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Biomedical subjects

G Yoshino

Publications and source records attributed to G Yoshino.

At least 19 recordsLinked to original sources
PubMed2001

Doxazosin reduces prevalence of small dense low density lipoprotein and remnant-like particle cholesterol levels in nondiabetic and diabetic hypertensive patients.

Small dense low density lipoprotein (LDL) and remnant lipoproteins are potent atherogenic lipoproteins, often elevated in the plasma of patients with type 2 diabetes. The alpha1-blocker doxazosin has been reported to favorably affect the plasma lipid profile. We examined whether doxazosin could reduce these atherogenic lipoproteins in hypertensive subjects with and those without type 2 diabetes. Seventeen nondiabetic hypertensive patients and 33 hypertensive patients with type 2 diabetes were studied. Doxazosin (2 to 4 mg) was administered alone or with other previously received antihypertensive drugs for 6 months. Mean LDL size was measured by 2% approximately 16% gradient gel electrophoresis. Remnant-like particle (RLP)-cholesterol was measured with the use of an affinity column containing anti-apoA1 and B100 monoclonal antibodies. Doxazosin effectively decreased blood pressure (BP) without significantly affecting glucose, glycosylated hemoglobin (HbA1c), or C-peptide levels in both nondiabetic and diabetic patients. Doxazosin significantly reduced triglyceride, apo CIII, and apo B, but did not alter total-, LDL- or HDL-cholesterol. Mean LDL particle diameter was significantly increased from 25.6+/-0.6 nm to 25.9+/-0.4 nm (P < .001) by doxazosin treatment, regardless of the presence of diabetes. Consequently, the prevalence of small dense LDL (<25.5 nm) was halved in both groups. The increase in LDL size significantly correlated with decrease in triglyceride level (r=-0.798, P < .0001). Doxazosin significantly reduced RLP-cholesterol in both groups. These results suggest that doxazosin may help to prevent coronary artery disease by reducing atherogenic lipoproteins, including small dense LDL and remnant lipoproteins, in hypertensive patients, regardless of the presence of diabetes.

Aged↗
PubMed2000

An impairment of barrier size and charge selectivity of glomerular basement membrane in streptozotocin-induced diabetes and prevention by pharmacological therapy.

We examined barrier size (pore size) and charge selectivity (anionic sites) of the glomerular basement membrane (GBM) in experimental diabetes. For estimation of the pore size we employed a new method, tissue negative staining. In diabetic rats, enlarged pores and decreased numbers of anionic sites of GBM were observed. Both insulin treatment and angiotensin-converting enzyme inhibitors prevented these changes. The renoprotective effect of the two drugs is discussed in the article.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Reactions of direct LDL-cholesterol assays with pure LDL fraction and IDL: comparison of three homogeneous methods.

According to the definition of the Lipid Research Clinic's protocol, low-density lipoprotein (LDL) refers to the lipoprotein of density (d)=1.006-1.063 g/ml which contains another atherogenic lipoprotein, IDL (d=1.006-1.019 g/ml). Because metabolic properties are largely different between LDL and IDL, LDL is now defined as the lipoprotein of d=1.019-1.063 g/ml. Recently direct LDL-cholesterol assay kits using novel surfactants (the homogeneous methods) have become commercially available and widely used in Japan. The aim of this study is to examine how three direct LDL-cholesterol assay kits, LDL-EX, Choletest-LDL and Determinor-L LDL, react with pure LDL (d=1. 019-1.063 g/ml) and IDL (1.006-1.019 g/ml) fractions isolated by ultracentrifugation. Thirty-one healthy subjects and one type III dysbetalipoproteinemic patient were enrolled in this study. All homogeneous methods highly correlated with LDL-cholesterol (r=0.95-0. 98), although the values for LDL-EX were closer to the values for ultracentrifugation than were those of the other two methods (95 vs. 86-87%, P<0.0001). Cross-reactivity with IDL was 31, 47 and 64% for LDL-EX, Choletest-LDL, and Determinor-L LDL, respectively. Similar results were obtained in the IDL from a type III dysbetalipoproteinemic patient. These results suggest that LDL-cholesterol measured by LDL-EX better reflects pure LDL fraction with weaker cross-reaction with IDL than other homogeneous methods.

