Patient-reported outcomes of immediate implant-based breast reconstruction with and without biological or synthetic mesh.

BACKGROUND: Biological and synthetic meshes may improve the outcomes of immediate implant-based breast reconstruction (IBBR) by facilitating single-stage procedures and improving cosmesis. Supporting evidence is, however, limited. The aim of this study was to explore the impact of biological and synthetic mesh on patient-reported outcomes (PROs) of IBBR 18 months after surgery. METHODS: Consecutive women undergoing immediate IBBR between February 2014 and June 2016 were recruited to the study. Demographic, operative, oncological and 3-month complication data were collected, and patients received validated BREAST-Q questionnaires at 18 months. The impact of different IBBR techniques on PROs were explored using mixed-effects regression models adjusted for clinically relevant confounders, and including a random effect to account for clustering by centre. RESULTS: A total of 1470 participants consented to receive the questionnaire and 891 completed it. Of these, 67 women underwent two-stage submuscular reconstructions. Some 764 patients had a submuscular reconstruction with biological mesh (495 women), synthetic mesh (95) or dermal sling (174). Fourteen patients had a prepectoral reconstruction. Compared with two-stage submuscular reconstructions, no significant differences in PROs were seen in biological or synthetic mesh-assisted or dermal sling procedures. However, patients undergoing prepectoral IBBR reported better satisfaction with breasts (adjusted mean difference +6.63, 95 per cent c.i. 1.65 to11.61; P = 0.009). PROs were similar to those in the National Mastectomy and Breast Reconstruction Audit 2008-2009 cohort, which included two-stage submuscular procedures only. CONCLUSION: This study found no difference in PROs of subpectoral IBBR with or without biological or synthetic mesh, but provides early data to suggest improved satisfaction with breasts following prepectoral reconstruction. Robust evaluation is required before this approach can be adopted as standard practice.

Experiences of implant loss after immediate implant-based breast reconstruction: qualitative study.

BACKGROUND: Immediate implant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure in the UK, but almost one in ten women experience implant loss and reconstructive failure after this technique. Little is known about how implant loss impacts on patients' quality of life. The first phase of the Loss of implant Breast Reconstruction (LiBRA) study aimed to use qualitative methods to explore women's experiences of implant loss and develop recommendations to improve care. METHODS: Semistructured interviews were conducted with a purposive sample of women who experienced implant loss after immediate IBBR, performed for malignancy or risk reduction across six centres. Interviews explored decision-making regarding IBBR, and experiences of implant loss and support received. Thematic analysis was used to explore the qualitative interview data. Sampling, data collection and analysis were undertaken concurrently and iteratively until data saturation was achieved. RESULTS: Twenty-four women were interviewed; 19 had surgery for malignancy and five for risk reduction. The median time between implant loss and interview was 42 (range 22-74) months. Ten women had undergone secondary reconstruction, two were awaiting surgery, and 12 had declined further reconstruction. Three key themes were identified: the need for accurate information about the risks and benefits of IBBR; the need for more information about 'early-warning' signs of postoperative problems, to empower women to seek help; and better support following implant loss. CONCLUSION: Implant loss is a devastating event for many women. Better preoperative information and support, along with holistic patient-centred care when complications occur, may significantly improve the experience and outcome of care.

