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Biomedical subjects

K Yagi

Publications and source records attributed to K Yagi.

At least 631 records · Page 35Linked to original sources
PubMed1982

Pharmacokinetic studies of AD-810, a new antiepileptic compound. Phase I trials.

Pharmacokinetics of 3-sulfamoylmethyl-1,2-benzisoxazole (AD-810), a new possible antiepileptic compound, were evaluated in Phase I trials in nine healthy male volunteers. The subjects, divided into three groups, were given single oral dose of 200 mg (Group A), and oral doses of 200 mg/d (B) and 400 mg/d (C) for two d, respectively. AD-810 was well tolerated by all subjects. No neurologic side effects were observed. Evaluation of the laboratory screening profiles (hematological and biochemical examination) showed no clinically significant abnormalities. Mean peak plasma concentrations of AD-810 at 5.3-6.0 h after intake were 2.9, 5.1 and 13.0 micrograms/ml in Group A, B and C, respectively, and mean elimination half-life was about 60 h. Mean concentrations of AD-810 in erythrocytes were higher than those in plasma. The unchanged AD-810 and a major metabolite, the glucuronide of the N-O cleft compound, were excreted at 48.7% and 12.4% of the given dose in the urine for 2 weeks in Group C, respectively. The results suggest that AD-810 would induce no severe adverse effects in man at plasma concentrations over 10 micrograms/ml, the therapeutic concentrations predicted from animal experiments.

Adult↗
PubMed1981

Lipid peroxide levels and lipids content of serum lipoprotein fractions of pregnant subjects with or without pre-eclampsia.

Total serum lipids in normal pregnant subjects were significantly higher than those in non-pregnant subjects. This was due to an increase in the lipid content in all of the lipoprotein fractions, especially in VLDL. Serum lipids in pre-eclamptic subjects were higher than those in normal pregnant subjects. This was due to the increase in both VLDL and LDL. Serum lipid peroxide levels in pregnant subjects were significantly higher than those in non-pregnant subjects and further elevation of the levels was observed in pre-eclamptic subjects. The elevation of the peroxide levels in normal pregnant subjects was due to changes in all of the fractions of serum lipoproteins, especially in VLDL. The further elevation of peroxide in pre-eclamptic subjects resulted from an increase in HDL fraction.

Female↗
PubMed1981

Homology of L-gulonolactone oxidase of species belonging to Mammalia, Aves, and Amphibia.

Immunological cross-reactivity of L-gulonolactone oxidase of different species (rat, chicken, and bullfrog) was tested by the Ouchterlony technique. Antiserum directed against the enzyme from chicken kidney reacted with rat liver enzyme as well as with bullfrog kidney enzyme. This finding suggests that there is, at least partly, sequence homology among the enzyme from species belonging to the three classes, Mammalian, Aves, and Amphibia.

Animals↗
PubMed1981

Ca2+-dependent modulator proteins from Tetrahymena pyriformis, sea anemone, and scallop and guanylate cyclase activation.

Previously, the guanylate cyclase activity of Tetrahymena pyriformis was shown to be activated by an endogenous modulator (calmodulin)-like protein (Na-gao, S., Suzuki, Y., Watanabe, Y., and Nozawa, Y. (1979) Biochem. Biophys. Res. Commun. 90, 261-268). This protein has now been identified as the modulator protein. The identification was based on the capability of this protein to activate the brain modulator-deficient phosphodiesterase and the mobility of this protein upon polyacrylamide gel electrophoresis. The activation of guanylate cyclase was specifically attributable to the Tetrahymena modulator protein since other modulator proteins examined (bovine brain, sea anemone, and scallop) were ineffective. Under the conditions where the activation of Tetrahymena guanylate cyclase occurred, guanylate cyclase activities from other sources, that include rat brain, rat lung, and human platelet, were not affected. In the phosphodiesterase activation, the potencies of scallop and Tetrahymena modulator proteins, which are represented by reciprocals of the quantities of proteins required for half-maximal activation of enzyme, were 66% and 55%, respectively, of that of the brain protein. The same decreasing order was seen for the affinity of these proteins for Ca2+ in enzyme activation. The results suggest a directional change of the modulator protein during the molecular evolution toward an increase in the capability in Ca2+-dependent enzyme activation.

Animals↗
PubMed1981

Pontine neurones: electrophysiological evidence of mediating carotid baroreceptor inputs to supraoptic neurones in rats.

Effects of pressure stimulation of the isolated carotid sinus, of occlusion of the common carotid artery and of tail pinching on the discharge activity of dorsal pontine area neurones and antidromically identified supraoptic neurosecretory neurones were studied in male rats anaesthetized with urethane. Electrical stimulation of the supraoptic nucleus (SON) produced antidromically conducted action potentials in a small number (24/384) of the units recorded in the dorsal pontine area. Pressure pulse stimulation of the isolated carotid sinus inhibited and carotid occlusion facilitated discharge activity in some of the tested dorsal pontine area neurones. In these responsive pontine neurones a transient excitation of grouped discharges was occasionally observed to concur with a small, spontaneous depression of the arterial blood pressure. Tail pinching excited some of these pontine neurones. Histological examination revealed that these responsive neurones were located in the dorsal pontine area close, but ventral and lateral, to the locus coeruleus. Electrical stimulation of the dorsal pons evoked a synaptically mediated excitation in 20 and inhibition in the other seven of the 52 SON units which were identified antidromically after stimulation of the pituitary stalk. Pressure stimulation of the isolated carotid sinus evoked an inhibition of discharge activity in some of th SON units which were excited by dorsal pontine area stimulation. All of the six tested units which showed inhibition after dorsal pontine area stimulation were unresponsive to pressure stimulation. Based on these data, it was concluded that at least some of the neurones which mediate carotid baroreceptor inputs to SON neurosecretory neurones are located in the dorsal pontine area close, but ventral and lateral, to the locus coeruleus and that these dorsal pontine area neurones also mediate converging synaptic inputs originating from somatic pain receptors.

