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Biomedical subjects

M Okubo

Publications and source records attributed to M Okubo.

At least 19 recordsLinked to original sources
PubMed2004

The effect of polymorphism in the intestinal fatty acid-binding protein 2 gene on fat metabolism is associated with gender and obesity amongst non-diabetic Japanese-Americans.

AIM: The role of the codon 54 polymorphism of the fatty acid-binding protein 2 (FABP2) gene on fat metabolism has been controversial. Assuming that the effects of the polymorphism were modulated by gender and obesity which were related to lipid and glucose metabolism, we investigated this polymorphism and its effect on fat metabolism according to such factors. METHODS: Subjects were Japanese-Americans (123 men and 126 women) who were diagnosed as non-diabetic by a 75 g oral glucose tolerance test at the baseline. RESULTS: During approximately 7.8 years, 49 (24 men and 25 women) were diagnosed with type 2 diabetes. In a Cox proportional hazards model, this polymorphism was not a significant variable in the incidence of diabetes in either gender. Amongst non-obese men with the Thr54 allele, there was a significant elevation of triglycerides (TGs) (p=0.033) compared with alanine (Ala) homozygotes. Women with the Thr54 allele had significantly elevated total cholesterol (p=0.033) and low-density lipoprotein-cholesterol (LDL-C) (p=0.023) compared with Ala54 homozygotes. CONCLUSIONS: These results therefore suggested that the effects of the FABP2 polymorphism on TG, LDL-C and body mass index were associated with gender difference and obesity amongst non-diabetic Japanese-American subjects.

Aged↗
PubMed2004

Post-challenge hyperglycaemia is an independent risk factor for arterial stiffness in Japanese men.

AIMS: Arterial stiffness is an independent predictor of cardiovascular disease, but the impact of post-challenge hyperglycaemia on arterial stiffness is unknown. To investigate the association between arterial stiffness and post-challenge hyperglycaemia, we measured the second derivative of photoplethysmogram as an indicator of arterial stiffness. METHODS: This study was done in 159 asymptomatic Japanese men aged 50.7 +/- 13.0 years. All subjects underwent a 75-g oral glucose tolerance test and measurement of the second derivative of photoplethysmogram. RESULTS: According to the World Health Organization criteria (1998), 110 subjects had normal glucose tolerance, 10 had impaired fasting glucose, 30 had impaired glucose tolerance, and nine had diabetes. The b/a ratio (an index of arterial stiffness) showed a significant relationship with age (r = 0.58, P < 0.0001), height (r = -0.33, P < 0.0001), 2-h post-challenge glucose (r = 0.32, P < 0.0001), systolic blood pressure (r = 0.22, P = 0.006), and diastolic blood pressure (r = 0.21, P = 0.009). After adjustment for age and height, there were significant correlations between the b/a ratio and diastolic blood pressure (r = 0.18, P = 0.02), fasting glucose (r = 0.16, P = 0.049), and 2-h post-challenge glucose (r = 0.21, P = 0.009). Stepwise multiple regression analysis showed that only age (beta= 0.006, SE = 0.0007, P < 0.001) and 2-h post-challenge glucose (beta = 0.0005, SE = 0.0002, P < 0.05) contributed significantly to the b/a ratio (adjusted R(2) = 0.38). CONCLUSIONS: These results indicate that post-challenge hyperglycaemia is an independent risk factor for arterial stiffness.

Age Factors↗
PubMed2001

Outcomes of transcatheter embolization in the treatment of coronary artery fistulas.

Thirteen children (seven male) with coronary artery fistula underwent percutaneous transcatheter occlusion. The age range was 8 months to 14 years (mean, 6.3 years). The fistulas had their origins from the right coronary artery (six), from the left anterior descending coronary artery (three), and from the left circumflex coronary artery (four). Drainage was to the right ventricle (seven), the right atrium (three), and one each to the pulmonary artery, left atrium, and superior caval vein. The fistulas were closed with coils in 10 patients, a Rashkind double-umbrella device in 1 patient, and an Amplatzer Duct Occluder in 2 patients. Complete occlusion was achieved in 9 of 13 patients. Complications consisted of migration of coils in four and transient arrhythmias or changes in the resting electrocardiogram in four patients. Follow-up studies 1 to 31 months (mean, 14.6 months) after occlusion noted only four patients with trivial (clinically insignificant) residual shunts. Owing to various coronary fistula morphologies, transcatheter occlusion requires availability of different embolization techniques. Short-term follow-up supports persistent clinical efficacy and transcatheter closure techniques as the initial form of therapy.

