Age-related composition changes in swallowing-related muscles: a Dixon MRI study.

BACKGROUND: Dysphagia is considered a social problem in the super-aging society. However, age-related changes in swallowing-related muscles have not been fully deciphered. AIMS: We aimed to identify intramuscular fatty infiltration and muscle atrophy in multiple swallowing-related muscles on magnetic resonance imaging (MRI). Moreover, an appropriate muscle strength parameter for the evaluation of swallowing-related muscle mass was examined. METHODS: We analyzed the Dixon MRI results of 20 elderly and 20 young adults without head and neck cancer, stroke, neuromuscular disease, or whole-body sarcopenia to evaluate intramuscular fatty infiltration (IMF) and lean muscle mass (LMM) in the tongue, geniohyoid, and pharyngeal muscles. The pharyngeal lumen size was also assessed. Tongue pressure, jaw-opening strength, occlusal force, and head-lifting strength were evaluated within a week before and after MRI. RESULTS: Aging significantly affected the IMF of the swallowing-related muscles, and the tongue muscle was most affected, followed by the pharyngeal muscle and then the geniohyoid muscle. Only the LMM of the geniohyoid muscle significantly decreased with aging. The pharyngeal lumen size did not significantly differ between the elderly and young participants, and only tongue pressure was significantly correlated with tongue, geniohyoid, and pharyngeal muscle mass. CONCLUSIONS: IMF is primarily associated with age-related composition changes in swallowing-related muscles, and it is commonly observed in the tongue and pharyngeal muscles. The geniohyoid muscle is more at risk of muscle atrophy rather than fatty infiltration. In addition, tongue pressure can be a parameter for the evaluation of swallowing-related muscle mass.

Association Among Age-Related Tongue Muscle Abnormality, Tongue Pressure, and Presbyphagia: A 3D MRI Study.

Muscle aging such as sarcopenia adversely affects motor activities. However, few studies have elucidated the aging physiological mechanism of tongue concerted with the changes muscle composition. The present study aimed to examine the tongue composition changes to detect the effect of tongue fat mass on tongue pressure and swallowing function with aging. Twenty community-dwelling elderly without head and neck cancer, stroke, or neuromuscular disease and 20 healthy young were included. Tongue volume, tongue fat mass, tongue lean muscle mass, and tongue fat percentage were evaluated with 3D magnetic resonance imaging (MRI) and Dixon MRI. Tongue pressure was also measured. Swallowing function among elderly individuals was assessed via videofluorography, which was evaluated using the penetration-aspiration scale (PAS) and normalized residue ratio scale (NRRS). Tongue fat mass and tongue fat percentage significantly increased with aging. The tongue fat percentage of elderly participants was 20%, which was two times greater than that of young participants. No significant difference was observed in tongue volume and tongue lean muscle mass. A significantly negative correlation was observed between tongue fat mass and tongue fat percentage as well as tongue pressure. Conversely, tongue volume was not significantly correlated with tongue pressure. Tongue muscle composition exhibited no effect in the PAS and NRRS. Increase of fat mass is a major change in tongue composition with aging, which is associated with low tongue pressure. Thus, attention must be paid not only to tongue quantity but also to the quality of tongue muscles.

Verification of permeability for ionic liquid into biological specimens by using a mass spectrometer.

The pretreatment method with ionic liquids (ILs) is convenient for scanning electron microscope (SEM) observation of biological specimens. It needs neither fixation nor vacuum vapor deposition of metals to prevent fracture, deformation and charge-up. Although it was pointed out that the reason why the specimens are not fractured or deformed under the vacuum without fixation is the penetration of the ILs into cells and replacement with the intercellular water of the specimen, the experimental results were not yet self-consistent. In this study, in order to verify this hypothesis, we investigated whether the components of 1-ethyl-3-methylimidazolium methylphosphonate ([EMIM][MePO3]) are detectable by using a time-of-flight secondary ion mass spectrometer (TOF-SIMS) and liquid chromatography. It was found that the components of [EMIM][MePO3] could be detected from inside of the biological specimens. Moreover, it was verified that there is no fracture and deformation of the specimen, whose residual concentration of the IL on the surface would be less than the limit of detection by TOF-SIMS. Therefore, these experimental results explicitly show that penetration of [EMIM][MePO3] into the specimen and subsequent replacement with the intercellular water inside the body is the reason for preventing fracture and deformation of the specimen under the vacuum.

