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Biomedical subjects

N Takemoto

Publications and source records attributed to N Takemoto.

At least 19 recordsLinked to original sources
PubMed2003

Splenic marginal zone lymphoma presenting as myelofibrosis associated with bone marrow involvement of lymphoma cells which secrete a large amount of TGF-beta.

We report here on a patient with splenic marginal zone lymphoma presenting diffuse fibrosis of bone marrow and spleen. After splenectomy and chemotherapy, bone marrow biopsy demonstrated an improvement of fibrosis. Plasma concentration of transforming growth factor (TGF)-beta was much higher in this patient than in those of age-matched non-Hodgkin's lymphoma patients ( n=5) at diagnosis, decreasing after resolution of myelofibrosis. Immunostaining with the TGF-beta antibody revealed that the lymphoma cells in bone marrow and spleen were positive for TGF-beta. TGF-beta secreted by tumor cells was thought to stimulate the growth of fibroblasts and synthesize collagen in bone marrow and splenic fibroblasts, and play an important role in the development of marrow and splenic fibrosis in this patient. This is the first report of a patient with splenic marginal zone lymphoma presenting as myelofibrosis associated with bone marrow involvement of lymphoma cells which secrete a large amount of TGF-beta.

Aged↗
PubMed2003

[Neuroleptic malignant syndrome after aortic valve replacement; report of a case].

A 64-year-old male with treated Parkinson's disease underwent mechanical valve replacement for aortic valve regurgitation. The antiparkinsonian drugs for internal use were interrupted on the morning of the operative day. After the operation, the patient developed fervescence, muscle rigidity, hidropoiesis and a rise in creatine kinase. The patient was diagnosed as neuroleptic malignant syndrome and given medication dantrolene sodium and antiparkinsonian drugs on the 5th postoperative day. The symptom of neuroleptic malignant syndrome disappeared on 12 postoperative days. As the stress of open heart surgery with extracorporeal circulation trigger off neuroleptic malignant syndrome, the patient with Parkinson's disease need early beginning of antiparkinsonian drugs on account of prevention of neuroleptic malignant syndrome after operation.

Aortic Valve↗
PubMed2001

Prevention of lethal acute graft-versus-host disease in mice by oral administration of T helper 1 inhibitor, TAK-603.

Acute graft-versus-host diseases (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT). T helper 1 (Th1)-type cytokines such as interferon-gamma or tumor necrosis factor-alpha have been implicated in the pathogenesis of acute GVHD. TAK-603 is a new quinoline derivative, which is now in clinical trials for use as a disease-modifying antirheumatic drug. In preclinical studies, it inhibited delayed-type hypersensitivity, but not Arthus-type reaction, in mice, and selectively suppressed Th1 cytokine production. Thus, the present study was designed to investigate whether the Th1 inhibitor (TAK-603) ameliorates lethal acute GVHD in a mouse model. Administration of TAK-603 into BALB/c mice given 10 Gy total body irradiation followed by transplantation of bone marrow and spleen cells from C57BL/6 mice markedly reduced the mortality in association with minimal signs of GVHD pathology in the liver, intestine, and skin. TAK-603 reduced not only the production of Th1-type cytokines, but also the proportion of Th1 cells in CD4(+) helper T cells in this GVHD mouse model. These results suggest that TAK-603 could be a potent therapeutic agent for acute lethal GVHD.

Acute Disease↗
PubMed2001

Prevention by lactic acid bacteria of the oxidation of human LDL.

Ether extracts of lactic acid bacteria were analyzed for prevention of the oxidation of erythrocyte membrane and human low-density lipoprotein in vivo. Streptococcus thermophilus 1131 and Lactobacillus delbrueckii subsp. bulgaricus 2038, yogurt starters, were chosen as test-strains, and ether extracts of these cultures were used as samples. Both strain 1131 and strain 2038 produced radical scavengers and inhibited oxidation of erythrocyte membranes and low-density lipoproteins. The antioxidative activity of strain 2038 was higher than that of strain 1131.

