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Biomedical subjects

M Takeuchi

Publications and source records attributed to M Takeuchi.

At least 379 records · Page 21Linked to original sources

FMLP actions and its binding sites in isolated human coronary arteries.

The chemoattractant f-Met-Leu-Phe (FMLP) can modulate human coronary arterial tone without the involvement of peripheral leukocytes. We investigated the actions of FMLP and its cellular mechanism in human coronary arteries isolated 2-3 h after death. A single dose of FMLP (0.01-10 microM) produced transient contraction (or, followed by relaxation) responses in most human coronary rings examined. These responses to FMLP were in large part mediated by the generation of cyclooxygenase products, mainly thromboxane A2 (TXA2) and prostaglandin I2 (PGI2). Radiolabeled N-formyl hexapeptide. 125I-f-Nle-Leu-Phe-Nle-Tyr-Lys bound densely to intimal and adventitial sites that accumulated macrophages (CD68-positive) with a Kd of 14-29 nM and, further, weakly to the media with a Kd of 2.4-3.6 microM. Several cell types including macrophages, endothelial cells and smooth muscle cells were positively immunostained for both TXA2 synthase and PGI2 synthase. However, there was no significant relation between the magnitude of the responses to FMLP and dense macrophage accumulation in the intimal plaques or the adventitia. A reverse transcription-polymerase chain reaction showed predominant expression of FMLP receptor homologues, FPRH1 and FPRH2 mRNA, in human coronary medial tissues relative to that in leukocytes. In conclusion. FMLP produced transient tension changes in human coronary arteries, mainly via the generation of TXA2 and PGI2. This effect of FMLP did not appear to be mediated by the activation of densely accumulated intimal and/or adventitial macrophages, but by the activation of unidentified medial tissue cells which might have functional FMLP receptor homologues.

Adolescent↗

Flow cytometric evaluation of transferrin receptor in transitional cell carcinoma.

We evaluated flow cytometric (FCM) analysis of transferrin receptor (TFR) expression as a marker for the malignant potential in transitional cell carcinoma (TCC). TCCs from 55 patients were analyzed by FCM using an anti-TFR monoclonal antibody (CD71) and a TCC-specific monoclonal antibody (EH14), which recognizes most TCC cells irrespective of the grade. The cells were divided into subpopulations according to DNA ploidy determined simultaneously. TFR expression correlated well with the grade and the stage of the tumors. TFR expression of the aneuploid tumors was significantly higher than that of the euploid tumors in all subpopulations. EH14 expression did not correlate with the grade or the stage of the tumors. EH14 expression of the aneuploid tumors was significantly higher than that of the euploid tumors in the whole cell population but not in the subpopulations. In moderately differentiated tumors or in T1 tumors, TFR expression was higher in multiple or recurrent tumors than in simple tumors. The cell size or shape were not the primary reasons for the enhanced expression of TFR in the high-grade or the high-stage tumors; instead, overproduction of TFR may take place in these tumors. Clinically, many of the TCC tumors are grouped into G2 or T1 tumors, some of which will be invasive cancers. Quantitative analysis of TFR expression using FCM may be useful to predict the prognosis of these tumors.

Aged↗

Anti-granulocyte antibody suppression of active and passive anaphylactic shock in WBB6F1-W/Wv mice.

Our previous study revealed that anaphylactic shock can be produced in WBB6F1-W/Wv (abbreviated as W/Wv) mice. Because they are congenitally deficient in mast cells, we are certain that some other cell types are involved as mediator sources. In the present study, with the aim of examining the role of circulatory granulocytes, the effect of monoclonal antibody to a mouse granulocyte antigen, Gr-1, upon active and passive anaphylactic shock was tested in W/Wv mice using several mast cell-bearing strains as references. An intravenous injection of 40 micrograms of anti-granulocyte antibody one day before the antigen challenge produced a marked decrease in neutrophils and nearly complete abolition of lethal shock in W/Wv mice regardless of the sensitizing method. Both prevention of shock and reduction of neutrophils lasted for three days after the treatment with the antibody but not for six days. From these results, a reasonable conclusion would be that circulating Gr-1+ cells (predominantly composed of neutrophils) are the major mediator source. Reference experiments using mast cell-bearing strains revealed that the suppressive effect of anti-granulocyte antibody was also observed against active anaphylactic shock in C3H/HeN mice but not against active and passive anaphylactic shock in the other mice.