Adolescent↗
PubMed2001

Outcomes of intraoperative device closure of muscular ventricular septal defects.

BACKGROUND: The surgical management of muscular ventricular septal defects (mVSD) in the small infant is a challenge particularly when multiple and associated with complex cardiac lesions. Devices for percutaneous implantation have the advantage of ease of placement and for the double umbrella designs a wide area of coverage. We reviewed our experience and clinical outcomes of intraoperative mVSD device closure for such defects in small infants. METHODS: Since October 1989, intraoperative VSD device closure was a component of the surgical strategy in 14 consecutive patient implants (median age, 5.5 months; range, 3 to 11 kg), whose defects were thought difficult to approach using conventional techniques. Nine patients had associated complex cardiac lesions, 10 multiple mVSDs, and 4 patients had a previous pulmonary artery banding. RESULTS: There were 2 early deaths, 1 in a severely ill child who preoperatively had pulmonary hypertension and left ventricular failure and another in a patient with a hypoplastic left heart. Mean pulmonary to systemic flow ratio before device insertion was 3.5:1. Complete closure was achieved in 5 patients and clinically insignificant residual shunts persisted in 7. In 2 infants with significant residual lesions concomitant pulmonary artery banding was required. Postoperative mean pulmonary to systemic flow ratio was 1.7:1. In follow-up of the 12 surviving infants (mean, 41 months), 8 had complete closure and 3 persistent residual shunts. One patient with no residual shunting required heart transplantation for progressive ventricular failure 9 years after operation. All devices were well positioned on postoperative echocardiograms. There was 1 late death due to aspiration in a patient with a tiny residual shunt. CONCLUSIONS: Infants requiring operative intervention with mVSDs are difficult to manage and have an increased mortality and morbidity. Intraoperative VSD device placement for closure of mVSDs is feasible, can avoid ventriculotomy, division of intracardiac muscle bands, and is ideally suited for the neonate or infant.

Echocardiography↗
PubMed2001

No evidence of accelerated atherosclerosis in a 66-yr-old chylomicronemia patient homozygous for the nonsense mutation (Tyr61-->stop) in the lipoprotein lipase gene.

Whether chylomicronemia is atherogenic or not has yet to be determined in humans. We investigated a 66-yr-old female with severe chylomicronemia resulting from a lipoprotein lipase (LPL) deficiency. The patient's plasma triglyceride level was approximately 2000 mg/dl. Both LPL activity and the mass of postheparin plasma in this patient were virtually absent. A nonsense mutation in exon 3 (Tyr61-->Stop) was identified in the patient's LPL gene, and a restriction fragment length polymorphism analysis established that the patient was homozygous for this mutation. The patient was neither a diabetic nor a smoker. Clinically, the patient had never experienced pancreatitis or angia pectoris. An examination of her carotid, femoral and coronary arteries by ultrasonogram and electrocardiogram after exercise-tolerance testing showed no accelerated atherosclerosis. This case suggests that atherosclerosis may not occur despite massive hyperlipidemia, when LPL bridging was not present due to the absence of LPL secretion and circulating mass.

Aged↗
PubMed2001

Clonal chromosomal aberrations accompanied by strong telomerase activity in immortalization of human B-lymphoblastoid cell lines transformed by Epstein-Barr virus.

