Biomedical subjects

Yasuhiro Ito

Publications and source records attributed to Yasuhiro Ito.

At least 73 records · Page 4Linked to original sources

PubMed2004

Expression of the components of the Cip/Kip family in malignant lymphoma of the thyroid.

OBJECTIVE: For evaluating the characteristics of human neoplasms, investigation of regulators of cell cycle progression is important. We studied three components of the Cip/Kip family, p57, p27 and p21, in malignant lymphomas of the thyroid. METHODS: We immunohistochemically investigated the expression of the three proteins for 49 cases of thyroid lymphomas, as well as 10 cases of chronic thyroiditis. RESULTS: In infiltrating lymphocytes in chronic thyroiditis, p57 and p27 were diffusely expressed, whereas p21 immunoreactivity was only occasionally observed. In lymphoma, decreased expression of p57 (less than 50% of lymphoma cells were positive) was observed in 24 cases (49.0%). p57 expression was inversely linked to the MIB-1 labeling index, grade of malignancy and aberrant p53 expression. Decreased expression of p27 was observed in 25 cases (51.0%), which was also related to the MIB-1 labeling index and aberrant p53 expression. On the other hand, p21 expression was occasional, and when the cut-off value was set at 3%, 38 cases (77.6%) were regarded as negative. P21 expression was not linked to any clinicopathological parameters. CONCLUSION: These findings suggest that, among the 3 components of the Cip/Kip family, p57 and p27 play a role in negatively regulating the cell proliferation of thyroid lymphoma cells and decreased expression of them contributes to the progression of this disease.

Biomarkers, Tumor↗

PubMed2004

S100A4 expression is an early event of papillary carcinoma of the thyroid.

OBJECTIVES: S100A4 is a calcium-binding protein related to the metastatic potential of carcinoma. In order to elucidate its contribution to the progression of thyroid carcinoma, we investigated S100A4 expression in various thyroid neoplasms. METHODS: We immunohistochemically examined S100A4 expression in 195 cases of thyroid neoplasms. RESULTS: Although S100A4 was absent in normal follicular cells and follicular adenoma, S100A4 was positive in all 115 cases of papillary carcinoma examined, including 58 microcarcinomas. However, a significant relationship could not be established between S100A4 expression and clinicopathological features of papillary carcinoma. In follicular carcinoma, the widely invasive type expressed S100A4 more frequently than the minimally invasive type (p = 0.0028). In anaplastic carcinoma, S100A4 was expressed in 61.9% of cases, but the incidence was significantly lower (p < 0.0001) than that in papillary carcinoma. CONCLUSIONS: These findings suggest that (1) S100A4 plays a constitutive role in papillary carcinoma and (2) S100A4 may be a useful marker for early the detection of this carcinoma.

Adenocarcinoma, Follicular↗

PubMed2004

Relation between the prefrontal cortex and cerebro-cerebellar functions: evidence from the results of stabilometrical indexes.

The relation between prefrontal cortex and cerebro-cerebellar functions of 50 normal healthy elderly people was examined. The function of the prefrontal cortex was measured by means of a letter fluency test and the Digit Cancellation Test (D-CAT, a test for the assessment of attention). Two indexes of postural tremor measured by the stabilometer were employed for the indication of cerebello-thalamo-cortical circuit functions. The results of groups consisting of participants showing higher or lower scores than the mean of the norm on the stabilometer index measurements were compared with their D-CAT and letter fluency test performances. The results showed that 2 indexes of cerebello-thalamo-cortical circuit functions related to the attention function while the relation to the language function was rather weak. The results of the behavioral measures demonstrated a mutual relation between prefrontal cortex and cerebello-thalamo-cortical circuit functions and strongly suggest the notion that the human brain functions as a system, which includes neocortex, subcortex, and cerebellum.

Aged↗

PubMed2004

Differential expression of three plastidial sigma factors, OsSIG1, OsSIG2A, and OsSIG2B, during leaf development in rice.

