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Keisuke Ishizawa

Publications and source records attributed to Keisuke Ishizawa.

At least 19 recordsLinked to original sources
PubMed2006

Langerhans cell histiocytosis on the penis: a case report.

BACKGROUND: Langerhans cell histiocytosis affects mainly young children and features an accumulation of CD1a+ dendritic Langerhans cells in the bone, skin, and other organs. A few cases of Langerhans cell histiocytosis on the penis have been reported in the literature. We present a case of Langerhans cell histiocytosis on the penis and review the similar cases in the literature. CASE PRESENTATION: The patient was a 13-year-old boy who had a history of lymph node, femur bone, and pituitary-thalmic axis lesions from Langerhans cell histiocytosis who noticed a painful nodule on the prepuce of his penis. The histological and immunohistochemical examination fulfilled the criteria of Langerhans cell histiocytosis. CONCLUSION: We herein describe the case reported of Langerhans cell histiocytosis on the penis.

Adolescent↗
PubMed2006

The novel Src kinase inhibitor M475271 inhibits VEGF-induced vascular endothelial-cadherin and beta-catenin phosphorylation but increases their association.

M475271, 4-quinazolinamine, N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl) methoxy]-(9Cl), is a new anilinoquinazoline derivative that displays selective inhibition of Src kinase activity and tumor growth in vivo. Vascular endothelial growth factor (VEGF)-induced angiogenesis plays a pivotal role in tumor growth and metastasis. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule that can interact with the cytoskeleton via several anchoring molecules such as beta-catenin. Here, we examined the effect of M475271 on VE-cadherin and beta-catenin phosphorylation and association. We also examined its effect on VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation. The findings reveal pretreatment with M475271 significantly inhibits VEGF-induced VE-cadherin and beta-catenin phosphorylation. However, M475271 significantly increases VE-cadherin and beta-catenin association compared to the VEGF-treated group. Confocal laser microscopic examination confirmed the augmentation effect of M475271 on VE-cadherin and beta-catenin association. Finally, M475271 was shown to have inhibitory effects comparable to those of PP2 and Herbimycin A on VEGF-induced HUVEC proliferation, migration, and tube formation. These findings suggest that M475271 attenuates VEGF-induced angiogenesis by maintaining cell-cell junction stability. Although the involvement of other signaling molecules cannot be ruled out, M475271 has potential as a drug for the inhibition of the angiogenesis needed for tumor growth and metastasis.

Cadherins↗
PubMed2006

The value of MDM2 and CDK4 amplification levels using real-time polymerase chain reaction for the differential diagnosis of liposarcomas and their histologic mimickers.

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and dedifferentiated liposarcoma (DDL) are reported to have murine double-minute type 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) amplification as a characteristic genetic alteration. To evaluate the diagnostic utility of this gene abnormality, we analyzed 19 liposarcomas, 21 malignant fibrous histiocytomas, 3 leiomyosarcomas, 5 malignant peripheral nerve sheath tumors, 23 lipomas, and 28 nonneoplastic fat tissues using real-time polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). In real-time PCR, all ALT/WDLs and DDLs had both MDM2 and CDK4 amplifications. The amplification levels in ALT/WDLs and DDLs were significantly higher than those in the other sarcomas, lipomas, and nonneoplastic fat tissues (P < .05); however, those in the other sarcomas and lipomas were not significantly higher than those in nonneoplastic tissues. In FISH, all ALT/WDLs and DDLs had both MDM2 and CDK4 amplifications, and all of the myxoid/round cell liposarcomas, leiomyosarcomas, malignant peripheral nerve sheath tumors, and all but one of the malignant fibrous histiocytomas did not have the amplifications. In this study, MDM2 and CDK4 amplifications were confirmed in ALT/WDLs and DDLs, and the amplification levels were significantly higher than those in the other tumors. An analysis of MDM2 and CDK4 amplification using real-time PCR, as well as FISH, is useful for the differential diagnosis of liposarcomas and their histologic mimickers.

