Biomedical subjects
T Miyata
Publications and source records attributed to T Miyata.
Collagen-induced platelet aggregation and release. I Effects of side-chain modifications and role of arginyl residues.
To investigate the mechanisms governing collagen interaction with blood platelets, the effects of side-chain modifications on collagen-induced platelet aggregation and release of serotonin were studied. Since many chemical modifications alter the ability of collagen to form fibers that, according to current theory, may complicate interpretation of data, we eliminated this possibility by using collagen stabilized in a native-type fibrillar structure by treatment with either glutaraldehyde or ultraviolet irradiation. Acetylation, methylation, succinylation, treatment with 2,4-dinitrofluorobenzene, 2,4,6-trinitrobenzene sulfonic acid or 1,2-cyclohexanedione, and deguanidination with hypobromite were used to modify collagen side-chain reactive groups: amino, carboxyl, hydroxyl and guanidino. Both unmodified monomeric dispersed and fibrillar collagen preparations initiated platelet aggregation and release, although the kinetics and magnitude of the response were different. Monomeric collagen which had been modified by deguanidination, methylation or succinylation, failed to polymerize in physiological conditions and did not induce platelet aggregation and release. However, none of the chemical modifications of stabilized native-type collagen fibers, except treatment with hypobromite or cyclohexanedione, had an effect on collagen-induced platelet aggregation and release. Both hypobromite and cyclohexanedione modified guanidino groups of arginyl residues. Results showed that the ability of a collagen sample to induce platelet aggregation and release of serotonin is dependent on the arginine content of fibrillar collagen. These data demonstrate that manipulation of amino, carboxyl and hydroxyl groups is unimportant as long as the native-type fibrillar structure is maintained, and that arginyl residues are directly involved in collagen-platelet interaction. Moreover, the data suggest that only the arginyl residues in the Y position of the tripeptide unit Gly-X-Y of collagen are responsible.
Collagen-induced platelet aggregation and release. II Critical size and structural requirements of collagen.
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Evolution of overlapping genes.
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Soluble gentamicin ophthalmic inserts as a drug delivery system.
A comparison was made of soluble 14C-gentamicin ophthalmic inserts with drop, ointment, and the subconjunctival routes of administration. The insert is a solid, solubilizable collagen polymer containing 14C-gentamicin. We compared the levels of 14C-gentamicin in the rabbit tear film and in multiple corneal and scleral biopsies to determine which route of administration gave the best results. The wafer route of administration gave the highest tear film and tissue concentration of drug. The tear film concentration by subconjunctival injection was surprisingly low. Soluble collagen inserts offer a new method of delivering high doses of gentamicin in infected corneal tissue in a convenient and atraumatic fashion.
[The effect of water of crystallization of berberine chloride on disintegration and dissolution behaviors of the tablet (author's transl)].
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[Water of crystallization of berberine chloride (author's transl)].
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Metabolites of piperidine in rat urine.
Piperidine is one of pharmacologically active biogenic amines. While two pathways for piperidine production have been reported, little is known about metabolism of the compound. In the present study, piperidine and its hydroxylated, conjugated and unknown metabolites were detected in rat urine by radiochromatographic analysis. Using GC-MS technique, it was confirmed that 3-hydroxypiperidine and 4-hydroxypiperidine are major metabolites of piperidine of either exogenous or endogenous origin. The findings substantiate the existence of a mechanism which inactivates piperidine in the living body, since both metabolites lack the potent pharmacological activities as those induced by piperidine.
[Evaluation of abnormalities of the pulmonary vascular bed in total correction of tetralogy of Fallot and their effects on the postoperative course (author's transl)].
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[Action of 4-amino-alpha-](tertbutylamino) methyl]-3, 5-dichlorobenzylalchol hydrochloride (N-AB 365, clenbuterol) on the respiratory system (author's transl)].
The bronchodilating effect and other related pharmacological properties of N-AB 365 were studied in comparison with those of isoproterenol, salbutamol and clorprenaline. N-AB 365 was found to produce a bronchodilating effect 1/20 approximately 1/100, 1/10 approximately 1/40 and was 2 to 5 times as strong as effects of isoproterenol, salbutamol and clorprenaline, respectively. The bronchodilating effect of N-AB 365 was sustained more than 10 times as long as those of isoproterenol and salbutamol, and in particular with oral administration, was much more potent. The bronchodilating effect of N-AB 365 seems to be due mainly to excitation of the adrenergic beta2-receptor and partially to papaverine-like action. N-AB 365 showed an inhibitory effect on experimentally induced bronchial asthma by spraying of bronchoconstrictors and the effect by oral administration was much stronger than those of isoproterenol and salbutamol. N-AB 365 affected neither the volume output of respiratory tract fluid nor the tracheal ciliary movement with the doses around ED50 in bronchodilating action, however, it increased ciliary activity and decreased the volume output of respiratory tract fluid with large doses. Antitussive effect was also demonstrated only with the large doses. N-AB 365 induced a moderate decrease in blood pressure through vasodilatation but did not influence respiration. The effect of N-AB 365 on heart rate varied. There were cases of no change, slight increase or slight decrease in heart rate.
