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Rationale and Objectives Severe calcifications of the coronary arteries are still a major challenge in coronary computed tomography (CT) angiography (CCTA). Subtraction CCTA using a 320-detector row CT scanner has recently been introduced for patients with severe calcifications. However, the conventional subtraction CCTA method requires a long breath-holding time of approximately 20–40 seconds. This is a major problem in clinical practice because many patients may not be able to perform such a long breath-hold. We explored a modified subtraction CCTA method with a short breath-holding time to overcome this problem. Materials and Methods This study was approved by our institutional review board, and all patients gave written informed consent. A total of 12 patients with a coronary calcium score of >400 were enrolled in this study. All patients were unable to hold their breath for more than 20 seconds. Modified subtraction CCTA was performed using the bolus-tracking method. The acquisition protocol was adjusted so that the mask scan was acquired 10 seconds after the postcontrast scan during a single breath-hold. The subtraction image was obtained by subtracting the mask image data from the postcontrast image data. The breath-holding times were recorded. Enhancement of the coronary arteries in the subtraction images was assessed. Subjective image quality was evaluated in a total of 32 segments using a 4-point scale. Results The mean breath-holding time was 12.8 ± 0.8 seconds (range, 12–14 seconds). The average CT number in the coronary arteries was 288.6 ± 80.5 Hounsfield units (HU) in the subtraction images. Average image quality was significantly increased from 2.1 ± 0.9 with conventional CCTA to 3.1 ± 0.7 with subtraction CCTA ( P P = 0.001). Conclusions This preliminary study has shown that our modified subtraction CCTA method allows the breath-holding time to be shortened to

Mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT) cause Lesch-Nyhan disease (LND) and its variants (LNV). Due to the technical problems for measuring the HPRT activity in vitro, discordances between the residual HPRT activity and the clinical severity were found. 5-Phosphoribosyl 1-pyrophosphate (PRPP) is a substrate for HPRT. Since increased PRPP concentrations were observed in erythrocytes from patients with LND and LNV, we have turned our attention to erythrocyte PRPP as a biomarker for the phenotype classification. In the present work, a method for determination of PRPP concentration in erythrocyte was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM). Packed erythrocyte samples were deproteinized by heating and the supernatants were injected into the LC-MS/MS system. All measurement results showed good precision with RSD6%. PRPP concentrations of nine normal male subjects, four male patents with LND and six male patients with LNV were compared. The PRPP concentrations in erythrocyte from patients with LND were markedly increased compared with those from normal subjects, and those from patients with LNV were also increased but the degree was smaller than those with LND. The increase pattern of PRPP concentration in erythrocyte from patients with HPRT deficiency was consistent with the respective phenotypes and was correlated with the disease severity. PRPP concentration was suggested to give us supportive information for the diagnosis and the phenotype classification of LND and LNV.

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is highly expressed in various kinds of tumors. In the present study, we investigated the cytotoxic mechanism of YM155, a unique small-molecule inhibitor of survivin, in human myelogenous leukemia cells. YM155 potently inhibited the cell growth of HL-60 and U937 cells with the half-maximal inhibitory concentration (IC 50 ) value of 0.3 nM and 0.8 nM, respectively. YM155 significantly suppressed the levels of mRNA expression and protein of survivin in HL-60 and U937 cells. In addition, we also found that YM155 down-regulated the level of Mcl-1, another critical anti-apoptotic protein, in both HL-60 and U937 cells. Treatment of HL-60 and U937 cells with YM155 induced apoptosis concomitant with the activation of caspase-8 and caspase-3. Interestingly, we have found that caspase-8 inhibitor Z-IETD-FMK strongly inhibited YM155-induced apoptosis in HL-60 and U937 cells. When cells were pretreated with Z-IETD-FMK, the activation of caspase-3 was completely abolished, suggesting that caspase-8 may be involved in the activation of caspase-3 during YM155-induced apoptosis. We demonstrated for the first time that YM155 induces caspase-8 dependent apoptosis through downregulation of survivin and Mcl-1 in human leukemia cells.

