Search PubMed⌕ Search

Biomedical subjects

T Saisho

Publications and source records attributed to T Saisho.

11 recordsLinked to original sources

Chlorinated alkaloids in Menispermum dauricum DC: root culture.

Feeding experiments using (36)Cl showed that Menispermum dauricum root culture produces four alkaloids containing chlorine. They included the novel alkaloids dauricumine and dauricumidine as well as the known alkaloids acutumine and acutumidine. The structures of novel alkaloids were established by spectroscopic, crystallographic, and chemical methods. These four alkaloids were labeled with (36)Cl, isolated, and fed independently to root cultures. Mutual conversion between acutumine and acutumidine, and between dauricumine and dauricumidine by N-methylation and N-demethylation, was demonstrated. Moreover, dauricumine was converted to acutumine and acutumidine. Epimerization of acutumidine to dauricumidine or vice versa was not observed. These results suggest that dauricumine is the first chlorinated alkaloid formed in cultured M. dauricum roots. Skewed distribution of radioactivity derived from labeled dauricumine is proof that epimerization at C-1 proceeds at a lower rate than N-demethylation.

Alkaloids↗

Bacterial meningitis observed in a phase I trial of vinorelbine, cisplatin and thoracic radiotherapy for non-small cell lung cancer: report of a case and discussion on dose-limiting toxicity.

Although neutropenia increases the risk of life-threatening infections, bacterial meningitis is rarely encountered as a complication during cancer chemotherapy in adults with a solid tumor. A 66-year-old male with adenosquamous carcinoma of the lung, cT2N3M0, stage IIIB, was enrolled in a phase I trial of chemoradiotherapy and treated with cisplatin 80 mg/m2 (122 mg/ body) on day 1, vinorelbine 20 mg/m2 (32 mg/body) on days 1 and 8 and thoracic radiotherapy 30 Gy/15 fractions, beginning on day 2, with dexamethasone administered for antiemesis at a dose of 16 mg on day 1, 8 mg on days 2 and 3, 4 mg on day 4 and 2 mg on day 5. The patient developed headache and fever on day 6 of the second cycle of the treatment and bacterial meningitis was diagnosed based on the findings of consciousness disturbance, an elevated peripheral blood leukocyte count and numerous leukocytes in the cerebrospinal fluid. In spite of the doctor's delay in establishing the exact diagnosis, the bacterial meningitis in this case was successfully treated with intensive antibiotic therapy. This life-threatening complication, equivalent to a grade 4 non-hematological adverse reaction, was not counted as dose-limiting toxicity in the current phase I trial, because there are only a few reports of bacterial meningitis associated with cancer chemotherapy and it developed in this case without any associated decrease in the peripheral blood leukocyte count.

Aged↗

Establishment of a novel cell line (TS-2) of pre-B acute lymphoblastic leukemia with a t(1;19) not involving the E2A gene.

The t(1;19)(q23;p13) translocation involving the E2A gene on chromosome 19p13.3 is a nonrandom translocation that is often seen in childhood pre-B-cell acute lymphoblastic leukemia (ALL). However, recent studies have demonstrated the presence of immunophenotypic and molecular heterogeneity among patients with the cytogenetically identical chromosome translocation. Here we report a novel pre-B ALL cell line, TS-2, with t(1;19) translocation not involving the E2A gene. The breakpoint of t(1;19) in TS-2 was demonstrated to be at 19p13.3, a region indistinguishable from the locus of the E2A gene, by cytogenetic study and fluorescence in situ hybridization. However, rearrangement of the E2A gene was not detected in TS-2 by Southern blot analysis. Moreover, the expressions of PBX1 or E2A/PBX1 fusion genes were not detected by an extensive study with Northern blot analysis and reverse transcription-polymerase chain reaction. These findings suggest that TS-2 may have a genetic abnormality involving uncharacterized gene(s) at 19p13.3 distinct from the E2A gene and, therefore, may be useful for investigating the heterogeneity of molecular pathogenesis in leukemias with t(1;19)(q23;p13) translocation.

Adenovirus E2 Proteins↗

Relationship between spontaneous aminoglycoside resistance in Escherichia coli and a decrease in oligopeptide binding protein.

Changes in the amount of oligopeptide binding protein (OppA) in spontaneous kanamycin-resistant mutants of Escherichia coli were investigated. Among 20 colonies obtained from 10(8) cells cultured in the presence of 20 microgram of kanamycin/ml, 1 colony had no detectable OppA and 7 colonies were mutants with reduced amounts of OppA. Sensitivity of wild-type cells to kanamycin increased slightly by transformation of the oppA gene, but the sensitivity of the mutants increased greatly by the transformation. A mutant with no OppA was found to be a nonsense mutant of the oppA gene at amino acid position 166. In a mutant having a reduced level of OppA, the reduction was due to the decrease in OppA synthesis at the translational level. These mutants were also resistant to other aminoglycoside antibiotics, including streptomycin, neomycin, and isepamicin. Isepamicin uptake activities decreased greatly in these two kinds of mutants. The results support the proposition that aminoglycoside antibiotics are transported into cells by the oligopeptide transport system, and that transport is an important factor for spontaneous resistance to aminoglycoside antibiotics.

