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Biomedical subjects

Satoshi Suzuki

Publications and source records attributed to Satoshi Suzuki.

106 records · Page 6Linked to original sources
PubMed2002

Tumours around the foramen of Monro: clinical and neuroimaging features and their differential diagnosis.

The clinical and neuroimaging features of 20 patients with lateral ventricular tumours located around the foramen of Monro were reviewed retrospectively with special emphasis on the differential diagnoses. Histologic types were: eight neurocytomas, four subependymal giant cell astrocytomas (SGCAs), three subependymomas, two fibrillary astrocytomas, and one each of pilocytic astrocytoma, malignant astrocytoma and malignant teratoma. The mean age of the patients with neurocytoma was 29.6 years, with SGCA 13.3 years and with subependymoma 55.3 years. All tumours appeared nodular in shape, and on computed tomography (CT) neurocytomas were either isodense or highdense with the brain, while all subependymomas and SGCAs were lowdense. Calcification was observed in two SGCAs, and one neurocytoma. Five neurocytomas and all four SGCAs showed mild to moderate contrast enhancement, while all three subependymomas showed either no, or scarce, enhancement. Magnetic resonance imaging (MRI) studies were available in 10 patients, with the signal characteristics of four neurocytomas and three SGCAs being nonspecific, while two subependymomas were both hypointense on T1-weighted images and hyperintense on T2-weighted images. Thus important features for differential diagnosis included age of the patient and density on precontrast CT. In this series, either an extensive excision of the tumour or a partial removal, thus relieving the obstruction of the foramina of Monro, usually provided long term survival, with 18 patients surviving a mean of 10.8 years.

Adolescent↗
PubMed2002

Development of gene therapy using prostate-specific membrane antigen promoter/enhancer with Cre Recombinase/LoxP system for prostate cancer cells under androgen ablation condition.

To enhance the efficacy of suicide gene therapy for prostate cancer under androgen deprivation, we designed a promoter system that consists of the prostate-specific membrane antigen (PSMA) promoter / enhancer (PEPM) and Cre-loxP DNA recombination system. We constructed two kinds of plasmids. One plasmid contains a Cre recombinase (Cre) under the control of PEPM and the other expresses CMV-lox-luciferase / herpes simplex virus thymidine kinase (TK). In PSMA-positive LNCaP cells, the promoter activity of the PEPM-Cre plus CMV-lox-luciferase demonstrated 800-fold greater activity compared with that of the PSMA promoter alone. However, no enhancement of the promoter activity was observed in the PSMA-negative cells. Furthermore, in contrast to prostate specific antigen promoter / enhancer (PP), the promoter activity of PEPM did not decrease when the LNCaP cells were cultured in charcoal-stripped fetal bovine serum (CFBS). In an in vitro gene therapy model with LNCaP cells, the cell growth inhibition in the presence of ganciclovir (GCV) was more evident in the cells transfected with the PEPM-Cre plus CMV-lox-TK than in the cells with the PP-TK, and the difference in efficacy between the two plasmids was more remarkable when the cells were maintained in CFBS medium. The therapeutic effect of PEPM-Cre plus CMV-lox-TK was also observed in xenografted LNCaP cells on nude mice when the plasmids were directly injected into tumors and GCV was administered intraperitoneally. These findings indicate that the combination of the PSMA promoter / enhancer and the Cre-loxP system can enhance the PSMA promoter activity even under androgen ablation conditions and can exert its anti-tumor effect both in vitro and in vivo.

Animals↗
PubMed2002

Stereoselective metabolism of bufuralol racemate and enantiomers in human liver microsomes.

A new HPLC method was developed using a chiral column to efficiently separate four 1"-hydroxybufuralol (1"-OH-BF) diastereomers that are major metabolites of bufuralol (BF). Employing this method, we examined diastereomer selectivity in the formation of 1"-OH-BF from BF racemate or enantiomers in four individual samples of human liver microsomes. Three different human liver microsomes showed a selectivity of 1"R-OH < 1"S-OH for BF enantiomers, which was similar to that of recombinant CYP2D6 expressed in insect cell microsomes, whereas one human liver microsomal fraction yielded a selectivity of 1"R-OH > 1"S-OH for BF enantiomers, which was similar to those of recombinant CYP2C19 expressed in insect cell microsomes. Recombinant CYP1A2 and CYP3A4 showed a selectivity similar to that of CYP2D6, but their BF 1"-hydroxylase activities were much lower than those of CYP2D6. In inhibition studies, quinidine, a known CYP2D6 inhibitor, markedly inhibited BF 1"-hydroxylation in the fractions of human liver microsomes that showed the CYP2D6-type selectivity. Furthermore, omeprazole, a known CYP2C19 inhibitor, efficiently suppressed the formation of 1"-OH-BF diastereomers from BF in the microsomal fraction that showed the CYP2C19-type selectivity. From these results, we concluded that the diastereomer selectivity in the formation of 1"-OH-BF from BF differs between CYP2D6 and CYP2C19, both of which can be determinant enzymes in the diastereoselective 1"-hydroxylation of BF in human liver microsomes.

