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Biomedical subjects

Takanori Ueda

Publications and source records attributed to Takanori Ueda.

At least 37 records · Page 2Linked to original sources
PubMed2005

Resistance to 9-beta-D-arabinofuranosyl-2-fluoroadenine due to reduced incorporation into DNA from competition by excess deoxyadenosine triphosphate: implications for different sensitivities to nucleoside analogues.

The cytotoxic action of the deoxyadenosine analogue 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-ara-A) depends on the incorporation into DNA after being phosphorylated to F-ara-A triphosphate (F-ara-ATP) by deoxycytidine kinase (dCK). The mechanisms of resistance to F-ara-A were investigated in a newly established variant of L1210 mouse leukemia cells (L1210/F). L1210/F was more than 41-fold more resistant to F-ara-A than the parental cell line and had a 55% lower dCK activity. Interestingly, L1210/F showed a modest level of cross-resistance to deoxycytidine analogues phosphorylated by dCK, for instance, 1-beta-D-arabinofuranosylcytosine (ara-C). The comparative study of F-ara-A and ara-C demonstrated that the difference in the accumulation of their respective triphosphates was minor. In contrast, the incorporation of F-ara-A into DNA was strikingly suppressed compared with that of ara-C. In general, the high natural triphosphate levels interfere with corresponding analogue incorporation into DNA. The deoxyadenosine triphosphate (dATP) and deoxycytidine triphosphate pool sizes in L1210/F cells were increased by 4.9-fold and 1.9-fold, respectively, compared with the parental cells. Treatment with hydroxyurea increased the ratio of F-ara-ATP to dATP 2.1-fold and enhanced the action of F-ara-A in L1210/F. This is the first cell line to show that the profoundly defective incorporation of F-ara-A into DNA during competition with excess dATP confers a high degree of resistance to F-ara-A.

Animals↗
PubMed2005

Different clinical features, biochemical profiles, echocardiographic and elctrocardiographic findings in older and younger patients with idiopathic dilated cardiomyopathy.

OBJECTIVE: To study the clinical features, biochemical profiles, echocardiographic and electrocardiographic findings in the elderly and younger with idiopathic dilated cardiomyopathy (IDCM). METHODS: We measured biochemical profiles and reviewed the clinical features, echocardiographic and electrocardiographic findings in 40 elderly (group A) and 70 younger (group B) patients with IDCM. RESULTS: The aldosterone level in group A was higher than in group B (304.8 +/- 69.1 vs. 213.3 +/- 54.5 pmol/l, P < 0.05). Triiodothyronine (T3) and free T3 in group A were lower than in group B (0.78 +/- 0.21 and 2.87 +/- 0.73 vs. 1.26 +/- 0.33 nmol/l and 3.55 +/- 0.64 pmol/l, all P < 0.05). The incidence of ventricular arrhythmia in group A was lower than in group B (61.3% vs. 92.1 %, P < 0.01). The incidence of hypokalaemia and hypomagnesaemia were higher in group A (51.3% and 27.5%). 28.8% patients in group A were susceptible to digitalis intoxication. Disease duration and mean survival period in group A were longer than in group B (11.0 +/- 4.7 and 6.9 +/- 4.2 vs. 5.2 +/- 2.5 y and 3.4 +/- 2.7 y, all P < 0.05). The main cause of death in group A was congestive heart failure (78.9%) and ventricular arrhythmia (61.9%) in group B. CONCLUSIONS: The prognosis in group A was better than in group B. The patients in group A usually showed low T3 syndrome. Ventricular arrhythmia in group A may be due to heart failure, electrolyte imbalance and sympathetic activation.

Adolescent↗
PubMed2005

Status of intracellular and extracellular magnesium concentration in patients with cardiac syndrome X.

OBJECTIVES: This study sought to clarify the differences of intracellular and extracellular magnesium levels in patients with cardiac syndrome X. METHODS: We evaluated the intracellular and extracellular magnesium status of 22 patients with cardiac syndrome X (group A) and 22 age--and gender--matched disorder-free control subjects (group B). Levels of magnesium were determined in serum, urine, erythrocytes, and the 24-h magnesium retention rate was calculated by a magnesium loading test. RESULTS: Group A showed a higher 24-h magnesium retention rate (49.8 +/- 1.3% vs. 32.6 +/- 7.5%, p < 0.05) and a lower intracellular concentration of magnesium in erythrocytes than group B (3.7 +/- 1.4 vs. 5.6 +/- 1.3 fg/cell, p < 0.05), demonstrating the presence of magnesium deficiency in group A. There were no significant differences in the serum concentration of magnesium between groups A and B (0.87 +/- 0.23 vs. 0.83 +/- 0.15 mmol/l). CONCLUSIONS: This study demonstrated that the intracellular magnesium level decreased in patients with cardiac syndrome X.

