山田 俊幸

Aim: One of the methods to evaluate oxidative stress in clinical medical settings is the reactive oxygen metabolites (d-ROMs) test. While metabolic syndrome (MetS) is considered an oxidative condition, the oxidative status in MetS has not been fully examined using this test. The aim of the present study was to investigate the possible association between oxidative stress as evaluated by the d-ROMs test and the MetS component number, in a Japanese female population. Methods: The serum oxidant capacity (measured by the d-ROMs test) was cross-sectionally determined in cardiovascular disease-free and non-smoking women who were not taking medications (n= 180 mean age, 60 ± 10 (standard deviation) years). Their MetS state was determined by the National Cholesterol Education Program Adult Treatment Panel recommendations with minor modifications for a Japanese population. Results: Patients with MetS (n= 60, 362 ± 53 CARR U) showed a significantly higher oxidant capacity by d-ROMs than those without MetS (n= 120, 324 ± 55 CARR U, P &lt 0.01). Moreover, the significant increase in the oxidant capacity by d-ROMs was closely associated with an increase in the MetS component number (trend P &lt 0.01). Conclusions: These results showed a significantly positive association between the oxidant capacity (by d-ROMs) and the MetS component number in this population. Further studies are required to establish the clinical applications of this test to MetS practice and clarify the biological mechanisms of the observed relationships. © 2012 The Authors. Australasian Journal on Ageing © 2012 ACOTA.

The complex of serum amyloid A(SAA) and low-density lipoprotein (LDL), SAA-LDL, is considered a new and unique marker of oxidatively-modified LDL particles, which is associated with atherosclerotic conditions. This study investigated the influence of atorvastatin treatment on circulating SAA-LDL levels among asymptomatic hypercholesterolemic patients. A total of 26 patients (mean age 63 years) received 10 mg/daily atorvastatin during a 12-week treatment period. The levels of LDL cholesterol and SAA-LDL, but not high-sensitivity C-reactive protein and SAA, were significantly reduced after the treatment. Stepwise adjusted regression analyses revealed that changes of SAA-LDL were significantly and positively correlated with those of SAA, while absolute changes were small, which warrants further investigation. The results suggest that atorvastatin may beneficially reduce SAA-LDL, and SAA-LDL may be a sensitive measure for monitoring the efficacy and antioxidant functions of atorvastatin. Copyright © 2012 by Institute of Pharmacology Polish Academy of Sciences.

Amyloidosis is usually diagnosed through the histological examination of biopsy samples. However, its quantitative evaluation can be difficult. In this study, we immunochemically measured amyloid A (AA) proteins in biopsy samples taken from the stomachs of patients with AA amyloidosis. Samples were treated with guanidine and were subjected to an enzyme immunoassay for serum amyloid A. The results were compared with histological findings. All patients who tested negative for amyloid deposits had low values that clearly distinguished them from amyloid-positive patients. Among the amyloid-positive patients, the AA values correlated significantly with histological findings. This method may be useful for the quantitative evaluation of AA amyloidosis. © 2012 by the Association of Clinical Scientists, Inc.

BACKGROUND: Limited studies have shown inconsistent data about the association between the uncoupling protein 1 (UCP1) gene A-3826G polymorphism and high-density lipoprotein (HDL) cholesterol levels. The present study investigated the association between the A-3826G polymorphism and low HDL-cholesterolemia in non-obese and obese subjects. METHODS: Anthropometric and biochemical factors, in addition to genotyping by an allele-specific DNA assay, were measured in 294 community-dwelling Japanese subjects (male/female: 127/167, mean age: 65 years). Obesity was defined as a body mass index (BMI) ≥ 25 kg/m(2), and low HDL-cholesterolemia was defined as < 1.04 mmol/L of HDL-cholesterol. RESULTS: The subjects with the G/G genotype (n = 27) showed a significantly higher prevalence of low HDL-cholesterolemia (37%) than those with the A/A + A/G genotype (13%) in the obese group (n = 102). There was a non-significant difference in the prevalence of low HDL-cholesterolemia between subjects with the G/G genotype (n = 45, 13%) and with the A/A + A/G genotype (15%) in the non-obese group (n = 192). A multivariate-adjusted logistic regression analysis of the presence of low HDL-cholesterolemia revealed that carrying the G/G genotype was an independent and significant factor positively associated with low HDL-cholesterolemia [odds ratio (OR): 6.85, 95% confidence interval (CI): 1.65-28.49] in the obese group, while carrying the G/G genotype exhibited a non-significant but reduced OR, by one-half, for low HDL-cholesterolemia (OR: 0.51, 95% CI: 0.13-1.96) in the non-obese group. CONCLUSIONS: The obesity status could have opposing impacts on the relationship between the G/G genotype and low HDL-cholesterolemia, providing insight into the need to consider the obesity levels when studying the association between the UCP-1 gene A-3826G polymorphism and HDL-cholesterol. KEYWORDS: Obesity; Body mass index; HDL-C; Atherosclerotic risk.