Summary Objectives The rapid diagnosis of bacteremia is crucial for patient management including the choice of antimicrobial therapy, especially in cases of hematological disease, because neutropenia occurs frequently during antineoplastic chemotherapy or disease progression. We describe a rapid detection and identification system that uses universal PCR primers to amplify a variable region of bacterial 16S ribosomal DNA (rDNA), followed by DNA microarray hybridization. Methods Probes for 72 microorganisms including most causal clinical pathogens were spotted onto a microarray plate. The DNA microarray and conventional methods of identification were applied to 335 cultures from patients with hematological diseases. Results Forty-one samples (12.2%) tested positive by conventional blood culture test in a few days, while 40 cases (11.9%) were identified by the new method within 24h. The sensitivity and specificity of this new method were 93% and 99%, respectively, compared with conventional blood culture testing. Conclusions PCR combined with a DNA microarray is useful for the management of febrile patients with hematological diseases.

Cytarabine (ara-C) is the key agent for treating acute myeloid leukemia (AML). After being transported into leukemic cells by human equilibrative nucleoside transporter 1 (hENT1), ara-C is phosphorylated to ara-C triphosphate (ara-CTP), an active metabolite, and then incorporated into DNA, thereby inhibiting DNA synthesis. Deoxycytidine kinase (dCK) and cytosolic 5'-nucleotidase II (cN-II) are associated with the production of ara-CTP. Because ara-C's cytotoxicity depends on ara-CTP production, parameters that are most related to ara-CTP formation would predict ara-C sensitivity and the clinical outcome of ara-C therapy. The present study focused on finding any correlation between the capacity to produce ara-CTP and ara-C-metabolizing factors. In vitro ara-CTP production, mRNA levels of hENT1, dCK, and cN-II, and ara-C sensitivity were evaluated in 34 blast samples from 33 leukemic patients including 26 with AML. A large degree of heterogeneity was seen in the capacity to produce ara-CTP and in mRNA levels of hENT1, dCK, and cN-II. Despite the lack of any association between each of the transcript levels and ara-CTP production, the ratio of dCK/cN-II transcript levels correlated significantly with the amount of ara-CTP among AML samples. The HL-60 cultured leukemia cell line and its three ara-C-resistant variants (HL-60/R1, HL-60/R2, HL-60/R3), which were 8-, 10-, and 500-fold more resistant than HL-60, respectively, were evaluated similarly. The dCK/cN-II ratio was again proportional to ara-CTP production and to ara-C sensitivity. The dCK/cN-II ratio may thus predict the capacity for ara-CTP production and ultimately, ara-C sensitivity in AML.

Myocardial flow reserve (MFR) in the non-infarct-related area (NIRA) has been reported to be impaired after the onset of myocardial infarction (MI). The aim of this study was to determine whether microvascular dysfunction in the NIRA is related to left-ventricular remodeling after MI.We prospectively studied 17 patients who suffered their first single-vessel MI, and who underwent successful revascularization. The MFR in the NIRA was assessed quantitatively using (13)N-ammonia positron emission tomography within 2 weeks after the onset. Peak creatinine kinase and the defect score on (99m)Tc-tetrofosmin myocardial perfusion imaging were used as an index of the severity of MI. The left-ventricular end-diastolic volume index (LVEDVI) was calculated using left ventriculography at 1 month and 6 months after the onset.Patients with severely impaired MFR (2.09) had higher peak creatinine kinase values (6000+/-5485 IU/L vs. 2250+/-1950 IU/L, p=0.0081), defect scores (16.3+/-5.9 vs. 7.9+/-6.5, p=0.0404), and LVEDVI at 1 month (125.6+/-34.4 mL/m2 vs. 82.8+/-17.7 mL/m2, p=0.0036) than those with mildly impaired MFR (or =2.09). Moreover, the differences of LVEDVI between 2 groups persisted over 6 months (133.3+/-43.6 mL/m2 vs. 89.5+/-17.3 mL/m2, p=0.0078). The MFR in the NIRA correlated inversely with the LVEDVI at 1 month and 6 months (r=-0.590, p=0.0127 and r=-0.729, p=0.0031, respectively).These data indicate that microvascular impairment in the NIRA might have contributed to left-ventricular remodeling after MI.

Using RNA interference (RNAi) to suppress gene expression, we attempted to identify tyrosine kinases involved in the extension of neurites from SH-SY5Y cells. A comprehensive analysis of gene "knock-down" profiles with small interfering RNAs (siRNAs) revealed candidate proteins that might control neurite extension. Phenotype-based screening of differentiating SH-SY5Y cells following retinoic acid (RA) stimulation indicated that twinfilin-2 is a protein that is involved in neurite outgrowth, as confirmed by morphological analysis of twinfilin-2-overexpressing cells.

