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Biomedical subjects

T Ono

Publications and source records attributed to T Ono.

At least 991 records · Page 55Linked to original sources
PubMed1988

Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins.

To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1 alpha (IL-1), and prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2 alpha had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2 alpha and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.

Animals↗
PubMed1988

Immunohistochemical distribution of hepatic fatty acid-binding protein in rat and human alimentary tract.

Tissues from rat and human alimentary tract were immunostained with rabbit antibodies to fatty acid-binding protein (FABP) isolated from rat liver, since the precise immunohistochemical localization of the protein in gut has not been determined. The results obtained indicated that FABP immunoreactivity was found almost exclusively in intestinal absorptive cells, the sole exception being its presence in the cytoplasm of a few goblet cells. In small bowel, FABP-positive cells were most often found in the upper and middle segments, and less frequently in the lower to terminal portion. Immunoreactive cells were also found in large bowel of rat and human, but with differing patterns of distribution. In rat, positive cells were found mainly in the lower portion of the large intestine, whereas in human positive cells were present in all portions. Immunoreactive cells were detected in rat and human cecum, in the upper half of human rectum, and in human vermiform appendix. No such cells were found in esophageal and nonmetaplastic gastric mucosa or in pancreatic tissue, whereas they were present in great numbers in metaplastic gastric mucosa. The results of this study therefore suggest that FABP is a useful marker for research into the physiology or pathology of absorptive cells in the gastrointestinal tracts of both species.

Animals↗
PubMed1988

Cell surface heparan sulphate and adhesive property of sublines of rat ascites hepatoma AH7974.

Two variants (74AD and 74FL) established from rat ascites hepatoma AH7974 were examined for the production of glycosaminoglycans in culture. There was no difference between the adhesive (74AD) and the floating (74FL) variants in quantity of glycosaminoglycans produced by their cultivation in minimum essential medium supplemented with 10% foetal calf serum. However, they were distinctly different in the distribution patterns of heparan sulphate. In 74FL, about 70% of total heparan sulphate was found in the culture medium in soluble form, whereas in 74AD, only 7% was found in the medium and the rest was in the cell-substratum complex. In a serum-free medium, 74AD cells grew without adhering to the substratum. After cultivation, more than 90% of total heparan sulphate was found in the cell-associated fractions and the rest in the substratum fractions. No heparan sulphate was detected in the culture medium. On the other hand, 74FL cells released heparan sulphate to the serum-free medium as much as to the serum-containing medium. The increase in amount of heparan sulphate in the culture medium of 74FL cells was supposed to be caused by failure of the cells to deposit heparan sulphate at the cell surface and not caused by increased production. Cell-substratum adhesion mechanisms involving cell surface heparan sulphate (heparan sulphate proteoglycan) and some serum intermediate(s) are discussed for 74AD cells.

Animals↗
PubMed1988

Early response to tumor necrosis factor of human promyelocytic leukemia cell lines sensitive and resistant to the factor.

Early cellular events with respect to protein synthesis and the steady-state level of cellular myc (c-myc) mRNA were analyzed in the tumor necrosis factor (TNF)-sensitive human promyelocytic leukemia cell line HL-60 and in its TNF-resistant variant HL-60R after their exposure to TNF. Addition of TNF at 100 units (U)/ml induced de novo synthesis of two proteins with apparent molecular masses of 100 kDa and 40 kDa in HL-60 cells. The induced synthesis of the 100 kDa protein continued for 6 h, while that of the 40 kDa protein was transient. The 100 kDa protein was detectable in HL-60R cells which were maintained in medium containing 1,000 U/ml TNF, whereas the synthesis of the 40 kDa protein could be transiently induced by TNF at 10(5) U/ml. Dot blot hybridization revealed that the steady-state level of c-myc mRNA in HL-60 cells was transiently reduced by TNF at 100 U/ml but remained at a reduced level for 6 h when 10(5) U/ml TNF was present. In HL-60R cells, TNF at 10(5) U/ml could transiently reduce the c-myc mRNA level. These results showed that induction of the synthesis of a 40 kDa protein and a reduction in the steady-state level of c-myc mRNA were concomitant with cellular sensitivity to the cytostatic action of TNF in HL-60 cells.

