No abstract

In patients with TSH-secreting tumors (TSHomas), serum TSH is poorly suppressed by thyroid hormone. The mechanism for this defect in negative regulation of TSH secretion is not known. To investigate the possibility of a somatic mutation of TR causing this defect, we performed mutational analysis of TRbeta by RT-PCR using RNA obtained from five surgically resected TSHomas. In one TSHoma, we identified a somatic mutation in the ligand-binding domain of TRbeta that caused a His to Tyr substitution at codon 435 of TRbeta1 corresponding to codon 450 of TRbeta2. Interestingly, this mutation occurred in the same codon as two mutations (TRbetaH435L and H435Q) previously identified in patients with the syndrome of resistance to thyroid hormone. This mutant TRbeta had impaired T3 binding and T3-mediated negative regulation. It also blocked the negative regulation by wild-type TRbeta2 on glycoprotein hormone alpha-subunit and TSHbeta reporter genes in cotransfection studies. Our results demonstrate that somatic mutation of TRbeta occurred in a TSHoma and was probably responsible for the defect in negative regulation of TSH by thyroid hormone in the tumor.

Background: Smoking and drinking alcohol among early adolescents are serious public health concerns, but few studies have been conducted in Japan to assess their prevalence and etiology. A regional survey was conducted in eight schools in two Japanese school districts to identify psychosocial factors associated with smoking and drinking behaviors for boys and girls.

This study evaluates the impact of a school-based intervention program on aggressive behavior among junior high school students in Japan. One hundred and four seventh-graders were enrolled in the program and completed Time 1, Time 2, and Time 3 surveys. The program was implemented in two classes between Time 1 and Time 2 surveys (the first treatment group) and in two other classes between Time 2 and Time 3 surveys (the delayed treatment group). The program included four weekly lessons related to problem solving, stress management, and communication. The initial intervention group reported a significant increase in appropriate relationships with classmates. Aggressive behavior significantly decreased from Time 1 to Time 3 in both groups and from Time 2 to Time 3 in the delayed treatment group, but no treatment group effect was noted. Additional modification of the program may be needed to achieve decreases in aggressive behavior.