Biomedical subjects
Publications and source records attributed to Akira Matsunaga.
We describe a case of 57-year-old man who presented with acute myocardial infarction (AMI) and heart failure with rapid progression of cardiomegaly. Cardiac multislice computed tomography and echocardiography showed the ventricular pseudoaneurysm, probably due to cardiac free wall rupture caused by AMI. Cardiac CT is another useful tool for the non-invasive diagnosis of cardiac rupture.
BACKGROUND: The present study examined the effects of atorvastatin and the in vitro effect of apolipoprotein (apo) A-I/phosphatidylcholine (POPC) discs on charge-based triglyceride-rich lipoprotein (TRL) subfractions in a patient with type III hyperlipoproteinemia (HLP) and the apoE2/2 phenotype. METHODS: Charge-based lipoprotein subfractions were characterized by capillary isotachophoresis (cITP). cITP analysis was performed using plasma that had been prestained with a lipophilic dye on a Beckman P/ACE MDQ system. RESULTS: Treatment with atorvastatin for 4 weeks markedly decreased the slow (s)-migrating TRL subfraction and both fast- and slow-migrating low-density lipoprotein (LDL) subfractions, but did not affect the fast (f)-migrating TRL subfraction in this patient. ApoA-I/POPC discs consisted of two major charge-based subfractions that had the mobility of cITP fTRL and sTRL. Incubation of plasma from this patient in the presence of apoA-I/POPC discs caused not only a reduction in cITP fast- and intermediate-migrating HDL and an increase in cITP sHDL but also a reduction in fTRL and sTRL and an increase in sLDL. CONCLUSION: Atorvastatin and apoA-I/POPC discs decreased cITP TRL subfractions in a complementary manner, suggesting that the combination of apoA-I/POPC discs and atorvastatin could be a promising therapeutic approach for hypertriglyceridemia.
PURPOSE: We assessed the effects of a neutrophil elastase inhibitor, sivelestat, on respiratory and organ functions as well as on the mortality of patients with acute respiratory distress syndrome (ARDS) associated with systemic inflammatory response syndrome (SIRS). METHODS: We retrospectively divided 25 patients who fulfilled the diagnostic criteria for SIRS and ARDS into two groups. One group (S group, n = 12) received a continuous infusion of sivelestat (0.2 mg.kg(-1).h(-1)), and the other did not (C group, n = 13). RESULTS: Between days 1 and 10, the Pa(O2)/FI(O2) ratio in the S group significantly improved from 119.1 +/- 51.1 to 214.4 +/- 88.2 mmHg (P < 0.05). Furthermore, the S group spent significantly fewer days on a ventilator than the C group (16.7 +/- 5.8 vs 26.6 +/- 14.3 days; P < 0.05). The length of the intensive care unit stay was also significantly shorter for the S group than for the C group (18.7 +/- 4.9 vs 27.5 +/- 13.5 days; P < 0.05). However, the mortality rate at 29 days did not statistically differ between the two groups. CONCLUSION: Our results suggested that sivelestat has a beneficial effect only on the pulmonary function of ARDS patients with SIRS.
OBJECTIVES: Durability remains the main problem of all bioprosthetic valves, and calcification is the major cause of failure. New tissue treatment processes are expected to reduce mineralization. A comparative animal study was undertaken to evaluate the behavior of a new-generation porcine bioprosthesis in contrast with a first-generation porcine bioprosthesis. The primary goal was to evaluate the efficacy of alpha-amino-oleic acid as an anticalcification treatment. METHODS: Seventeen Targhee sheep (aged 4.5-7 months) had a mitral valve replacement with a Mosaic or Hancock Standard. The animals were followed up to 20 weeks (144.1 +/- 4.0 days vs 144.3 +/- 8.2 days) and then euthanized as scheduled. After gross examination, the explants were radiographed for the presence of calcification. The central portions were preserved for histologic examination, and the remainder of the sample was analyzed for quantitative calcium content by atomic absorption spectroscopy. RESULTS: Four Mosaic sheep were excluded because of perioperative surgical mortality. The remaining 13 were enrolled in the study (9 Mosaic and 4 Hancock Standard). The mean calcium content was 1.97 +/- 2.21 microg/mg tissue weight for Mosaic versus 8.36 +/- 4.12 microg/mg for Hancock Standard valves (P < .01). Mild fibrous tissue overgrowth and fibrinous lining were observed regardless the xenograft type. CONCLUSIONS: The low level of calcification in the Mosaic versus Hancock Standard xenografts confirms the efficacy of alpha-amino-oleic acid treatment in mitigating mineralization. A longer durability is expected with the clinical use of the Mosaic porcine valve.
