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Yosuke Tanaka

Publications and source records attributed to Yosuke Tanaka.

11 recordsLinked to original sources
PubMed2003

Kinesin superfamily protein 2A (KIF2A) functions in suppression of collateral branch extension.

Through interactions with microtubules, the kinesin superfamily of proteins (KIFs) could have multiple roles in neuronal function and development. During neuronal development, postmitotic neurons develop primary axons extending toward targets, while other collateral branches remain short. Although the process of collateral branching is important for correct wiring of the brain, the mechanisms involved are not well understood. In this study, we analyzed kif2a(-/-) mice, whose brains showed multiple phenotypes, including aberrant axonal branching due to overextension of collateral branches. In kif2a(-/-) growth cones, microtubule-depolymerizing activity decreased. Moreover, many individual microtubules showed abnormal behavior at the kif2a(-/-) cell edge. Based on these results, we propose that KIF2A regulates microtubule dynamics at the growth cone edge by depolymerizing microtubules and that it plays an important role in the suppression of collateral branch extension.

Animals↗
PubMed2003

Endovascular stent-graft repair for penetrating atherosclerotic ulcer in the infrarenal abdominal aorta.

PURPOSE: Penetrating atherosclerotic ulcer (PAU) is an ulceration of an atherosclerotic plaque penetrating through the intima, which may lead to intramural hematoma, aneurysm formation, or rupture. This disease is predominantly found in the thoracic aorta and is uncommon in the infrarenal aorta. The effectiveness of endovascular repair of PAU in the infrarenal aorta was retrospectively investigated. METHODS: From 1999 to 2002, PAU was diagnosed with computed tomography and magnetic resonance imaging in the abdominal aorta in four patients. All patients were men; their average age was 78 years. All four patients had hypertension, and two patients had concomitant coronary artery disease. Three patients had abdominal pain or lumbago. RESULTS: All patients underwent endovascular grafting with a Gianturco Z-stent covered with thin-wall woven Dacron graft. Indications for endovascular intervention were aneurysm formation with or without intramural hematoma in two patients and contained rupture with extraaortic hematoma in two patients. The postoperative course was uneventful in all cases, and no endoleak or aneurysm expansion was recognized during follow-up (4-32 months; average, 14 months). CONCLUSIONS: Infrarenal aortic lesions caused by PAU were generally localized, and endovascular grafting appears to be a feasible alternative to surgical repair.

Aged↗
PubMed2002

Influence of interleukin-12 receptor beta1 polymorphisms on tuberculosis.

Host genetic factors may be important determinants of susceptibility to tuberculosis, and several candidate gene polymorphisms have been shown to date. A series of recent reports concerning rare human deficiencies in the type-1 cytokine pathway suggest that more subtle variants of relevant genes may also contribute to susceptibility to tuberculosis at the general population level. To investigate whether polymorphisms in the interleukin-12 receptor (IL-12R) gene predispose individuals to tuberculosis, we studied these genes by single-strand conformational polymorphism analysis and direct sequencing. Although no common polymorphisms could be identified in the IL-12R beta 2 gene ( IL-12RB2), we confirmed four single nucleotide polymorphisms (SNPs; 641A-->G, 684C-->T, 1094T-->C, and 1132G-->C) causing three missense variants (Q214R, M365T, G378R) and one synonymous substitution in the extracellular domain of the IL-12R beta 1 gene ( IL12RB1). All SNPs were in almost perfect linkage disequilibrium (D'=0.98), and two common haplotypes of IL12RB1(allele 1: Q214-M365-G378; allele 2: R214-T365-R378) were revealed. Polymerase chain reaction/restriction fragment length polymorphism and sequence analyses were used to type IL12RB1polymorphisms in 98 patients with tuberculosis and 197 healthy controls in Japanese populations. In our case-control association study of tuberculosis, the R214-T365-R378 allele (allele 2) was over-represented in patients with tuberculosis, and homozygosity for R214-T365-R378 (the 2/2 genotype) was significantly associated with tuberculosis (odds ratio: 2.45; 95% CI: 1.20-4.99; P=0.013). In healthy subjects, homozygotes for R214-T365-R378 had lower levels of IL-12-induced signaling, according to differences in cellular responses to IL-12 between two haplotypes. These data suggest that the R214-T365-R378 allele, i.e., variation in IL12RB1, contribute to tuberculosis susceptibility in the Japanese population. This genetic variation may predispose individuals to tuberculosis infection by diminishing receptor responsiveness to IL-12 and to IL-23, leading to partial dysfunction of interferon-gamma-mediated immunity.

