Publications

The integrin alphavbeta6 is expressed on a variety of epithelial cells during dynamic processes including organogenesis, tissue injury and malignant transformation. However, because of the lack of tools to specifically inhibit the function of this integrin, little is known about its effects on cell behavior. To directly examine the role of this integrin in cell migration, we used keratinocytes derived from wild-type mice or mice expressing a null mutation in the beta6 subunit (beta6-/-) to perform migration assays in vitro. Migration on the known alphavbeta6 ligand, fibronectin was reduced in keratinocytes from beta6-/- mice. Interestingly, keratinocytes from beta6-/- mice also demonstrated markedly reduced migration on vitronectin, a protein not previously known to be a ligand for alphavbeta6. An anti-alphavbeta6 monoclonal antibody 10D5, generated by immunization of beta6-/- mice with murine keratinocytes, inhibited adhesion and migration of wild-type keratinocyte on both vitronectin and fibronectin to levels similar to those seen with keratinocytes from beta6-/- mice. alphavbeta6-mediated migration on both ligands was dramatically augmented by treatment with phorbol myrisate acetate (PMA) or with hepatocyte growth factor, and augmentation of migration by either stimulus could be abolished by the PKC inhibitor GF109203X, suggesting a critical role for PKC in enhancement of alphavbeta6-mediated cell migration.

OBJECTIVE

To evaluate the impact of patient demographics, clinical features, and job-related factors on the time until return to work after carpal tunnel release surgery.

METHODS

We employed a cross-sectional community-based study of 59 patients who had undergone carpal tunnel release surgery. Sociodemographic, clinical, and job-related characteristics and time to return to work were obtained by interview and from medical records. Exposure to ergonomic risk was derived from an independently validated job matrix. Time to return to work after surgery was analyzed by survival techniques.

RESULTS

Median time to return to work was 5 weeks. After adjustment, the relative rate (RR) of return to work per week after surgery was most strongly decreased by the receipt of workers' compensation, RR 0.2 (95% confidence interval [CI] 0.1-0.5), and by the exposure to bending and twisting of the hand prior to surgery, RR 0.7 (95% CI 0.5-0.9) per hour. Female gender was another predictor of decreased return to work, RR 0.5 (95% CI 0.3-0.8).

CONCLUSIONS

Patients receiving workers' compensation, those exposed to higher levels of bending and twisting of their hands and wrists, and women were slower to return to work after carpal tunnel release surgery.

The development of monoclonal antibodies and the emergence of recombinant DNA technology has made it possible to identify and selectively inhibit distinct cell subsets, surface molecules and secreted products that contribute to normal and pathological immune responses. These advances have helped to clarify the mechanisms that promote autoimmune diseases. As a result, it is now possible to contemplate rational strategies for the treatment of these diseases. Some of these strategies are designed to influence the cell surface interactions that determine whether potentially autoreactive T cells become activated or tolerant following antigen stimulation. Other strategies are designed to augment or inhibit distinct cytokines that regulate autoimmunity. All of these strategies have shown promise in animal models for systemic lupus erythematosus, and they may soon be translated into effective new therapies for people.

Although most of the available prosthetic heart valves function remarkably well, the variety of available choices attests to the inability of any single one to fulfill the requirements of the ideal valve substitute. The mechanical prostheses include the caged-ball, tilting-disc, and bileaflet valves. Tissue valves available in the United States are the Carpentier-Edwards and Hancock porcine heterograft valves and the Carpentier-Edwards pericardial valve. Review of several large comparative studies on valve performance reveals that the overall results with tissue and mechanical valves are about equal at the end of 10 years. The characteristics of each type of valve substitute dictate the selection of one prosthesis in preference to others for a particular patient. Mechanical prostheses are recommended for patients without contraindications for anticoagulants. Tissue valves are reserved for patients over 65 years of age or for patients in whom anticoagulation is contraindicated. Multiple other patient-related factors need to be considered in selecting the appropriate valve, including the psychosocial situation and patient preference.