ANTECEDENTES: La reconstrucción mamaria inmediata con prótesis (implant-based breast reconstruction, IBBR) es el procedimiento reconstructivo más utilizado en el Reino Unido, pero casi una de cada diez mujeres presentará pérdida de la prótesis y fallo del procedimiento reconstructivo tras esta técnica. Se sabe poco de cómo la pérdida de la prótesis afecta la calidad de vida de las pacientes. La primera fase del estudio LiBRA tuvo como objetivo explorar la percepción de las mujeres ante la pérdida de la prótesis, utilizando métodos cualitativos, y proponer una serie de medidas para mejorar la atención sanitaria de estas pacientes. MÉTODOS: Se realizaron entrevistas semiestructuradas en una muestra de mujeres que padecieron la pérdida de la prótesis tras una IBBR inmediata, realizada por neoplasia o como procedimiento de reducción de riesgo, en seis centros. Las entrevistas analizaron la toma de decisiones con respecto a la IBBR inmediata, así como la percepción ante la pérdida del implante y el soporte recibido. Se utilizó un análisis por temas para examinar los datos de la entrevista cualitativa. El muestreo, la recopilación de datos y el análisis se realizaron de forma simultánea e iterativa hasta que se logró la saturación de datos. RESULTADOS: Se entrevistaron 24 pacientes; 19 en las que la indicación quirúrgica fue por cáncer y 5 por reducción de riesgo. La mediana del tiempo entre la pérdida del implante y la entrevista fue de 42 (rango 22-52) meses. Diez mujeres se habían sometido a una reconstrucción secundaria; dos estaban a la espera de la cirugía y 12 habían rechazado la reconstrucción posterior. Se identificaron tres temas clave, siendo las necesidades de: i) información precisa sobre los riesgos y beneficios de la IBBR, ii) más información sobre los signos de "alarma precoz" de las complicaciones postoperatorias que permitiesen a las mujeres buscar ayuda, y iii) mejor soporte tras la pérdida de la prótesis. CONCLUSIÓN: La pérdida de una prótesis es una complicación catastrófica para muchas mujeres. Una mejor información y apoyo preoperatorios, junto con una atención holística centrada en la paciente cuando se presentan las complicaciones, podrían mejorar significativamente la experiencia y el resultado de la atención.

Serological biomarker screening and host factor analysis elucidating immune response heterogeneity in active pulmonary tuberculosis.

While mortality and morbidity from pulmonary tuberculosis (PTB) have improved, diagnosis of this infectious disease remains suboptimal without a point-of-care test. Antibody/ antigen-based serodiagnostics is the most amenable for point-of-care translation but hampered by a lack of validated biomarkers and a heterogeneous patient antibody response. Using a case-control design, we assessed serodiagnostic potential of immunoglobulins G, A, and dimeric IgA responses against 18 antigenic preparations, followed by antibody-subclass responses against antigen 60 (A60), and four markers of host innate immunity by enzymelinked immunoassay using sera samples (n=110) collected from April to October 2007 in VietNam from human immunodeficiency-negative patients with provisional diagnosis of PTB. We further analyzed host variables to investigate factors driving biomarker heterogeneity observed in patients. Among active pulmonary tuberculosis patients, low correlation was observed between anti-A60 antibody-classes, and between anti-A60 immunoglobulin G subclasses, but anti-A60 immunoglobulin A subclasses were significantly correlated. The best diagnostic combination of anti-A60 immunoglobulin G/A and a C-reactive protein "ruleout" remains insufficient at 82%/92% sensitivity/specificity (95%CI: 72-92%/82-98%). Heterogeneity of anti-A60 immunoglobulins G2, G3, M, as well as C-reactive protein and serum amyloid A levels observed in this study population appeared to be significantly associated with history of previous tuberculosis, hemoptysis, age, vaccination, night sweats, smoking, chest pain, fever, alcohol, and solid culture count. Further research on tuberculosis serological biomarkers may require consideration of host factors and new approaches using multiple biomarkers.

Infection prevention in breast implant surgery - A review of the surgical evidence, guidelines and a checklist.

INTRODUCTION: As a result of increasing use of implant-based breast reconstruction, complications such as infection are being encountered more frequently. Surgical Site Infections (SSIs) cause morbidity for the patient, can lead to capsular contracture or implant loss and are costly to healthcare systems. National Guidelines suggesting methods to reduce SSI related complications have been produced, but are limited in the scope of interventions covered and underlying evidence presented. METHODS: We performed a literature review encompassing a wide variety of possible SSI prevention strategies. We aimed to present summaries of the available evidence and give pragmatic recommendations as to their validity to use as guidelines for infection prevention strategies for implant-based breast reconstruction. RESULTS: A lack of high quality data relating to the benefit of SSI prevention strategies in implant-based breast reconstruction exists. Many papers relate to orthopaedic implant surgery, or clean surgery in general. Following review of the evidence, sufficient data exists to support use of perioperative antibiotics at implant-based breast reconstruction, with continuation for an extended period in "high risk" patients. Alcohol containing skin preparations should be used over aqueous solutions. Laminar air flow use is suggested. Theatre traffic should be kept to a minimum, as should duration of operative procedure. The implant pocket should be washed prior to implantation. Double gloving and conductive warming are also endorsed. CONCLUSIONS: We have produced a perioperative "Theatre Implant Checklist" for SSI prevention in implant-based breast surgery, with a set of pragmatic up to date guidelines, which allows the reader to evaluate the evidence upon which our recommendations are based.

