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T Ochiai

Publications and source records attributed to T Ochiai.

At least 235 records · Page 13Linked to original sources
PubMed1988

Prolongation of skin allograft survival in rats by a novel immunosuppressive agent, FK506.

FK506, an immunosuppresant, was isolated from Streptomyces tsukubaensis. Intramuscular administration of FK506 (0.32 mg/kg or more) 5 days a week for two weeks after grafting prolonged the acceptance time of F344 skin allograft to WKA rats. Similar results were obtained with cyclosporine at 32 mg/kg or more, but other immunosuppressives (i.e., prednisolone, azathioprine, and bredinin) gave only a marginal prolongation. The prolonging effect of FK506 was obtained in various donor-recipient combinations across a major or minor histocompatibility barrier. The agent also prolonged the acceptance time of mouse skin xenografts to rats. Furthermore, maintenance doses of 3.2 or 0.32 mg/kg twice a week after an initial 14-day treatment with the agent at 3.2 mg/kg gave graft survival as long as the treatment was continued for more than 120 days. Our findings show that FK506 has a potent immunosuppressive effect in rats and suggest that the agent merits further investigation.

Animals↗
PubMed1988

A behavioral pharmacological study of mafoprazine, a new phenylpiperazine derivative.

Behavioral pharmacological studies on mafoprazine, a new drug for the prevention of aggressive behavior, were performed to compare its effects with those of an existing drug, azaperone (Stresnil). The acute toxicity of mafoprazine in mice was slightly stronger than that of azaperone. Mafoprazine showed the following effects (at 0.2 to 2.0 mg/kg, s.c.): a decrease in spontaneous motor activity, prolongation of the duration of pentobarbital anesthesia, inhibition of long-term isolation-induced aggressive behavior, inhibition of olfactory bulbectomy-induced hyperemotionality and muricide behavior in mice and rats, and a marked taming and tranquilizing effect on aggressive behavior in dogs. These effects of mafoprazine were qualitatively the same as those of azaperone. Mafoprazine showed cataleptogenicity in rats at 5 mg/kg, s.c. or more and motor incoordination in rats at 0.2 mg/kg, s.c. or more. In the experiment on operant behavior in rats, the effect of mafoprazine on differential reinforcement of the low rate (DRL) response was almost the same as those of azaperone and chlorpromazine. These results indicate that mafoprazine has substantially the same psychotropic effect as azaperone, while the former has a weaker action on the extrapyramidal system than the latter, suggesting that mafoprazine could be used as a unique aggression-inhibiting drug.

Aggression↗
PubMed1988

[Clinical evaluation of BRMs in gastric cancer patients].

The concept of BRM includes both immunotherapeutic agents and cytokines. We have tested the effects of various kinds of immunopotentiators on gastric cancer patients in terms of (1) the effects on postoperative survival, (2) the effects on tumor size and (3) immunological effects. The results obtained showed that immunopotentiators produced favorable effects. Cytokines should also be evaluated from the same standpoints as those for immunopotentiators.

Adjuvants, Immunologic↗
PubMed1988

[A fatal case of skin cancer 18 years after cadaveric donor renal transplantation].

A 39 years old man was admitted with chronic renal failure, and in June, 1968, he received renal transplantation from a cadaveric donor, 30 years old male, died from cerebral contusion. The graft had been well functioning for 18 years, and he had been engaged in his occupation. At the age of fifty-seven skin cancer (squamous cell carcinoma) occurred in his face, and surgical treatment was carried out. But it metastasized to left parotid, bilateral lungs and other areas of skin, and he died in October 1986, complicated by cerebral infarction. Some reports mention that the incidence of malignancies in posttransplant patients is greater than in general population. Our study reveals that immunological surveillance is weakened in posttransplant patients because of decrease of NK activity, but that the incidence of malignancies (male 0.78%, female 0.45%) is not so great as that reported. There is need of further investigation in this problem.

Adult↗
PubMed1987

Isozymes of isocitrate dehydrogenase from an obligately psychrophilic bacterium, Vibrio sp. strain ABE-1: purification, and modulation of activities by growth conditions.

Each of the two isozymes, which are different in thermostability and quaternary structure, of isocitrate dehydrogenase (NADP+) [IDH: EC 1.1.1.42] was purified to an electrophoretically homogeneous state from an obligately psychrophilic marine bacterium, Vibrio sp. strain ABE-1. Hydrophobic chromatography was an efficient procedure to separate the two isozymes from each other. The isoelectric points of isozyme I (IDH-I; a dimer, Mr 88,100) and isozyme II (IDH-II; a monomer, Mr 80,500) were found to be pH 4.9 and 5.2, respectively. The two isozymes were similar in amino acid compositions, though there were slight differences in the contents of nonpolar and hydroxyl amino acids. However, their NH2-terminal amino acid sequences and immunochemical properties were clearly different from each other. The NH2-terminal amino acid sequence analysis also indicated that the subunits of IDH-I are chemically identical or highly homologous. Non-immuno-crossreactivity between the isozymes enabled us to measure the intracellular contents of the isozymes. IDH-I and -II were found to be differentially regulated in vivo by various growth conditions. IDH-I was induced by acetate, while IDH-II remained almost unchanged.

Acetates↗
PubMed1987

Studies of the effects of FK506 on renal allografting in the beagle dog.

