Evaluation of heart murmurs in chinchillas (Chinchilla lanigera): 59 cases (1996-2009).

OBJECTIVE: To determine the prevalence of heart murmurs in chinchillas (Chinchilla lanigera) and determine whether heart murmurs were associated with cardiac disease. DESIGN: Retrospective multi-institutional case series. ANIMALS: 260 chinchillas. PROCEDURES: Medical records of all chinchilla patients evaluated at the Tufts University Foster Hospital for Small Animals between 2001 and 2009, the University of California-Davis William R. Pritchard Veterinary Medical Teaching Hospital between 1996 and 2009, and the University of Wisconsin Veterinary Medical Teaching Hospital between 1998 and 2009 were reviewed. RESULTS: Prevalence of heart murmurs was 23% (59/260). Of 15 chinchillas with heart murmurs that underwent echocardiography, 8 had echocardiographic abnormalities, including dynamic right ventricular outflow tract obstruction, mitral regurgitation, hypertrophy of the left ventricle, tricuspid regurgitation, and hypovolemia. Echocardiographic abnormalities were approximately 29 times as likely (OR, 28.7) to be present in chinchillas with a murmur of grade 3 or higher than in chinchillas without a murmur. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that heart murmurs are common in chinchillas and that chinchillas with heart murmurs often have echocardiographic abnormalities, with valvular disease being the most common. On the basis of these results, we believe that echocardiography should be recommended for chinchillas with heart murmurs, especially older chinchillas with murmurs of grade 3 or higher. Further prospective studies are needed to accurately evaluate the prevalence of cardiac disease in chinchillas with heart murmurs.

Cdx1 inhibits human colon cancer cell proliferation by reducing beta-catenin/T-cell factor transcriptional activity.

The cessation of proliferation and the induction of differentiation are highly coordinated processes that occur continuously in the intestinal crypts. The homeodomain transcription factors Cdx1 and Cdx2 regulate intestine-specific gene expression and enterocyte differentiation. Their roles in regulating proliferation are recognized but remain poorly understood. Previously, we demonstrated that Cdx1 expression diminished the proliferation of human colon cancer cells in part by reducing cyclin D1 gene expression. In order to elucidate further the molecular mechanisms underlying this phenomenon, we first hypothesized that Cdx1 or Cdx2 expression reduces colon cancer cell proliferation by inhibiting beta-catenin/T-cell factor (TCF) transcriptional activity. We report that Cdx1 or Cdx2 expression does inhibit beta-catenin/TCF transcriptional activity in colon cancer cells. This inhibitory effect is dose-dependent and is observed in different colon cancer cell lines, and the degree of inhibition correlates with the ability of Cdx1 to reduce cell proliferation. Cdx1 expression does not alter beta-catenin protein levels or intracellular distribution nor does it induce an inhibitory TCF isoform. We also find that Cdx1 expression is lost in Min mouse polyps with increased nuclear localization of beta-catenin, suggesting that Cdx1 does not support beta-catenin-mediated transformation. Finally, we show that colon cancer cells effectively reduce Cdx2-mediated inhibition of Wnt/beta-catenin/TCF transcriptional activity when compared with other model systems. This suggests that colon cancer and possibly crypt epithelial cells can modulate the effects of Cdx2 on beta-catenin signaling and proliferation. We conclude that Cdx1 and Cdx2 inhibit colon cancer cell proliferation by blocking beta-catenin/TCF transcriptional activity.