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Biomedical subjects

T Okazaki

Publications and source records attributed to T Okazaki.

At least 505 records · Page 28Linked to original sources

Prostaglandins in middle ear effusions.

Although otitis media with effusion is usually a self-limiting disease, there are certain cases in which there appears to be chronic progression of the disease with serious sequelae. It has been demonstrated that there are biological mediators of inflammation in the middle ear that are capable of producing mucous membrane pathologic features. Some of these mediators of inflammation may be the prostaglandins. These cyclic fatty acids have been found in ten consecutive middle ear fluids in concentrations that are usually higher than the corresponding serum or plasma. It is suggested that prostaglandins may play an active role in maintaining the inflammatory response in the middle ear in otitis media with effusion.

Chromatography↗

Prostaglandins and asthma: The use of blood components for metabolic studies.

Experiments were carried out to study a possible role of prostaglandins (PGs) in the pathogenesis of human bronchial asthma. Leukocyte, plasma, and serum of ambulatory asthmatic as well as nonasthmatic individuals were used. PGF was measured by competitive radioimmunoassay with anti-PGF2alpha antibody. It was found that PGF was spontaneously released from the leukocytes of both asthmatic and nonasthmatic individuals. The PGF release as studied with the cells of asthmatic individuals was enhanced by the additions of arachidonic acid and/or dibutyryl cyclic AMP. Antigenic challenge of sensitive cells failed to show any general effect on the amount of PGF released. The amount of spontaneously released PGF had no correlation with the amount of maximal antigenic histamine release. Preincubation of the cells with arachidonic acid had no effect on subsequent antigenic histamine release. Plasma PGF levels in nonasthmatic and in asthmatic individuals were not significantly different and both were considerably lower than the serum levels. The mean serum PGF level in the asthmatic group was higher than in the nonasthmatic, indicating probably a greater release of PGF from blood cells.

Antigen-Antibody Reactions↗

Inhibition of antigen-induced histamine release by ouabain.

The effect of ouabain, a specific sodium-potassium dependent adenosine triphosphatase (Na+-K+-ATPase) inhibitor, on antigen-induced histamine release was studied using guinea pig lung fragments sensitized in vitro with rabbit antibodies against bovine serum albumin. Histamine was assayed spectrofluorometrically. When sensitized tissue had been preincubated with ouabain (less than or equal to 1.0 x 10(-4) M) for 10 min prior to antigenic challenge, release of histamine was significantly inhibited (maximum 54%, p less than 0.001, N=9, paired t test). The most significant inhibition was obtained near the optimal concentration of antigen. The inhibition was dependent on the length of preincubation (less than or equal to 20 min), and was partially reversible upon washing the tissue removing the ouabain. Ouabain did not seem to prolong the duration of the histamine release process. Increase in potassium ion (less than or equal to 1.1 x 10(-2)M) inhibited the histamine release and had additive effects to ouabain action. Dibutyryl cyclic AMP (less than or equal to 5 x 10(-3) M), which could enhance the release, strongly antagonized the inhibition. Glucose removal from the medium did not abolish the ouabain effect. The results seem to indicate that immunologic release of histamine is under the influence of the membrane Na+-K+-ATPase activity.

Animals↗

Effect of ragweed hyperimmune human gamma globulin on in vivo and in vitro parameters of ragweed sensitivity.

The effect of ragweed hyperimmune human gamma globulin upon in vitro and in vivo parameters of ragweed sensitivity was examined. In a double-blind study, 40 ragweed sensitive patients were divided into 2 groups and received either ragweed hyperimmune human gamma globulin (treated) or normal pooled globulin (control). Parameters of ragweed sensitivity studied before and following injections of the gamma globulin included skin test and nasal provocation end point titration, specific IgE antibody as measured by the RAST, leukocyte histamine release, total serum ragweed antibody level, and total serum IgE. Changes in measured parameters varied in both groups of patients. In the "treated" patient group, 1 wk later nasal sensitivity decreased significantly, and there was a trend toward decreased histamine release from leukocytes. No discernable effect was noted upon the other parameters. Thus, with the dosage used, the parenterally administered hyperimmune gamma globulin did not influence most measurements of ragweed hypersensitivity. The concept of this therapeutic approach might warrant further investigation.

Adolescent↗

Studies of the antigenicity and allergenicity of phospholipase A2 of bee venom.

The antigenic and allergenic properties of phospholipase A2 (PLA2) and whole bee venom were compared by measuring the IgG and IgE antibody responses in animals and man. Precipitating antibodies raised in rabbits and reaginic and other antibodies raised in mice reacted about equally with both bee venom and PLA. The majority of human sera containing bee venom-specific IgE also contained PLA-specific IgE, although in somewhat lower titers. Similarly, most human sera with significant amounts of total antibodies reacting with bee venom also had antibodies reacting with PLA. Histamine and SRS-a release from leukocytes of sensitive patients followed challenge with whole bee venom and PLA in the majority of instances. However, mediator release from several patients' cells was obtained with bee venom only. These studies suggest that although PLA is a major allergen and antigen in bee venom, significant exceptions in patients' reactivity may limit its potential diagnostic and therapeutic usefulness.

