山田 俊幸

Mongolian people have higher mortality and morbidity rates due to cardiovascular disease (CVD) than Japanese people. The cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) are both atherosclerosis-related indexes. Presently, there is no comparative information on CAVI and ABI among young subjects between Mongolian and Japanese people. A total of one hundred Mongolian (men: 39%, mean age: 20.9±2.2 years) and 115 Japanese volunteers (men: 39%, mean age: 22.0±1.8 years) were recruited from among university students. The body mass index (BMI), heart rate (HR), blood pressure (BP), CAVI, ABI, carotid intima-media thickness, blood total cholesterol (TC), glucose and C reactive protein levels were measured. The levels of BMI, HR and diastolic BP were significantly higher, and TC and glucose were significantly lower in the Mongolian subjects than in the Japanese subjects. The CAVI values (median (interquartile range): 6.5 (5.8-7.0) vs. 5.6 (5.2-6.0)) and ABI (1.11 (1.05-1.17) vs. 1.09 (1.05-1.15)) were significantly higher in the Mongolian subjects than in the Japanese subjects. The patterns of correlation between CAVI, ABI and other atherosclerotic parameters were different: in age-, gender- and BMI-adjustment correlation tests for CAVI and ABI, HR (r=-0.25 for CAVI and ABI) showed a correlation in the Mongolian subjects, and for ABI systolic BP (r=-0.28) showed a correlation in the Japanese subjects. These results suggest that Mongolian subjects may be at higher risk of CVD, even among younger individuals, than Japanese subjects.

Objective. Genetic polymorphisms in serum amyloid A (SAA) have been shown to substantially influence the risk of developing type AA amyloidosis. Recently, a role for MMP-1 has been suggested in the pathogenesis of AA amyloidosis. Therefore, we investigated if the SAA1 isotypes are differentially degraded by MMP-1. Methods. Degradation of different SAA isotypes by MMP-1 was assessed by immunoblotting. MALDI-TOF mass spectrometry was used to identify degradation fragments. Results. We found that SAA1.5 is more resistant to degradation by MMP-1 than SAA1.1. This difference is caused by the capacity of MMP-1 to cleave at the site of the polymorphism at position 57. Conclusion. These results may explain the higher risk of amyloidosis in patients with a SAA1.1/1.1 genotype vs SAA1.5/1.5 or SAA1.1/1.5 genotype. In addition, the impaired degradation of SAA1.5 by MMP-1 could also explain the higher serum SAA concentrations in persons with a SAA1.5 genotype. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

We report three patients with AL amyloidosis manifesting as systemic lymphadenopathy, mainly in the cervical and supraclavicular regions. Histopathology of lymph nodes showed massive deposition of AL amyloid with no abnormal findings suggestive of lymphoproliferative disorders. Two of the patients were considered to be classifiable as primary systemic AL amyloidosis based on the presence of M-protein in serum and abnormal plasma cells or lymphoplasmacytoid cells in the bone marrow probably producing the precursor immunoglobulin, although no visceral organs were affected. The size of the involved lymph nodes in these two patients increased gradually, and one was treated with rituximab and VAD (vincristine, doxorubicin and dexamethasone) followed by high-dose melphalan with autologous peripheral blood stem cell transplantation (auto-PBSCT). The remaining patient showed no obvious change in the size of lymph nodes or detectable M-protein in serum. The prognosis of AL amyloidosis manifesting as lymphadenopathy is usually good as long as there are no hematological malignancies or rapid increases in the size of lymph nodes, but in cases of the systemic type, intensive chemotherapy, such as high-dose melphalan with auto-PBSCT, should be actively considered in order to avoid possible involvement of visceral organs. © 2008 Informa UK Ltd.

Inflammation is a risk factor for Alzheimer's disease. Serum amyloid A (SAA) is an acute phase protein that dissociates apolipoprotein AI (apoAI) from plasma HDL. In cerebrospinal fluid (CSF), the SAA concentration is much higher in subjects with Alzheimer's disease than in controls.. CSF-HDL is rich in apoE, which plays an important role as a ligand for lipoprotein receptors in the central nervous system (CNS). To clarify whether SAA dissociates apoE from CSF-HDL, we added recombinant SAA to CSF and determined the apoE distribution in the CSF using native two-dimensional gel electrophoresis. We found that SAA dissociated apoE from CSF-HDL in a dose-dependent manner. This effect was more evident in apoE4 carriers than in apoE3 or apoE2 carriers. After a 24-h incubation at 37 degrees C, SAA continuously dissociated apoE from CSF-HDL. Amyloid beta (A beta) fragments (1-42) were bound to large CSF-HDL but not to apoE dissociated by SAA. In conclusion, SAA dissociates apoE from CSF-HDL. We postulate that inflammation in the CNS may impair A beta clearance due to the loss of apoE from CSF-HDL. (c) 2006 Elsevier B.V. All rights reserved.

Serum amyloid A, an apolipoprotein of high density lipoproteins, is also present to a lesser degree in low density lipoproteins and is co-localized with apolipoprotein B in atherosclerotic lesions. This study examined the effect of serum amyloid A on cellular affinity of low density lipoprotein in vitro. I-125-labelled low density lipoprotein, when loaded with recombinant serum amyloid Al (acute phase isotype) or recombinant serum amyloid A4 (constitutive isotype), had enhanced binding to both human skin fibroblasts and a murine macrophage cell line, J774, while its degradation was slightly increased in both cells. The binding of oxidized low density lipoprotein to J774 cells was also enhanced by addition of recombinant serum amyloid Al or serum amyloid A4, and degradation of oxidized low density lipoprotein was moderately enhanced by recombinant serum amyloid A1. The effects of recombinant serum amyloid A on cellular binding of labelled low density lipoprotein were not competed by nonlabelled low density lipoprotein and were diminished in the presence of high density lipoprotein. These findings suggest that serum amyloid A in low density lipoprotein may promote association of low density lipoprotein with cells by non-specific adsorption, and high density lipoprotein may prevent such interactions by removal of serum amyloid A.

Serum amyloid A, an apolipoprotein of high density lipoproteins, is also present to a lesser degree in low density lipoproteins and is co-localized with apolipoprotein B in atherosclerotic lesions. This study examined the effect of serum amyloid A on cellular affinity of low density lipoprotein in vitro. 125I-labelled low density lipoprotein, when loaded with recombinant serum amyloid Al (acute phase isotype) or recombinant serum amyloid A4 (constitutive isotype), had enhanced binding to both human skin fibroblasts and a murine macrophage cell line, J774, while its degradation was slightly increased in both cells. The binding of oxidized low density lipoprotein to J774 cells was also enhanced by addition of recombinant serum amyloid Al or serum amyloid A4, and degradation of oxidized low density lipoprotein was moderately enhanced by recombinant serum amyloid Al. The effects of recombinant serum amyloid A on cellular binding of labelled low density lipoprotein were not competed by nonlabelled low density lipoprotein and were diminished in the presence of high density lipoprotein. These findings suggest that serum amyloid A in low density lipoprotein may promote association of low density lipoprotein with cells by non-specific adsorption, and high density lipoprotein may prevent such interactions by removal of serum amyloid A. © 1997, Walter de Gruyter. All rights reserved.