Action Potentials↗
PubMed1981

Studies on the sulfhydryl group of L-galactonolactone oxidase.

L-Galactonolactone oxidase was found to be inactivated by various sulfhydryl reagents: the order of inactivation rate was HgCl2 greater than p-chloromercuribenzoate greater than 4,4'-dipyridyldisulfide greater than 2,2'-dipyridyldisulfide greater than 5,5'-dithio-bis-(2-nitrobenzoate) greater than N-ethylmaleimide greater than iodoacetamide. The inactivation by 4,4'dipyridyldisulfide was studied in detail, and it was found that the maximum degree of inactivation attained with increasing reagent concentration was 93%, and that the kinetics of inactivation was first order with respect to the reagent concentration. The pH dependence of the second-order rate constant of the inactivation revealed that sulfhydryl group with a pKa of approximately 9.8 was involved in the inactivation process. The value of pKa is high compared with that of low-molecular weight thiols, indicating that the ionization of the sulfhydryl group is affected by the electric field of a negatively charged group located in its vicinity. The values of Km and Vmax for the L-galactonolactone oxidase reaction did not change greatly around pH 9.8. This finding is consistent with the view that the sulfhydryl group does not participate in the catalytic process. The velocity of inactivation in the presence of substrate was considerably greater than that observed in its absence. It appears that the sulfhydryl group becomes more reactive during the catalytic cycle of the enzyme. It was also noted that the absorption spectrum of the flavin prosthetic group (the oxidized form) was modified by adding p-chloromercuribenzoate.

Chloromercuribenzoates↗
PubMed1981

Amino acid sequence of calmodulin from scallop (Patinopecten) adductor muscle.

The complete amino acid sequence of scallop calmodulin was determined by isolating and sequencing the peptides obtained after cyanogen bromide cleavage and tryptic digestion. The protein consisted of 148 amino acid residues and its amino(N)-terminus was blocked with an acetyl group. Scallop calmodulin lacked tryptophan and cysteine residues and contained one mol each of N epsilon-trimethyllysine (Tml) and histidine residues per mol of the protein. Scallop calmodulin contained only one tyrosine residue, while vertebrate calmodulins contain two. On comparing its amino acid sequence with that of bovine calmodulin, three amino acid substitutions were found at positions 99(Tyr leads to Phe), 143(Gln leads to Thr), and 147(Ala leads to Ser).

Amino Acid Sequence↗
PubMed1981

Protective effect of riboflavin on suppression of growth caused by oxidized oil.

When oxidized corn oil (100 nmol in terms of malondialdehyde/day/rat) was administered to a riboflavin-deficient rat, the body weight gain was markedly suppressed. However, when 20 microgram of riboflavin/day/rat was administered with the oxidized corn oil, reasonable growth and normal flavin levels in the liver, kidney and heart could be attained, though they were somewhat less than those of the animals fed on the normal diet containing non-oxidized corn oil. It was noted that the elevation of lipid peroxide level in blood plasma of animals administered with the oxidized oil was effectively prevented by riboflavin. These results indicate the protective effect of riboflavin on suppression of growth caused by the oxidized oil.

Animals↗
PubMed1981

Plasma lipid peroxide levels in an urbanized Micronesian population--Nauru.

Plasma lipid peroxide levels of 419 inhabitants of Nauru, where a high prevalence of obesity is occurring, were measured. The plasma lipid peroxide level was 4.03 +/- 1.94 nmol/ml in subjects 20-24 years and rose to a peak of 5.78 +/- 3.21 in subjects 35-44 years. The values obtained with Nauruans are significantly higher than those of healthy Japanese people and the peak found in the former was shifted to a younger age than in the Japanese.

Adult↗
PubMed1981

Immunochemically detected structural difference in the heavy chains of chicken breast muscle myosin isozymes.

Antisera against the isozymes of heavy meromyosin from chicken breast muscle myosin were prepared by immunizing rabbits. Both antisera against heavy meromyosin containing g1 light chain (HMM(g1) and that containing g3 light chain (HMM(g3)) reacted with both heavy meromyosin isozymes and myosin, but not with whole light chain mixture. This indicates that only antibodies against the heavy chain of heavy meromysin were elicited. The antisera were applied successively to two columns, one coupled with subfragment-2 and the other with heterologous subfragment-1 isozymes. When the antiserum against HMM(g3) was absorbed with subfragment-1 containing g1 (S-1(g1)), it did not react with HMM(g1), but reacted with HMM(g3). On the other hand, when the antiserum against HMM(g1) was absorbed with subfragment-1 containing g3 (S-1(g3)), it lost its ability to react with both heavy meromyosin isozymes. This indicates the presence of a specific antibody against the heavy chain of HMM(g3). The head portion of myosin containing g3 may hold an unique antigenic determinant which is not present in the head of a myosin containing g1.

Animals↗