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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 73 records · Page 4Linked to original sources
PubMed2001

Regulation of acute nociceptive responses by the NMDA receptor GluRepsilon2 subunit.

Heterozygous mice mutant for the NMDA-type glutamate receptor (GluR) epsilon2 subunit with a highly homogeneous genetic background showed exaggerated responses to various acute noxious stimuli in the footshock, tail-flick, hot-plate and tail-pinch tests. Because the noxious stimuli in these behavioral tests were electrical, thermal and mechanical, the reduction of GluRepsilon2 proteins exerted stimulatory effects on acute nociceptive responses across modalities. Previous studies showed that GluRepsilon1 and GluRepsilon4 subunit mutant mice exhibited no alteration in the responses to acute noxious stimuli. Thus, among NMDA receptor subunits, the GluRepsilon2 subunit specifically plays an important role in the regulation of the acute nociceptive responses.

Acute Disease↗
PubMed2001

Possible role of orexin A in nonadrenergic, noncholinergic inhibitory response of muscle of the mouse small intestine.

The effect of a novel peptide, orexin A, on longitudinal muscle of ICR mouse small intestine was examined in vitro. Exogenous orexin A induced a transient contraction in duodenal, jejunal and ileal segments. Atropine and tetrodotoxin completely inhibited the contractions. Contraction of longitudinal muscle of jejunal segments induced by electrical field stimulation was still observed after the jejunal segment had been desensitized to orexin A, suggesting that orexin A is not a final neurotransmitter to induce the contraction. On the other hand, in the presence of atropine and guanethidine, orexin A induced a transient gradual relaxation in duodenal, jejunal and ileal segments. Electrical field stimulation also induced significant relaxation of the muscle in jejunal segments. The electrical field stimulation-induced relaxation was inhibited by 55% after the desensitization of the segments to orexin A. Although the electrical field stimulation-induced relaxation was inhibited by 47% by a nitric oxide synthesis inhibitor, NG-nitro-L-arginine (L-NOARG), orexin desensitization did not affect the relaxation which persisted after L-NOARG treatment. The exogenous orexin A-induced relaxation was completely inhibited by L-NOARG. The results suggest that orexin A partially mediates nonadrenergic, noncholinergic (NANC) relaxation via activation of nitrergic neurones in longitudinal muscle of ICR mouse small intestine.

Animals↗
PubMed2001

Moleculary imprinted polymers with metalloporphyrin-based molecular recognition sites coassembled with methacrylic acid.

A diastereoselective molecularly imprinted polymer (MIP) for (-)-cinchonidine, PPM(CD), was prepared by the combined use of methacrylic acid and vinyl-substituted zinc(II) porphyrin as functional monomers. Compared to MIPs using only methacrylic acid or zinc porphyrin as a functional monomer, PM(CD) and PP(CD), respectively, PPM(CD) showed higher binding ability for (-)-cinchonidine in chromatographic tests using the MIP-packed columns. Scatchard analysis gave a higher association constant of PPM(CD) for (-)-cinchonidine (1.14 x 10(7) M(-1)) than those of PP(CD) (1.45 x 10(6) M(-1)) and PM(CD) (6.78 x 10(6) M(-1)). The affinity distribution of binding sites estimated by affinity spectrum analysis showed a higher percentage of high-affinity sites and a lower percentage of low-affinity sites in PPM(CD). The MIPs containing a zinc(II) porphyrin in the binding sites, PPM(CD) and PP(CD), showed fluorescence quenching according to the binding of (-)-cinchonidine, and the quenching was significant in the low-concentration range, suggesting that the high-affinity binding sites contain the porphyrin residue. The correlation of the relative fluorescence intensity against log of (-)-cinchonidine concentrations showed a linear relationship. These results revealed that the MIP having highly specific binding sites was assembled by the two functional monomers, vinyl-substituted zinc(II) porphyrin and methacrylic acid, and they cooperatively worked to yield the specific binding. In addition, the zinc(II) porphyrin-based MIPs appeared to act as fluorescence sensor selectively responded by binding events of the template molecule.

Binding Sites↗
PubMed2001

Thiolutin, an inhibitor of HUVEC adhesion to vitronectin, reduces paxillin in HUVECs and suppresses tumor cell-induced angiogenesis.

