Biomedical subjects

T Nishimura

Publications and source records attributed to T Nishimura.

At least 235 records · Page 13Linked to original sources

PubMed1998

Effects of the GABAergic system on in vivo binding of [3H]N-methylspiperone.

The effects of flunitrazepam, a benzodiazepine receptor agonist and those of NNC-711, a GABA transporter blocker, on the in vivo binding of [3H]N-methylspiperone, a dopamine D2 receptor antagonist, were investigated in mouse brain. Treatment with either flunitrazepam or NNC-711 reduced the specific binding of [3H]N-methylspiperone in the striatum. Flumazenil, a central benzodiazepine receptor antagonist, blocked the effect of flunitrazepam, indicating that the reduction in specific binding in the striatum was mediated via the GABAergic system. The flunitrazepam significantly decreased the specific binding of [3H]N-methylspiperone in the striatum at all time points studied after tracer injection, whereas specific binding in the cerebellum and cerebral cortex was unaltered. This decrease in specific binding in the striatum was found to be due to a reduced input rate constant (k3) of [3H]N-methylspiperone. The maximum number of the binding sites available for dopamine D2 receptors in the striatum was not changed by the flunitrazepam treatment.

Animals↗

PubMed1998

Cerebellopontine angle lymphoma: a case report and review of the literature.

BACKGROUND: Although malignant lymphomas of the central nervous system have been reported to be increasing in frequency, cerebellopontine (CP) angle lymphoma is rare and only 13 cases have been reported previously in the literature. CASE PRESENTATION: A 63-year-old woman had progressive dizziness and nausea for 2 months. Computed tomography scanning and magnetic resonance imaging (MRI) revealed a mass lesion in the left CP angle, that was compressing the lateral-dorsal aspect of the pons and the fourth ventricle. This tumor was avascular on angiography. The tumor was surgically removed through a left lateral suboccipital approach. It was considered to arise from the subarachnoid space of the CP angle cistern. For some reason, the histologic diagnosis was not definitively made, and therefore radiation therapy was not planned. The tumor recurred within 50 days after the tumor excision. Surgical excision of the recurrent tumor was performed again. The histologic diagnosis was B-cell type malignant lymphoma. Radiation therapy was performed. In the 27 months since irradiation, a recurrent tumor has not been detected on MRI. CONCLUSIONS: Although erosion and expansion of the internal auditory canal suggest an acoustic neurinoma, CP angle lymphoma can, in rare circumstances, erode the internal auditory canal. There are three distinct patterns in which malignant lymphomas occupy the CP angle: (1) an extra-axial CP angle lymphoma, (2) an intra-axial lymphoma extending to the CP angle, and (3) a leptomeningeal lymphoma presenting as a CP angle lesion. Although malignant lymphomas rarely occupy the CP angle, it should be considered in the differential diagnosis of CP angle tumors. It is desirable to obtain a frozen section in all CP angle tumors during surgery to identify the tumor, because aggressive removal is not necessary, but radiation therapy should additionally be performed for malignant lymphomas.

Cerebellar Neoplasms↗

PubMed1998

Accumulation of IL-12-activated antitumor effector cells into lymph nodes of tumor-bearing mice.

Simultaneous administration of high dose of IL-12 into tumor-inoculated mice resulted in a marked reduction of tumor growth in parallel with the augmented generation of cytotoxic T-cells, natural killer (NK) cells and IFN-gamma-producing Th cells. We found that these IL-12-activated antitumor effector cells preferentially accumulated in peripheral lymph nodes concomitantly with lymphadenopathy. However, IL-12 rather induced disappearance of antitumor effector cells including CD4+ T, CD8+ T and NK cells from spleen in spite of inducing splenomegaly. Lymph node cells obtained from IL-12-treated B16F0-bearing mice showed a marked IFN-gamma production in response to not only IL-2, IL-12, anti CD3 mAb but also B16F0 melanoma cells. Moreover, they could lyse B16F0 melanoma cells in a long-term cytotoxicity assay. It was also confirmed that IL-12-activated IFN-gamma producing Th1 cells were accumulated in tumor local site. Thus, IL-12 appeared to have a capability of stimulating selective migration of antitumor cells into lymph nodes and tumor local sites.

