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Biomedical subjects

Hideaki Itoh

Publications and source records attributed to Hideaki Itoh.

At least 55 records · Page 3Linked to original sources

[A case of curatively resected schirrous gastric cancer effectively treated by combined chemotherapy of weekly paclitaxel (PTX) and CDDP].

The patient was a 40-year-old woman who had unresectable advanced gastric cancer with invasion of liver and dissemination to the peritoneal wall. Neoadjuvant chemotherapy consisting of paclitaxel (PTX) and CDDP was performed. PTX (80 mg/m2), and CDDP (25 mg/m2) was administered weekly on day 1, 8 and 15 as one cycle. After four cycles of PTX/CDDP administration,invasion of liver and gastric tumor had decreased to almost normal size, and total gastrectomy was performed. After operation, the patient was treated with six courses of PTX/CDDP and survived without recurrence as of this writing. PTX/CDDP was associated with few adverse events in hospital visits, and thought to be an effective chemotherapy against advanced gastric cancer.

Adenocarcinoma, Scirrhous↗

Mercury removal from water using activated carbons derived from organic sewage sludge.

Various types of activated carbons were developed from organic sewage sludge (SS) using H(2)SO(4), H(3)PO(4) and ZnCl(2) as chemical activation reagents, and the removal of Hg(II) from aqueous solution by these carbons was effectively demonstrated. The quality of the activated carbons was dramatically improved owing to chemical activation. ZnCl(2) activated carbon had the highest capability for Hg(II) adsorption, followed by H(3)PO(4) and H(2)SO(4) activated carbons. The adsorption was greatly affected by Hg(II) concentration, solution pH and carbon dosage, and followed Lagergren first order rate equation and Freundlich isotherm model. Desorption results indicated that around 60% to 80% of the adsorbed Hg(II) could be recovered from the carbons to 0.1 M HNO(3) solution by sonication treatment. Accordingly, it is believed that the activated carbons developed in this study are effective and practical for utilization in industrial wastewater treatment for mercury removal.

Adsorption↗

DNA topoisomerase II poison TAS-103 transactivates GC-box-dependent transcription via acetylation of Sp1.

Drug-induced modifications of transcription factors play important roles in both apoptosis and survival signaling. The data presented here show that the DNA topoisomerase II poison TAS-103 transactivated the SV40 promoter in a GC-box-dependent manner and induced Sp1 acetylation in cells expressing p300. This activity was not observed in cells lacking p300. TAS-103 treatment also enhanced the p300 content of the nucleus and the interaction of p300 with Sp1. Cellular susceptibility to TAS-103 was correlated with p300 expression but not with topoisomerase II expression. Furthermore, the presence of p300 significantly sensitized cancer cells to TAS-103 but not to cisplatin. Taken together, these findings demonstrate novel genomic responses to anticancer agents that modulate Sp1 acetylation and Sp1-dependent transcription in an apoptotic pathway.

Acetylation↗

Midkine protects hepatocellular carcinoma cells against TRAIL-mediated apoptosis through down-regulation of caspase-3 activity.

BACKGROUND: It is believed that midkine (MK), a heparin-binding growth factor, plays an important role in carcinogenesis. However, the biologic mechanism of MK in hepatocellular carcinoma has not been clarified to date. The objective of the current study was to investigate the antiapoptotic role of MK in a human hepatoma cell line. METHODS: The human hepatoma cell line HepG2 was used to study the antiapoptotic effect of MK. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/actinomycin D (ActD)-induced apoptosis was detected using a 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphophenyl)-2H-tetrazolium monosodium salt (WST-8) assay, a caspase-3 activity assay, a caspase-8 activity assay, and flow cytometric analysis. RESULTS: TRAIL had a potent, dose-dependent inductive effect on cell death in HepG2 cells, for which viable cell counts decreased to 6.3% of the control count at a TRAIL concentration of 100 ng/mL in the presence of 500 ng/mL ActD. Flow cytometry was used to demonstrate that apoptosis induced by TRAIL/ActD was in fact the cause of cell death. According to the WST-8 assay, MK pretreatment resulted in the suppression of TRAIL/ActD-mediated apoptosis in HepG2 cells, although cell viability did not increase when HepG2 cells were treated with MK alone. Caspase-3 activity was down-regulated when MK was added, but caspase-8 activity was high in both the absence and presence of MK. CONCLUSIONS: The results of the current study indicate that MK acts as an antiapoptotic factor in HepG2 cells through the down-regulation of caspase-3 activity.

