorized by age (20-29, 30-39, 40-49, and > or = 50 years) and subcategorized by sex. The differences between the groups in the number of nodes and in their appearance were evaluated. RESULTS: The mean number of nodes visualized on sonography was significantly higher (p < 0.05) in subjects aged 20-29 and 30-39 years than in subjects aged 40-49 and 50 years or older. The difference in the mean sizes of the cervical nodes between men and women was not statistically significant. The lymph nodes in subjects aged 20-29 and 30-39 years were commonly smaller than those in subjects aged 40-49 and 50 years or older, but the differences were not statistically significant. Neither the shape nor the border sharpness of the cervical lymph nodes varied significantly by age or sex. The incidence of an echogenic hilum within the lymph nodes increased significantly with age in both sexes (p < 0.05). CONCLUSIONS: This study provides information about the sonographic appearances of and variations between normal cervical lymph nodes. The presence of an increased number of cervical lymph nodes and the absence of an echogenic hilum within the nodes may help to identify an abnormality more in older patients than in younger patients.     

Immunohistochemical localization of histamine H3 receptors in rodent skin, dorsal root ganglia, superior cervical ganglia, and spinal cord: potential antinociceptive targets

Activation of histamine H3 receptors (H3Rs) reduces inflammation and nociception, but the existence of H3Rs on peripheral innervation has never been demonstrated. Here we use antibodies to locate H3Rs in whisker pads, hairy and glabrous hind paw skin, dorsal root ganglia (DRGs), and spinal cords of rats, wild type mice, and H3R knockout (H3KO) mice. Although H3Rs have been hypothesized to be on C and sympathetic fibers, H3R-like immunoreactivity (H3R-LI) was only detected on presumptive periarterial A delta fibers and on A beta fibers that terminated in Meissner's corpuscles and as lanceolate endings around hair follicles. The H3R-positive periarterial fibers were thin-caliber and coexpressed immunoreactivity for calcitonin gene-related peptide (CGRP), substance P, acid sensing ion channel 3, and 200 kDa neurofilament protein (NF). H3R-LI was also detected on epidermal keratinocytes and Merkel cells, but not on Merkel endings, C fibers, any other A delta fibers, or sympathetic fibers. In DRGs, H3R-LI was preponderantly on medium to large neurons coexpressing NF-LI and mostly CGRP-LI. In dorsal horn, CGRP-positive fibers with and without H3R-LI ramified extensively in lamina II; many of the former formed a plexus in lamina V. Low levels of H3R-LI were also present on A beta fibers penetrating superficial and into deeper laminae. The distribution of H3R-LI was similar in rats and wild type mice, but was eliminated or strongly reduced in A delta fibers and A beta fibers, respectively, in H3KO mice. Taken with recently published behavioral results, the present findings suggest that periarterial, peptidergic, H3R-containing A delta fibers may be sources of high threshold mechanical nociception.     

A comparative study of the experiences of violence of English and Swedish mental health nurses

Recent studies suggest that violence in health care environments, especially mental health care, appears to be increasing. Although there is a lack of cross-cultural studies to prove it, this increase in violence would seem to be an international phenomenon. The present study sought to compare the extent and nature of violence encountered by mental health nurses in Sweden and England. Systematic studies of violence have previously been carried out independently in both countries but this was the first attempt to compare levels of violence. Clearly defined study protocols were put in place, an operational definition of 'violence' adhered to, and random samples recruited. A specially designed questionnaire was sent to every subject (Swedish nurses n=720; English nurses n=296) enquiring about the extent of nurses' exposure to violence, the nature and severity of the violence experienced, and the effect of violence on self-esteem and job satisfaction. Significant differences were found with English nurses experiencing more violence than their Swedish counterparts. Yet support for English nurses appeared to be less good than for Swedish nurses. Reasons for the differences are discussed along with possible measures to minimise the frequency of violence against nurses and the negative effects on their work.     

Trochanteric Bursitis Following Primary Total Hip Arthroplasty: Incidence,Predictors, and Treatment

Background

Trochanteric bursitis (TB) remains a common complication after total hip arthroplasty (THA), with an incidence between 3% and 17%, depending on the surgical approach, with the posterior approach (PA) being relatively protective compared to the lateral approach. The purposes of this study were to determine the incidence of TB after primary THA, identify potential risk factors for TB, and examine the utility of different modes of treatment.