Animals↗

PubMed1998

The restraint stress drives a shift in Th1/Th2 balance toward Th2-dominant immunity in mice.

When mice were physically restrained in 50-ml tubes for 24 h, a marked decrease of NK activity was demonstrated in parallel with the elevation of serum corticosterone levels. The release of mice from restraint stress resulted in the recovery of NK activity, with a decrease of serum corticosterone levels within 48 h. Using this stress model, we also investigated the influence of restraint stress on mouse Th1/Th2 balance. Consistent with the decrease of NK activity, IFN-gamma production of mouse spleen cells greatly reduced after suffering from restraint stress. In contrast, the IL-4 producing ability of spleen cells was not so much affected by restraint stress. These results initially indicated that stress may induce the skewing of the Th1/Th2 balance toward Th2-dominant immunity, which stimulates the occurrence of infectious diseases and allergic disorders.

Animals↗

PubMed1998

Reconstitution of immune systems in RAG2-/- mice by transfer with interleukin-12-induced splenic hematopoietic progenitor cells.

The administration of a high dose of IL-12 into the mice resulted in the induction of splenomegaly. From the flow cytometry analysis of cellularity in an enlarged spleen, it was demonstrated that Thyl.2-CD45RB-c-Kit + Sca-1 + Lin- hematopoietic progenitor cells markedly increased in IL-12-administered mouse spleen compared with untreated mouse spleen. The IL-12-induced hematopoietic progenitor cells showed a greatly enhanced colony-forming activity in CFU-granulocyte/macrophage (CFU-GM), blast-forming units-erythroid (BFU-E) and CFU-spleen (CFU-S) assay. Moreover, it was initially demonstrated that the transfer of IL-12-induced splenic hematopoietic progenitor cells into immunodeficient RAG2-/- mice caused a complete reconstitution of their immune functions including T- and B-cell-mediated immunity. Thus, the evidence that IL-12 has a capability of inducing hematopoietic progenitor cells possessing stem cell-like activity in vivo, indicated another important immunomodulating activity of IL-12 in immunotherapy.

Animals↗

PubMed1998

Tetrahydropapaveroline and its derivatives inhibit dopamine uptake through dopamine transporter expressed in HEK293 cells.

Tetrahydropapaveroline (THP), an isoquinoline alkaloid, has been detected in brain and urine of Parkinsonian patients on L-dopa medication, and in the urine and brain of rats after L-dopa or acute ethanol administration. Since THP is considered to be synthesized from dopamine, it may affect dopaminergic neurons through the reuptake system, i.e. dopamine transporter (DAT). To determine whether THP has affinity for DAT, we generated a cell line which stably expresses DAT and examined whether THP and its derivatives could inhibit [3H]DA uptake in these cells. Ki of THP and three derivatives (1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), 1-(3',4'-dibydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline (3',4' DHBnTIQ) and 6,7-dihydroxy-1-benzyl-1,2,3,4-tetrahydroisoquinoline (6,7 DHBnTIQ)) for inhibition of [3H]DA uptake were about 41, 35, 23 and 93 microM, respectively, which were similar to the Ki of 1-methyl-4-phenylpyridinium ion (MPP+) (28 microM). These results suggest that THP and its derivatives might be uptaken through DAT and be involved in Parkinson's disease and/or alcohol addiction.

Animals↗

PubMed1998

Structural comparison of 1 beta-methylcarbapenem, carbapenem and penem: NMR studies and theoretical calculations.

Structural comparisons of meropenem (1), desmethyl meropenem (2) and the penem analogue (3) which contain the same side chains at both C-2 and C-6 were performed using 1H NMR measurements together with 3-21G* level of ab initio MO and molecular mechanics calculations. The ab initio MO calculations reproduced the skeletons of these strained beta-lactam rings in good agreement with the crystallographic data. 1H NMR measurements in aqueous solution together with molecular modeling studies indicated that there were conformational differences of the C-2 and C-6 side chains in this series of compounds. These observations suggested that the conformational differences could affect their biological activities.