[A case of subacute necrotizing lymphadenitis with recurrent aseptic meningitis associated with persistent high titer of anti-nuclear antibody occurring over a short period of time].

A 35-year-old woman developed recurrent aseptic meningitis three times over a period of 16 months. Each episode followed swelling of her cervical lymph nodes. During the third episode, microscopic findings of biopsied specimens from a cervical lymph node indicated subacute necrotizing lymphadenitis (SNL). While she responded poorly to NSAIDs, steroids rapidly improved her fever, headache and swollen lymph nodes. Since the first episode, anti-nuclear antibody (ANA) and anti-SS-A antibody was positive and the titer of ANA increased with each episode. SNL is a benign and self-limited disease, and the appearance of autoantibodies is usually transient. It is possible that a persistent immune abnormality is related to recurrences of aseptic meningitis with SNL.

Short-time pretreatment of wood with low-concentration and room-temperature ionic liquid for SEM observation.

A new pretreatment method using room-temperature ionic liquid (IL) was proposed for observing wood specimens in scanning electron microscopy (SEM). A variety of concentrations were examined for ethanol solution of the IL, [Emim][MePO3Me], to determine an optimal pretreatment procedure. It was concluded that 10% ethanol solution of the IL was the most adequate to acquire good SEM images. Using the procedure optimized, SEM images were taken for typical anatomical types of modern soft and hardwood species and archeological wood. SEM images taken were sufficiently good in observing wood cells. The pretreatment method was also effective to archeological wood dated ca. 1600 years ago. It was thus concluded that the method developed in this study is more useful than those conventionally used. Additionally, pretreatment at the high temperature was performed to confirm morphological changes in softwood. Deformation of latewood cells (tracheids) was occurred by treating with undiluted IL at the high temperature of 50°C, probably due to higher accessibility of the IL into intercellular space. Nonetheless, it was confirmed that this happens under far more extreme conditions than our proposed method.

Muscle mass, visceral fat, and plasma levels of B-type natriuretic peptide in healthy individuals (from the J-SHIPP Study).

A paradoxical negative association between obesity and the plasma B-type natriuretic peptide (BNP) level has been firmly established. An individual's fat mass increases and muscle mass decreases with aging. Because aging is a potent determinant of plasma BNP levels, BNP may be related not only to fat mass but also to muscle mass. However, no studies have evaluated the associations between body composition and plasma levels of BNP. We performed a cross-sectional study to investigate these associations in 1,431 apparently healthy middle-aged to elderly subjects. The abdominal visceral fat area and thigh muscle cross-sectional area (CSA) were quantified by computed tomography. Plasma adiponectin and leptin levels were measured as possible confounding parameters. The brachial-ankle pulse wave velocity was measured as an index of arterial stiffness, and the pulse pressure (PP) of the second peak of the radial systolic blood pressure waveform (PP2) was used as an estimate of the central PP. Plasma BNP levels were significantly and negatively associated with the visceral fat area (r = -0.13, p <0.0001) and thigh muscle CSA (r = -0.25, p <0.0001). Corrections with possible confounding parameters including age, gender, heart rate, mean blood pressure, body weight, body height, adiponectin, leptin, brachial-ankle pulse wave velocity, and PP2 eliminated the association of BNP with visceral fat area but not with thigh muscle CSA (ß = -0.27, p <0.0001). These findings indicate that along with adiposity, muscle mass is an independent determinant of plasma BNP.

Clinical characteristics of high plasma adiponectin and high plasma leptin as risk factors for arterial stiffness and related end-organ damage.