Although biological and clinical features differ between B-lineage acute lymphoblastic leukemia (ALL) and T-lineage ALL (T-ALL), there have been few reports that focused on the prognosis for T-ALL in adults, primarily due to its rarity. Here, we studied the long-term outcomes and prognostic factors specific for adult T-ALL by combining patient data from the three prospective trials conducted by the Japan Adult Leukemia Study Group (JALSG). Among 559 patients whose immunophenotypes could be evaluated, 87 (15.6%) were identified as T-ALL. Of them, 66 patients (75.8%) achieved complete remission, and relapse occurred in 41 patients. With a median follow-up for surviving patients of 7.5 years, the probability of overall survival was 35.0% at 5 years. Risk factor analysis revealed that serum albumin levels, initial white blood cell (WBC) counts, and age had independent values for predicting survival. For WBC, not only the high-count group (50 x 10(9)l(-1) or higher), but also the low-count group (less than 3 x 10(9)l(-1)) showed a significantly lower survival rates than the intermediate-count group (p=0.0055 and 0.0037, respectively). Although our findings need confirmation, these results will be helpful in the identification of prognostically distinct subgroups within adult T-ALL.

Background Although diabetes is associated with poor clinical outcomes after acute myocardial infarction, to date there have been no reports focusing on the myocardial oxygen metabolism in these patients. Thus, we evaluated the myocardial oxygen metabolism in patients with and without diabetes suffering from acute myocardial infarction using carbon-11 acetate positron emission tomography. Methods 20 patients (13 diabetic patients [group A] and 7 non-diabetic patients [group B]) underwent carbon-11 acetate positron emission tomography soon after the onset of acute myocardial infarction. The myocardial oxygen metabolism was evaluated within the infarct-related area and in the non infarct-related area. 6 healthy volunteers (group C) and 6 diabetic patients without coronary artery disease (group D) also participated as controls. Results There were no significant differences in gender, age, infarct-related artery, peak level of serum creatine phosphokinase, left-ventricular ejection fraction at onset, or the defect severity on myocardial perfusion images between group A and group B. In group A, the clearance rate (Kmono) of carbon-11 acetate in infarct-related area (0.042±0.010) was not significantly different from that in group B (0.049±0.016). In contrast, Kmono in non infarct-related area in group A (0.059±0.010) was significantly lower than that in group B (0.076±0.009; p =0.002), group C (0.072±0.004; p =0.026) and group D (0.078±0.005; p =0.001). Conclusions These data indicate that the myocardial oxygen metabolism even in non infarct-related area in diabetic patients was impaired after the onset of acute myocardial infarction.

Systemic inflammatory response syndrome (SIRS) and sepsis have been considered forms of hypercytokinemia in critically ill patients and immunocompromized hosts. It has been reported that some antimicrobial agents, including antifungal agents, not only have an antibiotic effect, but also they affect the host's immunological response. Immunofunctional cells, including monocytes and macrophages, were examined to determine whether they are influenced by the newly synthesized candin family antifungal agent micafungin (MCFG) using the human monocytic cell line THP-1 stimulated with lipopolysaccharide (LPS) as a model of hypercytokinetic conditions. LPS-induced production of TNF-alpha (tumor necrosis factor-alpha) and interleukin-8 (IL-8) in THP-1 cells was significantly suppressed dose-dependently by MCFG, although high concentrations of MCFG may reach toxic levels. It was clarified that MCFG inhibits the LPS-induced expression of TNF-alpha in THP-1 cells at the mRNA (messenger ribonucleic acid) level. In conclusion, administration of MCFG had an immunomodulatory effect on the host by reducing levels of TNF-alpha and IL-8. The effectiveness of MCFG in modulating hypercytokinemia is due not only to its direct antifungal effect, but also to the modulation of cytokine production in macrophages that regulates immunological activity and inflammation.