Molecular phenotypes of DCIS predict overall and invasive recurrence.

BACKGROUND: Molecular phenotypes of invasive breast cancer predict early recurrence. Ductal carcinoma in situ (DCIS) exhibits similar phenotypes, but their frequency and significance remain unclear. To determine whether DCIS molecular phenotypes predict recurrence, 314 women (median age 57.7 years) with primary DCIS who were screened or entered DCIS trials in a specialist breast unit from 1990 to 2010 were studied. PATIENTS AND METHODS: Expression of Ki67, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) within primary DCIS was established using immunohistochemistry (IHC). Patients were subdivided into molecular phenotypes using IHC surrogates [Luminal A (ER/PR+HER2-), Luminal B (ER/PR+/HER2+), HER2 type (ER and PR-/HER2+) or triple negative (ER/PR/HER2)] and recurrence rates compared. RESULTS: Overall, there were 57 (18.2%) recurrences, 35 (11.2%) DCIS and 22 (7%) invasive cancer. A low rate of recurrence at 5 years was seen in Luminal A DCIS (7.6%), compared with 15.8%-36.1% in other phenotypes. Independent predictors of overall recurrence on multivariate analysis were involved (<1 mm) surgical margins (HR 4.31, P < 0.001), high-grade lesions (HR 2.28, P < 0.024) and molecular phenotype (HR 5.14, P = 0.001 for Luminal B; HR 6.46, P < 0.001 for HER2 type and HR 3.27, P = 0.028 for triple-negative disease compared with Luminal A DCIS). Independent predictors for invasive recurrence were high Ki67 expression (HR 1.04, P = 0.021) and molecular phenotype (HR 13.4, P = 0.014 for Luminal B; HR 11.4, P = 0.027 for HER2 type and HR 10.3, P = 0.031 for triple negative compared with Luminal A DCIS). CONCLUSIONS: DCIS molecular phenotype predicts for both overall and invasive recurrence. HER2 testing of DCIS could help clinicians individualise the treatment of patients with DCIS.

The frequency of presentation and clinico-pathological characteristics of symptomatic versus screen detected ductal carcinoma in situ of the breast.

INTRODUCTION: DCIS accounts for 20% of screen-detected breast cancers, but also presents symptomatically. Historically, approximately 5% of DCIS was thought to be symptomatic, but accurate evaluation of the presentation of symptomatic DCIS is needed to determine its incidence and tumour biology. METHODS: Clinico-pathological details of a consecutive series of patients presenting to a single breast-unit, with a pre-operative diagnosis of DCIS, were selected. Data included age, mode of presentation, pre-operative clinical and radiographical findings. The final tumour histology, operation, size, grade, ER status (and HER2 expression in invasive cases) were recorded. RESULTS: 375 patients had a pre-operative histological diagnosis of DCIS. 308 (82%) screen-detected (median age 59), 67 (18%) presented via symptomatic clinics (median age 50). At final histology 286 (74%) were pure DCIS, and 67 (23%) had an invasive focus. 43% (29/67) of symptomatic cases had an invasive focus at final histology versus 19% (60/308) screen-detected (p ≤ 0.001). 31% (9/29) of symptomatic, versus 10% (6/60) of screen-detected cases with invasion were node positive (p = 0.05). 45% (28/62) intermediate/high-grade symptomatic cases had an invasive focus at final histology, compared to 19% (57/297) intermediate/high-grade screen-detected cases. 86% (212/248) screen-detected pure DCIS was ER positive compared to 68% (26/38) symptomatically presenting pure DCIS (p ≤ 0.001). Overall, 13% (38/248) pure DCIS presented symptomatically (p = 0.001). CONCLUSIONS: Overall, thirteen percent of pure DCIS present symptomatically. Nearly half of symptomatically presenting DCIS at core biopsy has an occult invasive focus and is more frequently ER negative. Symptomatic DCIS with an invasive focus is more likely to have lymph node involvement.

[Euthanasia, assisted suicide and palliative care: a review by the Ethics Committee of the French Society of Anaesthesia and Intensive Care]. / Fin de vie, euthanasie et suicide assisté : une mise au point de la Société française d'anesthésie et de réanimation (Sfar).