We isolated and characterized two rice nuclear genes, OsSIG2A and OsSIG2B, encoding the putative sigma-factor of the plastid RNA polymerase. Deduced protein sequences predicted a plastid-localizing signal in the N-terminus and subsequent polypeptides similar to known SIG2 proteins. Gene expression analysis revealed that the OsSIG2A transcript is more abundant than the OsSIG2B transcript in all tissues tested and that both rice SIG2s are expressed from earlier stages of leaf development than that in the case of OsSIG1. These results indicate differential expression of SIG genes in leaf morphogenesis, suggesting the existence of tissue- and stage-specific functions of SIG proteins for transcriptional regulation of chloroplast genes in plant development.

Amino Acid Sequence↗

PubMed2004

Spatial structure of quantitative representation of numbers: evidence from the SNARC effect.

Dehaene, Bossini, and Giraux (1993) revealed that subjects responded to large numbers faster with the choice on the right than with the choice on the left, whereas the reverse held true for small numbers (SNARC effect). According to Dehaene et al. (1993), the SNARC effect depends on the quantitative representation of number, such as a left-to-right-oriented analog number line. The main goal of the present study was twofold: first, to investigate whether the vertical SNARC effect could be observed, and, second, to verify whether Dehaene et al.'s (1993) explanation of the SNARC effect is correct. Experiments 2A and 2B showed the vertical SNARC effect in a parity judgment task. Subjects responded to large numbers faster with the top choice than with the bottom choice, whereas the reverse held true for small numbers. However, Experiment 3 failed to show the SNARC effect in a number magnitude judgment task, suggesting that the quantitative representation could be dissociated from the spatial code that produces the SNARC effect.

Adult↗

PubMed2004

Akt2 expression correlates with prognosis of human hepatocellular carcinoma.

Akt, a down-stream target of phosphatidylinositol-3 kinase, plays multiple roles in carcinogenesis. To elucidate its role in hepatocarcinogenesis, we immunohistochemically investigated the expression of Akt protein (Akt1 and Akt2) in tumor and non-tumor tissues from 56 patients with hepatocellular carcinoma (HCC). High expression of Akt2 in HCC tissues was detected in 21 cases (38%) while Akt1 expression was moderate or less in all cases. Low expression of Akt2 was associated with histopathological differentiation, portal invasion and number of tumor nodules (p=0.026, 0.023, and 0.001, respectively). Univariate analysis showed that Akt2, histopathological differentiation, and portal vein invasion were significant prognostic factors (p=0.001, 0.028, and 0.006, respectively). Multivariate analysis revealed that in addition to histopathological differentiation, Akt2 was an independent prognostic marker (risk ratio for cancer relapse, 6.35, p=0.012). In contrast, Akt1 expression did not correlate with any clinicopathological features. Our findings suggest that Akt2, but not Akt1, is a novel independent predictor for the development and progression of HCC.

Adult↗

PubMed2004

Cdc25A and cdc25B expression in malignant lymphoma of the thyroid: correlation with histological subtypes and cell proliferation.

Cdc25B and cdc25A phosphatases are representative stimulators of cell cycle progression, and recent studies have also indicated their oncogenic roles. In this study, we investigated the expression of these phosphatases in malignant lymphoma of the thyroid by immunohistochemistry. These phosphatases were not expressed in follicular cells in normal follicles, but were heterogeneously or diffusely expressed in the follicles in chronic thyroiditis and malignant lymphoma. In infiltrating lymphocytes in chronic thyroiditis, they were only occasionally expressed. Of the 47 cases of lymphoma, 30 (63.8%) were classified as high group for cdc25B because it was expressed in more than 25% of lymphoma cells. Cdc25B expression level was inversely associated with MIB-1 labeling index (p=0.0008), and aberrant p53 expression (p=0.0077). Furthermore, cases of marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MZBL) were more frequently classified as high group (p=0.0318) than those of diffuse large B-cell lymphoma (DLBL). On the other hand, 22 cases (46.8%) were regarded as high group for cdc25A, but its expression level was not linked to those parameters. These findings suggest that i) cdc25B plays a role in the early phase of thyroid lymphoma possibly including the malignant transformation from chronic thyroiditis, and ii) cdc25A may contribute to the progression of lymphoma.

Cell Cycle Proteins↗

PubMed2003

Expression and cellular localization of p8 protein in thyroid neoplasms.

