Biomedical subjects

Takeshi Yagi

Publications and source records attributed to Takeshi Yagi.

61 records · Page 4Linked to original sources

PubMed2003

Nonspecific interstitial pneumonia in collagen vascular diseases: comparison of the clinical characteristics and prognostic significance with usual interstitial pneumonia.

BACKGROUND: Nonspecific interstitial pneumonia (NSIP) has recently been described as a distinct clinicopathological entity among idiopathic interstitial pneumonias (IIP), having more favorable prognosis than usual interstitial pneumonia (UIP). Although NSIP was initially reported to also occur in patients with interstitial pneumonia associated with collagen vascular diseases (IP-CVD), the prevalence of NSIP and its prognostic significance in IP-CVD remains to be determined. Thus, we attempted to clarify clinical characteristics and prognostic significance of NSIP in IP-CVD. METHODS: We histologically examined surgical lung biopsies from 43 patients with IP-CVD based on a current classification of interstitial pneumonias, and compared the clinical characteristics and prognostic significance of NSIP with UIP in IP-CVD. We also studied 98 patients with biopsy-proven NSIP and UIP in IIP, and compared the prognostic significance of histopathologic subclassification in IIP with that in IP-CVD. RESULTS: In IP-CVD, twenty-six patients (60%) were classified as NSIP, 17 (40%) as UIP. In contrast, 76 (77%) were categorized into UIP and 22 (23%) into NSIP of the patients with IIP. No significant difference in survival rates was observed between UIP and NSIP in IP-CVD (p = 0.3863), while, in IIP, NSIP has a significant better survival than UIP (p = 0.022). CONCLUSIONS: These results suggest that NSIP is more common histologic pattern than UIP in IP-CVD and, unlike in IIP, the prognosis of NSIP patients may not be different from that of UIP patients in IP-CVD.

Aged↗

PubMed2002

Cutting edge: Fyn is essential for tyrosine phosphorylation of Csk-binding protein/phosphoprotein associated with glycolipid-enriched microdomains in lipid rafts in resting T cells.

In resting T cells, Csk is constitutively localized in lipid rafts by virtue of interaction with a phosphorylated adaptor protein, Csk-binding protein (Cbp)/phosphoprotein associated with glycolipid-enriched microdomains, and sets an activation threshold in TCR signaling. In this study, we examined a kinase responsible for Cbp phosphorylation in T cell membrane rafts. By analyzing T cells from Fyn-/- mice, we clearly demonstrated that Fyn, but not Lck, has its kinase activity in membrane rafts, and plays a critical role in Cbp phosphorylation, Cbp-Csk interaction, and Csk kinase activity. Naive CD44(low)CD62 ligand(high) T cells were substantially reduced in Fyn-/- mice, presumably due to the inhibition of Cbp phosphorylation. Thus, Fyn mediates Cbp-Csk interaction and recruits Csk to rafts by phosphorylating Cbp. Csk recruited to rafts would then be activated and inhibit the kinase activity of Lck to keep resting T cells in a quiescent state. Our results elucidate a negative regulatory role for Fyn in proximal TCR signaling in lipid rafts.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex.

Semaphorin-3A (Sema3A), a member of class 3 semaphorins, regulates axon and dendrite guidance in the nervous system. How Sema3A and its receptors plexin-As and neuropilins regulate neuronal guidance is unknown. We observed that in fyn- and cdk5-deficient mice, Sema3A-induced growth cone collapse responses were attenuated compared to their heterologous controls. Cdk5 is associated with plexin-A2 through the active state of Fyn. Sema3A promotes Cdk5 activity through phosphorylation of Tyr15, a phosphorylation site with Fyn. A Cdk5 mutant (Tyr15 to Ala) shows a dominant-negative effect on the Sema3A-induced collapse response. The sema3A gene shows strong interaction with fyn for apical dendrite guidance in the cerebral cortex. We propose a signal transduction pathway in which Fyn and Cdk5 mediate neuronal guidance regulated by Sema3A.

Animals↗

PubMed2002

Wengen, a member of the Drosophila tumor necrosis factor receptor superfamily, is required for Eiger signaling.