CONTEXT: Management of the end of life is a major social issue which was addressed in France by law, on April 22nd 2005. Nevertheless, a debate has emerged within French society about the legalization of euthanasia and/or assisted suicide (E/AS). This issue raises questions for doctors and most especially for anesthetists and intensive care physicians. OBJECTIVE: To highlight, dispassionately and without dogmatism, key points taken from the published literature and the experience of countries which have legislated for E/AS. RESULTS: The current French law addresses most of the end of life issues an intensive care physician might encounter. It is credited for imposing palliative care when therapies have become senseless and are withdrawn. However, this requirement for palliative care is generally applied too late in the course of a fatal illness. There is a great need for more education and stronger incentives for early action in this area. On the rare occasions when E/AS is requested, either by the patient or their loved-ones, it often results from a failure to consider that treatments have become senseless and conflict with patient's best interest. The implementation of E/AS cannot be reduced to a simple affirmation of the Principle of autonomy. Such procedures present genuine difficulties and the risk of drift. CONCLUSION: We deliver a message of prudence and caution. Should we address painful end of life and moral suffering issues, by suppressing the subject, i.e. ending the patient's life, when comprehensive palliative care has not first been fully granted to all patients in need of it ?

Adhesive bowel obstruction? Not always.

A 58-year-old man presented acutely with features of post-surgical adhesive small bowel obstruction. Following an unsuccessful trial of conservative management, computed tomography (CT) of the abdomen was performed. This revealed a mass in the ileocaecal region, for which he underwent a subsequent right hemicolectomy. Histology revealed diffuse B-cell Non-Hodgkin's lymphoma of the terminal ileum. Confounding obstructive lesion of the intestine in patients with a history of previous laparotomy is extremely uncommon. Early high resolution imaging may predict diagnosis and consolidate clinical management plans.

Development of the Fibromyalgia Burden Assessment: measuring the multifaceted burden of fibromyalgia.

OBJECTIVES: To develop a questionnaire assessing the burden of fibromyalgia's impacts on patients' lives. METHODS: A literature review was conducted to identify impacts of fibromyalgia and their consequences on patients' lives. Exploratory interviews were performed with 15 fibromyalgia patients in France, Germany and Spain. Using patients' wording, items were generated simultaneously in French, German, Spanish, and UK English. Relevance and comprehension of the resulting questionnaire versions were tested with 21 additional fibromyalgia patients; questionnaires were revised accordingly. RESULTS: Three domains, Burden associated with the impacts of fibromyalgia, Symptoms and Influencing factors, were identified from the literature review. Following patient interviews, the burden domain was further divided based on the nature of the impact: Pain, Physical impact (including tiredness, sleep problems and other symptoms), Activities of Daily Living impact (including autonomy and coping), Social and Family Life impact, Work, Studies and Personal Finances impact, Psychological impact (including cognitive impact), and Relationship to Medicine and Disease. The resulting test versions of the questionnaire contained 79 items. Comprehension tests identified problematic items and cultural differences and suggested deletions or rewording. After revision and linguistic harmonization, the pilot version of the questionnaire contained 62 items divided into 7 sections, and was named Fibromyalgia Burden Assessment (FMBA©). CONCLUSIONS: The FMBA is a self-reported questionnaire allowing the assessment and a better understanding of the impacts of fibromyalgia and the burden associated with these on patients' daily lives. It is available in UK English, French, German and Spanish. Its scoring and validation remain to be undertaken.

Montelukast and bronchial inflammation in asthma: a randomised, double-blind placebo-controlled trial.

BACKGROUND: Examination of bronchoalveolar lavage, induced sputum, and peripheral blood indicate that cysteinyl leukotriene receptor blockers decrease inflammatory cells in asthma but these do not examine airway tissue per se. OBJECTIVES: Our objective was to determine the effect of montelukast, a leukotriene receptor antagonist, on airway tissue inflammatory cells by direct bronchoscopic examination of the bronchial mucosa. METHODS: Adult subjects with mild asthma (pre-bronchodilator FEV(1)> or =70% predicted; PC(20) of < or =4 mg/mL) were given 10mg/day oral montelukast (N=38) or placebo (N=37) for 6 weeks. Bronchial mucosal eosinophils and mast cells were identified and counted. RESULTS: Change from baseline in numbers of biopsy EG2+ ("activated") eosinophils was the primary endpoint; numbers of total (chromotrope 2R+) eosinophils and (tryptase+) mast cells were secondary. Unexpectedly, there were many patients with zero EG2+ eosinophils at baseline. There was a within-group decrease in EG2+ cells, from 13.54 cells/mm (at baseline) to 0.79 cells/mm at 6 weeks in the montelukast group (LS mean change; 95% confidence interval=-13.59 [-25.45, -1.74]cells/mm; P<0.05), a change not observed in the placebo group (-1.17 [-13.26, 10.91]cells/mm; NS). The zero-inflated Poisson statistical model demonstrated that montelukast significantly reduced post-treatment EG2+ cells by 80% compared with placebo (95% CI [70.6-86.8%]; P<0.0001). The data for total eosinophils showed similar changes. The reduction in mast cell numbers was 12% (95% CI [7.9, 16.0]; P<0.0001). CONCLUSION: Direct examination of airway tissue confirms that montelukast decreases the number of eosinophils and mast cells in asthma.

