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Biomedical subjects

S Nagano

Publications and source records attributed to S Nagano.

At least 109 records · Page 6Linked to original sources
PubMed1991

Alteration of human myoglobin proximal histidine to cysteine or tyrosine by site-directed mutagenesis: characterization and their catalytic activities.

Two mutant proteins of human myoglobin (Mb) that exhibit altered axial ligations were prepared by site-directed mutagenesis of a cloned gene for human Mb. The normal axial ligand residue, histidine 93(F8), was replaced with cysteine or tyrosine, resulting in H93C or H93Y Mb, respectively. Cysteine or tyrosine coordination to the ferric heme iron is verified by electronic absorption, 1H-NMR, EPR spectra, and redox potentials of Fe2+/Fe3+ couple. Their mono-oxygenation activities of styrene are also discussed.

Bacteriophages↗
PubMed1991

Correlation of insulin deficiency and hypertriglyceridemia in diabetic rats.

The relationship between plasma insulin (IRI) and lipid concentration, or triglyceride (TG) kinetics was studied in streptozotocin-induced diabetic rats (DM) to examine how insulin deficiency is associated with the mechanism of hypertriglyceridemia (HTG) in diabetes. Plasma glucose and ketones were significantly elevated and IRI reduced in DM. Plasma glucagon concentration in DM was similar to controls. The plasma concentration of TG, total cholesterol phospholipid and apoprotein B was 3-4-fold higher in DM compared to control rats. The HTG in DM was mainly attributable to an increase in the concentration of TG-rich lipoprotein (TRL). Multiple linear regression analysis showed a positive relationship between the concentration of non-esterified fatty acid and plasma lipids, but the decrease in IRI best correlated with increased concentrations of lipids and apoprotein B in plasma and TRL. Neither glucose nor glucagon correlated significantly with lipids or apoprotein B concentration in plasma or TRL. The rate of entry of TG into blood was similar between DM and controls, and in DM this significantly correlated with IRI. Clearance of radiolabeled TRL-TG in DM was significantly decreased and correlated with IRI. Conversely, the removal of radiolabeled Intralipid-TG was similar for DM and controls. The data suggest that insulin critically regulates TRL-TG metabolism in DM and that a catabolic defect of TRL-TG due to insulin deficiency is a main reason for the HTG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The lowering effect of probucol on plasma lipoprotein and proteinuria in puromycin aminonucleoside-induced nephrotic rats.

Hyperlipidemia associated with nephrotic syndrome was treated with probucol and the changes in plasma lipoprotein lipid concentration and urinary protein excretion were examined in puromycin aminonucleoside-induced nephrotic rats. Rats made nephrotic exhibited severe hyperlipidemia with increases in all major lipoprotein fractions. Probucol treatment of nephrotic rats significantly lowered plasma triglyceride (TG), cholesterol (Ch) phospholipid (PL) and apoprotein B associated with very-low-density and low-density lipoprotein and Ch and PL in high-density lipoprotein (HDL). Malondialdehyde (MDA) associated with the lipoproteins was significantly elevated in nephrotic rats and probucol treatment also lowered MDA concentration in all major lipoproteins. In control rats probucol moderately, but significantly, reduced plasma TG and HDL-Ch concentrations. Proteinuria associated with nephrosis was decreased significantly by treatment with probucol. Probucol treatment did not affect blood urea nitrogen and plasma creatinine levels. A significant positive correlation existed between the amount of protein excreted in urine and the plasma lipid concentrations in all nephrotic rats, suggesting that the hypolipidemic effect of probucol may attenuate proteinuria associated with nephrosis. These results suggest that probucol may be a favorable treatment for hyperlipidemia associated with nephrotic syndrome.

Animals↗
PubMed1991

Effect of L-dopa in young patients with hypertension.