BACKGROUND: Inflammation, often accompanied by oxidation, caused by advanced glycation end products (AGEs) may be quenched by the soluble receptor for AGEs (sRAGE). The present study aimed to investigate the influence of physical activity on circulating sRAGE, and the association between changes of circulating sRAGE and paraoxonase1 (PON1) activity (as an antioxidative enzyme) in a physical activity intervention study on an elderly subject cohort. METHODS: Serum sRAGE, PON1 activity and cardiometabolic variables were measured in 30 community-dwelling asymptomatic Japanese volunteers (15 men/15 women, mean age 65 years) in the pre- and post-phase of a 6-month interventional program designed to increase physical activity. RESULTS: The body mass index and sRAGE levels (1103 ± 496 to 1030 ± 437 ng/L, P < 0.05) were significantly reduced during the intervention period. In addition, the change of sRAGE was significantly and inversely correlated with that of PON1 activity, independent of the other cardiometabolic variables (β = - 0.511, P < 0.01). CONCLUSIONS: This study showed a reduction of sRAGE levels, and an inverse correlation between sRAGE and PON1 activity, after the intervention study increasing physical activity on an elderly population. These findings represent a modest but significant modulation of sRAGE by this type of exercise intervention, which warranted future studies on the clinical relevance of sRAGE changes in physical activity. KEYWORDS: AGEs; RAGE; Paraoxonase1; Exercise; Atherosclerosis.

Objective.Acceleration of amyloid A (AA) amyloidosis induction by ageing has not been extensively studied in rheumatoid arthritis (RA). The aim of this study is to clarify contribution of ageing to the development of AA amyloidosis associated with RA in our large cohort. Methods.388 adult-onset RA patients whose RA was complicated by biopsy-proven AA amyloidosis were enrolled. The ages of RA onset and AA amyloidosis diagnosis were estimated in each patient. The contributions of ageing, inflammatory activity, SAA1 exon 3 polymorphism as well as gender to the pathogenesis of AA amyloidosis in 144 cases were also studied by multiple regression analysis. Results.Subjects with RA onset at older age had a shorter period to develop amyloidosis than those with disease onset at younger age (p &lt 0.001). The interval between RA onset and AA amyloidosis diagnosis was significantly shorter in the SAA1.3 positive group than in the SAA1.3 negative (p=0.001). Multiple regression analysis indicated that the interval from RA onset to diagnosis of AA amyloidosis is determined by age at RA onset (p &lt 0.001), the most recent median annual CRP concentration (p=0.006) and SAA1.3 allele (p=0.058). Gender did not significantly contribute to the onset of AA amyloidosis (p=0.569). Conclusion.Ageing is an independent risk factor for the induction of AA amyloidosis complicating RA. © 2011 Informa UK, Ltd.

To foster work-ready general physicians, Jichi Medical University has developed various clinical teaching practices since its foundation. The educational courses for clinical laboratory medicine, being one of them, adopt practical trainings in ultrasonography, which is essential in practical medicine today. The aims and the specifics of the trainings adopted in the seminar of ultrasound and the required or the optional subjects of Bedside Learning (BSL) at Jichi Medical University are reported.