Recent studies have shown that integrin alpha v beta 3, a receptor for vitronectin, plays an important role in tumor-induced angiogenesis and tumor growth and that antagonists of alpha v beta 3 inhibit angiogenic processes including endothelial cell adhesion and migration. On the other hand, most inhibitors of integrin alpha v beta 3 are peptide antagonists that include the Arg-Gly-Asp (RGD) motif. We therefore reasoned that non-peptide inhibitors of endothelial cell adhesion to vitronectin might be useful for inhibition of tumor angiogenesis in vivo. We screened for low-molecular-weight natural products able to inhibit adhesion of human umbilical vein endothelial cells (HUVECs) to vitronectin, and pyrrothine group compounds including aureothricin, thioaurin and thiolutin were isolated from microbial culture broths. Of these compounds, thiolutin inhibited adhesion of HUVECs to vitronectin the most effectively (IC(50), 0.83 microM). In vivo experiments showed that thiolutin significantly suppressed angiogenesis induced by tumor cells (S-180), a pathological form of neovascularization, in a mouse dorsal air sac assay system. To explore the mechanism of inhibition of HUVEC adhesion to vitronectin by thiolutin, we examined the effect of this agent on intracellular cell adhesion signaling. We found that the amount of paxillin in HUVECs was significantly reduced by thiolutin treatment, while those of other focal adhesion proteins including vinculin and focal adhesion kinase (FAK) were not. Metabolic labeling experiments showed that thiolutin enhanced degradation of paxillin in HUVECs. Protease inhibitors (MG115 and E64-D) decreased the rate of degradation of the paxillin induced by thiolutin and partially restored thiolutin-induced inhibition of HUVEC adhesion to vitronectin. Based on these findings, we concluded that thiolutin, an inhibitor of HUVEC adhesion to vitronectin, reduces the paxillin level in HUVECs and suppresses tumor cell-induced angiogenesis in vivo.

Animals↗
PubMed2001

Mechanism of urinary tract crystal formation following biphenyl treatment.

Coadministration of biphenyl and KHCO3 in the diet of male rats for 13 weeks produced urine crystals, which, by means of LC-MS/MS analyses, were determined to be composed of the potassium salt of 4-hydroxy-biphenyl-O-sulfate (4-HBPOSK). Biphenyl alone or biphenyl with KCl or NaHCO3 in the diet did not produce urine crystals. It was found that the higher concentration of potassium in the urine and the alkaline pH induced by feeding KHCO3 to rats resulted in the formation of urine crystals of 4-HBPOSK due to 4-HBPOSK solubility being lower in urine than in plasma. Urine crystals of 4-HBPOSK produced hyperplasia of the transitional epithelium of the ureter, ureteral obstruction, and hydronephrosis in the urinary tract.

Animals↗
PubMed2001

Integrated pulsed amperometric detection of glufosinate, bialaphos and glyphosate at gold electrodes in anion-exchange chromatography.

A rapid and practical method for direct detection of the herbicides (glufosinate, bialaphos and glyphosate) in anion-exchange chromatography has been developed with integrated pulsed amperometric detection (IPAD). The electrochemical behavior of these herbicides showed catalytic currents based on the oxidation of amines in their structures. Waveform in IPAD was similar to that for amino acids, which exhibited adsorption/desorption catalytic features at gold electrode surface in alkaline solution. Under optimized conditions, detection limits (signal-to-noise ratio of 3) for glufosinate, bialaphos and glyphosate were 20, 65 and 50 ng ml(-1), respectively, with correlation coefficients of 0.995, 0.997 and 0.996 over concentration ranges of 0.1-45, 0.3-32 and 0.1-50 microg ml(-1), respectively. The relative standard deviations (n=5) were 1.7-3.0%. The present method was successfully applied to the determination of glyphosate in urine and serum.

Aminobutyrates↗
PubMed2001

Postmenopausal obesity as a breast cancer risk factor according to estrogen and progesterone receptor status (Japan).

There have been inconsistent results on the association of postmenopausal obesity with breast cancer risk according to the estrogen (ER) and/or progesterone receptor (PR) status in the breast tissue, and this requires further evaluation. This study was designed to assess whether postmenopausal obesity differs according to receptor status. Information on risk factors was obtained from 1154 breast cancer cases and 21714 controls at Aichi Cancer Center Hospital, Nagoya, Japan between 1988 and 1992. The receptor status was known for 40% of cases. Obese postmenopausal women showed an increased risk of breast cancer (odds ratio (OR) for 5 kg of current weight=1.17, 95% confidence interval (CI)=1.10-1.25; OR for 1 kg/m(2) of body mass index (BMI)=1.07, 95% CI=1.04-1.10). The elevated OR was strongest for ER-positive, as well as with PR-positive, breast cancer among postmenopausal women who had a high BMI. The risk did not differ significantly according to ER status. However, obesity indices among postmenopausal women differed with borderline significance according to PR status. These results are consistent with the hypothesis that there is a gradient of risk for postmenopausal obesity according to hormonal receptor status, at least for PR status, although this was not statistically significant.

Adult↗
PubMed2001

Modulation of MUC1 mucin as an escape mechanism of breast cancer cells from autologous cytotoxic T-lymphocytes.

