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Biomedical subjects

T Satoh

Publications and source records attributed to T Satoh.

At least 19 recordsLinked to original sources

Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer.

Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the risk of venous thromboembolism (VTE). However, the mechanisms remain unclear. Tissue factor (TF) supposedly represents a major factor in the procoagulant activities of cancer cells. The present study examined the involvement of TF expression in VTE for patients with ovarian cancer. Subjects comprised 32 consecutive patients (mean age 49.8 years) with histologically confirmed ovarian cancer. Presence of VTE was examined using a combination of clinical features, D-dimer levels and venous ultrasonography. Immunohistochemical analysis was used to evaluate TF expression into 4 degrees. Venous thromboembolism was identified in 10 of the 32 patients (31%), including five of the 11 patients with clear cell carcinoma. Tissue factor expression was detected in cancer tissues from 24 patients and displayed significant correlations with VTE development (P=0.0003), D-dimer concentration (P=0.003) and clear cell carcinoma (P<0.05). Multivariate analysis identified TF expression as an independent predictive factor of VTE development (P<0.05). Tissue factor (TF) expression is a possible determinant of VTE development in ovarian cancer. In particular, clear cell carcinoma may produce excessive levels of TF and is more likely to develop VTE.

Adolescent↗

Differential taste coding of salt and acid by correlative activities between taste-sensitive neuron types in rat gustatory cortex.

Using a multi-electrode recording technique, the present study aimed to elucidate the role of broadly-tuned taste-sensitive neurons in the rat gustatory cortex in discriminating between salt and acid. A majority of taste-sensitive neurons (94/119 neurons; 78%) were classified as NaCl (N)-, HCl (H)- or NaCl and HCl (NH)-best neurons. Of 63 neuron pairs (94 neurons), 31 showed significant peaks and/or troughs in their cross-correlograms (CCs) during taste stimulation periods. During NaCl stimulation, the incidence of significant correlation and the mean frequency of correlated discharges (FC) in the N/N and NH/NH pairs were higher than those in the other best-taste pairs. In contrast, during HCl stimulation both indices in the N/N or H/H pairs were very low, while those in the NH/NH pairs were high. These results suggest that (1) correlated activities between N-best neurons and those between NH-best neurons play a significant role in taste quality coding of salt, and that (2) correlated activities between NH-best neurons may be important for sour taste coding as well. Peak formation in CCs tended to be more frequent in the homo-types (N/N, H/H and NH/NH pairs) than in the hetero-types (N/NH, N/H and H/NH pairs). In contrast, troughs were observed mostly in the hetero-types. Inhibitory interaction in hetero-type pairs together with coactivation in homo-type pairs may enhance taste discrimination by taste-sensitive neuron populations.

Algorithms↗

Adenoviral vector-mediated RTVP-1 gene-modified tumor cell-based vaccine suppresses the development of experimental prostate cancer.

We previously identified a novel p53 target gene, RTVP-1, that possesses unique cytotoxic and immunostimulatory activities which make it potentially useful for cancer gene therapy. To test the therapeutic potential of RTVP-1 in a gene-modified tumor cell-based vaccine model, we used an adenoviral vector capable of efficient transduction and expression of RTVP-1 (AdRTVP-1), together with a highly metastatic mouse prostate cancer cell line (178-2 BMA). A vaccine was prepared with 178-2 BMA cells transduced with AdRTVP-1 or a control adenoviral vector expressing beta-galactosidase (Adbetagal). After irradiation of the cells, syngeneic 129/Sv mice were vaccinated three times at weekly intervals. After 3 weeks, they were challenged with orthotopic 178-2 BMA cells. After 21 days, fewer than 60% of the RTVP-1-cell-vaccinated mice developed tumors compared to 100% of the control mice. The RTVP-1-cell vaccine significantly reduced primary tumor wet weight compared with control Adbetagal-cell vaccine (P<0.0001 at 7 and 14 days). Experimental metastasis to lung was also significantly reduced (P=0.0377), and survival significantly increased (P=0.0002). In addition, significantly increased NK and CTL activities were demonstrated in the AdRTVP-1-cell-vaccinated mice. These findings indicate that RTVP-1 gene-modified cell-based vaccines may be useful in the prevention of recurrent prostate cancer.

Adenoviridae↗

Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophilic [correction of electrophillic] phase II inducers.