Adult↗
PubMed2002

Involvement of a proline-rich motif and RING-H2 finger of Deltex in the regulation of Notch signaling.

The Notch pathway is an evolutionarily conserved signaling mechanism that is essential for cell-cell interactions. The Drosophila deltex gene regulates Notch signaling in a positive manner, and its gene product physically interacts with the intracellular domain of Notch through its N-terminal domain. Deltex has two other domains that are presumably involved in protein-protein interactions: a proline-rich motif that binds to SH3-domains, and a RING-H2 finger motif. Using an overexpression assay, we have analyzed the functional involvement of these Deltex domains in Notch signaling. The N-terminal domain of Deltex that binds to the CDC10/Ankyrin repeats of the Notch intracellular domain was indispensable for the function of Deltex. A mutant form of Deltex that lacked the proline-rich motif behaved as a dominant-negative form. This dominant-negative Deltex inhibited Notch signaling upstream of an activated, nuclear form of Notch and downstream of full-length Notch, suggesting the dominant-negative Deltex might prevent the activation of the Notch receptor. We found that Deltex formed a homo-multimer, and mutations in the RING-H2 finger domain abolished this oligomerization. The same mutations in the RING-H2 finger motif of Deltex disrupted the function of Deltex in vivo. However, when the same mutant was fused to a heterologous dimerization domain (Glutathione-S-Transferase), the chimeric protein had normal Deltex activity. Therefore, oligomerization mediated by the RING-H2 finger motif is an integral step in the signaling function of Deltex.

Amino Acid Motifs↗
PubMed2002

LET distributions measured at the CERF facility with the RRMD-III.

The LET distributions in front of the 80 cm-thick concrete side shield at the CERF facility were measured with a Si detector telescope (RRMD-III) covered with and without a 1 cm-thick acrylic plate. In these measurements, a slight difference between the LET distributions was seen as a result of recoil protons and/or carbon particles by neutrons. Also, the LET distributions are compared with the micro-dosimetric spectrum (i.e., lineal energy distribution) measured with a cylindrical TEPC under the same conditions.

Background Radiation↗
PubMed2002

Menstrual cycle effects on performance of mental arithmetic task.

The purpose of this research was to identify the relationship between task performance and menstrual cycle. The difference of performance on menstrual cycle phase was investigated. The task was the mental arithmetic task which involved the non-sequential and higher order cognitive processes. The duration of the experiment was twenty minutes. Two-way analysis of variance by repeated-measures design was used to examine the differences in task performance between phases and temporal variations. Results showed that there was a significant difference in correct input time during temporal variations though there was no significant difference between phases. Moreover, the relationships between phases and intra-individual variations in task performance were examined using coefficient of variance (CV). CVs were plotted in three dimensions to examine the relationships between intra-individual variations and phases. Based on CVs, the subjects who showed differences were classified into two groups: those with a small difference in three phases and those with a difference every phase. The phase which indicated large CV changed with individuals.

Adult↗
PubMed2002

Change in full-field ERGs after macular translocation surgery with 360 degrees retinotomy.

