Biomedical subjects

N Higashi

Publications and source records attributed to N Higashi.

15 recordsLinked to original sources

PubMed1992

Developmental change in subcellular location of Bp-1 protein with an ability to interact with both identifier sequence and its brain-specific transcript, BC-1 RNA.

Identifier sequences are transcribed to generate a brain-specific BC-1 RNA present as a ribonucleoprotein particle in the dendrites and somata of neurons. This ribonucleoprotein particle contains an identifier sequence-binding protein (Bp-1 protein). We report here the purification of BC-1 RNA and demonstrate that Bp-1 protein interacts directly with the RNA. We also demonstrate an accumulation of Bp-1 protein in the nucleus of brain cells from mouse fetus and newborns that precedes the postnatal increase in BC-1 RNA. Cytoplasmic Bp-1 protein present in a complex with BC-1 RNA increases postnatally with a concomitant decrease in nuclear Bp-1 protein. These observations suggest that Bp-1 protein may play a role(s) in the synthesis and nuclear export of BC-1 RNA.

Aging↗

PubMed1992

The 10 S BC-1 ribonucleoprotein particle contains identifier sequence-binding proteins that interact with an array of GCAAG/CTTGC motifs between split promoter sequences for RNA polymerase III.

BC-1 RNA is a brain-specific small RNA transcript of identifier sequences present in the somas and dendrites of neurons. We recently reported that the RNA is complexed with a protein(s) to form a 10 S ribonucleoprotein particle (Kobayashi, S., Goto, S., and Anzai, K. (1991) J. Biol. Chem. 266, 4726-4730). We demonstrate here that this 10 S BC-1 ribonucleoprotein particle contains a DNA-binding protein(s) (Bp-1 protein) capable of interacting with a region between split promoter sequences for RNA polymerase III within the identifier sequences. The region has short inverted repeats: a perfect octanucleotide repeat (GCGCTTGCCTAGCAAGCGC) and an imperfect heptanucleotide repeat (GCCTAGCAAGCGCAAGGC), each of which contains a GCAAG/CTTGC motif. We also demonstrate that the binding of this protein either to the array of pentamer motifs or to BC-1 RNA is mutually exclusive. The molecular masses of photo-cross-linking adducts of Bp-1 protein to a 32P-labeled GCAAG/CTTGC motif-specific probe were estimated to be about 31 and 36 kDa, indicating that two species of Bp-1 proteins may be present in the brain.

Animals↗

PubMed1992

Damage to mitochondrial respiration chain is related to phospholipase A2 activation caused by tumor necrosis factor.

Tumor necrosis factor (TNF) has been shown to be cytotoxic to tumor cell lines in vitro, but the mechanism by which TNF exerts its cell growth-regulatory effects is not known. In this report, we used various inhibitors to investigate the sequence of events that lead to cytotoxic effects of TNF on L.P3 cells, a highly sensitive, murine fibroblast cell line. Our results indicate that mitochondrial respiration chains are damaged by a hydroxyl radical at an early stage of the cell lysis after TNF treatment. This event is followed by the activation of phospholipase A2, and finally leads to cell lysis.

Animals↗

PubMed1992

Activation of human monocytes by interleukin-2 and various cytokines.

We previously reported that human macrophages cultured with IL-2 for a long period (lymphokine-activated macrophages, LAMs) showed high tumoricidal activity against human and murine leukemic cell lines through a different mechanism from lymphokine-activated killer (LAK) cells. In this report, we investigated the effects of various cytokines on the tumoricidal activity of IL-2-induced LAMs against HeLa cells. CSF-1 and IL-1 were found to enhance the tumoricidal activity of LAM in a dose-dependent manner, whereas IFN-gamma and TNF had inhibitory effects. CSF-1 in combination with a low dose of IL-2 synergistically induced LAMs with highly tumoricidal activity. We also found that monocytes from some donors that did not respond to IL-2 were differentiated to tumoricidal macrophages by treatment with a combination of CSF-1 and IL-2. Furthermore, IL-2-induced LAMs were found to produce cytotoxic factors in the culture medium when they were cocultured with tumor cells, and the cytotoxic activity in the culture supernatant of LAMs was also increased by the incubation of LAMs with CSF-1. The cytotoxicity of the supernatants from macrophages with different tumoricidal activity correlated with their cell-mediated cytotoxicity. It is suggested from these results that the cytotoxicity of LAMs is regulated by CSF-1, IL-1, IFN-gamma, and TNF, and that the production of cytotoxic molecules is involved in cell-mediated killing by LAMs.

Cytokines↗

PubMed1992

[Function, molecular structure and gene expression regulation of tumor necrosis factor and lymphotoxin].

Tumor necrosis factor (TNF, also called TNF-alpha) and lymphotoxin (LT, TNF-beta) have 32% homology in their primary structures, and it has recently been clarified that they also have closely related tertially structures. These two related cytokines share various biological functions, such as cytotoxic effect, immunomodulating effect, etc. although they produce different effects on several lymphoid, endothelial, and other cellular targets. In this paper, the structures of the two cytokines and their receptor binding sites are described. Furthermore, the structures of the two types of TNF receptors, as well as their role in TNF mediated signal transduction, and possible second messengers responsible for TNF action are also discussed.

Humans↗

PubMed1992

[On the fenestration of the vertebral and basilar arteries].

The fenestration of the vertebral and basilar arteries was investigated macroscopically in 370 human cases. Altogether 43 fenestrations were found in 32 (8.6%) out of 370 cases. The fenestrations could be divided in three groups according to the position where the fenestration appeared. Group I was the fenestration observed along the vertebral artery (Fig. 1), and 7 such fenestrations were found in 6 (1.6%) out of 370 cases; 3 fenestrations among them were located on the right side, 2 were located on the left side and 1 was found on the bilateral vertebral arteries. In 4 out of 7 fenestrations in this group, the hypoglossal nerve was found passing through the fenestration. Group II was the fenestration observed along the basilar artery (Fig. 2), and 26 fenestrations of this type were found in 20 (5.4%) out of 370 cases: 23 fenestrations (88.5%) were located at the caudal half, 3 (11.5%) were located on the rostral half of the basilar artery (Fig. 5). A close relation was indicated between the side on which the fenestration appeared in the basilar artery and the largeness in caliber of the vertebral artery of either side. Group III was the fenestration observed at the lateral area of the vertebral and basilar arteries (Fig. 3), and 10 fenestrations of this type were found in 9 (2.4%) out of 370 cases; all the fenestrations were located on the right side. In this group, the hypoglossal nerve was observed passing through the fenestratin in 4 out of the 10 fenestrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1979