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Takanori Ueda

Publications and source records attributed to Takanori Ueda.

At least 73 records · Page 4Linked to original sources
PubMed2003

Cutaneous arteriolar thioredoxin expression in patients with heart failure.

Cutaneous microangiopathic lesions exist in patients with heart failure, and heart failure is associated with increased oxidative stress. Thioredoxin (TRX) is stress-inducible and has a cytoprotective effect against oxidative stress. Accordingly, to investigate whether arteriolar TRX expression was increased in the skin of patients with congestive heart failure (CHF), skin biopsies were taken at the time of cardiac catheterization, and the results were compared with those of control subjects. The diagnosis of CHF was done by cardiac catheterization with reference to elevated plasma concentrations of TRX and brain natriuretic peptide (BNP). Increased TRX expression was found in the skin biopsies of 29 of the 35 patients with CHF, but in none of the 8 control subjects; the semiquantitative grade of arteriolar TRX immunoreactivity was 2.5+/-1.0 in patients with CHF and 1.0+/-0.0 in controls, respectively (p<0.01). The severity of arteriolar TRX expression did not correlate with the New York Heart Association functional class. These results indicate that cutaneous arteriolar TRX expression in patients with CHF may reflect the excessive oxidative stress of the peripheral circulation associated with the condition.

Aged↗
PubMed2003

The impact of liver metastasis on mortality in patients initially diagnosed with locally advanced or resectable pancreatic cancer.

BACKGROUND: Liver metastases are frequent in pancreatic cancer, although their impact on patient mortality is still unclear. METHOD: The extent of liver metastasis (H-III [diffuse], H-II [moderate], H-I [limited], H-0) and the magnitude of liver dysfunction (lf-III [failure], lf-II [severe], lf-I [moderate], lf-0) were reviewed in 89 locally advanced and resectable pancreatic cancer patients in order to determine possible relationships with mortality and survival. RESULTS: The extent of liver metastasis (H-III, 18; H-II, 20; H-I, 12; H-0, 39) and the magnitude of liver dysfunction (lf-III, 12; lf-II, 8; lf-I, 11; lf-0, 58) were quite variable. Based on the aforementioned two categories, pancreatic cancer patients could be divided into four groups: (A) extensive liver metastasis affecting patient mortality, 14% (12/89); (B) liver metastases that do not cause severe liver dysfunction, 38% (34/89); (C) severe liver dysfunction, not associated with liver metastasis, 9% (8/89); (D) spared liver function, with no liver metastasis, 39% (35/89). The median survival period of H-III patients (195 d) was quite short compared with those of H-I (288 d) and H-0 (240 d) patients. CONCLUSION: Considering patients with locally advanced and resectable pancreatic cancer, the fraction of cases with diffuse liver metastases is relatively small. Moreover, only a minor proportion of pancreatic cancer patients die from hepatic failure as a direct result of liver metastasis.

Adult↗
PubMed2003

Plasma homocysteine levels in patients with early coronary artery stenosis and high risk factors.

The aim of this study was to study the relationship between plasma homocysteine (Hcy), folic acid, vitamin B12 and early coronary artery disease (early-CAD) and high coronary risk factors. The plasma Hcy levels of 58 cases with early-CAD and 31 subjects without CAD were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. Plasma folic acid and Vitamin B12 levels were measured with radioassay method. The plasma Hcy level was significantly higher in the early-CAD patients than in the controls [(13.7 +/- 5.1) micromol/L vs (10.3 +/- 5.7) micromol/L]. The plasma folic acid and Vitamin B12 levels were significantly lower in the early-CAD patients than in the controls. The plasma Hcy level was higher in patients with more than 3 risk factors of CAD than in patients with 1 or 2 risk factors and in the controls [(17.3 +/- 5.1) micromol/ L vs (12.9 +/- 4.8) micromol/L, (7.8 +/- 2.5) micromol/L]. Other than gender, all classical coronary risk factors were related to the elevated Hcy level. Hcy levels were elevated in patients with early-CAD and with high risk factors. Hyperhomocysteinemia plays an important role in the pathogenesis of CAD.

Adult↗
PubMed2003

Expression of the anti-apoptotic gene survivin in myelodysplastic syndrome.