PURPOSE: One of the methods used in macular translocation (MT) surgery for subfoveal neovascularization is to create a temporary total retinal detachment followed by a 360 degrees retinotomy. The whole retina is then shifted from the original surface of the retinal pigment epithelium (RPE), resulting in an unusual retina and RPE complex. The purpose of this study was to assess retinal function after MT surgery. METHODS: Full-field electroretinograms (ERGs) were recorded before and 4 to 8 months (mean, 5.4 months) after MT surgery with a 360 degrees retinotomy in 15 consecutive patients with age-related macular degeneration (10 eyes), high myopia (4 eyes), and polypoidal choroidal vasculopathy (1 eye). Their ages ranged from 57 to 74 years. The angle of rotation of the retina ranged from 18 degrees to 45 degrees (mean +/- SE, 30 +/- 2 degrees). In addition to the recording of the standard rod and mixed rod-cone ERGs after 30 minutes of dark adaptation, the cone single flash and 30-Hz flicker ERGs were recorded immediately after a light-adapting background was turned on (LA(0)) and also after 10 minutes of light adaptation (LA(10)). RESULTS: The mean amplitude of the full-field ERGs was reduced after surgery by 44% for the rod response, by 24% for the mixed rod-cone b-wave, by 12% and 35% for the cone single-flash b-wave at LA(0) and 30-Hz flicker ERGs at LA(0), respectively. The mean implicit times were delayed by 8 msec for the rod response, by 2 msec for the mixed rod-cone oscillatory potential (OP1), by 4 msec for the cone single-flash b-wave at LA(0), and by 6 msec for the 30-Hz flicker at LA(0). CONCLUSIONS: These results demonstrated a functional alteration in both the rod and cone components of the ERGs for the entire retina after MT surgery.

Aged↗
PubMed2002

Increased spontaneous retinal ganglion cell activity in rd mice after neural retinal transplantation.

PURPOSE: To study the functional success of neural retinal transplantation by means of retinal surface ganglion cell recordings. METHODS: Eight-week-old C3H/HeJ (rd/rd) retinal degeneration mice received transplants (subretinal) in one eye only of neural retinal tissue isolated from newborn normal C57/BL6J mice. Four weeks after transplantation, ganglion cell responses were recorded directly from the retinal surface over the transplant, with a differential bipolar surface electrode. Measurements were performed, both with and without light stimulation. Similar recordings were performed in nontransplant areas of the transplant-recipient eyes, and in age-matched sham-treated and untreated control eyes. After the recordings, the eyes were processed for light and transmission electron microscopy. RESULTS: Histologic examination showed that in some areas, transplanted cells were organized into small sheets and differentiated into photoreceptors with outer segments in intimate contact with the host RPE. No light-driven ganglion cell responses were recordable from the transplant-recipient or control eyes. However, the spontaneous ganglion cell activity was higher in the transplant areas (mean: 10.8 +/-12.0 spikes/1.6 sec) compared with nontransplant areas of these recipient eyes (mean: 2.4 +/- 5.7spikes/1.6 sec; P < 0.001), sham-treated eyes (mean: 2.5 +/- 4.8 spikes/1.6 sec; P < 0.001), and the untreated control eyes (mean: 2.2 +/- 4.4 spikes/1.6 sec; P < 0.001). CONCLUSIONS: Subretinal transplantation of neural retinal tissue results in a local increase of spontaneous ganglion cell activity. The increased activity may be due to the release of neurochemically active substances as a result of the presence of the transplant. Although light responses were not recordable, the technique of retinal surface ganglion cell recording may be useful for assessing the functional success of transplantation.

Action Potentials↗
PubMed2002

[An intra-pulmonary lymphnode resembling typical pulmonary primary adenocarcinoma on high-resolution computed tomographic (HR-CT) chest images].

A 40-year-old man was admitted to our hospital for further evaluation of a pulmonary nodule in chest radiographs. The 8-mm nodular lesion was located in the right anterior basal lobe on a plain chest radiograph, and showed 1) spiculation, 2) pleural indentation and 3) a converging vessel formation in high-resolution computed tomography of the chest. The radiographic findings were highly suggestive of primary pulmonary adenocarcinoma and the patient underwent video-assisted thoracoscopic surgery (VATS) to obtain a precise diagnosis. The nodule was diagnosed histopathologically as an intrapulmonary lymph node. In cases with such radiographic findings, careful attention should be paid in the differential diagnosis to distinguish intrapulmonary lymph nodes from primary pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMedDate not supplied

Comparison of electrical stimulation thresholds in normal and retinal degenerated mouse retina.

PURPOSE: To compare the threshold for electrically elicited action potentials of retinal ganglion cells in normal mouse retina and photoreceptor degenerated (rd) mouse retina. METHODS: Microelectrode recordings were made from retinal ganglion cells of normal and rd mice. Mice with a genetically based retinal degeneration (rd mice) were grown to the age of 16 weeks, when light-evoked responses could no longer be recorded. A bare wire was placed in the vitreous to stimulate the retina with charge-balanced current pulses. The following pulse shapes were investigated: single, square biphasic pulse, single sine wave, and biphasic pulse trains. RESULTS: Normal mice had significantly lower stimulus thresholds than rd mice for all pulse shapes. In normal and rd mice, short pulses were more efficient with respect to total charge used, but required a higher current. In normal mice, sine wave stimulation was significantly more efficient than a biphasic pulse of the same duration. No difference was noted between sine wave and square wave stimulation in rd mice. Pulse trains offered little benefit over single pulses. CONCLUSION: The amount of electrical charge required to elicit an action potential is dependent on the condition of the retina and the shape of the stimulus pulse used to deliver the charge.

