Publications

The Towne, human cytomegalovirus (CMV) vaccine is safe and immunogenic but has not prevented infection at doses tested to date. We administered 3000 pfu Towne CMV vaccine, with or without adjuvant recombinant interleukin-12 (rhIL-12), to CMV-seronegative healthy volunteers and then measured CMV gB-specific IgG titers and CMV-specific CD4+ and CD8+ T cell proliferation and IFNgamma expression after stimulation with whole viral lysate and immunodominant peptide CMV antigens. Adjuvant rhIL-12 at doses up to 2 microg were well-tolerated and associated with (1) dose-related increases in peak anti-CMV gB IgG titers (though not in sustained titers), (2) dose-related increases in the weak CMV viral lysate-specific CD4+ T cell proliferation responses induced by vaccine alone after 360 days of follow-up, and (3) decreases in the very robust CMV IE-specific peak CD4+ T cell and Day 360 CD8+ T cell proliferation responses induced by the vaccine alone. Also, qualitative CD8+ T cell IFNgamma responses to stimulation with the immunodominant CMV antigen, pp65, tended to occur more frequently in vaccinees who received 0.5-2.0 microg rhIL-12 compared to lower dose or no rhIL-12. Thus, adjuvant IL-12 may be a promising strategy for improving antibody and T cell immune responses to a CMV vaccine.

To successfully engineer a bioartificial tracheal replacement, it is believed that the regeneration of a functional epithelial lining is a key requirement. In the present study, rabbit tracheal epithelial cells were cultured on temperature-responsive culture dishes, under normal culture conditions at 37 degrees C. By simple temperature reduction to 20 degrees C, the cultured epithelial cells were noninvasively harvested as intact sheets, without the use of any proteolytic enzymes. Support Dacron grafts that had been subcutaneously implanted for 4 weeks to allow for host tissue and vessel infiltration were then opened, and the tracheal epithelial cell sheets were transplanted to the luminal surface without sutures. These fabricated constructs were then used as tracheal replacements, in a rabbit model. Four weeks after transplantation, results showed that the tracheal grafts were covered by a mature, pseudostratified columnar epithelium. In contrast, control constructs that did not receive cell sheet transplantation demonstrated only a thin, immature epithelium at the center of the replacement graft. These results therefore demonstrate that these tracheal epithelial cell sheets can create an epithelial lining on the luminal surface of a bioartificial trachea.

BACKGROUND

The development of right ventricular dysfunction is a poor prognostic sign in patients with heart failure (HF). Although left ventricular dyssynchrony has been well described, it is not known whether right ventricular dyssynchrony coexists in HF. We used tissue Doppler imaging to determine whether right ventricular dyssynchrony is also present in HF patients.

METHODS AND RESULTS

In 34 HF patients (mean age 56 +/- 13 years), we measured longitudinal strain at the right ventricular free wall, interventricular septum, and left ventricular lateral wall. Right ventricular and left ventricular dyssynchrony were defined as the difference in time to peak strain between the right ventricular free wall and the septum and between the left ventricular lateral wall and septum, respectively. Mean right ventricular dyssynchrony was 59 +/- 45 ms and the mean left ventricular dyssynchrony was 80 +/- 62 ms. We found a strong correlation between right ventricular dyssynchrony and pulmonary artery systolic pressure (r = 0.73; P < .001) and a negative correlation between right ventricular dyssynchrony and right ventricular fractional area change (r = -0.43; P < .02).

CONCLUSION

HF patients exhibit right ventricular dyssynchrony by strain imaging which correlates with pulmonary hypertension and right ventricular dysfunction.