Allergens↗

An enzymologic study of corpora lutea in early pregnant rats treated with abortifacient agents.

Luteal metabolism was investigated in corpora lutea of early pregnant rats treated with four abortifacient agents. In corpora lutea of rats treated with prostaglandin F2alpha or of rats 1 day postpartum, glucose-6-phosphate dehydrogenase (G6PDH) activity increased 140 to 170% and 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) was activated to significantly high levels, whereas malic enzyme activity decreased to 29% of control values. In aminoglutethimide-treated rats, the activities of G6PDH and malic enzyme decreased, while 20alpha-HSD activity was maintained at a very low level. With the increased dose, complete abortion was observed. In corpora lutea of these aborted rats, 20alpha-HSD was activated moderately and G6PDH values were slightly higher than control values, whereas malic enzyme activity fell to lower levels. All rats treated with clomiphene citrate aborted within 63 hours after the last injection. The activities of G6PDH, malic enzyme, and ATP citrate lyase in these corpora lutea decreased to 66, 68, and 72% of control levels, respectively; 20alpha-HSD activity was maintained at a very low level, and activities of 3beta-hydroxysteroid dehydrogenase, 6-phosphogluconate dehydrogenase, and pyruvate kinase were not appreciably altered. These findings indicated that, at the beginning of luteolysis and fetal resorption, the activities of steroidogenic enzymes decreased and 20alpha-HSD was not yet activated. Therefore, we could gauge the early changes of luteolysis by measuring the activities of G6PDH, MALIC ENZYME, AND ATP citrate lyase as well as 20alpha-HSD.

ATP Citrate (pro-S)-Lyase↗

Studies on marine microorganisms. V. A new antibiotic, aplasmomycin, produced by a streptomycete isolated from shallow sea mud.

A new antibiotic, aplasmomycin, which inhibits growth of Gram-positive bacteria including myobacteria in vitro, and plasmodia in vivo was obtained from a strain of Streptomyces griseus isolated from shallow sea sediment in Sagami Bay. The antibiotic forms colorless needle-like crystals and has a molecular formula of C41H60O14Na. Based on its physical and chemical properties, aplasmomycin was concluded to be a new antibiotic. The antibiotic was produced in selected media devised to relate to a marine environment.

Animals↗

[Studies on the activities of steroidogenic enzymes in corpora lutea of early pregnant rats treated with abortifacient drugs (author's transl)].

The major role of the corpus luteum is biosynthesis of progesterone. Luteal function has been investigated by following plasma progesterone concentrations and by studying ultrastructural and histochemical changes in corpora lutea. Recently, changes in enzyme activities concerned with formation and degradation of progesterone are taken into investigation in order to understand the regulation of luteal function. In rat ovaries, progestational potency of ovarian secretions has been regulated by the activity of 20 alpha-hydroxysteroid dehydrgoenase (20 alpha-HSD), Which catabolizes progesterone to 20 alpha-hydroxypregn-4-en-3-one, progestatinally inert steroid. In regressing corpora lutea, extensive conversion of progesterone to 20 alpha-hydroxypregn-4-en-3-one occurred with a marked increase in 20 alpha-HSD activity as well as a decrease in plasma progesterone concentrations. On the other hand, histochemical studies of glucose-6-phosphate dehydrogenase (G 6 PDH) and delta5-3beta-hydroxysteroid dehydrogenase (3 beta-HSD) have been investigated without any remarkable changes in corporalutea at their early stages of luteolysis. In the present study the activities of steroidogenic enzymes in corpora lutea of pregnant rats are measured after treatment with a variety of abortifacient drugs, and compared with those in corpora lutea of 1 day post partum rats which showed changes characteristic of spontaneous luteolysis. On days 7 to 9 of pregnancy, Wistar-strain pregnant rats were injected with either prostaglandin F2alpha (PGF2alpha), aminoglutethimide or clomiphene citrate (clomid). Animals were sacrificed 15 to 63 hrs. after the last injection, and implantation sites were inspected. Ovaries were removed, and corpora lutea dissected free, weighed and homogenized. The homogenate was centrifuged at 105,000g for 60 min. The supernatant solution was assayed for the activities of G 6 PDH, 6-phosphogluconate dehydrogenase (6 PGDH), malic enzyme, ATP citrate lysase, 20 alpha-HSD and pyruvate kinase. The pellet fraction was re-homogenized, and centrifugated 2,000 g for 5 min. The supernatant solution was used for the assay of 3 beta-HSD. Complete fetal resorption was observed in all rats treated with PGF2alpha, while 7 out of 15 rats (47%) treated with both PGF2alpha and LH-RH maintained pregnancy. In intact rats after treatment with both drugs, lutein cells showed ultrastructures characteristic for luteolysis, although the degree of luteolysis was greatly diminished compared with PGF2alpha-treated ones. In agreement with these ultrastructural findings, 20alpha-HSD activity in corpora lutea was maintained at a rather low level in intact rats, while it was increased moderately in aborted ones after treatment with both drugs. In PGF2alpha-treated rats, G 6 PDH activity increased to 140% and malic enzyme activity decreased to 27% of the activity in control rats. In aminoglutethimide-treated rats, the activites of G 6 PDH and malic enzyme were decreased, while 2-alpha-HSD activity was maintained at a low level...