Lipoprotein glomerulopathy (LPG) is a unique entity of renal lipidosis characterized by peculiar histopathologic characteristics of lipoprotein thrombi and an abnormal plasma lipoprotein profile resembling type III hyperlipoproteinemia, with a marked increase in serum apolipoprotein E (apoE) concentrations. At present, 65 cases have been reported worldwide, although most patients are found in Japan and east Asian countries. Recently, we identified 4 types of novel apoE mutations associated with LPG. In particular, a mutation designated apoE Sendai, in which arginine 145 is substituted with proline, occurs in the majority of Japanese patients. The virus-mediated transduction of apoE Sendai resulting in the development of LPG in apoE-deficient mice confirms the etiologic role of apoE mutation in LPG. Conversely, experimental graft-versus-host disease induced in Fc receptor gamma-chain-deficient mice showed LPG-like lesions in glomeruli without apoE mutations. Considered together, we believe that intrinsic factors in the kidney also contribute to the induction of LPG. Today, apoE and related lipid abnormalities are reported to have an important role in the development of various renal diseases, eg, diabetic nephropathy and immunoglobulin A nephropathy. In this article, we review clinical and histopathologic features of LPG, describe the etiologic role of apoE variants and intrinsic renal factors, and discuss the impact of LPG on mechanisms of other renal diseases.
BACKGROUND: The coronary artery calcification (CAC) score measured by multidetector row computed tomography (MDCT) has emerged as a marker for predicting coronary artery disease (CAD). To evaluate the clinical significance of the CAC score, coronary artery stenosis as assessed by coronary angiography (CAG) was compared with the CAC score determined by MDCT, risk factors and medications. METHODS AND RESULTS: Subjects included 374 consecutive patients who underwent ECG-gate CT angiography using MDCT. The accuracy in patients with a CAC score >or=400 was 84%, and significantly lower than that in patients with a CAC score =0. In addition 92 patients (68 males, 24 females; mean age, 63+/-11 years) who underwent both MDCT and CAG within a 1-month period were selected for further investigation. Patients with significant coronary stenosis had a significantly higher CAC score than those without stenosis. In addition, a higher number of stenosed vessels was associated with a higher CAC score. The subjects were divided into 3 groups according to the CAC score: low (0-12), intermediate (13-444) and high (>or=445). The CAC score was significantly associated with age, and plasma levels of total cholesterol and hemoglobinA1c, and logistic regression analysis revealed that significant coronary stenosis as assessed by CAG was most closely correlated with the CAC score (p=0.03). CONCLUSIONS: The CAC score determined by MDCT can predict CAD independent of other factors, such as age, metabolic diseases and medications, when coronary stenosis can not be diagnosed because of severe calcification.
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BACKGROUND: A mildly modified LDL subfraction that is characterized by an increased negative charge exists in plasma. This electronegative LDL separated by ion-exchange chromatography has been shown to be inflammatory and its proportion is increased in patients with hyperlipidemia and diabetes mellitus. The present study examined the association between the level of fast (f)-migrating LDL subfraction characterized by capillary isotachophoresis (cITP) and carotid-artery intima-media thickness (CA-IMT). METHODS AND RESULTS: This study included 469 subjects who underwent a physical examination. CA-IMT was determined by high-resolution B-model ultrasonoraphy. Levels of charge-based LDL subfractions were measured by cITP on a Beckman P/ACE MDQ system. An increased serum LDL-C level and cITP fLDL level were associated with increased CA-IMT after adjusting for age. The extent of the associations between cITP fLDL and CA-IMT and between LDL-C and CA-IMT were similar as assessed by a receiver-operating characteristic curve analysis. LDL-C, triglyceride, and remnant-like particle cholesterol levels were independently correlated with cITP fLDL, and the LDL-C level had the strongest correlation with cITP fLDL. The association between the cITP fLDL level and CA-IMT was significant in the high LDL-C stratum but not in the low stratum, indicating that it is modified by the LDL-C level. The high-LDL-C-high-fLDL group had the highest relative risk for a high CA-IMT among the groups with each combination of LDL-C and cITP fLDL level. CONCLUSION: The cITP fLDL level was associated with CA-IMT and its combination with the LDL-C level is a stronger indicator for a high CA-IMT.
