Citations

Abstract Barrett's esophagus, a columnar metaplasia of the lower esophagus epithelium related to gastroesophageal reflux disease, is the strongest known risk factor for the development of esophageal adenocarcinoma (EAC). Understanding the signal transduction events involved in esophageal epithelium carcinogenesis may provide insights into the origins of EAC and may suggest new therapies. To elucidate the molecular pathways of bile acid–induced tumorigenesis, the newly identified inflammation-associated signaling pathway involving IκB kinases β (IKKβ), tuberous sclerosis complex 1 (TSC1), and mammalian target of rapamycin (mTOR) downstream effector S6 kinase (S6K1) was confirmed to be activated in immortalized Barrett's CPC-A and CPC-C cells and esophageal cancer SEG-1 and BE3 cells. Phosphorylation of TSC1 and S6K1 was induced in response to bile acid stimulation. Treatment of these cells with the mTOR inhibitor rapamycin or the IKKβ inhibitor Bay 11-7082 suppressed bile acid–induced cell proliferation and anchorage-independent growth. We next used an orthotopic rat model to evaluate the role of bile acid in the progression of Barrett's esophagus to EAC. Of interest, we found high expression of phosphorylated IKKβ (pIKKβ) and phosphorylated S6K1 (pS6K1) in tumor tissues and the Barrett's epithelium compared with normal epithelium. Furthermore, immunostaining of clinical EAC tissue specimens revealed that pIKKβ expression was strongly correlated with pS6K1 level. Together, these results show that bile acid can deregulate TSC1/mTOR through IKKβ signaling, which may play a critical role in EAC progression. In addition, Bay 11-7082 and rapamycin may potentially be chemopreventive drugs against Barrett's esophagus–associated EAC. [Cancer Res 2008;68(8):2632–40]

A custom computer-controlled rapid prototyping system was designed and developed in this research. This system for bio-manufacturing of polymer scaffolds included 3D motion control components, a nozzle, a pressure controller, and a temperature-controlled reservoir containing a biomaterial. Heating elements built into the reservoir melted the biomaterial. The pressure line attached to the reservoir provided a controllable force that extruded the polymer biomaterial through the nozzle and deposited the polymer biomaterial onto a platform to fabricate scaffolds. A low pressure (830 KPa) system was designed and fabricated to accommodate different temperatures, motion speeds, and viscosities of polymer biomaterials. The reservoir with the nozzle was mounted to servo motor-controlled linear x-y motion devices along with a third servo motor-controlled device that controlled the z-position of the platform. Poly(ε-caprolactone) [PCL] was used to fabricate scaffolds with designed structure that were used in cell and tissue regeneration studies. 3D computer-aided design (CAD) with Pro-Engineer and computational finite element analysis (FEA) programs with MSC_Patran and MSC_Marc were used to model scaffold designs with appropriate architecture and material selection. The CAD models were used in FEA to develop new methods for determining mechanical properties of tissue scaffolds of desired structure and geometry. FEA models were validated by mechanical testing and other published results. Technology developed in this research has potential for the advancement of bio-manufacturing, and design optimization of scaffolds for tissue engineering.

Background Although the use of rotator interval closure is frequently advocated as a useful supplement to shoulder instability repairs, the addition of a rotator interval closure after arthroscopic instability repair has not been fully investigated. Purpose The objective of this study was to investigate whether a rotator interval closure improves glenohumeral stability in an anterior and posterior instability shoulder model. Study Design Controlled laboratory study. Methods Fourteen fresh-frozen cadaveric shoulder specimens were dissected free of soft tissues, leaving the rotator cuff intact with simulated cuff loading. All specimens were mounted in a custom testing apparatus using infrared sensors to document glenohumeral translation and rotation. The specimens were then tested for stability in the following order: vented/subluxated state, after arthroscopic anterior (Group 1; 7 specimens) or posterior (Group 2; 7 specimens) instability repair with suture anchors, and then after rotator interval closure. For each of the 3 testing conditions, the following were measured: (1) external and internal rotation at neutral, (2) external and internal rotation at 90° of abduction, (3) posterior and anterior translation at neutral rotation (15 N and 25 N), (4) anterior translation at 90° of abduction and external rotation (Group 1; 15 N and 25 N), (5) posterior translation at 90° of flexion and internal rotation (Group 2; 15 N and 25 N), and (6) sulcus testing in neutral (7.5 N). Results Posterior stability was only improved after anchor capsulolabral repair (8.0 to 5.0 mm; P = .017, 25 N), but there was no improvement after rotator interval closure (5.0 to 4.6 mm; P = .453). However, anterior stability was improved after capsulolabral repair (8.6 to 4.0 mm; P = .016, 25 N) and also improved further by rotator interval closure (4.0 to 2.4 mm; P = .007). The mean loss of external rotation was significantly increased by the addition of the rotator interval closure in both neutral and abducted glenohumeral positions, with a mean external rotation loss of 28° in neutral ( P = .013). The addition of a rotator interval closure did not improve sulcus stability ( P = .4). Conclusion The addition of an arthroscopic rotator interval closure after posterior capsulolabral repair did not improve posterior stability; however, anterior stability was improved further after a rotator interval closure. Inferior stability was not improved. Arthroscopic rotator interval closure significantly decreased external rotation at both neutral and abducted arm positions. Clinical Relevance Arthroscopic closure may be beneficial in certain cases of anterior shoulder instability; however, posterior instability was not improved. Predictable losses of external rotation after rotator interval closure are of concern.

