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- Ljunghill Hedberg, Anna, et al.
(författare)
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Lower response to early T-cell-dependent vaccination after neurotrauma or neurosurgery in adults
- 2015
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Ingår i: Journal of Infection. - : Elsevier BV. - 0163-4453 .- 1532-2742. ; 70:6, s. 577-584
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent international guidelines recommend vaccination with a 13-valent pneumococcal conjugate vaccine to reduce the risk of meningitis after neurotrauma with cerebrospinal fluid leak. The antibody response and optimal time point for vaccination have not been established and because the risk of meningitis is at the highest shortly after trauma, early vaccination is preferable. This study aimed to investigate the antibody response and to ensure that central nervous system injury-induced immunodepression did not affect the response to a T-cell-dependent conjugate vaccine when administered shortly after the injury. Methods: So as not to interfere with routine pneumococcal vaccination, a conjugate vaccine against Haemophilus influenza type b (Hib) was chosen for the study. Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated within 10 days after trauma/surgery and 29 control patients at least three weeks after trauma/surgery. Sera were collected pre- and post-vaccination for analysis of anti-Hib concentration. Results: Four patients with post-vaccination target antibody concentration before vaccination were excluded from analysis. In the neurotrauma and neurosurgery groups 10/32 (31%) and 5/20 (25%) patients, respectively, were non-responders compared with 3/29 (10%) in the control group. Log(10) anti-Hib concentrations in the neurotrauma, neurosurgery and control groups were 1.52 +/- 0.15, 1.38 +/- 0.15 and 1.81 +/- 0.12 mu g/ml, respectively. Conclusions: The majority of the patients responded to vaccination. However, the number of responders was significantly decreased and antibody concentration significantly lower in patients vaccinated early after the trauma/surgery. Investigation of the pneumococcal conjugate vaccine response in neurotrauma patients is therefore urgent. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
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| 2. |
- Olde, Bjorn, et al.
(författare)
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G protein-coupled Receptor 30 (GPR30) PDZ-dependently and Constitutively Increases ERK1/2 Signaling Through Calcineurin and Kinase Suppressor of Ras 2 (KSR2)
- 2016
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Ingår i: FASEB Journal. - 0892-6638. ; 30:1 Suppl, s. 518-518
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Konferensbidrag (refereegranskat)abstract
- The objective of the present study was to map the mechanism whereby G protein-coupled receptor 30 (GPR30), also called G protein-coupled estrogen receptor (GPER), stimulates extracellular signal-regulated kinase (ERK)1/2 signaling. GPR30 plays important roles in cancer and cardiometabolic regulation. We showed recently that GPR30 forms a plasma membrane complex through its C-terminal type I PSD-95/Discs-large/ZO-1 homology (PDZ) motif with a membrane-associated guanylate kinase (MAGUK) and protein kinase A (PKA)-anchoring protein 5 (AKAP5), and AKAP5-anchored PKA regulatory subunit RII suppresses receptor endocytosis and enables the receptor to constitutively inhibit cAMP production. Here, we investigated if this PDZ-dependent GPR30 complex also regulates ERK1/2 signaling. To do so, human and mouse GPR30 were ectopically expressed in HEK293 cells and MDCK cells, and receptors and effectors were monitored by immunoblotting, immunoprecipitation, confocal immunofluorescence microscopy, split luciferase reporter techniques, and reporter gene assays. We found that GPR30 constitutively increased extracellular signal-regulated kinase (ERK) 1/2 activity in several cell systems. The response was dependent on an intact receptor PDZ motif. Furthermore, knocking down AKAP5 or inhibiting calcineurin with FK506 inhibited the receptor response. GPR30 PDZ-dependently inhibited basal NFAT signaling, consistent with the receptor favoring AKAP5-anchoring of calcineurin. The calcineurin substrate kinase suppressor of Ras 2 (KSR2), a mitogen-activated protein kinase (MAPK) scaffold, enhanced the GPR30-promoted response, also dependently on the receptor PDZ motif. GPR30 also PDZ-dependently favored a membrane KSR2 complex at the expense of the monomeric form. On the other hand, disrupting AKAP5-PKA RII interaction with St-Ht31, or inhibiting protein kinase C (PKC) with GF109203X or epidermal growth factor receptor (EGFR) tyrosine kinase with AG1478 had no effect on the GPR30-stimulated response. FK506 also increased the amount of GPR30 in the plasma membrane, thus acting opposite to St-Ht31, which increased receptor endocytosis. We conclude that the PDZ-dependent GPR30 complex with AKAP5 includes calcineurin, which favors GPR30 endocytosis and enables the receptor to constitutively increase ERK1/2 signaling through KSR2. Support or Funding Information Swedish Cancer Foundation
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| 3. |
- Regardt, M, et al.
(författare)
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Patients' Experience of Myositis and Further Validation of a Myositis-specific Patient Reported Outcome Measure - Establishing Core Domains and Expanding Patient Input on Clinical Assessment in Myositis. Report from OMERACT 12
- 2015
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 42:12, s. 2492-2495
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Tidskriftsartikel (refereegranskat)abstract
- The Outcome Measures in Rheumatology (OMERACT) myositis working group was established to examine patient-reported outcomes (PRO) as well as to validate patient-reported outcome measures (PROM) in myositis.Methods.Qualitative studies using focus group interviews and cognitive debriefing of the myositis-specific Myositis Activities Profile (MAP) were used to explore the experience of adults living with polymyositis (PM) and dermatomyositis (DM).Results.Preliminary results underscore the importance of patient input in the development of PROM to ensure content validity. Results from multicenter focus groups indicate the range of symptoms experienced including pain, fatigue, and impaired cognitive function, which are not currently assessed in myositis. Preliminary cognitive debriefing of the MAP indicated that while content was deemed relevant and important, several activities were not included; and that questionnaire construction and wording may benefit from revision. A research agenda was developed to continue work toward optimizing PRO assessment in myositis with 2 work streams. The first would continue to conduct and analyze focus groups until saturation in the thematic analysis was achieved to develop a framework that encompassed the patient-relevant aspects of myositis. The second would continue cognitive debriefing of the MAP to identify potential areas for revision. There was agreement that further work would be needed for inclusion body myositis and juvenile dermatomyositis, and that the inclusion of additional contributors such as caregivers and individuals from the pharmaceutical/regulatory spheres would be desirable.Conclusions.The currently used PROM do not assess symptoms or the effects of disease that are most important to patients; this emphasizes the necessity of patient involvement. Our work provides concrete examples for PRO identification.
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