Apoptosis↗

Pitavastatin enhances the anti-fibrogenesis effects of candesartan, an angiotensin II receptor blocker, on CCl4-induced liver fibrosis in rats.

It has been shown that a statin (3-hydroxy-3-methyl-glutaryl coenzyme reductase inhibitor) enhances a suppressive effect of angiotensin II type 1 receptor (AT1-R) blocker (ARB) on injury-induced transforming growth factor (TGF)-beta expression in kidneys. We have shown that TGF-beta plays a crucial role in the development of liver fibrosis. In this study, we tested whether a combinatory use of a statin (pitavastatin) and an ARB (candesartan) may further inhibit liver fibrogenesis in carbon tetrachloride (CCl4)-treated rats. Candesartan (8 mg/kg/day) significantly suppressed injury-induced TGF-beta 1 expression in livers, and attenuated fibrogenesis, as evaluated by masson-trichrome staining and hydroxyproline content in livers. Pitavastatin (2 mg/kg/day) alone did not affect liver fibrogenesis. However, it enhanced significantly the suppressive effects of candesartan on TGF-beta 1 expression and fibrogenesis. Although we do not know the underlying molecular mechanisms at this moment, these results suggest that a combinatory use of a statin and an ARB may confer beneficial effects on human liver fibrogenesis.

Angiotensin II Type 1 Receptor Blockers↗

Binding of RNA to p53 regulates its oligomerization and DNA-binding activity.

The C-terminus of p53 is responsible for maintaining the latent, non-DNA-binding form of p53. However, the mechanism by which the C-terminus regulates DNA binding is not yet fully understood. We show here that p53 interacts with RNA via its C-terminal domain and that disruption of this interaction, by RNase A treatment, truncation or phosphorylation of the C-terminus, restores DNA-binding activity. Furthermore, the oligomerization of p53 is significantly enhanced by disrupting the interaction between p53 and RNA. These findings suggest that binding of RNA to p53 is involved in the mechanism of p53 latency.

Biopolymers↗

Luminescence properties of rhodamine 6G intercalated in surfactant/clay hybrid thin solid films.

To develop the solid-state laser oscillator based on laser dye compounds, the incorporation of rhodamine 6G (R6G, a laser dye) in cetyltrimethylammonium (CTA+) cationic surfactant/montmorillonite clay hybrid (HpC) thin solid films was investigated. The R6G/HpC samples were prepared by immersing the HpC films into a R6G aqueous solution with various concentration. X-ray diffraction patterns of the films of HpC, measured before and after the intercalation of R6G, proved the coexistence of both the dye and surfactant in clay interlayer spaces. All prepared thin films exhibited luminescence. It indicates that CTA+ molecules play a role as a partial suppressor of the aggregation of R6G molecules which prevents fluorescence. Moreover, the luminescence property of the present thin films was observed to be dependent on the co-intercalated degree of R6G molecules, indicating that the R6G intercalating in HpC interlayer space molecules exist as two or more luminescence species in the clay interlayer space.

Journal Article↗

Synthesis of gold nanoparticles modified with ionic liquid based on the imidazolium cation.

The synthesis and processing of nanoparticles consisting of metallic nanocrystal cores and organic monolayer shells promise interesting technological applications. Here, we report the synthesis of gold nanoparticles modified with ionic liquids based on the imidazolium cation. Aggregation-induced color changes of the gold nanoparticles in an aqueous solution were used as an optical sensor for anions via anion exchange of ionic liquid moiety. We also demonstrated the phase transfer of the gold nanoparticles from aqueous media to ionic liquid.