Drug Resistance↗
PubMed1988

Inhibitory effects of ketoconazole and miconazole on cytochrome P-450-mediated oxidative metabolism of testosterone and xenobiotics in mouse hepatic microsomes--comparative study with cimetidine.

The inhibitory effects of ketoconazole (KCZ) and miconazole (MCZ), imidazole containing antimycotics, on the hydroxylations of testosterone as a model for endogenous steroids, and the N-demethylation of aminopyrine and the hydroxylation of aniline as models for xenobiotics were compared with those of cimetidine in mouse hepatic microsomes. In vitro, both KCZ and MCZ inhibited these enzyme activities in a dose-dependent manner. The inhibitory potencies of KCZ and MCZ for testosterone hydroxylations and aminopyrine N-demethylation were much greater, with 50% inhibition concentration (IC50) values 2-3 orders of magnitude lower than those of cimetidine, while the potencies of these antimycotics for aniline hydroxylation were similar to that of cimetidine. Although KCZ, MCZ and cimetidine produced type II difference spectra, the difference between the antimycotics (405 nm) and cimetidine (392-405 nm) was found in the trough position of the difference spectra. Spectral dissociation constants (Ks) of these antimycotics (2.2 x 10(-7) - 5.4 x 10(-6) M) were also 1-2 orders of magnitude lower than those of cimetidine (1.3 x 10(-5) - 1.6 x 10(-4) M), and both KCZ and cimetidine had two kinds of Ks, while MCZ had a single Ks. Pentobarbital sleeping time was prolonged in a dose-dependent manner by the i.p. administration of 10-50 mg/kg of KCZ, MCZ or cimetidine, and the potencies for the prolongation of sleeping time decreased in the order of MCZ greater than KCZ greater than cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopyrine N-Demethylase↗
PubMed1988

Effects of diltiazem on rheological properties of human blood.

The in vitro effects of diltiazem (DTZ), a coronary vasodilator, deacetyldiltiazem (D-M1), one of the metabolites of DTZ, and pentoxifylline (PTF) which is known to improve erythrocyte deformation, on the viscosity of platelet poor blood were compared. Furthermore the change in the viscosity of whole blood from patients with effort angina after intravenous administration of DTZ was examined ex vivo. The addition of DTZ into platelet poor blood at 37 degrees C caused a rapid reduction in blood viscosity and an enhancement of erythrocyte deformability within 5 min, which then diminished in a time-dependent manner. Similar effects were also found by adding D-M1. On the other hand, the effects of PTF appeared after an incubation period of more than 60 min and were enhanced in a time-dependent manner. These actions of PTF, but not those of DTZ and D-M1, paralleled the increase of erythrocyte adenosine-triphosphate content. DTZ and D-M1, but not PTF, had biphasic effects on the osmotic behavior of erythrocytes. Whole blood viscosity was reduced significantly during the period 5-30 min after intravenous administration of 10 mg of DTZ, which diminished with the elimination of plasma DTZ. In conclusion, the action mechanisms involved in the effect of DTZ and D-M1 on blood rheological properties appeared to be different from that of PTF. These effects of DTZ are clinically significant in improving the flow properties of blood in vascular diseases.

Adenosine Triphosphate↗
PubMed1988

Effects of ozagrel (OKY-046), a thromboxane synthase inhibitor, on oxidative drug-metabolizing enzymes in mouse hepatic microsomes.

The inhibitory effects of ozagrel (OZA), an imidazole derivative and a specific thromboxane synthase inhibitor, on a monooxygenase system in mouse hepatic microsomes were studied. Pentobarbital sleeping time was significantly prolonged by i.p. administration of a single dose of 100 mg/kg of OZA, and the potency of OZA for the prolongation of sleeping time was similar to that of cimetidine. In vitro, OZA inhibited aminopyrine N-demethylase, aniline hydroxylase and testosterone 6 beta- and 7 alpha-hydroxylase activities in hepatic microsomes with inhibition constants (Ki) of 0.19-3.72 mM. The potency and the mode of inhibition of OZA for these enzyme activities were similar to those of cimetidine, while no inhibitory effect of OZA on testosterone 16 alpha-hydroxylase activity was found. A spectrophotometric study revealed that the imidazole moiety of OZA binds to cytochrome P-450 and has little effect on reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase activity. These results indicated that OZA is an inhibitor of some cytochrome P-450-mediated drug metabolism in hepatic microsomes.