BACKGROUND: Platelet-activating factor acetylhydrolyse (PAF-AH) is an enzyme that degrades PAF and bioactive oxidized lipids. However, it has been reported to be a risk factor for coronary heart disease. The present study examined the effects of cholesterol feeding and simvastatin treatment on plasma PAF-AH activity. METHODS: Japanese White rabbits (n=22) were fed a diet containing 0.3% cholesterol and 3% corn oil for 1 month, and then divided into two groups that continued to receive this diet with (treated) or without (control) treatment with simvastatin (0.01%) for another 2 months. RESULTS: Cholesterol feeding increased and simvastatin treatment decreased apolipoprotein (apo) B-containing lipoprotein subfractions as characterized by capillary isotachophoresis, serum levels of total cholesterol, phospholipids, LDL-C, apoE, plasma and LDL-associated PAF-AH (LDL-PAF-AH) activities, and plasma lyso-PC concentration. Cholesterol feeding also increased apoB levels but decreased the LDL-PAF-AH/LDL-C ratio and did not change the plasma PAF-AH/lyso-PC ratio. Simvastatin treatment did not affect apoB levels and only slightly increased the LDL-PAF-AH/LDL-C ratio. Secretion of PAF-AH activity from monocyte-derived macrophages was increased by cholesterol feeding but not affected by simvastatin treatment. These results indicate that PAF-AH activity is increased by cholesterol feeding due to increased secretion of PAF-AH activity from macrophages and that PAF-AH activity is decreased by simvastatin due to increased removal of lipid and enzyme contents of LDL particles. CONCLUSION: Cholesterol elevation by cholesterol feeding and cholesterol-lowering by simvastatin modulate plasma PAF-AH activity by different mechanisms.
BACKGROUND: Despite correction of left-sided cardiac lesions, associated functional tricuspid regurgitation (TR) that was surgically ignored can persist. It can also appear de novo. The aim of this study was to analyze TR in a group of patients who underwent successful revascularization and mitral valve repair (MVRep) for functional ischemic mitral regurgitation (MR). METHODS AND RESULTS: Among 124 consecutive patients with MVRep, 70 left the operating room with MR < or =1+ and had a preoperative and follow-up transthoracic echocardiograph. Moderate or greater MR or TR was considered significant. Twenty-one patients (30%) had TR before surgery, and only 9 had TR repaired. The postoperative incidence of residual TR was not significantly different whether the tricuspid valve had been repaired (4 of 9 [44%]) or surgically ignored (8 of 12 [67%]). At last follow-up, 34 patients (49%) had significant TR. The incidence of TR increased from 25% at <1 year to 53% between 1 and 3 years and 74% at >3 years. Absence or presence of recurrent MR did not significantly affect TR (14 of 22 [64%] with MR versus 20 of 48 [42%] with no MR). Preoperative and postoperative tricuspid annulus size in patients with late TR was significantly larger than in patients without TR. CONCLUSIONS: Functional TR is frequently associated with functional ischemic MR. After MVRep, close to 50% of patients have TR. The incidence of postoperative TR increases with time. Preoperative tricuspid annulus dilation might be a predictor of late TR.
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BACKGROUND: The potency and usefulness of capillary isotachophoresis (cITP) for assessing whole-serum lipoprotein profiles and quantifying electronegative low-density lipoprotein (LDL) has been previously reported. METHODS AND RESULTS: A new cITP method to measure electronegative LDL in the small dense LDL fraction has been established. Both electronegative LDL and electronegative LDL in the small dense LDL fraction decreased after treatment with fenofibrate. CONCLUSIONS: This method appears to be useful for analyzing a marker of coronary heart disease risk and may be suitable for evaluating the effects of hypolipidemic agents.
We examined the histochemical characteristics of soleus muscle in the angiotensin-converting enzyme (ACE) gene (Ace in mice, ACE in humans) knockout mice. Serial sections of soleus muscle of wild-type (Ace+/+, n=20) and heterozygous mutant (Ace+/-, n=24) mice were stained for myosin adenosine triphosphatase activity to identify different muscle fiber types. Capillaries were visualized by amylase-periodic acid-Schiff staining. ACE activity in the serum and gastrocnemius muscle was higher in male mice than in female mice. Female and male Ace+/- mice had markedly lower ACE activity in the serum and the gastrocnemius muscle than did female and male Ace+/+ mice, respectively. In both male and female mice, the composition of fiber types (type I and IIa) did not differ significantly between Ace+/+ and Ace+/- mice. There was no significant gender difference in capillary density. Ace+/- mice had significantly more capillaries around type IIa fibers (5.44 +/- 0.18 vs. 5.01 +/- 0.13, p<0.05) than Ace+/+ mice. The differences in the number of capillaries around type I fibers and in the number of capillaries around per fiber (capillary:fiber ratio) between Ace+/- and Ace+/+ mice were not significant (p<0.1). There was no significant difference in the mean cross-sectional area occupied by one capillary and the number of capillaries per fiber area between Ace+/+ and Ace+/- mice. In conclusion, knockout of the Ace gene in mice increased capillary density, as expressed by the mean number of capillaries around type IIa fibers. This finding suggests a possible mechanism for the cardioprotective effects of ACE inhibitors.
