Biomedical subjects

Koichi Matsubara

Publications and source records attributed to Koichi Matsubara.

9 recordsLinked to original sources

PubMed2003

T-cell function in anti-GAD65(+)diabetes with residual beta-cell function.

We have recently reported that in patients with anti-glutamic acid decarboxylase (GAD) 65(+)diabetes with residual beta-cell function, most with a 'high-titer' (>10U/ml) required insulin within 5 years, whereas most with a 'low-titer' (1.3-9.9U/ml) did not need insulin for over 15-20 years after the onset. We therefore examined T-cell function to evaluate the difference between the high-titer and low-titer groups. Interleukin (IL)-10 production upon polyclonal activation was significantly lower in the high-titer group than in the low-titer group. The serum level of interferon-inducible protein-10 (IP-10) was higher in the high-titer than the low-titer group. Although GAD65-reactive CD4(+)cells in the periphery were detected in both groups, a significant positive correlation between serum IP-10 level and the number of GAD65-reactive CD4(+)cells was observed only in the high-titer group. Therefore, it has been speculated that the co-existence of GAD65-reactive IFN-gamma-producing CD4(+)cells and a high serum IP-10 level may be important for rapid disease progression as seen in the high-titer group. Based upon these results, T-cell function is considered to be different between the high-titer and low-titer groups in anti-GAD65(+)diabetes with residual beta-cell function, supporting our previous findings regarding the clinical outcome of insulin-dependence in the two groups.

Adult↗

PubMed2003

Vitamin D receptor gene polymorphism affects onset pattern of type 1 diabetes.

Type 1 diabetes mellitus is recognized as a T-cell-mediated autoimmune disease. Vitamin D compounds are known to suppress T-cell activation by binding to the vitamin D receptor (VDR); and thus, VDR gene polymorphisms may be related to T-cell-mediated autoimmune diseases. We, therefore, investigated a VDR gene polymorphism in type 1 diabetes. We examined the VDR gene Bsm I polymorphism in 203 type 1 diabetic patients and 222 controls, and the association between the VDR gene polymorphism and type 1 diabetes and their onset pattern. We found a significantly higher frequency of B allele in type 1 diabetics overall, compared with controls (P = 0.0010). Moreover, there was a significant difference in B-allele frequency between acute-onset type 1 diabetics and controls (P = 0.0002), whereas this difference was not observed between slow-onset type 1 diabetics and controls. Regardless of the existence of islet-associated autoantibody, we found a significant difference in B-allele frequency between acute-onset type 1 diabetics and controls. In conclusion, we found an association between a VDR gene polymorphism and acute-onset type 1 diabetes. Assessment of this VDR gene polymorphism may contribute to prediction of the onset pattern in individuals with a high risk of type 1 diabetes.

Acute Disease↗

PubMed2002

Single-nucleotide polymorphism analysis by hybridization protection assay on solid support.

The clinical need for high-throughput typing methods of single-nucleotide polymorphisms (SNPs) has been increasing. Conventional methods do not perform well enough in terms of speed and accuracy to process a large number of samples, as in clinical testing. We report a new DNA microarray method that uses hybridization protection assay (HPA) by acridinium-ester-labeled DNA probes. Probes were immobilized on the bottom of streptavidin-coated microtiter plates by streptavidin-biotin binding. We studied aldehyde dehydrogenase 2 (ALDH2) genotyping using two probes, discriminating A/G polymorphism. We also designed four probes to type the Alzheimer's disease-related gene ApoE, which has three genotypes (ApoE2, 3, and 4) determined by two SNP loci (C/T polymorphism). SNP analysis of the ALDH2 gene or the ApoE gene from human genome samples by solid-phase HPA was successful. Unlike other methods, the microarray by HPA does not require a washing step and can be completed within 30min. It also has advantages in discriminating one-base mismatch in targets. These characteristics make it a good candidate for practical SNP analysis of disease-related genes or drug-metabolizing enzymes in large numbers of samples.

Acridines↗

PubMed2002

Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol, independent of body mass index, in the Japanese population.

