A colony of cats affected with hypertrophic feline muscular dystrophy was used to study the occurrence of cardiomyopathy associated with dystrophin deficiency. Affected male and female cats, obligate carrier females, and unaffected healthy littermates were followed from 12 weeks of age into adulthood. Thoracic radiography, 2-D echocardiography, and 2-D-derived M-mode echocardiography were performed at 3-month intervals until 12 months of age and regularly thereafter. From 9 months of age, all affected cats had larger hearts than normal and carrier animals. Left ventricular wall thickness in systole and in diastole and interventricular septal thickness in systole were greater in affected cats 12 months and older when compared with normal or heterozygous animals (P < .05). The myocardium of affected cats was diffusely hypoechoic and thickened. Multiple hyperechoic foci were in the myocardium and papillary musculature. Shortening fraction was normal in all cats. Changes seen in carrier females included enlargement and hyperechogenicity of the papillary musculature after the age of 2 years. Gross and light microscopic examination revealed left ventricular wall thickening with multiple foci of mineralization in 2 of 5 hearts from dystrophin-deficient cats. Although approximately 10% of the normal dystrophin amount was present in the skeletal muscle, dystrophin could not be detected in the myocardium. Early onset concentric myocardial hypertrophy was present in all adult cats. Lesions were mainly localized in the myocardium of the left ventricular free wall and interventricular septum, papillary musculature, and the endocardium. Clinical signs of heart failure developed only infrequently in cats with hypertrophic feline muscular dystrophy.

No abstract

A colony of cats affected with hypertrophic feline muscular dystrophy was used to study the occurrence of cardiomyopathy associated with dystrophin deficiency. Affected male and female cats, obligate carrier females, and unaffected healthy littermates were followed from 12 weeks of age into adulthood. Thoracic radiography, 2-D echocardiography, and 2-D-derived M-mode echocardiography were performed at 3-month intervals until 12 months of age and regularly thereafter. From 9 months of age, all affected cats had larger hearts than normal and carrier animals. Left ventricular wall thickness in systole and in diastole and interventricular septal thickness in systole were greater in affected cats 12 months and older when compared with normal or heterozygous animals (P < .05). The myocardium of affected cats was diffusely hypoechoic and thickened. Multiple hyperechoic foci were in the myocardium and papillary musculature. Shortening fraction was normal in all cats. Changes seen in carrier females included enlargement and hyperechogenicity of the papillary musculature after the age of 2 years. Gross and light microscopic examination revealed left ventricular wall thickening with multiple foci of mineralization in 2 of 5 hearts from dystrophin-deficient cats. Although approximately 10% of the normal dystrophin amount was present in the skeletal muscle, dystrophin could not be detected in the myocardium. Early onset concentric myocardial hypertrophy was present in all adult cats. Lesions were mainly localized in the myocardium of the left ventricular free wall and interventricular septum, papillary musculature, and the endocardium. Clinical signs of heart failure developed only infrequently in cats with hypertrophic feline muscular dystrophy.

Deguelin, a natural component derived from leguminous plants, has been used as pesticide in some regions. Accumulating evidence show that deguelin has promising chemopreventive and therapeutic activities against cancer cells. This study shows that low concentrations of deguelin can lead to significant delay in zebrafish embryonic development through growth inhibition and induction of apoptosis. Furthermore, we identified fibroblast growth factor receptor 4 (FGFR4) as the putative target of deguelin. The candidate was initially identified by a microarray approach and then validated through in vitro experiments using hormone‐responsive (MCF‐7) and nonresponsive (MDA‐MB‐231) human breast cancer cell lines. The results show that deguelin suppressed cell proliferation and induced apoptosis in both cancer cell lines, but not in Hs 578Bst cells, by blocking PI3K/AKT and mitogen‐activated protein kinases (MAPK) signaling. The FGFR4 mRNA and protein level also diminished in a dose‐dependent manner. Interestingly, we found that forced FGFR4 overexpression attenuated deguelin‐induced proliferative suppression and apoptotic cell death in both zebrafish and MCF‐7 cell lines, p‐AKT and p‐ERK levels were restored upon FGFR4 overexpression. Taken together, our results strongly suggest that deguelin inhibition of PI3K/AKT and MAPK signaling in zebrafish and breast cancer cell lines is partially mediated through down‐regulation of FGFR4 activity.