Acrylates↗
PubMed1988

Effects of antimycotics on hepatic steroid metabolism.

When male ddY mice were treated with consecutive doses of 10 and 100 mg/kg of miconazole (MCZ) or ketoconazole (KCZ), imidazole-containing antimycotics, once a day for 3 d, a dose-dependent shortening of pentobarbital sleeping time was observed for MCZ, while no change in the sleeping time was observed for KCZ. Even at a low dose (10 mg/kg), MCZ significantly increased cytochrome P-450 content and reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase activity. Simultaneously, hydroxylase activities of testosterone as a model of endogenous steroids, and aminopyrine N-demethylase and 7-ethoxycoumarin O-deethylase activities were increased, while KCZ lacked inducing properties even at a high dose (100 mg/kg). The change in hepatic oxidative metabolism of cortisol (F) in a patient before, during and after treatment with progressively increasing doses of 2-10 mg/kg/d of MCZ for 14 d was examined by monitoring urinary 6 beta-hydroxycortisol (6 beta-OHF), an oxidative metabolite of F. The ratio of 6 beta-OHF to F in 24-h urine decreased by 15% from the original level on day 1, and then it began to increase on day 7 to reach 2.4 times the original level on day 14. These results suggest that MCZ, but not KCZ, has inducing activity for hepatic cytochrome P-450-dependent oxidative metabolism of steroids and xenobiotics, in addition to its known inhibitory activity.

Animals↗
PubMed1988

[Effect of tiapride on the activity of neuroleptics and other kinds of drugs in mice and rats].

Tiapride is a central dopamine receptor specific antagonist, and it has a benzamide chemical structure. This drug is very useful for the treatment of dyskinesia and such abnormal behaviors as delirium and psychomotor excitation in patients with arteriosclerosis. Most of these patients are elderly and generally suffer from other diseases. Since they are apt to be treated with several drugs for such diseases, the effect of tiapride in combination with various kinds of drugs was examined in rats and mice. Tiapride significantly potentiated the catalepsy-inducing effect of haloperidol and chlorpromazine in rats and tended to potentiate the muscle relaxing effect of diazepam at the highest dose in mice. Conversely, tiapride did not enhance or diminish the hypnotic effect of bromvalerylurea, the anticholinergic activity of trihexyphenidyl, the diuretic effect of bromvalerylurea, the anti-cholinergic activity of trihexyphenidyl, the diuretic effect of trichloromethiazide, or the anti-diabetic effect of glibenclamide. Our findings suggest that tiapride should be used with care in patients taking neuroleptics, but can be used freely in patients on other kinds of drugs.

Animals↗
PubMed1988

[Effects of omeprazole and famotidine on (H+-K+) ATPase and acid secretion in rabbit gastric glands].

Effects of omeprazole, an anti-ulcer drug, on (H+-K+) ATPase activity and gastric acid secretion in a gastric mucosal gland preparation from rabbits were investigated. The mode of action of the substance was compared with famotidine, and H2 antagonist, by examining the effects of both drugs on the (H+-K+) ATPase of the rabbit gastric mucosa and on gastric acid secretion from the isolated rabbit gastric glands. Optimal assay conditions for (H+-K+) ATPase activity differed slightly from that reported for pig gastric mucosa, and they were pH 7.0, 2 mM of MgCl2 and 50 mM of KCl. Omeprazole dose-dependently inhibited the enzyme activity with an IC50 of 4.2 microM, whereas famotidine was not inhibitory even at the highest concentration of 100 microM. Acid secretion in the glands was determined by measuring accumulation of 14C-aminopyrine. Omeprazole and famotidine showed almost the same inhibitory effect against histamine-stimulated gastric secretion, and their IC50 values were 0.35 microM. Omeprazole inhibited dibutyryl cyclic AMP-stimulated gastric acid secretion, but famotidine was not inhibitory even at the highest concentration of 100 microM. The reason for this difference was that (H+-K+) ATPase activity is linked to the final step of acid secretion. From these results, omeprazole can be expected to be useful for the treatment of peptic ulcer disease.