Journal Article↗

Photochemical assembly of gold nanoparticles utilizing the photodimerization of thymine.

Irradiation of UV light to the solution of gold nanoparticles modified with thymine units resulted in the formation of aggregates comprising chemical cross-linking gold nanoparticles through the photodimerization of the thymine units. Transmission electron microscopy and UV-visible absorption measurement showed the aggregates consisting of the gold nanoparticles. The effect of thymine unit density on the nanoparticle surface and the concentration of the gold nanoparticles in solution to the aggregation process were studied by UV-visible absorption measurement.

Dimerization↗

73-kDa molecular chaperone HSP73 is a direct target of antibiotic gentamicin.

Although gentamicin (GM) has been used widely as an antibiotic, the specific binding protein of the drug has not yet been understood sufficiently. Here we show that GM specifically associates with the 73-kDa molecular chaperone HSP73 and reduces its chaperone activity in vitro. In the present study, we investigated GM-specific binding proteins using a GM-affinity column and porcine kidney cytosol. After washing the column, only the 73-kDa protein was eluted from the column by the addition of 10 mm GM. None of the other proteins were found in the eluant. Upon immunoblotting, the protein was identical to HSP73. Upon CD spectrum analysis, the binding of GM to HSP73 resulted in a conformational change in the protein. Although HSP73 prevents aggregation of unfolded rhodanese in vitro, the chaperone activity of HSP73 was suppressed in the presence of GM. Using limited proteolysis of HSP73 by TPCK-trypsin, the GM binding site is a COOH-terminal for one third of the protein known to be a peptide-binding domain. During immunohistochemistry, HSP73 and GM were co-localized in enlarged lysosomes of rat kidneys with GM-induced acute tubular injury in vivo. Our results suggest that the specific association between HSP73 and GM may reduce the chaperone activity of HSP73 in vitro and/or in vivo, and this may have an interaction with GM toxicity in kidneys with GM-induced acute tubular injury.

Acetylglucosaminidase↗

Dopamine neurons can represent context-dependent prediction error.

Midbrain dopamine (DA) neurons are thought to encode reward prediction error. Reward prediction can be improved if any relevant context is taken into account. We found that monkey DA neurons can encode a context-dependent prediction error. In the first noncontextual task, a light stimulus was randomly followed by reward, with a fixed equal probability. The response of DA neurons was positively correlated with the number of preceding unrewarded trials and could be simulated by a conventional temporal difference (TD) model. In the second contextual task, a reward-indicating light stimulus was presented with the probability that, while fixed overall, was incremented as a function of the number of preceding unrewarded trials. The DA neuronal response then was negatively correlated with this number. This history effect corresponded to the prediction error based on the conditional probability of reward and could be simulated only by implementing the relevant context into the TD model.

Algorithms↗

Lymph node lesion in infectious mononucleosis showing geographic necrosis containing cytologically atypically B-cells. A case report.

Lymph node lesions in infectious mononucleosis (IM) show a marked histological diversity and may occasionally be confused with malignant lymphoma. We report on a rare case of IM showing geographic lymph node necrosis as well as angiocentric lymphoproliferative lesions, and containing numerous centroblasts, immunoblasts and Reed-Sternberg (RS)-like cells. The patient was a 40-year-old Japanese man with signs and symptoms of classical IM. This was later confirmed serologically, but the necrotic area comprised 50% of a cervical lymph node. The large lymphoid cells, including RS-like cells, were CD3-, CD5-, CD15-, CD20+, CD30+, CD45RO-, CD79a+, LMPI+, and EBNA2+. In situ hybridization study also disclosed that these cells were associated with Epstein-Barr virus (EBV). The patient was disease free during a follow-up of 15 years. Although the classical IM syndrome rarely shows a close resemblance to lymphomatoid granulomatosis of the lymph node or to EBV+ B- cell lymphoproliferative disorders associated with an immunodeficient state on histology, it is important for pathologists to be aware of this type of lesion in diagnostic practice.