Electrophilic neurite outgrowth-promoting prostaglandin (NEPP) compounds protect neurons from oxidative insults. At least part of the neuroprotective action of NEPPs lies in induction of hemeoxygenase-1 (HO-1), which, along with other phase II enzymes, serve as a defense system against oxidative stress. Here, we found that, by using fluorescent tags and immunoprecipitation assays, NEPPs are taken up preferentially into neurons and bind in a thiol-dependent manner to Keap1, a negative regulator of the transcription factor Nrf2. By binding to Keap1, NEPPs prevent Keap1-mediated inactivation of Nrf2 and, thus, enhance Nrf2 translocation into the nucleus of cultured neuronal cells. In turn, Nrf2 binds to antioxidant/electrophile-responsive elements of the HO-1 promoter to induce HO-1 expression. Consistent with this notion, NEPP induction of an HO-1 reporter construct is prevented if the antioxidant-responsive elements are mutated. We show that NEPPs are neuroprotective both in vitro from glutamate-related excitotoxicity and in vivo in a model of cerebral ischemia/reperfusion injury (stroke). Our results suggest that NEPPs prevent excitotoxicity by activating the Keap1/Nrf2/HO-1 pathway. Because NEPPs accumulate preferentially in neurons, they may provide a category of neuroprotective compounds, distinct from other electrophilic compounds such as tert-butylhydroquinone, which activates the antioxidant-responsive element in astrocytes. NEPPs thus represent a therapeutic approach for stroke and neurodegenerative disorders.

Cell Line↗

Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model.

We developed a preclinical prostate cancer model to study the feasibility of adoptive immunotherapy for residual tumor following neo-adjuvant in situ adenoviral-vector-mediated interleukin 12 (AdIL-12) gene therapy. Splenocytes were obtained from mice with orthotopic 178-2 BMA metastatic mouse prostate cancers treated previously with AdIL-12, or a vector with the IL-12 genes plus the costimulatory gene B7-1 (AdIL-12/B7), or a control gene (Adbetagal). The splenocytes were subsequently injected intravenously into syngeneic mice bearing orthotopic 178-2 BMA tumors generated 3 days previously. Significant orthotopic tumor growth suppression was achieved with splenocytes derived from mice whose tumors had been injected with AdIL-12 compared to splenocytes from control Adbetagal mice (P = 0.0005) and splenocytes from AdIL-12/B7-treated mice significantly suppressed spontaneous lung metastases compared to splenocytes from control mice (P = 0.0356). Adoptive transfer of splenocytes from either AdIL-12 (P = 0.004) or AdIL-12/B7 (P = 0.009)-treated mice significantly prolonged survival relative to controls. Transfer of NK and tumor-specific CTL activities was detected and depletion of CD4+ and CD8+ T cells by in vitro antibody-mediated complement lysis of the splenocytes prior to injection abrogated the effects. Systemic IL-12 administration delivered by intramuscular AdIL-12 injection enhanced the antitumor effects of adoptive splenocyte transfer and boosted the CTL response. Our data provide evidence that this form of adoptive immunotherapy can enhance the effectiveness of neo-adjuvant in situ IL-12 gene therapy in cases of persistent malignancy.

Adoptive Transfer↗

Technique and assessment of sentinel lymph node biopsy usefulness in laparoscopy-assisted distal gastrectomy.

BACKGROUND: Recently, some studies have suggested that sentinel node biopsy also can be applied to gastric cancer. The authors apply sentinel lymph node biopsy in laparoscopy assisted distal gastrectomy to perform it as safe limited surgery. Limited surgery is a procedure in which the extent of lesion resection and lymph node dissection is reduced. The authors demonstrate that intraoperative diagnosis of lymph node metastasis is useful in this respect. METHODS: The study was conducted with 38 patients (29 men and 9 women) who had a preoperative diagnosis of T1 tumor invasion. The patients had a mean age of 66.2 years. Patent blue (1%) was injected submucosally into four or five different sites around the primary tumor at 1 ml per site. Blue-stained lymphatics and lymph nodes could be seen by turning over the greater omentum and the lesser omentum extraperitoneally. If blue nodes were found, biopsy was performed. RESULTS: The mean number of blue nodes dissected was 2.5 +/- 1.9. Intraoperative identification and biopsy of blue nodes could be performed for 35 (92.1%) of the 38 patients. Of the 35 patients in whom blue nodes were identified, 4 (9.7%) had metastases in blue nodes confirmed by intraoperative frozen-section diagnosis. Intraoperative frozen-section diagnosis was negative for blue node metastasis in 31 patients. Postoperative permanent section diagnosis also showed no evidence of lymph node metastasis in these 31 patients (100% accuracy, 0% false-negative rates). CONCLUSION: The reported method allows observation of blue-stained lymphatics up to 2 h after patent blue injection. Sentinel node biopsy was performed in laparoscopy assisted distal gastrectomy, making it technically equivalent to open gastrectomy. Sentinel node biopsy can serve as a method to determine the appropriate use of laparoscopy assisted distal gastrectomy for management of T1 gastric cancer.

