Biomedical subjects
Publications and source records attributed to H Aoki.
FK-506, a novel immunosuppressant, has been isolated from the fermentation broth of Streptomyces tsukubaenis No. 9993 as colorless prism and the molecular formula was determined as C44H69NO12.H2O. The compound suppressed immune responses in vitro and in vivo with mice. This immunosuppressive effect was more potent than that of ciclosporin.
The immuno-pharmacological profile of a novel immunosuppressive agent, FK-506 produced by a streptomycete, is presented here. We proceeded to test the effect of the agent on various in vitro immune systems. It showed that mixed lymphocyte reaction, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 and gamma-interferon and the expression of the IL-2 receptor were suppressed by this agent. The IC50 values of FK-506 and ciclosporin (CS) in all tests were approximately 0.1 nM and 10 nM, respectively. Therefore, the novel agent, FK-506 suppressed in vitro immune systems at about hundred times lower concentration than CS.
A new antitumor antibiotic, WF-3405 was isolated from the culture of Amauroascus aureus F-3405. The structure has been determined as 1,5-dioxiranyl-1,2,3,4,5-pentanepentanol on the basis of spectroscopic and chemical evidence. WF-3405 exhibits strong inhibitory activity against various murine tumors including leukemia P388, leukemia L1210 and Lewis lung carcinoma.
A new species in the genus Streptomyces, for which the name Streptomyces sandaensis sp. nov. is proposed, is described. Soil isolate strain No. 6897 (FERM-P 7654), produces a new antitumor substance FR-900482. The strain has a gray to red spore mass color, Rectus Flexibilis to Retinaculum-Apertum spore chain morphology, smooth spores, and is nonchromogenic. Strain No. 6897 is closely related to Streptomyces aburaviensis and Streptomyces nitrosporeus. But, there are many differences in cultural characteristics and in the utilization of carbohydrates.
FR-900482 is a new antitumor antibiotic produced by a new actinomyces named Streptomyces sandaensis No. 6897. It exhibits potent cytotoxic activity against various tumor cells in vitro. Furthermore, it has weak antimicrobial activity against some Gram-positive or Gram-negative bacteria.
FR-900494 is a new type of immunoactive substances produced by an actinomycete named Kitasatosporia kifunense sp. nov. FR-900494 exhibits a competitive action against immunosuppressive factor produced in the serum of tumor bearing mice and has the capacity to restore the depression of lymphocytes.
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A case of traumatic aneurysm due to an arterial injury during removal of a tuberculum sellae meningioma is reported. A 43-year-old man had undergone craniotomy for removal of the tumor. It was very hard with many feeders from bilateral anterior cerebral arteries (ACA), so the resection between the left ACA and the tumor was difficult. A small artery was accidentally pulled out from the left ACA and bleeding occurred from the small artery in the artery. The ACA was trapped temporarily with two clips and was coated using Oxycell and Biobond. The bleeding was stopped by this procedure and the blood reflowed. This tumor was removed totally, but postoperative CT scan showed an enhancing small lesion in the anterior part of the left basal ganglia 10 days after operation. The angiograms performed next day revealed a fusiform aneurysm of the left proximal ACA near the anterior communicating artery. The skull was reopened to treat the aneurysm. The aneurysm arising from just a bleeding point in the previous operation was oval in shape without neck, so it was trapped by two small aneurysm clips and resected. The patient's condition was uneventful after the second operation. Pathological diagnosis of the aneurysm was confirmed a false aneurysm. Iatrogenic traumatic aneurysms caused by neurosurgical procedure has been reported in 29 cases. Eighteen cases showed bleeding from injured artery during surgery and a half of them showed rupture from the aneurysm within one month after operation. Such doubtful cases of traumatic aneurysm should be diagnosed by angiography and operated as early as possible.
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Cefbuperazone (CBPZ) was administered to inpatients with complicated urinary tract infections (UTI) at our department. Clinical efficacy and safety were evaluated in 22 chronic cases by the criteria for evaluation of clinical of antimicrobial agents on urinary tract infection. Overall clinical efficacy was excellent in 8 cases, moderate in 9 cases and poor in 5 cases with an effectiveness rate of 77%. Twenty-four of the 34 strains isolated from the patients were eradicated and eradication rate was 71%. Neither subjective nor objective adverse reactions were observed. Abnormal changes in laboratory tests were found in 9 patients, but were probably not related to CBPZ administration. Judging from these results, CBPZ is considered to be an effective and safe antibacterial for the treatment of complicated UTI.
In 8 cases of operable renal cancer, selective intraarterial infusion of the streptococcal preparation, OK-432 was performed and its cytocidal effects on the surgical specimens, which were removed on the 8th day after infusion, were investigated histopathologically with immunological parameters of the peripheral blood. The histopathological study revealed a high grade of sinus histiocytosis of the renal pedicle lymph nodes, but the anti-tumor effect on renal tumors was not so marked in any of the 8 cases. OK-Ia-positive lymphoid cells of peripheral blood were increased significantly and Con-A stimulation index of blastogenesis was lowered without any change in the PHA stimulation index after the OK-432 infusion. No serious complications of the selective intraarterial infusion were experienced except for high fever (less than 38 degrees C). In conclusion, OK-432 selective intraarterial infusion was an effective method for improving regional and systemic immunoactivity, but the cytocidal effect against tumor cells could not be confirmed histopathologically.