Antigens, CD↗

Methylprednisolone-induced expression of mitochondrial heat shock protein 60 protects mitochondrial membrane potential in the hypoxic rat liver.

This study investigated the contribution made by mitochondrial heat shock protein (hsp) 60 to methylprednisolone-mediated protection against mitochondrial membrane depolarization under hypoxic conditions. A low-flow hypoxia model was generated in isolated male, fasted, pathogen-free Sprague-Dawley rat livers by reducing perfusate inflow pressure from 10 to 2.5 cm H2O for 2 h. The effects of methylprednisolone on mitochondrial membrane potential and expression of mitochondrial hsp 60 protein and mRNA were determined. We measured mitochondrial membrane potential by imaging rhodamine 123 fluorescence. Induction of mitochondrial hsp 60 was detected using two different anti-hsp 60 antibodies: one against the N-terminal signal sequence, which reacted exclusively with cytoplasmic hsp 60, and one against a different epitope, which reacted with cytoplasmic and mitochondrial hsp 60. In addition, the distribution of hsp 60 mRNA was examined using in situ hybridization. We found that under hypoxic conditions, there was a significant decline in mitochondrial membrane potential that was accompanied by a mild decline in the level of mitochondrial hsp 60, and that cytosolic hsp 60 was translocated into mitochondria. Pretreatment with methylprednisolone inhibited the declines in mitochondrial membrane potential and hsp 60 protein, as well as the translocation of cytosolic hsp 60. This raises the possibility that one way in which methylprednisolone protects the mitochondrial membrane potential under hypoxic conditions is to induce expression of mitochondrial hsp 60.

Animals↗

Clinical implication of idiopathic plasmacytic lymphadenopathy with polyclonal hypergammaglobulinemia: a report of 16 cases.

Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia is considered identical to multicentric Castleman's disease (MCD) reported in western countries. Clinically, both IPL and MCD are characterized by multicentric lymphadenopathy, prominent polyclonal hypergammaglobulinemia, elevated erythrocyte sedimentation rate, elevated serum interleukin-6 concentration, bone marrow plasmacytosis, and various abnormal laboratory data such as anemia and positive autoantibodies. However, IPL has a significantly better 5-year survival rate than that of MCD. Moreover, none of the present 16 cases developed Kaposi's sarcoma or B-cell lymphoma. Histologically, the interfollicular area contains a sheet of polytypic mature plasma cells in both IPL and MCD. In MCD, the majority of lymphoid follicles had hyaline-vascular germinal centers. However, lymphoid follicles of IPL usually exhibit a hyperplastic germinal center. Immunostaining also demonstrated a normal/reactive follicular dendritic cell network pattern in the germinal center of IPL. Moreover, there were no human herpes virus-8-positive cells detected by immunohistochemistry. The overall clinicopathologic and immunohistochemical findings of our 16 cases suggest that IPL is distinct from MCD reported in Western countries.

Adult↗

Clinical implication of dermatopathic lymphadenopathy among Japanese: a report of 19 cases.

To clarify the clinicopathologic and immunohistochemical features of dermatopathic lymphadenopathy not associated with mycosis fungoides among Japanese, 19 patients were studied. Seventy-four percent of the patients were more than 50 years old (median; 63 years, mean 61 years). Systemic symptoms such as fever were recorded in 68% and multicentric lymphadenopathy was noted in 83% of patients. An association of autoimmune disease or positivity of autoantibodies was recorded in 6 patients. Five patients showed cutaneous hypersensitivity reactions to a drug. Histologically, in addition to the dermatopathic lymphadenopathy, numerous immunoblasts were observed in 2 cases and sheet-like proliferation of mature plasma cells in 3 cases. Various atypical or malignant lymphoproliferative disorders exhibiting immunologic abnormalities such as angioimmunoblastic T-cell lymphoma or autoimmune disease-associated lymphadenopathy frequently occur in middle-aged and elderly patients. At least some of the patients with dermatopathic lymphadenopathy should be clinicopathologically differentiated from these lymphoproliferative disorders.