Survivin is a member of the inhibitor of apoptosis protein (IAPs) family and considered to play a pivotal role in oncogenesis. We present the first report of survivin expression profile in myelodysplastic syndrome (MDS). Expression of survivin messenger RNA was evaluated by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with MDS and acute myeloid leukemia (AML). Eleven out of 12 patients with refractory anemia (RA) (91.6%), and all 3 patients with refractory anemia with excess blasts in transformation (RAEBt) (100%), were positive for survivin expression with the majority of cases showing abundant levels of the survivin transcript. On the other hand, expression of survivin was undetectable in the 4 patients with chronic myelomonocytic leukemia (CMMoL). The level and frequency of survivin expression in patients with refractory anemia were compared to those in patients with AML. Out of 12 patients with de novo AML, 5 patients (41.7%) showed detectable levels of survivin expression. Abundant survivin expression in RA was also confirmed by immunohistochemistry. In contrast, survivin was almost absent in two cases with aplastic anemia. We propose that high levels of survivin expression can serve as a reliable diagnostic marker of RA in MDS.

Anemia, Refractory↗
PubMed2003

Atypical nuclear apoptosis downstream to caspase-3 activation in ara-C treated CCRF-CEM cells.

The necessity of internucleosomal DNA fragmentation for the complete execution of apoptosis is still controversial. While investigating the apoptotic pathway induced by 1-beta-D-arabinofuranosylcytosine (ara-C) in the human T-lymphoblastic leukemia CCRF-CEM (CEM) cells, we could easily retrieve high molecular weight (HMW) DNA fragments with a predominant size of 50 kb. However, under the same circumstances, internucleosomal DNA fragmentation characteristic of apoptosis was undetectable despite estimated heightened caspase-3 activity. Paradoxically, generation of low molecular weight DNA fragments was readily demonstrable by flow cytometric and immunohistochemical evidence in the absence of any detectable DNA ladder formation. These findings present a proof that, within certain contexts, small-sized DNA fragmentation occurring in apoptosis may not necessarily be of the ladder yielding internucleosomal integer multiples' pattern. Our data also add to the evidence that the machinery underlying HMW DNA fragmentation is distinct from that responsible for the internucleosomal one.

Antimetabolites, Antineoplastic↗
PubMed2003

A comparison of the specificity and sensitivity of two Candida antigen assay systems for the diagnosis of deep candidiasis in patients with hematologic diseases.

BACKGROUND: Latex agglutination assay for detection of circulating Candida antigen (Cand-Tec, Ramco Laboratories), which is now commercially available, provides a rapid and simple means for the diagnosis and management of deep-seated Candida infections. MATERIAL/METHODS: The Cand-Tec microtiter system (Cand-Tec MT, Ramco Japan), new latex agglutination assay for Candida antigen, expresses Candida antigen level as the cutoff index (C.I.) value by means of colorimetric analysis and is expected to be more objective method. RESULTS: In this study, we evaluated the advantages, if any, of Cand-Tec MT compared with the original Cand-Tec for the diagnosis of deep-seated Candida infections in 25 patients with hematologic diseases. A total of 80 serum specimens were taken from the patients when they showed febrile neutropenia and were suspected of having infectious disease. The C.I. value in Cand-Tec MT well correlated with the Cand-Tec titer. The sensitivity and specificity of Cand-Tec MT were 100% and 80%, respectively. The change in C.I. value in the sera was followed up during antifungal therapy. The C.I. value decreased in 75% of cases that responded to antifungal therapy, but did not show any tendency in non-responsive cases. In some cases, the C.I. value showed improvement corresponding to the therapeutic effect, while the Cand-Tec titer did not. CONCLUSIONS: Cand-Tec MT is a useful method for the early diagnosis and accurate evaluation of the therapeutic effect of systemic candidiasis.

Antigens, Fungal↗
PubMed2003

Activation of caspases-3/7 is dispensable for idarubicin-induced apoptotic DNA fragmentation in human leukemia cells.

Idarubicin (IDA) is a 4-demethoxy-anthracycline analogue of daunorubicin (DNR). IDA has been recognized as a potent anti-leukemic agent. However, the molecular mechanism of IDA-induced cell death remains unclear. In the present study, we investigated the activity of IDA to induce apoptosis in human leukemia HL-60 and Jurkat cells, and studied its relationship with activation of caspases-3/7. IDA induced apoptotic DNA fragmentation in a time- and dose-dependent manner. The kinetics of apoptotic DNA fragmentation induced by IDA was well correlated with that of caspase-3/7 activation. We examined the effect of caspase-3/7 inhibitor Ac-DEVD-CHO on IDA-induced apoptosis in HL-60 and Jurkat cells. Ac-DEVD-CHO abolished IDA-induced caspases-3/7 activation in both cell lines. We have also found that L-carnitine can inhibit recombinant caspase-3 activity in vitro. L-carnitine treatment prevented IDA-induced caspases-3/7 activation in both cell lines in a dose-dependent manner. However, neither Ac-DEVD-CHO nor L-carnitine inhibited IDA-induced apoptotic internucleosomal DNA fragmentation in HL-60 or Jurkat cells. These data suggest that caspase-3/7 may be dispensable for idarubicin-induced internucleosomal DNA cleavage during apoptosis in human leukemia cells.