Anti-Bacterial Agents↗

PubMed1998

Assessment of affinities of beta-CIT, beta-CIT-FE, and beta-CIT-FP for monoamine transporters permanently expressed in cell lines.

We investigated the effects of three cocaine analogs, beta-CIT (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane), beta-CIT-FE (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(2.fluoroethyl)-nortropa ne), and beta-CIT-FP (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(3-fluoropropyl)-n ortropane), on the uptake of [3H]dopamine(DA), serotonin(5-HT), and 1-norepinephrine (NE) using cell lines permanently expressing DA, 5-HT, and NE transporters, respectively, to determine their affinities for these three transporters. We generated cell lines stably expressing DA, 5-HT, and NE transporters, respectively, by the Chen-Okayama method, and then tested the abilities of (-)cocaine, beta-CIT, beta-CIT-FE, beta-CIT-FP, and clomipramine to inhibit the uptake of [3H]DA, 5-HT, and 2-NE. Ki values of beta-CIT, beta-CIT-FE, and beta-CIT-FP for [3H]DA, 5-HT, 1-NE uptake were 6, 29, and 33 nM, 91, 133, and 130 nM, and 28, 113 and 70 nM, respectively, whereas those of cocaine and clomipramine were 316, 581, and 176 nM and > 10,000, 437, and 851 nM, respectively. Beta-CIT, beta-CIT-FE, and beta-CIT-FP were shown to be potent DA, 5-HT, and NE uptake inhibitors. Beta-CIT and beta-CIT-FP were highly potent and selective dopamine uptake inhibitors, and therefore might be useful for imaging of DA transporter with single photon emission computed tomography (SPECT) or positron emission tomography (PET).

Animals↗

PubMed1998

Photodegradation products of methylprednisolone suleptanate in aqueous solution--evidence of a bicyclo[3.1.0]hex-3-en-2-one intermediate.

Two major photodegradation products of methylprednisolone suleptanate (sodium 11 beta, 17 alpha-dihydroxy-6 alpha-methyl-21-[[8-[methyl(2-sulfoethyl)amino]-1,8-dioxooctyl+ ++]oxy]-pregna-1,4-diene-3,20-dione) in aqueous solution irradiated with white fluorescent light at 2000 lux for 28 days at 25 degrees C were isolated by preparative high-performance liquid chromatography and characterized. Structures of the photodegradation products were determined as sodium 11 beta,17 alpha-dihydroxy-5 alpha, 6 alpha-dimethyl-21-[[8-[methyl(2-sulfoethyl)amino]-1,8-dioxoocty l]-oxy]-19-norpregna-1(10),3-diene-2,20-dione and sodium 1 beta, 11 beta-epoxy-17 alpha-hydroxy-6 alpha-methyl-21-[[8-[methyl(2-sulfoethyl)amino]-1, 8-dioxooctyl]oxy]-19 alpha-pregn-4-ene-2.20-dione. Formation of these compounds, especially the 1,11-epoxy analogue, strongly supports the existence of the bicyclo[3.1.0]hex-3-en-2-one intermediate in the photorearrangement of steroidal cross-conjugated dienones. The intermediate can account for all the major ketonic and phenolic products; these products are generated from the intermediate after subsequent transformations and/or further skeletal rearrangements. The 1,11-epoxy analogues were obtained from the prednisolone steroids in high yields by irradiation with a high-pressure mercury lamp.

Drug Stability↗

PubMed1998

A novel method for determination of alpha1,6fucosyltransferase activity using a reducing oligosaccharide from egg yolk as a specific acceptor.

A new method for determination of alpha1,6fucosyltransferase activity has been described. Recently, the disialyl-biantennary undecasaccharide was prepared in high yield from egg yolk [(1996), Carbohydr Lett 2: 137-42]. By treatment of this oligosaccharide with neuraminidase and beta-galactosidase, we readily obtained an asialo-agalacto-biantennary heptasaccharide (GlcNAcbeta 1,2Manalpha1,6[GlcNAcbeta1,2Manalpha1,3]Manbeta1 ,4GlcNAcbeta1,4GlcNAc). Using this asialo-agalacto-oligosaccharide as an acceptor, fucosyltransferases from human plasma and extracts of various human hepatoma cell lines were assayed in the presence of GDP-[3H]fucose. The reaction mixture was applied to a column of GlcNAc-binding, Psathyrella velutina lectin coupled gel. All the fucosylated acceptor were bound to the column which was eluted with 50 mM GlcNAc. Structural analyses revealed that only the innermost GlcNAc residue of the acceptor was fucosylated through an alpha1,6-linkage, and the oligosaccharide prepared could be used as a specific acceptor for alpha1,6fucosyltransferase. The present method was used to screen plasma alpha1,6fucosyltransferase in several patient groups, and significantly elevated activities were found in samples from patients with liver diseases, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