Human B-lymphoblastoid cell lines transformed by Epstein-Barr (EBV-LCLs) are considered to be immortalized, although most of them show a normal diploid karyotype. Recently, we and others have shown that only part of EBV-LCLs is immortalized by developing strong telomerase activity that stabilizes the telomeres. In this study, we investigated the change in karyotypes during immortalization. All the eight immortalized cell lines developed clonal chromosomal aberrations accompanied by the development of strong telomerase activity. Interestingly, abnormal chromosomes were not shared among the immortalized cell lines. These results strongly suggest that chromosomal rearrangements and induction of strong telomerase activity are two events that take place in parallel in the process of immortalization of EBV-LCLs, and indicate that EBV-LCLs are clearly divided into two distinct groups, pre-immortal cell lines mostly with a normal diploid karyotype and post-immortal cell lines with a clonally abnormal karyotype.

B-Lymphocytes↗
PubMed2001

Insulin resistance precedes the appearance of albuminuria in non-diabetic subjects: 6 years follow up study.

Microalbuminuria is a marker of increased risk of cardiovascular mortality in type 1 and type 2 diabetes, and in non-diabetic subjects. Little is known about the association between prospective changes of microalbuminuria and the risk factors of atherosclerosis, or gene polymorphism in non-diabetic subjects. We conducted a 6-year prospective study of risk factors for progression of albuminuria in non-diabetic subjects. The participants were 116 non-diabetic subjects who consecutively underwent medical examinations for Japanese-Americans living in Hawaii. In the baseline examination in 1992, normoalbuminuria was found in all subjects. After 6 years, 101 subjects remained normoalbuminuria (non-progressors), 15 subjects changing from normoalbuminuria to microalbuminuria or proteinuria and were defined as progressors. In progressors, compared with non-progressors, the fasting insulin level and HOMA-R were significantly higher at 3 years follow-up, and the systolic and diastolic pressure and Sigma insulin level were significantly higher at 6 years follow-up. Insulin resistance appeared earlier than the appearance of hypertension and albuminuria. In progressors, there was no significant correlation with angiotensin-converting enzyme (ACE) genotype or angiotensinogen (AGT) genotype compared with non-progressors. Therefore, the appearance of insulin resistance should be regarded as a remarkable mediator of albuminuria.

Aged↗
PubMed2001

Beta(3)-adrenergic receptor gene variant is associated with upper body obesity only in obese Japanese-American men but not in women.

We investigated gender differences in the relationships between the Trp64Arg variant of the beta(3)-adrenergic receptor (AR) gene in obesity and insulin resistance in nondiabetic subjects. In 476 nondiabetic Japanese-Americans (M/F=204/272), the Trp64Arg variant of the beta(3)-AR gene was examined. The presence or absence of the Trp64Arg mutation was examined in DNA separated from leukocytes in peripheral blood using the PCR-RFLP method. The frequency of abnormal allele of the beta(3)-AR gene was 0.18 for males and 0.17 for females, almost the same as the reported values in Japanese. There was no difference in the frequency of the beta(3)-AR gene variant between obese and non obese subjects for each gender. However, among obese males (body mass index > or =24.2 kg/m(2)), with the beta(3)-AR gene mutation, the waist-to-hip ratio, fasting insulin, 2-h insulin, total insulin, and HOMA, an index of insulin resistance, were all significantly higher than obese males without the mutation. In females, the index of obesity, insulin resistance, or lipid metabolism did not differ significantly between the subjects with or without the beta(3)-AR gene variant either in the obese and non-obese group. We suggest that the beta(3)-AR gene variant is not important as an obesity-inducing factor in Japanese. However, in males, when obesity becomes obvious, the beta(3)-AR gene variant is considered to influence the enhancement of insulin resistance, in association with visceral obesity.

Aged↗
PubMed2001

Gln27Glu variant of the beta2-adrenergic receptor gene is not associated with obesity and diabetes in Japanese-Americans.