OBJECTIVES: p8 protein has mitogenic activity and is linked to the development of pancreatic carcinoma. However, little is known about the expression and physiological significance of this protein in other human carcinomas. METHODS: In this study, we immunohistochemically investigated p8 expression in thyroid neoplasms as well as in the normal thyroid gland. RESULTS: p8 was expressed in normal follicular cells, but no normal thyroid was regarded as overexpressing p8. On the other hand, 44.3% of papillary carcinoma overexpressed p8 and the incidence was directly linked to the tumor size (p=0.0340) and lymph node metastasis (p=0.0145). In follicular tumors, the incidence of p8 overexpression did not depend on histological type. In anaplastic (undifferentiated) carcinoma, p8 was overexpressed only in 5.0%, which was significantly lower than in papillary (p=0.0006) and follicular carcinomas (p=0.0049). In normal follicules and follicular tumors, p8 was localized mainly in the nucleus except for two adenomas. On the other hand, p8 localization was more cytoplasmic in papillary carcinoma larger than 1.0 cm (p=0.0186) and with a poorly differentiated lesion (p=0.0313). CONCLUSIONS: These results suggest that the overexpression and cytoplasmic localization of p8 protein may reflect disease progression of papillary carcinoma, whereas this protein plays little part in thyroid carcinoma after anaplastic transformation.

Adenocarcinoma, Follicular↗

PubMed2003

14-3-3 sigma possibly plays a constitutive role in papillary carcinoma, but not in follicular tumor of the thyroid.

14-3-3 sigma is a negative regulator of the cell cycle and contributes to G2 arrest. Thus far, the lack of its expression due to hypermethylation of the CpG islands has been reported in some carcinomas. In this study, we investigated the expression of 14-3-3 sigma in thyroid neoplasms by means of immunohistochemistry as well as Western blot analysis. Normal follicules did not express 14-3-3 sigma. In 82 papillary carcinomas, all the cases expressed 14-3-3 sigma and its expression was not reduced but even enhanced in the advanced stage and in poorly differentiated types. Furthermore, 21 of the 23 anaplastic carcinomas expressed 14-3-3 sigma and its expression level tended to be higher than in papillary carcinoma. On the other hand, none of the 34 follicular carcinomas or 29 follicular adenomas expressed 14-3-3 sigma. These results suggest that 14-3-3 sigma plays a constitutive role in papillary carcinoma rather than acting as a cell cycle regulator, whereas it is not required for the occurrence and development of follicular tumor.

14-3-3 Proteins↗

PubMed2003

Expression of alpha1,6-fucosyltransferase (FUT8) in papillary carcinoma of the thyroid: its linkage to biological aggressiveness and anaplastic transformation.

Previous studies have demonstrated that terminal fucosylation is associated with the biological aggressiveness of carcinomas, but the significance of core fucosylation (alpha1,6-fucosylation) through alpha1,6-fucosyltransferase (FUT8) has not been studied in depth. Herein, we investigated the expression of alpha1,6-fucosyltransferase (FUT8) in 133 cases of thyroid carcinomas using an immunohistochemical approach. The expression of FUT8 was quite low in normal follicules. A high expression of FUT8 was observed in 33.3% of papillary carcinoma and the incidence was directly linked to tumor size and lymph node metastasis. In contrast, this phenomenon was less frequently observed in follicular carcinoma and anaplastic (undifferentiated) carcinoma. These results suggest that FUT8 expression may be a key factor in the progression of thyroid papillary carcinomas, but not follicular carcinomas, and decreases in FUT8 expression might be linked to anaplastic transformation.

Carcinoma↗

PubMed2003

Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4.

Angiopoietins and angiopoietin-related proteins (ARPs) have been shown to regulate angiogenesis, a process essential for various neovascular diseases including tumors. Here, we identify ARP4/fasting-induced adipose factor/peroxisome proliferator-activated receptor gamma angiopoietin-related as a novel antiangiogenic modulatory factor. We hypothesized that ARP4 may regulate angiogenesis. In vitro experiments using purified recombinant ARP4 protein revealed that ARP4 markedly inhibited the proliferation, chemotaxis, and tubule formation of endothelial cells. Moreover, using corneal neovascularization and Miles permeability assays, we found that both vascular endothelial growth factor-induced in vivo angiogenesis and vascular leakiness were significantly inhibited by the addition of ARP4. Finally, we found remarkable suppression of tumor growth within the dermal layer associated with decreased numbers of invading blood vessels in transgenic mice that express ARP4 in the skin driven by the keratinocyte promoter. These findings demonstrate that ARP4 functions as a novel antiangiogenic modulatory factor and indicate a potential therapeutic effect of ARP4 in neoplastic diseases.

