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Biomedical subjects

K Iwata

Publications and source records attributed to K Iwata.

At least 379 records · Page 21Linked to original sources
PubMed1985

Mouse skin melanoma induced in two stage chemical carcinogenesis with 7,12-dimethylbenz[a]anthracene and croton oil.

Mouse skin melanomas were induced in two stage skin carcinogenesis with 7,12-dimethylbenz[a]anthracene as initiator and croton oil as promoter. After approximately 25 weeks of promotion, small black macules of the skin were observed in C57BL, CDF1 and BDF1 mice, and progressively grew with time. Macules less than 2 mm in diameter were localized mostly in the lower portion of the dermis and, histologically, these lesions were consistent with the diagnosis of melanocytoma and were composed of polygonal to round cells loaded with large numbers of melanin granules. The cells were closely packed forming well-demarcated cell-nests with occasional columnar arrangement. In the macules over 2 mm in diameter, the cells were closely packed to form irregularly bordered cell-nests, showing invasive growth into the surrounding tissues. The lesions were diagnosed as malignant melanomas. The incidence of benign and/or malignant melanoma differed among strains: 80% in BDF1, 70% in CDF1, 30% in C57BL/6 and 0% in DBA/2 mice. One example of tumor induced in a CDF1 mouse was transplantable to homologous CDF1 mice.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Pharmacokinetics of plasma and urine clenbuterol in man, rat, and rabbit.

Therapeutic dose (20, 40 and 80 micrograms/man) of clenbuterol hydrochloride, a beta 2-adrenergic stimulant, was orally administered to healthy volunteers, and the unmetabolized drug in plasma and urine was determined by enzyme immunoassay. The plasma levels of clenbuterol reached the maximum value of 0.1, 0.2 and 0.35 ng/ml, respectively, in a dose-dependent manner within 2.5 h, which lasted for over 6 h after the administration. The half-life of clenbuterol in plasma was estimated to be about 35 h. When the drug was orally administered repeatedly to men twice a day, the plasma level reached the plateau within 4 d after the initial administration. At that time, the plasma levels of the unchanged form were 0.2 to 0.3 ng/ml and 0.5 to 0.6 ng/ml at doses of 20 and 40 micrograms/man, respectively. The bound ratio of the drug to plasma protein was estimated to be 89-98% at a single administration of 80 micrograms of the drug. The cumulative urinary excretion of unchanged compound corresponded to about 20% of the administered dose as measured at 72 h following a single oral administration. When clenbuterol hydrochloride was orally administered to rats at a dose of 2 micrograms/kg, the plasma level reached the maximum at about 1 h after the administration. In rabbits, the plasma concentrations reached the maximum value of about 0.2 and 0.8 ng/ml within 2 h following administration of clenbuterol hydrochloride at doses of 0.5 and 2 micrograms/kg, respectively. The half-life of clenbuterol in plasma was about 30 h in rats and about 9 h in rabbits.

Animals↗
PubMed1985

[Threshold of penicillin induced epileptiform afterdischarge in brain slices of guinea pig].

Investigation of the regional threshold for epilepsy in many structures in the brain would contribute to the study of epileptogenesis. So we studied the threshold for epileptiform afterdischarge in the neocortex, hippocampus and cerebellar cortex using Na-Penicillin -G (Pc) of which epileptogenesis has been intensively investigated. In order to eliminate the influence from the outside of these structures, the brain slice method was utilized. Procedures for preparation of the tissue and incubation were about the same as those described by Yamamoto. In summary, after sacrifice, brain of the guinea pig was taken out and the hippocampus, neocortex and cerebellum were cut with a razor blade under a microscope. The thickness of the section was about 0.3 mm. Slices were incubated at 37 degrees C for about 30 min in the standard medium perfused with 95% O2 and 0% CO2. The chamber was continuously perfused with the standard medium which composed of NaCl, 124 mM, KCl, 5: KH2PO4, 1.24; MgSO4, 1.3; CaCl2, 2.4; NaHCO3, 26; and glucose, 10. Evoked potentials were elicited by electrical stimulation in the standard medium. Mossy fibers were stimulated and responses were recorded from the CA3 area in the hippocampus by glass pipette microelectrode. Subcortical white matter was stimulated and responses were recorded from the Purkinje cell layer in the cerebellum. Pc was added in the standard medium until epileptiform afterdischarges were superimposed on the evoked potentials. The results of this experiment demonstrated that each structure in the brain has a regional own threshold for Pc induced epileptiform afterdischarge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Bronchodilating and cardiovascular effects of intraduodenally and orally administered clenbuterol in dogs.