We identified Wengen, the first member of the Drosophila tumor necrosis factor receptor (TNFR) superfamily. Wengen is a type III membrane protein with conserved cysteine-rich residues (TNFR homology domain) in the extracellular domain, a hallmark of the TNFR superfamily. wengen mRNA is expressed at all stages of Drosophila development. The small-eye phenotype caused by an eye-specific overexpression of a Drosophila TNF superfamily ligand, Eiger, was dramatically suppressed by down-regulation of Wengen using RNA interference. In addition, Wengen and Eiger physically interacted with each other through their TNFR homology domain and TNF homology domain, respectively. These results suggest that Wengen can act as a component of a functional receptor for Eiger. Our identification of Wengen and further genetic analysis should provide increased understanding of the evolutionarily conserved roles of TNF/TNFR superfamily proteins in normal development, as well as in some pathophysiological conditions.

Amino Acid Sequence↗

PubMed2002

Light-potentiation of acoustic startle response (ASR) and monoamine efflux related to fearfulness in Fyn-deficient mice.

Fyn tyrosine kinase deficient mice are known to show increased fearfulness. We investigated the fear response of these mice using the light-potentiation of the acoustic startle response (ASR) and examined its neurochemical correlates using in vivo microdialysis. Female homozygous Fyn-deficient mice showed an enhancement of the startle amplitude under a bright light while heterozygotes and wild-types did not show such a change. Along with these behavioral findings, the homozygous Fyn-deficient mice showed an increase in extracellular serotonin (5-HT) and dopamine (DA) in the prefrontal cortex and 5-HT in the hippocampus when they were exposed to bright light, while heterozygous and wild-type mice did not show such changes. These results suggest that the increased fearfulness of Fyn-deficient mice is related to enhanced serotonergic and dopaminergic activity in the prefrontal cortex and limbic system.

Animals↗

PubMed2002

Fyn tyrosine kinase in Sertoli cells is involved in mouse spermatogenesis.

Fyn is a member of the Src family of non-receptor-type tyrosine kinases and plays an important role in signal transductions regulating cell proliferation and differentiation. Fyn immunoreactivity was localized in the Sertoli cells of mouse testes. Although fyn-deficient adult male mice were fertile, a significant reduction in testis weight and degenerated germ cells were observed at 3 and 4 wk of age. Electron microscopic examination revealed that fyn -/- testis has ultrastructural abnormalities in the specialized junctional structures of the Sertoli cells, the ectoplasmic specializations. Unusual vesicular structures were found in the actin filament layers of the ectoplasmic specializations of mutant mice. Immunohistochemical studies demonstrated that both Fyn and actin filaments were concentrated in the areas of ectoplasmic specializations. At these sites, a high level of phosphotyrosine was also immunostained in wild-type testes, whereas phosphotyrosine immunoreactivity was reduced in fyn -/- testes. Immunoblot analyses revealed that Fyn was mainly distributed within the Triton X-100-insoluble cytoskeletal fraction prepared from wild-type testes, suggesting that Fyn might be associated with cytoskeletal proteins such as actin filaments. These findings suggest that Fyn kinase functions at the ectoplasmic specializations of the Sertoli cells in the testes, regulating the dynamics of cytoskeletal proteins. Fyn-mediated signal transduction in the Sertoli cells may affect the survival and differentiation of germ cells at a specific stage during spermatogenesis.

Actins↗

PubMed2002

Requirement of neuropilin 1-mediated Sema3A signals in patterning of the sympathetic nervous system.

Neuropilin 1 is the specific receptor for Sema3A and plays a role in nerve fiber guidance. We report that neuropilin 1 and Sema3A mutant mouse embryos, generated by targeted gene disruption, showed displacement of sympathetic neurons and their precursors and abnormal morphogenesis in the sympathetic trunk. We also show that Sema3A suppressed the cell migration activity of sympathetic neurons from wild-type but not neuropilin 1 mutant embryos in vitro and instead promoted their accumulation into compact cell masses and fasciculation of their neurites. These findings suggest that the neuropilin 1-mediated Sema3A signals regulate arrest and aggregation of sympathetic neuron precursors and sympathetic neurons themselves at defined target sites and axon fasciculation to produce the stereotyped sympathetic nerve pattern.

Animals↗