Adipose Tissue↗
PubMed2006

Papillary glioneuronal tumor with minigemistocytic components and increased proliferative activity.

Papillary glioneuronal tumor (PGNT) is a rare and new type of glioneuronal neoplasm of the central nervous system. It is characterized by pseudopapillary structures composed of hyalinized vessels rimmed by cuboidal glial cells and the proliferation of neuronal cells. We report a peculiar PGNT arising in the parietal lobe of a 67-year-old man, which was characterized by proliferation of minigemistocytic cells as well as typical components. The minigemistocytic cells had eccentric nuclei and plump eosinophilic cytoplasm that was filled with glial filaments. The Ki-67 labeling index was as high as 10% in the minigemistocytic areas. Recently, the presence of oligodendroglial-like component was suggested in PGNT. Considering that oligodendroglioma sometimes accompanies minigemistocytic components, the minigemistocytic cells in PGNT were suggested to be a part of oligodendroglial differentiation. Although PGNT is defined as an indolent glioneuronal tumor, the presence of minigemistocytic components with the high Ki-67 labeling index may indicate more aggressive nature.

Aged↗
PubMed2006

Alzheimer's disease presenting as corticobasal syndrome.

A 60-year-old man presented with slowly progressive left hemi-Parkinsonism, left hand apraxia, myoclonus, dystonia, visuospatial disturbances, and alien limb phenomenon, resembling corticobasal syndrome. Eight years later, neuropathology revealed features of Alzheimer's disease, with asymmetrical (right more than left) cortical tau burden with image analysis. The videotaped clinical features, neuropsychological aspects, and neuropathological correlates are presented and discussed.

Alzheimer Disease↗
PubMed2006

Alpha-fetoprotein-producing clear cell carcinoma of the extrahepatic bile ducts.

A 79-year-old woman visiting our hospital with chief complaints of epigastric pain and jaundice was emergently admitted. Her alpha-fetoprotein (AFP) level was as high as 2265 ng/mL at admission. Her abdominal computed tomography scan revealed dilation of the intrahepatic bile duct and a tumorlike lesion protruding into the cystic duct and gallbladder from the junction between the middle portion of the bile duct and the right and left hepatic ducts. Surgery revealed a tumor extending from the extrahepatic bile duct (EHBD) to the cystic duct, with no intrahepatic tumor components. The tumor was histologically diagnosed as an AFP-producing cholangiocarcinoma of the clear cell type, originating from the EHBD. None of the previously reported cholangiocarcinomas of the AFP-producing clear cell type have been confined to the EHBD or have been resectable in a curative manner without hepatectomy.

Adenocarcinoma, Clear Cell↗
PubMed2006

Retroperitoneal lipomatous angiomyolipoma associated with amyloid deposition masquerading as well-differentiated liposarcoma.

Reported herein is a case of retroperitoneal angiomyolipoma associated with amyloid deposition, masquerading as well-differentiated liposarcoma. A 16 x 13 cm lipomatous tumor was resected from the perirenal retroperitoneum of a 71-year-old woman. Microscopically, the tumor was exclusively composed of mature adipose tissue and abnormal thick blood vessels, but bundles of smooth muscle were lacking. In addition, amyloid was deposited between fat cells. Initially, well-differentiated liposarcoma was highly suspected. However, there were a few epithelioid cells with clear vacuolated cytoplasm within the vessel walls, which were immunoreactive for smooth muscle markers and HMB-45. Real-time polymerase chain reaction failed to demonstrate the amplification of the murine double-minute type 2 gene and cyclin-dependent kinase 4 gene in this tumor. Therefore, the tumor was diagnosed as lipomatous angiomyolipoma. After the diagnosis, it was found that the patient had multiple myeloma and cardiac amyloidosis, suggesting that the amyloid deposition within the tumor was a complication of the myeloma. Lipomatous angiomyolipoma may be a diagnostic pitfall of retroperitoneal lipomatous tumors.