Adult↗
PubMed2005

Effects of copper and zinc on the production of homocysteine-induced extracellular matrix metalloproteinase-2 in cultured rat vascular smooth muscle cells.

OBJECTIVE: To study the effects of copper and zinc on the production of homocysteine-induced extracellular matrix metalloproteinase-2 in cultured rats vascular smooth muscle cells. METHODS: We examined the effects of different homocysteine levels (0-1000 micromol/l) on matrix metalloproteinase-2 (MMP-2) production, and the effects of different copper and zinc concentrations (0-300 micromol/l) on homocysteine-induced MMP-2 in cultured rat vascular smooth muscle cells (VSMCs) using gelatin zymography and western blotting. We further compared the changes of MMP-2 under various treatments for 24, 48 and 72 hours. RESULTS: Homocysteine (50-1000 micromol/l) increased the production of MMP-2 significantly in a dose-dependent manner. Copper decreased the homocysteine-induced MMP-2 under these conditions in a dose-dependent manner, but zinc did not. Production of MMP-2 under various treatments for 72 h increased more than 24 h and 48 h. CONCLUSIONS: Extracellular added copper decreased homocysteine-induced MMP-2 secretion.

Analysis of Variance↗
PubMed2005

Effect of erythromycin on homocysteine-induced extracellular matrix metalloproteinase-2 production in cultured rat vascular smooth muscle cells.

BACKGROUND & OBJECTIVE: Several lines of evidence have shown an association between Chlamydia infection and atherosclerosis, but clinical trials of preventive antibiotic (erythromycin) treatment in patients with coronary artery disease have shown conflicting results. Hyperhomocysteinaemia is an independent risk factor of coronary artery disease and causes an intense remodelling of the extracellular matrix in arterial walls, particularly an elastolysis involving metalloproteinases. In the present study we investigated the effects of erythromycin on the production of homocysteineinduced extracellular matrix metalloproteinase-2 (MMP-2) in cultured rat vascular smooth muscle cells (VSMCs). METHODS: Effects of different concentration of homocysteine (Hcy) (0-5000 micromol/l) on MMP-2 production, and the effects of different erythromycin concentrations (0-10 mmol/l) on homocysteine-induced MMP-2 production in cultured rat VSMCs were studied using gelatin zymography and Western blotting. The changes of MMP-2 under various treatments for 1, 3 and 5 days were also compared. RESULTS: Homocysteine (50-1000 mu mol/l) increased the production of MMP-2 significantly in a dose-dependent manner and reduced the production of MMP-2 at a high level (5000 mu mol/l). Increased production of MMP-2 induced by homocysteine was reduced by extracellularly added erythromycin in a dose-dependent manner. INTERPRETATION & CONCLUSION: Homocysteine increased the production of MMP-2 significantly in a dose-dependent manner. Extracellularly added erythromycin decreased homocysteine-induced MMP-2 secretion. The findings of the present study suggested that the beneficial effect of erythromycin on vascular disease processes might be due to its inhibitory effect on the Hcyinduced production of MMP-2 in VSMCs.

Animals↗
PubMed2005

[Adams-Stokes attack due to complete atrioventricular block in a patient with acute promyelocytic leukemia during remission induction therapy using all-trans retinoic acid].

