PubMed Health⌕ Search

Biomedical subjects

Y Minami

Publications and source records attributed to Y Minami.

At least 19 recordsLinked to original sources
PubMed2000

Mouse Ror2 receptor tyrosine kinase is required for the heart development and limb formation.

BACKGROUND: A mouse receptor tyrosine kinase (RTK), mRor2, which belongs to the Ror-family of RTKs consisting of at least two structurally related members, is primarily expressed in the heart and nervous system during mouse development. To elucidate the function of mRor2, we generated mice with a mutated mRor2 locus. RESULTS: Mice with a homozygous mutation in mRor2 died just after birth, exhibiting dwarfism, severe cyanosis, and short limbs and tails. Whole-mount in situ hybridization analysis showed that mRor2 was expressed in the branchial arches, heart and limb/tailbuds, in addition to the developing nervous system. The mutants had cardiac septal defects, mainly a ventricular septal defect. In addition, an examination of the skeletal systems revealed that the mutants had shorter limbs, vertebrae and facial structure, with a particular defect in their distal portions, and that almost no calcification was observed in their distal limbs. Histological examination showed abnormalities in the chondrocytes. CONCLUSIONS: Our findings suggest that mRor2 plays essential roles in the development of the heart and in limb/tail formation, in particular cardiac septal formation and ossification of distal portions of limbs and tails.

Animals↗
PubMed1999

H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells.

The adhesive function of integrins is regulated through cytoplasmic signaling. The present study was performed to investigate the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemokines. Adhesion of T cells induced by chemokines macrophage inflammatory protein (MIP)-1alpha and MIP-1beta was inhibited by pertussis toxin, wortmannin, and cytochalasin B, suggesting that both G protein-sensitive phosphatidylinositol (PI) 3-kinase activation and cytoskeletal assemblies are involved. The chemokine-induced T cell adhesion could be mimicked by expression of small G proteins, fully activated H-RasV12, or H-RasV12Y40C mutant, which selectively binds to PI 3-kinase, in T cells, inducing activated form of LFA-1alpha and LFA-1-dependent adhesion to ICAM-1. H-Ras expression also induced F-actin polymerization which colocalized with profilin in T cells. Adult T cell leukemia (ATL) cells spontaneously adhered to ICAM-1, which depended on endogenous MIP-1alpha and MIP-1beta through activation of G protein-sensitive PI 3-kinase. H-Ras signal pathway, leading to PI 3-kinase activation, also induced active configuration of LFA-1 and LFA-1-mediated adhesion of ATL cells, whereas expression of a dominant-negative H-Ras mutant failed to do. Profilin-dependent spontaneous polymerization of F-actin in ATL cells was reduced by PI 3-kinase inhibitors. In this paper we propose that H-Ras-mediated activation of PI 3-kinase can be involved in induction of LFA-1-dependent adhesion of T cells, which is relevant to chemokine-mediated signaling, and that profilin may form an important link between chemokine- and/or H-Ras-mediated signals and F-actin polymerization, which results in triggering of LFA-1 on T cells or leukemic T cells.

Actins↗
PubMed1999

A novel role for H-Ras in the regulation of very late antigen-4 integrin and VCAM-1 via c-Myc-dependent and -independent mechanisms.

Despite extensive studies on the crucial functions of Ras and c-Myc in cellular proliferation and transformation, their roles in regulating cell adhesion are not yet fully understood. Involvement of Ras in modulating integrin activity by inside-out signaling has been recently reported. However, in contrast to R-Ras, H-Ras was found to exhibit a suppressive effect. Here we show that ectopic expression of a constitutively active H-Rasv12, but not c-Myc alone, in a hemopoietic cell line induces activation of very late Ag-4 (VLA-4, alpha4beta1) integrin without changing its surface expression. Intriguingly, coexpression of H-Rasv12 and c-Myc in these cells results in not only the activation of VLA-4, but also the induction of expression of VCAM-1, the counterreceptor for VLA-4, thereby mediating a marked homotypic cell aggregation. In addition, H-Rasv12-induced VLA-4 activation appears to be partly down-regulated by coexpression with c-Myc. Our results represent an unprecedented example demonstrating a novel role for H-Rasv12 in the regulation of cell adhesion via c-Myc-independent and -dependent mechanisms.

