Biomedical subjects

K Morita

Publications and source records attributed to K Morita.

At least 19 recordsLinked to original sources

PubMed1992

Augmentation of retinoic acid-induced granulocytic differentiation in HL-60 leukemia cells by serine/threonine protein phosphatase inhibitors.

To evaluate the involvement of protein phosphatases (PP) in differentiation of human myelogenous leukemia HL-60 cells, we made use of potent inhibitors of PP1 and PP2A, calyculin-A (CAL-A) and okadaic acid (OKA). CAL-A and OKA could augment all-trans retinoic acid (ATRA)-induced granulocytic differentiation, whereas the differentiation toward macrophage lineage by 12-o-tetradecanoylphorbol acetate (TPA) was unchanged in the presence of CAL-A. CAL-A augmented the phosphorylation of 18K, 23K and 30K proteins induced by ATRA. The PP1 and PP2A were identified and were present mainly in the cytosol of HL-60 cells. These results suggest that either PP1 or PP2A or both may be involved in regulating granulocytic differentiation of HL-60 cells.

Cell Adhesion↗

PubMed1992

Simultaneous assay of adenosine deaminase and purine nucleoside phosphorylase activity as possible biochemical means to detect non-Hodgkin lymphomas of the oral cavity.

BACKGROUND AND METHODS: This study proposes the usefulness of simultaneous assay of adenosine deaminase (enzyme code [EC] 3.5.4.4; ADA) and purine nucleoside phosphorylase (EC 2.4.2.1; PNP) activities in a biopsy specimen as a biochemical test adjunctive to the histologic diagnosis of oral non-Hodgkin lymphomas (NHL). RESULTS: NHL tissues showed an ADA activity of more than 1428 nmol/h/mg of protein, and more than 3451 nmol/h/mg of protein was the sum of ADA and PNP activity. In contrast to this finding, all the 106 lesional tissues affected by various carcinomas, various benign tumors, various cysts, ameloblastomas, osteosarcomas, gingival hyperplasia, and inflammation showed an ADA activity of less than 1000 nmol/h/mg of protein, except for 2. The sum of ADA and PNP activity was less than 2249 nmol/h/mg of protein in these diseases, except for squamous carcinoma. Different control tissues of the oral cavity showed less than 766 nmol/h/mg of protein in ADA activity, and the highest sum of ADA and PNP activity in these was only 1384 nmol/h/mg of protein. CONCLUSIONS: These findings suggest that a strong suspicion of oral NHL is justified when the sum of ADA and PNP activity in a biopsy specimen exceeds 3000 nmol/h/mg of protein and ADA activity is greater than 1000 nmol/h/mg of protein.

Adenosine Deaminase↗

PubMed1992

A comparative ultrastructural and histochemical study of the metacercarial cyst walls of four species of Paragonimus (Troglotrematidae: Trematoda).

The metacercarial cyst walls of Paragonimus westermani, P. miyazakii, P. ohirai, and P. iloktsuenensis were examined using ultrastructural and histochemical techniques. The cyst walls of P. westermani, P. miyazakii, and P. ohirai were found to have five distinct layers, whereas the wall of P. iloktsuenensis had only two. The so-called outer cyst wall recognized on light microscopy by Miyazaki (1961) was composed of layers I-III and the so-called inner cyst wall comprised layers IV and V. The outermost layer (I) consisted of collagen fibers and probably originated from the host. Layer III detached easily from layer IV on removal of the cysts from the host tissues. Layer IV was composed of proteoglycans, and layer V consisted of protein alone. A regular hexagonal pattern in layer V appeared to be characteristic of P. westermani. Although the basic morphological patterns observed in the layers constituting the cyst walls were similar in all species examined, the thickness of each layer was apparently different. This characteristic seems to be a suitable criterion for the identification of metacercarial cysts of Paragonimus species.

Animals↗

PubMed1992

Hemoglobin Kansas found in a patient with polycythemia.

A 62-year-old woman, long suspected of having heart disease, was admitted to our hospital for thorough examination. Her hemoglobin level was 17.7 g/dl and her 2.3-DPG level was 8.90 microM/ml RBC. The patient proved to have polycythemia, hemoglobin Kansas, and diabetes mellitus. To our knowledge, this is the third case of hemoglobin Kansas in the world.