Adult↗
PubMed2001

Cross-reactive mechanism for the false elevation of free triiodothyronine in the patients treated with diclofenac.

We report three cases of patients exhibiting a false elevation of serum free triiodothyronine (FT3) as a result of a cross-reaction with diclofenac. The first case is a 66-yr-old woman with a long history of rheumatoid arthritis (RA). The patient was receiving diclofenac for the treatment of her RA. The patient was subsequently diagnosed as having thyroid papillary adenocarcinoma and received a subtotal thyroidectomy. After the operation, the patient exhibited postoperative hypothyroidism except for a gradual elevation of FT3. The other two patients also exhibited an elevated serum FT3 level after the administration of diclofenac. Serum FT3 levels in these patients decreased to normal or below normal after diclofenac administration was discontinued. In the first case, the elimination of immunoglobulin from the sera using polyethylene glycol precipitation did not reduce the FT3 level. In our hospital, Vitros ECi (enhanced chemiluminescence enzyme immunoassay) system and Vitros FT3 kit were used for FT3 assay. The patient's FT3 levels were normal or below normal when they were measured using other FT3 kits. FT3 was also detected when diclofenac was dissolved in a phosphate buffered saline. Therefore, we concluded that a cross-reaction between FT3 and diclofenac was the mechanism causing the false elevation of FT3 in these patients.

Aged↗
PubMed2000

Cutting edge: chromatin remodeling at the IL-4/IL-13 intergenic regulatory region for Th2-specific cytokine gene cluster.

During the differentiation of naive Th cells into Th2 effector cells, the entire IL-4/IL-13 locus is remodeled into an accessible chromatin conformation. Here we show that ectopic expression and activation of Stat6 or GATA-3 in Th cells developing under Th1-polarizing conditions lead to the induction of chromatin remodeling not only at the flanking regions of the IL-4 and IL-13 genes but also at the IL-4/IL-13 intergenic regulatory region for the IL-4/IL-13/IL-5 gene cluster. Furthermore, we demonstrate that GATA-3 and another Th2-specific, inducible protein complex interact with the IL-4/IL-13 intergenic DNase I hypersensitive region specifically in Th2 cells.

Animals↗
PubMed2000

GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells.

Committed T helper type 1 (Th1) and Th2 effector cells, resulting from chronic antigenic stimulation in interleukin (IL)-12 and IL-4, are implicated in the pathology of autoimmune and allergic diseases. Committed Th1 cells cannot be induced to change their cytokine profiles in response to antigenic stimulation and Th2 cytokine-inducing conditions. Here, we report that ectopic expression of GATA-3 induced Th2-specific cytokine expression not only in developing Th1 cells but also in otherwise irreversibly committed Th1 cells and a Th1 clone, HDK1. Moreover, cAMP, an inhibitor of cytokine production by Th1 cells, markedly augmented Th2 cytokine production in GATA-3-expressing Th1 cells. Ectopic expression of GATA-3 in developing Th1 cells, but not in Th1 clone HDK1, induced endogenous GATA-3, suggesting an autoregulatory mechanism for maintenance of GATA-3 expression in Th2 cells. Structure-function analyses of GATA-3 revealed that the NH(2)-terminal transactivation domain and the COOH-terminal zinc finger domain of GATA-3 were critical, whereas the NH(2)-terminal zinc finger domain was dispensable for the induction of IL-4. Both zinc fingers, however, were required for IL-5 induction. A Th2-specific DNaseI-hypersensitive site of the IL-4 locus was detected in GATA-3-expressing Th1 cells. Thus, GATA-3 can change the phenotype of committed Th1 cells, previously considered to be irreversible.

Animals↗
PubMed2000

Autoantibodies against the specific epitope of human tropomyosin(s) detected by a peptide based enzyme immunoassay in sera of patients with ulcerative colitis show antibody dependent cell mediated cytotoxicity against HLA-DPw9 transfected L cells.