Adult↗
PubMed2002

Role of KIFC3 motor protein in Golgi positioning and integration.

KIFC3, a microtubule (MT) minus end-directed kinesin superfamily protein, is expressed abundantly and is associated with the Golgi apparatus in adrenocortical cells. We report here that disruption of the kifC3 gene induced fragmentation of the Golgi apparatus when cholesterol was depleted. Analysis of the reassembly process of the Golgi apparatus revealed bidirectional movement of the Golgi fragments in both wild-type and kifC3-/- cells. However, we observed a markedly reduced inwardly directed motility of the Golgi fragments in cholesterol-depleted kifC3-/- cells compared with either cholesterol-depleted wild-type cells or cholesterol-replenished kifC3-/- cells. These results suggest that (a) under the cholesterol-depleted condition, reduced inwardly directed motility of the Golgi apparatus results in the observed Golgi scattering phenotype in kifC3-/- cells, and (b) cholesterol is necessary for the Golgi fragments to attain sufficient inwardly directed motility by MT minus end-directed motors other than KIFC3, such as dynein, in kifC3-/- cells. Furthermore, we showed that Golgi scattering was much more drastic in kifC3-/- cells than in wild-type cells to the exogenous dynamitin expression even in the presence of cholesterol. These results collectively demonstrate that KIFC3 plays a complementary role in Golgi positioning and integration with cytoplasmic dynein.

Animals↗
PubMed2002

Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites.

In cells, molecular motors operate in polarized sorting of molecules, although the steering mechanisms of motors remain elusive. In neurons, the kinesin motor conducts vesicular transport such as the transport of synaptic vesicle components to axons and of neurotransmitter receptors to dendrites, indicating that vesicles may have to drive the motor for the direction to be correct. Here we show that an AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) receptor subunit--GluR2-interacting protein (GRIP1)--can directly interact and steer kinesin heavy chains to dendrites as a motor for AMPA receptors. As would be expected if this complex is functional, both gene targeting and dominant negative experiments of heavy chains of mouse kinesin showed abnormal localization of GRIP1. Moreover, expression of the kinesin-binding domain of GRIP1 resulted in accumulation of the endogenous kinesin predominantly in the somatodendritic area. This pattern was different from that generated by the overexpression of the kinesin-binding scaffold protein JSAP1 (JNK/SAPK-associated protein-1, also known as Mapk8ip3), which occurred predominantly in the somatoaxon area. These results indicate that directly binding proteins can determine the traffic direction of a motor protein.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Mouse models of Charcot-Marie-Tooth disease.

A common peripheral neuropathy, Charcot-Marie-Tooth disease, progressively develops with distal muscle atrophy. Several genes expressed in Schwann cells and neurons have been identified to be responsible for this hereditary disease, and used in generating transgenic and knockout mice. Such mice are good disease models for cell biological and therapeutic studies.

Animals↗
PubMed2002

Molecular motor KIF1C is not essential for mouse survival and motor-dependent retrograde Golgi apparatus-to-endoplasmic reticulum transport.

KIF1C is a new member of the kinesin superfamily of proteins (KIFs), which act as microtubule-based molecular motors involved in intracellular transport. We cloned full-length mouse kif1C cDNA, which turned out to have a high homology to a mitochondrial motor KIF1Balpha and to be expressed ubiquitously. To investigate the in vivo significance of KIF1C, we generated kif1C(-/-) mice by knocking in the beta-galactosidase gene into the motor domain of kif1C gene. On staining of LacZ, we detected its expression in the heart, liver, hippocampus, and cerebellum. Unexpectedly, kif1C(-/-) mice were viable and showed no obvious abnormalities. Because immunocytochemistry showed partial colocalization of KIF1C with the Golgi marker protein, we compared the organelle distribution in primary lung fibroblasts from kif1C(+/+) and kif1C(-/-) mice. We found that there was no significant difference in the distribution of the Golgi apparatus or in the transport from the Golgi apparatus to the endoplasmic reticulum (ER) facilitated by brefeldin A between the two cells. This retrograde membrane transport was further confirmed to be normal by time-lapse analysis. Consequently, KIF1C is dispensable for the motor-dependent retrograde transport from the Golgi apparatus to the ER.

