Epidemiology of familial amyloid polyneuropathy in Japan: Identification of a novel endemic focus

BACKGROUND: Familial amyloid polyneuropathy (FAP) is distributed worldwide with several endemic foci including two major foci in Japan. OBJECTIVE: To elucidate a nationwide epidemiology of FAP in Japan. DESIGN, SETTING, AND PATIENTS: (i) We analyzed the data of FAP patients registered by the Ministry of Health, Labour, and Welfare, Japan, during 2003-2005. (ii) As Ishikawa prefecture was found to be a novel endemic focus, we examined 27 FAP patients in Ishikawa to characterize their clinical and genetic features in comparison with other endemic foci. RESULTS: (i) The prevalence of familial amyloidosis in Japan was estimated to be 0.87-1.1 per 1,000,000 persons. Nagano prefecture had the highest prevalence (11-15.5), followed by Kumamoto (10.1-10.3), and then Ishikawa (3.5-4.2). (ii) All the FAP patients in Ishikawa had transthyretin (TTR) type FAP; all the families had a TTR Val30Met mutation except one family with a Leu58Arg mutation. FAP with Val30Met mutation in Ishikawa was characterized by late onset, high penetrance, and moderate autonomic dysfunction. CONCLUSIONS: Ishikawa prefecture is the third endemic focus of FAP in Japan. FAP with TTR Val30Met mutation in Japan can be classified to (i) early-onset and endemic (Nagano and Kumamoto), (ii) late-onset and endemic (Ishikawa), and (iii) late-onset and non-endemic types.     

Living donor liver transplantation with hyperreduced left lateral segments

Liver transplantation is now an established technique to treat children with end-stage liver disease. Implantation of left lateral segment grafts (Couidaud's segments II and III) can be a problem in small infants because of a large-for-size graft. Reduced left lateral segmental liver transplantation has been recently introduced for small infants to mitigate the problem of large-for-size graft. Further reduction of the left lateral segment graft increases the possibility of supplying an adequate hyperreduced left lateral segment graft as an alternative surgical technique. We report 3 cases of our experience of transplantation using hyperreduced left lateral segment grafts from living donors.     

CYP17 and COMT gene polymorphisms can influence bone directly, or indirectly through their effects on endogenous sex steroids, in postmenopausal Japanese women

We aimed to assess whether circulating sex steroids would influence bone density and bone loss, whether part of this influence could be explained by genetic variation measured as polymorphisms in candidate genes affecting circulating hormone levels, or whether gene polymorphisms would have direct effects on bone in 229 postmenopausal Japanese women aged 46 years and over who had been followed for eight years (Yokohama Cohort). Bone mineral density (BMD) in the lumbar spine (L), femoral neck (FN), total hip (T) and distal radius (R) was measured every year, and endogenous sex steroid levels were determined at the start of the study. We investigated the polymorphisms of estrogen-metabolizing enzyme gene, CYP17; estrogen biosynthesis (high activity, A2/A2), CYP1A1; hydroxylation (high inducibility, vt/vt) and COMT; inactivation (low activity, L/L) with PCR-based restriction fragment length polymorphism assays. Dehydroepiandrosterone (DHEA) and androstenedione (AND) levels significantly correlated with bone density in both the axial (L) and the appendicular skeleton (FN, T and R) (r=0.194-0.229; P<0.05) whereas estradiol (E2) and AND showed significant correlations with bone change only at the axial skeleton (r=0.205 and r=-0.139, respectively; P<0.05) on the total cohort. These correlations remained significant in thin/normal-weight women [body mass index (BMI) <25 kg/m2)] even after adjustment for years since menopause (YSM) and BMI or age and BMI, suggesting an interaction of BMI and sex steroid/BMD association. On the total cohort, a difference in endogenous DHEA levels between CYP17 homozygote A2 and non-homozygote A2; an increasing trend in AND levels from COMT L/L, L/H, to H/H; and a difference in TS level between COMT homozygote L and non-homozygote L were separately observed. All observations were significant for unadjusted and adjusted analysis, except for COMT and TS. In thin/normal-weight women (BMI <25 kg/m2), the same effects of CYP17 genotypes on DHEA were observed as on the total cohort. CYP17 and COMT genes showed some direct influence on bone density. Mean percent change in T-BMD was negative for CYP17 non-homozygote A2 in contrast to a positive value for homozygote A2. Mean percent change in R-BMD showed the difference between COMT homozygote L and non-homozygote L with a larger decrease for the homozygote L. Together, CYP17 and COMT genotypes might have some effect on bone both directly and indirectly through their effects on endogenous sex steroids in postmenopausal Japanese women.     

