[Structure and evolution of movable genetic elements in eukaryotes].
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Biomedical subjects
Publications and source records attributed to K Saigo.
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In a previous communication (Saigo, K., Millstein, L. and Thomas, C.A., Jr. (1981) Cold Spring Harbor Symp. Quant. Biol. 45, 815-827), the overall structure of histone genes of Schneider line 2 cells was shown to extensively differ from that of Oregon-R embryo from which the cell line was established, and it was speculated that the histone genes might be reshuffled extensively during either the periods of the establishment, or maintenance of cell lines, or both. To establish the validity of this notion the structure of histone genes was examined in Drosophila melanogaster cultured cells. The overall organization of histone gene clusters was found to be stably maintained in both the periods for the establishment and maintenance of cultured cells, indicating that the previous assumption is inadequate. Instead of an extensive rearrangement, minor structural changes were found to occasionally occur probably by simple base substitutions and/or, deletion or insertion of very short DNA pieces. It was also shown that the extensive variation in structures of histone genes in cultured cells such as Schneider line 2 are attributable to polymorphism on the level of individual flies.
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The structure and organization of a human repetitive DNA family containing the HindIII 1.8-kb repetitive sequence were studied, using two-dimensional (2D) gel electrophoresis. The HindIII 1.8-kb sequence proved to be part of a repetitive sequence about 5 kb long and interspersed on the genome. The long repetitive sequence family contained several subgroups, as based on polymorphism of the restriction site. Recombinant phages containing the long repetitive sequence were isolated from the human genomic DNA library. Heteroduplex and restriction analysis showed that the structure of the repetitive sequence carried by the phages was close to that expected from 2D gel electrophoretic analysis. The 2D gel electrophoretic analysis was shown to be a reliable and useful approach for surveying and mass analysis of repetitive sequence families.
A new species of copia-like movable genetic element termed 17.6 was identified in Drosophila melanogaster, and the nucleotide sequences of its long terminal repeats (LTRs) were determined. The LTRs of 17.6 were not only homologous to those of 297, a sibling movable genetic element of 17.6, but also closely matched those of avian leukosis-sarcoma virus. This made it possible (i) to identify the nucleotide sequences in 17.6 and 297 that correspond to the crucial regulatory sequences for both transcription and reverse transcription in avian leukosis-sarcoma virus and (ii) to divide the LTRs of these two elements into three regions, U3, R, and U5, like those of retrovirus proviruses. Similarity in sequence was also found to a certain extent in other copia-like elements. From these results, we postulate that copia-like movable genetic elements in Drosophila originated from infection of a progenitor Drosophila with a retrovirus from which the present-day avian leukosis-sarcoma virus was derived.
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From a cloned library of Drosophila DNA, a recombinant phage was isolated which contained a nucleotide sequence homologous to both the histone gene and a movable genetic element, 297 [Saigo, K., Millstein, L. & Thomas, C.A., Jr. (1981) Cold Spring Harbor Symp. Quant. Biol. 45, 815-827]. We have determined the nucleotide sequences of the termini of 297 as well as its insertion site in the histone gene in the clone. Our results strongly suggest that (i) although 297 ends with typical long terminal repeats, integrated 297 is not bounded by 5' T-G...C-A 3', dinucleotides commonly found at the very ends of integrated forms of other similar genetic elements, and (ii) the insertion of 297 occurred exactly within the T-A-T-A box for the H3 histone gene containing T-A-T-A-T-A. The structures of the insertion sites of 297 were also examined by using two other recombinant clones of the histone gene. A 6-base-pair-long segment, T-A-T-A-T-A, was again found to be present at the insertion sites of 297 in both clones. Based on these results, it was concluded that, at least within the histone gene cluster, the insertion of 297 was carried out in a site-specific fashion with T-A-T-A-T-A as the target sequence.
Forty-six cases with hematological malignancies were treated with vindesine sulfate (VDS); a new semisynthetic vinca alkaloid. Six cases with ALL, 5 cases CML in blastic crisis, 3 Hodgkin's disease (HD) and 4 non-Hodgkin's lymphoma (NHL) were treated with VDS alone. Five out of 6 cases ALL, 2 out of 5 CML in blastic crisis were induced into partial remission with VDS alone. All of 3 HD, and 4 NHL were induced in complete remission (CR) or partial remission (PR). Out of 5 cases AML in CR who received VDS as the maintenance therapy in combination with cyclophosphamide, 6-MP and prednisone, one case relapsed during the treatment, but other four cases maintained CR for 4 to 24 months. One case of APL in relapse, which was treated with VDS and 6-MP, reinduced into CR after one month. Out of 16 cases with malignant lymphoma treated by combination chemotherapy including VDS, eleven cases entered in CR or PR. Out of four cases in which the disease became refractory to vincristine (VCR) or vinblastine (VLB) clinically, two achieved PR. VDS was administered intravenously with 3 mg/body/week. When undesirable effect such as leucocytopenia was observed, the dose was reduced to 2-2.5 mg/body/week or 3 mg/body/2 weeks or month. Neurotoxicity (i.e. Paresthesia 21.7%), alopecia (21.7%), leucocytopenia (19.6%), constipation (10.9%) and fever (6.5%) were main side effects of VDS. The neurotoxicity of VDS, however, seemed far less intensive than VCR.
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The likelihood of stroboscopic motion between different contour combinations was obtained under temporal conditions (duration, ISIs). Three kinds of contour figures were prepared; the real, the subjective and the control. Two stimulus figures for such combinations were chosen from these three; one as the first stimulus and the other as the second. The result was that the likelihood of seeing motion was reduced, when the contour figure of more form information was used as the first stimulus and that of less form information as the second than when they were in the reverse order. This was considered as the effect of order of stimulus presentation.
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Various cultured cell lines of Drosophila melanogaster contain 10 to 13 discrete double-stranded RNAs ranging in length from 1 to 4 kilobases. These RNAs were characterized by nuclease susceptibility, density, solubility in LiCl, thermostability, electron microscopy and gel electrophoresis. These RNAs, which are similar to Reo virus RNA could not be detected in adult or embryonic tissues.
The number of Langerhans' cells (LHC) in the prickle cell layer was increased after prick test in patients with Behçet's disease. LHC came into contact with lymphocytes in the prickle cell layer. Lattice-shaped granules were seen in the mitochondria of LHC.
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