Intermediate monomer-dimer equilibrium structure of native ICAM-1: implication for enhanced cell adhesion.

Dimeric intercellular adhesion molecule-1 (ICAM-1) has been known to more efficiently mediate cell adhesion than monomeric ICAM-1. Here, we found that truncation of the intracellular domain of ICAM-1 significantly enhances surface dimerization based on the two criteria: 1) the binding degree of monomer-specific antibody CA-7 and 2) the ratio of dimer/monomer when a mutation (L42→C42) was introduced in the interface of domain 1. Mutation analysis revealed that the positively charged amino acids, including very membrane-proximal 5°5R, are essential for maintaining the structural transition between the monomer and dimer. Despite a strong dimer presentation, the ICAM-1 mutants lacking an intracellular domain (IC1ΔCTD) or containing R to A substitution in position 505 (5°5R/A) supported a lower degree of cell adhesion than did wild-type ICAM-1. Collectively, these results demonstrate that the native structure of surface ICAM-1 is not a dimer, but is an intermediate monomer-dimer equilibrium structure by which the effectiveness of ICAM-1 can be fully achieved.

Mild to Moderate Varus Alignment in Relation to Surgical Repair of a Medial Meniscus Root Tear: A Matched-Cohort Controlled Study With 2 Years of Follow-up.

BACKGROUND: Increased varus alignment of the lower extremity is known to be a poor prognostic factor for the surgical repair for a medial meniscus root tear (MMRT). However, given the concept of constitutional varus, which is present in a substantial portion of the normal population, the generally accepted surgical indication for MMRT concerning a varus alignment of 5° may be unnecessarily narrow. PURPOSE: To compare the surgical outcomes of arthroscopic transtibial pullout repair of MMRT according to the degree of varus alignment of the lower extremity. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients who underwent isolated arthroscopic transtibial pullout repair of MMRT between January 2010 and July 2017 at one institution and had a minimum follow-up of 2 years were included in this study. Patients were classified into 1 of 2 groups: the experimental group (n = 22) included patients with a preoperative hip-knee-ankle angle between 5° and 10° varus (mild to moderate varus alignment) and the control group (n = 51) included those with a preoperative hip-knee-ankle angle <5° varus (neutral alignment). Clinical scores and radiographic parameters were compared between the groups to assess surgical outcomes, which were statistically matched for potential confounders (age, body mass index, the severity of cartilage lesion) by use of the inverse probability of treatment weighting. A noninferiority trial was performed comparing the experimental and control groups in terms of subjective outcomes (International Knee Documentation Committee subjective and Lysholm scores) and objective outcomes (postoperative medial meniscal extrusion and the rate of osteoarthritis progression). RESULTS: There were no statistically significant differences in surgical outcomes between the groups in subjective and objective aspects, which were consistent before and after inverse probability of treatment weighting. Apart from the clinical improvement observed in both groups, overall degenerative changes in the knee were found, although progression rates did not differ between the groups. In terms of the noninferiority trial, the overall surgical outcomes in the experimental group were not inferior to those in the control group. CONCLUSION: The short-term surgical outcomes of arthroscopic transtibial pullout repair for MMRT of patients with mild to moderate varus alignment were not inferior to but rather comparable with those with neutral alignment in terms of subjective and objective aspects. Therefore, it would be inappropriate to exclude patients with a diagnosis of MMRT from being indicated for the surgery simply because of mild to moderate varus alignment.

Impact of Renal Function on the Surgical Outcomes of Displaced Femoral Neck Fracture in Elderly Patients.

BACKGROUND: The aim of this study was to investigate the relationship between estimated glomerular filtration rate (eGFR) and outcomes of bipolar hemiarthroplasty for femoral neck fracture in elderly patients, and to compare postoperative complications and mortality among groups according to eGFR. METHODS: A total of 181 patients who underwent bipolar hemiarthroplasty for displaced femoral neck fracture were divided into three groups according to eGFR. Data were retrospectively analyzed. Group 1 had 96 patients with eGFR greater than or equal to 60 mL/min/1.73 m2; Group 2 had 54 patients with eGFR greater than or equal to 30 mL/min/1.73 m2 and lower than 60 mL/min/1.73 m2; and Group 3 had 31 patients with eGFR lower than 30 mL/min/1.73 m2. Postoperative complications and mortality were compared between groups at a minimum 2-year follow-up. RESULTS: Patients in Group 3 had the longest hospital stay of the three groups (p = 0.001). The rates of medical complications did not differ significantly among groups. However, Group 2 and 3 had higher rates of surgical complications (p = 0.001) and mortality (p = 0.043) than Group 1. Severe renal impairment was associated with increased risk of postoperative complications compared to mild renal impairment (odds ratio (95% confidence interval) = 4.33 (1.32-13.19), p = 0.015). CONCLUSION: Patients with moderate or severe decreased eGFR associated with chronic kidney disease (CKD) could have higher postoperative complications and mortality after bipolar hemiarthroplasty compared to patients with CKD stage 1 or 2.

IGSF4 is a novel TCR ζ-chain-interacting protein that enhances TCR-mediated signaling.

Immunoglobulin superfamily member 4 (IGSF4) is a known ligand of CRTAM, a receptor expressed in activated NKT and CD8(+) T cells, but its function in T cell immunity has not been elucidated. In this study, we show that IGSF4 directly interacts with the T cell receptor (TCR) ζ-chain and enhances TCR signaling by enhancing ζ-chain phosphorylation. Ectopic overexpression of IGSF4 enhances TCR-mediated T cell activation. In contrast, IGSF4 knockdown shows a dramatic decrease in markers associated with T cell activation compared with those in control small interfering RNA. The transmembrane domain is essential for TCR ζ-chain association and clustering to the immunological synapse, and the ectodomain is associated with T cell interaction with antigen-presenting cells (APCs). IGSF4-deficient mice have impaired TCR-mediated thymocyte selection and maturation. Furthermore, these mice reveal attenuated effector T cell functions accompanied by defective TCR signaling. Collectively, the results indicate that IGSF4 plays a central role in T cell functioning by dual independent mechanisms, control of TCR signaling and control of T cell-APC interaction.