Reflections on TORCH: potential mechanisms for the survival benefit of salmeterol/fluticasone propionate in COPD patients.

COPD is a disease with a multi-component pathophysiology in which inflammation plays a key role. An anti-inflammatory effect of salmeterol (S)/fluticasone propionate (FP) combination (SFC), as demonstrated in a number of biopsy studies, may be the mechanism by which it provides a potential survival benefit in COPD patients in the TORCH study. It is possible that the molecular synergy between S and FP shown in COPD results in enhanced anti-inflammatory in the airways. This may also contribute to the reduction in exacerbations and the increase in lung function seen in the TORCH study. Alternatively, SFC may prolong survival by impacting on systemic inflammation and disease co-morbidities in COPD.

Biología

Contenido: La unidad de la vida. Genética: las bases celulares y químicas de la herencia. Los genes en acción: estructura, expresión y control de la información genética. Evolución. La diversidad de la vida. Biología de los animales. Biología de las plantas. Ecología...

Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a pooled analysis.

Bronchial biopsy specimens from chronic obstructive pulmonary disease (COPD) patients demonstrate increased numbers of CD8+ T-lymphocytes, macrophages and, in some studies, neutrophils and eosinophils. Smoking cessation affects the rate of forced expiratory volume in one second (FEV(1)) decline in COPD, but the effect on inflammation is uncertain. Bronchial biopsy inflammatory cell counts were compared in current and ex-smokers with COPD. A pooled analysis of subepithelial inflammatory cell count data from three bronchial biopsy studies that included COPD patients who were either current or ex-smokers was performed. Cell count data from 101 subjects, 65 current smokers and 36 ex-smokers, were analysed for the following cell types: CD4+ and CD8+ T-lymphocytes, CD68+ (monocytes/macrophages), neutrophil elastase+ (neutrophils), EG2+ (eosinophils), mast cell tryptase+ and cells mRNA-positive for tumour necrosis factor-alpha. Current smokers and ex-smokers were similar in terms of lung function, as measured by FEV(1) (% predicted), forced vital capacity (FVC) and FEV(1)/FVC. The results demonstrate that there were no significant differences between smokers and ex-smokers in the numbers of any of the inflammatory cell types or markers analysed. It is concluded that, in established chronic obstructive pulmonary disease, the bronchial mucosal inflammatory cell infiltrate is similar in ex-smokers and those that continue to smoke.

Cyclooxygenase-2 inhibition: effects on tumour growth, cell cycling and lymphangiogenesis in a xenograft model of breast cancer.

Cyclooxygenase-2 (COX-2) is associated with poor-prognosis breast cancer. We used a nude mouse xenograft model to determine the effects of COX-2 inhibition in breast cancer. Oestrogen receptor (ER)-positive MCF7/HER2-18 and ER-negative MDAMB231 breast cancer cell lines were injected into nude mice and allowed to form tumours. Mice then received either chow containing Celecoxib (a COX-2 inhibitor) or control and tumour growth measured. Tumour proliferation, apoptosis, COX-2, lymphangiogenesis and angiogenesis were assessed by immunohistochemistry (IHC), Western blotting or Q-PCR. Celecoxib inhibited median tumour growth in MCF7/HER2-18 (58.7%, P=0.029) and MDAMB231 (46.3%, P=0.0002) cell lines compared to control. Cyclooxygenase-2 expression decreased following Celecoxib treatment (MCF7/HER2-18 median control 65.3% vs treated 22.5%, P=0.0001). Celecoxib increased apoptosis in MCF7/HER2-18 tumours (TUNEL 0.52% control vs 0.73% treated, P=0.0004) via inactivation of AKT (median pAKT(ser473) 57.3% control vs 35.5% treated, P=0.0001--confirmed at Western blotting). Q-PCR demonstrated decreased podoplanin RNA (lymphangiogenesis marker) in the MCF7/HER2-18 - median 2.9 copies treated vs 66.6 control (P=0.05) and MDAMB231-treated groups--median 160.7 copies vs 0.05 control copies (P=0.015), confirmed at IHC. Cyclooxygenase-2 is associated with high levels of activated AKT(ser473) and lymphangiogenesis in breast cancer. Cyclooxygenase-2 inhibition decreases tumour growth, and may potentially decrease recurrence, by inactivating AKT and decreasing lymphangiogenesis.

