山田 俊幸

<p>血清蛋白分画検査は，血清蛋白異常症のスクリーニング検査として広く用いられており，特に多発性骨髄腫の診断および治療効果の判定に欠かせないM蛋白の検出方法である．血清蛋白分画を院内で実施する最大の意義は，重要な所見を発見し，その病態を把握したうえでいち早く依頼医に報告できることである．当院における取り組みとしては以下のようなものがある．第一に，悪性M蛋白等異常所見を認めた患者においては，検査技師がカルテを閲覧し，検査目的や他の検査所見を参考に，疑われる病態を考察する．第二に特徴的なβ-γブリッジングが認められた時には，IgG4関連疾患を疑う．第三に生化学や免疫学的検査で非特異反応を認めたときに，その原因の一つと考えられるM蛋白の有無の確認をする．第4にクリオグロブリンの型判定にも利用する．このような取り組みにより医師の診断のサポートが行える．</p>

＜Point＞全身性アミロイドーシスとは,血漿蛋白がその量的・質的異常によりアミロイド線維化して全身組織に沈着する病態である.量的異常には,モノクローナルに増加した免疫グロブリンL鎖によるAL型,血清アミロイドAによるAA型,β2-ミクログロブリン(β2m)によるAβ2m型がある.質的異常には,変異トランスサイレチンによるもの,まれではあるが他の血漿蛋白の遺伝子異常に起因するものがある.アミロイドーシスの診断は病理組織学的に行われる.診断困難例については,切片から質量分析によってアミロイド構成蛋白の同定が行われている.補助診断として,Bence Jones蛋白(BJP)の検出,血清アミロイドA1の遺伝子解析,トランスサイレチンの変異解析(遺伝子解析だけでなく,質量分析による蛋白解析も)など,前駆物質である血漿蛋白へのアプローチがある.(著者抄録)

＜Point＞全身性アミロイドーシスとは,血漿蛋白がその量的・質的異常によりアミロイド線維化して全身組織に沈着する病態である.量的異常には,モノクローナルに増加した免疫グロブリンL鎖によるAL型,血清アミロイドAによるAA型,β2-ミクログロブリン(β2m)によるAβ2m型がある.質的異常には,変異トランスサイレチンによるもの,まれではあるが他の血漿蛋白の遺伝子異常に起因するものがある.アミロイドーシスの診断は病理組織学的に行われる.診断困難例については,切片から質量分析によってアミロイド構成蛋白の同定が行われている.補助診断として,Bence Jones蛋白(BJP)の検出,血清アミロイドA1の遺伝子解析,トランスサイレチンの変異解析(遺伝子解析だけでなく,質量分析による蛋白解析も)など,前駆物質である血漿蛋白へのアプローチがある.(著者抄録)

＜Point＞全身性アミロイドーシスとは,血漿蛋白がその量的・質的異常によりアミロイド線維化して全身組織に沈着する病態である.量的異常には,モノクローナルに増加した免疫グロブリンL鎖によるAL型,血清アミロイドAによるAA型,β2-ミクログロブリン(β2m)によるAβ2m型がある.質的異常には,変異トランスサイレチンによるもの,まれではあるが他の血漿蛋白の遺伝子異常に起因するものがある.アミロイドーシスの診断は病理組織学的に行われる.診断困難例については,切片から質量分析によってアミロイド構成蛋白の同定が行われている.補助診断として,Bence Jones蛋白(BJP)の検出,血清アミロイドA1の遺伝子解析,トランスサイレチンの変異解析(遺伝子解析だけでなく,質量分析による蛋白解析も)など,前駆物質である血漿蛋白へのアプローチがある.(著者抄録)

