Biomedical subjects

Noriko Sato

Publications and source records attributed to Noriko Sato.

At least 37 records · Page 2Linked to original sources

PubMed2005

Vitamin D3 treatment for locally advanced thyroid cancer: a case report.

There are many intricacies in the surgical treatment of locally advanced thyroid cancer, including the medical management of the remaining functional organ and any cosmetic impairments, which are sometimes very difficult to manage and eventually carry a relatively high morbidity and mortality. Here, we report on a case of a 65-year-old female with an extremely locally-advanced thyroid cancer involving both lobes of the thyroid, blood vessels, trachea and esophagus. Despite the severity of her condition, oral administration of vitamin D3 (alphacalcido) has stalled both the tumor growth and further increases of serum thyroglobulin (Tg) level, and has led to a good preservation of quality of life for the last two years. Several reports have previously demonstrated the efficacy of vitamin D3 to inhibit the proliferation of thyroid cancer cell lines in vitro, but clinical evidence has been limited so far. Therefore, this case report provides important evidence for the effectiveness of vitamin D3 therapy against advanced thyroid cancers.

Aged↗

PubMed2005

Detection of lymph node involvement in hematologic malignancies using micromagnetic resonance lymphangiography with a gadolinum-labeled dendrimer nanoparticle.

Animal models of lymphoma should reflect their counterparts in humans; however, it can be difficult to ascertain whether an induced disease is intralymphatic or extralymphatic based on direct visualization. Current imaging methods are insufficient for identifying lymphatic and intralymphatic involvement. To differentiate intralymphatic from extralymphatic involvement, we have developed a magnetic resonance imaging-based lymphangiography method and tested it on two animal models of lymphoma. A gadolinium (Gd)-labeled dendrimer nanoparticle (generation-6; approximately 220 kDa/ approximately 10 nm) was injected interstitially into mice bearing hematologic malignancies to perform dynamic micromagnetic resonance lymphangiography (micro-MRL). Both a standard T1-weighted 3D fast spoiled gradient echo and a T2/T1-weighted 3D fast imaging employing steady-state acquisition (3D-FIESTA-C) were compared in an imaging study to differentiate intralymphatic from extralymphatic involvement of tumors. The lymphatics and lymph nodes were visualized with both methods in all cases. In addition, 3D-FIESTA-C depicted both the lymphatic system and the extralymphatic tumor. In an animal model, 3D-FIESTA-C demonstrated that the bulk of the tumor thought to be intralymphatic was actually extralymphatic. In conclusion, micro-MRL, using Gd-labeled dendrimer nanoparticles with the combined method, can define both the normal and abnormal lymphatics and can distinguish intralymphatic from extralymphatic diseases in mouse models of malignant lymphoma.

Animals↗

PubMed2005

Normal cranial nerves in the cavernous sinuses: contrast-enhanced three-dimensional constructive interference in the steady state MR imaging.

BACKGROUND AND PURPOSE: Three-dimensional (3D) constructive interference in steady state (CISS) MR imaging is useful for demonstrating cranial nerves (CNs) in the cistern. The purpose of this study was to evaluate normal CNs III, IV, V1, V2, and VI in the cavernous sinuses by using contrast-enhanced, three-dimensional (3D), Fourier transformation CISS MR imaging. METHODS: In 76 normal cavernous sinuses from 38 patients, detectability of CNs III-VI in the bilateral cavernous sinuses was evaluated by using contrast-enhanced 3D CISS MR imaging. In 40 cavernous sinuses from 20 patients, contrast-enhanced 3D CISS and contrast-enhanced T1-weighted MR imaging were compared for the detectability of these CNs. RESULTS: Each CN was separately demonstrated, and in 11 patients (29%), all CNs in the cavernous sinuses were identified on contrast-enhanced 3D CISS MR imaging. The images depicted the intracavernous segments of CNs III, IV, V1, V2, and VI in 76 (100%), 46 (61%), 70 (92%), 67 (88%), and 73 (96%) of the 76 sinuses, respectively. In comparison of imaging techniques, contrast-enhanced 3D CISS MR imaging had a detection rate significantly higher than that of enhanced T1-weighting imaging (P < .05) in all CNs except for CN III, which was detected in 100% of cases with both techniques. CONCLUSION: Contrast-enhanced 3D CISS MR imaging provides clear images of each CN in the cavernous segment. This useful method may contribute to the diagnosis of diseases involving the cavernous sinuses, such as Tolosa-Hunt syndrome.