Abortifacient Agents↗

Acetyl-coenzyme-A carboxylase from rat liver. Subunit structure and proteolytic modification.

The subunit structure of rat liver acetyl-coenzyme-A carboxylase has been studied by polyacrylamide gel electrophoresis in the presence of dodecylsulfate. A number of individual preparations of the enzyme purified by the same procedures exhibited three different types of electrophoretic patterns as follows: first, a single slow-moving protein bands (Mr 230000); secondly, two adjacent fast-moving protein band (M4 124000 and 118 000); finally, all three protein bands. With the use of the [14C]biotin-labelled enzyme, the biotinyl prosthetic group was shown to be associated with the polypeptide of 230000 Mr as well as with that of 124000 Mr, but not with the polypeptide of 118000 Mr. Studies were next made with the labelled enzyme to examine the possibility that the two light polypeptides might have been formed by proteolytic modification of the heavy polypeptide during the procedures used for the purification of the enzyme. Treatment of the enzyme with trypsin or chymotrypsin resulted in cleavage of the heavy polypeptide into two nonidentical polypeptides with molecular weights of approximately 120000. Incubation of the enzyme with proteases derived from rat liver converted the heavy polypeptide into lighter polypeptides of 80000-130000 Mr. Acetyl-CoA carboxylase isolated from crude rat liver extracts by means of immunoprecipitation with specific antibody invariably showed only the heavy polypeptide. The biotin content of the enzyme was found to be 1 mol per 237000 g protein. These results indicate that rat liver acetyl-CoA carboxylase, unlike bacterial and plant biotin enzymes, has only one kind of subunit, which has a molecular weight of 230000 and contains one molecular of biotin. Thus, the mammalian enzyme exhibits a highly integrated subunit structure.

Acetyl-CoA Carboxylase↗

[Pseudogout].

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Adult↗

The effect of Tris-buffered media and Tyrode physiologic saline solution on the antigenic release of histamine from human leukocytes.

Allergic histamine release from leukocytes was compared in three different media: Tyrode physiologic saline solution, Tris-buffered saline containing human albumin, calcium, and magnesium (Tris-ACM), and Tris-ACM with homologous serum. In a selected group of low histamine releasers, the maximal amount of antigenic histamine release was significantly higher in Tyrode solution as compared to Tris-ACM buffer. When homologous serum was added to Tris-acm, an enhancement of histamine release greater than with Tyrode solution was obtained. These results suggest that Tris-ACM may not be the optimal buffer for leukocyte histamine release experiments. Since Tyrode solution contains no serum proteins that bind slow-reacting substance of anaphylaxis or prostaglandins, the use of this medium may be advantageous for the study of the release of the chemical mediators from human leukocytes.

Buffers↗

Glycogenolysis and control of anaphylactic histamine release by cyclic adenosine monophosphate--related agents.

The relationship of glycogen and glucose to anaphylactic histamine release from chopped sensitized guinea pig lung in vitro was studied. A parallelism was observed between the total amount of glycogen in the sensitized lung and the total amount of histamine released from the lung by antigen-antibody reactions. Removal of glucose from the medium for tissue suspension resulted in reduction in histamine release. Depletion of glycogen and/or glucose from the system was associated with (1) abolition of the inhibition of histamine release by isoproterenol and high concentrations of dibutyryl cyclic adenosine monophosphate (AMP) and (2) increase in the rate of enhancement of histamine release by lower concentrations of dibutyryl cyclic AMP. The results indicate that (1) glycogen may be one of the ultimate energy sources for anaphylactic histamine release, and (2) the presence of adequate amounts of glycogen and/or glucose in the sensitized tissue is necessary for the normal beta adrenergic effects on the histamine release in vitro from sensitized lung fragments.

Anaphylaxis↗

Glycogenolysis and control of anaphylactic histamine release by cyclic adenosine monophosphate-related agents. II. Modification of histamine release by glycogenolytic metabolites.

D-glucose-6-phosphate (less than or equal to 5 x 10(-3) M), pyruvate, lactate (less than or equal to 1 X 10(-2) M), and dibutyryl cyclic AMP (less than 5 X 10(-3) M) were capable of inhibiting anapylactic histamine release in vitro from chopped guinea pig lung. In lower concentrations, pyruvic acid and lactate, as well as dibutyryl cyclic AMP, enhanced the release. Significant synergism was observed betweenpyruvate (5 X 10(-3) M) and isoproterenol (1 X 10(-8) M) in the inhibition of histamine release. The inhibitory actions of isoproterenol, glucose-6-phosphate, and pyruvate were influenced by calcium ion concentration. However, beta blockade, which diminished the isoproterenol effect, was without efect on pyruvate (1 X 10(-2) M) to the release system. Glucose-6-phosphate and isoproterenol did not have this effect. The results, together with a prevouus study, suggest that glycogenolysis may possess a role in the anaphylactic istamine release in vitro from sensitized lung fragments...

Anaphylaxis↗