objective: This study compared the effect of alternating shift work and day work on weight gain in Japanese male workers. Methods and Procedures: A longitudinal cohort study was conducted in day workers (n = 4,328) and alternating shift workers (n = 2,926) of a steel company who received annual health checkups over a 14-year period between 1991 and 2005. The association between the type of job schedule and weight gain was investigated using multivariate pooled logistic regression analyses. The endpoints in the study were either a 5, 7.5, or 10% increase in BMI during the period of observation, compared to the BMI at entry. Results: The type of job schedule was significantly associated with all three BMI endpoints (5% increase in BMI; odds ratio (OR) for comparison between alternating shift workers and regular day workers, 1.14; 95% confidence interval (CI), 1.06-1.23): (7.5% increase in BMI; OR, 1.13; 95%CI, 1.03-1.24: 10% increase in BMI; OR, 1.13; 95%CI, 1.00-1.28). BMI at study entry was also positively associated with the 5, 7.5, and 10% increases in BMI during the study. On the other hand, age and drinking habits were negatively associated with 5, 7.5, and 10% increases in BMI. Discussion: Our study revealed that alternating shift work was an independent risk factor for weight gain in male Japanese workers. Efficient health screening and regular checkups, combined with support to control unhealthy lifestyle factors, would be of considerable benefit for maintaining the health of Japanese shift workers.

Tuberous sclerosis (TS) is characterized by the development of hamartomas in various organs and is caused by a germ-line mutation in either TSC1 or TSC2 tumor suppressor genes. From the symptomatic resemblance among TS patients, involvement of TSC1 and TSC2 products in a common pathway has been suggested. Here, to analyze the function of the Tsc1 product, we established a line of Tsc1 (TSC1 homologue) knockout mouse by gene targeting. Heterozygous Tsc1 mutant (Tsc1 ؉/؊ ) mice developed renal and extra-renal tumors such as hepatic hemangiomas. In these tumors, loss of wild-type Tsc1 allele was observed. Homozygous Tsc1 mutants died around embryonic days 10.5-11.5, frequently associated with neural tube unclosure. As a whole, phenotypes of Tsc1 knockout mice resembled those of Tsc2 knockout mice previously reported, suggesting that the presumptive common pathway for Tsc1 and Tsc2 products may also exist in mice. Notably, however, development of renal tumors in Tsc1 ؉/؊ mice was apparently slower than that in Tsc2 ؉/؊ mice. The Tsc1 knockout mouse described here will be a useful model to elucidate the function of Tsc1 and Tsc2 products as well as pathogenesis of TS.T uberous sclerosis (TS) is an autosomal dominantly inherited disease characterized by the development of hamartomas and benign tumors in various organs such as brain, kidney, and heart (1). A germ-line mutation in either TSC1 or TSC2 genes (2, 3), both of which act as tumor suppressors (4, 5), is a genetic factor responsible for pathogenesis of TS. The similar symptoms of TS patients associated with TSC1 or TSC2 mutations suggest that the products of TSC1 and TSC2 are involved in a common physiological pathway (1, 6). TSC1 encodes a protein with a molecular mass of Ϸ130 kDa, hamartin, which contains a coiled-coil domain in the carboxyl-terminal half (3). TSC2 encodes tuberin, a rap1-GTPase activating protein homology domain-containing protein with a molecular mass of Ϸ180 kDa (2). Although several studies concerned with functions of these products have been reported, in vivo functions of them remain to be elucidated (1,7,8).The tumor suppressor function of TSC2 became evident by studies of rodents with a germ-line Tsc2 mutation such as the Eker rat (9-13) and Tsc2 knockout mice (14, 15). Both heterozygous Tsc2 mutant rats and mice develop hereditary renal tumors and extra-renal tumors carrying a second hit of Tsc2 gene (14-17). Homozygosity of Tsc2 mutation leads to the embryonic lethality both in rats (9, 18) and mice (15,16), indicating that the function of tuberin is essential for mammalian development.We also isolated a rat homologue of TSC1 (Tsc1) and analyzed its mutation in chemically induced renal tumors in wild-type rats, in which Tsc2 mutations were found with high frequency (Ϸ50%) (19). In those tumors, we found Tsc1 mutations in a case with no Tsc2 mutation (19). These results suggest that mutations of Tsc1 and Tsc2 are involved in the development of chemically induced renal tumors in rats, although the latter is more common. These systems o...

The Eker rat hereditary renal carcinoma (RC) is an excellent example of a mendelian dominant predisposition to a specific cancer in an experimental animal. We have previously established a new conserved linkage group on rat chromosome 10q and human chromosome 16p13.3, and shown that the Eker mutation is tightly linked to the tuberous sclerosis (Tsc2) gene. We now describe a germline mutation in the gene encoding Tsc2 caused by the insertion of an approximately 5 kilobase DNA fragment in the Eker rat, resulting in aberrant RNA expression from the mutant allele. The phenotype of tuberous sclerosis in humans differs from that of the Eker rat, except for the occurrence of renal tumours. The Eker rat may therefore provide insights into species-specific differences in tumourigenesis and/or phenotype-specific mutations.