OBJECTIVE: The relationship between plasma levels of adiponectin and cardiovascular events is inconclusive. We evaluated the clinical characteristics of people with high plasma adiponectin and high plasma leptin levels. METHODS: Thousand seven hundred participants recruited from visitors to the Anti-Aging Doc were divided into four groups by combining the bipartiles of plasma adiponectin and leptin levels in men and women separately: AL, high adiponectin and high leptin; Al, high adiponectin and low leptin; al, low adiponectin and low leptin; aL, low adiponectin and high leptin. Body composition, including visceral fat area and thigh muscle cross-sectional area (CSA), brachial-ankle pulse wave velocity (baPWV), periventricular hyperintensity, and urinary albumin excretion, were determined. RESULTS: Twenty percent of the studied population fell within the AL group. This group had a significantly higher visceral fat area than the Al group. Thigh muscle CSA was lowest in the AL group among groups. baPWV, brain white matter lesions, and albuminuria findings in the AL group were significantly higher than those of the Al group. Multiple and logistic regression analyses with confounding parameters further confirmed that plasma adiponectin was not an independent determinant for brain and renal small vessel-related disease. CONCLUSION: These findings suggest that the plasma level of adiponectin alone is not enough for the risk stratification of cardiovascular disease. Leptin resistance associated with skeletal muscle loss in addition to obesity may need to be addressed to identify high risk people with high plasma adiponectin levels.

Establishment of a novel murine model of ischemic cardiomyopathy with multiple diffuse coronary lesions.

OBJECTIVES: Atherosclerotic lesions of the coronary arteries are the pathological basis for myocardial infarction and ischemic cardiomyopathy. Progression of heart failure after myocardial infarction is associated with cardiac remodeling, which has been studied by means of coronary ligation in mice. However, this ligation model requires excellent techniques. Recently, a new murine model, HypoE mouse was reported to exhibit atherogenic Paigen diet-induced coronary atherosclerosis and myocardial infarction; however, the HypoE mice died too early to make possible investigation of cardiac remodeling. Therefore, we aimed to modify the HypoE mouse model to establish a novel model for ischemic cardiomyopathy caused by atherosclerotic lesions, which the ligation model does not exhibit. METHODS AND RESULTS: In our study, the sustained Paigen diet for the HypoE mice was shortened to 7 or 10 days, allowing the mice to survive longer. The 7-day Paigen diet intervention starting when the mice were 8 weeks old was adequate to permit the mice to survive myocardial infarction. Our murine model, called the "modified HypoE mouse", was maintained until 8 weeks, with a median survival period of 36 days, after the dietary intervention (male, n = 222). Echocardiography demonstrated that the fractional shortening 2 weeks after the Paigen diet (n = 14) significantly decreased compared with that just before the Paigen diet (n = 6) (31.4±11.9% vs. 54.4±2.6%, respectively, P<0.01). Coronary angiography revealed multiple diffuse lesions. Cardiac remodeling and fibrosis were identified by serial analyses of cardiac morphological features and mRNA expression levels in tissue factors such as MMP-2, MMP-9, TIMP-1, collagen-1, and TGF-ß. CONCLUSION: Modified HypoE mice are a suitable model for ischemic cardiomyopathy with multiple diffuse lesions and may be considered as a novel and convenient model for investigations of cardiac remodeling on a highly atherogenic background.

Deletion of progranulin exacerbates atherosclerosis in ApoE knockout mice.

AIMS: Progranulin (PGRN) is a multifunctional protein known to be involved in inflammation. However, the relation between PGRN and atherosclerosis remains elusive. The aim of this study was to define the role of PGRN in the development of atherosclerosis. METHODS AND RESULTS: First, we checked the expression levels of PGRN in human atherosclerotic plaques. Immunohistochemical analysis showed that PGRN is strongly expressed in foam cells of atherosclerotic plaques. We also found that PGRN is expressed more abundantly in macrophages than in the smooth muscle cells of atherosclerotic lesions in ApoE(-/-) mice fed a high-fat diet for 12 weeks. Next, PGRN(-/-)ApoE(-/-) mice were generated to investigate the effect of PGRN on the development of atherosclerosis. PGRN(-/-)ApoE(-/-) mice exhibited severe atherosclerotic lesions compared with PGRN(+/+)ApoE(-/-) mice, despite their anti-atherogenic lipid profile. These results are partly due to enhanced expression of inflammatory cytokines, adhesion molecules, and decreased expression of endothelial nitric oxide synthase. In addition, lack of PGRN leads to accumulate excessive cholesterol in the macrophages and alter HDL-associated proteins. CONCLUSION: PGRN seems to be involved in the pathogenesis of atherosclerosis, possibly by various anti-atherogenic effects, including modulation of local and/or systemic inflammation.