Adolescent↗

PubMed2005

Pretargeted radioimmunotherapy of mesothelin-expressing cancer using a tetravalent single-chain Fv-streptavidin fusion protein.

UNLABELLED: Mesothelin is a glycoprotein that is overexpressed in several human tumors, including mesotheliomas and ovarian cancers, and has been identified as a potential target for therapy. We evaluated the biodistribution and tumor-targeting ability of an antimesothelin tetravalent single-chain Fv-streptavidin fusion protein (SS1scFvSA) in mice. METHODS: SS1scFvSA was labeled with 125I or 111In for evaluation of internalization in vitro and for optimization of its biodistribution. The A431-K5 mesothelin transfected cell line was used as the target. We used a 3-step pretargeting approach consisting of injections of (i) SS1scFvSA, followed 20 h later by (ii) a synthetic clearing agent, and (iii) 4 h later, radiolabeled (111In, 88Y/90Y, or 177Lu) 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-biotin. To optimize the tumor uptake, the effect of the specific activity of 111In-DOTA-biotin was evaluated. RESULTS: Approximately 60% of SS1sc FvSA internalized within 6 h. The optimal dose of SS1scFvSA for pretargeting was 600 microg. Decreasing the specific activity of DOTA-biotin by administering 0.1-5 microg of DOTA-biotin resulted in tumor uptake decreasing from 31.8 to 5.5 %ID/g (percentage injected dose per gram) at 2 h. Pretargeted therapy of A431-K5 tumor with 90Y doses of 11.1-32.4 MBq resulted in a dose-dependent tumor response. With 32.4 MBq, 86% of mice survived tumor free for 110 d. All nontreated mice died, with a median survival of 16 d. CONCLUSION: SS1scFvSA localized in the mesothelin-expressing tumor, resulting in a high accumulation of radiolabeled DOTA-biotin. The specific activity of DOTA-biotin had a significant effect on its tumor uptake. Therapeutic tumor doses were obtained without dose-limiting toxicity.

Animals↗

PubMed2004

Edaravone, a novel radical scavenger, inhibits oxidative modification of low-density lipoprotein (LDL) and reverses oxidized LDL-mediated reduction in the expression of endothelial nitric oxide synthase.

Edaravone, a newly synthesized synthetic radical scavenger, has been identified and adopted as an anti-stroke agent. However, its mechanism and the effect of edaravone on lipoprotein oxidation are not fully understood. Therefore, whether edaravone could suppress oxidation of low-density lipoprotein (LDL) and be involved in the expression of endothelial nitric oxide synthase (eNOS) in relation to anti-atherogenesis by improving and conserving vascular circulation was investigated. We investigated the in vitro effects of edaravone on copper- and endothelial cell-mediated LDL oxidation, and the expression of eNOS in human umbilical vein endothelial cells (HUVEC) modulated by oxidized LDL. The in vivo effect of edaravone on antioxidative effect was also studied in male rats intravenously administered with edaravone. Edaravone apparently inhibited copper- and HUVEC-mediated LDL oxidation at the concentration equivalent to serum concentrations in clinical use. The intravenous administration of edaravone also enhanced serum radical-scavenging property in rats. We tested the effect of edaravone on protein and mRNA expression of eNOS in HUVEC. Edaravone enhanced eNOS expression in HUVEC, presumably because of increased stability of eNOS mRNA, and reversed eNOS expression reduced by oxidized LDL nearly to the control levels. The present study demonstrates for the first time that edaravone increases eNOS expression with the inhibition of LDL oxidation, and that edaravone can reverse oxidized LDL-mediated reduction in eNOS expression in endothelial cells. The preventive action of edaravone from ischemic disease consequence may be attributed to these eNOS up-regulation with decreased oxidation.