Antineoplastic Agents↗
PubMed2002

Establishment of a first-order kinetic model of light chain-associated amyloid fibril extension in vitro.

Light chain-associated (AL) amyloidosis is a common and fatal systemic amyloidosis. AL amyloid fibrils (fAL) are composed of intact or fragmental monoclonal light chains (AL proteins). To elucidate the molecular mechanisms of fAL formation from AL proteins, we purified fAL and AL proteins from the amyloid-deposited organs of five AL amyloidosis patients. By electron microscopy and fluorometric thioflavin T method, we observed optimal fibril extension at pH 2.0-3.5 for the fibrils obtained from four patients, while at pH 7.5-8.0 for those obtained from one patient. Fragmental AL proteins were more efficient in the extension reaction than intact AL proteins. The fibrils obtained from all five patients showed clear fibril extension electron microscopically at pH 7.5. The extension of the fibrils obtained from all five patients could be explained by a first-order kinetic model, i.e., fibril extension proceeds via the consecutive association of AL proteins onto the ends of existing fibrils. Fibril extension was accelerated by dermatan sulfate proteoglycan, and inhibited by apolipoprotein E, alpha1-microglobulin, fibronectin, and an antioxidant nordihydroguaiaretic acid. These findings contribute to our understanding of the molecular mechanism underlying the pathogenesis of AL amyloidosis, and will be useful for developing a therapeutic strategy against the disease.

Adult↗
PubMed2002

Pure red cell aplasia developing into myeloproliferation with myelodysplasia and subsequent leukemia after cyclosporin A therapy.

We describe a very rare case of a patient who presented with red cell aplasia that later developed into myeloproliferation with myelodysplasia and eventually leukemia. A 63-year-old man presented with anemia and reticulocytopenia in May 1997. A bone marrow examination revealed erythroid aplasia with normal production of myeloid cells and megakaryocytes with a normal karyotype. After the diagnosis of pure red cell aplasia was made, the patient was treated with prednisolone and then with cyclosporin A (CyA). Two weeks after the initiation of CyA treatment, the peripheral reticulocyte count began to increase with a regrowth of erythroid cells in the bone marrow. Meanwhile, the peripheral white blood cell and platelet counts also increased to more than 10,000/microL and 1,000,000/microL, respectively. Examination of a bone marrow aspirate in December 1997 revealed myelodysplastic changes with trisomy 8. Despite the discontinuation of CyA and the administration of 1-beta-D-arabinofuranosylcytosine stearyl monophosphate, leukemia developed in August 1998. In September 1998, the patient died of sepsis during a neutropenic period that followed remission-induction therapy. In the mechanism of pathogenesis, CyA may induce upon pure red cell aplasia a secondary myeloproliferative disorder with myelodysplasia and leukemia. An alternative possibility is that CyA reduces autoimmune-mediated suppression of the underlying stem cell disorder and that the result of this reduction is the manifestation of myeloproliferation and leukemia.

Cell Division↗
PubMed2002

Alkylator-induced DNA excision repair in human leukemia CCRF-CEM cells in vitro, measured using the single-cell gel electrophoresis (comet) assay.

The capacity to repair DNA damage is an important factor that affects the therapeutic outcome in cancer treatment. To clarify the cellular repair response, we investigated the kinetics of DNA excision repair initiated by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in human leukemia CCRF-CEM cells at an exponential growth phase in vitro. Using the alkaline single-cell gel electrophoresis (comet) assay, we quantitated the repair kinetics as the amount of DNA single-strand breaks that were generated from the incision and were diminished by the rejoining in the repair process. CEM cells could initiate DNA excision repair in response to BCNU by starting an incision reaction. However, the incision capacity came to a plateau at a concentration of 80 to 100 microM or after an incubation time of 90 to 120 minutes. When the cells were pulsed with 40 microM BCNU, the maximal incision occurred at the end of the incubation period, and the repair process was completed within 4 hours When cells were treated with 100 microM BCNU, the incised DNA was not rejoined at 4 hours, suggesting that the repair was not completed. Higher concentrations might surpass the cellular capacity for repair and would be associated with increased cell death. Evaluation of the repair process may provide a clue for therapeutic strategies to improve clinical efficacy if accelerated DNA repair is responsible for the drug resistance.

Antineoplastic Agents, Alkylating↗
PubMed2002

Reversible defect of 123I-15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid indicates residual viability within infarct-related area.