Cholesterol↗
PubMed2000

Vascular endothelial markers, von Willebrand factor and thrombomodulin index, are specifically elevated in type 2 diabetic patients with nephropathy: comparison of primary renal disease.

To elucidate the hypothesis that albuminuria in diabetic subjects reflects widespread vascular damage, plasma markers for vascular endothelial damage was measured in diabetic subjects with various degrees of albuminuria and compared to results in patients with primary renal disease. The groups consisted of 31 non-diabetic patient controls with normoalbuminuria, 109 type 2 diabetic patients with normo- micro- and macro-albuminuria, and 16 proteinuric patients with primary renal disease. Endothelial markers, plasma von Willebrand factor (vWF) and thrombomodulin (TM), were measured by enzyme-linked immunosolvent assay and enzyme immunoassay (EIA) methods, respectively. Plasma vWF levels were similar in controls (119+/-7%, mean+/-S.E.M.) and diabetic patients with normoalbuminuria (139+/-6), but significantly elevated in diabetic patients with microalbuminuria (174+/-11) and macroalbuminuria (204+/-17), while the level was not increased in patients with primary renal disease (124+/-11). Because plasma TM level was strongly affected by kidney function, TM index (TM (FU/ml)/serum creatinine (mg %)) was used as an endothelial marker. The TM index was substantially increased in diabetic patients with overt nephropathy compared with controls (5.29+/-2.98 vs. 2.35+/-0.85), whereas this was not observed in patients with primary renal disease (3.25+/-0.29). Both vWF and TM index were significantly higher in diabetic patients with retinopathy than in the patients without retinopathy. These results suggest that generalized vascular endothelial damage occurs in diabetic nephropathy including the microalbuminuric stage, which is not attributed to kidney damage per se.

Aged↗
PubMed2000

Adenocarcinoma of the rectum with various grades of atypia in association with Crohn's disease: a case report and immunohistochemistry of p53 and Ki-67.

A case of adenocarcinoma of the rectum in a 41-year-old woman, in association with Crohn's disease is presented. The patient had suffered diarrhea and constipation, and Crohn's disease was suspected. Although the endoscopy did not reveal the presence of any tumors, biopsy specimens demonstrated adenocarcinoma. A Miles' operation was performed. The adenocarcinoma was composed of various grades of atypia and had invaded the non-peritonealized perirectal tissues. The infiltration of lymphocytes and plasma cells was moderate at the perimeter of the carcinoma and mild in the distant regions. Epithelioid cell granulomas were found. The p53 labeling index (LI) increased with the grade of atypia over the entire length of the carcinomatous gland. In carcinomas with high grade atypia, the p53 LI was high in both the upper and the lower halves of the gland. In carcinomas with low or moderate grade atypia however, the p53 LI was high in the lower half and low in the upper half of the gland. The Ki-67 LI over the entire gland was higher in carcinomas with high grade atypia than in carcinomas with low or moderate grade atypia.

Adenocarcinoma↗
PubMed2000

Preoperative diagnosis of ileal lipoma by endoscopic ultrasonography probe.

The occurrence of tumor in the small intestine is relatively rare. It has been demonstrated that lipoma of the ileum is a cause of intussusception. We report a 59-year-old man admitted to our hospital for lower abdominal pain. Diagnosis of intussusception was made by abdominal x-ray and ultrasonography. Enema contrast studies revealed ileocolic intussusception. Colonoscopy revealed a tumor with an submucosal tumor (SMT)-like head and coil-spring appearance in the ascending colon. Endoscopic ultrasonography (EUS) revealed a hyperechoic submucosal lesion with features compatible with lipoma. Subsequently, this was confirmed histopathologically after resection. To our knowledge, this is the first report of preoperative diagnosis of ileal lipoma by EUS.