Aged↗
PubMed2006

Calcium and reactive oxygen species mediated Zn2+ -induced apoptosis in PC12 cells.

The release of excessive Zn(2+) from presynaptic boutons into extracellular regions contributes to neuronal apoptotic events, which result in neuronal cell death. However, the mechanisms of Zn(2+)-induced neuronal cell death are still unclear. Therefore, we investigated the dynamics of intracellular Zn(2+), calcium, and reactive oxygen species in PC12 cells. The addition of Zn(2+) produced cell death in a concentration- and time-dependent manner. (45)Ca(2+) influx occurred just after the treatment with Zn(2+), although subsequent hydroxyl radical ((*)OH) production did not begin until 3 h after Zn(2+) exposure. (*)OH production was significantly attenuated in Ca(2+)-free medium or by L-type Ca(2+) channel antagonist treatment, but it was independent of the intracellular Zn(2+) content. Dantrolene treatment had no protective effects against Zn(2+)-induced cell death. Treatment with N-acetyl-L-cysteine blocked (*)OH generation and subsequent cell death. These data indicate that Ca(2+) influx and subsequent (*)OH production are critical events in Zn(2+)-induced toxicity in PC12 cells.

Acetylcysteine↗
PubMed2006

Effects of angiotensin II type 1 receptor blockade on the systemic blood nitric oxide dynamics in Nomega-nitro-L-arginine methyl ester-treated rats.

We previously succeeded in measuring the nitrosylhemoglobin (HbNO) level as an index of blood nitric oxide (NO) by the electron paramagnetic resonance (EPR) HbNO signal subtraction method. In this study, we examined the effects of olmesartan, an angiotensin II type 1 receptor blocker (ARB), on NO dynamics in N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated rats by the EPR-subtraction method. Oral administration of L-NAME for 2 weeks induced serious hypertension, and the HbNO concentration was reduced to 37.6% of the level in controls. Coadministration of olmesartan improved hypertension and increased the blood HbNO concentration of L-NAME-treated rats. In contrast, coadministration of hydralazine improved hypertension but did not affect the blood HbNO concentration. In conclusion, our findings suggested that chronic administration of olmesartan ameliorated the endothelial dysfunction in L-NAME-treated rats.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Multiple organ involvement in eosinophilic polymyositis: an autopsy report.

This report describes autopsy findings of eosinophilic polymyositis in a 29-year-old woman. She complained of muscle pain and tenderness. A serum examination disclosed elevated creatine kinase, and echocardiography showed lowered cardiac function. Electromyography demonstrated myopathic potentials, and the skeletal muscle biopsy revealed degeneration of muscle fibers accompanying marked eosinophilic infiltration. Peripheral eosinophilia was not prominent. A systemic examination excluded possible etiologic factors, such as hypereosinophilic syndrome, collagen vascular diseases, or parasites. The patient died of heart failure after a 4-month clinical course. The autopsy disclosed a set of histological changes indicating tissue injuries, that is, loss of muscle fibers, interstitial fibrosis, and/or infiltrates of lymphocytes not only in the skeletal muscles and heart but also in various visceral organs. Eosinophils were sparsely scattered. These results indicate that the overrun of eosinophils underlying eosinophilic polymyositis, regardless of the presence of hypereosinophilic syndrome or other systemic disorders, could involve wide-ranging visceral organs.

Adult↗
PubMed2005

Transactivation of fetal liver kinase-1/kinase-insert domain-containing receptor by lysophosphatidylcholine induces vascular endothelial cell proliferation.