Aged↗

Effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma total homocysteine concentrations in young Japanese male subjects.

OBJECTIVE: To investigate the effects of short-term folic acid and/or riboflavin supplementation on serum folate and plasma plasma total homocysteine (tHcy) concentrations in young Japanese male subjects. DESIGN: In a double blind, randomized controlled trial. INTERVENTION: Subjects were randomly assigned to one of four groups and received a placebo (control group), 800 microg/day folic acid (FA group), 8.4 mg/day riboflavin (R group), or both (FAR group) for 2 weeks. SETTING: Tokyo, Japan. SUBJECTS: In total, 32 healthy male volunteers aged 20-29 years. RESULTS: At the end of the 2 week supplementation period, the tHcy concentration decreased significantly in the FA group. Serum folate concentrations had increased between 2.7 and 2.0-fold in the FA and FAR groups, respectively, but the mean within-group changes in serum folate and plasma tHcy concentrations did not differ between these two groups. At the end of the study, alanine amino transferase was decreased in the R and FAR groups, while alanine amino transferase was increased in the FA group. CONCLUSION: Supplementation with folic acid, 800 microg/day, for 2 weeks, increased the serum and red blood cell folate concentrations and decreased the plasma tHcy concentrations in healthy young male subjects. Riboflavin supplementation may have blunted the effect of folic acid, which resulted in a diminished reduction of tHcy in our subjects.

Adult↗

In vitro differences of stress concentrations for internal and external hex implant-abutment connections: a short communication.

The aim of this study was to clarify the difference in the stress distribution patterns between implants with external-hex or internal-hex connection systems using in vitro models. Three 13 mm fixtures with external-hex and internal-hex connections were installed into an acrylic bone analogue. One piece abutments of 7 mm height was connected. Strain gauges were attached to the abutment surface, and the cervical and fixture tip areas of the bone analogue surface. Vertical and horizontal load applied was 30 N. Data were normalized for each model by obtaining values relative to the sum of the three values. Almost the same force distribution pattern was found under vertical load in both systems. Fixtures with external-hex showed an increase in strain at the cervical area under horizontal load, while in internal-hex fixtures the strain was at the fixture tip area. Within limitations of our model study, it was suggested that fixtures with internal-hex showed widely spread force distribution down to the fixture tip compared with external hex ones.

Dental Abutments↗

Regulatory mechanisms of galectin-9 and eotaxin-3 synthesis in epidermal keratinocytes: possible involvement of galectin-9 in dermal eosinophilia of Th1-polarized skin inflammation.

BACKGROUND: Skin eosinophilia is a common feature of allergic skin diseases, but it is unclear how epidermal and dermal eosinophil infiltration is controlled. To investigate regulation of localization of eosinophils in skin, we examined the regulatory mechanisms of expression of eosinophil-specific chemoattractants in dermal fibroblasts and epidermal keratinocytes. METHODS: We analyzed production of eotaxin, eotaxin-2, eotaxin-3 and galectin-9 by dermal fibroblasts and epidermal keratinocytes in response to several stimuli in vitro. RESULTS: Dermal fibroblasts produced eotaxin and eotaxin-3 in response to stimulation by interleukin (IL)-4 and/or tumor necrosis factor-alpha. Similarly, IL-4 stimulated epidermal keratinocytes to secrete eotaxin-3. However, we did not detect eotaxin mRNA expression or protein secretion by keratinocytes stimulated in vitro. Interferon (IFN)-gamma induced galectin-9 expression on dermal fibroblasts. Conversely, expression of galectin-9 on epidermal keratinocytes was dose-dependently inhibited by IFN-gamma. The immunohistochemical assays revealed that dermal fibroblasts (but not epidermal keratinocytes) in the lesional skin of psoriasis vulgaris (a Th1-polarized disease) express significant levels of galectin-9. CONCLUSION: Eotaxin-3 contributes to dermal and epidermal eosinophil infiltration in Th2-polarized skin inflammation in which IL-4 is produced. In contrast, IFN-gamma-dominated inflammation appears to mediate eosinophil extravasation into the dermis and eosinophil adhesion to dermal fibroblasts via galectin-9 in association with decreased chemoattractant activity of epidermal galectin-9. The present results reveal a novel mechanism of dermal eosinophilia in IFN-gamma-mediated skin inflammation, and reflect concerted chemoattractant production involving dermal and/or epidermal eosinophilia during changes in the local cytokine profile.