Treatment of Large Liver Cyst Evaluated with CA19-9 in the Cystic Fluid

A middle-aged woman was admitted with a diagnosis of liver cysts. The patient was symptomatic and was treated by injecting absolute ethanol into the largest cyst every week, but the secretion from the cyst persisted. The patient was then treated by absolute ethanol injection every day with good results. CA 19-9 was measured in the cystic fluid. The secretion was related to CA 19-9 activity.Thus, for patients with symptoms from a liver cyst, the injection of ethanol every day can be effective. CA19-9 level in the contents of the liver cyst was an important factor in assessing the effect of ethanol injection on the liver cyst.     

中国广州和日本东京母子对话方式比较研究

【目的】　比较中国广州和日本东京母子交流方式的异同点。　【方法】　 43对母子根据四幅主题图片进行自由对话将对话内容与日本东京母子的对话内容进行比较。　【结果】　广州和东京的母子对话涉及到日常生活事件 (86% ,70 % )和人物心理 (3 3 % ,5 0 % )的比例无差异。东京母子对话中涉及图片情节前因后果的比例明显多于广州母子 (70 % ,3 0 % ) (P <0 .0 1) ;广州母子比东京的母子更倾向于及时总结经验教训 (5 3 % ,3 0 % ) (P =0 .0 5 )。　【结论】　不同文化背景下亲子对话方式存在一定的差异     

Low-grade mucinous cystadenocarcinoma in the spleen.

A 69-year-old man with an enlarged spleen, found by computed tomography scan to be multicystic, underwent a splenectomy. Pathological examination revealed a Low-grade mucinous cystadenocarcinoma that was histologically analogous to a mucinous tumor of the ovary. The serum level of tumor markers carcinoembryonic antigen (CEA)and CA19-9 were elevated preoperatively and returned to normal after the operation. In the absence of a primary tumor elsewhere, we considered this tumor to be primary in the spleen, and it was presumed that the tumor arose either from invaginated capsular mesothelium of the spleen or from heterotopic pancreatic or enteric tissue within the spleen.     

Sustained molecular remission in a patient with CML in blastic crisis receiving dose-reduced hematopoietic stem-cell transplantation followed by early withdrawal of cyclosporine and prophylactic use of interferon-alpha

A 54-year-old man with chronic myelocytic leukemia in blastic phase received reduced-intensity transplantation (RIST) from an HLA-identical unrelated donor. The preparative regimen consisted of busulfan, fludarabine, and anti-thymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine alone. Because he had a high risk of relapse, we discontinued cyclosporine on day 37, but he did not develop any signs of acute GVHD. To induce GVHD and augment a graft-versus-leukemia effect, we initiated interferon-alpha therapy on day 80 to a maximum dosage of three million units five times a week. He achieved molecular remission on day 94 followed by the development of extensive chronic GVHD the severity of which paralleled to the dose of interferon-alpha GVHD gradually subsided after discontinuation of interferon-alpha and the patient remains in molecular remission 18 months after transplantation. This case suggests that early withdrawal of cyclosporine and the prophylactic use of interferon-alpha are promising in RIST for high-risk leukemia.     

Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL

Osteoclasts, the multinucleated cells that resorb bone, develop from hematopoietic cells of monocyte/macrophage lineage. Osteoclast-like cells (OCLs) are formed by coculturing spleen cells with osteoblasts or bone marrow stromal cells in the presence of bone-resorbing factors. The cell-to-cell interaction between osteoblasts/stromal cells and osteoclast progenitors is essential for OCL formation. Recently, we purified and molecularly cloned osteoclastogenesis-inhibitory factor (OCIF), which was identical to osteoprotegerin (OPG). OPG/OCIF is a secreted member of the tumor necrosis factor receptor family and inhibits osteoclastogenesis by interrupting the cell-to-cell interaction. Here we report the expression cloning of a ligand for OPG/OCIF from a complementary DNA library of mouse stromal cells. The protein was found to be a member of the membrane-associated tumor necrosis factor ligand family and induced OCL formation from osteoclast progenitors. A genetically engineered soluble form containing the extracellular domain of the protein induced OCL formation from spleen cells in the absence of osteoblasts/stromal cells. OPG/OCIF abolished the OCL formation induced by the protein. Expression of its gene in osteoblasts/stromal cells was up-regulated by bone-resorbing factors. We conclude that the membrane-bound protein is osteoclast differentiation factor (ODF), a long-sought ligand mediating an essential signal to osteoclast progenitors for their differentiation into osteoclasts. ODF was found to be identical to TRANCE/RANKL, which enhances T-cell growth and dendritic-cell function. ODF seems to be an important regulator in not only osteoclastogenesis but also immune system.