Animals↗

PubMed2004

Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance.

Interleukin 15 (IL-15) is a critical factor for the proliferation and activation of natural killer (NK) and CD8 T cells. Recently, we demonstrated that IL-15Ralpha expressed on monocytes/dendritic cells captures and presents IL-15 to neighboring cells in trans (trans-presentation of IL-15) through cell-cell contact. In the current study, we provide evidence that the IL-15 presented in trans, but not soluble IL-15 at physiologic concentrations, augments the killing activity mediated by NK cells in vitro. In addition, transfection of IL-15Ralpha into a colon carcinoma cell line (MC38) enabled these cells to present IL-15 in trans to NK cells and augmented their killing activity, resulting in the efficient lysis of MC38 cells by NK cells in vitro. Furthermore, these transfected MC38 cells no longer form fatal pulmonary metastases in mice. It was also shown that NK cells play an important role in the rejection of MC38 cells under these circumstances. These results collectively suggest that the IL-15 trans-presentation mechanism operates in vivo to augment the tumor immune surveillance mechanism. Furthermore, our observation provides the scientific basis for a novel strategy to prevent cancer development/metastasis.

Animals↗

PubMed2004

Domain structure of bi-functional selenoprotein P.

Human selenoprotein P (SeP), a selenium-rich plasma glycoprotein, is presumed to contain ten selenocysteine residues; one of which is located at the 40th residue in the N-terminal region and the remaining nine localized in the C-terminal third part. We have shown that SeP not only catalyses the reduction of phosphatidylcholine hydroperoxide by glutathione [Saito, Hayashi, Tanaka, Watanabe, Suzuki, Saito and Takahashi (1999) J. Biol. Chem. 274, 2866-2871], but also supplies its selenium to proliferating cells [Saito and Takahashi (2002) Eur. J. Biochem. 269, 5746-5751]. Treatment of SeP with plasma kallikrein resulted in a sequential limited proteolysis (Arg-235-Gln-236 and Arg-242-Asp-243). The N-terminal (residues 1-235) and C-terminal (residues 243-361) fragments exhibited enzyme activity and selenium-supply activity respectively. These results confirm that SeP is a bi-functional protein and suggest that the first selenocysteine residue is the active site of the enzyme and the remaining nine residues function as a selenium supplier.

Binding Sites↗

PubMed2004

Synthesis and pharmacological properties of benzamide derivatives as selective serotonin 4 receptor agonists.

A series of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamides with a polar substituent group at the 1-position of the piperidine ring was synthesized and evaluated for its effect on gastrointestinal motility. The benzoyl, phenylsulfonyl, and benzylsulfonyl derivatives accelerated gastric emptying and increased the frequency of defecation. One of them, 4-amino-N-[1-[3-(benzylsulfonyl)propyl]piperidin-4-ylmethyl]-5-chloro-2-methoxybenzamide (13a, Y-36912), was a selective 5-HT4 receptor agonist offering potential as a novel prokinetic with reduced side effects derived from 5-HT3- and dopamine D2 receptor-binding affinity. In the oral route of administration, this compound enhanced gastric emptying and defecation in mice, and has a possibility as a prokinetic agent, which is effective on both the upper and the lower gastrointestinal tract.

Animals↗

PubMed2004

Lymphatic drainage imaging of breast cancer in mice by micro-magnetic resonance lymphangiography using a nano-size paramagnetic contrast agent.