2,3-Diphosphoglycerate↗

PubMed1992

Accumulation of 99mTc-HM-PAO in photon deficient areas in bone scan of bone metastasis from hepatocellular carcinoma.

To evaluate bone metastasis from hepatocellular carcinoma (HCC), both bone and 99mTc-HM-PAO scintigraphies were performed in six patients with clinically and pathologically confirmed HCC. Two patients had a bone scintigram which revealed abnormal accumulation in the skull base, pelvic bone and thoracic spine. The 99mTc-HM-PAO scans of both these patients also showed abnormal accumulation in the same sites. The bone scintigrams in one patient revealed not only abnormal accumulation in the ribs but also photon deficient areas in the sternum, thoracic spine and femur, while 99mTc-HM-PAO scans showed abnormal accumulation in all these sites. In three patients, bone scintigraphy revealed photon deficient areas in the ribs, pelvic bone and femur, and their 99mTc-HM-PAO scintigrams showed abnormal accumulation in the same sites. Thus, it was shown that, in the detection of bone metastasis from HCC by means of bone scintigraphy, it was necessary to pay attention to hot and cold lesions, and that a combination study with 99mTc-phosphorous compounds and 99mTc-HM-PAO was useful in evaluating these lesions.

Aged↗

PubMed1992

Involvement of Ca2+ entry and inositol trisphosphate-induced internal Ca2+ mobilization in muscarinic receptor-mediated catecholamine release in dog adrenal chromaffin cells.

Catecholamine (CA) release from adrenal medulla evoked by muscarinic receptor stimulation has been studied using isolated perfused adrenal gland and cultured chromaffin cells from dogs. Muscarine and oxotremorine (1-100 microM), and bethanechol (0.1-1 mM) dose-dependently stimulated CA release. Muscarine-evoked CA release was antagonized with M1-antagonist, pirenzepine and, to a lesser extent, with atropine; and was reduced either by removal of extracellular Ca2+ or treatment with Ca2+ channel blockers. Muscarine caused an increase of 45Ca uptake and 22Na uptake. Tetrodotoxin (TTX) did not affect muscarine-evoked increase of 22Na uptake and CA release. Under the absence of extracellular Ca2+, muscarine stimulated a 45Ca efflux. Muscarine-induced CA release was attenuated by treating the cells with 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate-HCl (TMB-8) which blocks Ca2+ release from the intracellular store. A phospholipase C inhibitor, neomycin, markedly reduced muscarine-induced CA release but not nicotine- and high K(+)-evoked release. Cinnarizine, a Ca2+ channel blocker, attenuated muscarine-evoked but not caffeine-induced CA release and 45Ca efflux in the absence of extracellular Ca2+. Muscarine caused an increase in intracellular free Ca2+ concentration ([Ca2+]i) in the presence of extracellular Ca2+. It caused a similar increase, but to a lesser extent, in the absence of extracellular Ca2+. The increase of [Ca2+]i induced by muscarine without extracellular Ca2+ was reduced by neomycin and cinnarizine. Polymixin B and retinal, which reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced CA release, had little effect on muscarine-induced CA release. Muscarine increased cellular Ins(1,4,5)P3 production, and atropine inhibited this increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1992

Further studies on the relationship between tyrosine supply and catecholamine production in cultured adrenal chromaffin cells.

To elucidate a possible role of tyrosine supply as a factor modulating catecholamine biosynthesis in the adrenergic cell, the transport of [14C]tyrosine into cultured bovine adrenal chromaffin cells was first examined, and the relationship between [14C]tyrosine transport and [14C]catecholamine formation was then investigated. Under the conditions which were routinely employed to determine the rate of catecholamine biosynthesis, tyrosine was taken up into the cells in a manner independent of extracellular Na+ and Ca2+, and this uptake was also insensitive to ouabain and various metabolic inhibitors. The stimulation of these cells with high K+ and other secretagogues caused no significant alteration in the uptake. While, tyrosine transport was markedly inhibited by tyrosine analogues and other L-aromatic amino acids, and this inhibition was accompanied by the reduction of [14C]catecholamine formation. In contrast, tyrosine transport was markedly enhanced by flavone, and this enhancement was also accompanied by the augmentation of catecholamine production under the same experimental conditions. These results seem to indicate that the transport of tyrosine into the cells may be closely related to catecholamine formation within the cells, thus providing an evidence for a possible role of tyrosine supply as one of the factors affecting catecholamine production in the adrenal chromaffin cell.