Hyperglycemia predicts cardiovascular disease (CVD)-related outcomes. The resting heart rates (HRs) and serum amyloid A (SAA), an inflammatory marker, are respectively factors associated with CVD-related outcomes; however, little is known regarding the associations between these two factors. This study aimed to investigate the correlation between the HRs and SAA levels under hyperglycemic conditions. This study included 298 subjects (males, 44%; mean age, 61.1 years) without a history of CVD and/or hypertensive levels. Clinical data, including general laboratory measurements, HRs and SAA, were measured. The analyses were performed after dividing all of the subjects into two groups based on the blood glucose level (&lt; or &gt;= 6.1 mmol/L). There was a higher SAA level in the hyperglycemic group (n = 143; median [interquartile range] 6.1 [4.1-10.6] mu g/mL) than in the counterpart group (n = 155; 6.0 [3.5-8.5] mu g/mL; p &lt; 0.01). There was a trend toward increased HRs in the hyperglycemic group (mean [standard deviation] 65.3 [11.2] bpm) compared to the counterpart group (63.2 [9.4] bpm; p = 0.08). In the hyperglycemic group, there was a significant positive correlation between the HRs and SAA levels (multiple variables-adjusted analysis: beta = 0.21, p = 0.02), while no correlation was found in the counterpart group (beta = 0.06, p = 0.50). In summary, a positive correlation between the HRs and SAA levels can present under hyperglycemic conditions. These findings may provide relevant insights into the CVD-related pathologies associated with hyperglycemia. Further studies are warranted.

Hyperglycemia predicts cardiovascular disease (CVD)-related outcomes. The resting heart rates (HRs) and serum amyloid A (SAA), an inflammatory marker, are respectively factors associated with CVD-related outcomes; however, little is known regarding the associations between these two factors. This study aimed to investigate the correlation between the HRs and SAA levels under hyperglycemic conditio

Hyperglycemia predicts cardiovascular disease (CVD)-related outcomes. The resting heart rates (HRs) and serum amyloid A (SAA), an inflammatory marker, are respectively factors associated with CVD-related outcomes; however, little is known regarding the associations between these two factors. This study aimed to investigate the correlation between the HRs and SAA levels under hyperglycemic conditio

今回LBA-EATA法を原理とするミュータスワコーi30（和光純薬）によるAFP測定時に偽低値を示すHCC患者症例に遭遇した．約1年間における15％以上の偽低値の出現頻度は11,000検体中44検体で全検体数の0.4％，2,000 ng/mL以下では，770検体中5.7％であった．10％以上の偽低値を示した患者18症例は全例HCCと診断され，18例中15症例が末期であった．薬物療法を受けていたのは12症例であり，ネクサバールが9例，無治療は6例であった．偽低値検体の解析では，希釈することで偽低値が改善し，また，PEG処理やプロテインA処理で免疫グロブリンを除去することでも偽低値が改善した．さらに化学処理では10％TritonX-100処理，4 M尿素処理および1 M酢酸処理で偽低値が改善した．種々の検討結果から免疫グロブリン（特にIgG）が関係していることが示唆され，HCC末期状態により，

今回LBA-EATA法を原理とするミュータスワコーi30（和光純薬）によるAFP測定時に偽低値を示すHCC患者症例に遭遇した．約1年間における15％以上の偽低値の出現頻度は11,000検体中44検体で全検体数の0.4％，2,000 ng/mL以下では，770検体中5.7％であった．10％以上の偽低値を示した患者18症例は全例HCCと診断され，18例中15症例が末期であった．薬物療法を受けていたのは12症例であり，ネクサバールが9例，無治療は6例であった．偽低値検体の解析では，希釈することで偽低値が改善し，また，PEG処理やプロテインA処理で免疫グロブリンを除去することでも偽低値が改善した．さらに化学処理では10％TritonX-100処理，4 M尿素処理および1 M酢酸処理で偽低値が改善した．種々の検討結果から免疫グロブリン（特にIgG）が関係していることが示唆され，HCC末期状態により，

Hyperglycemia predicts cardiovascular disease (CVD)-related outcomes. The resting heart rates (HRs) and serum amyloid A (SAA), an inflammatory marker, are respectively factors associated with CVD-related outcomes however, little is known regarding the associations between these two factors. This study aimed to investigate the correlation between the HRs and SAA levels under hyperglycemic conditions. This study included 298 subjects (males, 44% mean age, 61.1 years) without a history of CVD and/or hypertensive levels. Clinical data, including general laboratory measurements, HRs and SAA, were measured. The analyses were performed after dividing all of the subjects into two groups based on the blood glucose level (&lt or ≥ 6.1 mmol/L). There was a higher SAA level in the hyperglycemic group (n = 143 median [interquartile range] 6.1 [4.1-10.6] μg/mL) than in the counterpart group (n = 155 6.0 [3.5-8.5] μg/mL p &lt 0.01). There was a trend toward increased HRs in the hyperglycemic group (mean [standard deviation] 65.3 [11.2] bpm) compared to the counterpart group (63.2 [9.4] bpm p = 0.08). In the hyperglycemic group, there was a significant positive correlation between the HRs and SAA levels (multiple variables-adjusted analysis: β = 0.21, p = 0.02), while no correlation was found in the counterpart group (β = 0.06, p = 0.50). In summary, a positive correlation between the HRs and SAA levels can present under hyperglycemic conditions. These findings may provide relevant insights into the CVDrelated pathologies associated with hyperglycemia. Further studies are warranted.