Adult↗

Antigen preservation in infarcted nodal B-cell lymphoma, with special reference to follicular center cell markers.

Among malignant lymphoproliferative disorders, an association with lymph node infarction appeared most frequently in diffuse large B-cell lymphoma (DLBCL), followed by that in follicular lymphoma (FL). However, little is known about antigen preservation in the infarcted lymphoid tissue. FLs eventually transformed to diffuse lymphomas, comprising a significant proportion of DLBCLs. To examine the antigen preservation of the follicular center cell markers in the infarcted lymphoma, we studied 7 DLBCLs and 4 FLs diagnosed concurrently with or following lymph node infarction. Sections of viable and infarcted tissue were immunostained in parallel by using a panel of antibodies effective in routinely processed, wax-embedded tissue. The panel included L26 (CD20), 56C6 (CD10), 124 (BCL-2), and polyclonal BCL-6 antibody. The present study indicated that CD20 (91%) and CD10 (80%) antigen appear to be well preserved even in infarcted lymphoma tissues and provide useful information regarding the infarcted material. However, BCL-2 (40%) and BCL-6 (0%) antigens were of little or no value in the infarcted lymphoid tissues.

Aged↗

Kuttner's tumor of salivary glands resembling marginal zone B-cell lymphoma of the MALT type: a histopathologic and immunohistochemical study of 7 cases.

Kuttner's tumor is a benign inflammatory process of the submandibular gland that presents as a hard mass mimicking a malignant neoplasm clinically. The histologic feature varies according to stage of evolution and severity of inflammation. We report here 7 cases of Kuttner's tumor that morphologically resemble primary salivary gland marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type. Histologically, the lobular architecture was distorted and the septa showed sclerosis. There was a dense lymphoplasmacytoid infiltration with lymphoid follicle formation accompanied by loss of acini and ducts. In 4 cases, a few salivary gland ducts contained the lymphoid cells within the epithelium. However, a true lymphoepithelial lesion was observed in none of the 7 cases. Immunohistochemical study demonstrated a disrupted follicular dendritic cell network, which is a characteristic finding of follicular colonization of MALT-type lymphoma. In 6 cases, there were a few small foci of lymphocytes somewhat resembling centrocyte-like cells of MALT-type lymphoma. However, immunohistological study demonstrated the mixed nature of the cells resembling centrocyte-like cells. Moreover, the polytypic nature of B lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction.

Aged↗

4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid inhibits angiogenesis in colon cancer through reduced expression of vascular endothelial growth factor.

4-[3,5-bis(trimethylsilyl)benzamido] Benzoic acid (TAC-101) has potent antiproliferative, antiangiogenic, and antitumor effects in vitro and in vivo. These effects might be due to TAC-101 binding to retinoic acid receptor alpha (RAR-alpha) and interfering with the binding of activator protein-1 (AP-1) to DNA. However, little is known about the detailed mechanism of TAC-101 function. We investigated the mechanism of the antiangiogenic effect of TAC-101 using a rat hepatic metastatic model in vivo and DLD-1 human colon cancer cells in vitro. Liver metastases were induced by portal injection of RCN-9 rat colonic cancer cells into F344 rats. TAC-101 (8 mg/kg) was orally administered 5 days per week for 4 weeks and then hepatic tumors were immunohistochemically evaluated for microvessel density (MVD) and vascular endothelial growth factor (VEGF). TAC-101 significantly reduced both MVD and VEGF expression. Northern blot analysis and ELISA indicated that TAC-101 efficiently inhibited production of VEGF mRNA and protein in DLD-1 cells in a time- and dose-dependent manner. These findings suggest that TAC-101 may inhibit progression and metastasis in colon cancer by interfering with tumor production of VEGF.

Angiogenesis Inhibitors↗