Biomedical subjects
Publications and source records attributed to K Isono.
Several novel immunosuppressive agents have been developed in recent years. They exhibited not only remarkable immunosuppressive potency but also side effects. They are still short of the final goal in terms of immunosuppression for organ transplantation. Combination treatment is more effective and safer to use, and it will prevail in the future.
BACKGROUND: Clinical usefulness of high-dose chemotherapy with autologous bone marrow transplantation (ABMT) in the treatment of gastric cancer was investigated. METHODS: Ten patients with late-stage gastric cancer (four recurrent and six primary cases) with measurable lesions were treated with high-dose combination therapy consisting of etoposide (VP-16) (1200 mg/m2), adriamycin (80 mg/m2), and cisplatin (120 mg/m2) or carboplatin (900 mg/m2) (high-dose etoposide, adriamycin, and cisplatin [EAP] therapy). Afterward, 1 x 10(7)/kg of mononuclear cells, which were prepared from autologous bone marrow before treatment and cryopreserved, were transfused intravenously. RESULTS: All patients recovered from the aplastic period without severe complications. Of nine assessable cases, partial response was observed in eight (89% response rate). CONCLUSION: High-dose EAP therapy with ABMT is recommended as adjuvant therapy accompanied with radical operation for late-stage gastric cancer.
Two mitochondrial ribosomal (mitoribosomal) proteins, YmL8 and YmL20, of the yeast Saccharomyces cerevisiae and their derivatives were synthesized in vitro and their transport into isolated yeast mitochondria was examined. Of the two proteins, YmL20 possesses an N-terminal presequence of 18 amino acid residues, while YmL8 has no such presequence. Both proteins were found to be transported into isolated mitochondria in an energy-dependent manner. Furthermore, YmL20 protein without its N-terminal presequence was also transported, despite the fact that the presequence alone was capable of transporting a fused passenger protein, Chinese hamster dihydrofolate reductase (DHFR). Therefore, YmL20 protein appears to possess redundant transport signals in its structure. Similarly, YmL8 derivatives lacking either 40 or 86 amino acid residues from the N-terminus and/or 52 amino acid residues from the C-terminus were transported. In addition, the N-terminal segment of this protein was capable of transporting Chinese hamster DHFR into mitochondria, while its C-terminal segment was not. Thus, YmL8 protein also appears to possess two or more transport signals in its structure. Perhaps the presence of many basic amino acid residues in these proteins might, at least partly, contribute to their mitochondrial transport.
Most of the 155 transcripts of the genes on chromosome III of S.cerevisiae that were identified by a series of Northern hybridization experiments (Yoshikawa, A. and Isono, K., Yeast 6, 383-401, 1990) have been correlated with the open reading frames (ORFs) deduced from the nucleotide sequence data for this chromosome (Oliver, S.G. et al., Nature 357, 38-46, 1992). This was performed by comparing the experimentally constructed physical map and the one produced from the nucleotide sequence data, and then the sizes and positions of observed transcripts and those of sequenced ORFs. The data thus provide information for possible products of the sequenced ORFs (genes) of chromosome III of S.cerevisiae as well as their likely levels of expression in vegetatively growing cells.
The immunosuppressive effect of rapamycin (RAPA), a macrolide antibiotic produced by Streptomyces hygroscopicus, was tested using allografts in the rat and dog. It was immunosuppressive at a dose of 3.0 mg/kg/day for 8 days in skin allografts and 0.1 mg/kg/day for 11 days using cardiac allografts in the rat. It prevented rejection of renal allografts in beagle dogs at a dose of 0.3 mg/kg; however, emaciation and gastrointestinal toxicity resulted in some deaths in dogs. Mucosal necrosis and vasculitis in the submucosal layer were the predominant findings at autopsy in dogs receiving RAPA. Serum amylase values rose soon after commencement of RAPA treatment. Combined drug treatment with CsA at a nonimmunosuppressive dose of 3.2 mg/kg in the rat or 2.5 mg/kg in the dog was synergistic, with a low dose of 0.1 mg/kg/week RAPA. Combined therapy of CsA and RAPA also inhibited the frequency of vasculitis and emaciation in dogs. The present data suggest that RAPA is immunosuppressive in organ allografting and that the combination of CsA and RAPA would be effective clinically.