Angiogenesis Inhibitors↗

PubMed2003

Ephrin-B2 induces migration of endothelial cells through the phosphatidylinositol-3 kinase pathway and promotes angiogenesis in adult vasculature.

OBJECTIVE: Ephrin-B2 plays a key role in vascular development. The purpose of this study was to elucidate the molecular mechanisms of ephrin-B2 signaling through the EphB receptor in endothelial cells and to determine whether ephrin-B2 contributes to in vivo angiogenesis in adult mice. METHODS AND RESULTS: A chemotaxis assay on a polycarbonate membrane revealed that ephrin-B2/Fc chimeric protein induced migration of human umbilical vein endothelial cells (HUVECs) at a level 98% greater than control (P<0.01). To determine the signaling pathways activated in the HUVECs by Eph stimulation, phosphatidylinositol-3 kinase (PI3 kinase) activity was determined in an immune complex PI3 kinase assay. Serum-starved HUVECs were stimulated with ephrin-B2/Fc and compared with unstimulated cells. PI3 kinase activity in stimulated cells was higher than that seen in unstimulated cells. In a chemotaxis assay, the PI3 kinase-specific inhibitor LY294002 blocked the migratory response of HUVECs induced by addition of ephrin-B2/Fc. Finally, ephrin-B2/Fc promoted angiogenesis in vivo in corneal neovascularization and Matrigel plug assays in adult mice, whereas LY294002 reduced angiogenesis in Matrigel that was induced by ephrin-B2/Fc. CONCLUSIONS: Ephrin-B2/Fc induces the migration of HUVECs through the PI3 kinase signaling pathway. Ephrin-B2/Fc promotes in vivo angiogenesis in adult mice, suggesting that it contributes to adult angiogenesis.

Animals↗

PubMed2003

Angiopoietin-related growth factor (AGF) promotes epidermal proliferation, remodeling, and regeneration.

We report here the identification of an angiopoietin-related growth factor (AGF). To examine the biological function of AGF in vivo, we created transgenic mice expressing AGF in epidermal keratinocytes (K14-AGF). K14-AGF mice exhibited swollen and reddish ears, nose and eyelids. Histological analyses of K14-AGF mice revealed significantly thickened epidermis and a marked increase in proliferating epidermal cells as well as vascular cells in the skin compared with nontransgenic controls. In addition, we found rapid wound closure in the healing process and an unusual closure of holes punched in the ears of K14-AGF mice. Furthermore, we observed that AGF is expressed in platelets and mast cells, and detected at wounded skin, whereas there was no expression of AGF detected in normal skin tissues, suggesting that AGF derived from these infiltrated cells affects epidermal proliferation and thereby plays a role in the wound healing process. These findings demonstrate that biological functions of AGF in epidermal keratinocytes could lead to novel therapeutic strategies for wound care and epidermal regenerative medicine.

Amino Acid Sequence↗

PubMed2003

14-3-3 sigma possibly plays a constitutive role in papillary carcinoma, but not in follicular tumor of the thyroid.

Jun activation domain-binding protein 1 (jab1) is known as a coactivator of the AP1 transcription factor. Recent studies have demonstrated that jab1 contributes to carcinoma progression by degrading p27/Kip1 protein. In this study, we immunohistochemically investigated jab1 expression in thyroid neoplasms. jab1 overexpression tended to be frequently observed in follicular carcinoma compared to adenoma. Larger-sized papillary carcinoma overexpressed jab1 in higher incidence than microcarcinomas (1.0 cm or less in maximum diameter). In anaplastic carcinoma, jab1 was more frequently overexpressed than in papillary and follicular carcinomas. An inverse relationship was detected between jab1 overexpression and p27 expression in papillary and anaplastic carcinomas, but not in follicular tumor. These results suggest that jab1 plays a role in the progression of thyroid carcinomas, especially those of aggressive phenotypes, and it may be responsible for p27 degradation in anaplastic and papillary carcinomas.