Adiponectin, which is secreted specifically by adipose tissue, has been shown to act as an anti-atherosclerotic protein by direct effects on endothelial cells. Clinical studies have shown that adiponectin levels are lower in individuals with obesity, diabetes and coronary artery disease. The present study investigated relationships between serum adiponectin levels and body mass index (BMI), blood pressure, insulin resistance index, lipid profile, uric acid and high-sensitivity C-reactive protein levels in a large number of Japanese subjects not taking any medication for metabolic disease and without severe illness (705 men and 262 women; age 30-65 years; BMI 22.5+/-2.9 kg/m(2)). The serum adiponectin concentration was measured by ELISA, without a protein-denaturing step. The insulin resistance index was assessed by homoeostasis model assessment (HOMA-IR). The serum concentration of adiponectin in women (13.5+/-7.9 microg/ml) was significantly higher than that in men (7.2+/-4.6 microg/ml). The serum adiponectin level was negatively correlated with BMI, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, insulin, HOMA-IR, total cholesterol, triacylglycerols, low-density lipoprotein (LDL)-cholesterol and uric acid, and positively correlated with high-density lipoprotein (HDL)-cholesterol. The correlations between serum adiponectin level and insulin, HOMA-IR, triacylglycerols, HDL-cholesterol, LDL-cholesterol and uric acid were significant even after adjustment for age, sex and BMI. Stepwise multiple regression analysis revealed that HDL-cholesterol, sex, BMI and HOMA-IR were independently correlated with the serum adiponectin level (R(2)=0.377). These findings suggest that the serum adiponectin level is negatively correlated with HOMA-IR and positively correlated with HDL-cholesterol, independent of age, sex and BMI, in the Japanese population.

Adiponectin↗

PubMed2002

Effects of pioglitazone on metabolic parameters, body fat distribution, and serum adiponectin levels in Japanese male patients with type 2 diabetes.

The aim of this study was to evaluate the effects of pioglitazone on clinical and metabolic parameters, body fat distribution, and serum adiponectin, a recently discovered antiatherosclerotic hormone, in Japanese patients with type 2 diabetes. Ten male patients aged 40 to 66 (57.7 +/- 7.4) years, who were being treated with dietary therapy alone (n = 7) or with a stable dose of sulfonylurea (n = 3), were studied at baseline and after 3 months of pioglitazone treatment (30 mg/d). Body mass index (BMI), blood pressure, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), serum insulin, adiponectin, and lipid profile were measured. Also, visceral adipose tissue area (VAT) and subcutaneous adipose tissue area (SAT) at the umbilical level were determined by computed tomographic (CT) scanning. Mean blood pressure (109 +/- 14 to 101 +/- 10 mm Hg), FPG (8.6 +/- 1.4 to 7.0 +/- 1.0 mmol/L), serum insulin (54 +/- 11 to 30 +/- 8 pmol/L, P <.01 for all), and HbA1c (6.7 +/- 0.8 to 6.1% +/- 0.6%, P =.013) decreased significantly during 3 months of pioglitazone treatment. BMI (26.4 +/- 3.2 to 27.0 +/- 3.5 kg/m2), low-density lipoprotein (LDL) cholesterol (124 +/- 24 to 138 +/- 24 mg/dL) and SAT (155 +/- 69 to 179 +/- 81cm2, P <.05 for all) increased, while triglycerides and high-density lipoprotein (HDL) cholesterol did not change significantly after 3 months of pioglitazone treatment. Serum adiponectin level increased in all patients (4.8 +/- 1.7 to 14.4 +/- 2.1 microg/mL, P =.005). VAT tended to increase (165 +/- 38 to 180 +/- 46 cm2) and VAT/SAT ratio tended to decrease (1.2 +/- 0.3 to 1.1 +/- 0.3), but these differences did not reach statistical significance. These results suggest that pioglitazone exerts good glycemic and blood pressure control despite increased BMI and SAT in Japanese male patients with type 2 diabetes. It is also suggested that pioglitazone may have an antiatherosclerotic effect by increasing serum adiponectin level.

Adiponectin↗

PubMed2002

L-cysteine prevents oxidation-induced block of the cardiac Na+ channel via interaction with heart-specific cysteinyl residues in the P-loop region.

The present study investigated the protective effects of L-cysteine on the oxidation-induced blockade of Na+ channel a-subunits, hH1 (cardiac) and hSkM1 (skeletal), expressed in COS7 cells. Na+ currents were recorded by the whole-cell patch clamp technique (n = 3-7). L-cysteine alone blocked hH1 and hSkM1 in a dose-dependent manner, with saturating L-cysteine block at 3,000 micromol/L. Hg2+, a potent sulfhydryl oxidizing agent, blocked hH1 with a time to 50% inhibition (Time50%) of 20s. Preperfusion of COS7 cells with 100 micromol/L L-cysteine significantly slowed the Hg2+ block of hH1 (Time50% = 179 s). L-cysteine did not prevent Hg2+ block of hSkM1 (Time50% = 37s) or the C373Y hH1 mutant (Time50% = 43s). As for other sulfo-amino acids, homocysteine prevented the Hg2+ block of hH1, with the Time50% (70s) being significantly smaller than that of L-cysteine, whereas methionine did not prevent the Hg2+ block of hH1. L-cysteine did not prevent the Cd2+ block of hH1. These results indicate that L-cysteine selectively acts on heart-specific Cys373 in the P-loop region of hH1 to prevent Cys373 from the oxidation-induced sulfur-Hg-sulfur bridge formation.