Adjuvants, Immunologic↗
PubMed1999

Coronary arteriovenous fistulas with giant aneurysm: two case reports.

Coronary arteriovenous fistulas are rare, particularly in association with coronary aneurysms. Two rare cases of patients with coronary arteriovenous fistulas and giant aneurysmal formation are described. A right coronary fistula that drained into the superior vena cava was demonstrated in one patient. The remaining patient had a documented left coronary fistula that drained into a main pulmonary artery and had evidence of several plexal vessels that transversed through the pulmonary trunk and toward the pericardial reflex. Under cardiopulmonary bypass, the fistulas and plexal vessels were successfully ligated without any injury to the native coronary circulation.

Adult↗
PubMed1999

Modulation of mPer1 gene expression by anxiolytic drugs in mouse cerebellum.

1. The mPer1 and mPer2 genes are putative mouse clock genes that regulate circadian oscillator present in the suprachiasmatic nucleus (SCN) neuron. While they are also expressed in the granular cell layer in the cerebellum, their function is unknown. In a first step to verify the physiological roles of mPer1 and mPer2 genes in the cerebellum, we examined the effects of benzodiazepines on the expression of the mPer1 and mPer2 genes. 2. mPer2 mRNA expression was higher at ZT16 than ZT4 in the mouse cerebellum. 3. High-dose administration of diazepam (10 mg kg-1) or triazolam (1 mg kg-1) reduced mPer1 mRNA level 1 h after treatment in the cerebellum. 4. Reduced expression of mPer1 by diazepam treatment was transient. No difference of mPer1 mRNA level between diazepam (10 mg kg-1)- and vehicle-treated group was observed 6 h after treatment. 5. Administration of high doses of tandospirone (30 mg kg-1), a non-benzodiazepine anxiolytic also reduced mPer1 mRNA expression 1 h after treatment. 6. Administration of high doses of clozapine (5 mg kg-1) or haloperidol (1 mg kg-1) impaired the rota-rod performance without affecting on mPer1 mRNA level. 7. Diazepam and tandospirone inhibited the expression of mPer1 mRNA in the primary cultured cerebellum granule cells. 8. Transient reductions of mPer1 mRNA levels by various benzodiazepines and tandospirone is associated with impairment of coordinated movement, such as rota-rod performance and equilibrium.

Animals↗
PubMed1999

Spatio-temporally regulated expression of receptor tyrosine kinases, mRor1, mRor2, during mouse development: implications in development and function of the nervous system.

BACKGROUND: Drosophila neurospecific receptor tyrosine kinases (RTKs), Dror and Dnrk, as well as Ror1 and Ror2 RTKs, isolated from human neuroblastoma, have been identified as a structurally related novel family of RTKs (Ror-family RTKs). Thus far, little is known about the expression and function of mammalian Ror-family RTKs. RESULTS: We have identified murine Ror-family RTKs, mRor1 and mRor2. Both mRor1 and mRor2 genes are induced upon neuronal differentiation of P19EC cells. During neuronal differentiation in vitro, the expression of mRor2 is transiently induced, although that of mRor1 increases continuously. During embryogenesis, the mRor1 gene is expressed in the developing nervous system within restricted regions and in the developing lens epithelium. The expression of mRor1 is sustained in the nervous system and is also detected in non-neuronal tissues after birth. In contrast, the expression of mRor2 is detected mainly in the developing nervous system within broader regions and declines after birth. Possible relationships of mRor1 and mRor2 genes with previously identified mutants have also been examined. CONCLUSIONS: The developmental expressions of mRor1 and mRor2, in particular in the nervous system, are differentially regulated, reflecting their expression patterns in vitro. mRor1 and mRor2 may thus play differential roles during the development of the nervous system.

Amino Acid Sequence↗
PubMed1999

Hsc70/Hsp40 chaperone system mediates the Hsp90-dependent refolding of firefly luciferase.