[A case of myositis associated with clonal expansion of γδ T cells in peripheral blood and bone marrow].

We report a 45-year-old man with myositis associated with clonal expansion of γδ T cells. He was referred to our hospital because of slowly progressive (over 10 years) muscle weakness. On neurological examination, weakness and muscle atrophy were noted in the proximal upper and lower limbs. The level of creatinine kinase (CK) was 1,436 U/L. Neutropenia and monoclonal gammopathy were found in the peripheral blood. Flow cytometric analysis of peripheral blood and bone marrow revealed proliferation of CD3(+)CD4(-)CD8(+) and CD3(+)CD4(-)CD8(-) γδ T cells, and Southern blotting demonstrated a clonally rearranged T-cell receptor Jγ gene in peripheral blood and bone marrow. A biopsy of the right quadriceps muscle showed variations in muscle fiber size, and endomysial mononuclear cell infiltration. The expression of MHC Class I antigen was increased on the surfaces of most of muscle fibers, and TCRδ1 positive-lymphocytes invaded nonnecrotic muscle fiber. After starting treatment with cyclosporin A and steroids, his muscle weakness gradually ameliorated, the CK level decreased and neutrophils increased. Although reports of myositis associated with clonal expansion of γδ T cells are extremely rare, the present case suggests that γδ T cells might play a role in mediating myositis.

Patients with CD36 deficiency are associated with enhanced atherosclerotic cardiovascular diseases.

AIM: The clustering of dyslipidemia, impaired glucose tolerance and hypertension increases the morbidity and mortality from cardiovascular events. A class B scavenger receptor, CD36, is a receptor for oxidized LDL and a transporter of long-chain fatty acids. Because of the impaired uptake of oxidized LDL in CD36-deficient macrophages and from the results of CD36 knockout mice, CD36 deficiency (CD36-D) was supposed to be associated with reduced risks for coronary artery disease (CAD); however, CD36-D patients are often accompanied by a clustering of coronary risk factors. The current study aimed to investigate the morbidity and severity of cardiovascular diseases in CD36-D patients. METHODS: By screening for CD36 antigen on platelets and monocytes using FACS or the absent myocardial accumulation of 123I-BMIPP by scintigraphy, 40 patients with type I CD36-D were collected, the morbidity of CAD and their features of atherosclerotic cardiovascular diseases were observed. Screening for CD36-D in both CAD patients (n = 319) and healthy subjects (n = 1,239) were underwent. RESULTS: The morbidity of CAD was significantly higher in CD36-D patients than in the general population; 50% of patients (20 out of 40) had CAD identified by BMIPP scintigraphy and 37.5% (3 out of 8) by FACS screening, respectively. Three representative CD36-D cases demonstrated severe CAD and atherosclerosis. The frequency of CD36-D was three times higher in CAD patients than in healthy subjects (0.9% vs 0.3%, p < 0.0001). CONCLUSION: The morbidity of CAD is significantly higher in CD36-D patients suffering from severe atherosclerosis, implying that the status of CD36-D might be atherogenic.

Apolipoprotein B-48 to triglyceride ratio is a novel and useful marker for detection of type III hyperlipidemia after antihyperlipidemic intervention.

AIM: Remnant lipoproteins are atherogenic and are accumulated in patients with type III hyperlipidemia (HL). Although type III HL is diagnosed by phenotyping apolipoprotein (apo) E, this procedure is time-consuming and inconvenient for routine clinical use. Clinical indices for screening type III HL in untreated HL patients have been proposed; however, in clinical settings, HL patients are promptly treated with lipid-lowering agents without diagnosing the underlying cause. We investigated whether existing clinical indices for screening type III HL as well as the apo B-48/triglyceride (TG) ratio, which was suggested to be related to the accumulation of small chylomicron (CM) remnants, are useful after the initiation of lipid-lowering therapies. METHODS: In 25 normolipidemic subjects and 191 treated HL patients (type I, n =6; IIa, 62; IIb, 66; III, 12; IV, 22; and V, 23) from Osaka University Hospital and related hospitals, fasting low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TG, and apolipoproteins were measured and clinical indices were evaluated statistically. RESULTS: Apo B-48 levels were significantly higher in patients with type I, III, and V HL, and TG levels were significantly higher in patients with type I and V HL. The apo B-48/TG ratio was significantly higher only in patients with type III HL compared with other types of HL (p<0.001), and was statistically significant among the other clinical indices (AUC-ROC value, 0.895; cut-off value, 0.110). CONCLUSION: The apo B-48/TG ratio is a novel and useful marker for detecting type III HL even after the initiation of lipid-lowering interventions.