Acetylglucosamine↗

PubMed1998

Intrathoracic and intraabdominal wall implantation of a centrifugal blood pump for circulatory assist.

An implantable centrifugal pump (ICP) 320 ml in volume and 830 g in weight has been developed for prolonged circulatory assist. The antithrombogenicity of the ICP is provided by a balancing hole in the center of the impeller. The watertightness and histocompatibility of the ICP are supported by its silicone ring seal and its casing of titanium and acrylic resin, respectively. The total efficiency of the ICP was 30% at a 5 L/min flow rate and a 100 mm Hg head. The heat generation, watertightness, and anatomical fitting of the ICP were assessed in an intrathoracic implantation in a goat (66 kg) and in an intraabdominal wall implantation in a goat (70 kg). Warfarin was given for anticoagulation in each experiment to keep the prothrombin time around 1.7 times that of the control. The temperatures of the pump surface, the pleura, and the room were measured every 3 h. Anatomical fitting was evaluated by pathological observation after the termination of the experiment. The ICP could run for 40 days in the chest cavity and for 11 days in the abdominal wall. The temperature of the motor remained about 1.8 degrees C higher than the reference in both experiments. The ICP was completely covered by a layer of smooth fibrous tissue. The moisture content of the seals remained normal. Although a small amount of atelectasis was found in the lingula, neither lung adhesion nor necrotic change of the chest wall was observed. The inflammation of the surrounding tissue including foreign body reaction and thermal burn was minimal. In conclusion, the ICP has satisfied in vivo testing of its watertightness, exothermicity, and anatomical fitting.

Abdominal Muscles↗

PubMed1998

Prolonged nonpulsatile left heart bypass with reduced systemic pulse pressure causes morphological changes in the aortic wall.

We investigated the morphological changes in the aorta due to reduced systemic pulse pressure in prolonged nonpulsatile left heart bypass (LHB). Nineteen adult goats were divided into 3 groups, the nonpulsatile group in which nonpulsatile LHB was conducted, the pulsatile group in which pulsatile LHB was conducted, and the control group used as the normal control. The average aortic pulse pressures were 12, 47, and 37 mm Hg, respectively. The descending aorta was subjected to morphological examination. In the nonpulsatile group, the wall was significantly thinner, and the volume ratio of smooth muscle cells (SMCs) was much lower. In terms of the SMC type classification, the proportion of SMCs with low activity and low contractility was higher, and the cell density of the SMCs was increased compared to those in the other groups. These results indicate that prolonged nonpulsatile LHB causes morphological atrophic changes in the aorta.

Animals↗

PubMed1998

Immunohistochemical examination of NOS and SOD in nasal mucosa.

An immunohistochemical examination was performed to detect the localization of neural-type nitric oxide synthase (nNOS), endothelial-type NOS (eNOS) and inducible-type NOS (iNOS) in the human and mouse nasal mucosa. nNOS-immunoreactive nerve fibers were found in the subepithelial layer and around the seromucous glands of mice. In these fibers, immunodouble staining revealed co-localization of nNOS and superoxide dismutase (SOD). In the human nasal mucosa of normal subjects, strong eNOS immunoreactivity and weak iNOS immunoreactivity were found in the columnar epithelium.

Animals↗

PubMed1998

Changes in rat liver cytochrome P450 enzymes by atrazine and simazine treatment.

