1,721,022 research outputs found
Exemplifying complexity of immune suppression by a “canonical” speech: A glimpse into TNFRSF‐activated signaling pathways in Treg cells
No full textRegulatory T (Treg) cells are crucial mediators of immune tolerance suppressing self-reactive T cells and preventing autoimmune diseases. Besides activation of the T cell receptor (TCR), empowerment of Treg cell functions requires co-accessory signals, such as those released by the TNF receptor superfamily (TNFRSF) that, however, can also promote immunostimulatory responses when engaged by effector T cells. In this issue of European Journal of Immunology, Lubrano di Ricco et al. [Eur. J. Immunol. 2020. 50: 972–985] have taken a closer look at the important question of the functional meaning of TNFRSF-activated signaling pathways in Treg cells. They have demonstrated that costimulation by TNFR2, 4-1BB, GITR, DR3, but not OX40 in mouse Foxp3+ Treg cells activates the same and unique signaling pathway, i.e., canonical NF-κB, which in turn leads to Foxp3 gene upregulation, cell expansion in vitro and in vivo, and suppressive activity in an experimental model of colitis. Moreover, induction of markers of T helper 2 (Th2) and Th17 as well as of genes encoding proteins involved in noncanonical NF-κΒ was also observed. We here discussed how these findings further highlight the emerging concept of Treg cell plasticity in immune tolerance
Facial bone distraction osteogenesis for correction of malocclusion: A more than 70-year-old concept in craniofacial surgery
No full textBone distraction has been used increasingly since McCarthy and associates showed in their clinical investigation new osseous formation in the elongated area while performing mandibular distraction in 1992. However, at the craniofacial skeletal level, the initial description of the classic technique of distraction osteogenesis should be credited to German craniofacial surgeons Rosenthal (for bone lengthening of the mandible in a microgenia patient around 1927) and Wassmund (for the clinical advancement of a maxilla in a patient with hypoplasia of the upper jaw in 1926). Both procedures are described, and their original schedules and cases are presented
Amino acid metabolism in rheumatoid arthritis: Friend or foe?
No full textIn mammals, amino acid metabolism has evolved to act as a critical regulator of innate and adaptive immune responses. Rheumatoid arthritis (RA) is the most common form of inflammatory arthropathy sustained by autoimmune responses. We examine here the current knowledge of tryptophan and arginine metabolisms and the main immunoregulatory pathways in amino acid catabolism, in both RA patients and experimental models of arthritis. We found that L-tryptophan (Trp) metabolism and, in particular, the kynurenine pathway would exert protective effects in all experimental models and in some, but not all, RA patients, possibly due to single nucleotide polymorphisms in the gene coding for indoleamine 2,3-dioxygenase 1 (IDO1; the enzyme catalyzing the rate-limiting step of the kynurenine pathway). The function, i.e., either protective or pathogenetic, of the L-arginine (Arg) metabolism in RA was less clear. In fact, although immunoregulatory arginase 1 (ARG1) was highly induced at the synovial level in RA patients, its true functional role is still unknown, possibly because of few available preclinical data. Therefore, our analysis would indicate that amino acid metabolism represents a fruitful area of research for new drug targets for a more effective and safe therapy of RA and that further studies are demanding to pursue such an important objective
Facial bone distraction osteogenesis for correction of malocclusion: A more than 70-year-old concept in craniofacial surgery
No full textBone distraction has been used increasingly since McCarthy and associates showed in their clinical investigation new osseous formation in the elongated area while performing mandibular distraction in 1992. However, at the craniofacial skeletal level, the initial description of the classic technique of distraction osteogenesis should be credited to German craniofacial surgeons Rosenthal (for bone lengthening of the mandible in a microgenia patient around 1927) and Wassmund (for the clinical advancement of a maxilla in a patient with hypoplasia of the upper jaw in 1926). Both procedures are described, and their original schedules and cases are presented
Renaissance of the Franz Konig bilateral lip repair procedure - Clinical experiences with an one hundred year old technique