Adrenal Medulla↗

PubMed1992

Inhibition of platelet aggregation by the cAMP-phosphodiesterase inhibitor, cilostamide, may not be associated with activation of cAMP-dependent protein kinase.

We examined the involvement of cAMP-dependent protein kinase (A kinase)2 in the inhibition by cilostamide, a specific inhibitor of the low Km cAMP-phosphodiesterase (PDE), on 9,11-epithio-11,12-methanothromboxane A2 (STA2)-induced platelet aggregation. For comparative purposes, the PGE1 analogue, 17S-20-dimethyl-trans-delta 2-PGE1 (OP-1206) was used. OP-1206 (IC50 = 18 +/- 0.55 nM) and cilostamide (IC50 = 40 +/- 4.5 nM) were both potent inhibitors of the platelet aggregation induced by STA2 (1 microM). OP-1206 and cilostamide dose-dependently inhibited elevations in intracellular free Ca2+ ([Ca2+]i) caused by STA2. OP-1206 caused an almost complete inhibition of Ca2+ mobilization, but cilostamide did not prevent the STA2-induced elevation in [Ca2+]i to the same extent as OP-1206, even at a high concentration (greater than 200 nM). Cilostamide did not increase the cAMP level at concentrations (5-100 nm) which affected STA2-induced aggregation. OP-1206 significantly increased cAMP contents in platelets, and the degree of aggregation inhibition by OP-1206 appears to be related to the size of increase in cAMP. OP-1206 increased phosphorylation of the 50,000 mol. wt vasodilator-stimulated phosphoprotein, at concentrations of 7.9-79 nM, which inhibited aggregation induced by STA2. Cilostamide treatment resulted in a marginal increase in the 50,000 mol. wt phosphorylation at concentrations (10-100 nM) which completely inhibited the STA2-induced aggregation. (8R*, 9S*, 11S*)-(-)-9-Hydroxy-9-n-hexyloxy-8-methyl-2,3,9,10- tetrahydro-8,11-epoxy-1H, 8H, 11H-2, 7b, 11a-triazadibenzo(a,g)-cycloocta(c,d,e)trinden-1-one (KT-5720), a specific inhibitor of A kinase, not only reversed the inhibition by OP-1206 of STA2-induced platelet aggregation, but also inhibited the OP-1206-induced protein phosphorylation. However, the inhibition by cilostamide of STA2-induced aggregation was not prevented by pretreatment with KT-5720. Inhibition of the STA2-induced aggregation by OP-1206 may be associated with cAMP-dependent protein phosphorylation, while cilostamide may have inhibitory effects on STA2-induced platelet activation through mechanisms other than the activation of A kinase.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1992

Substance P inhibits activation of calcium-dependent potassium conductances in guinea-pig myenteric neurones.

1. Intracellular recordings were made from myenteric AH neurones of the guinea-pig ileum in vitro. Some experiments were done with a single-electrode voltage clamp to measure membrane currents. 2. Substance P (SP) applied by superfusion (10 nM-300 nM), pressure ejection (100 nM-10 microM, 760 mmHg, for 10-20 ms) or ionophoresis (1 mM, 100 nA, for 0.2 s) caused a membrane depolarization and an inward current, associated with a decrease in potassium conductance. 3. The SP-induced depolarization was abolished within 15 min by superfusion with calcium-free/high-magnesium (10 mM) solution or solutions containing cobalt, manganese or nickel at 1-3 mM. The response persisted even after 40-60 min of superfusion with calcium-free/normal-magnesium (1.2 mM) solution. In all these solutions, synaptic potentials were abolished within 5 min. 4. SP inhibited a slowly developing outward current and an outward tail current during and after a long depolarizing command pulse (2-10 s), and an outward after-current following single or multiple brief depolarizing command pulses (10-50 ms). These outward currents were suppressed in calcium-free/high-magnesium solution. 5. SP depressed both a calcium-dependent slow after-hyperpolarization following the action potential and an outward after-current preceded by a brief depolarizing command. Both the SP-induced depolarization and the SP-induced inward current were augmented when the peptide was pressure-ejected during the recovery phase of the slow after-hyperpolarization and during that of the slow outward after-current, but both of them were inhibited or almost abolished when SP was applied immediately after spike initiation or a brief depolarizing command. 6. The SP-induced response was depressed by barium (1-2 mM). The SP response was not inhibited by tetraethylammonium at low concentrations (5-10 mM), but was depressed at high concentration (20 mM). 7. Superfusion (1-10 nM) or pressure application of a calcium ionophore, A23187, inhibited or even reversed the SP depolarization and the SP-induced inward current. 8. These results indicate that SP inhibits activation of a calcium-dependent potassium conductance which contributes to both the slow after-hyperpolarization and the resting membrane potential. SP may affect the process by which calcium activates this potassium conductance.