Background: Oxidized lipoprotein(a) (oxLp(a)) can be a more potent marker of atherogenesis than native Lp(a), although Lp(a) is considered to be a risk factor for atherosclerotic diseases. Limited clinical data are available regarding the significance of oxLp(a) in atherosclerotic manifestations. This study aimed to investigate the association between the serum oxLp(a) and carotid artery intima-media thickness (CIMT), in comparison to the serum Lp(a) levels, among asymptomatic subjects. Methods. The atheroscrerosis-related variables including Lp(a) and oxLp(a) were measured in 136 cardiovascular disease-free subjects (61 males and 75 females, mean age of 64 years). The serum oxLp(a) level was quantified using a sandwich ELISA system. The CIMT level was ultrasonographically measured on bilateral carotid arteries. Results: The median level of Lp(a) was 120 mol/L, oxLp(a) was 0.06 nmol/L, and CIMT was 0.7 mm, respectively. A simple correlation test showed that the CIMT was significantly and positively correlated with age, systolic blood pressure and oxLp(a) (r = 0.208, P &lt 0.05). A multiple linear regression analysis revealed that oxLp(a) continued to show a significant and positive correlation with the CIMT ( = 0.202, P = 0.01). Although the similar analyses were conducted for Lp(a), it showed only a weak correlation with the CIMT (r = 0.011, = 0.041, both P &lt 0.05). Conclusions: These results suggest that oxLp(a) may be more closely associated with accelerated carotid atherosclerosis, in comparison to Lp(a), in this population. This finding can be important for obtaining a better understanding of the different atherogenic roles played by oxLp(a) in comparison to Lp(a). © 2011 Kotani et al licensee BioMed Central Ltd.

Background: Cardiometabolic disorders including cardiovascular disease (CVD) where the relevance of regular coffee consumption is debatable, has been linked with the development of chronic kidney disease (CKD). A more recent study suggests that coffee consumption is associated with normal or increased kidney function as assessed by the estimated glomerular filtration rate (eGFR). The present study investigated whether the association between coffee and the eGFR was independent of chronic inflammation, and whether adding sugar to coffee could affect the eGFR. Methods: A total of 114 age- and gender-matched Japanese individuals (females/males=68/46, mean age=59.5 years), without CVD and severe CKD, were studied. Clinical variables, such as body mass index, blood pressure, blood glucose, lipids and high-sensitivity C-reactive protein (hsCRP), in addition to eGFR [the Modification of Diet in Renal Disease (MDRD) study equation], were measured. Results: Coffee drinkers had higher eGFR values [73.9±16.5 (SD) mL/min/1.73 m2] than non-coffee drinkers (68.6±11.7). The difference remained significant (F=5.04, p=0.027), independently of clinical variables, including hsCRP. The eGFR values among coffee drinkers were similar between the subjects with and without use of sugar. Conclusions: The association of coffee drinking habits to eGFR may occur independently of inflammation as assessed by hsCRP. The use of sugar may have no effect on GFR. Further research is needed to clarify this phenomenon. © 2010 by Walter de Gruyter Berlin New York.

Objective: It was the aim of this study to investigate whether there is any relationship between oxidative stress, as assessed by the diacron reactive oxygen metabolite (d-ROM) test, and carotid atherosclerosis among hypercholesterolemic patients. Subjects and Methods: A well-defined group of patients with type II hypercholesterolemia (n = 81, mean age 59 years) was studied to observe the correlation between the levels of serum d-ROMs and carotid artery intima-media thickness (IMT) using B-mode ultrasound, in relation to the traditional atherosclerotic risk factors (age, sex, smoking, body mass index, blood pressure, glucose and lipid panels). Results: The mean level in low-density lipoprotein cholesterol (LDL-C) in this population was 4.45 mmol/l, d-ROMs were 323.2 Carr U, and IMT was 0.91 mm. A multiple regression analysis revealed a positive and significant correlation between IMT and d-ROMs (β = 0.27, p &lt 0.05), along with age and LDL-C. Conclusion: These results indicate that the increased oxidative stress levels using the d-ROM test, independent of aging and increased LDL-C levels, may be associated with carotid atherosclerosis even in hypercholesterolemic patients. Copyright © 2010 S. Karger AG, Basel.