The beta(3)-adrenergic receptor (AR) gene variant (Trp64Arg) has been reported to be associated with obesity and insulin resistance in humans. However, this association remains controversial. We investigated the relationships between the beta(2)-AR gene variant (Gln27Glu) and obesity, insulin resistance, and serum lipids in Japanese-Americans. The frequency of an abnormal Gln27Glu allele in the beta(2)-AR gene in 652 subjects was 0.092 in males, 0.077 in females, and 0.084 overall, markedly lower than the previously reported value of 0.4 in Caucasian men and women. In both males and females, there were no differences in the indices of obesity, insulin resistance, and serum lipid levels between the subjects with and without the beta(2)-AR gene (Gln27Glu) variant in patients with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes (DM). The frequency of the beta(2)-AR gene (Gln27Glu) variant tended to increase with worsening of glucose tolerance, but the differences were not statistically significant. Furthermore, there were no differences in the frequency of the beta(2)-AR gene variant in either males or females with obesity (body mass index [BMI], > or = 25.2). Even in Japanese-Americans, who have a more westernized life style than Japanese, the association of the beta(2)-AR gene (Gln27Glu) variant with the parameters of obesity, insulin resistance, and serum lipid level has yet to be clarified. We conclude that the beta(2)-AR gene (Gln27Glu) variant might not be an important factor for obesity or IGT in Japanese subjects.

Aged↗
PubMed2001

Intravascular and intracardiac stents used in congenital heart disease.

Intravascular or intracardiac stenoses occur in many forms of congenital heart disease or after attempted surgical repair. Although balloon dilation is one option for management, restenosis can occur due to elastic recoil immediately after the procedure. To address to such stenotic lesions, many reports support implanting endovascular stents to provide a framework for vessel expansion. Both balloon-expandable fixed tubular mesh stainless steel devices, and self-expandable stents have had an extensive clinical application. In pediatric patients, stents are used for a variety of stenoses, such as systemic venous obstruction pathways (eg, Mustard, Fontan baffle, or bidirectional cavopulmonary connections), pulmonary artery, right ventricular to pulmonary conduits, aortic coarctation, the arterial duct, aorticopulmonary collaterals, or postoperative systemic to pulmonary shunts. Because of improvements in device profile, implantation rates have increased. Complications such as stent fracture, migration, aneurysm formation, and in-stent restenosis occur but only rarely. This latter event may be because of intimal hyperplasia and/or continued vessel (and patient) growth related to the stent diameter. As such, some instances require redilation to manage the acquired lesion. Stent application has importantly altered management algorithms in congenital heart disease.

Adolescent↗
PubMed2001

Association of apolipoprotein E phenotype with hypertension in Japanese-Americans: data from the Hawaii-Los Angeles-Hiroshima Study.

We evaluated the association between the phenotypes or alleles of apolipoprotein E and hypertension in Japanese-Americans living in Hawaii or Los Angeles. The study consisted of 932 nondiabetic participants aged 40-79 years. Of these participants, 315 were hypertensive, while the remainder were normotensive. The prevalence of hypertension was higher in subjects with the e2 allele than in those without. Using a multivariable prediction model that included age, serum glucose, insulin, lipids, and body mass index, we found the epsilon2 allele to be associated with hypertension in men (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.05-2.24) and for both sexes combined (OR, 1.35; 95% CI, 1.05-1.73). In a follow-up study, 37 of the 352 (11%) normotensive subjects had developed hypertension 4 years after the baseline examination. The frequencies of the apolipoprotein E phenotype E3/2 and the epsilon2 allele were higher in the subjects who became hypertensive than in those who remained normotensive. The E3/2 phenotype was associated with incidence of hypertension after adjustment for age, sex, baseline body mass index, and systolic blood pressure (OR, 1.75; 95% CI, 1.01-2.90). When serum lipids, glucose, and insulin were included in this analysis, the E3/2 phenotype tended to be associated with the incidence of hypertension. In conclusion, the epsilon2 allele of apolipoprotein E was associated with hypertension in Japanese-Americans. This association may be mediated via high levels of serum triglycerides that in turn are mediated in part by the epsilon2 allele. Nonlipid mechanisms may also be responsible for the effect of the epsilon2 allele on hypertension.

Aged↗
PubMed2001

Hyperinsulinemia for the development of hypertension: data from the Hawaii-Los Angeles-Hiroshima Study.