今回LBA-EATA法を原理とするミュータスワコーi30（和光純薬）によるAFP測定時に偽低値を示すHCC患者症例に遭遇した．約1年間における15％以上の偽低値の出現頻度は11,000検体中44検体で全検体数の0.4％，2,000 ng/mL以下では，770検体中5.7％であった．10％以上の偽低値を示した患者18症例は全例HCCと診断され，18例中15症例が末期であった．薬物療法を受けていたのは12症例であり，ネクサバールが9例，無治療は6例であった．偽低値検体の解析では，希釈することで偽低値が改善し，また，PEG処理やプロテインA処理で免疫グロブリンを除去することでも偽低値が改善した．さらに化学処理では10％TritonX-100処理，4 M尿素処理および1 M酢酸処理で偽低値が改善した．種々の検討結果から免疫グロブリン（特にIgG）が関係していることが示唆され，HCC末期状態により，

BACKGROUND: White blood cell (WBC) count and C-reactive protein (CRP) level are the most common markers of inflammation. There is a growing need for point-of-care testing (POCT) of WBC and CRP, and more advances in convenient devices are required. We developed an analyzer-free POCT system for measuring WBC and CRP using a low volume blood sample. METHODS: The POCT-WBC is based on the granulocyte esterase assay, while the POCT-CRP is based on the immunochromatographic assay. These kits were examined for precision as well as correlation with currently used popular commercial automated assays. The correlations were clinically analyzed in children with acute infection (n=62; mean age 4.2y). The correlations regarding the monitoring of values were further examined in several follow-up subjects. RESULTS: The POCT-WBC and POCT-CRP kits demonstrated good precision. POCT-WBC exhibited a significantly close correlation with those of the control assay (r=0.94, p<0.05). The results of POCT-CRP also exhibited a significantly close correlation with those of the control assay (r=0.94, p<0.05). In the follow-up study, the results of the respective kits were similar to those of the control assays. CONCLUSIONS: The POCT-WBC and POCT-CRP are promising tools for assessing infection in clinical practice.

INTRODUCTION: Oxidative stress, assessed using 8-hydroxy-2'-deoxyguanosine (8-OHdG), can be associated with arterial stiffness in patients with type 2 diabetes mellitus (T2DM) and/or hypertension (HT). We investigated the correlation between urinary 8-OHdG and pulse wave velocity (PWV) in hypertensive and non-hypertensive T2DM patients with fair glycaemic control to determine the clinical significance of HT as a comorbidity in the diabetic state. METHODS: Clinical data, including traditional cardiovascular risk factors, diabetic complications, prescribed agents, urinary 8-OHdG level and brachial-ankle PWV, was collected from T2DM patients with and without HT. RESULTS: There were 76 patients (45 men, 31 women; mean age 61 years; mean haemoglobin A1c level 6.5%) in the study cohort. T2DM patients with HT had significantly higher mean PWV than patients without HT (1,597 cm/s vs 1,442 cm/s; p < 0.05). Patients with HT showed no significant difference in 8-OHdG levels relative to those without HT (median 7.9 ng/mg creatinine vs 8.8 ng/mg creatinine; p > 0.05). Simple linear correlation and stepwise multiple linear regression analyses revealed that 8-OHdG levels correlated independently, significantly and positively with PWV among T2DM patients with HT (r = 0.33, p < 0.05; β= 0.23, p < 0.05). No significant correlation was observed between 8-OHdG levels and PWV among T2DM patients without HT. CONCLUSION: In the hypertensive state, oxidative stress can be responsible for the development of arterial stiffness, even in patients with fairly well controlled T2DM. Oxidative stress management may be necessary for the prevention of cardiovascular disease in this population.

