Mutations in the small heterodimer partner gene increase morbidity risk in Japanese type 2 diabetes patients

Mutations in the small heterodimer partner gene (NR0B2; alias SHP) are associated with high birth weight and mild obesity in Japanese children. SHP mutations may also be associated with later obesity and insulin resistance syndrome that induces diabetes. To investigate this possibility, the prevalence of SHP mutations in Japanese with and without type 2 diabetes mellitus and the functional properties of the mutant proteins were evaluated. Direct sequencing of two exons and flanking sequences of SHP in 805 diabetic patients and 752 non-diabetic controls identified 15 different mutations in 44 subjects, including 6 novel mutations. Functional analyses of the mutant proteins revealed significantly reduced activity of nine of the mutations. Mutations with reduced activity were found in 19 patients (2.4%) in the diabetic group and in 6 subjects (0.8%) in the control group. The frequency difference between DM and control subjects adjusted for sex and age was statistically significant (P=0.029, odds ratio 2.67, 95% CI 1.05-6.81, 1-beta=0.91). We conclude that SHP mutations associated with mild obesity in childhood increase susceptibility to type 2 diabetes in later life in Japanese.     

First brain dead donor heart transplantation under new legislation in Japan

The first heart transplantation was carried out in Japan successfully, after the brain death and organ transplantation law was settled in 1997. The recipient patient was a 47-year-old man with the dilated phase of hypertrophic cardiomyopathy who had been on a Novacor implantable left ventricular assist system for the previous 4 months. Since the donor hospital was about 200 km from the recipient hospital which took approximately 2 hours for transportation, the total ischemic time was 3 hours and 24 minutes. The post-transplant course was smooth, and the patient was discharged on postoperative day 75.     

Pediatric cardiac xenograft growth in a rhesus monkey-to-baboon transplantation model

Abstract: It is unclear that organs from other species could grow successfully in the environment of another species. We evaluated the growth capacity of a cardiac xenograft in a rhesus monkey-to-juvenile baboon orthotopic heart transplantation model where there exists a discrepancy of the organ size and its growth rate between donor and recipient species. Eight recipient baboons who survived over 60 days were followed for body weight (BW) and the size of xenografts (left ventricular end-diastolic volume, LVEDV; left ventricular mass, LVM; and left ventricular posterior wall thickness, LVPWT) by echocardiography at 1 week and monthly after xenotransplantation. One baboon is growing along the normal growth curve. The other three baboons gained BW in parallel with normal growth curve except for a few months after surgery. LVEDV, LVM, and LVPWT increased constantly in these four baboons. In one baboon, BW increased over 1 year to 5.5 kg (which was almost the same as BW of adult rhesus monkey) and then plateaued. LVEDV, LVM, and LVPWT increased until 1 year posttransplantation, but then stopped when BW plateaued. In the other four baboons who did not gain BW because of infectious complications or side effects by immunosuppressive therapy, LVEDV, LVM, and LVPWT did not change significantly. We conclude that a cardiac xenograft from a rhesus monkey can successfully grow and support normal growth of a juvenile baboon, but whether a recipient can grow beyond the donor size is yet unknown.