Lysophosphatidylcholine (LPC), a major lipid component of oxidized low-density lipoprotein, is a bioactive lipid molecule involved in numerous biological processes including the progression of atherosclerosis. Recently orphan G protein-coupled receptors were identified as high-affinity receptors for LPC. Although several G protein-coupled receptor ligands transactivate receptor tyrosine kinases, LPC-stimulated transactivation of receptor tyrosine kinase has not yet been reported. Here we observed for the first time that LPC treatment of human umbilical vein endothelial cells (HUVECs) induces tyrosyl phosphorylation of vascular endothelial growth factor receptor 2 [fetal liver kinase-1/kinase-insert domain-containing receptor, Flk-1/KDR)]. Flk-1/KDR transactivation by LPC was inhibited by vascular endothelial growth factor receptor tyrosine kinase inhibitors, SU1498 and 4-[(4'-chloro-2'-fluoro) phenylamino]6,7-dimethoxyquinazoline (VTKi) in immunoprecipitation. Furthermore, we examined the effects of the Src family kinases inhibitors, herbimycin A and 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2), on LPC-induced Flk-1/KDR transactivation. Results from Western blots, c-Src is involved in LPC-induced Flk-1/KDR transactivation because herbimycin A and PP2 inhibited this transactivation. Kinase-inactive (KI) Src transfection also inhibited LPC-induced Flk-1/KDR transactivation. In addition, results from Western blots, ERK1/2 and Akt, which are downstream effectors of Flk-1/KDR, were also activated by LPC, and this was inhibited by SU1498, VTKi, herbimycin A, PP2, and KI Src transfection in HUVECs. LPC-induced stimulation of HUVEC proliferation was shown to be secondary to transactivation because it was suppressed by SU1498, VTKi, herbimycin A, PP2, and KI Src transfection in dimethylthiazoldiphenyltetra-zoliumbromide assay. These findings suggest that LPC-induced Flk-1/KDR transactivation via c-Src may have important implications for the progression of atherosclerosis.

Atherosclerosis↗
PubMed2005

ERK1/2 activation by angiotensin II inhibits insulin-induced glucose uptake in vascular smooth muscle cells.

Clinical evidence suggests a relationship between hypertension and insulin resistance, and cross-talk between angiotensin II (Ang II) and insulin signaling pathways may take place. We now report the effect of Ang II on insulin-induced glucose uptake and its intracellular mechanisms in vascular smooth muscle cells (VSMC). We examined the translocation of glucose transporter-4 (GLUT-4) and glucose uptake in rat aortic smooth muscle cells (RASMC). Mitogen-activated protein (MAP) kinases and Akt activities, and phosphorylation of insulin receptor substrate-1 (IRS-1) at the serine and tyrosine residues were measured by immunoprecipitation and immunoblotting. As a result, Ang II inhibited insulin-induced GLUT-4 translocation from cytoplasm to the plasma membrane in RASMC. Ang II induced extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) activation and IRS-1 phosphorylation at Ser307 and Ser616. Ang II-induced Ser307 and Ser616 phophorylation of IRS-1 was inhibited by a MEK inhibitor, PD98059, and a JNK inhibitor, SP600125. Ang II inhibition of insulin-stimulated IRS-1 tyrosyl phophorylation and Akt activation were reversed by PD98059 but not by SP600125. Ang II inhibited insulin-induced glucose uptake, which was also reversed by PD98059 but not by SP600125. It is shown that Ang II-induced ERK1/2 activation inhibits insulin-dependent glucose uptake through serine phophorylation of IRS-1 in RASMC.

Angiotensin II↗
PubMed2005

Aldosterone stimulates vascular smooth muscle cell proliferation via big mitogen-activated protein kinase 1 activation.