Action Potentials↗
PubMedDate not supplied

Reduction of MDR3 mRNA levels by forskolin in Chang liver cells.

BACKGROUND: MDR3 is a phospholipid translocator and a putative transporter of several drugs in the canalicular membrane of hepatocytes. To clarify the regulatory system for the expression of MDR3 mRNA in comparison with MDR1 mRNA, we examined the effect of cyclic AMP using forskolin. MATERIALS AND METHODS: Chang liver cells were treated with forskolin, and then MDR3 and MDR1 mRNA levels were examined by RT-PCR and the MDR3 protein level was examined by Western blotting. RESULTS: The MDR3 mRNA level decreased while the MDR1 mRNA level increased, and the effects of forskolin were inhibited by a protein kinase A inhibitor, H-89. The MDR3 protein level was not changed by forskolin. However, forskolin decreased the induction of MDR3 mRNA expression by doxorubicin. CONCLUSION: The level of MDR3 mRNA was negatively-regulated by a cyclic AMP- and protein kinase A-dependent system.

ATP Binding Cassette Transporter, Subfamily B↗
PubMedDate not supplied

Alterations of the K-ras and p53 genes and microsatellite instability in sporadic colorectal carcinomas.

BACKGROUND: The international guidelines for the evaluation of microsatellite instability (MSI) in colorectal cancer were defined in 1997 by the National Cancer Institute (NCI). Here, the relationship between MSI, cancer-associated genes and their clinicopathological variables were revaluated using these guidelines. PATIENTS AND METHODS: Mutations of K-ras at exon 1 and p53 at exons 5, 6, 7 and 8 were analyzed in 43 cases of sporadic colorectal carcinoma. MSI was analyzed using the 5 markers recommended by the NCI reference panel. RESULTS: The proportion of p53 mutations in the MSI-H cases (0 out of 5; 0%) was lower than that of non-MSI-H cases (23 out of 38; 60.5%) (p=0.0117). The proportion of p53 mutations in microsatellite stable (MSS) cases (21 out of 34; 61.8%) was higher than that of non-MSS cases (2 out of 9; 22.2%) (p=0.0366). The proportion of K-ras mutations in MSI-H tumors (1 out of 5; 20.0%) was less frequent than in non-MSI-H tumors (19 out of 38; 50.0%) (p=0.2115). CONCLUSION: p53 mutations in MSI-H tumors were much less common than in non-MSI-H tumors. This result suggested that alterations of the p53 gene are not closely associated with carcinogenesis in MSI-H carcinomas.

Aged↗
PubMedDate not supplied

Effects of PSK on T and dendritic cells differentiation in gastric or colorectal cancer patients.

BACKGROUND: Vaccine therapy targeting tumor antigens recognized by cytotoxic T cells (CTL) has been tried extensively. However, in a cancer-bearing state, the Th1/Th2 balance shifts to Th2 dominance, and this has been the obstacle to vaccine therapy to induce the CTL. DC1/DC2 subsets have also been reported to control the differentiation of Th subsets. The key to tumor immunotherapy is how to activate the DC1-Th1 lineage. PATIENTS AND METHODS: Six normal adults and 14 patients with gastric or colorectal cancers, who gave informed consent, were studied. The Th1/Th2 and DC1/DC2 ratios were determined by FACS. IL-12 and IL-10 production from PBMC were measured by ELISA. RESULTS: The Th1/Th2 and DC1/DC2 ratios were all significantly lower in the patients with gastric or colorectal cancers compared to normal adults. After protein-bound polysaccharide K (PSK) therapy in cancer patients, the Th1/Th2 balance shifted to Th1 dominance and the DC1/DC2 balance to DC1 dominance. IL-10 production was significantly decreased by PSK therapy. CONCLUSION: In the cancer-bearing state, the Th1/Th2 and DC/1/DC2 balance becomes Th2- and DC2-dominant. PSK therapy results in a shift of the Th1/Th2 and DC1/DC2 balance towards Th1 and DC1 dominance. We plan to examine whether combining dendritic cells (DC) vaccination therapy with oral PSK enhances the induction of T cell and DC differentiation in cancer patients.

Adult↗