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Biomedical subjects

K Saku

Publications and source records attributed to K Saku.

At least 55 records · Page 3Linked to original sources
PubMed1998

Deposition of oxidized low-density lipoprotein and collagenosis occur coincidentally in human coronary stenosis: an immunohistochemical study of atherectomy.

BACKGROUND: Coronary stenosis involves lipid accumulation, fibrosis and cell proliferation. OBJECTIVE: To clarify the role of oxidized low-density lipoprotein (LDL) in coronary stenosis by examining atherectomized coronary lesions from patients with primary stenosis and restenosis after percutaneous transluminal coronary angioplasty (PTCA). METHODS: Atherectomized coronary tissue from 28 patients with primary stenosis and restenosis at 4.3 +/- 1.0 months after PTCA were examined using morphometrical and immunohistochemical techniques. RESULTS: Serum lipids in all of the patients were within the normal range and no differences were noted between the two groups. There were no differences in the mean cross-sectional areas of whole specimens obtained from each group, and sclerotic lesions with atheroma or calcification were found to a similar extent in both groups. However, the restenosis group had a significantly greater area (6-fold) of immature smooth-muscle-rich lesions than the primary stenosis group, although there was no difference in lipid-laden foam-cell containing lesions. In foam-cell-containing lesions, apolipoprotein B was accumulated extracellularly, while oxidized LDL was primarily deposited intracellularly in lipid-laden foam cells. However, no deposition of apolipoprotein B, oxidized LDL or lipids was noted in smooth-muscle-rich lesions. Proline hydroxylase, a key enzyme for collagen synthesis, was detected in most of the foam-cell-containing lesions, but not in smooth-muscle-rich lesions. CONCLUSIONS: Atherectomized lesions from patients with coronary stenosis contained smooth-muscle-rich lesions in restenosis and lipid-laden cellular lesions in both stenosis and restenosis, in which the deposition of oxidized LDL and increased collagen synthesis occur coincidentally. Therefore, the mechanism of atherogenesis may involve coronary stenosis regardless of the occurrence of restenosis after PTCA therapy.

Adult↗
PubMed1998

Parasympathetic tone affects electrocardiographic preconditioning during right coronary angioplasty.

We investigated whether parasympathetic tone may affect ischemic preconditioning in terms of ST segment alteration during coronary angioplasty. Coronary balloon angioplasty was performed in 19 patients with angina and isolated right coronary artery disease. Parasympathetic tone was assessed by frequency domain parameters of heart rate variability using 24-hour electrocardiographic recordings obtained before angioplasty. Logistic regression analysis showed the high frequency component to be an independent predictor of the change in ST elevation induced by the second balloon inflation. An increase in parasympathetic tone was related to ischemic preconditioning with respect to the electrocardiographic alterations observed in these patients.

Aged↗
PubMed1998

Long-term effect of low-density lipoprotein apheresis in a patient with heterozygous familial hypercholesterolemia: follow-up study using coronary angiography.

A 62-year-old man with old myocardial infarction and familial hypercholesterolemia was treated by both probucol and low-density lipoprotein (LDL) apheresis. Coronary angiography was performed before and after 3.5 years of LDL apheresis treatment, and no new lesion or progression of coronary atherosclerosis was observed. LDL apheresis drastically reduced the serum total cholesterol. However, it is still unclear whether LDL apheresis effectively prevented the recurrence of cardiac events and the progression of coronary atherosclerosis in this patient.

Anticholesteremic Agents↗
PubMed1997

Fractional esterification rate of cholesterol in high density lipoprotein (HDL) can predict the particle size of low density lipoprotein and HDL in patients with coronary heart disease.

Fractional esterification rate of cholesterol in high density lipoprotein (HDL) (FER[HDL]) can predict the size distribution and physicochemical characteristics of HDL in plasma. In the present study, we investigated the correlation of FER(HDL) with the particle size of low density lipoprotein (LDL) (LDL-size) in 111 patients (81 males and 30 females) with coronary heart disease (CHD). The correlations of FER(HDL) and LDL-size with conventional lipid and lipoprotein parameters were also studied. FER(HDL) was closely associated with LDL-size (males: r = -0.618, females: r = -0.629, P < 0.001). Plasma levels of TG, HDL-cholesterol (HDL-C), HDL2-cholesterol (HDL2-C) and apo B were also associated with LDL-size in male CHD patients (r = -0.534, 0.314, 0.358, and -0.482, P < 0.01 or 0.001), while plasma levels of TG and apo B were associated with LDL-size in female patients (r = -0.350 and -0.348, P < 0.05). In a stepwise multiple regression analysis, FER(HDL) alone accounted for 38 and 40% of the variability in LDL-size in male and female CHD patients, respectively. Other parameters accounted for an additional 6-10%. With respect to the relation between FER(HDL) and HDL subfractions, FER(HDL) related only to HDL2-C (males: r = -0.640, females: r = -0.652, P < 0.001). This result suggests that FER(HDL) is better able to predict the presence (or absence) of large HDL, rather than that of small HDL. All these data taken together, suggest that FER(HDL) is a useful tool to predict the particle size of both LDL and HDL, even in CHD patients.

