Expression of osteopontin at sites of bone erosion in a murine experimental arthritis model of collagen-induced arthritis: possible involvement of osteopontin in bone destruction in arthritis

OBJECTIVE: To investigate the involvement of osteopontin (OPN) in bone destruction in a murine experimental arthritis model of collagen-induced arthritis (CIA). METHODS: The expression of OPN was examined at both the messenger RNA (mRNA) and protein levels in various arthritic lesions in mice with CIA by in situ hybridization and immunohistochemistry, respectively. In addition, the expression of alpha(v)beta3 integrin, a receptor for OPN, the ligation of which is thought to be essential for bone resorption by osteoclasts, was examined by immunohistochemistry. Plasma concentrations of OPN were measured at different time points in the course of CIA by enzyme-linked immunosorbent assay. RESULTS: OPN mRNA was detected mainly at sites of bone erosion in arthritic lesions, where activated osteoclasts were present; OPN protein was also detected at sites of bone erosion. In the arthritic synovium, OPN was predominantly expressed in the synovial lining layer, but not in lymphoid aggregates. In addition, alpha(v)beta3 integrin was detected coincident with OPN at sites of bone erosion (bone-pannus junction). Plasma OPN levels were markedly elevated at the time points that corresponded to arthritis flares, and higher levels were maintained during the progression of arthritis. CONCLUSION: OPN may mediate bone resorption by osteoclasts in arthritis through ligation with its receptor, alpha(v)beta3 integrin. OPN may be a useful therapeutic target molecule in the prevention of bone destruction in arthritis.     

Relationship between navicular drop and measuring position of maximal plantar flexion torque of the first and second-fifth metatarsophalangeal joints

[Purpose] The purpose of this study was to determine the relationship between navicular drop and plantar flexion torque of the first and second-fifth metatarsophalangeal joints. [Subjects] Ten healthy young men participated in this study. [Methods] The Pearson product-moment correlation coefficient was calculated to determine the relationship between navicular drop and plantar flexion torque of the first and second-fifth metatarsophalangeal joints. [Results] Significant negative correlations were observed between navicular drop and plantar flexion torques in the lengthened position of the intrinsic toe plantar flexion muscles, but no correlations were found between navicular drop and plantar flexion torques in the neutral position of the ankle and metatarsophalangeal joints. Moreover, the intrinsic toe plantar flexion muscles were found to contribute to the formation of the medial longitudinal arch. [Conclusion] Navicular drop correlates with metatarsophalangeal joint muscle strength in plantar flexion where the intrinsic toe muscles are capable of exerting force.Key words: Toe flexor strength, Intrinsic foot muscle, Medial longitudinal arch     

Precancerous mucosal changes in the gallbladder of patients with occult pancreatobiliary reflux

BACKGROUND: Pancreatobiliary reflux can occur even if the pancreaticobiliary junction is normal (occult pancreatobiliary reflux), and it may be associated with gallbladder carcinoma. The aim of the present study was to examine precancerous mucosal changes in the gallbladder from patients with occult pancreatobiliary reflux. METHODS: The mucosa of the gallbladder from 13 patients who underwent cholecystectomy was examined histopathologically. These patients had an anatomically normal pancreatobiliary junction and a biliary amylase concentration greater than 10,000 IU/L. The gallbladder of patients without carcinoma was further examined by using immunohistochemical techniques to detect Ki-67, and the results were compared with those from control patients. RESULTS: Of the 13 patients, 5 (38%) had gallbladder carcinoma and 8 (62%) did not. Of the 8 patients without carcinoma, 4 (50%) had dysplasia accompanied by hyperplasia, and 2 (25%) had hyperplasia alone of the gallbladder mucosa. The Ki-67 labeling index was significantly higher in hyperplastic and dysplastic mucosa than in control gallbladder mucosa (p < 0.0004). CONCLUSIONS: Occult pancreatobiliary reflux could be associated with precancerous mucosal changes in the gallbladder, such as hyperplasia and dysplasia with increased cellular proliferation, and could be a possible risk factor for gallbladder carcinoma.     

Is a Type A behavior pattern associated with falling among the community-dwelling elderly?

The aim of this report is to investigate the relationship between Type A behavior patterns and the likelihood of falling among community-dwelling elderly, and to compare differences in the prevalence, reasons, locations, injuries and frequency of falls between Type A and non-Type A personalities. Persons aged 60 or older living in 3 communities of Nanjing, China participated in a baseline survey conducted in 2000 (n=879), and falling incidents were followed for 1 year. The survey employed a self-administered questionnaire designed to elicit demographic data, current health problems and medications taken, intake of alcohol, exercise habits, physical function, environmental hazards and Type A behavior patterns. Several factors associated with falling such as health condition, physical function and environmental factors did not differ between the Type A and non-Type A groups except in the male tendency toward heart disease and their inability to walk fast. The results of logistic regression analyses showed that a Type A behavior pattern was independently associated with falling in males but not in females. Findings in the present study suggest that a Type A behavior pattern might play an important role in the rate of falling incidents in elderly males, since some characteristics of this personality pattern might lead to risk-taking behavior. More studies are needed to evaluate the association of certain behavior patterns with falling incidents.     

A murine model of acute liver injury induced by human monoclonal autoantibody

We have previously reported an immunoglobulin (Ig) M autoantibody to hepatocyte-related 190-kd molecules in patients with type 1 autoimmune hepatitis (AIH). This molecule was first isolated by hepatocyte-specific human monoclonal antibody (MoAb). To elucidate the role of this IgM autoantibody in hepatocyte injury, we examined the reactivity of this MoAb to murine hepatocytes and then questioned whether acute hepatic injury could be induced in mice via injection of this MoAb. The reactivity of MoAb was examined via both FACS analysis using murine hepatocytes and immunostaining of liver tissues. We then identified the murine hepatocyte membrane molecule recognized by this MoAb. The role of this MoAb in the immunopathogenesis of AIH was assessed by testing whether its injection into mice could increase serum aminotransferase levels as well as cause changes in liver histology. The present results demonstrate that this MoAb cross-reacted with murine hepatocytes and recognized a 190-kd molecule on the murine hepatocyte membrane just as in human hepatocytes. One hour after the injection of MoAb, the deposition of both IgM and complement component 3 was found in liver tissues. At 8 hours after the injection, serum aminotransferase levels were significantly increased in MoAb-injected mice compared with controls. Histological study revealed massive hepatocyte necrosis in MoAb-injected mice. In conclusion, human MoAb recognized a 190-kd molecule of both human and murine hepatocytes, and the injection of this MoAb to mice resulted in acute liver injury, indicating that this type of autoantibody may play an important role in the immunopathogenesis of AIH.