The multiple roles of major histocompatibility complex class-I-like molecules in mucosal immune function

The human major histocompatibility complex (MHC) on chromosome 6 encodes three classical class-I genes: human leukocyte antigens (HLA) A, B, and C. These polymorphic genes encode a 43- to 45-kDa cell surface glycoprotein that, in association with the 12-kDa β₂-microglobulin molecule, functions in the presentation of nine amino acid peptides to the T-cell receptor of CD8-bearing T lymphocytes and killer inhibitory receptors on natural killer cells. In addition to these ubiquitously expressed, polymorphic proteins, the human genome also encodes several nonclassical MHC class-I-like, or class Ib, genes that, in general, encode nonpolymorphic molecules involved in various specific immunological functions. Many of these genes, including CD1, the neonatal Fc receptor for IgG, HLA-G, HLA-E, the MHC class-I chainrelated gene A, and Hfe, are prominently displayed on epithelial cells, suggesting an important role in epithelial cell biology.     

Property evolution during vitrification of dimethacrylate photopolymer networks

Objectives

This study seeks to correlate the interrelated properties of conversion, shrinkage, modulus and stress as dimethacrylate networks transition from rubbery to glassy states during photopolymerization.

Methods

An unfilled BisGMA/TEGDMA resin was photocured for various irradiation intervals (7–600 s) to provide controlled levels of immediate conversion, which was monitored continuously for 10 min. Fiber optic near-infrared spectroscopy permitted coupling of real-time conversion measurement with dynamic polymerization shrinkage (linometer), modulus (dynamic mechanical analyzer) and stress (tensometer) development profiles.

Results

The varied irradiation conditions produced final conversion ranging from 6% to more than 60%. Post-irradiation conversion (dark cure) was quite limited when photopolymerization was interrupted either at very low or very high levels of conversion while significant dark cure contributions were possible for photocuring reactions suspended within the post-gel, rubbery regime. Analysis of conversion-based property evolution during and subsequent to photocuring demonstrated that the shrinkage rate increased significantly at about 40% conversion followed by late-stage suppression in the conversion-dependent shrinkage rate that begins at about 45–50% conversion. The gradual vitrification process over this conversion range is evident based on the broad but well-defined inflection in the modulus versus conversion data. As limiting conversion is approached, modulus and, to a somewhat lesser extent, stress rise precipitously as a result of vitrification with the stress profile showing little if any late-stage suppression as seen with shrinkage.

Significance

Near the limiting conversion for this model resin, the volumetric polymerization shrinkage rate slows while an exponential rise in modulus promotes the vitrification process that appears to largely dictate stress development.     

No Effect of Hole Geometry in Microfracture for Talar Osteochondral Defects

Background

Débridement and bone marrow stimulation is an effective treatment option for patients with talar osteochondral defects. However, whether surgical factors affect the success of microfracture treatment of talar osteochondral defects is not well characterized.

Questions/purposes

We hypothesized (1) holes that reach deeper into the bone marrow-filled trabecular bone allow for more hyaline-like repair; and (2) a larger number of holes with a smaller diameter result in more solid integration of the repair tissue, less need for new bone formation, and higher fill of the defect.

Methods

Talar osteochondral defects that were 6 mm in diameter were drilled bilaterally in 16 goats (32 samples). In eight goats, one defect was treated by drilling six 0.45-mm diameter holes in the defect 2 mm deep; in the remaining eight goats, six 0.45-mm diameter holes were punctured to a depth of 4 mm. All contralateral defects were treated with three 1.1-mm diameter holes 3 mm deep, mimicking the clinical situation, as internal controls. After 24 weeks, histologic analyses were performed using Masson-Goldner/Safranin-O sections scored using a modified O’Driscoll histologic score (scale, 0–22) and analyzed for osteoid deposition. Before histology, repair tissue quality and defect fill were assessed by calculating the mean attenuation repair/healthy cartilage ratio on Equilibrium Partitioning of an Ionic Contrast agent (EPIC) micro-CT (μCT) scans. Differences were analyzed by paired comparison and Mann-Whitney U tests.

Results

Significant differences were not present between the 2-mm and 4-mm deep hole groups for the median O’Driscoll score (p = 0.31) and the median of the μCT attenuation repair/healthy cartilage ratios (p = 0.61), nor between the 0.45-mm diameter and the 1.1-mm diameter holes in defect fill (p = 0.33), osteoid (p = 0.89), or structural integrity (p = 0.80).

Conclusions

The results indicate that the geometry of microfracture holes does not influence cartilage healing in the caprine talus.

Clinical Relevance

Bone marrow stimulation technique does not appear to be improved by changing the depth or diameter of the holes.