The bronchodilating and cardiovascular effects of intraduodenally and orally administered 4-amino-alpha-[tert-butylamino)methyl]-3,5-dichlorobenzylalcohol hydrochloride (clenbuterol, NAB 365) in anesthetized and conscious dogs were investigated and compared with those of salbutamol, isoprenaline (isoproterenol) and (4-amino-3,5-dichlorophenyl) glycolic acid (M-7), a metabolite of clenbuterol. In pentobarbitalized dogs, clenbuterol, 3-100 micrograms/kg i.d., inhibited the increase in airway resistance induced by histamine in a dose-related manner; clenbuterol was approximately 2 and 100 times more potent than salbutamol and isoprenaline, respectively. The plasma level of clenbuterol increased within 15 min and reached the maximum level within 60 to 90 min, which lasted for over 4 h after administration. The inhibitory effect was abolished by pretreatment with propranolol. M-7 showed no significant effect. In anesthetized dogs, clenbuterol and salbutamol, 10 and 100 microgram/kg i.d., decreased arterial blood pressure and increased heart rate and maximum rate of rise of left ventricular pressure. Isoprenaline, 10 and 100 micrograms/kg i.d., caused no marked changes in these parameters. In conscious dogs, clenbuterol, 10 and 100 micrograms/kg p.o., and salbutamol, 100 micrograms/kg p.o., increased heart rate; the maximum responses were observed 1 to 2 h after administration and lasted for over 3 h. No marked effects were observed after salbutamol, 10 micrograms/kg p.o., isoprenaline, 10 and 100 micrograms/kg p.o., and M-7, 100 micrograms/kg p.o.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1984

A rapid, simple screening method for skin-tumor promoters using mouse peritoneal macrophages in vitro.

The enhancing effects in vitro of a potent skin-tumor promoter, phorbol myristate acetate (PMA), and its derivatives on nitroblue tetrazolium (NBT) reduction, phagocytosis and cell spreading of mouse peritoneal macrophages were compared. The enhancing effects on these markers of macrophage function, especially NBT reduction, were found to correlate well with the skin-tumor promoting activities of the phorbol esters. Another potent promoter, teleocidin, strongly enhanced NBT reduction, although teleocidin is structurally different from phorbol esters. Other tumor promoters, namely saccharin, phenobarbital, cantharidin and Tween 60 did not enhance NBT reduction by macrophages. These data indicate that this test system is appropriate for screening of PMA-type tumor promoters such as phorbol esters and teleocidin.

Animals↗
PubMed1984

Chromosomal aberrations in V79 cells induced by superoxide radical generated by the hypoxanthine-xanthine oxidase system.

The effect of the superoxide radical, generated by the hypoxanthine-xanthine oxidase system, on chromosomal mutation was examined in Chinese hamster V79 cells. When cells were treated with this system for 1 h in Hanks' solution, the incidence of metaphases with chromosomal aberrations was increased with hypoxanthine at concentrations of 2.5 to 10 micrograms/ml. On the other hand, in Eagle's minimum essential medium (MEM) or MEM supplemented with 10% fetal bovine serum, only hypoxanthine at 5 micrograms/ml plus xanthine oxidase induced chromosomal aberrations and higher concentrations of hypoxanthine were cytotoxic to V79 cells. The increased frequency of chromosomal aberrations and the cytotoxicity of hypoxanthine plus xanthine oxidase were not affected by superoxide dismutase, but were strongly inhibited by catalase.

Animals↗
PubMed1984

Granulocytic sarcoma presenting as a mediastinal tumor. Report of a case and cytological and cytochemical studies of tumor cells in vivo and in vitro.