1. We examined the effect of two chloro-s-triazines (atrazine and simazine) on hepatic microsomal cytochrome P450 enzymes in rat. Rats were treated intraperitoneally with atrazine or simazine daily for 3 days with 100, 200 and 400 mumol/kg. 2. Among the P450-dependent monooxygenase activities, testosterone 2 alpha-hydroxylase (T2AH) activity in rat, which is associated with CYP2C11, was significantly decreased at all doses of atrazine and simazine. The levels relative to control activities were 59-46 and 60-32% respectively. Similarly, oestradiol 2-hydroxylase (ED2H) activity was also significantly decreased by 28-51% by atrazine and simazine at all doses. However, no change in CYP2C11 protein level by either chloro-s-triazine was observed. K(m) for T2AH was significantly increased only by simazine (200 mumol/kg), whereas the Vmax and Cl(int) for T2AH were significantly decreased by atrazine and simazine at all doses. 3. 7-Ethoxyresorufin O-deethylase (EROD), 7-methoxyresorufin O-demethylase (MROD) and 7-pentoxyresorufin O-depentylase (PROD) activities were significantly increased by 1.4-1.6-, 1.7-3.2- and 1.5-2.2-fold respectively, by both chloro-s-triazines at 200 or 400 mumol/kg. Lauric acid omega-hydroxylase (LAOH) was also increased by 1.4-fold by simazine at 200 and 400 mumol/kg. Immunoblotting showed that only simazine induces CYP1A2 and CYP4A1/2 protein expression. 4. The activities of 7-ethoxycoumarin O-deethylase (ECOD), bufuralol 1'-hydroxylase (BF1'H), chlorzoxazone 6-hydroxylase (CZ6H), testosterone 6 beta-hydroxylase (T6BH) and testosterone 7 alpha-hydroxylase (T7AH) were not affected by either chloro-s-triazine. 5. These results suggest that the pattern of changes in P450 isoforms by chloro-s-triazines differs between atrazine and simazine, that these herbicides change the constitutive and/or male specific P450 isoform(s) in rat liver, and that these changes closely relate to the toxicity of chloro-s-triazines.

Animals↗

PubMed1998

Changes in hepatic cytochrome P450 enzymes by cis- and trans-1,2-dichloroethylenes in rat.

1. We examined the effect of cis- and trans-1,2-dichloroethylenes (DCEs) on hepatic microsomal cytochrome P450 (P450) enzymes in the male and female rat. Rats were treated intraperitoneally with 7.5 mmol/kg cis- or trans-1,2-DCE daily for 4 days. 2. Among the hepatic microsomal P450-dependent monooxygenase activities tested, testosterone 2 alpha-hydroxylase (T2AH) activity in the male rat, which is associated with CYP2C11, was decreased by both cis- and trans-1,2-DCE isomers. The levels to control activities were 53 and 63% respectively. Furthermore, immunoblotting showed that both isomers significantly reduced the CYP2C11/6 protein level in liver microsomes from the male. The levels of testosterone 6 beta-hydroxylase (T6BH) activity and CYP3A2/1 protein in the male rat were reduced by cis-1,2-DCE but not trans-1,2-DCE. 3. cis-1,2-DCE decreased ethoxycoumarin O-deethylase (ECOD), benzyloxyresorufin O-debenzylase (BROD), chlorzoxazone 6-hydroxylase (CZ6H) and testosterone 7 alpha-hydroxylase (T7AH) activities in the male rat by 29, 28, 34 and 27% respectively. On the other hand, trans-1,2-DCE significantly increased 7-ethoxyresorufin O-deethylase (EROD) and 7-methoxyresorufin O-demethylase (MROD) activities in the male rat 1.4- and 1.9-fold respectively. Immunoblotting showed that cis-1,2-DCE reduced CYP1A1/2 and CYP2B1/2 protein levels, whereas trans-1,2-DCE increased CYP1A1/2 and CYP2B1/2 protein levels in the male rat. 4. The activities of other P450-dependent monooxygenases, namely benzphetamine N-demethylase (BZND), aminopyrine N-demethylase (APND), erythromycin N-demethylase (EMND) and lauric acid omega-hydroxylase (LAOH), in the male rat were hardly affected by either 1,2-DCE isomer. In the female rat there were no apparent changes in P450-dependent monooxygenase activities upon treatment with the 1,2-DCE isomers. 5. These results suggest that 1,2-DCEs mainly affect male-specific P450 isoforms in the rat liver and that these changes may relate to the toxicity of 1,2-DCEs.