We describe a case of Adams-Stokes syncope due to complete atrioventricular block which occurred in a leukemic patient receiving all-trans retinoic acid (ATRA). Remission induction therapy was performed for a 46-year-old Japanese man with acute promyelocytic leukemia using ATRA (45 mg/m2), enocitabine (170 mg/m2, 5 days), and mitoxantrone (4 mg/m2, 3 days). On the 25th day of chemotherapy, syncope suddenly occurred. Electrocardiography revealed a complete atrioventricular block, and a temporary pacemaker was inserted on the following day. The block was persistent and the cardiac rhythm was dependent on the pacemaker. ATRA was discontinued on the 29th day because the arrhythmia was believed to be an adverse reaction to the ATRA regimen. The normal sinus rhythm was restored 15 days thereafter, and the patient eventually reached remission. He subsequently received 4 courses of consolidation therapy without any cardiovascular complications. Although ATRA sometimes induces arrhythmias, to the best of our knowledge this is the first report in the literature of such a critical ATRA-related arrhythmia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Inhibition of repair of carboplatin-induced DNA damage by 9-beta-D-arabinofuranosyl-2-fluoroadenine in quiescent human lymphocytes.

Previous studies including ours have demonstrated that DNA repair is one of the important targets of fludarabine. The aim of this study is to clarify a mechanistic interaction of carboplatin and F-ara-A, from the perspective of F-ara-A-mediated inhibition of DNA repair initiated by carboplatin. Using human quiescent lymphocytes, we focused on DNA repair, since these cells provide a model of dormant cells. To evaluate the carboplatin-induced DNA incision and its repair, we used the alkaline comet assay. When lymphocytes were incubated with carboplatin, a dose-dependent increase in the tail-moment was observed. Then, tail-moment decreased in proportion to the incubation period in fresh media and recovered to the control level at 4 h. DNA rejoining was completely inhibited by F-ara-A at 10 microM through 0 to 6 h after washing out of these drugs and this F-ara-A-induced inhibition was concentration-dependent. Cellular damage after drug exposure was evaluated with the induction of apoptosis as well as cytotoxic effect. Exposure to carboplatin alone did not induce any apparent cellular damage in quiescent lymphocytes. In contrast, a more than additive induction of apoptosis as well as an enhancement of cytotoxic action was observed in cells treated with a combination of carboplatin and F-ara-A. In the CEM cell line, there was no enhancement of the cytotoxic action of these drugs, despite the clear demonstration of an inhibitory effect on DNA repair. These results indicate that chemotherapy with carboplatin opened a new target for F-ara-A by initiating DNA repair in quiescent cells.

Antineoplastic Agents↗
PubMed2004

Effects of magnesium on matrix metalloproteinase-2 production in cultured rat cardiac fibroblasts.

The precise correlation between magnesium and cardiac disease remains to be established. Matrix metalloproteinases (MMPs) are important in cardiac disease such as heart failure. Cardiac fibroblasts are the most abundant cell type in the heart and play an important role in the regulation of collagen degradation by MMPs. To assess the association between magnesium and MMPs, we examined the effects of different extracellular magnesium concentrations (0-3.0 mmol/L) on MMP-2 production in cultured rat cardiac fibroblasts. Using gelatin zymography and western blotting, we found that magnesium reduced MMP-2 production dose-dependently, and this effect was inhibited by the tyrosine kinase inhibitors, genistein or herbimycin A. The results of this study indicated that the beneficial effect of magnesium supplementation on the cardiac disease may be due, at least in part, to the inhibitory effect of magnesium on production of MMPs in cardiac fibroblasts, which appears to be mediated by a protein tyrosine phosphorylation related signal transduction pathway.

Animals↗
PubMed2004

Identification of a novel splice variant of the human anti-apoptopsis gene survivin.

Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, has been reported to be expressed in many cancers but not in differentiated normal tissues. In the present study, we describe the identification of a novel alternatively spliced survivin transcript, designated as survivin-3B. It comprises 5 exons including novel exon 3B derived from a 165-bp long portion of intron 3. Acquisition of a new in-frame TGA stop codon within the novel exon 3B results in an open reading frame (ORF) of 363 nucleotides, predicting a truncated 120 amino acid protein. Expression of survivin-3B was detected in human colon and gastric adenocarcinoma cell lines as well as mononuclear cells prepared from patients with myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Survivin-3B contains a single baculovirus IAP repeat (BIR), which is critical for apoptosis inhibition. However, it lacks a carboxyl-terminal coiled-coil domain, suggesting that survivin-3B may not be associated with G2/M phase. These data indicate that the function of survivin-3B may be different from that of regular survivin.

Alternative Splicing↗
PubMed2004

Simple and sensitive method for quantification of fludarabine triphosphate intracellular concentration in leukemic cells using isocratic liquid chromatography.