The effects of L-dopa on blood pressure, heart rate, plasma renin activity, norepinephrine, epinephrine and prolactin were studied in a randomized single-blind trial in 36 patients with essential hypertension. In response to L-dopa, 250 mg administered orally, the blood pressure decreased significantly as compared with the results of placebo treatment. The heart rate and plasma norepinephrine and epinephrine were unchanged. The plasma renin activity and prolactin decreased as a result of L-dopa administration. The administration of a peripheral DA2 dopamine receptor blocker, domperidone (20 mg, orally) prevented the L-dopa-induced reduction in plasma prolactin but failed to block the fall in blood pressure and plasma renin activity. These results suggest that the blood pressure-lowering effect of L-dopa may be mediated through multiple sites involving D1 dopamine receptors, the central nervous system, and the renin-angiotensin system.

Adult↗
PubMed1990

Effect of pravastatin sodium, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on very-low-density lipoprotein composition and kinetics in hyperlipidemia associated with experimental nephrosis.

The effect of Pravastatin sodium (CS-514), a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA R) on very-low-density lipoprotein (VLDL) composition and kinetics was studied in normal and experimental nephrotic rats under fasting conditions. Nephrotic rats, induced by a single intraperitoneal injection of puromycin aminonucleoside (100 mg/kg body weight), had significantly higher plasma lipids and apoprotein (apo) B concentrations than controls. The hypertriglyceridemia associated with nephrosis was mainly due to a markedly elevated VLDL-triglyceride (TG) concentration. Pravastatin sodium was administrated as a 0.04% solution in drinking water for 7 days to normal control and nephrotic rats. Plasma TG concentration in both control and nephrotic rats was significantly reduced by the treatment with Pravastatin, but plasma cholesterol levels were not reduced by the treatment in either group of rats. TG, cholesterol, phospholipid, and apo B concentrations in nephrotic VLDL were significantly reduced by Pravastatin treatment, whereas only TG was decreased in control VLDL. Pravastatin reduced the apo B 100 + 95/48 ratio in nephrotic VLDL. Pravastatin did not alter the lipid concentration of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in control and nephrotic rats. VLDL-TG turnover studies showed that TG secretion rate was significantly suppressed by Pravastatin administration without affecting its removal in both groups of rats. These suggested that Pravastatin, an inhibitor of cholesterol biosynthesis, can reduce VLDL concentration by rectifying the overproduction of VLDL exhibited in nephrotic rats.

Animals↗
PubMed1990

Catabolic defect of triglyceride is associated with abnormal very-low-density lipoprotein in experimental nephrosis.

Very-low-density lipoprotein (VLDL)-triglyceride (TG) kinetics were examined in puromycin aminonucleoside-induced nephrotic rats in order to establish the nature of the hypertriglyceridemia associated with this condition. Nephrotic rats had a plasma TG concentration 10-fold higher than the controls. In nephrotic rats TG secretion rate was elevated only 1.2-fold above the controls, suggesting that the catabolism of TG was also impaired. Lipolytic activities were determined in postheparin plasma (PHP) of the control and the nephrotic rats. There were no significant differences in either the activity of lipoprotein lipase (LPL) or hepatic lipase (HL). VLDL-TG was endogenously radiolabeled in donor rats with [2-3H]-glycerol. The half life (T1/2) was then determined by monitoring the clearance of plasma [3H]-VLDL-TG in normal recipient animals. The T1/2 of VLDL-TG from nephrotic rats was twice that of normal rats. The defect in VLDL-TG clearance could be partially rectified by preincubation with high-density lipoprotein (HDL) from normal rats, but not with HDL from nephrotic rats. VLDL from either nephrotic or normal rats were incubated with PHP of normal rats to assess the effectiveness of VLDL-TG as a substrate for PHP. The lipolytic rate for nephrotic VLDL was significantly lower than that for normal VLDL, suggesting that VLDL from nephrotic rats was somewhat resistant to the action of LPL and HL. When VLDL from nephrotic rats was preincubated with HDL from normal rats, the low lipolytic rate of VLDL-TG improved significantly. This was not observed when HDL from nephrotic rats was used for the preincubation. The results suggested that physical and/or chemical change of VLDL particles due to nephrosis results in a catabolic defect of VLDL-TG.