Aged↗
PubMed1997

Quantification of the effects of troglitazone on insulin sensitivity and beta-cell function in Watanabe heritable hyperlipidemic rabbits: a minimal model analysis.

Troglitazone is a newly developed antidiabetic drug that has been shown to improve insulin resistance and hyperinsulinemia both in diabetic animal models and in patients with non-insulin-dependent diabetes mellitus. The Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model of familial hypercholesterolemia, is characterized by hyperinsulinemia, which reflects insulin resistance. In this study to determine the effects of troglitazone on glucose and insulin metabolism in WHHL rabbits, we quantified the rate of glucose utilization (glucose tolerance index [Kg]), sensitivity of first-phase posthepatic insulin secretion to glucose (phi1), sensitivity of second-phase posthepatic insulin secretion to glucose (phi2), insulin sensitivity to glucose disposal ([Si] inversely related to insulin resistance), insulin-independent glucose disposal (glucose effectiveness [Sg]), and rate of insulin clearance (Ki) by incorporating our previously reported two-compartment model of a glucose/insulin system with the glucose disappearance model of Bergman. Galvin insulin sensitivity (GIS) was also computed for comparison with Bergman Si. When troglitazone was administered as a food admixture (24 mg/d per animal) for 6 months, it did not significantly affect beta-cell function as measured by phi2, glucose tolerance as measured by Kg, or Sg, but increased both Si and Ki and reduced phi1, leading to a decreased plasma insulin response during the intravenous glucose tolerance test (IVGTT). Si was strongly and significantly correlated with GIS. These data indicate that in WHHL rabbits, troglitazone improves insulin sensitivity and posthepatic insulin clearance without affecting beta-cell function or glucose tolerance.

Animals↗
PubMed1997

Troglitazone lowers blood pressure and enhances insulin sensitivity in Watanabe heritable hyperlipidemic rabbits.

Although an association has been demonstrated between insulin resistance and hypertension, the mechanism of this association is not clear. Clarification of this point is important in hyperinsulinemic Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of familial hypercholesterolemia, as hypertension markedly stimulates atherosclerosis in WHHL rabbits. The purpose of the present study was to determine whether troglitazone, a new thiazolidinedione drug for insulin resistance, could reduce blood pressure (BP) by improving hyperinsulinemia in WHHL rabbits. The effects of troglitazone, administered as a food admixture (24 mg/day) for 6 months, on hyperinsulinemia and BP were examined in WHHL rabbits. Insulin sensitivity (IS) was measured by the minimal model method using an intravenous glucose tolerance test (IVGTT). Troglitazone significantly reduced fasting insulin levels and the area-under-the-curve of insulin IVGTT profiles, indicating improved hyperinsulinemia. Troglitazone also significantly increased IS and reduced BP and heart rate (HR). Due to a significant correlation between HR and BP, a covariance analysis was performed. When BP was considered as a covariance factor, the change in HR was significant in treated rabbits. However, when HR was considered as a covariance factor, the change in BP was not significant, suggesting that reduced BP may be partly associated with changes in the sympathetic nervous system activity. In conclusion, troglitazone increases insulin sensitivity and lowers blood pressure in WHHL rabbits. Due to its dual effects on insulin resistance and hypertension, troglitazone offers a new pharmacological approach for the treatment of insulin-resistance syndrome.

Animals↗
PubMed1997

Mechanism of action of gemfibrozil on HDL metabolism and atherosclerosis in WHHL rabbits.