Morphometric analyses were performed on 11 cases of well-differentiated gastric adenocarcinoma and six cases of gastric adenoma. The values for the mean nuclear area (AN), the index for roundness of the nucleus (FX), and the nucleus/cytoplasm ratio (N/C) were larger in the carcinoma group than in the adenoma group (P < 0.01; t-test). The value of nuclear numerical density (NA) was larger in the adenoma group than in the carcinoma group (P < 0.01; t-test). There was an overlap between the N/C ratio in the carcinoma and adenoma groups. It was concluded that roundness and enlargement of the nucleus, and a low nuclear density are important prerequisites for distinguishing the common type of adenocarcinomas from adenomas. An additional morphometric analysis was performed on seven cases of mucosal carcinoma. A three-dimensional discriminant analysis using AN, FX and NA revealed that of these seven cases, three were consistent with the carcinoma group while one case was consistent with the adenoma group. The remaining three cases were judged as borderline.
A protein phosphatase inhibitor, tautomycin induces blebs on the surface of human myeloid leukemia K562 cells within 10 min. In this paper we examined the cytoskeleton of tautomycin-treated cells. In the presence of tautomycin, cells with blebs turned into segmented forms with smooth surfaces after 15 min and into smooth round shapes without microprotuberance after 60 min. Observation with fluorescence microscopy showed that F-actin detached from the plasma membrane at the site of the blebs. Further treatment with tautomycin induced the accumulation of F-actin at the segmentation centers. Under electron microscopy, an electron dense ring-structure was detected at the segmentation center. Tautomycin did not induce major changes of the microtubule network although F-actin accumulated near the microtubule organizing center. The amount of F-actin increased in tautomycin-treated cells. These results indicate that the morphological changes are induced by reorganization of actinfilaments.
Based on the experiences in performing vertical banded gastroplasty (VBG) for 8 years, its results were analyzed and particularly its operative complications were examined. As a result, its weight-reducing effect and safety were favorable, but serious complications, although few, were observed. These major complications were the loss of gastric reduction effect due to staple-line dehiscence, gastric band exposure, reflux esophagitis, channel narrowing, pouch ulcer, etc. As a preventive measure against these complications, to supplement the defects of VBG without losing its characteristics, K-gastroplasty was devised and performed; its operative mode is discussed.
The rpIU and rpmA genes that encode ribosomal proteins (r-proteins) L21 and L27 of Escherichia coli K-12 have been isolated from the ordered clone bank of this bacterium. They were found to be located at coordinates 3,351.7-3,352.3 kb on the physical map of E. coli. The nucleotide sequence of the cloned genes and their flanking regions indicated that the two r-protein genes compose an operon. Upstream of the two genes there is an open reading frame (ORF) in the opposite direction. The deduced polypeptide encoded by this ORF has a molecular weight of 35,215 and shows a significant degree of sequence similarity to the enzyme that is involved in the carotenoid biosynthesis and encoded by the crtE gene of carotenogenic bacteria and to prenyltransferases found in various organisms.
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Respinomycins are a novel group of anthracycline antibiotics produced by Streptomyces xanthocidicus. Respinomycins A1, A2, B, C and D were isolated by EtOAc extraction, silica gel column chromatography, centrifugal partition chromatography and preparative silica gel thin layer chromatography. Respinomycins A1 and A2 induced the terminal differentiation of human leukemia K-562 cells.
Respinomycins A1, A2, B, C and D were revealed to be novel anthracycline antibiotics with molecular formulae of C51H72N2O20, C43H58N2O15, C35H43NO14, C36H45NO14 and C51H70N2O22, respectively. Their structures were determined by means of 1H-1H COSY, 13C-1H COSY and HMBC spectra. The structure of the aglycone of respinomycins was unambiguously determined by LSPD experiments and NOESY. The common skeleton of respinomycins is a new type and is distinguished from that of the nogalamycin group.
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In this study 39 cases of abdominal benign disease were examined by PET using 18F-fluorodeoxyglucose (FDG), and 11 cases of them (i.e. 4 cases of liver abscess, 1 of pelvic abscess, 1 of omental abscess, 2 of chronic pancreatitis, 1 of inflammatory pseudotumor of liver, 1 of retroperitoneal leiomyoma and 1 of solid and cystic tumor of pancreas) which showed as high accumulation of FDG as malignant lesion were investigated of their clinical and pathological feature. We used Ci/Cp ratio as index to express the accumulation of FDG in the lesion, which was calculated from radioactivities of the lesion (Ci) and the plasma (Cp) at 60 mins after injection of FDG. The Ci/Cp ratio of the 11 cases was 3.64 +/- 0.77. The pathological feature of the 9 inflammatory cases was high accumulation of inflammatory cells and that of the 2 benign tumor cases was solid proliferation of tumor cells. The serum of the 9 inflammatory cases showed high CRP value. It was considered that the high accumulation of FDG in inflammatory lesions was due to piles of FDG uptake of the many inflammatory cells, while the 2 benign tumors of high accumulation were considered that the tumor cell had as high glucose metabolism as malignancies.