Objective: Atherosclerotic risk factors contribute to carotid atherosclerosis. Carotid intima-media thickness (IMT), as assessed using a non-invasive high-resolution ultrasound, can predict cardiovascular disease (CVD). Whereas the control of CVD is crucial for the Mongolian people, the studies on carotid atherosclerosis are lacking. The present population-based survey was a crosssectional investigation of the determinants of carotid IMT in the general Mongolian population. Methods: A total of 344 Mongolian volunteers, aged 18 to 69 years, without CVD and on no medication, were recruited from a health screening setting. The current smoking habits, body mass index, mean blood pressure (MBP), blood total cholesterol (TC), glucose, insulin and carotid IMT (maximum level) were measured. Results: Mongolian males had a significantly higher prevalence of current smoking and a higher level of IMT than females (average5 .58 mmin males vs .46 in females). Both a single and multiple regression analysis adjusted for all the measures revealed that IMT was significantly and positively correlated with age, male sex, MBP, TC and glucose among all of the participants. IMT was significantly and positively correlated with age, followed by MBP, TC and glucose among males, while among females, IMT was significantly and positively correlated with age, followed by MBP and TC. Conclusions: Age was the strongest determinant of carotid atherosclerosis, and the increases in blood pressure and cholesterol levels were also important measures in both sexes as well as glucose levels in males in particular, thus suggesting a preventive strategy for CVD in the general Mongolian population.

Hypertension (HT) and C-reactive protein (CRP) are risk factors of cardiovascular diseases (CVD). The current study's purpose was to investigate the relationship between serum CRP levels and daily lifestyles, including physical activity, in Japanese HT patients. Lifestyle factors, blood pressure (BP), blood cholesterol, glucose, and CRP were measured in a total of 312 HT patients (153 men/159 women, mean age: 62.6 y). Women with physical activity of ≥ 1 time/week showed significantly lower CRP levels than those without it (p &lt 0.05). The data suggest that regular physical activity could reduce the CRP levels in HT patients, thereby maybe preventing CVD. © 2010 Informa Healthcare USA, Inc.

Background. Oxidized low-density lipoprotein (LDL) may act as an atheroprotective (anti-atherosclerotic) agent under some conditions. While the 1-antitrypsin (AT)-LDL complex is considered a type of oxidized LDL, its clinical relevance remains unknown. The aim of the present study was to investigate the association between AT-LDL and anti-atherosclerotic variables such as HDL-cholesterol and adiponectin in subjects with and without metabolic syndrome (MetS). Methods. In asymptomatic females (n = 194 mean age, 54 years) who were divided into non-MetS (n = 108) and MetS groups (n = 86), the fasting levels of serum AT-LDL, adiponectin and glucose/lipid panels were measured, in addition to body mass index (BMI) and blood pressure. Results. The MetS group showed significantly higher BMI, blood pressure, glucose and triglyceride levels as well as significantly lower levels of HDL-cholesterol and adiponectin than the non-MetS group. A multivariate-adjusted analysis revealed that in the non-MetS group, AT-LDL was significantly, independently and positively correlated with adiponectin (β = 0.297, P &lt 0.05), along with HDL-cholesterol (β = 0.217, P &lt 0.05). In the MetS group, AT-LDL was significantly, independently and positively correlated with LDL-cholesterol only (β = 0.342, P &lt 0.05). Conclusions. These data suggest that AT-LDL may exert anti-atherosclerotic effects in female subjects without MetS. More studies are required to clarify the clinical roles of AT-LDL in relation to the pathophysiology of MetS. © 2010 Kotani et al licensee BioMed Central Ltd.

Background. Oxidized lipoproteins play important roles in the atherosclerotic processes. Oxidized lipoprotein(a) (oxLp(a)) may be more potent in atherosclerotic pathophysiology than native Lp(a), a cardiovascular disease-relevant lipoprotein. Increased blood glucose concentrations can induce oxidative modification of lipoproteins. The aim of this study was to investigate the association between circulating oxLp(a) and cardiometabolic variables including blood glucose in healthy volunteers within the normal range of blood glucose. Methods. Several cardiometabolic variables and serum oxLp(a) (using an ELISA system) were measured among 70 healthy females (mean age, 22 years). Results. Lp(a) and glucose were significantly and positively correlated with oxLp(a) in simple correlation test. Furthermore, a multiple linear regression analysis showed oxLp(a) to have a weakly, but significantly positive and independent correlation with only blood glucose ( = 0.269, P &lt 0.05). Conclusions. These results suggest that increased glucose may enhance the oxidization of Lp(a) even at normal glucose levels. © 2010 Kotani et al licensee BioMed Central Ltd.