Animals↗
PubMed1990

Effect of acute hyperglycemia on plasma triglyceride concentration and triglyceride secretion rate in non-fasted rats.

The effect of an intravenous infusion of glucose on plasma triglyceride (TG) concentration in fed rats was determined in order to partially elucidate the mechanism of diabetes-induced hypertriglyceridemia. Glucose infused at 8 mg/kg per min caused the plasma TG concentration to be elevated significantly when compared to controls infused with saline alone. In rats which were euglycemic (clamped, insulin infused at 2.5 mU/kg per min), plasma TG concentration remained constant throughout the glucose infusion period (8 mg/kg per min). Hyperglycemic rats infused with insulin (2.5 mU/kg per min) as well as with glucose (16 mg/kg per min) were also hypertriglyceridemic. Infusion of insulin alone did not change the concentration of plasma TG over a 150 min period. Glucose was also infused (8 mg/kg per min) with somatostatin (1 micrograms/kg per min) to block endogenous production of insulin. Somatostatin infusion did not suppress glucose-induced hypertriglyceridemia. For all treatments, the net change in TG concentration was found to positively correlate with the net change in plasma glucose concentration at 150 min after the infusions (r = 0.83, P less than 0.001). The higher TG concentration in the glucose infused, hyperglycemic clamp and glucose plus somatostatin groups reflected an increased rate of TG secretion, in the presence of a lower concentration of plasma free fatty acids. These results suggest that in a non-fasted state, acute hyperglycemia increases plasma TG by stimulating hepatic TG secretion, in a manner which is independent of either plasma insulin or free fatty acids levels.

Animals↗
PubMed1990

Comparison of clinic and home blood pressure levels and the role of the sympathetic nervous system in clinic-home differences.

Plasma and urine norepinephrine, epinephrine and home blood pressure were measured in 48 young hypertensive men (mean age, 21 years) and 25 matched normotensive controls. Plasma samples were drawn following 30 min rest in the clinic and 24 h urine samples were collected at home. Twenty-one hypertensive patients were given a single dose of clonidine (150 micrograms orally). Changes in blood pressure, heart rate and plasma norepinephrine were assessed. Twenty-five of the hypertensive patients were found to have a normal home blood pressure (defined from records of the normotensive subjects). The other group of patients maintained a high home blood pressure. In comparison to normal subjects, patients with a high home blood pressure were characterized by higher urinary norepinephrine and epinephrine excretion and higher plasma epinephrine. Patients with a normal home blood pressure had normal heart rate at home, normal plasma and urinary catecholamines. However, the two groups of hypertensives could not be distinguished on the basis of clinic blood pressure, plasma or urinary catecholamines due to considerable overlap. At 90 min after oral clonidine administration, the plasma norepinephrine and blood pressure levels were decreased in both groups of hypertensives to a similar extent. The changes in heart rate were significantly smaller in patients with a high home blood pressure than in those with a normal home blood pressure. These results suggest that the patients with a high home blood pressure tended to have a high sympathetic nerve activity. However, the two groups of hypertensives could not be separated on the basis of plasma or urinary catecholamine measurements.

Administration, Oral↗
PubMed1990

Involvement of lipoproteins in suppression of interleukin 2-dependent cell proliferation by sera from aged humans.

Sera from the elderly, but not young, inhibited markedly interleukin 2 (IL-2)-dependent proliferation of cloned T cells. Sera of aged humans contained high levels of triglyceride, cholesterol, very low density lipoproteins (VLDL) and low density lipoproteins (LDL). VLDL and LDL inhibited the proliferation in a dose-related manner. The inhibition correlated with levels of serum VLDL and LDL. These results suggest that lipoproteins may act as a regulator of IL-2-dependent proliferation and that disturbance of lipid and lipoprotein metabolism may be partially responsible for diminished immune responses in the elderly.

Adult↗
PubMed1990

Effect of captopril on plasma prolactin in patients with essential hypertension.