BACKGROUND AND AIMS: Recent studies suggest that tropomyosin (TM) may act as a putative autoantigen in ulcerative colitis (UC). Recently, we identified, by computer homology analysis, a specific peptide (HIAEDADRK) in human TM that can bind to HLA-DPw9. The aim of this study was to investigate the presence of autoantibodies against this peptide in UC. METHODS: Antibodies were measured by ELISA with a synthetic peptide in 20 healthy volunteers, 48 patients with UC, 26 with Crohn's disease (CD), eight with primary sclerosing cholangitis (PSC), and six with primary biliary cirrhosis (PBC). The functional significance of antibodies was investigated by antibody dependent cell mediated cytotoxicity (ADCC) against DPw9 transfected L cells using a standard (51)Cr release assay. RESULTS: Optical density values (mean (SD)) of sera from patients with UC (1.40 (0. 52)) and PSC (1.65 (0.12)) were significantly higher than those from healthy volunteers (0.32 (0.28)) (p<0.05), CD (0.50 (0.34)) (p<0.05) and PBC (0.14 (0.09)) (p<0.05). Values in UC decreased with clinical improvement. The ADCC activity of UC sera correlated well with antibody titre against this synthetic peptide. CONCLUSIONS: Anti-TM antibody was detected in UC sera by a specific peptide based ELISA with high reproducibility. This peptide may be an antigenic epitope of TM involved in the immunopathogenesis of UC and, perhaps, PSC.

Adolescent↗
PubMed2000

[Isolation of FDC-lymphocyte clusters from human tonsillar tissues].

Follicular B cells and follicular dendritic cells (FDCs) form FDC-lymphocyte clusters and play a central role in events related to humoral immunity in the lymphoid follicle (LF). The secondary LF is divided into five zones, each of which exhibits functional differences. However, the distribution of the clusters across the five follicular zones remains unclear. We here report a procedure for isolating FDC-lymphocyte clusters from fixed tonsillar tissues and compare of the structure of clusters isolated from three follicular zones: the mantle, light and dark zones. First, the germinal centers (GCs) of the secondary LFs were removed under a stereoscope, and the GCs were enzymatically digested for 20, 30, 40 and 50 minutes at 37 degrees C. The FDC-lymphocyte clusters were then isolated using a discontinuous density gradient and a Magnetic Particle Concentrator, followed by microbeads. The number of isolated medium sized clusters composed of 6-25 cells was greatest when the samples were incubated for 40 minutes. To detect the mantle, light and dark zones, and GCs, isolated FDC-lymphocyte clusters from each zone were immunostained. Their cell structures were then compared. The clusters were composed mainly of B cells (comprising about 80% of the cells in each cluster, on average), T cells, natural killer/T cells and macrophages were also observed, but less frequently. The proportions of CD 45 RO-positive cells and CD4-positive cells were clearly different for each zone, with CD4-positive cells in the majority. No clear differences in isolated clusters from fixed and unfixed tonsillar tissues were observed. Our data indicate that this procedure is suitable for isolating FDC-lymphocyte clusters from fixed lymphoid tissues and that the proportions of cells composing the clusters differ in the three follicular zones.

Antibody Formation↗
PubMed2000

[Coronary artery bypass grafting for a patient with bronchial asthma seceeded from cardiopulmonary bypass by additional bypass for spasm of radial artery graft: a case report].

A 78-year-old male who had a bronchial asthma underwent coronary artery bypass grafting (CABG) using the left internal thoracic artery and the radial artery. The patient could not be weaned from the cardiopulmonary bypass because the radial artery which anastomosed to the obtuse marginal artery (OM) had a spasm after CABG. An additional bypass using a long saphenous vein to OM was carried out immediately. It brought a weaning from cardiopulmonary bypass. If the cardiac function after CABG is insufficient in patients with bronchial asthma, CABG must be re-done immediately, considering that they cause the arterial spasm more than patients without bronchial asthma.

Aged↗
PubMed1999

The advantages of normocalcemic continuous warm cardioplegia over low calcemic cardioplegia in myocardial protection.

