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Biomedical subjects

T Shibuya

Publications and source records attributed to T Shibuya.

At least 379 records · Page 21Linked to original sources

Mouse spot tests with dimethylbenz[a]anthracene with and without phenobarbital pretreatment.

Mouse spot tests using dimethylbenz[a]anthracene (DMBA) were carried out on PW strain male mice and female C57BL/6 mice. DMBA induced somatic gene mutations in developing mouse embryonic cells. Pretreatment of pregnant females with phenobarbital (PB) reduced the incidence of somatic mutation by DMBA. The testes of males treated with DMBA in utero, whether treated with PB or not, showed severe retardation of development. The amount of cytochrome p-450 in the liver of C57BL/6 females increased about 2-fold by the pretreatment schedule, carried out on days 10-12 of pregnancy.

9,10-Dimethyl-1,2-benzanthracene↗

Structure-affinity relationships between several new benzodiazepine derivatives and 3H-diazepam receptor sites.

Several new benzodiazepines were studied with respect to their ability to bind specifically to benzodiazepine receptor sites in rat cerebral cortex membrane fraction. The IC50 values of new benzodiazepines were compared to that of diazepam. A group of triazolo-[1,4] benzodiazepines displaced 3H-diazepam very effectively. The most potent of this group was brotizolam . Its potency was about ten times higher than that of diazepam. In this study, camazepam, which differs from diazepam in its C-3 substitution, had the lowest affinity to the benzodiazepine receptor site. This potency was about 0.006 that of diazepam. CM 7116 bound with the highest affinity to the benzodiazepine receptor site among the metabolites of CM 6912. The length of the side chain at the C-3 position of this compound is shorter than that of the other metabolites of CM 6912. These results indicated that the long side chain at the C-3 position might inhibit a close interaction between the receptor site and the substrate molecule, thereby leading to low-affinity binding.

Animals↗

Differential, postnatal ontogeny of opiate and benzodiazepine receptor subtypes in rat cerebral cortex: binding characteristics of tifluadom and brotizolam.

The postnatal development of 3[H] ethylketocyclazocine (EKC) binding characteristics was examined using membranes from the cerebral cortex of rats at various ages. Binding site affinity did not vary significantly between postnatal days 1 and 90. However, the apparent density of cortical binding sites increased fivefold between birth and adulthood. These results were similar to another ontogenic study of brain opiate receptor binding. Whereas EKC was equally potent as a competitor for 3[H] EKC binding in cortex from neonatal and adult rats, tifluadom was three times more potent in neonatal cortex than in adult cortex as a displacer of specific EKC binding. Brotizolam, a new thienodiazepine and a potent sedative hypnotic, also was distinctly more potent as an inhibitor of 3H-diazepam binding in neonatal rat brain cortex than in adult rat brain cortex. These results suggest that subtypes of benzodiazepine receptors, as well as some opiate receptor subtypes, exhibit different rates of postnatal development.

Animals↗

Chronic intermittent atrial standstill with intraatrial block and split atrial potentials.

A 24-year-old male with chronic atrial standstill underwent an electrophysiologic study. No atrial activity was recorded from the right atrium which did not respond to stimulation with up to 10 volts. After the administration of atropine, non-localized split atrial potentials appeared, and intraatrial phase 4 block and atrial flutter with intraatrial 2:1 block were observed. The atrium then responded to electrical stimulation (less than 2 volts). Persistent sinus node activity with intraatrial block was found during post-pacing atrial pauses.

Action Potentials↗

Pharmacological profile of a new beta-adrenoceptor blocker, 4-[3-(tert-butylamino)-2-hydroxypropoxy]-N-methylisocarbostyril hydrochloride (N-696).

To characterize the pharmacological profile of a new beta-adrenoceptor blocker, 4-[3-(tert-butylamino)-2-hydroxypropoxy]-N-methylisocarbostyril hydrochloride (N-696), experiments were performed in the isolated atria and trachea of the guinea pig, in the pithed rat, in the anesthetized rabbit, in anesthetized dogs and in anesthetized open-chest dogs. Antiarrhythmic action was assessed in conscious as well as in anesthetized dogs. Although N-696 was a non-selective beta-blocker 15-20 times less potent than propranolol under in vitro conditions, it was as effective a blocker as propranolol under in vivo conditions. N-696 produced a fall of the blood pressure in the pithed rat and attenuated the blood pressure rise produced by stimulation of the preganglionic sympathetic nerve. In the anesthetized rabbits, it produced a hypotensive effect associated with an increased discharge of the renal nerve. In anesthetized dogs it produced a hypotensive effect and a decrease in the myocardial blood flow. However, the decrease in the myocardial blood flow was smaller than that produced by propranolol. All these findings indicate that N-696 has a direct vasodilatory effect besides its beta-blocking action. As a beta-blocker N-696 was unique in that it produced a potent antiarrhythmic effect in two-stage coronary ligation arrhythmia.