Anaphylaxis↗

Immunohistochemical and immuno-electron-microscopic detection of interferon-gamma-inducing factor ("interleukin-18") in mouse intestinal epithelial cells.

The novel cytokine interferon-gamma-inducing factor ("interleukin-18") is produced by macrophage-like cells in mice with endotoxin shock and induces the production of interferon-gamma by T cells in vitro. To determine the physiological role for mouse interferon-gamma-inducing factor, we studied its tissue distribution in several organs (intestine, spleen, thymus, kidney, and liver) in healthy mice of different ages, including fetal stages. Activity of the cytokine in the organ extracts of adult mice was measured by enzyme-linked immunosorbent assay, and the cellular distribution of interferon-gamma-inducing factor in organs from fetal and adult mice was determined by immunohistochemistry. Intestinal extracts of adult mice showed the highest concentrations among the organs studied. Other organ extracts of adult mice showed lower concentrations of the cytokine. Immunohistochemical analysis revealed that interferon-gamma-inducing factor was localized in the cytoplasm of intestinal epithelial cells from fetal and adult mice. These results show for the first time that intestinal epithelial cells may be the main producers of interferon-gamma-inducing factor under normal physiological conditions and suggest that its constitutive expression in intestinal epithelial cells may have an important role in the induction of mucosal immunity.

Animals↗

Beneficial effects of a Ca2+ sensitizer, MCI-154, on the myocardial oxygen consumption-cardiac output relation in patients with left ventricular dysfunction after myocardial infarction: comparison with dobutamine and phosphodiesterase inhibitor.

Although conventional inotropic agents such as catecholamines increase myocardial oxygen consumption, a newly developed inotropic agent, a Ca2+ sensitizer, may be able to increase cardiac output with less myocardial oxygen consumption. By using right-side heart catheterization, we assessed the ratio of the increase in myocardial oxygen consumption per unit increase in cardiac output during beta-adrenergic receptor stimulation (dobutamine, n = 15), phosphodiesterase inhibition (E-1020, n = 10), and Ca2+ sensitization (MCI-154, n = 17) in patients with coronary artery disease. Dobutamine increased cardiac output and myocardial oxygen consumption. E-1020 increased cardiac output but did not change myocardial oxygen consumption. MCI-154 increased cardiac output and decreased myocardial oxygen consumption. The oxygen cost of increasing cardiac output with dobutamine and with E-1020 was different from that with dextran infusion (n = 18); in contrast, the oxygen cost with MCI-154 was significantly smaller. Thus a newly developed Ca2+ sensitizer, MCI-154, may be beneficial for the treatment of heart failure.

Cardiac Output↗

Implication of the negative U wave during dobutamine stress echocardiography.

Although the development of negative U waves during exercise is a highly specific marker for detecting coronary artery disease, their assessment during exercise is difficult. The clinical significance of the negative U wave during dobutamine stress echocardiography was investigated in 181 patients who had suspected coronary artery disease. Dobutamine-induced negative U waves appeared in 28 patients (16%) during dobutamine infusion. Coronary angiography showed coronary artery disease in 114 of the 181 patients. The sensitivity and specificity of the negative U wave for detecting coronary artery disease were 22 and 96%, respectively, while the corresponding values for ischemic ST-T changes were 49 and 76%, respectively. The negative U wave appeared during low-dose infusion of dobutamine (5-10 microg/kg/min) in 82% of the patients with this wave. In the 21 patients who had both a negative U wave and an inducible regional wall motion abnormality during dobutamine infusion, the development of the negative U wave was either simultaneous with or earlier than that of the wall motion abnormality. Although its sensitivity was low, the negative U wave during dobutamine stress echocardiography is a highly specific marker for detecting coronary artery disease. Because of its earlier appearance as compared with that of the wall motion abnormality, the dobutamine-induced negative U wave may be considered to be an early and useful adjunctive sign for detecting coronary artery disease during dobutamine stress echocardiography.