Establishment of chemiluminescence enzyme immunoassay for apolipoprotein B-48 and its clinical applications for evaluation of impaired chylomicron remnant metabolism.

BACKGROUND: Apolipoprotein B-48 (apoB-48) is a constituent of chylomicron remnants synthesized in the small intestines. The serum concentration of apoB-48 at fasting has been reported to be a marker of postprandial hyperlipidemia, a presumed risk factor for atherosclerosis. METHODS: We evaluated the basal performance of a recently developed chemiluminescent enzyme immunoassay (CLEIA). We also examined the correlations between serum apoB-48 concentrations and other lipid concentrations or life style patterns, including smoking and drinking. We analyzed the data of 273 clinical samples by multiple regression analysis to examine the influence of other serum lipid values, age, sex, smoking, drinking status and BMI on serum apoB-48 values. RESULTS: Within-run and between-run precision was obtained with 1.7-2.7% and 1.2-7.3%, respectively. The correlativity of enzyme-linked immunosorbent assay was correlation coefficient r=0.953, and regression y=1.02×-1.59. Serum apoB-48 concentrations were higher in males than in females, and were correlated with the status of smoking as well as with remnant-like particle-cholesterol (RLP-C) concentrations. Patients with the metabolic syndrome showed higher values of serum apoB-48 compared with control subjects. CONCLUSION: Serum apoB-48 measurement by CLEIA was satisfactory for clinical use to assess abnormalities in the chylomicron remnant metabolism.

Serum adiponectin level is correlated with the size of HDL and LDL particles determined by high performance liquid chromatography.

OBJECTIVE: Adiponectin (APN) improves insulin resistance and prevents atherosclerosis, and HDL removes cholesterol from atherosclerotic lesions. We have demonstrated that serum HDL-cholesterol (HDL-C) and APN concentrations are positively correlated and that APN accelerates reverse cholesterol transport (RCT) by increasing HDL synthesis in the liver and cholesterol efflux from macrophages. We previously reported that APN reduced apolipoprotein (apo) B secretion from the liver. It is well-known that insulin resistance influences the lipoprotein profile. In this study, we investigated the clinical significance of APN levels and insulin resistance in lipoprotein metabolism. MATERIAL/METHOD: We investigated the correlation between serum APN concentration, HOMA-R, the lipid concentrations and lipoprotein particle size by high-performance liquid chromatography (HPLC) in 245 Japanese men during an annual health checkup. RESULTS: Serum APN level was positively correlated with the cholesterol content in large LDL and HDL particles, but inversely correlated with the cholesterol content in large VLDL and small LDL particles. HOMA-R was negatively correlated with the cholesterol content in large LDL and HDL particles and positively correlated with the cholesterol content in large VLDL and small LDL particles. By multivariate analysis, APN was correlated with the particle size of LDL-C and HDL-C independently of age, BMI and HOMA-R. CONCLUSIONS: APN may be associated with the formation of both HDL and LDL particles, reflecting the enhancement of RCT and the improvement in TG-rich lipoprotein metabolism and insulin resistance.

Serum apolipoprotein B-48 levels are correlated with carotid intima-media thickness in subjects with normal serum triglyceride levels.

