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Biomedical subjects

Masaru Sakurai

Publications and source records attributed to Masaru Sakurai.

12 recordsLinked to original sources

Factors associated with improvement of fasting plasma glucose level by mealtime dosing of a rapid-acting insulin analog in type 2 diabetes.

This study investigated whether strict control of plasma glucose levels with mealtime dosing of a rapid-acting insulin analog improves early morning fasting plasma glucose (FPG) levels in patients with type 2 diabetes. A rapid-acting insulin analog was administered at each mealtime to 40 Japanese patients with type 2 diabetes whose existing antidiabetic medication was discontinued. Approximately one-half (52.5%) of the patients achieved a minimum early morning FPG levels achievable (nadir FPG) of <120mg/dL with mealtime dosing of a rapid-acting insulin analog alone; no basal insulin replacement was needed in these patients. Nadir FPG levels were independent of duration of diabetes, baseline body mass index (BMI) or glycemic control. All patients who had been treated with sulfonylureas needed basal insulin replacement. Low responses of insulin to glucagon and to arginine, and high response of glucagon to arginine may explain the failure to improve FPG levels with postprandial insulin replacement alone. In conclusion, approximately one-half of the patients with type 2 diabetes achieved appropriate control of FPG by rapid-acting insulin analog monotherapy. Basal insulin secretory defects in type 2 diabetes may be estimated by the responses of insulin to glucagon and to arginine and the response of glucagon to arginine. This study contributes to a better understanding of the pathophysiology contributing to the heterogeneity in the characteristics of insulin secretion in type 2 diabetes.

Aged↗

Separation of CD34+ cells from human peripheral blood through polyurethane foaming membranes.

Cell separation from peripheral blood was investigated using polyurethane (PU) foaming membranes and PU membranes (pore size, 5 or 12 mum) at different blood permeation speeds. Permeation ratio of hematopoietic stem cells (CD34(+) cells) through the PU membranes was the lowest among the blood cells at any blood permeation speed. This is thought to be because CD34(+) cells are more adhesive than red blood cells (RBCs), platelets, T cells, and B cells. Primitive hematopoietic stem and progenitor cells tend to adhere to the surface of mature blood cells, because of the high expression of cell-adhesion molecules on the surface of the cells. Human serum albumin solution was exposed to PU-COOH membranes to detach adhered cells from the surface of the membranes, allowing isolation of CD34(+) cells and reduction of RBCs in the permeate solution. Most purified CD34(+) cells (high recovery ratio of CD34(+) cells divided by recovery ratio of RBCs) were obtained in the recovery process using PU-COOH membranes (pore size, 5.2 microm) at a permeation speed of 0.3-1 mL/min.

Adult↗

Tumor necrosis factor-alpha-induced production of plasminogen activator inhibitor 1 and its regulation by pioglitazone and cerivastatin in a nonmalignant human hepatocyte cell line.

Plasminogen activator inhibitor 1 (PAI-1) is an important mediator of atherosclerosis and liver fibrosis in insulin resistance. Circulating levels of PAI-1 are elevated in obese individuals, and PAI-1 messenger RNA is significantly higher in the livers of obese type 2 diabetic individuals than in nonobese type 2 diabetic individuals. To address the mechanism underlying the up-regulation of hepatic PAI-1 in obesity, we tested the effects of tumor necrosis factor alpha (TNF-alpha), an important link between obesity and insulin resistance, on PAI-1 production in the nonmalignant human hepatocyte cell line, THLE-5b. Incubation of THLE-5b cells with TNF-alpha stimulated PAI-1 production via protein kinase C-, mitogen-activated protein kinase-, protein tyrosine kinase-, and nuclear factor-kappaB-dependent pathways. A thiazolidinedione, pioglitazone, reduced TNF-alpha-induced PAI-1 production by 32%, via protein kinase C- and nuclear factor-kappaB-dependent pathways. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin inhibited TNF-alpha-induced PAI-1 production by 59%, which was reversed by coincubation with mevalonic acid. In conclusion, obesity and TNF-alpha up-regulation of PAI-1 expression in human hepatocytes may contribute to the impairment of the fibrinolytic system, leading to the development of atherosclerosis and liver fibrosis in insulin-resistant individuals. A thiazolidinedione and a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor may thus be candidate drugs to inhibit obesity-associated hepatic PAI-1 production.

Cell Line↗

Gender differences in the association between anthropometric indices of obesity and blood pressure in Japanese.