BACKGROUND: The presence of lymph node metastases is an important factor in breast cancer patient prognosis. Therefore, the precise identification of sentinel lymph nodes in these patients is critical. Improving current magnetic resonance (MR) imaging methods using a newly synthesized nano-size paramagnetic molecule, G6, as a contrast agent, provides an attractive means toward attaining this goal. METHODS: A four-dimensional method of micro-MR lymphangiography using G6 (9 nm/240 kd) was developed to visualize the lymphatic ducts and lymph nodes draining mouse mammary tumors over time. The ability of micro-MR lymphangiography with the G6 contrast agent to visualize lymphatic drainage of normal mouse mammary tissue was compared with that of the conventional MR contrast agent, Gd-[DTPA]-dimeglumine (<1 kd). Lymphatic drainage in spontaneous and xenografted breast tumor models was visualized using the G6 contrast agent. RESULTS: Draining lymphatic ducts and lymph nodes were clearly visualized in the mammary tissue of normal mice and in spontaneous and xenografted breast tumor models after a direct mammary gland or peritumoral injection of G6. Gd-[DTPA]-dime-glumine, by contrast, failed to depict lymphatic flow from the mammary tissue in normal mice using the same method. Micro-MR lymphangiography using the G6 contrast agent revealed the absence of filling in the metastatic foci of affected lymph nodes. CONCLUSIONS: The superior temporal and spatial resolution of micro-MR lymphangiography using the contrast agent G6 may facilitate the study of tumor lymphatic drainage and lymphatic metastasis in both experimental animals and clinical medicine. In addition, this may be a powerful new method for sentinel lymph node localization in human breast cancer.

Animals↗

PubMed2004

Physical and functional interactions between Daxx and DNA methyltransferase 1-associated protein, DMAP1.

Daxx has been shown to play an essential role in type I IFN-alphabeta-mediated suppression of B cell development and apoptosis. Recently, we demonstrated that Tyk2 is directly involved in IFN signaling for the induction and translocation of Daxx, which may result in growth arrest and/or apoptosis of B lymphocyte progenitors. To clarify how Daxx regulates B cell development, we examined Daxx interacting partners by yeast two-hybrid screening. DNA methyltransferase 1 (DNMT1)-associated protein (DMAP1) was identified and demonstrated to interact with Daxx. The interaction regions in both proteins were mapped, and the cellular localization of the interaction was examined. Both Daxx and DMAP1 formed a complex with DNMT1 and colocalized in the nucleus. DMAP1 enhanced Daxx-mediated repression of glucocorticoid receptor transcriptional activity. Furthermore, Daxx protected protein degradation of DMAP1 in vivo. These results provide the novel molecular link between Daxx and DNMT1, which establishes a repressive transcription complex in the nucleus.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Hepatocyte targeting of 111In-labeled oligo-DNA with avidin or avidin-dendrimer complex.

To establish an effective nonviral gene transfer vector to hepatocytes, various oligo-carrier complexes were developed employing dendrimer (G4) and avidin-biotin systems (Av-bt), and their biodistribution were evaluated. In-111-labeled-oligo, without any carriers, showed low uptake in normal organs other than the kidney (21.48% ID/g at 15 min, 18.48% ID/g at 60 min). In contrast, 111In-oligo coupled with avidin through biotin (111In-oligo-bt-Av) showed very high accumulation in the liver (50.95% at 15 min, 47.88% at 60 min). 111In-oligo complexed with G4 showed high uptake in the kidney and spleen, but its hepatic uptake was relatively low (13.12% at 15 min, 10.67% at 60 min). When both G4 and Av-bt systems were employed, 111In-oligo/G4-bt-Av showed extremely high uptake in the lung (182.33% at 15 min, 125.54% at 60 min), probably due to the formation of large molecular weight complex and aggregates which are trapped in the lung, and its hepatic uptake was lower than 111In-oligo-bt-Av. 111In-oligo-bt-Av, which exhibited the highest hepatic uptake in vivo, also showed high and rapid internalization into hepatocytes. The avidin-biotin system seems to have potential as a carrier of oligo-DNA to the liver.