Animals↗

A cross sectional study of the respiratory health of workers handling printing toner dust.

BACKGROUND: Although recent case reports have suggested possible respiratory effects of solid toner dust inhalation, this hypothesis has not been verified by epidemiological studies. OBJECTIVES: To conduct a cross sectional study to evaluate the association between the biological indices of lung fibrosis and toner dust exposure in an occupational cohort handling solid toner dust in their work life. METHODS: A total of 600 male toner workers and 212 control subjects were surveyed in terms of their subjective respiratory symptoms, pulmonary functions, and chest radiographic findings. In addition to the exposure history, the current working conditions and personal exposure levels to toner dust were also examined. RESULTS: Although subjects handling toner for more than 20 years tended to show a higher prevalence of respiratory symptoms and minimal chest x ray abnormalities, there was no consistent relation between the exposure to toner dust and the biological responses of the respiratory system. CONCLUSION: Deterioration of respiratory health related to toner dust exposure is less likely to occur in current well controlled work environments, especially if the powdered toner is handled carefully. Nonetheless, it is important to collect further epidemiological evidence on the biological effects of toner dust inhalation, preferably using a longitudinal study design.

Adult↗

Pharmacology and toxicology of Bupleurum root-containing Kampo medicines in clinical use.

Kampo (Japanese traditional herbal) medicines have been produced by combining multiple crude drugs, almost all of plant origin but with some of animal or mineral origin, and contain a great many substances. Their effect is a combination of the various interactions of the constituent substances, whether they are enhancing, synergistic or suppressive. Kampo medicine has an overall effect that is different from the combined effects of individual crude drugs, and several side effects such as anorexia, slight fever and nausea have been reported in the treatment of certain disorders and disease states with Kampo medicines. Among 210 medical formulations used in Japan, some relevant information on the clinical uses, pharmacology and toxicology of six manufactured Kampo medical formulations, Shosaikoto, Daisaikoto, Saikokeishito, Hochuekkito, Saibokuto and Saireito, containing Bupleurum root are reviewed. Studies of some potential interactions between Kampo medicine and western drugs are also considered.

Animals↗

Differential diagnosis of the infundibular dilation and aneurysm of internal carotid artery: assessment with fusion imaging of 3D MR cisternography/angiography.

Fusion imaging of 3D MR cisternography/angiography was used for the assessment of the vascular bulging finding detected by MR angiography from the viewpoint of the outer wall configuration of the corresponding internal carotid artery depicted by MR cisternography. With a fusion image, useful information was obtained to distinguish an infundibular dilation and enlarged origin of the normal posterior communicating artery from an aneurysm. This imaging technique can be a feasible addition to a noninvasive screening of cerebrovascular lesions with MR angiography alone.

Adult↗

Autoantibody to CD40 ligand in systemic lupus erythematosus: association with thrombocytopenia but not thromboembolism.

OBJECTIVES: To examine the prevalence, clinical associations and pathogenic roles of autoantibodies to CD40 ligand (CD40L) in patients with systemic lupus erythematosus (SLE). METHODS: Plasma anti-CD40L antibodies from 125 patients with SLE, 24 with primary antiphospholipid syndrome (APS) and 90 with idiopathic thrombocytopenic purpura (ITP) and from 62 healthy individuals were measured with an enzyme-linked immunosorbent assay (ELISA). HeLa cells transfected with human CD40L cDNA (HeLa/CD40L) were used to confirm the presence of anti-CD40L autoantibodies. The effect of anti-CD40L antibodies on the CD40L-CD40 interaction was evaluated by observing CD40L-induced IkappaB activation in CD40-expressing fibroblasts. RESULTS: Anti-CD40L autoantibody was detected in seven (6%) SLE, three (13%) primary APS and 11 (12%) ITP patients, but in no healthy controls. Antibody binding in an ELISA was competitively inhibited by membrane components of HeLa/CD40L. Anti-CD40L antibody-positive IgG specifically bound the surface of living HeLa/CD40L, as shown by flow cytometry. The frequency of thrombocytopenia was significantly higher in SLE patients with the anti-CD40L antibody than in those without (100 vs 14%; P<0.00001), whereas there was no association between the anti-CD40L antibody and thrombosis. Binding of the anti-CD40L antibodies in patients' plasma to CD40L was competitively inhibited by a series of mouse anti-CD40L monoclonal antibodies. Anti-CD40L antibody-positive IgG failed to inhibit CD40L-induced IkappaB activation. CONCLUSIONS: Anti-CD40L autoantibody is associated with thrombocytopenia but not thromboembolism. Our findings are potentially useful in understanding the complex roles of CD40L in the pathophysiology of thrombosis and haemostasis as well as the thromboembolic complications that occur during treatment with anti-CD40L humanized antibody.