The nongenomic effects of aldosterone have been implicated in the pathogenesis of various cardiovascular diseases. Aldosterone-induced nongenomic effects are attributable in part to the activation of extracellular signal-regulated kinase 1/2 (ERK1/2), a classical mitogen-activated protein (MAP) kinase. Big MAP kinase 1 (BMK1), a newly identified MAP kinase, has been shown to be involved in cell proliferation, differentiation, and survival. We examined whether aldosterone stimulates BMK1-mediated proliferation of cultured rat aortic smooth muscle cells (RASMCs). Mineralocorticoid receptor (MR) expression and localization were evaluated by Western blotting analysis and fluorolabeling methods. ERK1/2 and BMK1 activities were measured by Western blotting analysis with the respective phosphospecific antibodies. Cell proliferation was determined by Alamar Blue colorimetric assay. Aldosterone (0.1 to 100 nmol/L) dose-dependently activated BMK1 in RASMCs, with a peak at 30 minutes. To clarify whether aldosterone-induced BMK1 activation is an MR-mediated phenomenon, we examined the effect of eplerenone, a selective MR antagonist, on aldosterone-induced BMK1 activation. Eplerenone (0.1 to 10 micromol/L) dose-dependently inhibited aldosterone-induced BMK1 activation in RASMCs. Aldosterone also stimulated RASMC proliferation, which was inhibited by eplerenone. Aldosterone-mediated phenomena were concluded to be attributable to a nongenomic effect because cycloheximide failed to inhibit aldosterone-induced BMK1 activation. Transfection of dominant-negative MAP kinase/ERK kinase 5 (MEK5), which is an upstream regulator of BMK1, partially inhibited aldosterone-induced RASMC proliferation, which was almost completely inhibited by MEK inhibitor PD98059. In addition to the classical steroid activity, rapid nongenomic effects induced by aldosterone may represent an alternative etiology for vascular diseases such as hypertension.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed2005

Dedifferentiated liposarcoma with rhabdomyoblastic differentiation.

Dedifferentiated areas of dedifferentiated liposarcoma (DDL) usually show malignant fibrous histiocytoma (MFH)- or fibrosarcoma-like features and lack any histologic signs of specific differentiation. However, some reports have demonstrated specific differentiation in these areas, with histologic features resembling those of rhabdomyosarcoma, leiomyosarcoma, and osteosarcoma. We report here a pathologic and genetic analysis of three cases of DDLs with rhabdomyosarcomatous areas. MFH- or fibrosarcoma-like areas of one primary DDL and two recurrent DDLs contained various amounts of rhabdomyoblasts, which were immunoreactive for desmin, myoglobin, muscle actin (HHF-35), and myogenin. An ultrastructural examination demonstrated rhabdomyoblasts with abundant cytoplasm containing thin and thick filaments and Z-bands. By real-time PCR, amplification of mdm2 and cdk4 was confirmed in both well-differentiated and dedifferentiated areas with rhabdomyoblasts of all cases. To our knowledge, only seven cases of DDLs with rhabdomyosarcomatous components have been reported, and furthermore, the genetic profiles of the rhabdomyosarcomatous components in DDLs have not been investigated. This study demonstrates that DDLs with rhabdomyosarcomatous areas have genetic alterations that are common to well-differentiated/dedifferentiated liposarcomas.

Biomarkers, Tumor↗
PubMed2005

A novel Src kinase inhibitor, M475271, inhibits VEGF-induced human umbilical vein endothelial cell proliferation and migration.

Vascular endothelial growth factor (VEGF) was reported to be a potent proangiogenic factor that plays a pivotal role in both physiological and pathological angiogenesis. M475271, 4-quinazolinamine, N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl) methoxy]-(9Cl), is a new anilinoquinazoline derivative that showed selective inhibition of Src kinase activity and tumor growth in vivo. Here, we examined the effect of M475271 on VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation and migration and their intracellular mechanisms. Our findings showed that M475271 pretreatment resulted in a significant inhibition of VEGF-induced HUVEC proliferation, [(3)H]thymidine incorporation, and migration. M475271 inhibited VEGF-induced Flk-1 and Src phosphorylation and their association. Confocal laser microscopic examination confirmed the inhibitory effect of M475271 on VEGF-induced Flk-1/Src association. M475271 inhibited VEGF-induced extracellular signal-regulated kinase1/2 (ERK1/2) and p38 but not Akt activation in a concentration-dependent manner. M475271, PI3-K inhibitor, and p38 inhibitor inhibited VEGF-induced HUVEC proliferation and migration. However, a MEK1/2 inhibitor inhibited VEGF-induced proliferation but not migration. These findings suggest that M475271 attenuates VEGF-induced HUVEC proliferation and migration through the inhibition of signaling pathways involving Src, ERK1/2, and/or p38. Taken together, these data indicate that M475271 may be a useful candidate for inhibition of endothelial cell proliferation and migration relevant to angiogenesis.