Reactive AA amyloidosis develops secondary to chronic inflammatory disorders. Serum amyloid A protein (SAA) and its degradation products, named AAs, are the main components of amyloid deposits, while apolipoprotein E (apoE) fragments are the minor components. To further understand the molecular mechanism of AA amyloidosis, we examined SAA/AAs moieties and apoE in the spleen and plasma throughout the amyloid-generating and amyloid-absorbing phases in a mouse model. SAA and four AA species (8.5kDa, 7.8kDa, 7.0kDa, and 6.2kDa) were detected in the spleen. SAA and the 8.5 kDa and 7.8 kDa AAs were prominent in the acute phase, whereas the 7.0kDa AA, the second smallest AA corresponding to the most common form in the human disease, was prominent in the chronic phase. These results indicate that the higher molecular weight species first constituted the fibril, followed by the 7.0kDa species, which were finally absorbed. ApoE was a component of the amyloid deposits at a degradation size from the beginning and was absorbed without being converted to another size. Degradation products, either from SAA or apoE, did not appear in the plasma during the course of the disease. A more detailed understanding of the moieties of amyloid-related peptides may help in the development of a method that can indicate the disease activity of AA amyloidosis.

Serum amyloid A4 (SAA4) is a constitutive apolipoprotein of high-density lipoprotein. It exhibits N-linked glycosylation in its second half. There are both glycosylated and nonglycosylated forms in plasma and the ratio of these two forms varies among individuals. This study was conducted to examine the influence of genetic polymorphism of SAA4 on its glycosylation status. In 55 healthy subjects, SAA4 polymorphism was analyzed by PCR combined direct sequencing and its glycosylation status was analyzed by immunoblotting. The results showed that the percentage of glycosylation in subjects with amino acid substitutions at positions 71 and/or 84 was significantly (P&lt 0.05) higher than that in subjects with the wild type. The polymorphism had no influence on the plasma concentration of SAA4. These findings suggest that the changes in protein structures alter the efficiency of glycosylation in the SAA4 molecule. The functional implication of this should be of interest. © 2014 Toshiyuki Yamada et al.

While oxidized lipoprotein(a) (oxLp(a)) has been indicated to be involved in atherogenesis more than native lipoprotein(a) (Lp(a)), there is still a need to elucidate the associations among oxLp(a), hypertension, and atherosclerosis. The cardio-ankle vascular index (CAVI) is a recently developed index used to assess arterial stiffness that is independent of blood pressure components. The present study investigated the correlation between oxLp(a) and the CAVI among hypertensive subjects. Clinical data, including general atherosclerotic risk factors, in addition to Lp(a), oxLp(a), and the CAVI, were collected from 72 non-smoking, asymptomatic, and untreated female subjects (mean age: 64.3 years). Correlations between the CAVI and Lp(a) or oxLp(a) were examined in a hypertensive group (n = 34) and a non-hypertensive control group (n = 38). There was a significant and positive correlation between the CAVI and subject age in the control group, while there was a significant and positive correlation between the CAVI and subject age, systolic blood pressure, and oxLp(a) (r = 0.38, p < 0.05) in the hypertensive group. A stepwise multiple linear regression analysis identified the oxLp(a) to be correlated independently, significantly, and positively with the CAVI (β = 0.30, p < 0.05) in the hypertensive group, while this correlation was not significant in the control group. These findings suggest that the oxidative modification of Lp(a) may be associated with arterial stiffness in hypertensive, but not non-hypertensive, female subjects.

Paraoxonase 1 (PON1) and serum amyloid A (SAA) are proteins carried by high-density lipoprotein (HDL) particles. Among the HDL-associated protein molecules, SAA, an inflammation-related marker, and PON1, an antioxidant marker, tend to change in relatively clear opposite directions in physiological situations. In clinical chemistry, paired measurements of both markers may provide useful information to understand dysfunctional HDL in diseases with inflammation and oxidative stress conditions. Actually, limited clinical studies have suggested that the combined use of PON1 and SAA may be a tool for observing the pathophysiology of some disease entities. From the findings of experimental studies, PON1 appears to be cooperatively regulated by inflammation- and oxidative stress-related molecules linked with SAA regulation in humans. More studies remain to be performed to ascertain the value of paired measurements of both promising markers in clinical practice.