Adult↗

Preparation and characterization of spherical polymer packings from polybutadiene for size-exclusion chromatography.

Porous polymer spherical particles for column packings in nonaqueous size-exclusion chromatography (SEC) were prepared from 1,2-syndiotactic polybutadiene by suspension and evaporation method. The polymer microbeads obtained were crosslinked by radical reaction between 2-vinyl groups in polybutadiene with ultraviolet radiation, to render them insoluble. These microbeads have wider chromatographic separation width than polystyrene column packings. In addition, the polybutadiene microbeads did not show the excessive retention observed with commercial polystyrene columns for polycyclic aromatic compounds. Therefore, a close correlation between the elution volume and M, for polycyclic aromatic compounds was observed with polybutadiene microbeads columns.

Butadienes↗

Preliminary study of using imaging plates to map skin dose of patients in interventional radiology procedures.

A method using europium-doped BaFBr imaging plates (IPs) has been studied for mapping entrance skin doses during interventional radiology (IR); the mapping is useful for detecting overlap between irradiation fields and determining the most exposed skin areas. IPs, which are two-dimensional radiation sensors made of photostimulated luminescence materials, have a linear dose response up to approximately 100 Gy, can accurately measure doses from 1 microGy to 10 Gy and can be used repeatedly. Because the energy dependence of IPs is rather high, the IPs were characterised in this study and a sensitivity variation of approximately 13% was observed for effective energies of 32.7 to 44.7 keV, which are used in IR procedures. Simulation of actual interventional cardiology procedures showed that the variation of sensitivity was within 5%, meaning that IPs are practical for measuring skin doses during IR. Moreover, the patient data can be stored online and easily called up when IR procedures must be repeated, helping to prevent radiation injuries.

Dose-Response Relationship, Radiation↗

Transparent color-coded three-dimensional diffusion-weighted magnetic resonance imaging for the numerical analysis of reversible and irreversible hyperacute ischemic stroke--case report.

Although diffusion-weighted (DW) magnetic resonance (MR) imaging can detect hyperacute ischemic parenchyma with high sensitivity, the ability of DW images to reveal subtle change in abnormal diffusion may be limited by the conventional visual evaluation. To overcome the limitation, we have developed a method of transparent color-coded three-dimensional (3D) DW MR imaging for the computer-aided numerical analysis of hyperacute ischemic stroke. The 3D images were reconstructed from volume data of source DW images by using a parallel volume-rendering algorithm with transluminal imaging technique. By selecting a threshold range from a signal intensity opacity chart of volume-rendering data set, several high signal intensity areas were depicted and assigned to different colors, transparently through contours of the brain. This imaging was applied in a case of a recanalized middle cerebral artery (M2) occlusion with partially reversible ischemic parenchyma accompanied by partial recovery from ischemic neurological deficit. Complex and dynamic change in hyperacute ischemic parenchyma, with regression of subtle high signal intensity areas and progression of ischemic parenchyma, was depicted three-dimensionally. Transparent color-coded 3D DW MR imaging may provide computer-aided numerical analysis of hyperacute ischemic stroke appearing as a high signal intensity area on the source DW images.

Aged↗

Pharmacological study of BRS, a new bicarbonated Ringer's solution, in partially hepatectomized rabbits.

BACKGROUND AND OBJECTIVE: The effects of bicarbonated Ringer's solution were evaluated and compared with those of acetated Ringer's, lactated Ringer's and Ringer's solutions in partially hepatectomized rabbits. METHOD: Animals were randomly divided into six groups (n = 6 in each group): a sham-operated group, an operated group without infusion, and four operated groups with infusions of each of the four Ringer's solutions. Each Ringer's solution was intravenously administered at 40 mL kg(-1) h(-1) for 1.5 h. Arterial blood gases, plasma magnesium concentrations and cardiovascular parameters were analysed. RESULTS: The partial hepatectomy-induced decrement of base excess was inhibited by bicarbonated Ringer's solution more remarkably than by either lactated or plain solutions (P < 0.01). The alkalinizing effect of bicarbonated Ringer's solution tended to be more marked than that of the acetated solution but not significantly so. Plasma magnesium concentrations were well maintained by bicarbonated solution as compared to the other solutions (P < 0.01). CONCLUSIONS: These results suggest that bicarbonated Ringer's solution is the most suitable perioperative solution for metabolic acidosis and plasma electrolyte balance among the Ringer's solutions tested.

Acidosis↗