No full textSurgical correction of bilateral cleft lips is known to have a lot of problems. The surgical principles of treatment of bilateral cleft lips are similar to those of unilateral clefts but differ in the area of the prolabium due to specific anatomical disorders of the orbicularis oris muscle. The postoperative results of simultaneous bilateral cleft lip repair according to Konig were analysed retrospectively in 15 young children (6.1 +/- 1.1 years) paying special emphasis to the aesthetic and functional postoperative outcome of the upper lip and nose. The mean values were compared with measurements from normal infants at ages 8.3 +/- 1.8 years. Lip height and lip length were in 87% similar to those of the age-matched normal group. Only two cleft patients showed a slightly shorter lip. Distortions of the lip function were not obvious. Our data show that Konig's surgical procedure of bilateral cleft lip closure meets the requirements of modern surgical concepts of cleft lip repair and should belong to the armamentarium of modern face surgery
Intraindividual comparative animal study of alpha- and beta-tricalcium phosphate degradation in conjunction with simultaneous insertion of dental implants
No full textAn intraindividual comparative study of proximal tibial marrow defects in nine adult Goettinger miniature pigs (GMPs) was undertaken. The left side of the defect was filled with granular beta -tricalcium phosphate (TCP) ceramic ad modum Cerasorb, and the right side was filled with granular alpha -TCP ceramic ad modum Biobase alpha pore. Simultaneously, dental screw implants were inserted in each ceramic and fixed within the orthotopically replanted corticalis lids. Control defects were made in two other animals. The survival period ranged from 4 to 86 weeks (control study, 16 and 20 weeks). The reorganization and degree of bone regeneration, dynamics of ceramic degradation, and remodeling characteristics of the bone regenerate referring to osseo-integration of the dental implants were examined histomorphologically in nondecalcified specimens. The results reveal that both ceramic types were osteoconductive exclusively. Centripetally oriented angiogene bone regeneration occurred at the margins of the circular defects. Ceramic degradation was performed hydrolytically and within cells. Furthermore, it was demonstrated that decomposition of the intratrabecularly integrated ceramic residues underlies a dynamic process of degradation. Within 86 weeks, nearly 80% to 90% of the larger alpha -TCP granules, and nearly 90% to 95% of the beta -TCP granules were degraded. At this time, especially for the alpha -TCP modification, ceramic microparticles were found in the marrow, either unbound or within polynuclear macrophages. The predictable degradation of both ceramic types provides an early functional adaptation of bone regenerates and facilitates a biofunctional, anisotropic orientation of the neotrabeculae without delay. It is concluded that because of the initially pronounced accumulation of macrophages, dental implants should not be inserted simultaneously with ceramic, but after further progress of ceramic degradation (5 to 6 months after TCP implantation)
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Preclinical discovery and development of fingolimod for the treatment of multiple sclerosis
Full text linkIntroduction: Fingolimod, the first oral disease-modifying treatment (DMT) in multiple sclerosis (MS), is a sphingosine 1-phosphate receptor (S1PR) ligand. Approved in 2010, fingolimod has been extensively studied and has been credited with several mechanisms of actions that contribute to its efficacy in MS, among which is the regulation of lymphocyte circulation between the central nervous system and the periphery. Concerns about toxicity, off-target effects, and real-life performance have been raised over time in post-marketing studies of such that next-generation sphingosine-1 phosphate receptor ligands are now being developed. Areas covered: Herein, the authors expand upon previous systematic reviews obtained via PubMed and through their expert opinion on fingolimod use in clinical practice. Long-term data including long-term efficacy, safety, tolerability, and management especially within growing DMT options and pre-treatment constellation in MS patients are discussed, together with the results of an increased understanding of the chemistry underlying the structure–activity relationship. Expert opinion: Despite the limitations illustrated in this article, fingolimod still constitutes a paradigm shift in MS treatment. However, although immunomodulation via S1PRs on lymphocytes has represented a major breakthrough in the clinical management of MS, modifying the evolution of progressive MS will likely require the development of approaches other than merely targeting S1PRs
- …