In the treatment of heart failure, the effects of therapeutic agents on life prognosis remains unclear. We investigated the effects of long-term oral administration of a nonpeptide, selective, vasopressin V2 receptor antagonist, OPC-31260, on Sprague-Dawley rats that were treated with adriamycin to induce progressive water retention.Intraperitoneal saline was administered to 14 rats as a control (Group 1). A total cumulative dose of 15 mg/kg of adriamycin was administered intraperitoneally in six equal doses over a period of 2 weeks to another 52 rats. Adriamycin-treated rats were further divided into Group 2, which received saline (p.o.), and Group 3, which received 50 mg/kg (p.o.) of V2 antagonist. Oral administration continued every day for 6 weeks. Group 1 rats also received saline (p.o.) for 6 weeks.The V2 antagonist decreased urine osmolality and increased diuresis of rats in Group 3. Urinary excretion of electrolytes was not increased by the V2 antagonist in Group 3. Serum osmolality was likewise unchanged by the V2 antagonist in Group 3. Plasma concentrations of vasopressin were significantly higher in Group 3 than in the other groups (Group 1, 4.0+/-1.1 pg/ml; Group 2, 4.2+/-1.5 pg/ml; Group 3, 8.5+/-1.0 pg/ml; p0.05). During the experimental period, survival rate was higher in Group 3 than in Group 2 (Group 1, 100%; Group 2, 59%; Group 3, 83%).Our data show that administration of orally active V2 antagonist did not reduce the survival of adriamycin-treated rats through continuous aquaretic action, despite elevated plasma levels of vasopressin.

Matrix metalloproteinase (MMP) may contribute to myocardial remodeling after myocardial infarction. The goal of this study was to characterize the effects of pravastatin on circulating levels of MMP and on left ventricular dilatation after acute myocardial infarction (AMI).Thirty-four consecutive patients with successful reperfusion following AMI were assigned to either pravastatin group (group P, n=12) or non-pravastatin group (group NP, n=22). Serum MMP-2 and tissue inhibitor of MMP (TIMP)-2 were measured immediately after reperfusion, on days 2, 3, 7, 30, and at 6 months after MI. Left ventriculography was performed after reperfusion and at 4 weeks and 6 months.MMP-2 levels were higher in patients with MI than control on days 1, 30, and at 6 months. Left ventricular end-diastolic volume index (LVEDVI) at 6 months correlated with MMP-2 levels on day 30 (r=0.47, p0.01) and at 6 months (r=0.56, p0.001). MMP-2 levels at 6 months were significantly lower in group P than group NP. Further, LVEDVI at 6 months tended to be smaller and DeltaLVEDVI was significantly smaller in group P when compared with group NP.Serum MMP-2 varied in a time-dependent manner following AMI and correlated with late changes in LVEDVI. Serum MMP-2 levels were significantly lower in treatment group than in non-treatment group and DeltaLVEDVI was significantly smaller in treatment group after long-term pravastatin administration. Use of statins in AMI patients may provide beneficial effects in terms of preventing heart failure over and above its lipid-lowering effects.

We isolated four novel cDNA clones for monoterpene synthase genes, CitMTSE1, CitMTS3, CitMTS61, and CitMTS62, from Satsuma mandarin (Citrus unshiu Marc.). Functional tests of in vitro translation demonstrated that CitMTSE1, CitMTS3, CitMTS61, and CitMTS62 coded d-limonene synthase, gamma-terpinene synthase, gamma-terpinene synthase, and beta-pinene synthase, respectively. Their predicted proteins possessed typical characteristics for monoterpene synthases, such as transit peptides in the N-terminus, RR sequences, and DDXXD motifs. In citrus monoterpene synthase genes, the enzymatic product-specific interval length variations among conservative domains were conserved among interspecies, and they were conspicuous between limonene synthase genes and other cyclic monoterpene synthase genes, although the total amino acid length of each clone was similar. A phylogenetic tree indicated that differentiation in citrus monoterpene synthases might occur before the divergence of Citrus species. Besides, the mRNA expressions of most clones were active in the peel at an early stage of fruit development. CitMTSE1 and CitMTS3 were also powerfully expressed in the flower at anthesis, suggesting a different regulation mechanism.

We describe the successful treatment of pyoderma gangrenosum (PG) that developed in a patient with myelodysplastic syndrome (MDS). A 63-year-old Japanese man with MDS was admitted to our hospital because of a large skin ulcer on his neck in November 2001. The initial diagnosis was infectious dermatitis, and antimicrobial therapy was performed, using imipenem/cilastatin, isepamicin, and amphotericin B. However, this therapy was not effective, and the lesion worsened. Cultures of blood, throat swab, and ulcer pus yielded no microorganisms. A biopsy of the skin lesion revealed a severe infiltration of neutrophils in the dermis, without any evidence of infection. The lesion was finally diagnosed as PG, and systemic administration of corticosteroid hormone was started in December 2001. The patient was initially pulsed with 1 g methylprednisolone daily for 3 days. The dose was immediately reduced, and the treatment was maintained with 30 mg prednisolone daily. The skin lesion responded markedly to the therapy, and C-reactive protein became negative. The patient was discharged in February 2002 because the lesion was almost cured. Prednisolone administration was tapered after 6-month maintenance therapy. No recurrence of PG was seen, although his MDS transformed into leukemia in April 2003. Only 31 cases of MDS developing PG have been reported in the past 20 years in Japan. This report describes one such rare patient who was successfully treated with the use of high-dose pulse methylprednisolone and long-term maintenance therapy.