Adrenergic alpha-Antagonists↗

A case of adult T-cell leukemia initiated with central nervous system symptoms.

We treated a 52-year-old Japanese woman with adult T-cell leukemia (ATL) initiated with central nervous system (CNS) symptoms. Her chief complaints were paraplegia and left facial palsy. CNS-ATL was diagnosed because of the following three features. 1) Various sized lymphoid cells with marked nuclear convolution were numerous in her cerebrospinal fluid. 2) These cells were a monoclonal proliferation of T lymphocytes with OKT 4 marker. 3) The patient's serum was positive for anti-ATL associated antigen (ATLA). Although the neurological signs and symptoms improved markedly after intrathecal administration of combined chemotherapy (methotrexate, cytarabine and corticosteroid), these ATL cells were highly resistant to radiation therapy. The abdominal mass which developed in the course of the disease was diagnosed as a tumor formed of ATL cells, and VEPA (vincristine, endoxan, prednisolone and adriamycin) was administered with marked success.

Antigens, Neoplasm↗

Effect of stimulation and blockade of mononuclear phagocyte system on the treatment of microfilaremia of Litomosoides carinii in the cotton rat and the jird.

The role of mononuclear phagocyte system (MPS) in the effect of diethylcarbamazine (DEC) for clearing microfilariae of Litomosoides carinii from the blood stream was studied in the cotton rat and the jird, using diethylstilbestrol (DES) for the stimulation of MPS and carrageenan (CGN) for the blockade of MPS. The level of microfilaremia was not influenced by administration of DES subcutaneously or CGN intraperitoneally, indicating that the circulating microfilariae in naturally infected animals were affected neither by the activation nor suppression of MPS. DEC-mediated clearance of microfilariae in the cotton rat was remarkably enhanced by the activation of MPS. Unlike the cotton rat, microfilaricidal effect of DEC in the jird was not influenced by pretreatment with DES. This result corresponds to the fact that the phagocytic activity of MPS was enhanced by DES in the cotton rat, but not in the jird. On the other hand, although the phagocytic activity of MPS was depressed by CGN in the cotton rat, there was no distinct change in the effect of DEC both in the cotton rat and the jird by pre-treatment with CGN, suggesting that CGN-mediated blockade of MPS was a transient phenomenon.

Animals↗

The establishment of a human myeloma cell line elaborating lambda-light chain protein.

A human myeloma cell line (KMM-56) producing lambda-light chain protein was established in vitro by cultivation of the cells in the pleural effusion obtained from a patient with IgD-lambda-myeloma. The cells proliferate in suspension and do not aggregate or attach to the culture dish. Surface marker analysis revealed that the cells were negative for E-rosette, and surface immunoglobulin. Immunoelectrophoresis, immunodiffusion, and immunofluorescence with various antibodies demonstrated no heavy chains, while lambda-light chains were detected in the cytoplasm of the cells. Using the immunodiffusion technique, only lambda-light chains were detected in the frozen and thawed cell extract, the concentrated supernatant of the cell culture, and the urine of the patient. Electron microscopic examination revealed the plasmablastoid appearance of the cells. This cell line may be useful for future studies of human immunoglobulin genes and for the material of human-human hybridoma, which could produce monoclonal human immunoglobulin.

Aneuploidy↗

Prenatal and postnatal exposure to diazepam: effects on opioid receptor binding in rat brain cortex.

The effects of chronic perinatal or postnatal administrations of diazepam on opiate receptor development in cerebral cortex and striatum were studied at two different post-treatment ages, using tritiated ethylketocyclazocine, the prototypic kappa-opiate, for measurements of opiate binding site ontogeny. Prenatal plus postnatal exposure to diazepam markedly decreased the total number of binding sites for [3H]ethylketocyclazocine in the rat cerebral cortex and striatum at 14 days of age. Postnatal diazepam treatment alone did not alter [3H]ethylketocyclazocine binding site development in cortex or striatum. These results suggest that development of opiate receptors in rat brain can be altered by prenatal exposure to diazepam.

Animals↗