Animals↗

PubMed2004

Effect of phytate-removal and deamidation of soybean proteins on calcium absorption in the in situ rats.

Soybean proteins were deamidated by cation-exchange resins after phytate, the inhibitor for calcium absorption from the small intestine, was removed in order to provide the enhancement function of calcium absorption to soybean proteins. About 92% of the phosphorus was removed from the soybean proteins by anion-exchange-resin treatment, indicating that most of the phytate was removed. About 70% of the acid amide was deamidated by cation-exchange-resin treatment, and phytate-removed and deamidated soybean proteins (PrDS) having high calcium binding properties were obtained. PrDS were hydrolyzed by digestive enzymes and their calcium-binding properties and the enhancement function of the calcium absorption from the small intestine of rats were examined. As a result, PrDS retained their high calcium binding properties even after hydrolysis by digestive enzymes. In situ experiments showed that PrDS and their hydrolysates enhanced the calcium absorption from the intestine.

Animals↗

PubMed2004

Increased serum iron may contribute to enhanced oxidation of low-density lipoprotein in smokers in part through changes in lipoxygenase and catalase.

BACKGROUND: Increased oxidative stress is considered to be causative for cardiovascular disease (CVD) in smokers, but its mechanisms are still unclear. We compared oxidative stress markers between male smokers and male nonsmokers. METHODS: Twenty-three healthy men (11 nonsmokers and 12 smokers) were enrolled, and blood samples after 12 h of fasting were collected to assess plasma lipids and oxidative stress markers. The effects of iron loading on 12-lipoxygenase (12-LO) expression and activity in human umbilical vein endothelial cells (HUVECs) were tested in vitro to investigate the relevance of iron to oxidation potential in vivo. RESULTS: Higher levels of plasma-oxidized low-density lipoprotein (LDL) and lipid peroxide (LPO), and higher oxidizability of LDL were observed in smokers than in nonsmokers. Higher levels of serum iron and lower levels of plasma vitamin E were observed in smokers than in nonsmokers. Stepwise multiple regression analysis showed that serum iron was an independent determinant for both plasma-oxidized LDL and lag time of LDL oxidation. Iron loading enhanced 12-LO expression threefold and its activity 1.5-fold. Moreover, iron loading decreased catalase expression by 50% and significantly reduced its activity by 75%. CONCLUSIONS: Enhanced oxidative stress in smokers may be due to increased iron levels. Iron-induced modulation of expression and activity of 12-LO and catalase may be relevant to increased iron-related oxidative stress as observed in smokers.

Adult↗

PubMed2004

Fluctuation of chromatin unfolding associated with variation in the level of gene expression.

We examined whether spontaneous alteration of chromatin structure, if any, correlates with variation in gene expression. Gene activation is associated with changes in chromatin structure at different levels. Large-scale chromatin unfolding is one such change detectable under the light microscope. We established cell clones carrying tandem repeats (more than 50 copies spanning several hundred kb) of the GFP (green fluorescent protein)-ASK reporter genes driven by a tetracycline responsive promoter. These clones constitutively express the transcriptional transactivator. Flow cytometry and live-recording fluorescence microscopy revealed that, although fully activated by a saturating amount of doxycycline, GFP-ASK expression fluctuated in individual cell clones, regardless of the cell cycle stage. The GFP-ASK expression changed from lower to higher levels and vice versa within a few cell cycles. Furthermore, the levels of GFP-ASK expression were correlated with the degrees of chromatin unfolding of the integrated array as detected by FISH (fluorescent in situ hybridization). The chromatin unfolding was not coupled to a mitotic event; around one-third of the daughter-pairs exhibited dissimilar degrees of chromatin unfolding. We concluded that fluctuation of chromatin unfolding was likely to result in variation in gene expression, although the source of the fluctuation of chromatin unfolding remains to be studied.

Blotting, Southern↗

PubMed2004

Acute nephrotoxicity of aristolochic acids in mice.