The effects of the angiotensin-converting enzyme inhibitor captopril on blood pressure, heart rate, plasma prolactin, and renin activity were examined in a single-blind, placebo-controlled trial on 30 patients with essential hypertension (15 given drug, 15 placebo). Captopril, 25 mg administered orally, reduced the blood pressure and increased the plasma renin activity. Captopril decreased mean plasma prolactin from 17.5 +/- 1.4 ng/mL to 9.1 +/- 1.0 ng/mL (p less than 0.001). Significant correlation was found between captopril-induced change from control values of plasma prolactin (delta plasma prolactin) vs delta plasma renin activity (r = -0.688, p less than 0.001). These results suggest that acute administration of captopril was accompanied by a reduction in plasma prolactin and that this reduction may be of clinical significance during therapy of hypertension.

Adult↗
PubMed1990

[Flow cytometric measurement of NBT-reducing activity in peripheral leukocytes applying THMS H.1TM].

Nitroblue tetrazolium (NBT) is reduced to a blue dye (blue formazan, gamma max 560 nm) by superoxide (O2-.) released from phagocytes upon phorbol myristate acetate-stimulation, resulting in the blue dye-deposition on the cell membrane. Thus, we tried to develop a semi-quantification method for determining the NBT-reducing activity in the peripheral leukocytes (NBT-staining intensity -SI- and its distribution in the cell) by flow cytometry. The SI (mean +/- SD) was 28.4 +/- 2.2 (n = 30) in normal subjects and 0.9 in a patient with chronic granulomatous disease, whereas it was 37.6 in a patient with malaria. In addition, patients with myelodysplastic syndrome showed values of 29.2 +/- 7.0 (n = 11), while a patient with partial monosomy of chromosome No. 7 had an SI of 10.8. The present assay of NBT-reducing activity in phagocytes may be useful for screening of peripheral leukocyte function.

Flow Cytometry↗
PubMed1989

[Mass screening for endometrial cancer according to the Law of Health for the Elderly].

Due to the gradual increase of endometrial cancer, mass screening for this type of cancer began from 1987 in Japan in accordance with the Law of Health for the Elderly. However, a screening system for endometrial cancer has many controversial problems when compared with that for cervix cancer. Criteria for screening, methods of screening, management after screening, and executive systems are all controversial points in the performance of mass screening. The actual condition in the detection of endometrial cancer in Fukuoka Prefecture based on a questionnaire is discussed in this paper.

Aged↗
PubMed1989

Cytotoxicity of galactose, tyrosine and methionine in cultured suckling rat hepatocytes: relation to liver immaturity.

Monolayers of suckling rat hepatocytes cultured for 24 hours were treated with galactose, I-tyrosine and I-methionine. The purpose was to study the reasons for the clinical improvement of patients with neonatal hepatitis after dietary restriction of these nutrients. Galactose, tyrosine, and methionine was cytotoxic on suckling rat hepatocytes, yet had no effect on adult rat hepatocytes. Furthermore, the pretreatment of suckling rat hepatocytes with dexamethasone ameliorated the cytotoxicity and induced a differentiation of the cells. These results suggested that the cytotoxicity resulted from the immaturity of suckling rat hepatocytes and therefore dietary restriction of galactose, tyrosine and methionine might be a useful treatment for patients with neonatal hepatitis.

Animals↗
PubMed1989

Increased sympathetic nerve activity at home in young subjects with hypertension.

Plasma and urine norepinephrine, epinephrine, plasma renin activity and aldosterone were measured in 11 young men (mean age, 21 years) with a high blood pressure in the clinic who maintained a high home blood pressure and 12 men with an elevated clinic blood pressure who had a normal home blood pressure. Plasma samples were drawn following 30 min rest in the clinic, and 24-hour urine samples were collected at home. The two groups of hypertensives could not be distinguished on the basis of clinic blood pressure, plasma norepinephrine, epinephrine, renin activity or aldosterone. Patients with a high home blood pressure were characterized by a high urinary norepinephrine excretion. These results suggest that the patients whose blood pressure remained elevated at home had an increased sympathetic nerve activity at home.

Adolescent↗