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Biomedical subjects

T Akagi

Publications and source records attributed to T Akagi.

At least 163 records · Page 9Linked to original sources
PubMed1995

Tumorigenicity of human T-cell leukemia virus type I-infected cell lines in severe combined immunodeficient mice and characterization of the cells proliferating in vivo.

The mechanism involved in leukemogenesis and neoplastic cell growth of adult T-cell leukemia (ATL) still remains unclear. We examined the tumorigenicity of human T-cell leukemia virus type I (HTLV-I)-infected cell lines in an in vivo cell proliferation model using severe combined immunodeficient (SCID) mice. Eleven HTLV-I-infected cell lines were injected into SCID mice and we found that 4 of them were capable of proliferating in SCID mice. Three of four transplantable cell lines are derived from the leukemic cell clone and 6 of 6 HTLV-I-infected cell lines of nonleukemic cell origin could not engraft in SCID mice. Interestingly, it was shown that some HTLV-I-infected and interleukin-2 (IL-2)-dependent cell lines could successfully engraft in SCID mice. The expression of IL-2 mRNA was not detected in these cell lines growing either in vivo or in vitro. HTLV-I viral products were not detected in 3 of 4 transplantable cell lines proliferating in vivo. Peripheral blood T cells immortalized by introduction of tax gene of HTLV-I were found to have no tumorigenic potential in SCID mice. These data suggest that (1) HTLV-I-infected cell lines of nonleukemic cell origin do not have enough leukemogenic changes to acquire the tumorigenic potential in SCID mice; (2) the IL-2 autocrine mechanism is not directly involved in the tumor cell growth; (3) viral gene expression is not needed for the maintenance of neoplastic cell growth; and (4) the expression of tax gene is not sufficient for the neoplastic cell growth in vivo.

Animals↗
PubMed1995

Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity.

Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin's lymphoma characterized by the CD30+ large neoplastic cells and sometimes carries a t(2;5)(p23;q35). Recently, we found a novel hyperphosphorylated 80-kD protein tyrosine kinase, p80, in ALCLs with t(2;5). Subsequent cDNA cloning showed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene (Morris et al, Science 263:1281, 1994). Meanwhile, the clinicopathologic features of p80-carrying ALCLs have remained unclear. Paraffin sections of 105 cases of ALCL were immunostained using anti-p80 antibody, and 30 of them were shown to express p80. Clinicopathologic comparison between p80-positive and -negative ALCLs showed that p80-positive cases occurred in a far younger patient age group (16.2 +/- 12.9 years; p80-negative cases, 51.0 +/- 22.3 years; P < .0001) and the patients showed a far better 5-year survival rate (79.8%; p80-negative group, 32.9%; P < .01). These data showed that p80-positive ALCL is a distinct entity both clinically and pathogenetically and should be differentiated from p80-negative ALCL.

Adolescent↗
PubMed1995

A model of antimycin A binding based on structure-activity studies of synthetic antimycin A analogues.

The structural factors of antimycin A molecule required for inhibitory action were studied using newly synthesized antimycin A derivatives with bovine heart submitochondrial particles, in order to probe the interaction between antimycin A and its binding site. In particular, we focused upon the roles of the amide bond bridge, which connects the salicylic acid and dilactone ring moieties, and the 3-formylamino group in the salicylic acid moiety. The lack of formation of an intramolecular hydrogen-bond between phenolic OH and amide carbonyl groups resulted in a remarkable loss of the activity (by four orders of magnitude), indicating that this hydrogen-bond is essential for the inhibition. This result suggested that both the phenolic OH and the carbonyl groups form a hydrogen-bond with some residues at a fixed conformation. In addition, the inhibitory potency was remarkably decreased by N-methylation of the amide bond moiety, indicating that the NH group might function in hydrogen-bond interaction with the binding site. The N-methylation of 3-formylamino group also resulted in a decrease in the activity, probably due to a loss of the rotational freedom of this functional group. Molecular orbital calculation studies with respect to the conformation of the 3-formylamino group indicated that this group takes an active conformation when the formyl carbonyl projects to the opposite side of the phenolic OH group. Based upon a series of structure-activity studies of synthetic antimycin A analogues, we propose a tentative model for antimycin A binding in its binding cavity.

Amides↗
PubMed1995

Increased protein tyrosine-phosphorylation in primary T-cells transduced with Tax1 of human T-cell leukemia virus type I.

Protein tyrosine-phosphorylation in primary human T-cells transduced with Tax1 of Human T-cell leukemia virus type I was investigated. In comparison with control T-cells, the level of protein tyrosine-phosphorylation after stimulation with anti-CD3 antibody increased significantly in Tax1-transduced T-cells. This enhancement in tyrosine-phosphorylation possibly accounted for the augmented proliferation response of these cells, which has been reported previously [J. Virol. 67 (1993) 1211-1217].

Cell Line, Transformed↗
PubMed1995

Developmental alteration and neuron-specific expression of bone morphogenetic protein-6 (BMP-6) mRNA in rodent brain.

Bone morphogenetic proteins (BMPs) are a group of proteins which induce bone formation from mesenchymal cells. The existence of BMPs in the nervous system as well as in bone tissue has recently been reported. In this study, we show that BMP-6 is neuron-specific, and describe the temporal and spatial expression patterns of BMP-6 mRNA in the developing rat and gerbil brain. Northern blot analysis showed that the BMP-6 transcript level was specifically high from newborn to 3 weeks after birth compared with those in fetal and adult rats. In situ hybridization showed that most of the neurons possessed high levels of BMP-6 mRNA in the neonatal brain, while in the adult brain, BMP-6 mRNA level was significantly decreased in most of the neurons except those in hippocampus which retained high levels. Furthermore, to show that the BMP-6 expression was specific to neurons, we induced delayed neuronal cell death and compensative glial cell proliferation in the gerbil hippocampus by transient ischemia. Our findings collectively suggest that BMP-6 is neuron-specific and may play important roles in neuronal maturation and synapse formation.

Animals↗