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.

A retrospective study was performed on 125 patients with de-novo acute myeloid leukemia (AML) who had received first remission induction therapy at Fukui Medical University Hospital in the 16 years between 1983 and 1998. For remission induction therapies, patients in the 1980s received mainly behenoylcytarabine (BHAC), 6-mercaptopurine (6-MP), and prednisolone (PSL), plus aclarubicin (ACR) or daunorubicin (DNR). Patients in the 1990s received mainly BHAC, 6-MP, and etoposide (VP-16) plus DNR or mitoxantrone (MIT) or idarubicin (IDA). Patients with hypoplastic bone marrow received low-dose cytarabine (Ara-C) therapy or cytarabine ocfosfate (SPAC). Since 1992, patients with French-American-British disease classification of M3 have received all-trans retinoic acid (ATRA) (+/-chemotherapy). In the 1990s, more intensified postremission therapy was performed compared with that done in the 1980s. The complete remission (CR) rate of all patients was 58%. Predicted 6-year overall survival (OS) and disease-free survival (DFS) rates in the CR patients were 22% and 28%, respectively. Multivariate analysis showed age and leukocyte counts as significant prognostic factors regarding CR, OS, and DFS rates. The CR and OS rates in the 1990s were improved significantly from those in the 1980s, at 69% versus 48% (P = 0.016), and 32% versus 15% (P = 0.0014), respectively. The early death rate, within 30 days, was decreased from 26% in the 1980s to 9% in the 1990s (P = 0.013). This decrease was thought to be the main cause of the high CR rate in the 1990s. However, DFS was not significantly improved. It is necessary to establish more effective postremission therapies in order to reduce the relapse rate and improve the prognosis.

Inosine 5'-monophosphate (IMP) dehydrogenase catalyzes the rate-limiting reaction of guanine nucleotide biosynthesis and has been implicated in the reaction of cell growth and differentiation. We investigated the ability of mycophenolate mofetil, a prodrug of mycophenolic acid, to induce differentiation in HL-60 and U937 leukemic cells as well as in fresh leukemia cells from patients with non-lymphocytic leukemia. Treatment with mycophenolate mofetil reduced the intracellular guanosine 5'-triphosphate (GTP) levels and induced morphologic and functional differentiation in HL-60 and U937 cells dose-dependently. HL-60 and U937 cells developed macrophage-like cytoplasm as well as the expression of CD11b and CD14 antigens and the ability to oxidize nitroblue tetrazorium (NBT). These changes became evident when the intracellular GTP levels decreased to approximately 20-30% of the untreated control level and were abrogated by the addition of guanosine. In the fresh leukemic cells, differentiation induction was shown in the cells derived from seven of 13 patients. The fresh leukemia cells responding to mycophenolate mofetil revealed significant higher positivity to CD11b, CD14, and NBT before treatment and significantly reduced intracellular GTP levels after treatment compared to the non-responding cells. These findings suggest that mycophenolate mofetil induces differentiation in HL-60 and U937 cells and some fresh leukemia cells with moderate tendency to maturation, by causing a decrease in the intracellular GTP levels. Mycophenolate mofetil could be a promising differentiation inducer in vivo.

