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Biomedical subjects

O Narumi

Publications and source records attributed to O Narumi.

6 recordsLinked to original sources
PubMed2001

In vivo function of a differentiation inhibitor, Id2.

Cell differentiation is an essential process for the development of various cell types that constitute multicellular organisms. During development, the large family of factors bearing a helix-loop-helix (HLH) motif participates profoundly in this process and these factors serve as good experimental tools for investigating mechanisms underlying tissue-specific differentiation. The HLH family includes both positive and negative regulators of cell differentiation: basic HLH (bHLH)-type transcription factors and Id proteins, respectively. Following an exciting decade focusing on bHLH factors, advances achieved in studies of the inhibitory factors in the last couple of years have placed them in the front line of the research on differentiation and proliferation control. Here, we present and discuss recent results obtained using Id2-deficient mice, which manifest intriguing phenotypes in various systems.

Animals↗
PubMed2000

OUT, a novel basic helix-loop-helix transcription factor with an Id-like inhibitory activity.

Transcription factors belonging to the basic helix-loop-helix (bHLH) family are involved in various cell differentiation processes. We report the isolation and functional characterization of a novel bHLH factor, termed OUT. OUT, structurally related to capsulin/epicardin/Pod-1 and ABF-1/musculin/MyoR, is expressed mainly in the adult mouse reproductive organs, such as the ovary, uterus, and testis, and is barely detectable in tissues of developing embryos. Physical association of OUT with the E protein was predicted from the primary structure of OUT and confirmed by co-immunoprecipitation. However, unlike other bHLH factors, this novel protein failed to bind E-box or N-box DNA sequences and inhibited DNA binding of homo- and heterodimers consisting of E12 and MyoD in gel mobility shift assays. In luciferase assays, OUT inhibited the induction of E-box-dependent transactivation by MyoD-E12 heterodimers. Deletion studies identified the domain responsible for the inhibitory action of OUT in its bHLH and C-terminal regions. Moreover, terminal differentiation of C2C12 myoblasts was inhibited by exogenous introduction of OUT. These inhibitory functions of OUT closely resemble those of the helix-loop-helix inhibitor Id proteins. Based on these findings, we propose that this novel protein functions as a negative regulator of bHLH factors through the formation of a functionally inactive heterodimeric complex.

Amino Acid Sequence↗
PubMed1999

The leukemic oncogene tal-2 is expressed in the developing mouse brain.

tal-1 (T-cell acute leukemia-1; also known as SCL) and tal-2 genes belong to a family of basic helix-loop-helix transcription factors and were originally isolated from the breakpoints of chromosomal translocations in human T-cell leukemia cell lines. tal-1 is expressed not only in hematopoietic cells but also in several endothelial structures and the central nervous system during development. On the other hand, the detailed function and the sites of expression of tal-2 have remained obscure. We cloned the tal-2 cDNA from a mouse embryonic cDNA library and examined its expression pattern in the mouse, comparing with that of tal-1. In situ analyses revealed that tal-2 transcripts are detected at embryonic day 12.5 in the following regions; 1) the diencephalon-the zona limitans intrathalamica and the pretectum, 2) the mesencephalon-the tectum, and the anterior and posterior tegmentum, 3) the metencephalon-the isthmus and the anterior pons. In the diencephalon and the mesencephalon, the expression sites of tal-2 gene were similar to those of tal-1, and its expression was stronger than that of tal-1. In the metencephalon, tal-2 expression was observed in the anterior pons, whereas tal-1 transcripts were detected in the entire pons, and showed stronger expression than tal-2. The tal-2 messages were barely detectable in the brain at birth. These results suggest that tal-1 and tal-2 are involved in the development of specific areas of the central nervous system.

Amino Acid Sequence↗
PubMed1999

Hepatoma-specific antitumor activity of an albumin enhancer/promoter regulated herpes simplex virus in vivo.

Targeting viral vectors to appropriate cell types so that normal cells are not adversely affected is an important goal for gene therapy. Previously, we described a novel approach to viral gene therapy using a conditional, replication-competent herpes simplex virus (HSV), where replication and associated cytotoxicity are limited to a specific cell-type by the regulated expression of an essential immediate-early viral gene product. In this report we analyze the hepatoma-specific replication, cytotoxicity and anti-tumor effect of recombinant HSV G92A, regulated by the albumin enhancer/promoter. G92A efficiently replicated in vitro in two human hepatoma cell lines expressing albumin, but not in four human non-hepatoma, albumin-non-expressing tumor cell lines, while all cell lines were equally susceptible to a tissue nonspecific HSV recombinant, hrR3. In vivo, G92A replicated well in subcutaneous xenografts of human hepatoma cells (Hep3B) in athymic mice, but not in non-hepatoma subcutaneous tumors (PC3 and HeLa), whereas, hrR3 replicated well in both tumor types. Intratumoral inoculation of G92A inhibited the growth of established subcutaneous hepatoma tumors in nude mice, but not prostate tumors. Replication-competent viral vectors controlled by cell-specific transcriptional regulatory sequences provide a new therapeutic strategy for tumor therapy.

Albumins↗
PubMed1996

An unusual cervical chordoma: CT and MRI.

We report CT and MRI findings of an unusual cervical chordoma. CT showed only minimal bony destruction with a lobulated prevertebral mass. Sagittal MRI, however, clearly demonstrated a lesion involving the body of C2 extending prevertebrally and into the spinal canal.

Aged↗