Aim: The aim of this study was to investigate the relationship between atherosclerotic manifestations and brachial and radial arterial wall elasticity (AWE) measured using the phased tracking method in patients with type 2 diabetes mellitus (T2DM). Methods: This study included T2DM patients (n=220, mean age 59 years) without a history of stroke or coronary artery disease. The brachial AWE, radial AWE, carotid mean intima-media thickness (IMT), max-IMT and flow-mediated vasodilation (FMD) were measured. The patients were classified according to the number of atherosclerotic risk factors, including obesity, dyslipidemia and hypertension. Group 1 included T2DM patients only, group 2 included patients with two risk factors, group 3 included patients with three risk factors and group 4 included patients with four risk factors. The patients were also divided into two groups according to microangiopathic complications, including retinopathy and nephropathy. The between-group differences were analyzed. Results: The brachial AWE (548, 697, 755 and 771 kPa for groups 1, 2, 3 and 4, respectively) and radial AWE (532, 637, 717 and 782 kPa for groups 1, 2, 3 and 4, respectively) significantly increased in association with an increasing number of risk factors. The brachial AWE and radial AWE were significantly higher in the patients with microangiopathic complications than in those without microangiopathic complications (brachial AWE 797 and 694 kPa and radial AWE 780 and 660 kPa, respectively). Receiver operating characteristic curve analyses revealed that, for brachial AWE and radial AWE, the area under the curve was equal to the max-IMT and higher than the mean-IMT and FMD. Conclusions: Upper limb AWE measurement can reflect the degree of atherosclerosis risk overload and may be useful for evaluating vascular complications in T2DM patients.

Aim: Considering the beneficial effects of physical activity on health and disease in older people, the aim of the present study was to investigate the changes in reactive oxygen metabolites and paraoxonase 1 (PON1) activity during an intervention period on increased physical activity among older people. Methods: Serum diacron reactive oxygen metabolites (d-ROMs), PON1 activity and cardiometabolic variables were measured in 43 asymptomatic Japanese volunteers (18 men/25 women, mean age 68.9 years) in the pre- and post-phase of a 6-month intervention program aiming at a mild but sustained increase in physical activity. Results: While the d-ROMs and PON1 activity levels were not significantly altered after the intervention, there was an inverse correlation between percentage changes of d-ROMs and PON1 activity during this intervention period. Multiple regression analysis revealed their significant and inverse correlation as independent of percentage changes of the other cardiometabolic variables (β=-0.3, P &lt 0.05). Conclusions: The inverse d-ROMs-PON1 relationship may indicate the value of concurrent measurement of these two components of oxidation-antioxidation balance when studying the effects of physical activity in an older population. Further studies are necessary to confirm the observed relationship. © 2012 The Authors. Australasian Journal on Ageing © 2012 ACOTA.

Chronic inflammation has received a great deal of attention due to the role it plays in cardiovascular disease (CVD). The cardio-ankle vascular index (CAVI) has recently been developed to evaluate arterial stiffness. This index is independent of blood pressure at the time that it is measured, making it a better measure for clinical studies on the prevention of CVD. Information on the association of serum amyloid A (SAA) with arterial stiffness in relatively healthy subjects is still scarce. The aim of the present study was to investigate the potential correlation between SAA and CAVI in asymptomatic Japanese subjects. In addition to SAA and CAVI, data on smoking status, body mass index, blood pressure, and serum/plasma biochemical indices such as glucose and total cholesterol were collected in 387 nonmedicated and CVD-free adult subjects during a health check examination (male/female 191/196, mean age 61.8 years). Among them, a randomly selected subgroup of 256 subjects (male/female 133/123, mean age 62.4 years) had a full dataset, including low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and hemoglobin A1c. Among the whole population, CAVI levels were significantly higher in males than in females [mean 8.5 ± (SD 1.1) vs. 8.2 ± 1.1, p &lt 0.05], while SAA levels were slightly but nonsignificantly higher in females than in males [median 6.4 (interquartile range 4.0-9.3) μg/mL vs. 5.1 (3.5-8.4)]. In a multiple linear regression analysis, CAVI was weakly but significantly, independently, and positively correlated with SAA (β-coefficient 0.200, p &lt 0.01). The results of the same analyses for the randomly selected subgroup were relatively similar to the findings for the whole population. SAA may be a positive inflammatory factor associated with arterial stiffness, and the clinical relevance and the biological mechanism for this relationship should be established in future studies. © Springer 2011.