To evaluate the relationship between the reversible defect of 123I-15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid (9MPA) and residual viability within an infarct-related area, we performed resting single photon emission computed tomography (SPECT) with 9MPA and positron emission tomography (PET) with 18F-deoxyglucose (FDG) and 13N-ammonia (NH3) in 7 patients with prior myocardial infarction. 9MPA-SPECT was obtained 2 min (early) and 50 min (delayed) after tracer injection. Tomographic images of the left ventricle were divided into 13 segments to correlate the regional uptake of each tracer. Residual viability within an infarct-related segment was confirmed by NH3- and FDG-PET. Twenty-six infarct-related segments, confirmed by NH3-PET, showed reduced uptake of 9MPA on early images. In these 26 segments, 6 showed reversible defect of 9MPA and 20 showed fixed defect on delayed images. Residual viability was present in all segments exhibiting reversible 9MPA defect and 7 segments (35%) exhibiting fixed defect (p < 0.05). The sensitivity, specificity and accuracy of reversible 9MPA defect for the detection of myocardial viability were 46%, 100%, and 73%, respectively. Myocardial clearance of 9MPA was significantly slower in non-viable segments than in ischemic but viable segments (4.9+/-5.1% vs. 10.1+/-5.3%; p < 0.05). These data suggest that a reversible 9MPA defect indicates residual viability within the infarct-related area.

Aged↗
PubMed2002

An autopsy case of disseminated mucormycosis in a neutropenic patient receiving chemotherapy for the underlying solid malignancy.

Mucormycosis is a rare, opportunistic infection caused by fungi of the order Mucorales, class Zygomycetes. These fungi produce fatal opportunistic infections in immunocompromised patients, especially in those with severe neutropenia. Recently, mucormycosis has become more widespread, because potent, myelosuppressive chemotherapies are performed more often than before. Nevertheless, this infection rarely occurs in patients with solid malignancies. Here, we describe an autopsy case of disseminated mucormycosis in a neutropenic patient who was receiving chemotherapy for an underlying solid malignancy. A 31-year-old Japanese man received cytotoxic chemotherapy with etoposide for the pulmonary metastasis of a secondary malignant fibrous histiocytoma. This patient had long been treated with chemotherapeutic agents for this solid cancer and for the preceding eosinophilic granuloma, both of which were highly resistant to the therapy. During the treatment with etoposide, his neutrophil count declined to less than 100/microl. He presented with high fever and severe dyspnea. Pneumonia was highly suspected. The chemotherapy was discontinued, and granulocyte colony-stimulating factor was administered. Although the neutrophil count recovered, the pneumonia progressed. The patient experienced respiratory failure and died 17 days after the onset of this episode. An autopsy revealed dissemination of mucormycosis not only in the lungs but also in the liver, the spleen, the kidney, and in the digestive tract. The therapy-related severe neutropenia, and the probable impairment of the immune system, because of the previous chemotherapies, would have been responsible for this fatal infection.

Adult↗
PubMed2002

Doxycycline induces apoptosis by way of caspase-3 activation with inhibition of matrix metalloproteinase in human T-lymphoblastic leukemia CCRF-CEM cells.

Evidence for nonantibiotic activity displayed by tetracycline has been extensively reported in the field of antiinflammation. Here, we report a growth-inhibitory effect of doxycycline on CCRF-CEM, a T-lymphoblastic human leukemic cell line. Cells were incubated with doxycycline at concentrations ranging from zero to 50 micromol/L. We examined the hypothesis that induction of apoptosis is one of the mechanisms by which doxycycline inhibits CCRF-CEM proliferation. Caspase-3 activity of cells grown in the presence of 10 micromol/L and 50 micromol/L doxycycline increased dose-dependently after 24 hours in culture. The demonstration that doxycycline induces APO 2.7 expression in CCRF-CEM cells in vitro also supports its capacity for induction of apoptosis. The level of matrix metalloproteinase-2 was significantly lower in the medium cultured with 50 micromol/L doxycycline than the control. These phenomena suggest that this well-tolerated oral agent has the potential to be of value in antileukemic therapy.

Anti-Bacterial Agents↗
PubMed2002

Serum cytokine level during continuous venovenous hemofiltration in toxic shock-like syndrome due to group G beta Streptococcus bacteremia in a patient with idiopathic thrombocytopenic purpura.

We report a case of toxic shock-like syndrome due to a rare infection of group G Streptococcus bacteremia in a patient with idiopathic thrombocytopenic purpura and its successful treatment with continuous venovenous hemofiltration (CVVH). As the result of sepsis treatment with CVVH, in addition to administration of vasopressors and antibiotics, serum levels of interleukin-1beta, interleukin-10 and tumor necrosis factor-a fell and shock was controlled.

Aged↗