Background: It has been reported that matrix metalloproteinase (MMP) was expressed in coronary arterial atherosclerotic lesions. However, not much is known about the relationship between the production of MMP and the progression of atherosclerosis. Purpose and method: To demonstrate the association between the protein-tyrosine phosphorylation (PTP) and the activation of extracellular MMP in the proliferation and migration of vascular smooth muscle cells (VSMCs), the effect of platelet-derived growth factor (PDGF) and vanadate (an inhibitor of protein-tyrosine phosphatase and an activator of certain protein-tyrosine kinases) on mitogenesis ([ 3 H]thymidine incorporation after 24 hours), migration, PTP (Western blot analysis using anti-phosphotyrosine antibodies), and production of MMP (gelatin zymography) was examined in cultured VSMCs. Results: Both vanadate (1–5 μmol/l) and PDGF (1–10 ng/ml) caused a dose-dependent increase in thymidine incorporation and migration and produced 72-kDa type IV gelatinase (MMP-2) in VSMCs. The combination of vanadate and PDGF resulted in a dose-dependent synergistic effect on thymidine incorporation and MMP-2 production. Western blot analysis revealed that PDGF caused an increase in PTP, extracellular signal-regulated kinases (ERK1, ERK2) and PDGF receptor in VSMCs. Vanadate given together with PDGF induced a marked increase in the intensity of tyrosine phosphorylation in these proteins. Tyrosine kinase inhibitors (genistein and herbimycin A) and a synthetic inhibitor of MMP (1,10-phenanthroline) and an anti-MMP-2 neutralizing antibody inhibited the mitogenic effect induced by vanadate and/or PDGF. Conclusions: The data suggest that the proliferation and migration of cultured VSMCs was closely related to the stimulation of MMP-2 production that was induced through activation of PTK.

There have been few reports on examining the susceptibility of variant angina. Accordingly, the major histocompatibility complexes (HLA-A, -B, -C, -DR) of unrelated Japanese patients with variant angina were examined. There were no significant differences in the frequency of HLA-A,-B, -C, and -DR antigens between patients and controls (n = 100). Although endothelial dysfunction with pathological abnormalities is suggested to be one of the etiological factors in vasospasm, immunogenetic abnormalities linked to HLA system might not play a role in the pathogenesis of variant angina.

OBJECTIVESWe evaluated the clinical significance of reciprocal ST-segment depression associated with exercise-induced ST-segment elevation for detecting residual viability within the infarcted area.BACKGROUNDAlthough the relation between residual viability and exercise-induced ST-segment elevation has been described, there are no reports focusing on the relation between myocardial viability and reciprocal ST-segment depression associated with exercise-induced ST-segment elevation.METHODSWe evaluated regional blood flow and glucose utilization using N-13 ammonia (NH3) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in 30 patients with a previous Q-wave myocardial infarction (anterior in 15, inferior in 15). All subjects had single-vessel disease and had exercise-induced ST-segment elevations (≧1 mm) in electrocardiographic leads.RESULTSReciprocal ST-segment depression (≧1 mm) was present in 16 patients (Group A; anterior in 6, inferior in 10) but not in the remaining 14 patients (Group B). The degree of exercise-induced ST-segment elevation (1.8 ± 0.2 vs. 2.0 ± 0.2 mm) and the time from the onset of infarction to the study (75 ± 49 vs. 74 ± 52 days) did not differ between groups. There were no significant differences between groups in the severity of left ventricular dysfunction and the residual luminal narrowing in the infarct-related artery (45 ± 21 vs. 48 ± 25%). The presence and site of infarction were confirmed by NH3-PET in all patients. FDG-PET demonstrated residual tissue viability within infarct-related area in all patients in Group A and in 3 (21%) of 14 patients in Group B (p < 0.01). The sensitivity, specificity and accuracy of reciprocal ST-segment depression associated with exercise-induced ST-segment elevation for detecting residual viability were 84%, 100% and 90%, respectively.CONCLUSIONSThe occurrence of reciprocal ST-segment depression associated with exercise-induced ST segment elevation in patients with a previous Q-wave infarction who had single-vessel disease indicates residual tissue viability within the infarct-related area.

A large amount of EGR was introduced into a direct injection gasoline engine. According to the increase of EGR rate, it was found that the combustion at the late period is hastened in spite of reduction of the initial burning rate. In consequence, both HC and NOx were reduced by EGR. This suggests that the effect on acceleration of the leaner mixture's flame propagation by hot EGR gas becomes varied under the condition of the stratified mixture's stabilized ignition.

Objectives. We evaluated whether the severity of magnesium deficiency was correlated with the frequency of attacks of variant angina.Background. Magnesium deficiency may be associated with the development of variant angina. However, the relation between the activity of variant angina and magnesium deficiency remains to be elucidated.Methods. We assessed the body magnesium status of 18 men with variant angina: Group 1 (≥4 attacks/week, n = 7) and Group 2 (

The separation of C60 and C70 all-carbon compounds has been examined using new multi-legged phenyl group bonded silicas as the stationary phase in liquid chromatography. Two-legged biphenyl bonded silica gave the best separation because this phase offers the most suitable cavity-like structure to retain the C70 molecule, and this provides good separation between C60 and C70.