The stimulative effect of polyethylenimine on the reaction of RNA polymerase from cauliflower.
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Soluble artifical tear inserts.
This article reports a new concept in the treatment of tear film abnormalities. Solubilization of an artifical tear insert provides a continuous flow of polymer into the tear film in place of intermittent drop therapy. The physiochemical properties of succinylated collagen were studied in vitro and compared favorably with presently available tear substitutes. The use of this polymer as a solid solubilizable insert was evaluated in normal patients. It was found to be comfortable, resulted in no blurring of vision, and prolonged the tear film breakup time.
[Pharmacology of benzoctamine, a new psychotropic agent].
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A cough-like respiratory response induced by electrical stimulation of the amygdaloid complex in the cat.
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Neural mechanism for production of spasmodic expiratory response like cough induced by amygdala stimulation in the cat. I. Pathways from the amygdala to the lower brain stem.
The pathways descending from the amygdala to neural structures in the lower brain stem responsible for production of spasmodic expiratory response like cough (SER), which occurred upon electrical stimulation of the cortical nucleus of amygdala (Aco), were investigated using microinjection and ablation techniques in the cat. 1) Following transection of the bilateral stria terminalis (STT), the threshold for SER production was remarkably elevated. 2) SER was suppressed by administration of procaine (20 microgram) or diazepam (5 microgram) into either side of the hypothalamic ventromedial nucleus (Hvm); furthermore, SER completely disappeared after lesion of bilateral Hvm. After lesion of the ipsilateral Hvm to the side of stimulation, the threshold for SER was obviously elevated, but SER was not affected by lesion of the contralateral Hvm. 3) After section of the substantia grisea centralis at the midcollicular level, SER disappeared. 4) Both SER and peripherally-induced coughs were depressed by codeine (10 microgram), dextromethorphan (10 microgram) or procaine (20 microgram) administered into the solitary tract nucleus (STN) or the nucleus reticularis parvocellularis. 5) SER and coughs disappeared after lesion of the bilateral STN or nucleus ambiguus (AM). These results demonstrate that most of the efferent fibers from Aco get to Hvm via STT, and further to STN and AM in the medulla.
Neurobiology of piperidine: its relevance to CNS function.
Piperidine is a normal constituent in mammalian brain, affects synaptic mechanism in the CNS, and influences neural mechanisms governing regulation of emotional behavior, sleeping, and extrapyramidal function. In addition, there are enzyme systems within the brain that synthesize and metabolize piperidine, and uptake and storage mechanisms for piperidine are found in the nerve endings. In conclusions, piperidine seems to be intimately connected with the neuronal function of the brain.
Deposition of platelets and fibrin on chemically modifide collagen hollow fibers.
A new technique was devised for interaction studies between human blood and chemically modified amorphous collagen surfaces. Blood is drawn directly from an antecubital vein, through saline-filled collagen hollow fibers, at either constant flow for varying time or constant time at varying flow. Platelets and fibrin were deposited more rapidly and in greater numbers on methylated surfaces and more slowly and to a lesser extent on succinylated surfaces than on native surfaces. Increasing blood flow was associated with increased fibrin formation. Adherent platelets spread over 3-8 mu of methylated surface, but retained a spherical shape (1-2 mu) on succinylated and native surfaces. Thus, charge modification of collagen significantly alters platelet adhesion, subsequent platelet morphology, and fibrin deposition. Methylated surfaces are thrombogenic and succinylated ones are relatively thrombo-resistant.
Antitussive activity and other related pharmacological properties of d-3-methyl-N-methylmorphinan (AT-17).
Antitussive activity and some other related pharmacological properties of d-3-methyl-N-methylmorphinan were studied. Toxic symptoms in mice and dogs were due to the CNS excitation. Acute toxicity of (AT-17) in mice was slightly (s.c.) or far (p.o.) weaker than that of codeine, but it was three times as toxic as codeine in dogs (i.v.). Antitussive efficacy was about 40% of that of codeine in dogs, whereas 77% as potent as codeine in cats. It showed no relaxing effect on the bronchial muscle of guinea pigs in either normal tone or histamine-induced spasms. It had analgesic effect 1/3 as potent as codeine in mice but it was not antagonized by levallorphan. The prolongation of hexobarbital sleeping time by AT-17 was similar extent to that by codeine. Anti-electroshock effect was half as potent as that of phenobarbital. The inhibitory effect on the transportation of intestinal contents in mice was far weaker than that of codeine. Effect on the respiratory and circulatory systems were also investigated.