Cardiovascular intervention for high-risk families: the Heart Smart Program

The Heart Smart Family Health Promotion Program is a multidisciplinary, school-based program for cardiovascular risk reduction among high-risk children and their families. As a program that includes young adults at high risk, it is adaptable to a clinical practice. Nineteen fourth and fifth graders were selected as probands for elevated risk factors after a general screening to identify families for an intervention program. Twenty-three parents participated in a 12-week program focused on eating, exercise, and smoking behavior changes enhanced by behavicral support strategies. Weekly sessions were held in the auditorium/cafeteria of the elementary school and consisted of orientation and presentations, cardiovascular (CV) screening with medical feedback, activities, self-monitoring, counseling, and contingency contracting. Information gathered before and after the program included medical history, CV health knowledge and relevant behavior, blood pressure, serum lipid and lipoprotein values, anthropometric measurements, and urine electrolyte excretion. Both children and parents showed positive changes in eating habits and physical activity and significant changes in knowledge and blood pressure levels, while the children halted their weight gain. We believe this multidisciplinary, behavior-oriented, school-based program can be an effective cardiovascular risk intervention adaptable for a clinical office practice.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.