This study evaluated the effects of soft tissue integrity on patellar tracking and patellofemoral joint force after total knee arthroplasty. The results indicate that partial dissection of the soft tissue integrity in the in vitro biomechanical studies of the patellofemoral joint can alter patellar tracking and joint force significantly, leading to improper conclusions.

Abstract MUC1 (MUC1 in humans and Muc1 in nonhuman species) is a transmembrane mucin-like glycoprotein expressed in epithelial cells lining various mucosal surfaces as well as hematopoietic cells. Recently, we showed that Muc1−/− mice exhibited greater inflammatory responses to Pseudomonas aeruginosa or its flagellin compared with their wild-type littermates, and our studies with cultured cells revealed that MUC1/Muc1 suppressed the Toll-like receptor (TLR) 5 signaling pathway, suggesting its anti-inflammatory role. Here we demonstrate that other TLR signaling (TLR2, 3, 4, 7, and 9) is also suppressed by MUC1/Muc1. The results from this study suggest that MUC1/Muc1 may play a crucial role during airway infection and inflammation by various pathogenic bacteria and viruses.

The measurement of intradiscal stress has been primarily limited to nucleus pulposus pressure. Intradiscal stress profilometry is a technique that measures stress in both the nucleus pulposus (hydrostatic) and annulus fibrosus (compression). Evidence from animal studies suggests that distraction may affect disc physiology and promote repair. A study was performed to determine the reliability of intradiscal stress profilometry measurements in the anterior, posterior, and nucleus regions of cadaveric lumbar discs. Four fresh-frozen human lumbar motion segments were prepared and tested. Five profiles were obtained during two conditions of compression and three conditions of distraction. Discs were then graded for degenerative change. Reliability was judged by within-specimen coefficients of variation. The coefficients of variation were smaller (more reliable) for compression conditions than for distraction conditions. Within-specimen coefficients during compression ranged from 1.58% to 37.2% in the nucleus, 3.9% to 67.4% in the anterior annulus, and 2.3% to 25.5% in the posterior annulus. The reliability of intradiscal stress profilometry is acceptable for repeated measures studies evaluating within-specimen changes, but the sample size will vary depending on the test conditions used and the disc region of interest.

In this pilot study, hypertonic dextrose solution was used to induce fibrosis of the subsynovial connective tissue (SSCT) and create an animal model of potential use in the study of carpal tunnel syndrome (CTS). The SSCT of the carpal tunnel in 15 New Zealand white rabbits were injected with 0.05 ml of 10% dextrose solution in 1 paw and 0.05 ml of saline in the contralateral paw, to serve as a control. The animals were killed at 1, 2, 4, 8, or 12 weeks. While the saline side showed minimal changes at any time period, the hypertonic dextrose side showed progressive noninflammatory SSCT fibrosis, with vascular proliferation and thickening of collagen bundles. Demyelination of the median nerve developed at 12 weeks after the injection on the dextrose side. These findings are similar to the progression of pathology noted in humans with CTS.

Ankle disk training has been used as an exercise in sports medicine clinics to help protect against ankle sprains. This study investigated the effects of ankle disk training on the contraction pattern of the anterior tibialis, posterior tibialis, peroneus longus, and flexor digitorum longus muscles in a simulated ankle sprain. Twenty adults were recruited and divided into a control group and an experimental group. A platform with a trapdoor was used to simulate a lateral ankle sprain. Electromyographic data were recorded from each sub ject in pretraining and posttraining tests. The experi mental group underwent ankle disk training for 8 weeks between the pretraining and posttraining tests. In the pretraining test, the four muscles started to contract simultaneously; in the posttraining test, the contrac tions of the anterior and posterior tibialis muscles were delayed. This delay favors the correction of excessive ankle inversion. This study examined the effects of one form of proprioceptive training on muscle reaction times, and its results may explain why such training can help protect against ankle sprains.