To investigate which of four anthropometric variables of obesity has the strongest association with blood pressure (BP), and to investigate whether there are gender differences in these relationships in Asian adults, we evaluated the associations of four anthropometric variables, body mass index (BMI), waist circumference, waist-to-hip ratio and waist-to-height ratio, with BP and the prevalence of hypertension in a cross-sectional study. A total of 4,557 employees of a metal-products factory in Toyama, Japan (2,935 men and 1,622 women, aged 35 to 59 years) were included in the study. Waist circumference in men and BMI in women had the strongest associations with BP. As for the age-adjusted rate ratio (RR) of the prevalence of hypertension for one standard deviation increase in each anthropometric variable, RR was the highest for waist circumference in men (RR, 1.44; 95% confidence interval [CI], 1.31-1.58), and for BMI in women (RR, 1.61; 95% CI, 1.38-1.88). The associations of waist circumference in men and BMI in women remained significant after adjustment for each of the other variables. The associations of waist-to-height ratio with BP and the prevalence of hypertension were a little weaker than those of waist circumference for both men and women. In conclusion, among four anthropometric variables of obesity--i.e., BMI, waist circumference, waist-to-hip ratio, and waist-to-height ratio-waist circumference had the strongest association with BP and the prevalence of hypertension in men and BMI had the strongest association with BP and hypertension in women. Waist circumference in men and BMI in women should be given more importance in the screening of and guidelines on hypertension in Asians.

Adult↗

Pancreatic exocrine and endocrine events occur concomitantly but independently during the course of fulminant type 1 diabetes.

Although pancreatic exocrine enzymes are often elevated in patients with fulminant type 1 diabetes, the onset of this elevation and its significance in disease development remain unclear. We therefore investigated the significance of elevated serum enzyme concentrations and pancreatic swelling in the development of fulminant type 1 diabetes. Serum pancreatic exocrine enzymes, including amylase, elastase-I, lipase and trypsin, were measured during the course of the disease in 11 patients with fulminant type 1 diabetes (3 men and 8 women; a range of age 24-73 years, median 33 years; a range of HbA1c at onset 4.5-6.7%, median 6.0%), all of whom developed ketotic diabetes requiring intensive insulin therapy within a month. At least one pancreatic exocrine enzyme was elevated in each patient during the course of the disease. The concentration of enzymes on admission could not be correlated with urinary excretion of C-peptide. The time course of increase in serum amylase varied in these patients. In conclusion, neither the level of serum amylase nor the swelling of pancreas was associated with the onset or severity of fulminant type 1 diabetes. The pancreatic exocrine and endocrine events may occur concomitantly but independently during the course of fulminant type 1 diabetes.

Adult↗

Measurement of thyroid blood flow area is useful for diagnosing the cause of thyrotoxicosis.

We have utilized color Doppler ultrasonography (CDU) to evaluate the thyroid blood flow area (TBFA) quantitatively, and we propose criteria to differentiate Graves' disease (GD) and destruction-induced thyrotoxicosis (DT) in patients with thyrotoxicosis. We studied 32 patients with diffuse toxic goiter, 21 with GD in the euthyroid state, 12 with chronic thyroiditis in the euthyroid state, and 31 normal individuals. TBFA was calculated as (thyroid blood flow area/thyroid area) x 100%. CDU showed high sensitivity (84%) and specificity (90%) in distinguishing GD from DT when TBFA was between 7.7% and 8.8%. Using CDU to diagnose GD in cases with TBFA >or=8% or positive serum anti-thyrotropin receptor antibody (TRAb), the sensitivity was 95% and the specificity was 90%, which are similar results to those obtained when GD was diagnosed by radioactive iodine uptake (sensitivity 100%, specificity 90%). Therefore, CDU is a more useful and economical method of distinguishing GD patients with TBFA of 8% or above from DT than measurement of TRAb or radioactive iodine uptake.

Adult↗

Relationship between plasma hANP level and pretibial edema by pioglitazone treatment.

Pioglitazone is an insulin-sensitizer with a thiazolidinedione structure. It is used to reduce hyperglycemia and is frequently prescribed to type 2 diabetic patients. However, it causes edema as an adverse effect in some patients. Although the mechanism of edema is unclear, it may bring an increased risk of congestive heart failure. We investigated whether pioglitazone correlates with the level of plasma human atrial natriuretic peptide (hANP), a marker for congestive heart failure. We administered 15 mg/day of pioglitazone for 3 months to 49 patients (34 men and 15 women; mean age: 64+/-12 years) with type 2 diabetes and no history of pretibial edema. Three of the patients complained of pretibial edema during the 3-month period, and their plasma hANP levels were higher than those of the other 46 before and during the treatment. We therefore suspect that pretibial edema appearing after administration of low-doses of pioglitazone coincides with the level of plasma hANP, and that the appearance of pretibial edema may reflect an increase in circulating blood volume induced by pioglitazone.

Aged↗

Term delivery choriocarcinoma patient with brain and lung metastases successfully treated by etoposide, methotrexate, actomycin D, cyclophosphamide and vincristine (EMA-CO) chemotherapy.

It is well known that antecedent term delivery and metastasis to sites other than the lungs and vagina are high risk factors for patients with gestational trophoblastic neoplasia. Here we report on a patient with choriocarcinoma who presented with brain and lung metastases after term delivery and was treated by EMA-CO chemotherapy. A 31-year-old woman delivered a healthy infant at term. Frequent episodes of hemoptysis occurred beginning 3 weeks after the delivery. On admission to our hospital, she had lesions in the uterus, lungs and brain as well as motor aphasia and hemiplagia. The pretreatment beta-hCG level was 21,000 ng/ml and the WHO score was 16 (high-risk group). The EMA-CO regimen was administrated as first-line chemotherapy and the patient achieved complete remission after 7 courses. Treatment was terminated after 11 courses and maintained with etoposide (25 mg/day) for 6 months. The patient has remained in complete remission for more than 16 years without other adjuvant therapies. We believe that EMA-CO can currently be considered the regimen of first choice for most high-risk patients with gestational trophoblastic neoplasia in view of its effectiveness and excellent tolerability.