Amino Acid Sequence↗
PubMedDate not supplied

Thin-section CT evaluation and pathologic correlation of therapeutic effect of neoadjuvant chemotherapy for axillary lymph nodes of clinically node-positive breast cancer patients.

In breast cancer patients, the number of surgically resected metastatic axillary lymph nodes has been considered to correlate closely with patient prognosis. Therefore, if metastatic lymph nodes could be controlled by neoadjuvant chemotherapy pre-operatively, we would be able to select a more appropriate regimen of post-operative chemotherapy for the individual patient and expect prognostic advantages of each patient with node-positive breast cancer. In this study, we aimed to evaluate the therapeutic effect of neoadjuvant chemotherapy for metastatic lymph nodes of node-positive breast cancer patients, using thin-section (5 mm) helical CT (prone-position) with bolus injection of contrast agent. Between April 1994 and March 2002, 49 patients with node-positive breast cancer who had undergone thin-section CT study both before and following neoadjuvant chemotherapy enrolled in the study. The mean age of the patients was 48.9 years and all were female. Concerning metastatic lymph nodes status, 45 patients were classified as N1, 2 patients as N2, and another 2 as N3. In the evaluation, if at least one lymph node of >5 mm in the short diameter was detected on the CT study, the case was classified as node-positive. For lymph nodes of >1 cm in short diameter, fine-needle aspiration biopsy guided by ultrasonography was performed in order to obtain pathological confirmation of the existence of cancer metastasis. The diagnostic results of the CT study were compared with the pathologic findings of the resected specimen operatively. The neoadjuvant chemotherapy consisted of 3 to 4 times of CAF chemotherapy and an anti-estrogen agent, and intra-arterial infusion chemotherapy was also performed in patients with lymph node status of N2 or N3. The axillary status of 15 (30.6%) out of the 49 patients was evaluated as N0 after neoadjuvant chemotherapy, and 14 out of the 15 patients were confirmed as node-negative based on the pathological results. Therefore, the diagnostic accuracy of the second CT study performed following the neoadjuvant chemotherapy was 85.7%, with a sensitivity of 96.6%, a specificity of 70.0%, a positive predictive value of 82.4%, and a negative predictive value of 93.3%. The results described above demonstrate that such a sophisticated and precise CT study performed following neoadjuvant chemotherapy and evaluating the therapeutic effect on metastatic lymph nodes following the neoadjuvant chemotherapy can help to determine an appropriate regimen of post-operative chemotherapy and be of prognostic advantage in patients with node-positive breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

CT findings of breast cancer with clinically complete response following neoadjuvant chemotherapy--histological correlation.

In breast cancer patients, several regimens of neoadjuvant chemotherapy have been developed in order to achieve prognostic advantages for individual patients. Though some percentages of breast cancer patients show clinically complete response to neoadjuvant chemotherapy, the histopathological specimens of these patients demonstrate a considerably high frequency of the existence of residual disease. In this study, we aimed to evaluate the therapeutic effect of neoadjuvant chemotherapy for breast cancer patients showing clinically complete response (cCR) to neoadjuvant chemotherapy, using thin-section (5 mm) helical CT (prone position) with bolus injection of contrast agent. Between April 1994 and March 2002, 9 patients with breast cancer showing cCR to the neoadjuvant chemotherapy, who had undergone thin-section CT study both before and following neoadjuvant chemotherapy, enrolled in the study. The mean age of the patients was 46.2 years and all of them were female. The clinical stages were, 8 patients in stage II, and one in stage IIIA. In the CT evaluation, residual disease was visualized in 5 out of the 9 patients. Histopathological examination disclosed the existence of residual cancers in 6 out of the 9 patients, but only non-invasive cancer was revealed in 1 out of the 6. As patients having residual disease composed only of non-invasive cancer are classified into the pathologically complete response group according to the WHO classification, 4 out of these 9 patients showing clinically complete response to the neoadjuvant chemotherapy were classified into pCR (pathologically complete response) group, and another 5 were classified into the pPR (pathologically partial response) group. As a result, the diagnostic accuracy of the second CT study performed after neoadjuvant chemotherapy was evaluated as 77.8%, with a sensitivity of 80.0%, a specificity of 75.0%, a positive predictive value (PPV) of 80.0%, and a negative predictive value (NPV) of 75.0%. Therefore, for precise evaluation of the neoadjuvant chemotherapeutic effect for breast cancer, thin-section CT studies are considered to be essential.

Adult↗