Adult↗

Chlorpromazine inhibits concanavalin A-induced liver injury independently of cytokine modulation.

We investigated the effect of chlorpromazine (CPZ) in a murine model of T-cell-dependent liver injury caused by concanavalin A (ConA). CPZ (3 and 10 mg/kg) treatment 1 h before ConA injection prevented liver injury. CPZ (3, 10 mg/kg) administered 1 h after a ConA injection was also hepatoprotective, whereas cyclosporin (CsA, 100 mg/kg) was active only when given before ConA. Under either condition, CsA but not CPZ prevented concurrent increases in splenic ornithine decarboxylase (ODC) activity, a putative index of T-cell proliferation/differentiation. CPZ down-regulated tumor necrosis factor-alpha (TNF-alpha) and up-regulated IL-10 in mice that then received ConA, whereas delayed administration of CPZ had no effect. These results suggest that CPZ prevented liver injury without affecting the proliferation/differentiation of T-cells. The dissociation of hepatoprotection by CPZ from cytokine modulation indicates that this drug intervenes in the adherence of T-cells or the death of hepatocytes in the ConA-model.

Adjuvants, Immunologic↗

Immune privilege, T-cell tolerance, and tissue-restricted autoimmunity.

The eye is one of several specialized organs/tissues that display immune privilege, i.e. sites that permit foreign tissue grafts to enjoy prolonged (or even indefinite) survival. Immune privilege is an active, rather than a passive, process in which specialized tissues/sites and the immune system collaborate in providing immune protection without the risk of immunopathogenic injury to the tissue itself. Among the mechanisms that have been found to contribute to immune privilege is tolerance of peripheral T cells. Over the past few years, investigators have demonstrated at least four different pathways by which immune privilege can lead to T-cell tolerance: clonal deletion, clonal anergy, immune deviation, and T-cell suppression. In the case of the eye, privilege exists in part because antigens introduced into the eye are captured by distinctive local antigen-presenting cells that migrate via the blood to the spleen. At that site, they generate a stereotypic systemic immune response that is deficient in CD4+ T cells that mediate delayed hypersensitivity and that help B cells to secrete complement-fixing antibodies, yet replete with CD8+ T cells that function as cytotoxic cells and as regulatory cells. This response, termed anterior chamber associated immune deviation (ACAID), is mediated by antigen-specific regulatory T cells that secrete TGFbeta in an autocrine fashion and suppress effector functions of inflammogenic CD4+ T cells. Because intraocular inflammation is deleterious to vision, ACAID and immune privilege are considered to be evolutionary adaptations that enable the eye to benefit from immune protection against pathogens without suffering blindness from immune injury.

Animals↗

Reconstruction of burn deformity using artificial dermis combined with thin split-skin grafting.

Twelve patients with post-burn contracture were treated using artificial dermis combined with thin split-skin grafting during the period January 1994 to April 1996. Bilayer artificial dermis was grafted onto full thickness open wounds of the skin, after excision of scar contracture tissue. About 3 weeks later, the silicone layer was removed and thin split-skin, 8/1000 in. thick, was grafted onto the newly synthesized dermis-like tissue in the wound bed. Scalp was chosen as the donor site in 11 of the 12 cases. Artificial dermis grafting was undertaken to ensure that morbidity at the donor site could be reduced as much as possible in the treatment of burn deformity. The skin grafts took completely in all cases. Postoperative management was performed in accordance with conventional skin grafting. Postoperative contraction or hypertrophic scar was observed in three cases, but a soft, favorable quality was obtained in the other nine cases. Treatment of burn deformity with artificial dermis may be beneficial in selected cases.

Adolescent↗

The effect of L-menthol stimulation of the major palatine nerve on subjective and objective nasal patency.