Endosonography↗
PubMed2000

Intratumor heterogeneity of centromere numerical abnormality in multiple primary gastric cancers: application of fluorescence in situ hybridization with intermittent microwave irradiation on paraffin-embedded tissue.

Our recent success in retrieving distinct fluorescence signals in response to centromere specific probing of paraffin-embedded tissues after intermittent microwave (MW) treatment provided the opportunity to analyze chromosome numbers or centromere abnormality in situ in human tumors in various clinicopathological settings. In this study, centromere numerical abnormality (CNA) was investigated by fluorescence in situ hybridization (FISH) in a case of multiple gastric cancer having intratumor histological heterogeneity. The different profiles as determined using a total of 20 specific probes on 4 multifocal lesions in the stomach confirmed the multi-clonality of these tumors. FISH with probes specific for chromosomes 10, 11, 16 and 18 revealed intratumor heterogeneity of the CNA, which corresponded to the histological heterogeneity. Our report clearly demonstrates, for the first time, intratumor heterogeneity of CNA and its association with the histological picture, and substantiates the applicability of the MW-assisted FISH protocol to paraffin-embedded pathological specimens.

Centromere↗
PubMed1999

Low density lipoprotein particle diameter in young, nonobese, normolipidemic Japanese men.

BACKGROUND: prospective studies have demonstrated that a predominance of small, dense LDL particles (pattern B) precedes the clinical onset of coronary heart disease. Prevalence and characteristics of subjects with this LDL size abnormality were studied in young, nonobese, Japanese normolipidemic men. METHODS AND RESULTS: LDL peak particle diameter (PPD) was measured by continuous disc polyacrylamide gel electrophoresis in 223 nonobese normolipidemic men aged 18-20 years (mean+/-S.D. body mass index: 21.9+/-3.7 kg/m2, total cholesterol: 180+/-29 mg/dl, triglyceride: 62+/-34 mg/dl, HDL cholesterol: 58+/-12 mg/dl). Men with small LDL (PPD < 25.8 nm) were found in only 5.4% (n=12) whereas 197 men (88.3%) had a preponderance of large LDL (PPD 26.3 nm). As compared with men in a top tertile (PPD 27.5 nm) those in a low tertile (PPD < 26.9 nm) had higher serum levels of LDL cholesterol (120+/-31 vs 104+/-24 mg/dl), triglyceride (72+/-39 vs 49+/-16 mg/dl) and apolipoprotein (apo) B (84+/-21 vs 68+/-14 mg/dl), and lower HDL cholesterol (54+/-10 vs 60+/-12 mg/dl). They also had greater body mass index (23.2+/-4.6 vs 20.9+/-3.1 kg/m2) and percent body fat (21.5+/-7.7 vs 17.5+/-4.9%). LDL-PPD was positively correlated with HDL cholesterol (R=0.20, P=0.002) and was negatively correlated with apoB (R=0.34, P < 0.001), triglyceride (R=0.32, P < 0.001). percent body fat (R=0.26, P < 0.001), body mass index (R=0.24, P < 0.001), fat mass (R=0.23, P=0.001), total cholesterol (R=0.20, P=0.002). In multiple regression analysis, apoB, triglyceride, HDL cholesterol, apoAI and percent body fat explained 18% of LDLPPD variability. CONCLUSION: even in young, nonobese, normolipidemic men, LDL size appears to be associated with triglyceride-rich lipoprotein metabolism and body fat.

Adolescent↗
PubMed1999

Fasting insulin and leptin serum levels are associated with systolic blood pressure independent of percentage body fat and body mass index.