Amino Acids↗

Peripheral blood stem cell transplantation for hepatoblastoma with microscopical residue: a therapeutic approach for incompletely resected tumor.

We report a nine-month-old boy with stage III B hepatoblastoma of caudate lobe origin. Surgical resection was attempted following six courses of chemotherapy, but viable tumor cells remained microscopically at resection margins. Subsequently, he received peripheral blood stem cell transplantation (PBSCT), whose preparative regimen being consisted of carboplatin, etoposide, tetrahydropyranyl adriamycin, and melphalan. Since then, the patient shows no relevance of local relapse or distant metastasis without any chemotherapy. PBSCT for patients with post-operative residue may improve the outcome of advanced hepatoblastoma and worth of a further clinical investigation.

Disease-Free Survival↗

Improved survival of children with advanced tumors by myeloablative chemotherapy and autologous peripheral blood stem cell transplantation in complete remission.

Five children with neuroblastoma (NB) stage IV and five children with rhabdomyosarcoma (RMS) stage III were treated with myeloablative chemotherapy and autologous peripheral blood stem cell transplantation (MCT/PBSCT) in the state of complete remission (CR) achieved by conventional therapy. PBSCs were collected in CR status using a cell separator with blood access through a double-lumen central venous catheter. PBSCs with 1.9+/-0.8x10(5) of CFU-GM per patient weights (kg) were infused following MCT after a period of conventional therapy for 11.1+/-2.1 or 9.7+/-0.9 months in NB or RMS patients, respectively. Regimen-related toxicity of MCT was tolerable and peripheral white blood cell count recovered beyond 1.0x10(3)/microl 10-12 days after infusion of PBSCs in all patients. All of RMS patients and three of five NB patients survived for an average of 31.6 months (ranged 10.8-58.1). The survival rate of these patients was improved as compared with our historical controls, and presumably, with that of conventional chemotherapy previously reported. Despite a limited number of patients, it appears that MCT/PBSCT may be effective in improving survival by preventing relapse which may occur thereafter if treated with conventional therapy alone. Furthermore, MCT/PBSCT reduced the duration of treatment, as compared with that of conventional chemo-therapy. Therefore, this study may suggest the feasibility and promise of the therapy including MCT/PBSCT for children with advanced stages of NB and RMS.

Antineoplastic Agents↗

Molecular mechanism of polyamine stimulation of the synthesis of oligopeptide-binding protein.

Polyamine stimulation of the synthesis of oligopeptide-binding protein (OppA) was shown to occur mainly at the level of translation by measuring OppA synthesis and its mRNA level. Several artificial oppA genes were constructed by site-directed mutagenesis. These synthesize different kinds of OppA mRNAs: mRNAs differing in the size of 5'-untranslated region; mRNAs having the Shine-Dalgarno (SD) sequence in a different position; mRNAs having different secondary structure in the region of the SD sequence; and fusion mRNAs consisting of the 5'-untranslated region of OppA mRNA and the open reading frame of beta-galactosidase. By measuring the synthesis of OppA or beta-galactosidase from these mRNAs, we found that the 171-nucleotide 5'-untranslated region and 145 nucleotides of the ORF of OppA mRNA are involved in the polyamine stimulation of OppA synthesis. When the secondary structure of the above region of OppA mRNA was analyzed by optimal computer folding, it was shown that the degree of polyamine stimulation of OppA protein synthesis was dependent on the structure of the SD sequence in addition to its position. Loose base pairing of the SD sequence with other regions of the mRNA caused strong polyamine stimulation, while intense base pairing of the SD sequence with other regions of the mRNA resulted in insignificant or weak polyamine stimulation.

Bacterial Proteins↗

Acute myelogenous leukaemia with t(8;21) translocation of normal cell origin in mosaic Down's syndrome with isochromosome 21q.

We report a 13-year-old girl with Down's syndrome (DS) having a mosaic karyotype of 46,XX/46,XX, -21,+i(21q), who developed acute myelogenous leukaemia (AML) (FAB M1). The t(8;21) translocation generating a AML1/MTG8 chimaeric gene of her blasts was demonstrated by cytogenetic analysis and reverse transcription-polymerase chain reaction. Interestingly, the leukaemic clone with t(8;21) did not have isochromosome 21q, indicating that the blasts were of normal cell origin. These findings suggest that, in older patients with DS, 21 trisomy cells have no greater predisposition to develop AML than normal karyotypic cells.

Adolescent↗