To determine whether L-menthol stimulation of the major palatine nerve can affect nasal patency, we noted subjective and measured objective nasal patency before and after L-menthol stimulation of the palatal mucosa. L-Menthol stimulation of the palatal mucosa enhanced nasal sensation of airflow but nasal resistance was unaffected. By contrast, L-menthol stimulation after local anesthesia of the palatine nerve or of the nasal mucosa substantially diminished the subjective response of increased nasal patency but without affecting objective nasal patency. It is suggested that the effect of both direct stimulation by L-menthol of the major palatine nerve and its vapor action on the sensory nerve endings of the nasal mucosa produce an increase in the sensation of nasal patency without an increase in objective nasal patency.

Administration, Oral↗

Reproducibility of dobutamine digital stress echocardiography.

The aim of this study was to investigate the temporal variability and interobserver agreement of dobutamine digital stress echocardiography. We performed two dobutamine stress echocardiographic studies (dobutamine up to 40 micrograms/kg/min and atropine up to 1 mg) in 15 patients with previous myocardial infarction at a mean of 19 days apart. Two observers assessed the wall motion using a six-point score in a 16-segment model and calculated the wall motion score index at rest and at peak stress by using a quad screen display. Analysis of the wall motion was performed separately on the day after each dobutamine stress test (analysis A), and all images from the serial studies in the same patient were simultaneously retrieved and compared side-by-side in the same view (analysis B). The mean values of heart rate and blood pressure were comparable for each in the two studies except for the heart rate at rest. Regarding the presence and absence of positive findings of dobutamine stress echocardiography, interobserver agreement was 93% (70% to 99% with 95% confidence limits, kappa value 0.86) in the patients and 93% (70% to 99% with 95% confidence limits, kappa value 0.80) in the three major vascular regions with the use of analysis A. these values did not improve with the use of analysis B. The agreement of the temporal variability was 93% (70% to 99% with 95% confidence limits, kappa value 0.86) in the patients and 84% (71% to 92% with 95% confidence limits, kappa value 0.66) in the vascular regions with the use of analysis A. These values further improved with the use of analysis B. With the comparison of the wall motion score index, interobserver variability showed a correlation coefficient of 0.88 at rest and 0.90 at peak stress with analysis A and 0.78 and 0.82, respectively, with analysis B. Corresponding analysis of temporal variability showed correlation coefficients of 0.99 at rest and 0.99 at peak stress when both analysis were used. Although dobutamine digital stress echocardiography has good reproducibility and negligible interobserver variability, even if the digital quad screen format is used, it requires strict standardization of the reading criteria and the objective measurements of wall motion in the expansion of this test to the evaluation of the changes in left ventricular function during more than two serial studies in the same patient.

Aged↗

Frequent detection of hepatitis B virus X-gene DNA in hepatocellular carcinoma and adjacent liver tissue in hepatitis B surface antigen-negative patients.

Hepatitis B virus is associated with human hepatocellular carcinoma. We performed polymerase chain reaction for the X, C, S, and preS2/S regions of the viral genome in 23 hepatitis B surface antigen-negative hepatocellular carcinomas and adjacent liver. Hepatitis B viral genomes were detected in 17 of 23 tumors and adjacent tissues (73.9%). Among recognized transactivators, the X gene was present in 16 (69.6%) cases of hepatocellular carcinoma, but preS2/S was detected in only 7 (30.4%). Hepatitis B virus C and S regions were detected in 3 (13.0%) and 9 (39.1%) hepatocellular carcinomas, respectively. Serologic study revealed antibodies to hepatitis B surface antigen, hepatitis B core antigen, and hepatitis B e antigen in 14 patients; among these, X-gene DNA was detected in 12 of 14 tumors (85.7%). The X gene was also detected in 4 of 9 tumors of seronegative patients. The X gene, present in many hepatocellular carcinomas, may promote hepatocellular carcinoma in hepatitis B surface antigen-negative patients.

Adult↗

Re-induction of complete remission with a new synthetic retinoid, Am-80, for relapse of acute promyelocytic leukaemia previously treated with all-trans retinoic acid.

