Application of the fracture risk assessment tool (FRAX®) and determination of suitable cut-off values during primary screening in specific health check-ups in Japan

Specific health check-ups, which do not include osteoporosis screening, are conducted more frequently than periodic osteoporosis screening in Japan. In this study, we investigated the usefulness of the fracture risk assessment tool (FRAX^®) during specific health check-ups, evaluated the variations in its usefulness for 2 consecutive years, and determined FRAX^® cut-off values for osteoporosis screening. FRAX^® questionnaires were distributed to subjects who underwent specific health check-ups in 2009 and 2010 at Asahi-machi. Subjects who exhibited FRAX^® cut-off values of ≥10 % were advised to be screened at a medical institution. Bone mineral densities (BMDs) were measured in 201 subjects in 2009 and 105 subjects in 2010 after specific health check-ups, and treatment was initiated for 79 subjects in 2009 and 24 subjects in 2010. The number of subjects examined and the rate of treatment initiation following specific health check-ups were higher than those in subjects following periodic osteoporosis screening in 2009. However, the number and the rate following specific health check-ups dropped in 2010. According to receiver operating characteristic curves analyses, the sensitivity and specificity of FRAX^® to determine osteoporosis treatment were highest when the cut-off values were 8 % for men and 10.5 % for women. In conclusion, the combination of FRAX^® and specific health check-ups was more useful than periodic osteoporosis screening to narrow down the subjects and to motivate them to seek follow-up. Cut-off values for specific health check-up using FRAX^® should be approximately 8 % for men and 10.5 % for women     

Porphyromonas gingivalis FimA fimbriae: Roles of the fim gene cluster in the fimbrial assembly and antigenic heterogeneity among fimA genotypes

In order for bacteria to exert their pathogenicity, they must adhere to and colonize the host tissues. Porphyromonas gingivalis, a periodontal pathogen, primarily exploits FimA fimbriae for adhesion and colonization. FimA fimbriae are polymers composed of FimA protein encoded by the fimA gene. The fimA gene exists as a single copy within the fim gene cluster. This fim gene cluster contains 7 genes: fimX, pgmA, and fimABCDE. In this article, we address the roles of these genes in fimbrial formation. P. gingivalis strains 381 and ATCC 33277 express long fimbriae several micrometers in length, but we found that the FimB protein is absent in these strains because of a nonsense mutation in the fimB gene. Moreover, we found that FimB restoration resulted in the production of short FimA fimbriae approximately 150 nm in length. These findings indicate that FimB regulates fimbrial length. We also demonstrate that genes in the fim gene cluster, except fimA, are not required for FimA fimbrial assembly. It has been reported that there are several fimA genotypes, and these are associated with differential virulence. As such, we describe a serological analysis of FimA fimbriae across genotypes. We obtained antisera elicited by FimA fimbriae from genotypes I to V. The antisera showed low cross-reactivity between genotypes, indicating that the FimA fimbriae of each genotype were antigenically heterogenic. In addition, the antisera preferentially recognized the polymeric conformation of the fimbriae, which may be responsible for the heterogeneity. Notably, however, the amino acid sequences are partially common among each genotype.     

Endoscopically proven case of rapid esophagogastric variceal progression and rupture as a result of portal hypertension with liver sarcoidosis

Sarcoidosis is a multi‐systemic disease of unknown etiology that results in the development of non‐caseating epithelioid granulomas. The liver is the third most frequently involved organ after the lymph nodes and the lungs. Most cases of liver sarcoidosis do not present with symptoms and involve minimal liver dysfunction, but some cases display progression to portal hypertension and liver cirrhosis, and finally to liver failure. The mechanism and the risk of progression in liver sarcoidosis are still unknown because of the diagnostic difficulty associated with this condition, and because follow‐up examinations can only be done in an invasive manner. Here, we present an informative case of liver sarcoidosis with rapid progression of esophagogastric varices. Four months prior to the definitive diagnosis, no signs of varices were observed on endoscopy, and developmentof esophagogastric varices, rapid progression, and eventual rupture occurred in a short period of time. A liver biopsy, carried out after endoscopic sclerotherapy, revealed that granulomas primarily affected the portal area without fibrotic and cirrhotic changes, which is considered a primary cause of portal hypertension and esophagogastric varices. Following the liver biopsy, the patient was given systemic steroids and is currently receiving outpatient care. Thus, we should consider the possibility that liver sarcoidosis, even in the absence of cirrhotic changes, can cause serious events such as esophagogastric variceal rupture following rapid progression as a result of portal hypertension.     

Characterization of pancreatic islet cell tumors and renal tumors induced by a combined treatment of streptozotocin and nicotinamide in male SD rats

We herein investigated the histopathological features, including proliferative activity and immunoexpression, of pancreatic islet cell tumors (ICTs) in male SD rats induced by streptozotocin (STZ) and nicotinamide (NA), and discussed their relevance to biological behaviors and prognoses. A total of 70 and 43% of rats developed ICTs 37–45 weeks after the treatment with STZ (50 or 75 mg/kg, i.v.) and NA (350 mg/kg, twice, p.o.), respectively. Among the islet tumors observed in the STZ/NA-treated groups, 75% were adenomas, while 25% were carcinomas. Most STZ/NA-induced carcinomas were characterized by well-differentiated tumor cells with/without local invasion into the surrounding tissues, and weak proliferative activity. No outcome such as distance metastasis and death was noted. All of the ICTs strongly expressed insulin, part of which had hormone productivity; however there were no hypoglycemia-related clinical signs such as convulsion in these rats 36 weeks after the treatment. These results suggested that rat ICTs induced STZ/NA have small impact on biological activity or prognosis. STZ/NA treatment significantly increased of focal proliferative lesions in the kidney, liver and adrenal glands other than pancreatic islets. Of the STZ/NA-induced kidney tumors, more than 60% were renal cell adenomas, and many of them were basophilic type. The incidence of eosinophilic or clear cell type of tumors was less than 10%, respectively. Immunohistochemical analyses revealed that many of the STZ/NA-induced basophilic type of renal tumors were derived from proximal tubules, whereas the clear cell and eosinophilic types were derived from collecting tubules.