Cell Line↗
PubMed2005

Expression of E-cadherin and catenins in meningioma: ubiquitous expression and its irrelevance to malignancy.

The expression of cell adhesion molecules in 107 meningiomas was analyzed with immunohistochemical methods using antibodies to epithelial (E)-cadherin and catenins (alpha, beta and gamma). According to the provided World Health Organization (WHO) grading, 84, 18 and five cases were classified as grade I, II and III, respectively. In addition, hemangioblastoma (15 cases) and hemangiopericytoma (four cases) were also evaluated. In most meningiomas, E-cadherin, alpha- and beta-catenins were expressed along the cell membrane or inside the cytoplasm. The tumor cells constituting whorls and glandular structures of secretory type showed a strong immunoreactivity. gamma-Catenin expression tended to be weak and infrequent in fibrous meningiomas, while other types exhibited diffuse stainings. Even in meningiomas of more than grade II, the expressions of cell adhesion molecules were detected in all cases. Hemangiopericytoma was positive for alpha- and beta-catenins, and hemangioblastomas were positive for beta-catenin alone, which was distinct from the expression pattern in meningiomas. Quantitatively, there were no correlations between the histological variants, Ki-67 indexes, or grades of meningiomas and the immunoreactive scores except for gamma-catenin scores of fibrous meningiomas. The present study demonstrates that cell adhesion molecules are ubiquitously expressed in all variants of meningioma and may be involved in the tumor morphogenesis. This result suggests that the expression of cell adhesion molecules is not a reliable indicator of malignancy in meningiomas. The present study also suggests that these markers may be useful for the differential diagnosis of meningioma.

Adult↗
PubMed2005

Stromal cells in hemangioblastoma: neuroectodermal differentiation and morphological similarities to ependymoma.

The histogenesis of stromal cells in hemangioblastoma is inconclusive despite a long-term controversy. An immunohistochemical and ultrastructural study was conducted for 17 cases of cerebellar hemangioblastoma. A wide range of immunohistological markers, targeting epithelial, mesenchymal, endothelial and neuroectodermal tissues, was used. In all cases, the microscopic hallmark characterizing hemangioblastomas, that is, lipid-containing stromal cells and a fine capillary network, known as a reticular variant, was noted. Stromal cells showed a variable immunoreactivity for neuroectodermal markers, such as S-100 protein, CD56, CD57, CD99, and neuron-specific enolase. This result, in conjunction with the absence of immunoreactivity for epithelial, mesenchymal, and endothelial markers, likely suggests neuroectodermal differentiation of stromal cells. In three cases, another component, known as a cellular variant, where epithelioid tumor cells were arranged in nests encircled by capillaries and/or in pseudorosette-like structures, was noted. Glial fibrillary acidic protein-immunoreactivity, which was totally absent in cases only showing the reticular pattern, was noted in two of them, suggesting a distinctive sign of glial differentiation in a proportion of hemangioblastomas. Ultrastructurally, microvilli-like projections in intracytoplasmic vacuoles were demonstrated in stromal cells. This result, taken together with the neuroectodermal hypothesis of stromal cells, suggests that hemangioblastomas may occasionally exhibit morphological similarities to ependymomas.

12E7 Antigen↗