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Biomedical subjects

Y Sako

Publications and source records attributed to Y Sako.

At least 109 records · Page 6Linked to original sources

Improvement in early saphenous vein graft patency after coronary artery bypass surgery with antiplatelet therapy: results of a Veterans Administration Cooperative Study.

To determine whether specific antiplatelet therapies improved vein graft patency after coronary artery bypass grafting (CABG) we compared (1) aspirin, 325 mg daily, (2) aspirin, 325 mg three times daily, (3) aspirin plus dipyridamole (325 mg and 75 mg, respectively, three times daily), (4) sulfinpyrazone (267 mg three times daily), and (5) placebo (three times daily). Therapy, except aspirin, was started 48 hr before CABG. When aspirin was a treatment, one 325 mg dose was given 12 hr before surgery and therapy was maintained thereafter according to the assigned regimen. Angiographic graft patency data were obtained within 60 days of surgery. Analysis of early graft patency in 555 patients (1781 grafts), revealed the following graft patency rates: aspirin daily, 93.5%; aspirin three times daily, 92.3%; aspirin and dipyridamole, 91.9%; and sulfinpyrazone, 90.2%. All aspirin-containing therapeutic regimens improved (p less than .05) graft patency compared with placebo (85.2%). Chest tube drainage measured within the first 35 hr after CABG revealed that the median loss with aspirin daily (965 ml), aspirin three times daily (1175 ml), and aspirin plus dipyridamole (1000 ml) exceeded (p less than .02) that with placebo (805 ml), while median loss with sulfinpyrazone (775 ml) did not. The reoperation rate was greater (p less than .01) in all the treatment groups that received aspirin (6.5%) compared with the two nonaspirin groups (1.7%). Overall operative mortality was 2.3%, without significant differences among treatment groups. Transient renal insufficiency occurred in 5.3% of patients taking sulfinpyrazone. Thus, early vein graft patency was improved after CABG with all aspirin-containing drug regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection.

A simple, sensitive and precise method for the determination of both free and total homocysteine in human plasma is presented. The total homocysteine in plasma consists of free homocysteine (i.e. reduced plus oxidized homocysteine in the non-protein fraction of plasma) and protein-bound homocysteine. The thiol compounds in plasma, which are reduced or liberated from plasma proteins with tri-n-butylphosphine, are derivatized with a thiol-specific fluorogenic reagent, ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate. The derivatives are separated by reversed-phase high-performance liquid chromatography. The concentrations (mean +/- S.D.) of free and total homocysteine in plasma from 35 normal subjects were 1.94 +/- 0.46 and 6.18 +/- 1.19 nmol/ml, respectively.

Adult↗

Hypersomatostatinemia in chronic renal failure.

Plasma concentrations of somatostatin-like immunoreactivity (SLI) were determined in uremic patients on maintenance hemodialysis. Plasma SLI levels were significantly (p less than 0.001) elevated in 26 diabetic uremic patients (67.1 +/- 6.8 pg/ml, mean +/- SE) and in 24 non-diabetic uremic patients (43.5 +/- 7.2 pg/ml), when compared with 60 healthy subjects (5.0 +/- 0.7 pg/ml). Paired pooled plasma from uremic patients before and after hemodialysis was subjected to a reverse-phase octadecasilyl-silica (C-18) cartridge and then the extract was gel filtered on a Sephadex G-25 column (1.6 X 90 cm). Both elution profiles showed two peaks of SLI which coeluted with synthetic somatostatin (SS)-28 and SS-14 markers, respectively. The SS-28-like immunoreactivity (LI) peak, which was estimated by using SS-14 as a reference standard, was 3-fold larger than that for SS-14 LI. On the basis of immunoequivalency of the two components in the present assay, SS-28 LI constitutes approximately 75% of circulating somatostatin. In conclusion, plasma SLI is substantially high in uremic patients of both diabetic and non-diabetic etiology and the SS-28 is a predominant form of circulating SLI in these patients, probably, in part, for a lower clearance of this molecule.

Chromatography, Gel↗

Effect of glibenclamide on pancreatic hormone release from isolated perifused islets of normal and cysteamine-treated rats.

