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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 811 records · Page 45Linked to original sources

Intracoronary adenosine enhances myocardial reactive hyperemia after brief coronary occlusion.

Adenosine is a prime candidate for the role of mediator between myocardial metabolic state and coronary blood flow. However, there are few reports concerning the direct effects of exogenously added adenosine on coronary autoregulation. The present investigation in the open-chest dog studied the effects of a threshold dose of intracoronary adenosine infusion on reactive hyperemia following brief coronary occlusions. The infused dose did not increase nonocclusive flow by greater than 10%. Adenosine enhanced total hyperemic flow at all occlusions tested (5, 10, 15, 20, and 30 s). Aminophylline pretreatment reduced reactive hyperemia below the control level even in the presence of an intracoronary infusion of adenosine. Adenosine injected into the left atrium and intracoronarily infused papaverine did not affect hyperemic response to 5- and 15-s coronary occlusions. The results suggest that a minimum dose of exogenously added adenosine enhances myocardial reactive hyperemia, possibly by potentiating the effects of endogenous adenosine released during ischemia.

Adenosine↗

Role of adenosine in coronary blood flow regulation after reductions in perfusion pressure.

We employed intracoronary infusion of adenosine deaminase to test the hypothesis that endogenous adenosine contributes to regulation of coronary blood flow following acute reductions in coronary artery pressure. In 16 closed-chest anesthetized dogs, we perfused the left circumflex coronary artery from a pressurized arterial reservoir and measured coronary blood flow following changes in perfusion pressure before and 10 minutes after the start of intracoronary adenosine deaminase, 5 U/min per kg body weight. Parallel studies showed that this dose of enzyme resulted in cardiac lymph adenosine deaminase concentrations of 3.2 +/- 0.4 U/ml. Adenosine deaminase abolished the vasodilator response to intracoronary adenosine, 4 and 8 micrograms, but had no effect on the vasodilator response to intracoronary papaverine, 200 and 300 micrograms, demonstrating enzyme efficacy and specificity. Additional experiments demonstrated that adenosine deaminase reversibly attenuated myocardial reactive hyperemia following 5- and 10-second coronary occlusions by 30% (P less than 0.05), evidence that the infused enzyme effectively degraded endogenous adenosine. However, adenosine deaminase did not alter the time course for coronary autoregulation or the steady state autoregulatory flow response over the pressure range between 125 and 75 mm Hg. Further, adenosine deaminase did not alter steady state coronary flow when perfusion pressure was reduced below the range for effective autoregulation (60-40 mm Hg). Such results show that adenosine is not essential for either coronary autoregulation or for the maintenance of coronary vasodilation when autoregulatory vasodilator reserve is expended.

Adenosine↗

[Effect of a new sleep inducer, 1H-1,2,4-triazolyl benzophenone derivative 450191-S on rat liver drug-metabolizing enzyme system].

The effect of a new sleep inducer, 450191-S, on the hepatic drug-metabolizing enzyme system was examined using rats and compared with those of nitrazepam and phenobarbital. Cytochrome P-450-dependent 7-alkoxycoumarin O-dealkylation activity determined using liver homogenate and isolated microsomes increased after successive oral administrations of 450191-S, and induction of the enzyme system was observed by administration of 150 approximately 200 mg/kg of the drug for at least 3 approximately 5 days. Normal activity was recovered with withdrawal of the drug for 3 approximately 5 days after induction of the hepatic enzyme system. Administration of higher amounts of 450191-S (200 approximately 600 mg/kg/day) for 3 days caused remarkable increases in the O-dealkylase and UDPGA-glucuronyltransferase activities and cytochrome P-450 and b5 contents. Similar changes in the hepatic enzyme system were observed with administration of nitrazepam (200 approximately 600 mg/kg for 3 days, p.o.) or phenobarbital (10 approximately 40 mg/kg for 3 days, i.p.). We concluded that the inducing activity of 450191-S is almost the same as that of nitrazepam, but weaker than that of phenobarbital. When the hepatic enzyme system was induced by the administration of either 450191-S or phenobarbital, the pentobarbital-induced sleeping time was shortened with increasing doses of the drugs. On the other hand, sleeping time was prolonged by the administration of another type of inducer, beta-naphthoflavone. The results suggest that the inductive pattern of 450191-S is similar to that of phenobarbital.