BACKGROUND: The 90-kDa heat shock protein, Hsp90, was previously shown to capture firefly luciferase during thermal inactivation, thereby preventing its irreversible off-pathway aggregation and maintaining it in a folding-competent state. However, subsequent refolding of the luciferase required addition of rabbit reticulocyte lysate. RESULTS: Here we demonstrate that Hsc70 (cytosolic Hsp70) and Hsp40/Hdj1 (cytosolic DnaJ homologue) are the effective components in a reticulocyte lysate, while other unidentified factor in the lysate is also required for the refolding of Hsp90-captured luciferase. Though another cytosolic DnaJ homologue, Hdj2/HSDJ, was more efficient than Hsp40 in suppressing the aggregation of rhodanese, Hdj2 was less effective for the refolding of luciferase than Hsp40. In the absence of the third factor, Hsp40 could bind to the luciferase captured by Hsp90, which suggested that Hsp40 on its own was able to bind the substrate protein, but Hsc70 could not. CONCLUSIONS: Hsc70, Hsp40 and at least another additional component in the reticulocyte lysate are necessary for full accomplishment of the refolding of Hsp90-captured luciferase. The third factor may be required for the loading of Hsc70 on to the substrate protein bound to Hsp90.

Animals↗
PubMed1999

Protein tyrosine kinase Lyn mediates apoptosis induced by topoisomerase II inhibitors in DT40 cells.

Several sets of non-receptor protein tyrosine kinases (PTK) play important roles in apoptosis induced by various extracellular stresses. Anti-cancer drugs induce cellular DNA damage and cytotoxic events, leading to apoptotic cell death. We utilized the established chicken B cell line, DT40 cells and their derived mutants, lacking the respective PTK [DT40/Syk(-), DT40/Lyn(-) and DT40/Btk(-)], to examine a role of these PTK in apoptotic processes induced by anti-cancer drugs. All anti-cancer drugs examined induced apoptosis of wild-type DT40 cells. Interestingly,DT40/Lyn(-), but not DT40/Syk(-) and DT40/Btk(-) cells, become resistant to apoptosis induced by adriamycin and etoposide, topoisomerase II (Topo II) inhibitory agents, compared to wild-type DT40 cells, as assessed by DNA fragmentation and TUNEL analyses. Ectopic expression of Fyn, another Src family member, in DT40/Lyn(-) cells restores largely the susceptibility of the cells against Topo II inhibitor-induced apoptosis. Furthermore, it was found that Topo II inhibitors activate c-Jun N-terminal kinase (JNK) slightly in both wild-type and DT40/Lyn(-) cells to similar extents. Collectively, these results suggest that Lyn is involved in Topo II inhibitor-induced apoptotic signaling in DT40 cells independent of JNK.

Animals↗
PubMed1999

Risk of breast cancer in Japanese women with benign breast disease.

To investigate the risk of breast cancer development in women with benign breast disease (BBD), 387 screen-detected BBD women and 1,489 normal women, taken from participants in the breast cancer screening program during 1978-1986, were followed through 1991. While 2,811 person-years in the BBD group and 11,018 person-years in the normal group were accumulated, 5 women in the BBD group and 6 women in the normal group developed breast cancer. Using the Mantel-Haenszel method, relative risks (RR) were estimated for all women with BBD and women in some BBD types. Significantly elevated risk of breast cancer was observed in all women with BBD (RR = 3.26, 95% confidence interval (CI) 1.08-9.83). Women with proliferative BBD were at high risk of breast cancer (RR = 8.48, 95% CI 2.99-24.10), but no increased risk was observed for women with non-proliferative BBD (RR = 0.93, 95% CI 0.11-7.66). These results are consistent with those in high-risk countries for breast cancer. In the management of women with BBD, histopathological diagnosis of the breast lesion is essential and women with proliferative BBD should be followed up carefully.

Adult↗
PubMed1999

Paraganglioma of the urinary bladder: A case report and review of the Japanese literature.

We describe a patient with primary paraganglioma of the urinary bladder associated with typical clinical symptoms. Systolic blood pressure frequently increased to 300 mm Hg immediately after micturition. Levels of urinary vanillylmandelic acid excretion and serum norepinephrine were significantly elevated. The tumor was removed by partial cystectomy. Histological examination of the tumor revealed paraganglioma of the urinary bladder. Compared with a review of 53 similar cases reported in Japan, the distribution of age, sex and tumor location in the bladder differed from those described worldwide.