The effects of changing the calcium content of a continuous warm hyperkalemic crystalloid cardioplegia (CWCP) were investigated in an isolated rat heart preparation. The hearts were divided into eight groups of six each. A control group consisted of fresh nonarrested hearts and the remaining seven groups consisted of hearts perfused with continuous hyperkalemic (20 mM) modified Krebs-Henseleit bicarbonate buffer solution with calcium concentrations of 0.1, 0.3, 0.5, 1.0, 1.5, 2.0, or 2.5 mM, for either 180 or 240 min at 37 degrees C. In the hearts arrested for 180 min, there were no significant differences in postarrest cardiac functions between the control group and any of the groups perfused with calcium concentrations of 0.5 mM or more. With a calcium concentration of 0.1 mM, the calcium paradox was provoked. The change in the calcium content of CWCP perfused for 240 min significantly affected myocardial protection. Maximum aortic flow recovery, of 74.7% +/- 2.7%, and minimum CK release, of 15.7 +/- 2.4 IU/15 min/g dry weight, were observed in hearts perfused with a calcium concentration of 1.5 mM. The calcium paradox occurred even at a calcium concentration of 0.3 mM; therefore, normal calcium concentrations should be maintained in cardiac surgery to prevent cardiac injury.

Animals↗
PubMed1999

Pulmonary artery aneurysm.

Main pulmonary artery aneurysm is an exceedingly rare entity. We present a case of main pulmonary artery aneurysm with patent ductus arteriosus in a sixty-year-old woman. The aneurysm was successfully treated with aneurysmectomy and primary anastomosis of the defect of the main pulmonary artery, and the patent ductus arteriosus was divided. The etiology, operative indication and surgical intervention of main pulmonary artery aneurysm are discussed along with a review of the literature.

Anastomosis, Surgical↗
PubMed1999

Risk of low calcium and high magnesium in continuous warm hyperkalemic cardioplegia.

BACKGROUND: The recent introduction of operations on a warm heart has prompted clinical reports on the usefulness of continuous blood cardioplegia, but no in-depth basic evaluation of continuous cardioplegia has been done. The cardioprotective effects of magnesium (Mg) and calcium (Ca) in continuous warm hyperkalemic crystalloid cardioplegic solutions were investigated in an isolated rat heart model. METHODS: Isolated rat hearts were arrested for 180 minutes at 37 degrees C with a continuous warm hyperkalemic (20 mmol/L) modified Krebs-Henseleit bicarbonate buffer solution containing 1.2, 8.0, or 16.0 mmol/L of Mg and 0.1 to 2.5 mmol/L of Ca in different concentrations. Recovery of cardiac function and tissue damage were estimated. RESULTS: For each Mg concentration, the percentage recovery of aortic flow generated dose-response curves depending on Ca concentration. However, as Mg concentration increased, the recovery of aortic flow decreased in the groups with 0.5 mmol/L of Ca or less. CONCLUSIONS: In continuous warm cardioplegia the combination of low Ca and high Mg concentration caused severe cardiac injury, and normal Ca concentration avoids cardiac injury regardless of Mg concentrations.

Animals↗
PubMed1999

Tumor markers CEA, CA19-9 and CA125 in monitoring of response to systemic chemotherapy in patients with advanced gastric cancer.

BACKGROUND: To evaluate whether tumor markers can be used to assess response to systemic chemotherapy, we analyzed preliminarily the relationship between the response to chemotherapy based on serial imaging and on change in serum tumor marker level of CEA, CA19-9 and CA125. METHODS: We analyzed 26 patients with advanced gastric cancer in whom at least one of the tumor markers CEA, CA19-9 and CA125 was elevated before systemic chemotherapy with regard to the relationship between the change in serum tumor marker level and response assessment by imaging studies throughout the treatment course. A responder was defined as showing a > or = 50% drop in tumor marker level for more than 4 weeks. RESULTS: The sensitivity and negative predictive value of falling tumor marker level after chemotherapy for a partial response in imaging was 100%. When patients were categorized as responders or non-responders, a significant correlation was observed between the assessment of response by tumor markers and by imaging studies. The survival time of responders assessed by tumor markers was significantly longer than that of non-responders. CONCLUSIONS: The measurement of tumor markers might be useful in monitoring response and in predicting the prognosis of patients with advanced gastric cancer treated with systemic chemotherapy. Tumor markers may be used as a means of monitoring treatment in patients when in an imaging study it is difficult to assess response to chemotherapy in clinical practice. Further studies are required to confirm these findings.