OBJECTIVE: To examine the relationship between leptin and insulin serum levels and systolic and diastolic blood pressure in young men. SETTING: Kobe University of Mercantile Marine, Kobe, Japan. PARTICIPANTS: One hundred and ninety-eight male students aged 18-20 years (comprising 100% of those eligible). DESIGN AND MEASUREMENTS: A cross-sectional survey of a sample of male college students was performed, with measurements to include anthropometry, blood pressure and blood tests after overnight fasting. RESULTS: Compared with 90 men with an optimal blood pressure, 56 men with high-normal and high blood pressure had an increase in body mass index (23.7 +/- 5.2 versus 20.4 +/- 2.2 kg/m2), percentage body fat (21.7 +/- 8.0 versus 16.3 +/- 4.2%) and serum leptin (3.7 +/- 4.7 versus 1.5 +/- 0.8 ng/ml). In addition, they had greater serum insulin (59 +/- 31 versus 43 +/- 12 pmol/l) despite there being no differences in plasma glucose, resulting in a reduction of the ratio of glucose to insulin (x 10(6)) (107 +/- 43 versus 126 +/-, which is an estimate of insulin sensitivity in a nondiabetic population. Furthermore, the 56 men had higher serum triglyceride levels, although there was no difference in low density lipoprotein-cholesterol and high density lipoprotein-cholesterol between men with optimal and high-normal plus high blood pressure. Similar differences were found between men in a top versus low tertile of systolic and diastolic blood pressure. In multiple regression analysis, both log leptin and log insulin emerged as determinants for systolic blood pressure independent of body mass index and percentage body fat, but an association with diastolic blood pressure was only shown for log leptin. CONCLUSION: Hyperleptinemia and hyperinsulinemia may be regulators of arterial pressure, independent of body mass index or percentage body fat.

Adipose Tissue↗
PubMed1999

Initial ultrastructural changes in pore size and anionic sites of the glomerular basement membrane in streptozotocin-induced diabetic rats and their prevention by insulin treatment.

BACKGROUND/AIM: The present study was conducted to elucidate the mechanism(s) of the development of early diabetic nephropathy, examining ultrastructural changes employing electron microscopy, especially changes in pore size of the glomerular basement membrane (GBM) of streptozotocin (STZ)-induced diabetics rats. METHODS: Urinary albumin excretion rate (UAE), pore size of the lamina densa of the GBM visualized directly by the tissue negative staining method, and number of anionic sites (AS) in the corresponding portion of the lamina rara externa were determined for 6 weeks in diabetic rats without and with insulin treatment. RESULTS: The UAE of the diabetic rats increased with time and was significantly greater than that of the nondiabetic control rats after 4 weeks (p < 0.01), while insulin treatment suppressed the increased UAE of diabetic rats. The median values in both short diameter and long dimension of the pores in the diabetic group were markedly increased at the 2nd week as compared with those in the nondiabetic control rats, whereas no significant change was found in the pore size of the diabetic rats with insulin treatment. Moreover, the number of AS in the GBM of the diabetic rats was significantly (p < 0.001) decreased from the 2nd week onward. Insulin treatment also prevented a decrease in AS number in diabetic rats. CONCLUSIONS: It is suggested from these results that an impairment of barrier size selectivity occurs at a very early stage of STZ-induced diabetes in rats, which may enhance the abnormality of the charge-selective properties of the GBM. In addition, insulin treatment may protect this barrier system through normalizing blood glucose control in STZ-diabetic rats.

Albuminuria↗
PubMed1999

Increased urinary transferrin excretion predicts microalbuminuria in patients with type 2 diabetes.