The effect of glibenclamide, a sulfonylurea agent, on islet hormone secretion, particularly on glucagon was studied using isolated perifused pancreatic islets of normal and cysteamine-treated rats. In normal rat islets, glibenclamide enhanced both insulin and somatostatin release in normoglycemic (50 mg/dL) and glucopenic (0 mg/dL) states, as well as under the condition of arginine stimulation. In contrast, glibenclamide stimulated glucagon release only transiently, then suppressed it in a sustaining manner in each state. In the cysteamine-treated islets, as expected, somatostatin concentrations in the perifusate remained unchanged during the infusion of arginine and/or glibenclamide. Under this condition, glibenclamide enhanced insulin release to the same extent as seen in normal islets, and again markedly inhibited glucagon release. These observations indicate that in isolated perifused rat pancreatic islets, glibenclamide suppresses glucagon secretion independently of D cell stimulation. It is concluded that glibenclamide may exert its inhibitory effect directly on A cell rather than through paracrine action of concomitant somatostatin release, and that the suppression of glucagon secretion by glibenclamide may, in part, contribute to the antidiabetogenic effect of this compound.

Animals↗

A novel method for isolating specific endocytic vesicles using very fine ferrite particles coated with biological ligands and the high-gradient magnetic separation technique.

We have developed a novel method for isolating specific endocytic vesicles using magnetic ligands and high-gradient magnetic separation. Ligands were prepared by coating extremely fine ferrite particles (10-20 nm) with bovine serum albumin and then conjugating asialoglycopeptides. These ligands were introduced into rat liver by perfusion at 16 or 37 degrees C, or by injection through the tail vein. The ligand particles were observed as electron-dense small grains in membrane-bound vesicles in Kupffer as well as parenchymal cells by electron microscopy. Livers were taken out, homogenized and lightly centrifuged. The supernatant was pumped into a separator glass tube filled with very fine ferritic stainless steel fibers and placed in a magnetic field of 0.9-2 T. Vesicles containing ferrite particles were collected with a high efficiency (ca. 70% of endocytosed magnetic ligands). About 70% of uptake appeared to be mediated by the asialoglycoprotein receptors. The captured vesicles were practically free from marker enzymes for plasma membranes, endoplasmic reticulum, and Golgi apparatus. Lysosomal enzyme activity of the vesicles increased with the time of perfusion at 37 degrees C but not at 16 degrees C. Protein composition of the captured vesicles was analyzed by one- and two-dimensional gel electrophoresis. The composition changed characteristically with time on perfusion at 16 and 37 degrees C. The present method provides a powerful tool to collect prelysosomal endocytic vesicles containing specific ligands and lysosomes fused with these specific endocytic vesicles.

Animals↗

Plasma somatostatin response in normal and gastrectomized subjects.

The present work was undertaken to investigate a possible contribution of the stomach to plasma concentrations of somatostatin-like immunoreactivity (SLI) in humans. For this purpose, plasma SLI responses were determined in previously gastrectomized subjects during lipid-heparin induced elevation of plasma free fatty acids (FFA), which gave a consistent rise of plasma SLI in normal controls. Fasting plasma SLI levels in both the subjects with antral and total gastrectomy did not differ from the values in normal controls. Acute elevation of plasma FFA resulted in about 5-fold increase of plasma SLI above basal level in the controls. In contrast, in both the gastrectomy groups there was no significant rise in plasma SLI, despite a comparable elevation of plasma FFA levels. In conclusion, these findings demonstrate that the stomach, probably the antral region of the stomach, accounts for the most part of increase of plasma SLI when hyperfatty-acidemia is induced and suggest that following the stimulation by nutrients the stomach makes a greater contribution to plasma SLI levels than does the pancreas or extragastric intestinal tract in humans.

Adult↗

Changes in insulin secretion after secretin administration and the implications in diabetes mellitus.