Background Oxidized high-density lipoprotein (oxHDL) has reduced capacity for cholesterol efflux and some of other anti-atherogenic properties of HDL, but the role of oxHDL in the pathogenesis of cardiometabolic disease has not been fully demonstrated. This study investigated the association of oxHDL with plasma glucose (PG) and the other atherosclerotic risk variables in non-diabetic dyslipidemic subjects. Methods Conventional atherosclerotic markers and LDL particle size (LDL-PS), as determined by gel electrophoresis, were measured in 155 non-diabetic subjects (mean age of 57 years) with dyslipidemia. Serum oxHDL levels were quantified using an antibody against oxidized human apoA-I in a sandwich ELISA format. Results Multiple regression analysis adjusted for possible confounders revealed that HDL-cholesterol was independently, significantly and positively correlated with LDL-PS and oxHDL. By multiple regression analysis, oxHDL was independently, significantly and positively correlated with fasting PG (β = 0.19, P = 0.01). Subjects in the highest PG tertile group had approximately 30% higher oxHDL levels than the lowest PG tertile group. Conclusions These results suggest that high PG levels may contribute to the HDL oxidation, irrespective of HDL-cholesterol levels, even in non-diabetic subjects with dyslipidemia, and that the measurement of oxHDL may be a useful marker of dysfunctional HDL.

Objective: Chronic inflammation and oxidative stress are associated with lifestyle-related diseases. Research into the pathophysiology of lifestyle-related diseases is important for Mongolian people. Our study investigated the correlation among the d-ROMs test (a measure of the total oxidant capacity of blood), serum amyloid A (SAA) and high-sensitivity C-reactive protein (hs-CRP) levels in a young Mongolian population. Methods: The data, including anthropometric and biochemical markers, were collected from 78 Mongolian volunteers (male/female = 27/51, mean age 21 years). The correlation between the SAA and d-ROMs levels was examined, as well as the correlation between the hs-CRP and d-ROMs levels. Results: The SAA levels were 3.2 μg/mL (median), hs-CRP .04 mg/dL (median) and d- ROMs 309 CARR U, respectively. There was a significant and positive correlation between the SAA and d-ROMs levels (r5.40, P&lt .01), in addition to a significant and positive correlation between the hs-CRP and d-ROMs levels (r5.32, P&lt .01). These significant correlations remained independent in a multiple linear regression analysis. A subgroup analysis by sex revealed the positive correlation between the SAA and d-ROMs levels to be greater, relative to that between the hs-CRP and d-ROMs levels, particularly in the female group. Conclusions: The coexistence of chronic inflammation and oxidative stress can be present even in young Mongolian people, suggesting that their coexistence may be a target of early prevention of lifestyle-related diseases. In addition, not only hs-CRP, but also SAA can be used to evaluate the relationship of oxidative stress in this population. Further studies are necessary to confirm the observed relationship.

Objective: The relationship among alcohol metabolism, lipid profile and cardiovascular disease has been a matter of concern, and aldehyde dehydrogenase-2 (ALDH2) is one of the key enzymes involved in alcohol metabolism. The frequency of ALDH2 gene G/A polymorphism (with the substitution of glutamic acid to lysine) varies widely among ethnic groups the polymorphism is prevalent among Asian people but rare in other ethnic groups. The objective of our study was to investigate the association between the ALDH2 gene G/A polymorphism and lipid profile, including the low-density lipoprotein cholesterol (LDL-C) status, in a general Japanese population with no or light-to-moderate alcohol drinking habits. Methods: Anthropometric and biochemical variables including lipid- and glucose-related factors were measured in a total of 383 Japanese participants (170 males and 213 females mean age, 45 ± 8.6 years), free of cardiovascular disease. All participants were genotyped by an allele-specific DNA assay. Results: The numbers of participants with the G/G, G/A and A/A genotypes were 213, 139 and 31, respectively. The percentages of hyper-LDL-cholesterolemia (identified by LDL-C ≥ 3.63 mmol/L) were 31.9%, 45.3% and 29.0% in participants with the G/G, G/A and A/A genotypes, respectively. Carrying the G/A + A/A genotype was a significant and positive factor related to hyper-LDL-cholesterolemia with an odds ratio of 1.62 (95% CI: 1.04-2.52) after adjusting for the other variables including drinking status. Conclusion: Our findings suggest that the ALDH2 gene G/A polymorphism can affect the lipid profile such as LDL-C status in this population. The association between the polymorphism and LDL-C status warrants further investigation.

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.