1. Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes of male Otsuka Long Evans Tokushima Fatty (OLETF) rats. 2. Our congenic lines, produced by transferring Dmo1 chromosomal segments from the non-diabetic Brown Norway (BN) rat into the OLETF strain, have confirmed the strong, wide-range therapeutic effects of Dmo1 on dyslipidaemia, obesity and diabetes in the fourth (BC4) and fifth (BC5) generations of congenic animals. Analysis of a relatively small number of BC5 rats (n = 71) suggested that the critical Dmo1 interval lies within a
Lymphoepithelial carcinoma commonly occurs at the nasopharynx and rarely occurs at other sites in the head and neck region. It is well known to occur at limited patients of local area as Asia or Arctic Circle. Related to this point, it is pointed out that this tumor has strong relation with Epstein-Barr Virus (EBV) infection. In this time, we experienced to treat lymphoepithelial carcinoma with metastatic cervical lymph nodes occurring at parotid gland. The morbidity ratio of this tumor is less than one percent of all parotid gland tumors. Moreover, we proved the infection of EBV to tumor cell by in situ hybridization (ISH). Incidentally, because it is considered that this tumor has well sensitivity against irradiation or anti-tumor drugs, prognosis of this tumor is better than that of other head and neck tumors with different pathological type. Actually, we tried to perform chemotherapy twice in (Nedaplatin (CDGP) 60mg/m(2)?day 2 and 5-FU 600mg/m(2)?day 5) and to irradiate about 70Gy dose against parotid gland and cervical lymph nodes. It could not find local recurrence or metastasis as of now after five years from treatment.
1. We have confirmed the Diabetes Mellitus OLETF type I (Dmo1) effect on hyperphagia, dyslipidaemia and obesity in the Otsuka Long-Evans Tokushima Fatty (OLETF) strain. The critical interval was narrowed down to 570 kb between D1Got258 to p162CA1 by segregation analyses using congenic lines. 2. Within the critical 570 kb region of the Dmo1 locus, we identified the G-protein-coupled receptor gene GPR10 as the causative gene mutated in the OLETF strain. The ATG translation initiation codon of GPR10 is changed into ATA in this strain and, so, is unavailable for the initiation of translation. 3. The GPR10 protein has a cognate ligand, namely prolactin-releasing peptide (PrRP). Centrally administered PrRP suppressed the food intake of congenic rats that have a Brown Norway derived Dmo1 region (i.e. with wild-type GPR10), but did not suppress that of the OLETF strain, indicating that GPR10 is without function and could explain hyperphagia in the OLETF strain. 4. Moreover, when restricted in food volume to the same level consumed by the congenic strain, OLETF rats showed few differences in the parameters of dyslipidaemia and obesity compared with congenic strains. 5. Taken together, these results demonstrate that the mutated GPR10 receptor is responsible for the hyperphagia leading to obesity and dyslipidaemia in the obese diabetic strain rat.