We investigated the mechanism of action of gemfibrozil on high-density lipoproteins (HDL) and apolipoprotein (apo) A-I metabolism and atherogenesis in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of familial hypercholesterolemia and HDL deficiency. Two-month-old WHHL rabbits were fed either a normal control diet or a diet containing 0.5% gemfibrozil for 12 months. In vivo apo A-I kinetics, the fractional rate of cholesterol esterification in HDL (FER[HDL]), which reflects the reactivity of HDL to lecithin:cholesterol acyltransferase, and a morphometrical analysis of atherosclerotic lesions in the descending thoracic aorta, were examined. At 12 months, the mean levels of serum total cholesterol, LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) in both groups had decreased to approximately 53%, 57%, and 87% of the initial levels (at 0 month), respectively, which is characteristic of homozygous WHHL rabbits of the physiologic influence of aging, and no differences in the levels of serum LDL-C, HDL-C, and triglycerides were found between the two groups. Rabbits treated with gemfibrozil exhibited a decreased FER(HDL) (38% of the controls, P = 0.039). Gemfibrozil induced a significant increase in the total mass of apo A-I (1.7-fold, P < 0.05) and in the rate of apo A-I synthesis (1.6-fold, P < 0.05). The atherosclerotic intimal area was positively correlated with serum LDL-C (P = 0.02) in both groups, but gemfibrozil did not affect the atherosclerotic intimal area. These results indicate that 12 months of treatment with gemfibrozil did not protect against atherosclerosis despite a significant increase in apo A-I synthesis and enhanced HDL function through FER(HDL). It is possible that both the qualitative and quantitative improvement in HDL by gemfibrozil cannot overcome the massive and long-term exposure of the vascular wall to LDL in these animals.

Animals↗
PubMed1997

Three-dimensional spiral computed tomography angiography as an alternative imaging modality for a silent dissecting aortic aneurysm--a case report.

The authors report a patient with silent dissecting aortic aneurysm in whom three-dimensional spiral computed tomography (CT) angiography (3D-CTA) provided important imaging data. Images obtained by 3D-CTA were compared with the results of both conventional angiography and CT. They conclude that 3D-CTA was a powerful diagnostic modality for this patient, in addition to conventional CT and angiography.

Aortic Dissection↗
PubMed1997

Fractional esterification rate of cholesterol in high density lipoprotein is correlated with low density lipoprotein particle size in children.

Small low density lipoprotein (LDL) particles are thought to be more atherogenic than larger LDL particles, although this association may depend on plasma triglyceride (TG) and high density lipoprotein (HDL) levels. To help prevent coronary artery disease (CAD), it may be useful to understand risk factors during childhood and adolescence. In the present study, we evaluated low density lipoprotein particle size (LDL-size) by 2-16% gradient gel electrophoresis in 70 healthy children (30 boys and 40 girls) along with conventional lipid and lipoprotein parameters which are thought to affect LDL-size. The fractional and molar esterification rates (FER and MER) of cholesterol in plasma and HDL were also determined. As expected, plasma levels of TG, HDL-cholesterol (HDL-C) and apoA-I were closely associated with LDL-sizes in both sexes (boys: r = -0.694, 0.708 and 0.701, girls: r = -0.579, 0.551 and 0.539, P < 0.001). However, a closer association was found between FER in HDL (FER(HDL)) and LDL-size (boys: r= -0.874, girls: r= -0.642, P < 0.001). In a stepwise multiple regression analysis, FER(HDL) alone accounted for 76% and 41% of the variability in LDL-size in boys and girls, respectively. MER in HDL accounted for additional 4% and 19% in boys and girls, respectively. Other parameters, including plasma TG, HDL-C and apoA-I had no significant additional effects. Thus, the determination of FER(HDL) is useful to predict the particle size of LDL in children.

Adolescent↗
PubMed1997

Long-term follow-up by coronary angiography in a patient with heterozygous familial hypercholesterolemia: a case report.

A 47-year-old man with heterozygous familial hypercholesterolemia was followed up by coronary angiography for 9 years. During these 9 years, he experienced inferior myocardial infarction twice, at segment 1 of the right coronary artery. A coronary atherosclerotic lesion (50% stenosis) was also present at segment 6 of the left anterior descending coronary artery. This lesion remained unchanged for the first 7 years, but then rapidly progressed to 90% stenosis in the 8th year. While the rate of the progression of coronary atherosclerosis is generally unpredictable, it may progress rapidly in this case of heterozygous familial hypercholesterolemia.

Angioplasty, Balloon, Coronary↗
PubMed1997

Thrombomodulin levels in patients with coronary artery disease.

