Leukotriene C4 induces migration of human monocyte-derived dendritic cells without loss of immunostimulatory function

Generation of human monocyte-derived dendritic cells (DCs) for cancer vaccination involves ex vivo maturation in the presence of proinflammatory cytokines and prostaglandin E(2) (PGE(2)). Although the inclusion of PGE(2) during maturation is imperative for the induction of DC migration, PGE(2) has unfavorable effects on the immunostimulatory capacity of these cells. Like PGE(2), leukotrienes (LTs) are potent mediators of DC migration. We therefore sought to characterize the migratory and immunologic properties of DCs that matured in the presence of LTB(4), LTC(4), LTD(4), and PGE(2). Here, we demonstrate that DCs matured in the presence of LTC(4), but not LTB(4) or LTD(4), are superior to PGE(2)-matured DCs in stimulating CD4(+) T-cell responses and in inducing antigen-specific cytotoxic T lymphocytes (CTLs) in vitro without concomitant induction or recruitment of regulatory T cells (Tregs). LTC(4)-matured DCs migrate efficiently through layers of extracellular matrix and secrete higher levels of immunostimulatory IL-12p70 while producing reduced levels of immune-inhibitory IL-10, IL12p40, indoleamine-2,3-dioxidase, and TIMP-1 (tissue inhibitor of matrix metalloproteinases). Intracellular calcium mobilization and receptor antagonist studies reveal that, in contrast to LTD(4), LTC(4) did not signal through CysLTR(1) in DCs. Collectively, our data suggest that LTC(4) represents a promising candidate to replace PGE(2) in DC maturation protocols for cancer vaccination.     

Cricopharyngeal Dilatation for the Long-term Treatment of Dysphagia in Oculopharyngeal Muscular Dystrophy

Oculopharyngeal muscular dystrophy (OPMD) is a rare autosomal dominant, progressive degenerative muscle disorder featuring dysphagia with limited therapeutic options. The aim of this study was to evaluate the safety and efficacy of repeated endoscopic dilatation for OPMD over a 15-year period. All patients seen at our Regional Swallowing Clinic with OPMD confirmed by genetic analysis were included. Cricopharyngeal dilatation was performed as an outpatient procedure using a wire-guided 18-mm (54 Fr) Savary-Gilliard bougie with the patient under sedation. Patients were offered repeat endoscopic dilatation when symptoms recurred. Symptom severity prior to initial dilatation and at follow-up was evaluated using the Sydney Swallow Questionnaire (SSQ). Nine patients (7 female, 2 male) were included for analysis. Median total treatment period was 13?years (range?=?3-15), median number of dilatations per patient was 7.2 (range?=?1-16), and median interval between treatments was 15?months (range?=?4.5-45). All patients recorded sustained symptom improvement. Mean SSQ score (out of 1,700) was 1,108.11 (SD?±?272.85) prior to first dilatation and 297.78 (SD?±?189.14) at last follow-up, representing a 73% decrease (95% CI?=?52-94) in degree of dysphagia symptoms (paired t-test, P?=?0.0001). All mean scores for individual questions also showed significant improvement (P?相似文献   

Paediatric traumatic brain injury: A review of pertinent issues

Children with traumatic brain injury (TBI), regardless of the severity of the injury, often face challenges when living in home, school and community. Their needs are often overlooked and recognition of the long-term consequences is not always central to the management of the child in the school or community. This article provides references to pertinent literature and suggestions for intervention from the clinical experiences of four individuals with extensive experience of the family stresses, educational, cognitive-communicative and behavioural challenges that occur after TBI in children. It provides information regarding these issues, particularly educational situations, and suggests methods that may be useful for service providers and family members.     

Composite polymerization stress as a function of specimen configuration assessed by crack analysis and finite element analysis

Objectives

To test the null hypothesis that polymerization-induced stress was not influenced by cavity dimensions and geometries.

Methods

Four experimental groups, with different C-factors and specimen volumes were defined using bottom-less glass disks (height: 1 or 2 mm) with a central hole 3 or 6 mm in diameter, and 3 mm wall thickness. Another four groups were created by bonding a glass plate to the bottom of the disks. Additionally, disks with 2-mm height, 3 mm in cavity diameter, and 4.5-mm thick walls were prepared. Vickers indents (9.8 N, 20 s) were made at the top surface at 600 μm from the cavity margin. The lengths of the indentation diagonal and the corner cracks parallel to the cavity margin were measured. Ten minutes after restoration (Majesty Esthetic, Kuraray), cracks were re-measured. Stresses at the indent site were calculated based on glass fracture toughness and increase in crack length. Data were subjected to ANOVA/Tukey or Kruskal–Wallis/Mann–Whitney tests (alpha: 5%, n = 8). Finite element analysis (FEA) was used to estimate stress at the interface and the effective structural rigidity of the substrate.

Results

Overall, for experimental and FEA results, cavities developed higher stress than bottom-less disks. Increasing wall thickness did not affect stress. When similar geometries and C-factors were compared, higher volumes developed higher stress and had greater incidence of margin cracking.

Clinical significance

C-factor is a suitable predictor for polymerization stress in low compliance environments, particularly due to its simplicity. However, the influence of cavity size cannot be disregarded especially for the development of marginal cracking. The interaction between size, geometry and stiffness is likely to become more complex according to the complexity of the cavity shape.