14-3-3 Proteins↗

PubMed2003

Neuroradiologic and clinical abnormalities in dementia of diffuse neurofibrillary tangles with calcification (Kosaka-Shibayama disease).

We describe a characteristic dementia patient diagnosed as diffuse neurofibrillary tangles with calcification (DNTC). Neuropsychologically, dementia, including a decline in memory retention and intelligence, and anomic aphasia were recognized. Imaging revealed circumscribed temporal dominant atrophy and calcification of the basal ganglia and cerebellum. SPECT and FDG-PET revealed a remarkable reduction of blood flow and metabolism in the temporal lobes; however, there is no reduction in the basal ganglia and cerebellum, and FDOPA-PET also disclosed no abnormalities. This suggests that calcification and neuronal degeneration occur independently in DNTC.

Aged↗

PubMed2003

p130 expression in thyroid neoplasms: its linkage with tumor size and dedifferentiation.

p130 belongs to the retinoblastoma-related gene family, and its gene product works to negatively regulate cell cycle progression in the G1 phase. In this study, we investigated p130 expression in thyroid neoplasms. p130 overexpression was observed in 33.3% of follicular adenoma and 50% of follicular carcinoma and the incidences were not significantly different. In papillary carcinoma, it was overexpressed in 36.5% of cases, but in microcarcinoma, the incidence was significantly lower (14.3%). Furthermore, in anapalstic carcinoma, p130 overexpression was less frequently seen than in papillary carcinoma except for microcarcinoma and follicular carcinoma, and only 14.3% of cases overexpressed this protein. These findings suggest that: (1) reduced p130 expression may contribute to the aggressive character of anplastic carcinoma; and (2) p130 may specify the growth characteristics of microcarcinoma.

Carcinoma↗

PubMed2003

Distinct roles of ephrin-B2 forward and EphB4 reverse signaling in endothelial cells.

OBJECTIVE: The transmembrane ligand ephrin-B2 and its receptor tyrosine kinase EphB4 are specifically expressed on arterial and venous endothelial cells, respectively, and bidirectional signals mediated by both proteins play an important role in vascular development. However, how such bidirectional signals are required for cell-cell adhesion or repulsion remains unclear. METHODS AND RESULTS: Using a cell line and sorted primary endothelial cells, we show that ephrin-B2 forward signaling through the EphB4 receptor inhibits cell adhesion, whereas EphB4 reverse signaling by the transmembrane ephrin-B2 ligand does not. Cell migration is also inhibited on immobilized ephrin-B2-Fc but not on EphB4-Fc protein. CONCLUSIONS: Ephrin-B2 forward signaling and EphB4 reverse signaling differentially affect cell adhesion and migration between arterial and venous endothelial cells.

Actins↗

PubMed2003

Tryptophan metabolism was accelerated by exercise in rat.

We have already reported that exercise activates kynurenine pathway. But, the mechanism for this activation by exercise is still unclear. Kynurenine is metabolized to NAD, which is an essential factor for energy metabolism. In this study, exercise on treadmill was loaded to rats until all-out and tryptophan metabolites and tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) activities were determined in the blood, livers, and macrophages, respectively, in the exercise-loaded rats. The mean values of serum tryptophan concentration decreased from 92.6 +/- 6.0 nmol/ml to 52.4 +/- 10.2 nmol/ml (p<0.05) just after treadmill load. The serum kynurenine concentration had increased from 2.06 +/- 0.25 nmol/ml to 3.08 +/- 0.62 nmol/ml (p<0.005). And whole blood NAD concentration increased from 68.8 +/- 14.6 nmol/ml to 77.9 +/- 19.1 nmol/ml (p<0.005). These results showed that exercise activated the kynurenine pathway of tryptophan metabolism and made NAD which will be concerned with energy metabolism in mitochondria. Tryptophan-NAD pathway was initiated by cleavage of indole ring of tryptophan by TDO in the liver and IDO in many organs. We had also found that the exercise increase IDO activity of macrophages, but not TDO activity.

Animals↗