We examined the relationship between the coefficient of variation in the R-R intervals (CVR-R) using electrocardiograms and the ultrasonic intima-media thickness (IMT) of the carotid artery, an atherosclerotic parameter, in type 2 diabetes mellitus (DM) patients with diabetic neuropathy (n=47, males/females: 29/18 mean age: 62 years). In this study, the CVR-R-related indexes, including CVR-R at rest (CVR-Rrest), CVR-R with deep breaths (CVR-Rbreath) and their difference (CVR-Rbreath minus CVR-Rrest: CVR-Rdif), were defined. Data such as body mass index, smoking habits, hemoglobin A1c, blood pressure, and serum low-density lipoprotein were collected. A significant inverse correlation was observed between max-IMT and CVR-Rdif (β=-0.34, p=0.042), but not CVR-Rrest or CVR-Rbreath, in multivariate analyses adjusted for all the data. Therefore, the CVR-Rdif may serve as a clinical index for the diabetic autonomic neuropathy-atherosclerosis relation in type 2 DM patients.

OBJECTIVE: Metabolism of aspirin (acetylsalicylic acid), commonly used in older people for the prevention of cardiovascular disease, is important to the effectiveness of this drug. Whereas part of aspirin hydrolysis occurs in blood, there is a paucity of information in regards to circulating aspirin esterase activity in various physiological and pathological conditions. High aspirin esterase activity, corresponding to faster aspirin hydrolysis (thus aspirin non-responsiveness), may occur in cardiovascular disease-prone states. The objective of this study was to inv estigate the effects of cardio-metabolic variables such as cholesterol on serum aspirin esterase activity in older people who participated in an intervention study on physical activity. METHODS: A total of 18 non-medicated subjects (7 men/11 women, mean age 67.8 years, body mass index = 23.4 ± 3.3 kg/m2), who completed a 3-month interventional program for a mild-to-moderate increase in physical activity, were analyzed. The body mass index, plasma glucose, serum total cholesterol and aspirin esterase activity were measured in the pre- and post-interventional phases of the study. RESULTS: During the interventional period, the changes in aspirin esterase activity correlated significantly and positively with those of total cholesterol concentrations (r = 0.542, P = 0.020 β = 0.609, P = 0.035 in a multiple linear regression analysis after adjusting for all the measured variables). CONCLUSION: The results suggest that cholesterol metabolism alterations may be associated with aspirin metabolism in older people. © Ivyspring International Publisher.

Aim: Cardiovascular disease is becoming increasingly more problematic in Mongolia. The cardioankle vascular index (CAVI) and circulating C-reactive protein (CRP) are new atherosclerosis-related parameters, but no comparative studies of atherosclerotic parameters including CAVI and CRP are available between Mongolian and Japanese populations, such as disease populations of hypertension (HT) and diabetes mellitus (DM). Our study objective was to examine atherosclerotic profiles in HT and DM patients in both countries. Methods: From a hospital-based population, 156 Mongolian outpatients with HT and DM (men: 46%, mean age: 57.1 years) and 156 age- and sex-matched Japanese outpatients with HT and DM (men: 46%, age: 57.7) were recruited. Body mass index (BMI), heart rate (HR), blood pressure (BP), pulse pressure (PP), ankle-brachial index (ABI), ultrasonographic carotid intima-media thickness (IMT), blood total cholesterol (T-Cho), glucose, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were measured, in addition to CAVI and CRP. Results: The levels of BMI, HR, BP, PP, insulin and IMT were significantly higher and T-Cho and glucose were significantly lower in the Mongolian patients in comparison to the Japanese patients. Particularly, the levels of CAVI (mean ± SD) (8.1 ± 1.1 vs. 8.8 ± 1.2) and CRP (median [interquartile range]) (0.05 [0.03-0.12] vs. 0.19 [0.09-0.42] mg/dL) were significantly higher in Mongolian than Japanese patients. These significant differences remained unchanged, even after taking into account multiple variables, including BP and HOMA-IR. In addition, except for CAVI in the subgroup of DM, generally similar trends regarding atherosclerotic parameters were seen in the subgroup by sex and disease (HT, DM and HT plus DM). Conclusion: These findings suggest that Mongolian patients with HT and DM may be at higher risk for cardiovascular disease than Japanese patients.

