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Biomedical subjects

S Okamoto

Publications and source records attributed to S Okamoto.

At least 19 recordsLinked to original sources
PubMed1992

Metabolism of intravenously administered 7 alpha-hydroxycholesterol-3 beta-stearate in the hamster.

In order to investigate the metabolic fate of serum esterified 7 alpha-hydroxycholesterol, [4-14C]7 alpha-hydroxycholesterol-3 beta-stearate was synthesized from labeled cholesterol and administered to bile fistula hamsters intravenously. Bile samples were collected at every 20 min for 7 h. Radioactivity was detected in bile 40 min after the beginning of the infusion of the labeled compound and 56.5 +/- 5.7% (48.7-66.0%) of the administered radioactivity was recovered in bile during 7 h. The liver contained appreciable radioactivity (19.5 +/- 7.6% of the administered dose) at the time of sacrifice. Only a trace amount of radioactivity was detected in urine and blood. Cumulative recovery of the radioactivity was 76.3 +/- 8.6% (63.3-90.4%). Major radioactive metabolites in the bile samples were identified to be taurine- and glycine-conjugated cholic acid and chenodeoxycholic acid by radioactive thin-layer chromatographic analysis of the bile samples before and after enzymatic hydrolysis and 3 alpha-hydroxysteroid dehydrogenase treatment. The conversion was nearly complete and we could not detect neutral metabolites, such as the mother compound, free 7 alpha-hydroxycholesterol and bile alcohols, as well as glucuronidated or sulfated bile acids. It is concluded that serum esterified 7 alpha-hydroxycholesterol could be effectively taken up by the liver, hydrolyzed by cholesterol esterase and metabolized via the normal biosynthetic pathway to taurine- or glycine-conjugated primary bile acids to be excreted into bile.

Animals↗
PubMed1992

Tumor necrosis factor alpha and interferon gamma synergistically induce interleukin 8 production in a human gastric cancer cell line through acting concurrently on AP-1 and NF-kB-like binding sites of the interleukin 8 gene.

Interleukin 8 (IL-8) is a novel cytokine which possesses neutrophil chemotactic and activating activities in addition to chemotactic activity for basophils and T lymphocytes. It has been shown that IL-8 is produced by a variety of human somatic cells including monocytes/macrophages, dermal fibroblasts, vascular endothelial cells, keratinocytes, mesangeal cells, and several types of tumor cell lines. We have examined here whether or not human gastric cancer cell lines produce IL-8 in vitro. The production of IL-8 protein was detected by enzyme-linked immunosorbent assay in the culture supernatants derived from eight of nine human gastric cancer cell lines stimulated with either interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), or TNF alpha plus interferon gamma (IFN gamma). In some of the gastric cancer cell lines such as MKN 45 and KATO, TNF alpha plus IFN gamma synergistically induced the production of IL-8. In MKN 45 cells, synergistic increase of the steady state level of IL-8 mRNA by TNF alpha plus IFN gamma was not inhibited by cycloheximide treatment. Scatchard analysis revealed that IFN gamma changed neither the number nor the affinity constant of TNF alpha binding sites on a gastric cancer cell line, suggesting that the synergism was a post-receptor event. Furthermore, synergistic induction of chloramphenicol acetyltransferase activity by TNF alpha plus IFN gamma was observed in MKN 45 that were transiently transfected with chimeric chloramphenicol acetyltransferase reporter genes driven by the transcriptional regulatory region of human IL-8 gene. Through the mutation of the regulatory region of the IL-8 gene, both AP-1- and NF-kB-like factor binding elements were presumed to be involved in conferring the responsiveness to TNF alpha plus IFN gamma. Moreover, gel retardation analyses revealed that TNF alpha and IFN gamma synergistically induced the binding of NF-kB like as well as AP-1 like proteins bound to these sites. These results indicated that IFN gamma synergistically enhanced TNF alpha-induced IL-8 production in a human gastric cancer cell line through synergistic activation of transcription factors without up-regulating TNF alpha receptor.

Base Sequence↗
PubMed1992

Biosynthesis of prostaglandins from 17(18)epoxy-eicosatetraenoic acid, a cytochrome P-450 metabolite of eicosapentaenoic acid.