Animals↗

Hyperlipidaemia in patients with hypopituitarism.

Five patients with hypopituitarism due to Sheehan's syndrome showed hyperlipidaemia of various lipoprotein phenotypes. Postheparin plasma lipoprotein lipase activity was subnormal in 4 of the 5 patients and hepatic triglyceride lipase was markedly decreased in all patients studied. After supplementation of both corticosteroid and thyroid hormones, lipoprotein lipase activity was restored to normal within 2 months, while it took longer for hepatic triglyceride lipase to return to normal. Together with the normalization of the two lipase activities, hyperlipidaemia subsided. The findings suggest that reduced activities of the two lipases may, at least in part, account for the development of hyperlipidaemia in hypopituitarism. The study identifies a new group of patients with hyperlipidaemia secondary to a disorder in endocrine function.

Adult↗

Effects of respiration on the vectorcardiogram obtained with the Frank lead system.

Vectorcardiograms were recorded with the Frank lead system using electrodes positioned at the level of the 5 th intercostal space with the subject in the supine position. Deep inspiration produced the following significant changes compared with deep expiration: (1) the maximum leftward forces of the P, QRS, and T vectors decreased, whereas the maximum anterior and posterior forces of the QRS and T vectors increased; (2) the maximum spatial QRS vector decreased in magnitude; (3) the maximum spatial P, QRS, and T vectors shifted vertically, posteriorly and vertically, and anteriorly, respectively; and (4) the spatial QRS-T angle increased remarkably. The spatial instantaneous QRS vectors were analyzed at 5 msec intervals in 35 of the 61 subjects. With inspiration, the 35- through 50-msec vectors shifted posteriorly with markedly reduced leftward forces and increased posterior forces. It was suggested that the respiration-related vectorcardiographic changes reflected cardiac anatomic positional change, distortion of lead-field potential by lung gases, and other mechanisms. Since the respiratory effect is potentially important for vectorcardiographic interpretation, vectorcardiograms should be recorded under identical respiratory status.

Adolescent↗

Effects of insulin on hypercholesterolemia in the streptozotocin-induced diabetic rats fed a high cholesterol diet.

The effect of dietary cholesterol (Ch) on plasma lipoprotein and apolipoproteins (apo) in diabetic rats was investigated. Ch-fed diabetic rats were severely hypercholesterolemic and hypertriglyceridemic. They had higher concentrations of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL). Concentration of high density lipoprotein (HDL) was decreased. beta-VLDL increased predominantly in Ch-fed diabetic rats, whereas IDL increased in the Ch and propylthiouracil-fed control rats. According to sodium dodecyl sulfate polyacrylamide gel electrophoresis, VLDL and IDL from Ch-fed diabetic rats were unusual in that they contained more apo E, A-I and A-IV. Concentrations of plasma apo A-I and apo E were measured by radioimmunoassay. The diabetic rats fed a labo chow showed a significantly lower concentration of plasma apo E than control rats. Plasma apo E was extremely higher in the diabetic rats fed a cholesterol diet. Plasma apo A-I was significantly increased in the diabetic rats fed a labo chow and those fed a cholesterol. Insulin treatment significantly decreased the concentrations of VLDL, IDL and LDL and plasma concentration and distribution of apolipoproteins in lipoprotein subfractions changed toward normal. However, decreased HDL in the Ch-fed diabetic rats was not recovered by insulin treatment.

Animals↗

Wide variations of plasma triglyceride concentrations in guinea pigs.