Action Potentials↗

PubMed1992

[O serogroup and virulence factors of motile Aeromonas].

A total of 182 isolates of motile Aeromonas from patients with diarrhea and environmental sources was investigated for hemolytic activity to rabbit erythrocyte and cytotoxicity to HeLa 229 cell. Furthermore, the relation between O serogroup and virulence factors, which were lethal to mouse and autoagglutination, were investigated. There were many strains possessing both the hemolytic and cytotoxic activities in A. hydrophila from overseas traveller's diarrhea, suggesting that these activities were associated with intestinal pathogenecity. Although there was a clear correlation between hemolytic and cytotoxic activities in A. hydrophila from overseas traveller's diarrhea, the correlation was not found in A. hydrophila from domestic cases of diarrhea and A. sobria from overseas traveller's diarrhea. Especially, some A. hydrophila isolates from domestic case of diarrhea produced only hemolysin. These results indicated that there was a difference in specificity between the toxins accounted for hemolytic and cytotoxic activities, and more than two different toxins were developed. O serogroups 11, 34, 14, 16, and 35 in that order were the most frequent serogroups. About half of O11 and O34 strains possessed lethal activity to mouse. Autoagglutination phenomenon did not seem to be associated with the lethal activity. In O11 strains, high cytotoxic titer was more frequently found in lethal activity positive-strains than in the activity negative-strains, suggesting that cytotoxicity contributed preferentially to lethal activity to mouse. But such a correlation was not found in O34 strains, so other virulence factors than hemolysin and cytotoxin may be associated with the lethal activity.

Aeromonas↗

PubMed1992

Polymerase chain reaction-based detection of Trypanosoma cruzi DNA in serum.

DNAs prepared from chagasic patients' sera were amplified by the polymerase chain reaction using oligonucleotide primers which anneal specifically to a highly repetitive sequence of Trypanosoma cruzi nuclear DNA. Samples from both acutely and chronically infected patients yielded positive results by this method. No significant difference was observed when either whole blood or serum samples of the patients were used. These results indicate that serum instead of whole-blood samples could be used for polymerase chain reaction-based detection of T. cruzi in field studies without the need of applying any special chemical treatment to the specimens. This would represent a considerable advantage due to the easier handling and transportation of serum as compared with whole-blood samples, especially in tropical climates.

Adolescent↗

PubMed1992

Detection of subtle microcalcifications: comparison of computed radiography and screen-film mammography.

Observer performance tests were conducted to compare the effects of image-processing technique (unsharp mask filtering) on the diagnostic accuracy of computed radiography (CR) with storage phosphors in the detection of microcalcifications. Comparison of detectability of microcalcifications with CR and with screen-film mammography was also performed. Clusters of microcalcifications (125-250 microns in diameter) were randomly superimposed on human breast specimens. Observer performance tests were carried out with receiver operating characteristic (ROC) analysis. The area under the ROC curve and the cumulative true-positive-localization fraction were both used as indexes of performance. Observer performance experiments with nine observers indicated that the two types of screen-film images used provided higher detectability than the CR images. The detectability of microcalcifications on the CR images improved slightly with use of the unsharp masking technique. However, no statistically significant difference was found between processed and unprocessed CR images, and detectability still did not reach the level achieved with the screen-film images.

Breast Diseases↗

PubMed1992

Ki-1-positive large-cell anaplastic lymphoma with protean manifestations including central nervous system involvement.