A simple, isocratic HPLC method was newly developed for quantitating intracellular fludarabine triphosphate (F-ara-ATP). Samples (500 microl) were injected onto an anion-exchange column and eluted isocratically with phosphate-acetonitrile buffer (flow rate: 0.7 ml/min) at an ambient temperature. F-ara-ATP was quantitated according to its peak area at the absorbance of 261 nm. The standard curve was linear with minimal within-day and inter-day variability. The low and high quantification limits were 50 pmol and 20 nmol, respectively. The method was capable of measuring F-ara-ATP generated in cultured leukemic cells in vitro. Thus, our method will be useful because of its sensitivity and simplicity as well as applicability to biological materials.

Antineoplastic Agents↗
PubMed2004

Relationship between the degree of intracellular magnesium deficiency and the frequency of chest pain in women with variant angina.

OBJECTIVES: This study sought to clarify the relationship between the degree of intracellular magnesium deficiency and the frequency of anginal attacks in women with variant angina. PATIENTS AND METHODS: We evaluated the intracellular and extracellular magnesium status of twelve women with variant angina: group A (> or = 4 attacks/week, n = 5) and group B (< 4 attacks/week, n = 7). Magnesium levels were determined in serum, urine, and erythrocytes, and the 24-h magnesium retention rate was calculated by magnesium loading test. RESULTS: Group A showed a higher 24-h magnesium retention rate (58.2 +/- 9.1% vs. 31.3 +/- 4.4%; p < 0.01) and a lower intracellular concentration of magnesium in erythrocytes than group B (3.1 +/- 1.1 vs. 5.0 +/- 0.8 fg/cell; p < 0.05), demonstrating the presence of magnesium deficiency in group A. The 24-h magnesium retention rate and intracellular concentrations of magnesium in erythrocytes correlated well with the activity of variant angina (r = 0.61, p < 0.01; and r = -0.74, p < 0.01, respectively) for these patients. CONCLUSION: This study demonstrates that the degree of intracellular magnesium deficiency in women with variant angina is closely related to the frequency of chest pain.

Aged↗
PubMed2004

Circulating matrix metalloproteinase-2 is elevated in patients with congestive heart failure.

BACKGROUND AND AIMS: It has been reported that matrix metalloproteinase (MMP) protein concentration and activity are upregulated in the failing human heart. However, there are few reports describing the role of elevated level of circulating MMPs in congestive heart failure (CHF) patients. This study examined whether circulating matrix metalloproteinases (MMPs) are also related to the pathogenesis of CHF. METHODS: We measured circulating levels of matrix metalloproteinase-2 (MMP-2) in 52 patients with CHF (left ventricular ejection fraction (LVEF) <50%). The patients were also subdivided into two groups according to NYHA functional class; mild CHF (class II, n=43) and severe CHF (class III, n=9). RESULTS: The serum level of MMP-2 and MMP-2/TIMP-2 ratio were significantly higher in CHF than in controls (P<0.01). Among patient groups, serum levels of MMP-2 were significantly higher in patients with severe CHF than in patients with mild CHF (P<0.01). Plasma levels of BNP had a significant positive correlation with circulating levels of MMP-2 (r=0.78; P<0.01) and MMP-2/TIMP-2 ratio (r=0.60; P<0.01). CONCLUSIONS: Our data showed that the circulating MMP-2 concentration was increased in CHF patients and that the levels were related to the plasma levels of BNP in CHF, suggesting that the elevated levels are related to developing heart failure syndrome.

Aged↗
PubMed2004

Modulation of the human interleukin-12p40 response by a triazole antifungal derivative, itraconazole.

Some types of antimicrobial agents such as fosfomycin, clarithromycin, and erythromycin have been known to affect the host's immunological response. We investigated whether itraconazole (ITCZ) can modulate the serum cytokine levels (tumor necrosis factor (TNF-alpha, interleukin (IL)-10, IL-12p40) in both patients and healthy subjects. Serum samples were collected and TNF-alpha, IL-10 and IL-12p40 were measured using a sandwich enzyme-linked immunosorbent assay (ELISA). We showed increased levels of IL-12p40 in patients treated with ITCZ. In healthy subjects, moreover, ITCZ treatment significantly increased the production of IL-12p40, but not TNF-alpha or IL-10. These findings suggest that the effectiveness of ITCZ in the treatment of fungal infection may be due not only to its direct antifungal effect, but also to induction of an immunomodulative effect on the host defense systems by regulation of cytokine production.