An unusual case of granulocytic sarcoma in a 23-year-old man is reported. The patient initially presented with mediastinal tumor and was diagnosed clinically as having thymoma. The patient was treated by radiotherapy and surgical removal of the tumor. Histology of the excised tumor had been nondiagnostic because of extensive fibrous changes. Eight months later, the patient developed pleural effusion on the right, which soon was followed by blood and bone marrow pictures consistent with acute promyelocytic leukemia. In vitro culture of pleural effusion cells unexpectedly gave rise to a continuously growing peroxidase-positive myeloid cell line. Autopsy revealed the recurrent mediastinal tumor to be positive for intracytoplasmic naphthol AS-D chloroacetate esterase and lysozyme activity. From these findings, the patient retrospectively was diagnosed as having mediastinal granulocytic sarcoma, which terminated in pleural effusion and acute promyelocytic leukemia.

Adult↗
PubMed1984

[3H]Ro 22-1319 (piquindone) binds to the D2 dopaminergic receptor subtype in a sodium-dependent manner.

Ro 22-1319, a novel pyrroloisoquinoline compound, is a potent antipsychotic agent with low potential for extrapyramidal effects and tardive dyskinesia. In this study, the specific binding of [3H]Ro 22-1319 to the rat striatal homogenates has been examined. The binding of [3H]Ro 22-1319 was found to be critically dependent on the presence of sodium in the incubation medium. There appeared to be a single saturable binding component for [3H]Ro 22-1319 with a high affinity. The binding sites showed a stereochemical specificity for (-)Ro 22-1319, (+)butaclamol, and (alpha)flupenthixol. Ro 22-1319 and three D2 antagonistic antipsychotics (sulpiride, metoclopramide, and molindone) exerted a more potent inhibition of [3H]Ro 22-1319 binding than of [3H]spiroperidol binding, whereas other classical antipsychotics were almost equipotent at both binding sites. The requirement for sodium to detect Ro 22-1319 binding was also verified by the use of [3H] spiroperidol binding. The competition curves of Ro 22-1319, sulpiride, metoclopramide, and molindone for [3H]spiroperidol binding were shifted to the right by the omission of sodium in the incubation medium, whereas spiroperidol, chlorpromazine, and domperidone were equiactive under both conditions. These results suggest that Ro 22-1319 has a sulpiride-like property and binds to a D2 dopaminergic receptor subtype in a sodium-dependent manner. Nineteen pyrroloisoquinoline derivatives were also tested for their inhibitory effects on [3H]Ro 22-1319 and [3H] spiroperidol binding. An interesting finding was that small changes in chemical structure modulated the potency at D2 dopaminergic receptor subtypes. Thus, the compounds having a nonlipophilic functional group on the basic nitrogen (Ro 22-1319, Ro 22-3822, etc.) showed a stronger potency at [3H]Ro 22-1319 receptors whereas the compounds having a lipophilic group (Ro 22-6600, etc.) were nonselective antagonists at both [3H]Ro 22-1319- and [3H]spiroperidol-binding sites. However, all pyrroloisoquinoline derivatives including Ro 22-6600 showed a sodium dependency for [3H]spiroperidol-binding sites, indicating that the functional moiety which displays a sodium dependency may be the pyrroloisoquinoline moiety itself.

Animals↗
PubMed1984

Establishment of a new peroxidase-positive human myeloid cell line, PL-21.

A myeloid cell line, designated PL-21, was established from the peripheral blood of a patient with acute promyelocytic leukemia. The PL-21 cell line grew in single-cell suspension, with a doubling time of 48-64 hr, and consisted of promyelocytes with fine immature nuclei and prominent azurophilic granules in the cytoplasm. PL-21 cells were positive for peroxidase, naphthol AS-D chloroacetate esterase, and Sudan Black B staining. Under the usual culture conditions, a small proportion of these cells differentiated into mature granulocytes, and this differentiation was enhanced by the addition of dimethyl sulfoxide in the culture medium. PL-21 cells had receptors for the Fc portion of IgG and complement, intracytoplasmic lysozyme and phagocytic activity, but lacked Epstein-Barr virus-associated nuclear antigen. Chromosome analysis of this cell line revealed a human male polyploid karyotype with 13q+ and double minute chromosomes. This new myeloid cell line may provide useful material for the study of proliferation and differentiation of human leukemia cells.

Adult↗