Adenosine Triphosphatases↗
PubMed1988

Effects of acetyl-L-carnitine on the brain lipofuscin content and emotional behavior in aged rats.

The effects of long-term dosing with acetyl-L-carnitine (ALC) were examined in aged rats, and they were compared with those in young rats. ALC significantly reduced the lipofuscin deposition in the brain of aged rats. Emotional parameters such as locomotor activity and rearing behavior are lower in aged rats than in young rats, and these behaviors decreased in both age groups during the experiments. ALC diminished the decrease of these emotional behaviors, especially in rearing behavior in the aged rats. Furthermore, ALC had no effect on body weight gain. These results might reflect one of the main beneficial pharmacological mechanisms of ALC in clinical use.

Acetylcarnitine↗
PubMed1988

[Morphometrical study of physical growth in infant cynomolgus monkeys using multivariate analysis].

We describe the relative growth in infant cynomolgus monkeys (Macaca fascicularis). The multivariate analyses using the principal component analysis and multivariate allometric analysis were applied to biometrical data of laboratory-bred cynomolgus monkeys aged from birth to 12 weeks. All the animals had been bred and reared under uniform environmental conditions at Tsukuba Primate Center for Medical Science, N. I. H., Japan. As the result of the principal component analysis, the cumulative contribution ratio of the 1st and 2nd principal components (PC1 and PC2) accounted for 88.2% and 85.7% in males and females, respectively. This indicates that the morphologic traits (15 traits) grow normally in size, but the analysis did not detect any differences in growth rate among the traits. So, the multivariate allometric analysis was applied to the same data. The traits concerning the face and truck showed relatively high growth rates compared to head breadth, whereas the limbs and arms grew slowly.

Analysis of Variance↗
PubMed1988

[A comparison of the sialyl SSEA-1 antigen and CEA in the histology of malignant mesothelioma, with special reference to adenocarcinoma of the lung].

Tumor tissues obtained from 5 cases of malignant mesothelioma and from 5 cases of primary adenocarcinoma of the lung have been studied on staining with the sialyl SSEA-1 antibody by the PAP method. Results in all cases of a malignant mesothelioma (both Epithelioid and Sarcomatous pattern) were absolutely negative. All cases of lung cancer, however, were positive, though in differing degrees. In evaluating a malignant mesothelioma, many reports have indicated that the negativity of CEA staining is useful in achieving the differential diagnosis from lung cancer. The sensitivity of the staining by sialyl SSEA-1 was found to be far better than that of CEA in examining either malignant mesothelioma or lung cancer. Thus, we found that not only CEA but also sialyl SSEA-1 antigen staining was useful for the diagnosing of a malignant mesothelioma.

Adenocarcinoma↗
PubMed1988

Restriction fragment length polymorphism of bcr in Japanese patients with hematological malignancies.

We surveyed DNAs from patients with various hematological malignancies by Southern blot hybridization to analyze bcr rearrangements, and detected a new restriction fragment length polymorphism (RFLP) of the breakpoint cluster region at a BamHI site in three patients. By using a 1.2-kb HindIII-BglII 3' bcr probe, unusual BamHI restriction enzyme fragments (1.9 kb and 1.4 kb) were detected from the DNAs of three patients with hematological malignancies. DNAs from cultured fibroblasts derived from the skin of a patient, as well as from peripheral leukocytes of the father of a patient and the mother of another patient, showed identical 1.9- and 1.4-kb additional bands, besides a 3.3-kb germline band, establishing that polymorphism, rather than gene arrangement, was responsible for these additional restriction enzyme fragments. However, RFLP was not detected in the DNAs of 40 normal unrelated individuals.

Blotting, Southern↗