The pharmacokinetics of retinol palmitate were studied, and a therapeutic trial was performed in patients with ANLL. In the pharmacokinetics study, retinol was the only metabolite that was detected in plasma, and the peak concentration was 332 μg/dl (about 1.2 × 10 −5 M) 2.1 h after administration of retinol palmitate. Five patients with ANLL (4 with ANLL-M3 and one with ANLL-M2) were treated with retinol palmitate. In all patients with ANLL-M3, bone marrow suspension culture studies revealed that retinol induced both morphological and functional differentiation of immature leukemic cells. During the course of the treatment with retinol palmitate, morphological differentiation of bone marrow immature leukemic cells was observed in all patients with ANLL-M3 within 3–4 days after initiation of the therapy. In three of the four patients who underwent conventional chemotherapy, the sequential treatment with retinol palmitate resulted in a complete remission: controlling residual bone marrow leukemic cells. None of the patients showed any signs of aggravation of DIC in the coagulation parameters. These findings suggest the possibility that retinol palmitate functions as salvage therapy by inducing maturation and slowing proliferation, there by clearing out the residual leukemic cells following conventional chemotherapy.

Multidentate phenyl-bonded phases have been evaluated as stationary phases which can recognize molecular non-polarity of polycyclic aromatic hydrocarbons. The results clearly indicate that these multidentate give a higher non-polarity recognition capability than that with typical octadecylsilicas such as polymeric and monomeric phases. The reason for this mechanism can be interpreted by the molecular—molecular interaction between a solute and a stationary phase and this kind of approach will open the possibility of designing new stationary phases which offer more selective of specific separations.

A 77-year-old man treated with prednisolone for pemphigus developed severe sepsis by Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Several antibiotics were administered. A peripheral blood smear showed growth of a large number of yeast extending pseudohyphae which could be seen both inside and outside of leucocytes. Antifungal agents were added immediately; however, he did not recover. Several days later, blood culture showed Candida albicans septicemia. The autopsy revealed microabscesses in the lung, heart, liver and kidney. A large amount of neutrophil invasion and yeast with pseudohyphae were also detected.

We encountered a patient with microvascular angina (MVA) who was died suddenly, and observed ST-segment elevation during attack without epicardial coronary arterial vasoconstriction, suggesting the occurrence of microvascular spasm. Doppler guide wire (DGW) and N-13 ammonia positron emission tomography (PET) demonstrate severe impairment of the coronary microcirculation extending throughout the whole of the left ventricle. Conventional medical treatment was not effective in this case. We speculate that the prognosis of microvascular angina with severe coronary microcirculatory disturbance and accompanied by microvascular spasm might not always be good. Therefore, methods for treating such cases need to be established.

To investigate the changes in myocardial glycolytic and fatty acid metabolism during progression of ADR-induced heart failure, sixty five 8-weeks male S-D rats were injected intraperitoneally with ADR (15 mg/kg) or equivalent volume of saline, divided into 6 times for 2-weeks. Rats were sacrificed and the left ventricles were removed, at 1 day (ADR 10 group, Control 10 group), at 3 weeks (ADR 3W group, Control 3W group) and at 6 weeks (ADR 6W group, Control 6W group) after the last ADR or saline injection. By using proton-MRS, we measured myocardial metabolites (lactate and alanine as indices of glycolytic metabolism, and free carnitine as an index of fatty acid metabolism). As an index of energy production, high energy phosphate (ATP) in the myocardium was also measured by HPLC. Results The cumulative mortality rate was 0% in control groups and 48% in ADR-treated groups during observed period. The mortality rate was abruptly increased 3 weeks after the last injection. lactate alanine free carnitine ATP Control 1D (n = 6) 11.85 ± 0.98 1.12 ± 0.0 1.07 ± 0.08 8.52 ± 0.32 Control 3W In = 6) 11.22 ± 0.91 1.14 ± 0.09 1.12 ± 0.09 8.60 ± 0.38 Control 6W (n = 4) 13.10 ± 1.68 1.58 ± 0.23 1.05 ± 0.12 8.90 ± 0.19 lactate, alanine, free carnitine, μ mol/wet g, ATP, nmol/mg protein No significant changes in tissue levels of lactate, alanine, free carnitine and ATP were observed among Control groups lactate alanine free carnitine ATP ADR 10 (n = 6) 15.72 ± 1.38 2.10 ± 0.23 1.05 ± 0.07 7.23 ± 0.51 ADR 3W(n = 6) 3.47 ± 0.41 1.02 ± 0.24 0.83 ± 005 598 ± 0.16 ADR 6W(n = 6) 9.10 ± 0.76 1.28 ± 0.17 0.60 ± 007 4.70 ± 038 In ADR 1D, the tissue levels of lactate and alanine were significantly higher than those of Control 1D (p l 0.05), although the tissue levels of free carnitine and ATP were preserved. However, in ADR 3W, the tissue levels of free carnitine and ATP were significantly lower than those of Control 3W (p l 0.05). The tissue levels of free carnitine and ATP appeared to be further reduced in ADR 6W. Conclusion This study demonstrated that the impaired energy production had already occurred even at early stage of ADR-induced heart failure.