Animals↗

PubMed1998

Ex vivo evidence for asymmetric tyrosine phosphorylation of ZAP-70 on double-positive thymocytes in the positive selection process.

Antigen stimulation via TCR in mature T cells provides rapid induction of tyrosine phosphorylation of intracellular substrates including ZAP-70. To study the potential involvement of tyrosine phosphorylation in CD4+CD8+ [double-positive (DP)] thymocytes in the positive selection process in vivo, we isolated and analyzed them in the presence of phosphatase inhibitor. DP thymocytes were obtained from TCR transgenic mice (TCR-Tg) expressing MHC class I- or class II-restricted TCR in selecting and non-selecting MHC backgrounds respectively. The phosphorylation of ZAP-70 in DP thymocytes of class I-restricted TCR-Tg was significantly higher in the positively selecting background than in the non-selecting one. However, such a phosphorylation difference between selecting and non-selecting TCR-Tg was found to be considerably less in class II-restricted TCR-Tg. A similar bias for ZAP-70 phosphorylation was also observed on selecting DP thymocytes when I-A(beta) deficient- and beta2-microglobulin-deficient mice were compared. These ex vivo studies suggest that TCR-mediated signaling on DP thymocytes induces ZAP-70 phosphorylation under a different manner of engagement of TCR to class I and class II molecules in the positive selection process.

Animals↗

PubMed1998

Patterns of care study of radiation therapy for cervix cancer in Japan: the influence of the stratification of institution on the process.

BACKGROUND: To improve the quality of radiation oncology in Japan, Patterns of Care Study (PCS), a widely known quality assurance (QA) program in the USA, was introduced. The feasibility was tested by collecting nationwide data by extramural audit for cervix cancer. METHODS: From July 1996 through February 1997, PCS audits were performed for 29 institutions nationwide. On the basis of the facility survey by Tsunemoto, 13 institutions were classified as A1 (university hospital/cancer center), 10 as B1 (other institutions treating >120 patients/year) and six as B2 (other institutions treating <120 patients/year). Medical charts for the patients treated for cervix cancer between 1992 and 1994 were reviewed based on the data format of the US PCS. The total number of patients surveyed was 432. RESULTS: Simulation was used for >90% of the patients in both A1 and B1-2 institutions. However, in B1-2, planning for 5% of the patients was performed with only a clinical set-up (p = 0.0287). A daily fraction with a size of 200 cGy was given to >65% of patients in A1 and to <47% in B1-2. On the other hand, >50% of those in B1-2 were treated with daily fractions of 180 cGy and less compared with 25% in A1 institutions (p < 0.0001). Brachytherapy was utilized more frequently for patients in Stages II (p = 0.0365), III (p = 0.0015) and IV (p = 0.0483) in A1 than in B1-2. As for external beam equipment, linear accelerators with 10 MV or more were used for 83% of the patients in A1. However, in B1-2 institutions, machines with lower energy were used for 38% of the patients (p < 0.0001). The median number of full-time-equivalent (FTE) radiation oncologists was 2.7 in A1, 0.65 in B1 and 0.2 in B2. CONCLUSIONS: Institutional stratification, including equipment and personnel, was found to affect significantly the patterns of care for cervix cancer. Therefore, to improve the quality of radiation therapy nationwide, improvements in equipment and in supply of FTE personnel are extremely important. PCS was found to have great potential for a practical evaluation of how much improvement will be required in Japan.

Adult↗

PubMed1998

Reversible ischemia in hippocampal areas by retrograde cerebral circulation surgery for thoracic aortic aneurysm with Tc-99m ECD brain SPECT.

Because hippocampal neurons are quite vulnerable to the anoxic brain injury that sometimes occurs in aortic arch surgery in humans, hippocampal ischemia should be a sensitive indicator of global cerebral ischemia. It was concluded that the hypothermic retrograde cerebral circulation technique for aortic arch surgery could not only be performed safely with respect to the brain, but could also increase blood flow to the hippocampal areas, probably as a result of restoration of blood flow in the thoracic aorta.

Adult↗