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Biomedical subjects

Akira Kudo

Publications and source records attributed to Akira Kudo.

41 records · Page 3Linked to original sources

The pre-B cell receptor signaling for apoptosis is negatively regulated by Fc gamma RIIB.

Many studies have shown that FcgammaRIIB is a negative regulator of B cell receptor signaling, and even though FcgammaRIIB is expressed through all developmental stages of the B cell lineage, its involvement in pre-B cell receptor (pre-BCR) signaling has not been examined. To investigate FcgammaRIIB function at the pre-B cell stage, we have established pre-BCR positive pre-B cell lines from normal mice and FcgammaRIIB-deficient mice, named PreBR and Fcgamma(-/-)PreBR, respectively. These cell lines are able to differentiate into immature B cells in vitro by removal of IL-7. In PreBR, apoptosis was moderately induced by F(ab')(2) anti-mu Ab, but not by intact anti-mu Ab. Phosphorylation of SH2-containing inositol 5-phosphatase (SHIP) and Dok, which are involved in FcgammaRIIB signaling, was induced by anti-mu cross-linking in PreBR. In contrast, apoptosis was strongly induced by both the F(ab')(2) and intact anti-mu Abs in Fcgamma(-/-)PreBR, and the level of phosphorylation of SHIP or Dok was much lower in Fcgamma(-/-)PreBR than those observed in PreBR. Restoration of FcgammaRIIB to Fcgamma(-/-)PreBR followed by anti-mu cross-linking blocked severe apoptosis, and up-regulated SHIP and Dok phosphorylation. The results demonstrate that FcgammaRIIB negatively regulates pre-BCR-mediated signaling for apoptosis.

Animals↗

A novel mechanism for the regulation of osteoblast differentiation: transcription of periostin, a member of the fasciclin I family, is regulated by the bHLH transcription factor, twist.

Periostin is a secreted protein that is highly expressed in early osteoblastic cells in vitro and in periosteum and periodontal ligament tissues in vivo. It is known that periostin supports cellular adhesion and spreading in vitro. Although, the mechanisms of transcriptional regulation of periostin are poorly understood, gene-profiling data have revealed that overexpression of Twist, a basic helix-loop-helix (bHLH) transcription factor, resulted in increased periostin expression as validated by Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses. Twist is an important transcription factor for cell type determination and differentiation and has been shown to play an important regulatory role in early osteogenesis. In situ hybridization of mouse calvarial bones indicated that periostin and Twist mRNA are co-localized at the osteogenic fronts of calvarial bones. To characterize the 5' flanking region of the periostin gene, primer extension was carried out to identify the transcription start site, and DNA sequence analysis confirmed the presence of a 'Twist-box' response element. The results of electrophoretic mobility shift assay (EMSA) using nuclear extracts of MC3T3-E1 cells revealed that Twist bound to the Twist-box sequence on the periostin promoter. In vivo footprinting experiments using ligation-mediated PCR (LM-PCR) indicated that the Twist-box sequence was protected in undifferentiated MC3T3-E1 preosteoblasts but not in differentiated MC3T3-E1 osteoblasts. To determine whether Twist actually regulates the periostin expression, 293T cells were transiently co-transfected with the periostin promoter construct and the human Twist expression vector. Reporter analysis indicated that the periostin promoter activities were enhanced by overexpression of Twist. These data suggest that Twist can bind to the periostin promoter in undifferentiated preosteoblasts and up-regulate periostin expression, consistent with the up-regulation of periostin expression by Twist as observed in the gene-profiling data.

5' Flanking Region↗

Expression of zisp, a DHHC zinc finger gene, in somites and lens during zebrafish embryogenesis.

The zebrafish zisp gene encodes a putative transmembrane protein with a DHHC zinc finger motif. At the segmentation period zisp is expressed in the adaxial cells and the somites in a striping pattern. The zisp transcripts are localized to the posterior parts within the individual somites. In fused somites mutants, zisp is expressed throughout the somitic mesoderm. These expression patterns are similar to those of myoD. In addition to the somitic expression, the zisp expression was observed in lens cells at the late segmentation period and the early pharyngula period.

Animals↗

Expression of zisp, a DHHC zinc finger gene, in somites and lens during zebrafish embryogenesis.

The zebrafish zisp gene encodes a putative transmembrane protein with a DHHC zinc finger motif. At the segmentation period zisp is expressed in the adaxial cells and the somites in a striping pattern. The zisp transcripts are localized to the posterior parts within the individual somites. In fused somites mutants, zisp is expressed throughout the somitic mesoderm. These expression patterns are similar to those of myoD. In addition to the somitic expression, the zisp expression was observed in lens cells at the late segmentation period and the early pharyngula period.

Amino Acid Sequence↗

Amino acid concentrations in the blood of the jugular vein and peripheral artery after traumatic brain injury: decreased release of glutamate into the jugular vein in the early phase.

The gross behavior of excitatory amino acids in patients with traumatic brain injury (TBI), including uptake, transport, metabolism, and clearance, was investigated by analysis of the levels of 41 amino acids in the blood of the jugular vein (JV), which is the primary venous drainage conduit of the brain, and a peripheral artery. Blood samples from the JV and a peripheral artery of eight patients with TBI were collected at 6 h, 6 to 24 h, and over 24 h after TBI, and analyzed using high performance liquid chromatography. Blood samples from 101 normal subjects were also measured. The levels of glutamate (Glu), gamma-aminobutyric acid (GABA), aspartate, glutamine, and cystine deviated from the normal range, and were considered pathological. The level of Glu in the JV was significantly lower than that in the artery (p < 0.05), and the level of GABA in the JV was significantly higher than that in the artery (p < 0.01), but the other three amino acids showed no significant differences. Significantly chronological changes in the difference between the blood levels in the JV and artery were observed for Glu. Measurement of the Glu level in the JV and artery may indicate gross metabolic change in the brain following TBI.

Adolescent↗