A 26-year-old female with Ki-1-positive large-cell anaplastic lymphoma is reported. The neoplastic cells were phenotypically and genotypically of T cell origin. Initially, neoplastic cells invaded the skin and lymph nodes, and then invaded the sternal and vertebral bones, ribs and the iliopsoas muscle. Central nervous system (CNS) involvement with paraplegia, large tumor mass formation in her breast and pleural infiltration ensued in succession. This case illustrates the protean manifestations of Ki-1-positive large cell anaplastic lymphoma complicated with CNS involvement.

Adult↗

PubMed1992

Fluconazole: a potent inhibitor of cytochrome P-450-dependent drug-metabolism in mice and humans in vivo. Comparative study with ketoconazole.

The inhibitory effect of fluconazole (FCZ), a bis-triazole antimycotic, on mouse hepatic microsomal cytochrome P-450-mediated drug-metabolizing enzyme system was compared with those of ketoconazole (KCZ) in vivo and in vitro. Additionally, the change in the hepatic oxidative drug-metabolizing capacity in humans treated with FCZ was followed. The pentobarbital sleeping time in mice given a single dose of 1-10 mg/kg of FCZ or 30-50 mg/kg of KCZ was prolonged significantly, and the potency of FCZ for the prolongation of sleeping time was greater than that of KCZ. In contrast, in vitro the affinity and the inhibitory potency of FCZ for cytochrome P-450 and aminopyrine N-demethylation were 4- to 6-fold smaller than those of KCZ. However, the order of the inhibitory potencies among antimycotics for this enzyme systems in vitro was reversed by the addition of albumin into the reaction mixture. These results indicate that the difference in the plasma protein binding properties between FCZ and KCZ is an important factor which leads to a reverse in the order of their inhibitory potencies for this enzyme system in vitro and in vivo. The ratio of 6-beta-hydroxycortisol (6 beta-OHF) to cortisol (F) in urine, used as an indicator of oxidative drug-metabolizing capacity in humans, decreased to 50% of the original level during treatment with 200 mg/d of FCZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

[Stereoselectivity in N-dealkylation of disopyramide enantiomers in mouse hepatic microsomes].

The oxidative metabolism of disopyramide (DIS) enantiomers to mono-N-dealkyldisopyramide in mouse hepatic microsomes was studied in vitro. When (R-)-DIS was used as a substrate Lineweaver-Bulk plot was a single line with the apparent Km value of 0.23 mM and Vmax value of 1.05 nmol/mg protein/min. When S(+)-DIS was used as a substrate the plot was biphasic, and two apparent Km values (Km1 = 0.04 and Km2 = 0.77, mM) and two Vmax values (Vmax1 = 0.58 and Vmax2 = 1.53, nmol/mg protein/min) were obtained. When racemic DIS was used as a substrate the plot was also biphasic, while the plot observed at the lower concentration region was shifted to the upper region in comparison with that estimated from the sum of the individual N-dealkylase activities of each enantiomer. These results suggest that the N-dealkylation of R(-)-DIS is carried out by very limited cytochrome P-450 isozyme(s), but that of S(+)-DIS is carried out by multiple cytochrome P-450 isozymes; that is, N-dealkylations of R(-)- and S(+)-DIS are involved in the different cytochrome P-450 isozymes each other, particularly at relatively higher concentration of the substrates.

Animals↗

PubMed1992

[Single dose toxicity studies of suplatast tosilate (IPD-1151T)].

Single dose toxicity studies of suplatast tosilate (IPD-1151T) were carried out in mice, rats and dogs of both sexes. The results were as follows: 1. The LD50 values of IPD-1151T were as follows: Mice, 12,500 (both sexes) mg/kg or more in oral route (maximum dose for technical manner); Mice 81 (male) and 96 (female) mg/kg in intravenous route; Rats, 10,000 (both sexes) mg/kg or more in oral route (maximum dose for technical manner); Rats, 96 (male) and 93 (female) mg/kg in intravenous route; Dogs, 2,124 (male) and 2,660 (female) mg/kg in oral route. On the LD50 values, no sexual difference was apparent in all species, but the species difference was noted between the rodent and dog. LD50 values of dog were lower level than those of rodent. 2. As toxic signs, mucous diarrhea with specific smell was noted in orally administered rodent. In addition, rats showed soiled fur in the perianal. In intravenous route, the rodent showed dyspnea, tonic convulsion and lateral position and deaths occurred within 10 min in mice and within 30 min in rats after administration. Dog showed toxic signs similar to those in rodents and deaths occurred within 3 hours. 3. In pathological examinations, dead mice and dogs administered orally showed lung congestion, liver fading or slight hemorrhage in the endo-and/or exocardium. Dead rodent administered intravenously showed only slight hemorrhage and congestion in the lung. Alive mice, rats and dogs showed no remarkable changes. 4. The main cause of deaths seemed to be respiratory disturbance in all species.