OBJECTIVE: We studied whether increased urinary transferrin excretion rates (TERs) (urinary transferrin-to-urinary creatinine ratio > or = 107 micrograms/mmol, which is the sum of an average and 2 SDs in 431 healthy nondiabetic individuals) would predict the development of microalbuminuria (urinary albumin-to-urinary creatinine ratio > or = 2.8 mg/mmol) in patients with type 2 diabetes and normal urinary albumin excretion rates (AERs) (albumin-to-creatinine ratio < 2.8 mg/mmol). We also studied the influence of blood pressure, glycemic control, and serum levels of lipids and apolipoproteins on the later development of microalbuminuria. RESEARCH DESIGN AND METHODS: In 77 diabetic patients with normal AER, AER and TER were measured at baseline and after 24 months of follow-up. Blood pressure, glycemic control, and serum levels of lipids and apolipoproteins were measured at 1- to 2-month intervals during the follow-up period. RESULTS: Of the 16 patients who initially had increased TER, 5 (31%) developed microalbuminuria. In contrast, of the 61 who initially had normal TER, 4 (7%) developed microalbuminuria (P = 0.016). At baseline, no difference was found in age, sex, diabetes duration, diabetic medications, prevalence of hypertension, blood pressure, HbA1c levels, or serum lipid and apolipoprotein concentrations between the two group of patients with normal and increased TER. There was also no difference in duration of hypertension and prevalence of users of ACE inhibitors between two subgroups of hypertensive patients with normal and increased TER. During the 24 month follow-up period, those whose condition progressed to microalbuminuria had increased serum levels of triglycerides (1.87 +/- 0.49 vs. 1.29 +/- 0.64 mmol/l, P = 0.003) and apolipoprotein B (114 +/- 20 vs. 102 +/- 24 mg/dl, P = 0.05) and tended to have increased HbA1c levels (7.7 +/- 1.0 vs. 7.1 +/- 1.1%, P = 0.10) compared with those in whom microalbuminuria did not develop. Blood pressure, however, did not differ. In multivariate stepwise logistic regression analysis, the association between increased TER at baseline and subsequent development of microalbuminuria was significant (odds ratio 7.04 [95% CI 1.02-48.5], P = 0.04). CONCLUSIONS: In patients with type 2 diabetes and normal AER, increased TER may predict the development of microalbuminuria and abnormalities in triglyceride-rich lipoprotein metabolism, and poor glycemic control may be associated with this progression.

Albuminuria↗
PubMed1999

[New clinical application of direct and chemical measurement of low density lipoprotein cholesterol-estimation of compositional changes in triglyceride-rich lipoprotein fraction].

Recently several new direct assay systems for chemical measurement of LDL-cholesterol (Ch) have been developed. These systems allow us to estimate LDL-Ch value even in samples under non-fasting condition as well as samples from prominent hypertriglyceridemics without ultracentrifugation. Since it is possible that the difference between LDL-Ch value measured using new direct method and that calculated using Friedewald's formula can indicate compositional abnormalities of triglyceride-rich lipoprotein (TGRL) fraction (if VLDL-Ch equal to 1/5 of plasma triglyceride, this difference must always be zero), this difference (estimated remnant-Ch) may represent the presence of remnant or intermediate density lipoprotein (IDL) fraction. LDL-Ch is not detected by means of this direct method (LDL-EX, Denka Seiken Co.) in the eluate of the affinity column, which contains anti-apoA1 and anti-B100 antibody, indicating that RLP fraction can be excluded from the assay system. Estimated remnant-Ch correlated well with RLP-Ch, IDL-Ch and apoE. Furthermore, there is no significant correlation between LDL-Ch measured by LDL-EX and Lp(a), indicating that this direct assay system does not include Lp(a) in plasma. Thus, this new direct assay method for LDL-Ch enables us to measure LDL-Ch value with ease and also to estimate compositional abnormalities of TGRL fraction and/or appearance of remnant or IDL fraction without ultracentrifugation.

Cholesterol, LDL↗
PubMed1999

[Antioxidants and cardiovascular disease].

Oxygen-free radical reactions have been implicated in many chronic diseases, including atherosclerotic cardiovascular disease (CVD). Epidemiologic studies have demonstrated an association between increased intake of naturally occurring antioxidant vitamins such as vitamin E and vitamin C and reduced morbidity and mortality from CVD. By contrast, most of the completed randomized trial did not show any clear reduction in CVD. However, the trials were not specifically designed to assess CVD, did not provide data on nonfatal CVD, may have had insufficient treatment durations, and used suboptimal vitamin E doses. Despite the lack of a general consensus, recent data reinforce the concept that the regular intake of antioxidants present in foods limits the progression of atherosclerotic CVD.

Antioxidants↗