Aristolochic acids (AA), present in Aristolochia plants, are the toxin responsible for Chinese herbs nephropathy (CHN), a rapidly progressive tubulointerstitial nephritis (TIN). To clarify the mechanisms of the development of CHN, we tried to induce TIN in mice using AA. Three strains of inbred mice, BALB/c, C3H/He and C57BL/6, received 2.5 mg kg(-1) of AA or AA sodium salt (AANa) daily by intraperitoneal or oral administration, 5 days a week for 2 weeks. Serum and renal tissue were obtained at sacrifice. Twelve-hour urine samples were individually collected in a metabolic cage at one-week intervals. In the AA-injected groups, severe tubular injury, with the appearance of acute tubular necrosis, and rare cell infiltration into the interstitium, were seen in BALB/c mice. C3H/He mice also developed TIN with prominent cell infiltration into the interstitium and interstitial fibrosis. In C57BL/6 mice, only mild and focal tubulointerstitial changes were seen. Serum creatinine and blood urea nitrogen increased in BALB/c and C3H/He mice. Immunofluorescent study revealed no deposition of immune components in kidneys. In the AANa-treated groups, TIN was also seen in all groups, but even more severe tubulointerstitial changes were induced by intraperitoneal injection. Further examination using purified AAI, AAII, AAIVa and aristolactam I (ALI) revealed that AAI induced strong nephrotoxicity in mice, and that AAII resulted in mild nephrotoxicity. However, AAIVa and ALI caused no nephrotoxicity in this experimental system. There are strain differences in mice in their susceptibility to AA nephropathy. AAI exerted the strongest nephrotoxic effect in mice.

Acute Disease↗

PubMed2004

Pulmonary thromboembolism. Evaluating the indication and effect of a vena caval filter with indium-111-platelet scintigraphy.

A 63-year-old woman complained of chest pain and was referred to hospital where she was found to have left pleural effusion and swelling, local heat and edema of the right lower leg. Initial pulmonary perfusion scintigraphy demonstrated multiple defects and pulmonary thromboembolism (PTE) was confirmed during the anticoagulant and thrombolytic therapy against thrombophlebitis. A Greenfield filter was inserted in the inferior vena cava to prevent recurrence of PTE from the thrombosis that was resistant to therapy. In-111-labeled platelet scintigraphy (platelet scintigraphy) showed abnormal uptake of platelets in the chest, femoral veins and abdomen, which suggested active thrombus formation in those regions, including the filter, and a risk of recurrent PTE. Therefore, the thrombolytic therapy was terminated and the anticoagulant therapy intensified. A computed tomography (CT) scan revealed thrombus at the filter, which was markedly decreased 1 month later on platelet scintigraphy. Pulmonary ventilation and perfusion scintigraphy revealed remarkable improvement of the PTE. In this case, platelet scintigraphy complemented CT in demonstrating the activity and localization of the thrombus and can be used to evaluate the risk of recurrence during thrombolytic therapy after insertion of a filter.

Blood Platelets↗

PubMed2004

Enhanced calcium absorption in the small intestine by a phytate-removed deamidated soybean globulin preparation.

Soybean globulins were deamidated after removing phytate using ion-exchange resins, and then hydrolyzed by digestive enzymes. The phytate-removed deamidated soybean globulins (PrDS) retained high calcium-binding ability even after the hydrolysis by digestive enzymes. PrDS and its hydrolysates enhanced calcium absorption from the small intestine when injected into the small intestine together with a calcium solution.

Animals↗

PubMed2004

Serous surface papillary carcinoma of the peritoneum: clinical, radiologic, and pathologic findings in 11 patients.

OBJECTIVE: The purpose of our study was to describe the clinical, radiologic, and pathologic findings of serous surface papillary carcinoma of the peritoneum in 11 patients. CONCLUSION: Serous surface papillary carcinoma of the peritoneum should be included in the differential diagnosis when ascites, omental caking, and peritoneal nodules or enhancement are observed in a postmenopausal woman with or without ovarian enlargement.

Aged↗