Cystectomy↗
PubMed1999

Prognostic value of nucleolar protein p120 in patients with resected lung adenocarcinoma.

PURPOSE: In this study we investigated the prognostic significance of proliferation-associated nucleolar protein p120 in primary resected lung adenocarcinoma because it reflects tumor growth fractions in vitro. PATIENTS AND METHODS: Expression levels of p120 in tumors were assessed by immunohistochemistry in 74 patients who underwent radical resection. With clinical follow-up data, the prognostic significance of p120 calculated by labeling indices was evaluated using the Cox proportional hazards model. RESULTS: p120 protein was clearly detected in nucleoli of adenocarcinoma cells. Its expression levels widely varied in each sample from 8.5% to 67. 2%, with a mean +/- SD of 35.2% +/- 15.1%. No significant correlation was found between expression levels of p120 and clinicopathologic factors. However, the expression levels of p120 were negatively correlated with the tumor doubling time calculated with retrospective chest roentgenograms. Using a cutoff value of 35% in the labeling index of p120, patients with high expression of p120 experienced early recurrence and shorter survival compared with those who had low expression of p120. Multivariate analysis showed that p120 served as an independent, as well as the strongest, prognostic factor for resected lung adenocarcinoma. CONCLUSION: This report provides the first evidence that expression levels of p120 in tumor tissues can be used as an independent and powerful prognostic marker for resected lung adenocarcinoma.

Adenocarcinoma↗
PubMed1999

Distribution and intracellular localization of a mouse homologue of Ca2+/calmodulin-dependent protein kinase Ibeta2 in the nervous system.

Ca2+/calmodulin-dependent protein kinases (CaMKs) are believed to play important roles in the development and function of the nervous system. We report here the identification and expression of mouse CaMKIbeta (mCaMKIbeta), in particular mCaMKIbeta2, an isoform of mCaMKIbeta. During embryogenesis, the mCaMKIbeta2 gene is expressed mainly in the nervous system, including brain, spinal cord, trigeminal ganglion, and retina. Within the CNS, the expression of mCaMKIbeta2 is detected in the mantle zone, but not in the ventricular zone, suggesting its possible involvement in the differentiation of neurons. In the adult brain, mCaMKIbeta2 transcripts are detected at high levels in the anterior olfactory nuclei, piriform cortex, septal nuclei, bed nuclei of the stria terminalis, hippocampal pyramidal cells, dentate granule cells, amygdala, hypothalamic nuclei, parabrachial nucleus, and nucleus of the solitary tract. The distinct gene expression pattern suggests that mCaMKIbeta2 may also be involved in different mature neuronal functions from other CaMKs. In addition, mCaMKI/beta2 proteins are localized to the cytoplasm and nuclei, but not to nucleoli, suggesting that mCaMKIbeta2 proteins might be involved in the cytoplasmic and nuclear signal transduction of the nervous system.

Amino Acid Sequence↗
PubMed1998

Functional cooperation of cyclin C and c-Myc in mediating homotypic cell adhesion via very late antigen-4 activation and vascular cell adhesion molecule-1 induction.

Very late antigen-4 (VLA-4)/vascular cell adhesion molecule-1 (VCAM-1) are a pair of adhesion molecules mediating cell-cell interaction. The binding activity of each depends on its surface expression, yet integrin activity can also be modulated through inside-out signaling. However, the specific intracellular molecules involved in modulating integrin VLA-4 activation via inside-out signaling or in regulating VCAM-1 expression are poorly understood. We show here that constitutive coexpression of cyclin C and c-Myc in hematopoietic BAF-B03 cells induces homotypic cell adhesion, which results from enhanced VLA-4 ligand-binding activity and induced expression of VCAM-1. Furthermore, regulation of cell adhesion appears to be a feature unique to cyclin C, but not other G1 cyclins, E and D3, and its regulatory function is independent of CDK8 kinase activity. Our results provide a novel role for cyclin C and c-Myc in the regulation of cell adhesion through distinct mechanisms.

Animals↗