MUC1 mucin is known to serve as a target molecule in the killing of breast cancer cells by cytotoxic T-lymphocytes (CTLs). We searched for a possible mechanism allowing tumour cells to escape from autologous CTLs. When the killing of breast cancer cells by autologous lymphocytes was examined in 26 patients with breast cancer, significant tumour cell lysis was observed in 8 patients, whereas virtually no autologous tumour cell lysis was detected in as many as 18 patients. In the patients who showed negligible tumour cell lysis, the autologous tumour cells expressed MUC1-related antigenic epitopes much more weakly than the tumour cells in the patients who exhibited strong cytotoxicity (significant statistically at P< 0.0005-0.0045), suggesting that the unresponsiveness of cancer cells to CTLs observed in these patients was mainly due to loss of MUC1 expression or modulation of its antigenicity. A breast cancer cell line, NZK-1, established from one of the cytotoxicity-negative patients, did not express MUC1 and was resistant to killing by CTLs, while control breast cancer cell lines expressing MUC-1 were readily killed by CTLs. Transfection of NZK-1 cells with MUC1 cDNA induced significant lysis by autologous T-lymphocytes. These results supported the importance of MUC1 mucin in autologous anti-tumour immunity, but suggested that the major escape mechanism of tumour cells from autologous T-lymphocytes is the loss and/or modulation of MUC1 antigenicity on tumour cells, which would limit the effectiveness of possible immunotherapy designed to target the MUC1 mucin.

Antigenic Variation↗
PubMed2001

Application of microcolumn ion chromatography using anion exchangers modified with dextran sulfate for the determination of alkali and alkaline-earth metal ions.

Microcolumn ion chromatography using anion exchangers modified with dextran sulfate has been applied to the determination of alkali and alkaline-earth metal ions contained in guinea pig serum and bovine serum. These serums contained Na+, NH4+, K+, Mg2+ and Ca2+ and they were indirectly detected at 200 nm. The determination was done without any pretreatment procedure other than dilution.

Animals↗
PubMed2001

Aichi Cancer Center 10-year experience with conservative breast treatment of early breast cancer: retrospective analysis regarding failure patterns and factors influencing local control.

PURPOSE: We analyzed the clinical results of conservative breast therapy in our institute to determine the risk factors influencing local and distant disease recurrence. METHODS AND MATERIALS: From 1989 to 1997, 301 breasts of 295 women with early breast cancer were treated with conservative surgery and adjuvant radiotherapy. There were 212 incidences of Stage I breast cancer, and 89 of Stage II. Patients were routinely treated with local resection, axillar dissection, and 46--50 Gy irradiation given in 23--25 fractions. Some also received a radiation boost to the tumor bed. RESULTS: The 5-/8-year overall survival, disease-free survival, and local control rates were 93.2/91.5%, 86.0/80.6%, and 95.1/92.5%, respectively. Using both univariate and multivariate analyses, tumor volume, estrogen receptor status, and age < 40 years were significant prognostic factors for disease-free survival. Both age < 40 years and surgical method had a strong effect on local control by uni- and multivariate analysis. Surgical margin status was a significant prognostic factor for local control at the univariate level (p < 0.0001), though it had only borderline significance at the multivariate level (p = 0.08). No patient experienced severe morbidity due to radiotherapy. CONCLUSION: The results obtained are comparable to previously reported data. Although the follow-up period was too short to draw definite conclusions about long-term outcomes, the outcome from conservative breast treatment was acceptable.

Adult↗
PubMed2001

Fluorimetric determination of magnesium and aluminum via complexation with oxine in high-performance liquid chromatography.

Aluminum and magnesium were determined by fluorimetric detection via pre-column and/or in-column derivatization with 8-hydroxyquinoline (oxine) in high-performance liquid chromatography. The oxine complex of aluminum was selectively detected when the eluent contained no oxine, whereas the aluminum and magnesium complexes could be simultaneously detected when the eluent contained oxine. The sensitivity was improved by using eluents containing oxine by a factor of 7.1 for aluminum, and the detection limits at S/N=3 were 18 and 16 ng/ml for magnesium and aluminum, respectively. The present system was applied to the determination of magnesium and aluminum in various water samples.

Aluminum↗
PubMed2001

Silencing of the caspase-1 gene occurs in murine and human renal cancer cells and causes solid tumor growth in vivo.