The immunosuppressive activities of a newly discovered macrolide extracted from Streptomyces tsukubaensis, FK506, were examined using 38 renal allografts in the beagle dog. The median survival time was 15.5 days in dogs without treatment, 61 days with a dose of 0.08 mg/kg/day and 176 days with a dose of 0.16 mg/kg/day of intramuscularly administered FK506. Prolongation of survival was statistically significant when compared with controls (P = 0.02, 0.0044, respectively). None of 6 recipient dogs receiving the agent at a dose of 0.16 mg/kg/day encountered rejection during the treatment course. Three of them survived over 200 days. Oral administration of FK506 at a dose of 0.32 mg/kg/day did not prolong the median survival time (20.5 days) compared with the placebo treated control (16.5 days), but oral treatment with 1.0 mg/kg/day resulted in all of the recipient dogs surviving over 130 days. Histological studies of 7 kidney graft biopsy specimens of the dogs surviving over 3 months revealed no cell infiltration or only some degree of reversible interstitial cell infiltration, but vascular and glomerular changes were not observed in any of the specimens. Irregularity of nuclear shape and cytoplasmic vacuolation of the pars recta of the proximal tubules were observed in one dog each. Liver biopsy specimens showed no consistent evidence of hepatocellular damage. Three dogs died of intussusception 2-3 weeks posttransplant. The dogs treated intramuscularly with 0.32 mg/kg/day suffered from anorexia. Two dogs receiving oral treatment at a dose of 1.0 mg/kg developed papilloma of the skin around day 60, but the tumors disappeared by day 120. We conclude that FK506 is a powerful immunosuppressant in the dog with tolerable side effects.

Administration, Oral↗
PubMed1987

Studies of the induction and maintenance of long-term graft acceptance by treatment with FK506 in heterotopic cardiac allotransplantation in rats.

Immunosuppressive activities of the newly discovered FK506, isolated from Streptomyces tsukubaensis, were examined by using cardiac allotransplantation in the rat, and the mechanisms underlying induction and maintenance of FK506-induced long-term allograft survival were studied. Male rats of WKA (RT1k) and F344 (RT1lvl) strains were used as recipients and donors, respectively, and those of BN (RT1n) strain were used as third-party donors. Treatment with FK506, beginning from the day of allografting for 14, 10, or as few as 4 days, prolonged allograft survival significantly across the major histocompatibility barrier. The minimum doses for prolonging graft survival were 0.1 mg/kg/day by intramuscular treatment and 1.0 mg/kg/day by oral treatment. Treatment with FK506 at a dose of 0.32 mg/kg/day from day 4 until day 10 resulted in all the grafts surviving indefinitely and from days 5 to 10, half the grafts survived indefinitely, suggesting that the agent inhibited ongoing rejection. On the other hand, cyclosporine treatment at a dose of 20 mg/kg/day from day 2 did not prolong graft survival time statistically significantly. Induction of prolonged graft survival was not obtained by pretreatment of the prospective donor or recipient; prolonging effects were observed only when the agent was administered after allografting. Thus, the primary effect of the agent is exerted on responder lymphocytes reacting to the donor antigens in the induction phase of long-term graft acceptance. The mechanisms underlying the maintenance of long-term grafts were analyzed by testing the capacity of lymphocytes or serum of long-term graft-bearing rats to inhibit graft rejection in irradiated grafted hosts. Transfer of 2 x 10(8) lymphocytes from FK506-induced long-term F344 graft-bearing WKA rats resulted in indefinite survival of F344 heart allografts, but it did not prolong survival of third-party BN hearts. Transfer of 2.5 ml serum from long-term graft-bearing rats also prolonged graft survival of F344 hearts, but not BN hearts. These results suggest that donor strain-specific suppressor cells and humoral factor(s) are induced by treatment with FK506 in the presence of allografts, and that they play at least partial roles in the maintenance of long-term allograft acceptance.

Administration, Oral↗
PubMed1987

Basal cell epithelioma with giant tumor cells: light and electron microscopic study.

A case of basal cell epithelioma (BCE) with multiple large nuclei on the right buttock of a 69-year-old woman is reported, and the skin was studied by light and electron microscopy. This represented the only case (0.85%) of giant tumor cells with multiple nuclei among 117 patients with BCE. Ultrastructural studies revealed that giant tumor cells were not different from ordinary tumor cells of BCE, except for large convoluted nuclei. In the cytoplasms of giant tumor cells, we observed autophagic vacuoles which were derived from autophagocytosis. Scattered among the giant tumor cells, there were many degenerate tumor cells, some of which were phagocytized by giant tumor cells with multiple nuclei (referred to as macrophagocytosis). It is indicated that tumor cells have considerable phagocytic activities, and degrade the autophagic vacuoles or the degenerate tumor cells with the lysosomes. These findings suggest that the presence of the giant tumor cells with multiple nuclei does not indicate a increased malignant potential or anaplasia of the tumor, and that autophagocytosis or macrophagocytosis is a factor in initiating giant tumor cell formation.

Aged↗
PubMed1987

Obesity-related nonalcoholic fatty liver: CT features and follow-up studies after low-calorie diet.

The features on computed tomographic (CT) scans of nonalcoholic fatty liver were investigated in 24 patients with nonalcoholic fatty liver related to overweight. CT examinations were performed before and after 3 months of a low-calorie diet. The reversibility of fatty infiltration during diet therapy could be monitored by changes in appearance on repeated CT scans. Hepatic steatosis improved, as assessed from increases in attenuation values on CT scans after 3 months of the diet, and the improvement was accompanied by a decrease in the elevated serum glutamic-pyruvic transaminase activity. Hepatic fatty infiltration in these patients was not always uniform, and attenuation values in the right lobe of the liver were significantly lower than those in the left lobe. After the 3-month diet therapy, the mean liver volume was significantly reduced, while the spleen volume was unchanged. Two sequential CT examinations, performed before and after diet therapy, may be useful for evaluating obese patients with elevated serum transaminase activity.

Adult↗