Eicosapentaenoic acid (20:5(n - 3)) is oxygenated to 17S(18R)epoxyeicosatetraenoic acid (EpETE) by microsomes of monkey seminal vesicles, which also are rich in prostaglandin (PG) H synthase. The metabolism of racemic [14C]17(18)EpETE by PGH synthase of sheep vesicular glands was investigated in the present report. The two main metabolites were identified by GC-MS as 17(18)epoxyprostagland E2 (17(18)EpPGE2) and 17(18)EpPGF2 alpha. The structures were confirmed by chemical synthesis of these prostaglandins from PGE3. 17(18)EpPGE1 was synthesized from 17,18-dehydro-PGE1 by the same method. Alkali treatment of 17(18)EpPGE2 yielded 17(18)EpPGB2, which could be resolved by RP-HPLC into the 17R(18S) and 17S(18R) stereoisomers. The 17S(18R) stereoisomer was identified by co-chromatography with [14C]17S(18R)EpPGB2, which was formed by PGH synthase from biosynthetic [14C]17S(18R)EpETE. The 17(18)epoxyprostaglandins were found to be relatively unstable during acidic extractive isolation. 17(18)EpPGE1 and 17(18)EpPGE2 could not be detected in seminal vesicles of the cynomolgus monkey in significant amounts relative to 19-hydroxy-PGE1. Nevertheless, biosynthesis of 17(18)epoxyprostaglandins should be considered when the biological effects of 17S(18R)EpETE are investigated.

Animals↗
PubMed1992

Purification and molecular cloning of a butyrolactone autoregulator receptor from Streptomyces virginiae.

In streptomyces, low molecular weight compounds termed "autoregulators" have been isolated as primary signal molecules for triggering secondary metabolism and/or cytodifferentiation. Streptomyces virginiae produces a set of autoregulators termed virginiae butanolide A-E which trigger virginiamycin production, and possesses a high-affinity virginiae butanolide receptor (Kim, H.S., Nihira, T., Tada, H., Yanagimoto, M., and Yamada, Y. (1989) J. Antibiot. (Tokyo) 42, 769-778). The virginiae butanolide receptor has now been purified to apparent homogeneity with 14,000-fold purification and an 8.6% activity yield. The purified receptor showed a Mr of 36,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and a maximum ligand binding of 33.0 nmol/mg protein, indicating a 1:1 binding stoichiometry (1.18 mol of virginiae butanolide/36 kDa of protein) between virginiae butanolides and the receptor. Due to a blockage at the amino terminus, fragment peptides were generated by lysyl endopeptidase and five partial amino acid sequences were determined. The gene (vbrA) encoding the virginiae butanolide receptor was identified on a 5.0-kbp BamHI fragment by hybridization to synthetic oligonucleotide probes, cloned, and sequenced. Nucleotide-sequence analysis predicted a 319-amino acid open reading frame (vbrA) in which all the partial amino acid sequences of the receptor appeared, and 166 bp downstream from it another open reading frame for a 144-amino acid protein which was designated as a ribosomal protein L11 from its high homology (62-64%) to the amino acid sequences of ribosomal protein L11 of several origins, and thus denoted as rplK. The C-terminal half of VbrA showed 36% overall homology to the amino acid sequence of an essential protein (NusG) of Escherichia coli. Furthermore, the gene assembly of vbrA-rplk of S. virginiae closely resembled that of nusG-rplK of E. coli, suggesting that vbrA may constitute a part of an essential gene cluster encoding components of transcriptional and translational apparatuses.

Amino Acid Sequence↗
PubMed1992

A finding of highly selective synthetic inhibitor of plasma kallikrein; its action to bradykinin generation, intrinsic coagulation and experimental DIC.

We found a novel and highly selective synthetic inhibitor of plasma kallikrein (PK), called PKSI-527; the Ki value was 0.81 microM. PKSI-527 inhibited the bradykinin (BK) generation induced by kaolin and prolonged partial thromboplastin time (PTT). PKSI-527 prevented the decrease of fibrinogen (Fg) levels due to i.v. injection of ellagic acid in mice and ameliorated the endotoxin (ET)-induced DIC in rats.