The present study was to assess the association of metabolic factors including hyperinsulinemia, with the development of hypertension in Japanese-Americans. One hundred forty normotensive (<140/90 mmHg) subjects aged 40 to 69 years old from the Hawaii-Los Angeles-Hiroshima study were followed for 15 years. Patients with cardiovascular disease were excluded. Body mass index (BMI), blood pressure (BP), serum total cholesterol (TC), triglycerides (TG), uric acid (UA), and glucose and insulin responses at baseline, 1 h, and 2 h after a glucose load were analyzed. Seventeen subjects became hypertensive (systolic BP > or = 160 mmHg, diastolic BP > or = 95 mmHg, or received drug treatment) during follow-up. Age- and sex-adjusted BMI, BP, serum UA, TG, insulin, and changes in fasting glucose during follow-up were higher in subjects who later became hypertensive than in those who did not. There was no difference in the change in BMI. Age- and sex-adjusted relative risks for the development of hypertension by quartiles of BMI, serum UA, TG, and the sum of insulin values (sigmainsulin) during a glucose load were highest in highest quartile of the distribution. When age, sex, systolic BP, BMI, serum UA, TC, TG, fasting glucose, sigmainsulin, and the change in BMI were used in a proportional hazard analysis, hyperinsulinemia, hyperuricemia, and systolic BP were found to be significant risk factors for hypertension. In conclusion, hyperinsulinemia, as well as obesity, hyperuricemia, and hypertriglyceridemia were associated with hypertension in Japanese-Americans. Hyperinsulinemia and hyperuricemia were independent predictors of the development of hypertension.

Blood Glucose↗
PubMed2001

Regression of both pituitary and ovarian cysts after administration of thyroid hormone in a case of primary hypothyroidism.

We report a 19-year-old woman who was diagnosed as polycystic ovary. Hypothyroidism with a markedly elevated TSH level and an enlarged pituitary gland on MRI were noted. The 123I uptake was decreased to 6.5%. After treatment with thyroid hormone, regression of the enlarged pituitary and the ovarian cysts was observed. In the present case, hypothyroidism was considered to have caused a reversible enlargement of the pituitary gland and concomitant polycystic ovary. We concluded that the polycystic ovary might have resulted from the effects of an excessive amount of TSH on immature ovaries.

Adult↗
PubMed2001

Evidence of primary beta-cell destruction by T-cells and beta-cell differentiation from pancreatic ductal cells in diabetes associated with active autoimmune chronic pancreatitis.

OBJECTIVE: Diabetes associated with autoimmune chronic pancreatitis (ACP) is a subtype of diabetes that is responsive to corticosteroid treatment of progressive endocrine and exocrine dysfunction. However, little is known about pathological changes of islet and exocrine pancreas in ACP. RESEARCH DESIGN AND METHODS: We examined pancreatic specimens obtained on biopsy from four diabetic men with ACP (mean [range]: age 62 years [48-78], duration of ACP 3 months [1-5], duration of diabetes 1 month [0-3]) morphologically, immunohistochemically, and morphometrically. RESULTS: The pancreatic specimens in all cases exhibited inflammatory cell infiltration surrounding ductal cells and extensive fibrosis. Some islets were infiltrated with mononuclear cells with disrupted beta-cells. The subsets of T-cells infiltrated to the islets were mainly CD8(+). Islet beta-cell volume was decreased; the mean percentage area of beta-cells in the islets in four cases with ACP were 16% (range 13-20) (P = 0.0015 vs. type 2 diabetic patients, 48% [27-73], n = 8; P = 0.0002 vs. nondiabetic control subjects, 58% [39-77], n = 7). Preserved ductal cells were surrounded predominantly by CD8(+) or CD4(+) T-cells. Some cytokeratin 19-positive ductal cells contained insulin and glucagon, representing upregulated differentiation of islet cells from ductal cells. Insulin promoter factor-1 (IPF-1) was hyperexpressed in insulin-containing ductal cells. CONCLUSIONS: Diabetes associated with ACP is caused by T-cell-mediated mechanisms primarily involving islet beta-cells as well as pancreatic ductal cells. In ACP, ductal islet precursor cells were associated with IPF-1 hyperexpression, suggesting a critical role of IPF-1 on islet cell differentiation and eventual beta-cell restoration.

Acute Disease↗