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Yutaka Uchida

Publications and source records attributed to Yutaka Uchida.

8 recordsLinked to original sources
PubMed2006

Collapsin response mediator protein 1 mediates reelin signaling in cortical neuronal migration.

Collapsin response mediator protein 1 (CRMP1) is one of the CRMP family members that mediates signal transduction of axon guidance molecules. Here, we show evidence that CRMP1 is involved in Reelin (Reln) signaling to regulate neuronal migration in the cerebral cortex. In crmp1-/- mice, radial migration of cortical neurons was retarded. This phenotype was not observed in the sema3A-/- and crmp1+/-;sema3A+/- cortices. However, CRMP1 was colocalized with disabled-1 (Dab1), an adaptor protein in Reln signaling. In the Reln(rl/rl) cortex, CRMP1 and Dab1 were expressed at a higher level, yet tyrosine phosphorylated at a lower level. Loss of crmp1 in a dab1 heterozygous background led to the disruption of hippocampal lamination, a Reeler-like phenotype. In addition to axon guidance, CRMP1 regulates neuronal migration by mediating Reln signaling.

Animals↗
PubMed2006

Regulation of dendritic branching and spine maturation by semaphorin3A-Fyn signaling.

A member of semaphorin family, semaphorin3A (Sema3A), acts as a chemorepellent or chemoattractant on a wide variety of axons and dendrites in the development of the nervous systems. We here show that Sema3A induces clustering of both postsynaptic density-95 (PSD-95) and presynaptic synapsin I in cultured cortical neurons without changing the density of spines or filopodia. Neuropilin-1 (NRP-1), a receptor for Sema3A, is present on both axons and dendrites. When the cultured neurons are exposed to Sema3A, the cluster size of PSD-95 is markedly enhanced, and an extensive colocalization of PSD-95 and NRP-1 or actin-rich protrusion is seen. The effects of Sema3A on spine morphology are blocked by PP2, an Src type tyrosine kinase inhibitor, but not by the PP3, the inactive-related compound. In the cultured cortical neurons from fyn(-/-) mice, dendrites bear few spines, and Sema3A does not induce PSD-95 cluster formation on the dendrites. Sema3A and its receptor genes are highly expressed during the synaptogenic period of postnatal days 10 and 15. The cortical neurons in layer V, but not layer III, show a lowered density of synaptic bouton-like structure on dendrites in sema3A- and fyn-deficient mice. The neurons of the double-heterozygous mice show the lowered spine density, whereas those of single heterozygous mice show similar levels of the spine density as the wild type. These findings suggest that the Sema3A signaling pathway plays an important role in the regulation of dendritic spine maturation in the cerebral cortex neurons.

Actins↗
PubMed2005

Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2: implication of common phosphorylating mechanism underlying axon guidance and Alzheimer's disease.

Collapsin response mediating protein-2 (CRMP2) has been identified as an intracellular protein mediating Semaphorin3A (Sema3A), a repulsive guidance molecule. In this study, we demonstrate that cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase 3beta (GSK3beta) plays a critical role in Sema3A signalling. In In vitro kinase assay, Cdk5 phosphorylated CRMP2 at Ser522, while GSK3beta did not induce any phosphorylation of CRMP2. Phosphorylation by GSK3beta was exclusively observed in Cdk5-phosphorylated CRMP2, but barely in CRMP2T509A. These results indicate that Cdk5 primarily phosphorylates CRMP2 at Ser522 and GSK3beta secondarily phosphorylates at Thr509. The dual-phosphorylated CRMP2, but not non-phosphorylated or single-phosphorylated CRMP2, is recognized with the antibody 3F4, which is highly reactive with the neurofibrillary tangles of Alzheimer's disease. 3F4 recognized the CRMP2 in the wild-type but not cdk5-/- mouse embryonic brain lysates. The phosphorylation of CRMP2 at Ser522 caused reduction of its affinity to tubulin. In dorsal root ganglion neurones, Sema3A stimulation enhanced the levels of the phosphorylated form of CRMP2 detected by 3F4. Over-expression of CRMP2 mutant substituting either Ser522 or Thr509 to Ala attenuates Sema3A-induced growth cone collapse response. These results suggest that the sequential phosphorylation of CRMP is an important process of Sema3A signalling and the same mechanism may have some relevance to the pathological aggregation of the microtubule-associated proteins.

Alzheimer Disease↗
PubMed2004

[The role of pharmacists for promotion of cancer chemotherapy in outpatients].

To promote cancer chemotherapy among outpatients, a special room for cancer chemotherapy (outpatient drip infusion room) was established in Yamaguchi University Hospital in April 2002. Since then, pharmacists have played a central role in all aspects, including decisions on the flow rate for prescriptions/injections, protocol checking, preparation of injections, aseptic preparation of anticancer agents, provision of information to patients, and financial impact analysis. In this study, we analyzed the current status of these activities and conducted a questionnaire survey regarding the involvement of pharmacists in chemotherapy at the outpatient clinic among patients and physicians. Pharmacists contributed to the administration of anticancer agents, including protocol checking and aseptic preparation, and no malpractice incident has occurred since the outpatient drip infusion room was established. According to responses from patients, 28 of 29 patients reported that they underwent treatment without anxiety. According to responses from physicians, 15 of 18 physicians considered the involvement of pharmacists beneficial. In addition, the amount claimed for health insurance as of March 2003 was 500000 yen, which was about 5-fold that before the establishment of the outpatient drip infusion room. These results suggest that pharmacists contribute to the promotion of cancer chemotherapy in outpatients with respect to the safety of medical practice, patient services, and hospital management. Therefore participation in cancer chemotherapy at the outpatient clinic may become a primary activity of pharmacists.

Antineoplastic Agents↗
PubMed2003

Supersensitive detection of sodium in water with use of dual-pulse laser-induced breakdown spectroscopy.

Laser-induced breakdown spectroscopy has been used to detect sodium (Na) in water. Laser-induced breakdown was formed by dual-pulse and crossed beam Nd:YAG lasers on a water film. To improve the detection sensitivity, the fluorescence intensity dependence on timing between laser pulses, the delay time of fluorescence detection timing, the gate width of fluorescence detection period, and the laser energy were investigated. Under the optimized conditions, the detection limit of Na in water was achieved in the range of 0.1 parts per billion. The developed system is applicable for quick and supersensitive detection of Na atoms in water.

Journal Article↗
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

[A checking system for injectable anticancer drugs using each patient's own data and its evaluation].

A checking system was developed for risk management of injectable anticancer drug use. Because the dosage and administration of injectable anticancer drugs vary with each patient, checking the prescription and aseptic i.v. admixing can be markedly complicated and time-consuming for pharmacists. The system we investigated in this study provided real-time checking of dosage, drip infusion rate, dosing periods, and dosing-free periods. The prescription parameters for this check included height, weight, body surface area, the medical history of each patient, the patient's ICD10 code' and disease indication from the package insert. Moreover, when preparing for aseptic i.v. admixing, the liquid volume after the anticancer drug has been mixed with other injectable drugs is calculated automatically. The time limits for stability after mixing and clinical laboratory test results are listed on the Work Sheet. As a result, 24 medication errors were prevented in the first 6 months of use of this system. These consisted of over- and under-doses, excessive dosing periods, insufficient dosing-free periods' etc. The time required for preparation of aseptic i.v. admixing decreased by 73% after introducing this system. Because clinical laboratory test results were referenced beforehand, patients to whom the drug should not be administered were recognized in advance. Thus 13 such cases were identified before i.v. admixing. Therefore this system may be useful in terms of rational anticancer drug use and risk management.

Antineoplastic Agents↗