Animals↗
PubMed1992

Multiple colorectal carcinomas and colorectal carcinoma associated with extracolonic malignancies.

In this study, we analyzed 149 surgical cases of colorectal cancer between January 1983 and August 1989. Thirteen cases (8.7 percent) of colorectal primary cancer associated with extracolonic primary malignancy of 14 lesions and 10 cases (6.7 percent) of multiple primary colorectal cancers were included. Among the 14 lesions of extracolonic primary malignancy, there were 6 gastric carcinomas, 2 endometrial carcinomas, 2 urinary bladder carcinomas, and one each in the esophagus, liver, bile duct and jejunum. The second tumor was not detected preoperatively in 3 of 4 cases of synchronous multiple primary colorectal carcinoma. A curative resection was done in 10 (77 percent) out of 13 cases of colorectal cancer associated with extracolonic malignancy, while 7 (88 percent) out of 8 cases of multiple colorectal cancers had a curative resection. Nine patients (69 percent) with colorectal cancer associated with extracolonic malignancy were disease-free for 2 months to 14 years. Seven patients (88 percent) with multiple colorectal cancers were disease-free for one to 22 years. We recommend, therefore, that in any patient with colorectal cancer, the entire large bowel should be thoroughly searched for any other primary tumors, by taking the existence of extracolonic tumors into account. A curative resection should be performed, and the follow-up period should be life-long.

Adenocarcinoma↗
PubMed1992

Efficacy of combination treatment--(TAE with adriamycin and ethanol)--for hepatocellular carcinoma.

Among 44 patients with hepatocellular carcinoma (HCC), combination treatment with both transhepatic arterial embolization (TAE) and ethanol injection therapy (EIT) was performed in 10 patients. Only two had tumors measuring less than 3 cm in diameter. In all, eight patients had solitary tumors and two had multiple tumors. The tumor was classified as stage I in one patient, stage II in six subjects, stage III in two patients, and stage IV in one subject prior to TAE, but one stage II case was changed to stage III after laparotomy. The clinical stage was I in two patients, II in six subjects and III in two patients. Five patients with tumors of stages I and II achieved either a complete response (CR) or partial response (PR). However, three patients with tumors of stages III and IV showed progressive disease (PD). Thus, the response rate (CR+PR) was 50%. For tumor stages I and II, the 1-, 2-, and 3-year survival values were 100%, 100%, and 83%, respectively. For tumor stages III and IV, the 1- and 2-year survival values were 75% and 25%, respectively. Combination treatment of HCC appears to be efficacious for tumor stages I and II.

Adult↗
PubMed1992

Spontaneous bacterial peritonitis due to Clostridium perfringens in a patient with liver cirrhosis and pure red cell aplasia.

A 63-year-old man with decompensated liver cirrhosis and pure red cell aplasia complained of pyrexia, abdominal distention and abdominal pain. A diagnosis of spontaneous bacterial peritonitis (SBP), Conn's syndrome, was made upon the isolation of an anaerobe Clostridium perfringens from both ascitic fluid and peripheral blood. The bacteria were found to be susceptible to piperacillin, and administration of the antimicrobial agent markedly improved his SBP. The anaerobes should be kept in mind as one of the possible pathogens of SBP, although anaerobic infection has been reported to be quite rare in the disease.

Clostridium Infections↗
PubMed1992

Effects of trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, in preventing restenosis after percutaneous transluminal coronary angioplasty.

Trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, is a potential inhibitor of intimal proliferation after percutaneous transluminal coronary angioplasty (PTCA). To study its efficacy, 72 patients were randomized to receive Trapidil (600 mg/day orally for 1 week before PTCA and for 4 to 6 months after PTCA; n = 36) or aspirin and dipyridamole (aspirin, 300 mg/day, and dipyridamole, 150 mg/day; n = 36). At entry, both groups were comparable with regard to age, sex, dilated vessels, severity of pre-PTCA stenosis, residual stenosis after PTCA, and prevalence of coronary risk factors. Repeat coronary angiography was performed 6 months after PTCA. Restenosis, defined as the loss of at least 50% of the gain in luminal diameter accomplished by dilation, was present in seven patients (19.4%) in the trapidil group and 15 patients (41.7%) in the aspirin-dipyridamole group (p less than 0.05). The progression of stenosis in patients with less than 30% residual stenosis was significant in both groups. Furthermore, in the patients with residual stenosis of more than 30%, progression of stenosis was less in the trapidil group than in the aspirin-dipyridamole group. Thus trapidil was useful in preventing intimal proliferation after PTCA, especially in patients with more than 30% residual stenosis after PTCA.

Angioplasty, Balloon, Coronary↗
PubMed1992

The changes in body temperature, oxygen consumption, CO2 production and muscle protein turnover rate by selection for body size in Japanese quail, Coturnix coturnix japonica.

1. Body temperature, oxygen consumption, CO2 production and muscle protein degradation rate were measured in the three quail lines selected for body size, a random bred line (RR) and two lines selected for large (LL) or small (SS) body size. 2. The body temperature at 15 weeks of age was highest for small body size line and lowest for large body size line. 3. The body temperature, oxygen consumption and CO2 production of females were significantly higher than that of males. 4. The fractional degradation rate of muscle protein of SS, RR and LL lines were measured as 2.4, 1.6 and 1.2% per day in male, and 2.6, 1.7 and 1.4% per day in female.

Animals↗
PubMed1992

Case report: alternation therapy with antileukemic agents and recombinant human granulocyte colony-stimulating factor for RAEB in transformation.

Under the assumption that in some patients with refractory anemia with excess of blasts (RAEB), the abnormal clones might be less responsive to granulocyte colony-stimulating factor than normal clones, the authors tried alternation therapy with a recombinant form of this factor (rhG-CSF) and antileukemic agents in the treatment of two patients with RAEB in transformation. After repetition of the short-cycled alternation therapy, the hematologic findings of both patients were completely normalized and have remained so without any adverse side effects under the continuation of this therapy for more than 5 months. Judging from our clinical experience, the alternation therapy may be a new efficient therapeutic strategy for RAEB and some types of slowly progressive leukemia.

Adult↗
PubMed1992

Heterotopic pancreas diagnosed by endoscopic ultrasonography and endoscopic injection of ethanol to make a histologic diagnosis.

A gastric submucosal tumor in a 56-year-old man was presumed to be heterotopic pancreas on the basis of endoscopy and endoscopic ultrasonography. To obtain a histologic diagnosis we injected ethanol at the tumor site to create an artificial ulcer. This facilitated the removal of endoscopic biopsy specimens from the submucosal layer so that histologic examination could confirm the presence of heterotopic pancreatic tissue.

Choristoma↗
PubMed1992

The alloantigen-specific immunosuppressive activity of estradiol-chlorambucil conjugate (KM2210) and its beneficial effect on allogeneic bone marrow transplantation in mice.

KM2210, a conjugate of estradiol and chlorambucil (CBL), which was originally developed as an anti-breast cancer agent, inhibits proliferative response of human mononuclear cells to alloantigens in mixed lymphocyte culture in a dose-dependent manner, but has no effect on their response to phytohemagglutinin. Neither estradiol benzoate nor CBL alone showed these unique actions. The suppressive effect of KM2210 on MLC was abrogated by adding of anti-transforming growth factor-beta (TGF-beta) antibody to the culture, but was not affected by the addition of interleukin-2, suggesting that KM2210, unlike CBL, displays its actions via TGF-beta. In experimental allogeneic bone marrow transplantation using mice, daily oral administration of KM2210 (2 mg/kg/day) for 30 days posttransplant significantly inhibited the alloantigen-specific immune reactions. Furthermore, the survival rate of the KM2210-treated mice was significantly higher than that of the cyclosporine-treated (2 mg/kg/day, p.o.) mice, and no adverse effect of KM2210 on hematopoietic recovery was found. These results strongly suggest possible clinical benefits of KM2210 as a new immunosuppressive agent for the prevention and treatment of graft-versus-host disease and other allospecific immune reactions.

Animals↗