Renal cell cancer is a unique solid tumor that occasionally shows spontaneous regression even at an advanced stage, of which the underlying mechanism is not well understood. To investigate a potential role of the pro-apoptotic molecule caspase-1 in the growth regulation of renal cell cancer, we created transfectants expressing exogenous caspase-1 from a murine renal cancer cell line, Renca. Overexpression of caspase-1 did not affect the growth of Renca cells in vitro at the exponential phase but induced apoptotic cell death at 50% to 75% confluence, whereas control cells underwent apoptosis only after reaching 100% confluence. When implanted into the flank of a syngeneic BALB/c mouse, caspase-1-overexpressing Renca cells did not effectively establish growth as a solid tumor, forming a measurable tumor in only 7 of 11 (64%) animals, whereas control cells formed a tumor in 6 of 6 (100%) animals. The growth of tumors from caspase-1-overexpressing cells slowed down markedly after the tumors reached 5 to 10 mm in diameter, and histological examination of such tumors revealed numerous apoptotic cells positively stained by TUNEL assay. Interestingly, endogenous caspase-1 was not detected in the tumors from control cells, which re-expressed caspase-1 when they were re-cultured and exposed to a demethylation reagent, 5-aza-2'-deoxycytidine. Furthermore, treatment of a human renal cancer cell line, ACHN, with 5-aza-2'-deoxycytidine also caused recovery of caspase-1 expression, which was not detected before treatment. These data suggest that silencing of caspase-1 through DNA methylation may be involved in the oncogenesis of some renal cell cancers growing as a solid tumor.

Animals↗
PubMed2001

Adrenergic stimulation of osteoclastogenesis mediated by expression of osteoclast differentiation factor in MC3T3-E1 osteoblast-like cells.

It is well known that adrenergic agonists efficiently activate beta-adrenoceptors on osteoblastic cells and can stimulate bone resorption in intact mouse calvaria. Recently, an osteoclastogenic factor of osteoblastic origin was found to be a novel tumor necrosis factor ligand family member and was termed osteoclast differentiation factor (ODF). Using a reverse transcription-polymerase chain reaction approach, we investigated the effect of epinephrine on mRNA levels of ODF and its decoy receptor, osteoclastogenesis inhibitory factor (OCIF), in MC3T3-E1 cells. Treatment with epinephrine (1 microM) rapidly increased ODF and OCIF mRNA levels, which peaked after 0.5 hr of treatment. Epinephrine (1 microM) also increased interleukin (IL)-6, IL-11, and cyclooxygenase (COX)-II mRNA levels, as well as increased prostaglandin E(2) (PGE(2)) accumulation in the culture medium. Treatment of the cells with IL-11 (10 ng/mL) or PGE(2) (1 microM) increased ODF and OCIF mRNA levels as observed with epinephrine. However, increases in ODF and OCIF mRNA levels by epinephrine were more rapid than those by IL-11, and were not influenced by NS-398 (100 microM; an inhibitor of COX-II), suggesting a direct effect of epinephrine on ODF and OCIF mRNA expressions as well as an indirect effect mediated by IL-11 and PGE(2) production. Epinephrine-induced increases in ODF and OCIF mRNA levels were inhibited by pretreatment with timolol (1 microM; beta-antagonist) and phentolamine (1 microM; alpha-antagonist), respectively. Furthermore, the formation of tartrate-resistant acid phosphatase-positive multinucleated cells from mouse bone marrow cells was stimulated by isoproterenol (0.1 to 10 microM) or epinephrine (0.1 to 10 microM). The action of isoproterenol, a beta-agonist, was clearly stronger than that of epinephrine, suggesting the importance of the physiological balance between ODF and OCIF productions for osteoclastogenesis. These findings suggest that beta-adrenergic stimulation induces not only IL-6, IL-11, and PGE(2) but also ODF expression in osteoblastic cells, leading to a stimulation of osteoclastogenesis.

Adrenergic Agonists↗
PubMed2001

Magnetic circular dichroism at transition metal L2,3 edges in D03-type (Fe(1-x)Mn(x))3Al alloys.

We have measured magnetic circular dichroism (MCD) spectra at the transition-metal L2,3 edges in D03-type (Fe(1-x)Mn(x))3Al in order to investigate their local magnetic moments. The analysis of the spectra shows that Fe has moments much larger than Mn, whose moment is ferromagnetically coupled with the Fe one. This does not lend support to the antiferromagnetic mechanism proposed for the reduction in magnetization as well as a large Mn moment predicted for x = 1/3. The evolution of satellites found in the Mn spectrum with x increased suggests that the change in the electronic state may result in the magnetization reduction.

Journal Article↗
PubMed2001

Magnetic circular dichroism at transition metal L2,3 edges in D03-type (Fe(1-x)Vx)3Al alloys.

Magnetic circular dichroism (MCD) spectra have been measured at the Fe and V L2,3 edges of DO3-type (Fe(1-x)Vx)3Al in order to investigate their local magnetic moments and electronic structures. Large MCD is observed at the Fe L2,3 edges, while the V L2,3 MCD shows relatively small intensity with complicated features. Signs of these MCD spectra indicate an antiferromagnetic coupling between the magnetic moments on Fe and V. According to the analysis based on the magneto-optical sum rules, the magnetic moment decreases with x, but remains fairly large for Fe2VAl, which might arise from its marginally magnetic nature.

Journal Article↗