Adult↗

Peripheral blood cell separation through surface-modified polyurethane membranes.

Cell separation from peripheral blood was investigated using surface-modified polyurethane (PU) membranes with different functional groups. Both red blood cells and platelets could pass through unmodified PU and PU-SO(3)H membranes, whereas the red blood cells preferentially passed through PU-N(C(2)H(5))(2) and PU-NHC(2)H(4)OH membranes. The permeation ratio of T and B cells was <25% for the surface-modified and unmodified PU membranes. CD34(+) cells have been recognized as various kinds of stem cells including hematopoietic and mesenchymal stem cells. The adhesiveness of CD34(+) cells on the PU membranes was found to be higher than that of red blood cells, platelets, T cells, or B cells. Overall, the adhesiveness of blood cells on the PU membranes increased in the following order: red blood cells </= platelets < T cells </= B cells < CD34(+) cells. Treatment of PU-COOH membranes with a human albumin solution to detach adhered blood cells, allowed recovery of mainly CD34(+) cells in the permeate, whereas both red blood cells and platelets could be isolated in the permeate using unmodified PU membranes. The PU membranes showed different permeation and recovery ratios of specific cells depending on the functional groups attached to the membranes.

Antigens, CD↗

Serum protein adsorption and platelet adhesion on aspartic-acid-immobilized polysulfone membranes.

Polysulfone (PSf) membranes that covalently conjugated with aspartic acid (ASP-PSf) were prepared and analyzed for hemocompatability. Compared to PSf or other types of surface-modified PSf membranes, the ASP-PSf membranes had a reduced ability to adsorb protein from either a plasma solution or a mixed solution of albumin, globulin and fibrinogen. This appears to be due to the creation of a hydrophilic surface by the aspartic acid zwitterion immobilized on the ASP-PSf membranes. Furthermore, the analyses of membrane protein adsorption showed that a mixed protein solution recapitulates the cooperative adsorption of proteins that occurs in plasma. We also found that the number of adhering platelets was the lowest on the ASP-PSf membranes and, in general, that platelet adhesion decreased in parallel with fibrinogen adsorption. In summary, aspartic acid immobilized on the ASP-PSf membranes, which have zwitterions with a net zero charge, effectively contributes to the hydrophilic and hemocompatible sites on the surface of the hydrophobic PSf membranes.

Adsorption↗

Serum protein adsorption and platelet adhesion on pluronic-adsorbed polysulfone membranes.

We examined plasma protein adsorption and platelet adhesion to polysulfone (PSf) flat membranes coated with Pluronic with varying polyethylene oxide (PEO) block length. Adsorption of albumin, globulin and fibrinogen to Pluronic-coated PSf membranes was independent of plasma dilution when concentrations of human blood plasma above 20% were applied. Increasing coating concentrations of aqueous Pluronic solution resulted in decreased protein adsorption by the PSf membranes. Pluronic F68, which was more hydrophilic than Pluronic L62 or L64 and had 80% of PEO content, was the most effective at suppressing the adsorption of plasma proteins and platelet adhesion to PSf membranes. We developed a mixed protein solution containing human albumin, gamma-globulin and fibrinogen to attempt to mimic the competitive and cooperative binding effects found in plasma. Fibrinogen adsorption from plasma could be recapitulated by the mixed protein solution. The number of platelets adhering to the PSf membranes decreased as the coating concentration of Pluronic solution was increased, and platelet adhesion decreased in parallel with fibrinogen adsorption. These results suggest that the bioinert property of PEO segments in the Pluronic, which is ascribed to their high flexibility in aqueous media, suppresses the adsorption of plasma proteins and platelets to the Pluronic-coated PSf membranes.

Adsorption↗

Fulminating onset type 1 diabetes with positivity for anti-GAD antibody and elevated pancreatic exocrine enzyme concentrations.

A 52-year-old man was admitted to our hospital for diabetic ketoacidosis. On admission, Hb(A1c) was 6.5%, anti-GAD antibody 10.3 U/ml, serum amylase 144 IU/l, lipase 169 U/l and elastase-I 1,000 ng/dl. There were no abdominal symptoms, and abdominal CT showed unremarkable findings. He was treated with intensive insulin therapy. After 1 month, urinary excretion of C-peptide was 3.8 microg/day. Serum pancreatic exocrine enzyme concentrations returned to normal after 3 months. After 10 months, anti-GAD antibody had become negative, but insulin therapy was still needed for glycemic control. This report concerns a case of autoimmune fulminating onset type 1 diabetes.

Aspartate Aminotransferases↗