Guinea pigs have varying plasma triglyceride concentrations ranging from 28 to 1392 mg/dl, with relatively uniform plasma cholesterol and phospholipid levels. To understand why the animals exhibit such wide variations of plasma triglyceride concentrations, we have explored the triglyceride hydrolyzing system by measuring tissue lipoprotein lipase activities and plasma activator for the enzyme. Lipoprotein lipase activities of epididymal adipose tissue of these animals were 759 +/- 117 (mean +/- SE) n moles FFA X min-1 X g wet tissue-1, markedly low compared with those of rats. There were no relationships between plasma triglyceride concentrations and tissue lipase activities. Plasma activator for lipoprotein lipase was lacking in this animal. Guinea pigs with ascorbic acid deficiency for 2 weeks also showed marked variations of plasma triglyceride concentrations, without any changes in tissue lipoprotein lipase activities. Low adipose tissue lipoprotein lipase activities with deficient plasma activator for the enzyme suggest that the lipoprotein lipase-mediated triglyceride degradation could be impaired in this animal, and this may account for the marked variation of plasma triglyceride concentrations.

Adipose Tissue↗

Plasma lipoproteins in streptozotocin-diabetic rats, after Triton WR-1339 treatment.

In an attempt to examine whether the VLDL secreted by diabetic rats may be different from that by normal rats, plasma obtained after Triton WR-1339 treatment was analyzed. After Triton treatment, a marked increase in plasma triglyceride levels with lesser increases in cholesterol and phospholipids was observed in both diabetic and control rats. The degree of such increases was almost equal between two groups of rats. The large increases in plasma lipid levels presumably reflect the increase in plasma VLDL fraction. The lipid composition of VLDL of diabetic rats was very similar to that of normal controls. The LDL fraction of diabetic rats was low in its contents of both cholesterol and phospholipids compared with that of normal controls. The composition of IDL and HDL in diabetic rats was similar to that of controls. From these data, we suggest that the VLDL of diabetic rats secreted under basal fasting condition is not different in its lipid composition as well as in amounts from that of controls.

Animals↗

Reciprocal changes of plasma apo AI and apo E levels in streptozotocin-induced diabetic rats.

Amounts of plasma lipids, apolipoprotein AI (apo AI) and apolipoprotein E (apo E) were measured in streptozotocin-induced diabetic rats. Plasma triglyceride and cholesterol levels of diabetic rats were not significantly different from those of control rats. Plasma apo AI levels of diabetic rats were significantly higher than those of control rats (78.2 +/- 29.3 vs 27.2 +/- 3.4 mg/dl, P less than 0.001), while plasma apo E levels of diabetic rats were significantly lower than those of control rats (4.2 +/- 1.0 vs 13.9 +/- 5.3 mg/dl, P less than 0.001). Insulin treatment (12U/day) of diabetic rats decreased plasma apo AI levels significantly (treated: 32.8 +/- 3.4, untreated: 48.7 +/- 6.2, control: 28.5 +/- 2.4 mg/dl) and normalized plasma apo E levels (treated: 16.1 +/- 1.7, untreated: 5.4 +/- 0.7, control: 15.8 +/- 1.3). Insulin injection (4U/day) to normal rats did not cause any changes in both plasma apo AI and apo E levels. The data indicate that diabetes is not always accompanied by hyperlipidemia, however this inevitably carries apoprotein abnormalities characterized by the high plasma apo AI and low apo E levels, which are reversible with insulin treatment. The changes in the levels of plasma apo AI and apo E could be related to the development of atherosclerosis in diabetes.

Animals↗

Capping one end of an actin filament affects elongation at the other end.

The rates of elongation at the free ends of actin filaments were compared to those of intact filaments, when the one end was masked with muscle beta-actinin or cytochalasin D, using fixed actoheavy meromyosin and Limulus acrosomal actin bundles as seeds. Experimental conditions were chosen so as to prevent spontaneous filament formation as far as possible. The rate of elongation at the barbed end of fixed actoheavy meromyosin was reduced to about one-fourth when the other pointed end was capped by beta-actinin, and that at the pointed end was reduced to one-third when the barbed end was blocked by cytochalasin D. Similar effects were also observed with the packed actin bundles of horseshoe crab sperm, although the decreases in elongation were less marked: 50-60% of the control both in the presence of beta-actinin and cytochalasin D. To explain the peculiar "end effect" described above, it is proposed that possible conformational changes at one end of an actin filament caused by the binding of a capping substance are transmitted successively to the other end so as to affect the elongation there.

Actinin↗