Serum amyloid A (SAA), a precursor of reactive amyloid deposits, is a multigene product. SAA1, predominant both as an amyloid precursor and in plasma, consists of three allelic variants (SAA1.1, SAA1.3, and SAA1.5). Several investigations have shown that the SAA1.3 allele is associated with susceptibility to AA-amyloidosis in Japanese, and the SAA1.5 allele is related with higher serum concentrations of SAA. However, these results have not been interpreted functionally. This study assessed the affinity of SAA isotypes for high-density lipoprotein (HDL), to which SAA binds in plasma. Using a surface plasmon resonance-based apparatus (BIAcore), the affinity between immobilized recombinant human SAAs and HDL was determined. The SAA concentration was measured in fractions after ultracentrifugation (d=1.23) of sera from patients with rheumatoid arthritis, whose SAA1 genotypes were determined. In the BIAcore analysis, as the dissociation reaction under the conditions used was too rapid to fit the typical kinetic model, the steady-state affinity model was used. The affinity (kd) of SAA1.1, SAA1.3, and SAA1.5 for HDL was 1.4 × 10 -5, 1.8 × 10-5, and 3.7 × 10-6, respectively. rSAA1.5 showed significantly (p&lt 0.05) stronger affinity than the other two. The fraction of lipid-free SAA in serum was significantly (p&lt 0.001) lower in the patients with larger numbers of the 1.5 allele at the SAA1 locus. These results suggest that the relatively high affinity of SAA1.5 may cause the high serum concentration and may be related to the low susceptibility to amyloidosis. © 2009 Informa UK Ltd.

Background: Lifestyle modification improves the pathophysiology of lipid disorder, leading to the development of cardiovascular disease (CVD). While oxidized low-density lipoprotein (oxLDL) may be involved in this mechanism, various oxLDL measurements have recently been developed and therefore further detailed studies are called for in this area. Our aim was to investigate the effects of lifestyle modification on serum amyloid A-LDL (SAA-LDL), a new oxLDL, in subjects with primary lipid disorder. Methods: A total of 141 asymptomatic subjects (women/men = 100/41, mean age 57.6 years) with ≥ 1 lipid abnormality (circulating high levels of low-density lipoprotein cholesterol [LDL-C] and triglyceride [TG] or low levels of high-density lipoprotein cholesterol [HDL-C]), who completed a 6-month lifestyle modification program in combination with diet and exercise, were analyzed. In the pre- and post-intervention, the metabolic variables including SAA-LDL were assessed. Results: During our intervention, the body mass index, blood pressure, LDL-C, TG, glucose and SAA-LDL significantly decreased, while HDL-C significantly increased. Multiple regression analysis revealed that the change levels of TG (positive) and HDL-C (inverse) were significantly and independently correlated to those of SAA-LDL. Conclusions: These results suggest that SAA-LDL may contribute to the link between lipid disorder and the development of CVD, and that the application of SAA-LDL measurements may be useful for the assessment of the risk of CVD as a biochemical marker. © 2009.

Apolipoprotein E is commonly present in systemic amyloid deposits. To investigate the possibility of using apolipoprotein E immunotargeting in the diagnosis and treatment of amyloidosis, we examined whether anti-apolipoprotein E monoclonal antibody was bound to murine amyloid deposits in vivo and whether it influenced amyloidogenesis. This study utilized a radiolabeled monoclonal antibody specific to human apolipoprotein E fragments and human apolipoprotein E-knock-in mice, in which AA amyloidosis was induced. Accumulation of the injected radiolabeled antibody was significantly higher in the organs of amyloidotic mice than in those of non-amyloidotic mice. Plasma clearance of the antibody did not differ between the amyloidotic and non-amyloidotic mice. The antibody was given to mice during amyloid induction but failed to prevent amyloidogenesis. The results of this initial study are encouraging, but considerable improvement is necessary, particularly in regard to development of a high affinity antibody. © 2009 by the Association of Clinical Scientists, Inc.

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.