Citations

Abstract Negative selection refers to the selective deletion of autoreactive thymocytes but its molecular events have not been well defined. In this study, we demonstrate that a cellular ligand for herpes virus entry mediator and lymphotoxin receptor (LIGHT), a newly identified member of the TNF superfamily, may play a critical role in negative selection. Using TCR transgenic mice, we find that the blockade of LIGHT signaling in vitro and in vivo prevents negative selection induced by peptide and intrathymically expressed Ags, resulting in the rescue of thymocytes from apoptosis. Furthermore, the thymi of LIGHT transgenic mice show severe atrophy with remarkably reduced CD4+CD8+ double-positive cells caused by increased apoptosis, suggesting that LIGHT can delete immature T cells in vivo. Taken together, these results demonstrate a critical role of LIGHT in thymic negative selection of the T cell repertoire.

Abstract To investigate the role of HLA-DQ molecules and/or CD4+ T cells in the pathogenesis of allergic asthma, we generated HLA-DQ6 and HLA-DQ8 transgenic mice lacking endogenous class II (Aβnull) and CD4 genes and challenged them intranasally with short ragweed allergenic extract (SRW). We found that DQ6/CD4null mice developed a strong eosinophilic infiltration into the bronchoalveolar lavage and lung tissue, while DQ8/CD4null mice were normal. However, neither cytokines nor eosinophil peroxidase in the bronchoalveolar lavage of DQ6/CD4null mice was found. In addition, the airway reactivity to methacholine was elevated moderately in DQ6/CD4null mice compared with the high response in DQ/CD4+ counterparts and was only partially augmented by CD4+ T cell transfer. The DQ6/CD4null mice showed Th1/Th2-type cytokines and SRW-specific Abs in the immune sera in contrast to a direct Th2 response observed in DQ6/CD4+ mice. The proliferative response of spleen mononuclear cells and peribronchial lymph node cells demonstrated that the response to SRW in DQ6/CD4null mice was mediated by HLA-DQ-restricted CD4−CD8−NK1.1− T cells. FACS analysis of PBMC and spleen mononuclear cells demonstrated an expansion of double-negative (DN) CD4−CD8−TCRαβ+ T cells in SRW-treated DQ6/CD4null mice. These cells produced IL-4, IL-5, IL-13, and IFN-γ when stimulated with immobilized anti-CD3. IL-5 ELISPOT assay revealed that DN T cells were the cellular origin of IL-5 in allergen-challenged DQ6/CD4null mice. Our study shows a role for HLA-DQ-restricted CD4+ and DN T cells in the allergic response.

ABSTRACTBACKGROUND AND PURPOSEHypertrophic olivary degeneration (HOD) is an uncommon type of transneuronal degeneration. Case reports and case series described in the literature provide a foundation of our current knowledge of HOD. These reports have described HOD most frequently to be unilateral and occurring in association with lesions in the dentato‐rubro‐olivary pathway. Our purpose was to evaluate the rate of bilateral versus unilateral HOD in a large case series.METHODSA retrospective review was performed to identify patients in which the phrase “hypertrophic olivary degeneration” occurred in the radiology report. A diagnosis of HOD was confirmed on imaging if there was focal hyperintensity on T2‐weighted images confined to either or both inferior olivary nuclei.RESULTSA total of 102 patients had findings consistent with HOD. Of these, 76% had findings bilaterally. In 44%, a lesion could not be identified to explain HOD. Bilateral HOD was common in both lesional and nonlesional group, though more common in the nonlesional group.CONCLUSIONThis study demonstrates that HOD is frequently bilateral. In slightly over 50% of patients with HOD, a lesion can be identified. In just under 50% patients with HOD, a lesion could not be identified and in these cases HOD was present bilaterally in the majority.

Purpose The purposes of this study were to determine the frequency of acute and subacute complications (within 6 months) of arthroscopic knee procedures in patients aged 17 years or younger and to determine associated risk factors. Methods We identified all patients aged 17 years or younger who underwent arthroscopic knee procedures at our institution from 1997 to 2009. Patient demographic and surgical data were collected from the medical and surgical records, with specific focus on intraoperative and postoperative complications. Results During the study period, 1,002 knee arthroscopies were reviewed. The overall complication rate was 14.7%. Major complications occurred in 21 surgeries (2.1%) and included the following: septic arthritis (n = 3, 0.3%), wound complication requiring operative revision (n = 9, 0.9%), arthrofibrosis requiring manipulation (n = 4, 0.4%), other unplanned subsequent surgery (n = 4, 0.4%), and death (n = 1, 0.1%). Surgeries with an anesthesia time of 265 minutes or greater ( P = .026), operative time of 220 minutes or greater ( P = .013), or tourniquet time of 114 minutes or greater ( P < .001) and surgeries with 3 or more Current Procedural Terminology codes ( P = .003) had a statistically significant increase in risk of major complications. The incidence of minor complications was 12.6%, which included persistent effusion/hemarthrosis requiring arthrocentesis (n = 59, 5.9%) and superficial wound infection (n = 18, 1.8%). Conclusions Major complications after knee arthroscopy in children and adolescents are rare, but minor complications are more common. If possible, surgeons should avoid prolonged anesthesia, surgery, and tourniquet times. The pediatric patient's medical and family history should be reviewed to identify important risk factors. Level of Evidence Level IV, therapeutic case series.

Objective: Endoscopic medial partial arytenoidectomy has been described previously for expansion of the posterior glottic airway in bilateral vocal fold paralysis. Superomedial submucosal partial arytenoidectomy (SSPA), a modification of this technique, can improve glottic closure in the setting of an obstructing anteromedially prolapsed arytenoid. We present our surgical technique and a case example. Methods and Results: A 45-year-old man presented with dysphonia attributable to unilateral true vocal fold paralysis. Laryngoscopy revealed right true vocal fold atrophy and an anteriorly prolapsed right arytenoid cartilage preventing posterior glottic closure during adduction. Right SSPA and ipsilateral vocal fold injection augmentation were performed without complication. One-month and 11-month postoperative evaluations showed marked improvement in voice, with complete glottic closure. Quality-of-life assessment and patient report showed a durable result at 50 months. Conclusion: SSPA may be a valuable technique in the management of breathy dysphonia associated with posterior glottic gap and other sequelae of the malpositioned arytenoid.