Animals↗

PubMed1992

[A thirteen-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T) in rats].

A 13-week oral repeated dose toxicity study of Suplatast tosilate (IPD-1151T), a new anti-allergic agent, as well as a 5-week recovery study were carried out at dose levels of 0 (control), 200, 600, 1800 and 5400 mg/kg/day using male and female rats. The results were as follows: 1. In general conditions, salivation were observed in some rats of both sexes given 1800 mg/kg/day. Both sexes given 5400 mg/kg/day disclosed salivation and soft stool and then died after showing ataxic gait, hyperesthesia and convulsion of legs. 2. Inhibition of body weight gain in both sexes given 5400 mg/kg/day were observed from the early stage of the treatment period. 3. The food consumption was decreased from about 3-week and the water consumption was increased from the initiation of study to about 3-week in both sexes given 5400 mg/kg/day. However, both of them were remarkably decreased prior to death. 4. Fecal examination for occult blood showed an increasing tendency in the incidence of positive findings in both sexes given 1800 mg/kg/day. 5. Hematological examination showed slight decreases in erythrocytic parameters in both sexes given 1800 mg/kg/day. In both sexes given 5400 mg/kg/day hemoconcentration was observed, some animals showing decreases in leucocyte and lymphocyte counts and lymphocyte percentage. 6. Biochemical examination showed increases in total and free cholesterol levels in males given 600 mg/kg/day or more, an increased cholinesterase and decreased levels of triglyceride and cholesterol ester ratio in males given 1800 mg/kg/day. An increase in LDH was observed in both sexes given 5400 mg/kg/day and half of these animals also showed increases in GOT and Urea N. 7. The absolute weights of the pituitary, brain, thymus, heart, lungs and kidneys were increased. However, no histopathological lesion was observed in these organs. As treatment-related histological changes, atrophy in the thymus and spleen, dilation in digestive tracts, neuronal necrosis and necrotic foci in the central nervous system, necrosis of lymphocytes in the lymphoid organs and a decrease in bone marrow cell were observed in both sexes given 5400 mg/kg/day. 8. After a 5-week recovery period, above-mentioned changes had disappeared. 9. From the above results, the non-effective dose level was estimated to be 200 mg/kg/day in males and 600 mg/kg/day in females, and toxic dose level 1800-5400 mg/kg/day in both sexes.

Administration, Oral↗

PubMed1992

[A thirteen-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T) in dogs].

A 13-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T), a new anti-allergic agent, as well as a 5-week recovery study were carried out at dose levels of 0 (control), 50, 150, 450 and 1350 mg/kg/day using male and female beagle dogs. The results were as follows: 1. In general conditions, soft feces and diarrhea with specific smell were dose-dependently observed in males and females given 450 mg/kg/day or more. Both sexes given 1350 mg/kg/day, revealed reeling with dropped head, abnormal gait, dysstasia, lying at lateral or prone position, sedation, and tremor, and one male and one female in this group died after showing respiratory depression, collapse and cyanosis. 2. There were no significant or remarkable changes in body weight, food consumption, water consumption, ophthalmology, electrocardiogram, urinalysis, hematology, biochemistry, fecal occult blood test, and absolute and relative organ weights. 3. Pathological examination in dead animals revealed hemorrhagic change in the heart and slight vacuolar changes in hepatocytes. In survived animals, there were no pathological changes attributable to the IPD-1151T. 4. In electron microscopic examination, there were no abnormalities in the liver and kidney attributable to the IPD-1151T. 5. After 5-week recovery period, above-mentioned changes disappeared. 6. From the above results, the non-effective dose level and the toxic dose level were estimated to be 150 mg/kg/day and 1350 mg/kg/day, respectively, and no sex differences were found.

Administration, Oral↗