This study compared the effects of fluvastatin and pravastatin on the in vivo oxidation of LDL in a crossover design to evaluate whether or not it is justified to switch between the two statins with regard to serum levels of lipids, lipoproteins, and apolipoproteins (apo), and circulating autoantibodies to oxidized LDL (OxLDL-Ab). Patients with hypercholesterolemia (n = 46) were randomly assigned into groups who received fluvastatin (20 mg/d) or pravastatin (10 mg/d). After 3 months, they were crossed to receive the other statin for another 3 months. Circulating levels of OxLDL-Ab were measured by an OxLDL IgG ELISA test. Fluvastatin and pravastatin similarly decreased serum levels of total cholesterol (TC), LDL-C, and apo B, and increased HDL(2)-C levels. After crossover to the other statin, these lipid parameters were not further changed by either statin. Before crossover, circulating levels of OxLDL-Ab were decreased in patients with fluvastatin treatment, but not in those with pravastatin treatment. After switching from the other statin, both fluvastatin and pravastatin further decreased OxLDL-Ab levels. In conclusion, fluvastatin at 20 mg/d and pravastatin at 10 mg/d are similar with regard to their efficacy in decreasing TC, LDL-C, and apo B levels and increasing HDL(2)-C levels. Fluvastatin lowered circulating levels of OxLDL-Ab, and these effects continued after switching to pravastatin.
BACKGROUND AND AIM OF THE STUDY: Mitral valve (MV) repair is generally accepted as the preferred treatment of mitral regurgitation (MR) with MV prolapse secondary to myxomatous mitral valve disease (MMVD). However, the incidence of successful valve repair is variable between hospitals and among different surgeons at one hospital, and often results in needless MV replacement. The study aim was to measure the impact of a dedicated echocardiography/surgery team on MV repair at a community hospital. METHODS: The outcome was analyzed of a group of 116 consecutive patients with severe MR secondary to MMVD who underwent surgery by the same surgeon over a six-year period. A dedicated team approach, comprising one echocardiographer and one surgeon was established in January 1999. The results of MV repair between 1996 and 1998 (group I; n = 37) were compared to results obtained between 1999 and 2001 (group II; n = 79). RESULTS: In group I, MV repair was attempted in 25 patients (67.6%) and was successful in 21 (56.8%). In group II, MV repair was attempted in 68 patients (86.1%) and was successful in 67 (84.8%). The success rate between groups was significantly (p = 0.001) different. The rate of successful MV repair in patients with a diffusely redundant prolapsing valve involving both leaflets and multiple segments with chordae elongation was significantly higher in group II (14/20; 70%) than in group I (1/6; 14.3%) (p = 0.011). CONCLUSION: A greater incidence of successful MV repair, even with more diffuse pathology of MMVD, was realized following the institution of dedicated echocardiography/surgery team at a community hospital. It is proposed that a combination of dedicated intraoperative echocardiography and surgical expertise is required for optimal results in MV repair.
Pulmonary sequestration in infants and children is conventionally treated by resecting the sequestered lung parenchyma (sequestrectomy) or by performing lobectomy through a standard thoracotomy. We performed lobectomy by video-assisted thoracic surgery, using an original tracheal tube that we designed, in a 6-year-old boy with extralobar pulmonary sequestration and bronchiectasis in the left lower lobe.
Familial HDL deficiency (FHD) is a rare autosomal dominant lipoprotein disorder. We describe a novel genetic variant of the apolipoprotein A-I (apoA-I) gene resulting in FHD. The proband is a 51-year-old woman who was hospitalized due to severe heart failure. Her plasma HDL-cholesterol (C) and apoA-I concentrations were 0.08mmol/l and 1mg/dl, respectively. She exhibited corneal opacities and planar xanthomas on eyelids and elbows. Coronary angiography demonstrated extensive obstructions in two major vessels. Genomic DNA sequencing of the patient's apoA-I gene revealed a homozygosity for a GC deletion between 5 GC repeats in exon 4, creating a frameshift and a stop codon at residue 178. We designated this mutation as apoA-I Shinbashi. The proband's father, son, and daughter were found to be heterozygous for this mutation and their HDL-C and apoA-I levels were about half of normal levels, demonstrating a gene dosage effect. The father underwent coronary bypass surgery at age of 70 years. Lecithin-cholesterol acyltransferase (LCAT) activity was decreased by 63% in the homozygote and 31% in heterozygotes, respectively. This new case of apoA-I deficiency, apoA-I Shinbashi, is the first case involving a single gene defect of the apoA-I gene to develop all the characteristics for apoA-I deficiency, including premature coronary heart disease.
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