Two patients with relapsed acute promyelocytic leukaemia previously treated with all-trans retinoic acid (ATRA), were treated with a new synthetic retinoid, Am-80. In both patients pancytopenia gradually resolved without an increase in leukaemic cells, and differentiation of leukaemic cells was observed morphologically in bone marrow. Without the use of anti-leukaemic agents, both cases achieved complete remission (CR) on days 52 and 38 of treatment, respectively. On the day of CR, PML gene rearrangement and the t(15;17) translocation disappeared, though PML-RAR alpha chimaeric messenger RNA was still detected by reverse transcriptase polymerase chain reaction. Both patients then received conventional chemotherapy for consolidation of CR. These clinical experiences suggest that Am-80 may be an active agent for APL patients who have relapsed from ATRA-induced remission.

Adult↗

cDNA cloning of nuclear localization signal binding protein NBP60, a rat homologue of lamin B receptor, and identification of binding sites of human lamin B receptor for nuclear localization signals and chromatin.

We previously purified and characterized a nuclear localization signal (NLS) binding protein, NBP60, in rat liver nuclear envelopes. In this study, we cloned and sequenced the cDNA of rat NBP60, and predicted an amino acid sequence comprising 620 amino acids. The sequence revealed that NBP60 is a rat homologue of lamin B receptor (LBR), and is 79 and 63% identical in amino acids to human and chicken LBR, respectively. Using three fusion proteins containing different parts of the amino-terminal domain of human LBR, it was shown that the stretch comprising amino acids 1 to 89, which contains a Ser-Arg rich region (RS region), binds to nucleoplasmin and that the binding was inhibited by a common NLS-peptide. These results suggested that the amino-terminal domain of LBR contains an NLS-binding site. Furthermore, it was shown that the stretch comprising amino acids 1 to 53, which does not contain the RS region or the predicted DNA-binding site, binds to Xenopus laevis sperm chromatin.

Amino Acid Sequence↗

Perinuclear membrane localization of alphaKAP, a protein produced from a gene within the gene of calmodulin-dependent protein kinase IIalpha.

AlphaKAP is a protein produced from a gene within the gene of the a isoform of calmodulin-dependent protein kinase II (CaM-kinase IIa). It consists of the association domain of CaM-kinase IIa and a highly hydrophobic amino-terminal stretch consisting of 25 amino acids which is absent from CaM-kinase IIalpha. We previously demonstrated that alphaKAP is an integral membrane protein by subcellular fractionation analysis [Sugai, R., Takeuchi, M., Okuno, S., and Fujisawa, H. (1996) J. Biochem. 120, 773-779], but the exact subcellular localization of alphaKAP was not well understood. Here we demonstrate that alphaKAP is localized on the nuclear membrane of COS-7 cells transiently expressing alphaKAP. The nuclear membrane and perinuclear small vesicles were immunostained with an antibody against a synthetic peptide corresponding to the carboxyl-terminal 15 amino acids of alphaKAP. In contrast to the intact alphaKAP, the mutant alphaKAP, from which the hydrophobic amino-terminal segment had been deleted, accumulated within nuclei. Thus, alphaKAP may function as an anchoring protein for CaM-kinase II and/or other proteins in the perinuclear membrane.

Animals↗

Endoscope-assisted intraoral approach for masseteric hypertrophy.

Although conventional intraoral surgery for masseteric hypertrophy is a useful technique, it is considerably difficult to resect the mandibular angle due to the narrow visual field. For the purpose of compensating for the drawbacks of this procedure, we performed endoscope-assisted intraoral surgery on 5 patients with bilateral masseteric hypertrophy, who were successfully treated. The use of an endoscope offers a clear view of the mandibular angle region, thus facilitating accurate and easy resection of the spur.

Adult↗

Endoscopic-assisted transaxillary removal of lipomas in the back and shoulder region.

The experience with endoscopic-assisted transaxillary extraction of lipomas on the upper back and shoulder region in 10 patients is reported. This technique enables tumor removal through a short skin incision placed in an inconspicuous region. In addition, hemostasis and complete removal of gross tumor are confirmed by endoscopic visualization. No complications or recurrences have been observed over a follow-up period of up to 2 years. The results were cosmetically satisfactory.

Adult↗