We investigated the association between the serum level of thrombomodulin and known coronary risk factors in 119 men who underwent coronary angiography. Total cholesterol level was significantly higher in patients with coronary atherosclerosis than in those without. Significantly higher frequency of hypertension was noted in patients with coronary atherosclerosis. Uric acid level and frequency of smoking tended to be higher in patients with coronary atherosclerosis but the differences were short short of the significant level. The serum level of thrombomodulin between patients with coronary atherosclerosis and those without was not statistically significant. Age, blood urea nitrogen, and creatinine were positively correlated and creatinine clearance was inversely correlated with the serum level of thrombomodulin. Serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, uric acid, and fasting blood sugar, plasma level of fibrinogen, and body mass index were not related to the serum level of thrombomodulin. There was no significant correlation between the severity of coronary atherosclerosis, hypertension, alcohol use, or smoking and the serum level of thrombomodulin. Restenosis was present in 8 of 16 patients who underwent percutaneous transluminal coronary angioplasty and had a follow-up angiogram at 6.0 +/- 3.0 months. Univariate analysis revealed no significant difference in the thrombomodulin level with and without restenosis. The present findings suggest that elevated thrombomodulin levels in patients with coronary artery disease may reflect retention of thrombomodulin due to decrease in thrombomodulin clearance in the kidney.

Adult↗
PubMed1996

A missense mutation (Thr-6Pro) in the lysosomal acid lipase (LAL) gene is present with a high frequency in three different ethnic populations: impact on serum lipoprotein concentrations.

A frequent missense mutation (Thr-6Pro) found in the prepeptide of the lysosomal acid lipase (LAL) gene was analyzed in a cohort of 1003 randomly selected samples from Germany, Japan and Sardinia (Italy). Using the mutagenically separated polymerase chain reaction (MS-PCR), allele frequencies of 0.269, 0.238 and 0.245 were determined in the three populations, respectively. Statistical analysis showed a lack of association with a dyslipidemic phenotype in all three groups. Additionally, in a subgroup of 126 German individuals no association was observed between genotype and LAL activity. We conclude that this mutation appears to be a frequent LAL gene polymorphism causing no impaired function of the enzyme and no measurable dyslipidemia in the general population.

Base Sequence↗
PubMed1996

Polymorphism of the apolipoprotein A-IV gene and its significance in lipid metabolism and coronary heart disease in a Japanese population.

Apolipoprotein A-IV (apo A-IV) is involved in the metabolism of both triglycerides and high-density lipoproteins (HDLs). Apo A-IV has been suggested as participating in several stages of reverse cholesterol transport. Uncertainty about the exact biochemical function of apo A-IV has made the use of genetic apo A-IV polymorphism (variants) attractive in evaluating its physiological role. To date, although some reports indicate that DNA polymorphisms at this locus play an important role in the metabolism of lipids and lipoproteins in western (Caucasian) populations, no similar comprehensive analysis has been performed in a distinct Japanese population. Using DNA sequencing and a restriction fragment length polymorphism (RFLP) study with polymerase chain reaction (PCR), the following allele frequencies were established: (a) codon -8 (G-->A, non-synonymous) allele 2 = 0 (n = 105); (b) codon 9 (A-->G, synonymous) allele 2 = 0.388 (n = 152); (c) codon 347 (A-->T, non-synonymous) allele 2 = 0 (n = 900); (d) codon 360 (T-->G, non-synonymous) allele 2 = 0 (n = 800); (e) VNTR exon 3 [(CTGT)3 and (CTGT)4] (CTGT)3 = 0.262 (n = 105); and (f) MspI (newly detected polymorphic site) polymorphism (C C/T GG) within intron 2, allele 2 = 0.096 (n = 193). The frequencies of these polymorphisms, except for that of the newly identified MspI site, are completely different from those reported in western populations. Among the 900 subjects examined, we found one ACT (Thr) to ACG (Thr) synonymous mutation at codon 347, which does not change the primary structure of apo A-IV. The apo A-IV allele frequency in patients (166 men and 56 women) with angiographically proven coronary heart disease (CHD) was also studied [codon 9 allele 2 = 0.329 (n = 217); VNTR exon 3 (CTGT)3 = 0.262 (n = 84); MspI within intron 2, allele 2 = 0.092 (n = 222)]. Furthermore, we evaluated serum lipid and lipoprotein levels quantitatively in control subjects and Japanese CHD patients. These polymorphisms did not show any consistent and significant association with lipid and lipoprotein parameters. In addition, no gender-specific effects of apo A-IV polymorphisms on lipid parameters adjusted for confounding factors were observed in either CHD patients or control subjects. Our results indicate that the apo A-IV gene is not a major determinant of the risk for CHD in Japanese.