Variability of bronchial inflammation in chronic obstructive pulmonary disease: implications for study design.

There is variability in the distribution of inflammatory cells in bronchial tissue in chronic obstructive pulmonary disease (COPD). Better strategies for biopsy sampling of the airway mucosa may improve the capacity to show a difference between study populations where variability in distribution exists. The current authors have examined sources of biological variability in the quantification of inflammatory cells in endobronchial biopsies using immunostained samples taken from 51 subjects with COPD, with a mean forced expiratory volume in one second of 1.71 L, 55% predicted. The distribution of variance contributed by different sources was similar for different inflammatory cell types. For CD8+ cells, a key inflammatory cell in COPD, the largest contribution to intra-subject variability (39%) was time (i.e. 10 weeks between biopsies of placebo-treated subjects), followed by airway generation (23%), biopsy (2.5%), zone (within section; 1.4%) and section (0.4%). Power calculations demonstrated that examining one section from one biopsy, from each of two airway generations, would require a sample size of 32 subjects per group to show a difference of one doubling or halving in CD8+ cells, compared with 47 subjects per group if only one airway generation was sampled. Therefore, biopsies from more than one airway generation should be examined in order to maximise statistical power to detect a difference between study groups.

Survivin expression in in situ and invasive breast cancer relates to COX-2 expression and DCIS recurrence.

In lung cancer cyclooxygenase-2 (COX-2) expression has been reported to stabilise survivin, an inhibitor of apoptosis (IAP) which prevents cell death by blocking activated caspases. COX-2 expression limits the ubiquitination of survivin, protecting it from degradation. To determine if COX-2 expression in breast cancer showed an association with survivin expression, we assessed the levels of each protein in ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC); relating expression patterns to recurrence of DCIS after surgery. Patterns of COX-2 and survivin expression were determined by intensity-graded immunohistochemistry of the primary tumours. Patients with DCIS (n=161) which had either recurred (n=47) or shown no evidence of recurrence (n=114) 5 years following primary surgery were studied. These were compared to 58 cases of IBC. Survivin was expressed in the cytoplasm of 59% of DCIS and 17% of IBC. High levels of both cytoplasmic survivin and COX-2 expression significantly correlated to DCIS recurrence. COX-2 expression was present in 72% of DCIS, and levels of expression positively correlated with cytoplasmic survivin expression in DCIS and invasive disease. The majority of DCIS that recurred expressed both proteins (69%) vs 39% nonrecurrent. Recurrence was not seen in DCIS lacking both proteins at 5 years (P=0.001). Expression of the IAP survivin is increased in DCIS and correlates closely with COX-2 expression. Increased expression of IAP, (leading to reduced apoptosis) may explain the effect of COX-2 in increasing recurrence of DCIS after surgical treatment.

Raft localisation of FcgammaRIIa and efficient signaling are dependent on palmitoylation of cysteine 208.

Ligand-dependent aggregation of FcgammaRIIa initiates multiple biochemical processes including the translocation to detergent resistant membrane domains (DRMs) and receptor tyrosine phosphorylation. Palmitoylation of cysteine residues is considered to be one process that assists in the localisation of proteins to DRMs. Within the juxtamembrane region of FcgammaRIIa there is cysteine residue (C208) that we show to be palmitoylated. Mutation of this cysteine residue results in the disruption of FcgammaRIIa translocation to DRMs as empirically defined by insolubility at high Triton X-100 concentrations. This study also demonstrates that the lack of lipid raft association diminishes FcgammaRIIa signaling as measured by receptor phosphorylation and calcium mobilisation functions suggesting that FcgammaRIIa signaling is partially dependent on lipid rafts.