Secrepan (Eisai Co. Tokyo, Japan) was administered to 9 healthy volunteers and 36 patients with non-insulin dependent diabetes mellitus (NIDDM) to clarify the effect of secretin on the pancreatic B-cell, by determining the changes in blood of insulin (IRI). Whereas IRI in healthy subjects showed a monophasic change, reaching a peak (delta IRI = 43 +/- 7.3 microunits/ml, M +/- SE) 5 min after secretin loading and returning to the basal level in 15 min, NIDDM patients on diet therapy (delta IRI = 40.2 +/- 7.6 microunits/ml) showed no significant difference from the control group, but NIDDM patients on sulfonylurea (SU) (15.5 +/- 2.4 microunits/ml) and those on insulin therapy (5.3 +/- 1.4 microunits/ml), both showed a significant depression in responsiveness. Further, the changes in insulin secretion after atropine administration in healthy subjects and the changes in IRI response to Secrepan in vagotomized patients were also determined. As a result, data which preclude the possibility of association of the vagus nerve and cholinergic nerve with the stimulation of insulin secretion by secretin were obtained, and a direct action of secretin on the cell of islets of Langerhans was suggested. The maximum IRI response after a secretin load had a significant positive correlation with the IRI response after a 75-gm GTT and the content of C-peptide immunoreactivity in 24-hour urine. Therefore, insulin response to a secretin load can be useful in assessing endogenous insulin secretion and provides a pertinent clinical guide for the selection of an appropriate therapy for diabetes mellitus.

Adult↗

The effects of pantethine on lipid and lipoprotein abnormalities in survivors of cerebral infarction.

A daily 1000 mg of pantethine was orally administered to 12 male survivors of cerebral infarction for 3 months. Before and after the medication, plasma lipoproteins were ultracentrifugally separated. Plasma concentrations of total cholesterol, triglyceride, phospholipid, and VLDL- and LDL-cholesterol tended to decrease. On the contrary, HDL-cholesterol concentration and HDL:LDL-cholesterol ratio significantly increased. HDL2-cholesterol concentration significantly increased, whereas HDL3-cholesterol concentration remained unchanged, resulting in a significant elevation of HDL2:HDL3-cholesterol ratio. In HDL2 the percentage content of cholesterol and triglyceride decreased, while that of phospholipid increased. However, no significant changes were found in the chemical composition of HDL3. The plasma concentrations of apo A-I and, to a lesser extent, A-II increased, with a slight increase in A-I:A-II ratio but A-I:A-II ratio in either HDL2 or HDL3 remained unchanged.

Apolipoprotein A-I↗

Clinical use of blood flowmeters.

The concept of an electromagnetic flowmeter was first described by Kolin in 1936. He demonstrated that with the flowmeter which required surgical exposure of the blood vessel for probe contact but not requiring cannulation, it was possible to follow rapid flow changes and that the deflection bore a linear relationship to flow. Twenty years later a greatly improved circuitry and design was described by Denison and Spencer. Soon thereafter, a number of investigators, notably Schenk and his colleagues utilizing the square wave electromagnetic flowmeter and Cannon and his colleagues with the sine wave electromagnetic flowmeter reported on a number of experimental and clinical studies on blood flow measurements. My introduction to blood flow measurements was through Ferguson who had had a flowmeter and flowmeter probes constructed according to the design of Denison and Spencer. Our first report on flow measurements in patients with peripheral arterial disease was made in 1960. Electromagnetic flowmeters and probes available today are a vast improvement in ease of use, reliability and accuracy, thus the pertinent question is whether or not the information that can be obtained with it would warrant its routine clinical use. We started with a flowmeter constructed by following a schematic diagram and hand winding our own probes, then to the purchase of Medicon 2000, then Medicon 4000, and to our present unit, the SP2204. The advancement in instrumentation has been truly remarkable. All intraoperative blood pressure measurements are made with direct arterial puncture with 23 size needle with the hub removed and needle tip fitted to polyethylene tube connected to a strain gauge.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗

Abnormalities of lipoprotein and carbohydrate metabolism in degenerative diseases of the nervous system--motor neuron disease and spinocerebellar degeneration.

The levels of plasma high density lipoprotein (HDL) cholesterol and plasma triglyceride were determined in 44 patients with motor neuron disease (MND) and in 36 patients with spinocerebellar degeneration (SCD). In both groups the HDL cholesterol levels were significantly lower than those in healthy controls, whereas the plasma triglyceride levels were higher than those in the controls. Glucose levels during the oral glucose tolerance test (GTT) were significantly higher in both MND and SCD groups than in healthy controls. Immunoreactive insulin (IRI) levels during GTT were rather higher at 0 and 120 min in both MND and SCD groups than in healthy controls. Glycosylated hemoglobin levels were lower in MND than in the controls. These results indicate that both lipoprotein and carbohydrate metabolisms were impaired in MND and SCD groups. The possibility was presented that denervation might play a part in the pathogenesis of abnormalities of lipoprotein and carbohydrate metabolisms.

Adult↗