Adult↗
PubMed1996

[A case of empyema caused by Salmonella enteritidis in a patient with sequela of pulmonary tuberculosis].

A 69-year-old male was admitted to our hospital on Jan. 10, 1995 complaining of bloody sputum, left back pain and fever of 39 degrees C. He had a history of pulmonary tuberculosis 45 years ago. His chest X-ray and CT showed the presence of air-fluid level in the left pleural cavity with thickening and calcification of the pleura. Salmonella Enteritidis was isolated from the sputum, bronchoalveolar lavage fluid and stool. He was diagnosed as suffering from Salmonella-empyema with an internal fistula. Based on the in vitro sensitivity test, sulfamethoxazole/trimethoprim was started. However, the efficacy of the antimicrobia was not sufficient. He then underwent left pleuropneumonectomy. Salmonella was cultured also from the specimen obtained at the operation. His course after operation was uneventful. Thus, although Salmonella Enteritidis is known as a common pathogen of food poisoning, it can cause empyema, especially in a case with an impaired host defence system.

Aged↗
PubMed1996

Evaluation of the coagulation and fibrinolytic systems in men with intermittent claudication.

The authors evaluated elements of the coagulation and fibrinolytic systems in 18 male patients with intermittent claudication vs 19 men matched for risk factors who served as controls. Prothrombin time and activated partial thromboplastin time did not significantly differ in the patients and the controls. The plasminogen level in the two groups was not significantly different. The level of lipoprotein(a) was significantly higher in the patients than in the controls. The levels of antigen and the activity of protein C did not differ significantly between the two groups. The thrombomodulin level was significantly higher in the patients than in the controls. There were no significant differences between the two groups in the levels of alpha 2-macroglobulin, C1-inactivator, or antithrombin III. The levels of fibrinogen and alpha 1-antitrypsin were significantly higher in the patients vs the controls. Significantly lower levels of alpha 2-plasmin inhibitor and higher levels of alpha 2-plasmin inhibitor/plasmin complex and thrombin/antithrombin III complex were found in the patients vs the controls. These findings suggest that the levels of thrombin/antithrombin III complex, alpha 2-plasmin inhibitor/plasmin complex, and thrombomodulin may perhaps serve as indicators for injury to the peripheral endothelium and that the coagulation and fibrinolytic systems may be activated in patients with intermittent claudication.

Aged↗
PubMed1996

Medium-term effects of betaxolol monotherapy and combination therapy with nitrendipine on lipoprotein and apolipoprotein metabolism in patients with mild to moderate essential hypertension.

The objective of this study was to assess the medium-term effects of betaxolol, a long-acting, lipid-soluble, cardioselective, beta-adrenergic antagonist, alone and in combination with nitrendipine on blood pressure (BP) and metabolism of lipid, lipoprotein and apolipoprotein in patients with mild to moderate hypertension. Forty-seven patients (21 men, 26 women, average age 54 years) participated in an open controlled clinical trial. After a 4-week washout period, all of the patients received betaxolol monotherapy at a dose of 5-10 mg daily for 6 months (Phase I). From month 7 through month 12 (Phase II), half of the total patients (Group B, n = 23) with diastolic blood pressure (DBP) of 95 mm Hg or more at the end of Phase I were also given nitrendipine (10-20 mg, once daily), while the remaining patients (Group A, n = 24) continued to receive only betaxolol. Systolic blood pressure (SBP), DBP, and heart rate (HR) were monitored once monthly. Serum lipid profiles were measured at study entry and after 6 and 12 months of therapy. Betaxolol significantly reduced SBP, DBP, and HR in both groups during Phase I, and the reductions in SBP and DBP were markedly less in Group B than in Group A. During Phase II, the additional reduction of SBP and DBP to levels similar to those in Group A was achieved by betaxolol in combination with nitrendipine, and HR was slightly but significantly increased. Betaxolol monotherapy reduced serum levels of high density lipoprotein cholesterol (HDL-C) and increased levels of triglyceride, apolipoprotein (apo) C-II and apo C-III. Combination therapy with betaxolol and nitrendipine increased serum apo A-I but did not affect other lipid profiles. Our results indicate that betaxolol is an effective antihypertensive drug which has a preferable effect on HR and HDL profiles when combined with nitrendipine.

Adrenergic beta-Antagonists↗