To characterize the gene expression and regulation associated with anthesis stage of fruit development a total of 824 clones were randomly selected and sequenced from a cDNA library prepared from ovary tissue of Satsuma mandarin (Citrus unshiu Marc) at the anthesis stage. Clones derived from rDNA, mitochondrial and chloroplastic DNAs were removed and the remaining 544 cDNA clones were analyzed for homology with known sequences. From this analysis 455 clones were identified as homologues of a known gene or an expressed sequence tag (EST). We found 103 cDNA clones that were not detected in our previous analyses of Citrus ESTs including gene homologues related to transcription factors, molecular chaperones, and plant hormone biosynthesis/regulation. In addition, gene homologues related to amino acid biosynthesis, secondary metabolism and stress response were frequently detected, indicating that the ovary tissue may be metabolically active and have the intrinsic ability to react to biotic and abiotic stresses.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. The present study assessed retrospectively the clinical significance of the serum soluble interleukin-2 receptor (sIL-2R) level in patients with advanced DLBCL. Twenty-one patients (age; range, 56–87, median, 73-year old, 14 males/7 females) were newly diagnosed as having advanced DLBCL (stages III and IV) based on pathological findings of the biopsy specimen and by using computed tomography and positron emission tomography between 2006 and 2009. All the patients received 6–8 cycles of the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) (R-CHOP) or THP-COP (pirarubicin, cyclophosphamide, vincristine and prednisolone) (R-THP-COP) and attained complete response at the end of the treatment. The follow-up period ranged between 12 and 73 months with the median of 37 months. The serum sIL-2R levels (normal range, 144–518 U/ml) were determined at least before and after the second and the sixth cycles of the chemotherapy were carried out. Although all the patients reached complete remission, six patients experienced the disease relapse within 1 year from the initiation of the treatment. sIL-2R levels before the chemotherapy ranged from 416 to 21300 U/ml (median 2609 U/ml). sIL-2R levels after the second cycle of the chemotherapy ranged from 276 to 1980 U/ml (median 675 U/ml). sIL-2R levels after the sixth cycle of the chemotherapy ranged from 364 to 822 U/ml (median 548 U/ml). The early relapse was significantly associated with the high sIL-2R levels at the sixth cycle of the treatment, while the sIL-2R levels were low in the patients with the durable remission. sIL-2R levels at the disease onset or after the second cycle of the treatment were not correlated to the duration of the remission. Thus, the present study suggested that the sIL-2R levels after the sixth cycle of the chemotherapy might predict the early relapse in patients with advanced DLBCL.

Purpose: Tranilast, an antiallergenic drug, has been reported to reduce restenosis rate after angioplasty, but its mechanism is still unclear. Vascular smooth muscle cells (VSMC) proliferation, excessive matrix metalloproteinases (MMPs) expression and nitric oxide (NO) deficiency are thought to be key events in the development of restenosis after angioplasty. We investigated the effect of tranilast on proliferation, MMPs production, and NO production in cultured VSMC under basal and stimulated conditions. Method: Cell proliferation was evaluated by [3H]thymidine incorporation. MMPs production by VSMC were assessed by gelatin zymography. NO production by VSMC was measured by Griess reaction. Results: Tranilast (30-500/z M) did not change proliferation and MMP-2 production in quiescent VSMC. However, tranilast dose-dependently inhibited PDGFstimulated cell proliferation and PDGF-stimulated MMP-2 production. Tranilast also dose-dependently inhibited ILl/~ stimulated MMP-9 and MMP-2 productions. Moreover, tranilast increased basal and ILl/3-stimulated NO production. Conclusion: Our results suggest that prevention of restenosis after angioplasty by tranilast may be madiated by not only its antiproliferative effect but also inhibition of MMPs production and activation of NO production in VSMC.