Adult↗
PubMed2004

Different effects of calcium channel blockers on matrix metalloproteinase-2 expression in cultured rat cardiac fibroblasts.

The cardiac effects of calcium channel blockers (CCBs) related to cardiac remodeling are inconsistent. Matrix metalloproteinases (MMPs) contribute to tissue remodeling. Cardiac fibroblasts play an important role in the regulation of collagen degradation by MMPs. Using gelatin zymography, Western blotting, Griess reagent, and a calcium kit-fluo 3, we investigated the effects of nifedipine, verapamil, diltiazem, and amlodipine on MMP-2 expression and further elucidate the mechanisms in cultured rat cardiac fibroblasts. Nifedipine increased and amlodipine decreased the expression of MMP-2; however, neither verapamil nor diltiazem altered MMP-2 expression. Nifedipine also increased nitrite production, and this increase was blunted by a nitric oxide (NO) synthases inhibitor (L-NAME). Nifedipine-induced MMP-2 expression was also blunted by L-NAME. An NO donor (sodium nitroprusside) induced MMP-2 expression. Data indicated that nifedipine might increase MMP-2 expression through a possible NO-dependent pathway. Amlodipine had no influence on nitrite production. The amlodipine-induced decrease of MMP-2 expression was abolished by two protein tyrosine kinase inhibitors, genistein and herbimycin A, indicating that amlodipine might decrease MMP-2 expression through a possible protein tyrosine kinase pathway. None of the four CCBs could alter the fluoscence intensity of fluo 3, indicating that the effects of CCBs on MMP-2 expression were independent of the variation in intracellular C2+ concentration. Our findings revealed that different CCBs exerted different effects on MMP-2 expression in cardiac fibroblasts.

Amlodipine↗
PubMed2004

Reduced intensity allogeneic stem cell transplantation for systemic primary amyloidosis refractory to high-dose melphalan.

Complete elimination of the plasma cell dyscrasia is a rational therapeutic goal, as intercepting supply of precursor protein is a necessary condition for a major regression of amyloid deposits. High-dose melphalan with autologous stem cell transplantation has shown the ability to induce complete hematological response (HR) along with recovery of organ dysfunction. However, the rate of HR with this treatment rarely exceeds 40%. We describe here the first known case of successful reduced intensity allogeneic stem cell transplantation (RIST) for a patient with primary amyloidosis complicated with nephrotic syndrome but without cardiac disease, who had obtained only partial HR by high-dose melphalan with autologous stem cell transplantation. RIST may be feasible and be capable of achieving complete HR along with recovery from nephrotic syndrome with acceptable toxicity.

Amyloidosis↗
PubMed2004

[A pilot study of antibiotic cycling for the treatment of febrile neutropenia patients with hematological diseases].

Two antibiotics recommended by the guideline of Infectious Diseases Society of America (IDSA) were selected for treatment of febrile neutropenia, and these paired antibiotics were changed periodically three times. The clinical efficacy of each antibiotic was retrospectively evaluated at the end of the final period. There was no significant difference about efficacy rate between two kinds of antibiotics in the same sequential period. However, the efficacy rate has been rising and febrile duration has been shortening by degrees. Only a few drug resistant bacteria were recognized by the surveillance culture during antibiotic cycling. Recently, antibiotic cycling therapy has attracted attention especially in the ICU. However, a clinical study of treatment for febrile neutropenia has not been reported. Our trial suggests that cycling therapy may be useful for febrile neutropenia. However, Some deviation in the patients characteristics of each period may affect the result. It seems that further examination is necessary about usefullness of the cycling therapy for febrile neutropenia.

Adult↗
PubMed2004

An integrated comprehensive workbench for inferring genetic networks: voyagene.

We propose an integrated, comprehensive network-inferring system for genetic interactions, named VoyaGene, which can analyze experimentally observed expression profiles by using and combining the following five independent inferring models: Clustering, Threshold-Test, Bayesian, multi-level digraph and S-system models. Since VoyaGene also has effective tools for visualizing the inferred results, researchers may evaluate the combination of appropriate inferring models, and can construct a genetic network to an accuracy that is beyond the reach of a single inferring model. Through the use of VoyaGene, the present study demonstrates the effectiveness of combining different inferring models.

Algorithms↗