Adult↗
PubMed1998

Regulation of intracellular calcium concentrations by calcium and magnesium in cardioplegic solutions protects rat neonatal myocytes from simulated ischemia.

The effects of calcium and magnesium ions in cardioplegic solutions on cardioprotection and intracellular calcium ion handling during ischemia and reoxygenation were investigated in cultured neonatal rat myocardial cells. Myocytes were subjected to simulated ischemia for 60 min at 37 degrees C in hyperkalemic cardioplegic solutions containing various concentrations of calcium and magnesium ions, followed by 30 min of reoxygenation. For each Ca2+ concentration (0.1, 0.6, 1.2, or 2.4 mM), the Mg2+ concentration was either 0, 1.2, 8, or 16 mM. The increase in intracellular Ca2+ concentration during ischemia and reoxygenation was suppressed by the addition of magnesium ion, independent of cardioplegic Ca2+ concentration. The recovery of spontaneous contraction rate and enzyme leakage (creatine phosphokinase and lactate dehydrogenase) during both ischemia and reoxygenation correlated with the degree of inhibition of intracellular Ca2+ accumulation. However, in the 0.1 mM Ca2+ groups in which the Mg2+ concentration was greater than 8 mM, the intracellular Ca2+ concentration increased during reoxygenation in a dose-dependent fashion of Mg2+, and was associated with increased enzyme leakage. The findings suggest that in immature cardiac myocytes, the concentrations of Ca2+ and Mg2+ present in cardioplegic solutions control the intracellular Ca2+ concentration during ischemia and reoxygenation, which, in turn, influences the cardioprotective effect of the cardioplegic solution.

Animals↗
PubMed1998

Th2-specific DNase I-hypersensitive sites in the murine IL-13 and IL-4 intergenic region.

IL-4 and IL-13 are cytokines preferentially produced by Th2 cells, and their genes are located in close proximity on human chromosome 5 and mouse chromosome 11. To identify potential regulatory elements that confer Th2-specific expression of IL-4 and IL-13 genes, we constructed a physical map of the IL-13/IL-4 locus and conducted DNase I-hypersensitive (DH) site analysis using Th clones and in vitro-differentiated effector Th cells obtained from TCR transgenic mice. Three DH sites, HSS1, HSS2 and HSS3, were identified within the intergenic region between IL-13 and IL-4 genes. HSS3 was observed both in Th1 and Th2 cells as well as CD4+ naive T cells, while HSS1 and HSS2 were detected exclusively in Th2 cells. The correlation between differentiation into Th2 subtype and the appearance of HSS1 and HSS2 suggests that these regions may play a role in subtype-specific expression of the IL-13/IL-4 locus.

3' Untranslated Regions↗
PubMed1998

[Progress in diagnosis of gastric cancer and improvement of treatment results].

The diagnosis of gastric cancer has made remarkable progress in the last 20 years, thanks to the establishment of diagnostic methodology including double contrast radiography, endoscopy (gastrocamera and fiberscope), and endoscopic biopsy. The treated number of early gastric cancers began to account for more than 50% around 1985 in the majority of Japanese institutions which specialized in gastroenterology. It is considered that the improvement of the treatment result is mostly due to the increasing number of early gastric cancers, although the progress in surgery for advanced cancer may also be a contributing factor. Now endoscopic mucosal resection has become a common treatment method for small early cancer, and the use of laparoscopic surgery has been increasing. We are now in an era seeking for rationalization of treatment options in view of reductive and function preserving surgery.

Biopsy↗