BACKGROUND: Postprandial hyperlipidemia (PPHL) is an independent risk factor for coronary heart disease (CHD) which is based on the accumulation of chylomicrons (CM) and CM remnants containing apolipoprotein B-48 (apoB-48). Since atherosclerotic cardiovascular diseases are frequently observed even in subjects with normal serum triglyceride (TG) level, the correlation between fasting apoB-48 containing lipoproteins and carotid intima-media thickness (IMT) was analyzed in subjects with normal TG levels. METHODS: From subjects who took their annual health check at the Osaka Police Hospital (n=245, male), one-hundred and sixty-four male subjects were selected to take part in this study; the excluding factors were: systolic blood pressure ≥ 140 mmHg, intake of antihypertensive or antihyperlipidemic drugs, or age >65 years. The association between biochemical markers and IMT was analyzed and independent predictors of max-IMT were determined by multiple regression analysis in all subjects and in groups N-1 (TG<100mg/dl, n=58), N-2 (100 ≤ TG<150 mg/dl, n=53) and H (150 ≤ TG mg/dl, n=53), respectively. RESULTS: Fasting total cholesterol, LDL-cholesterol, HDL-cholesterol, apoB-100 and lnRemL-C (remnant lipoprotein-cholesterol) levels were not correlated with max-IMT, but lnTG and lnapoB-48 were significantly correlated with max-IMT in all subjects. LnapoB-48 and apoB-48/TG ratio were significantly correlated with max-IMT in group N-2. By multiple regression analysis, age and lnapoB-48 were independent variables associated with max-IMT in group N-2. CONCLUSION: Serum apoB-48 level might be a good marker for the detection of early atherosclerosis in middle-aged subjects with normal-range levels of blood pressure and TG.

Fasting serum apolipoprotein B-48 can be a marker of postprandial hyperlipidemia.

AIM: Postprandial hyperlipidemia (PH) is thought to be caused by the impaired postprandial metabolism of triglycerides (TG)-rich lipoproteins in both endogenous and exogenous pathways; however, there is no consensus. It is difficult to estimate the presence of PH without performing a time-consuming oral fat loading (OFL) test, so postprandial lipoprotein metabolism was analyzed by measuring the postprandial levels of apolipoprotein (apo) B-48 and apo B-100, and the correlation between postprandial TG increase and fasting apoB-48 levels was assessed to establish a good marker of PH without performing an OFL test. METHODS: Ten male normolipidemic subjects were loaded with a high-fat (HF, 1045 kcal) or standard (ST, 566 kcal) meal, and the lipids, apolipoproteins and lipoprotein profiles were analyzed after each meal. RESULTS: TG, apo B-48, remnant-like particles (RLP)-cholesterol and RLP-TG levels were increased and their levels were significantly higher after intake of the HF meal than the ST meal; however, there was no postprandial increase in apo B-100 and LDL-C levels. Postprandial increases in TG levels of CM, VLDL, LDL and HDL were significantly higher after intake of the HF meal than the ST meal. Fasting apo B-48 levels were strongly correlated with the incremental area under the curve of TG after intake of the HF meal, but not the ST meal. CONCLUSION: Postprandial TG increase was mainly due to increased CM and CM-R, but not VLDL. Measurement of fasting serum apo B-48 may be a simple and useful method for assessment of the existence of PH.

Combination of serum adiponectin level and metabolic syndrome is closely associated with coronary artery disease in Japanese subjects with good glycemic control.

OBJECTIVE: Metabolic syndrome (MetS) and decreased adiponectin level have been reported to be clinically associated with type 2 diabetes mellitus and coronary artery disease (CAD). However, it has not been fully defined whether they are associated with the severity of CAD, independent of hyperglycemia. In the current study, we investigated the clinical relationship between serum adiponectin level and MetS, and its association with the severity of CAD in patients with good glycemic control. PATIENTS AND METHODS: In this study, we enrolled 97 subjects with an HbA1c concentration of < 7.0% (5.5+/-0.6%), who underwent coronary angiography. We measured serum adiponectin levels and various metabolic variables, and assessed the severity of CAD by angiography. RESULTS: Multivariate analysis revealed that the number of MetS components was not correlated with adiponectin level, despite their significant correlation in the univariate analysis. Low adiponectin levels (< 4.5 microg/mL) or > or = 3 of 5 MetS components showed significant association with the severity of CAD (adiponectin, p=0.002; MetS, p=0.049). The correlation of adiponectin levels (divided by tertiles or quartiles) with the severity of CAD was not significant after adjustment for age and gender. On the other hand, two models of combined scores from adiponectin levels and the number of MetS components showed a significant correlation with the severity of CAD even after adjustment for age and gender (model 1, p=0.023; model 2, p=0.018). CONCLUSION: Our findings suggest that the combination of adiponectin levels and the number of MetS components is linked to the severity of CAD in subjects with good glycemic control.