Cysteine↗

PubMed2002

The status of hypertension management in Japan in 2000.

To evaluate the current status of the management of hypertensive patients in Japan, we investigated 907 treated hypertensive patients (486 females and 421 males; mean age, 66.7 years) followed by cardiologists. According to the guidelines for the management of hypertensive patients in Japan in 2000 (JSH-2000), only 41.5% of the subjects achieved the target blood pressure, with a mean systolic blood pressure of 140.0+/-14.9 mmHg and a mean diastolic blood pressure of 80.0+/-10.7 mmHg. There were no differences between patients with and without concurrent disease or among age groups (<60, 60-69, 70-79, and 80 years and over) in systolic blood pressure levels achieved. However, the diastolic blood pressure decreased with age, indicating an increase of the pulse pressure. Overall, the prescription rates were: calcium channel blockers (CCBs), 73.0%; angiotensin converting enzyme inhibitors (ACE-inhibitors), 31.3%; angiotensin receptor blockers (ARBs), 18.9%; beta-blockers, 16.2%; and diuretics, 10.1%. Although some selection of antihypertensive drugs was based on evidence from previous trials on hypertensive patients with diabetes mellitus, chronic heart failure and renal insufficiency, overall, CCBs were selected in all age groups and in all comorbid conditions. In conclusion, Japanese cardiologists do not appear to consider age and comorbidity when choosing antihypertensive managements. Based on current evidence, the management of hypertension should be individualized, with the blood pressure target level and antihypertensive medications chosen on the basis of age and comorbidity.

Adult↗

PubMed2002

Effect of the angiotensin II receptor antagonist losartan on uric acid and oxypurine metabolism in healthy subjects.

OBJECTIVE: The acute effects of the angiotensin II receptor antagonist losartan on uric acid and oxypurine metabolism were evaluated. METHODS: Losartan (50 mg) was administered orally to 6 healthy males. Blood and urine samples for uric acid and oxypurine were collected before and up to 6 hours after losartan administration. The same examinations were performed later using enalapril (5 mg). RESULTS: Losartan decreased the serum uric acid concentration (from 5.9 +/- 0.9 to 5.2 +/- 1.0 mg/dl) and increased its fractional clearance, which reached a maximum after 2 hours, while enalapril did not. Losartan also induced an increase in the plasma concentration of hypoxanthine, peaking in the fourth hour, and a decrease in its urinary clearance, while the plasma xanthine concentration and its urinary clearance were unchanged. The extent of uric acid excretion was much greater than that of the oxypurines. CONCLUSIONS: Losartan, which has a high affinity for the urate/anion exchanger, has a transient uricosuric effect. Our data indicate that losartan induces a significant decrease in the urinary excretion of hypoxanthine without changes in xanthine.

Adult↗

PubMed2002

Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population.

An adipocyte-derived peptide, adiponectin (also known as GBP28), is decreased in subjects with type 2 diabetes. Recent genome-wide scans have mapped a diabetes susceptibility locus to chromosome 3q27, where the adiponectin gene (APM1) is located. Herein, we present evidence of an association between frequent single nucleotide polymorphisms at positions 45 and 276 in the adiponectin gene and type 2 diabetes (P = 0.003 and P = 0.002, respectively). Subjects with the G/G genotype at position 45 or the G/G genotype at position 276 had a significantly increased risk of type 2 diabetes (odds ratio 1.70 [95% CI 1.09-2.65] and 2.16 [1.22-3.95], respectively) compared with those having the T/T genotype at positions 45 and 276, respectively. In addition, the subjects with the G/G genotype at position 276 had a higher insulin resistance index than those with the T/T genotype (1.61 +/- 0.05 vs. 1.19 +/- 0.12, P = 0.001). The G allele at position 276 was linearly associated with lower plasma adiponectin levels (G/G: 10.4 +/- 0.85 microg/ml, G/T: 13.7 +/- 0.87 microg/ml, T/T: 16.6 +/- 2.24 microg/ml, P = 0.01) in subjects with higher BMIs. Based on these findings together with the observation that adiponectin improves insulin sensitivity in animal models, we conclude that the adiponectin gene may be a susceptibility gene for type 2 diabetes.

Adiponectin↗