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Takashi Murakami

Publications and source records attributed to Takashi Murakami.

At least 19 recordsLinked to original sources
PubMed2026

The tumor suppressor NDRG2 recruits protein phosphatase 2A to suppress STAT5 phosphorylation in adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell malignancy with a poor prognosis that is caused by human T-cell leukemia virus type 1 infection. We previously demonstrated that N-myc downstream-regulated gene 2 (NDRG2) is significantly downregulated in ATL, resulting in aberrant activation of the signal transduction pathways through the dissociation of serine/threonine protein phosphatase 2A. To identify potential targets of NDRG2, we performed comprehensive mass spectrometry of differentially phosphorylated peptides in ATL cells with overexpression of NDRG2 using a TiO2-based enrichment method. Kyoto Encyclopedia of Genes and Genomes and gene ontology analysis revealed that the downregulated phosphopeptides correlated with signaling pathways, T-cell differentiation, and proliferation. Our results identified signal transducer and activator of transcription 5B as a novel NDRG2-regulated protein that is dephosphorylated at serine 193 and tyrosine 699. Although enforced expression of NDRG2 in ATL cell lines does not change the phosphorylation of Janus kinase 3, an upstream regulator of STAT5, phosphorylated STAT5 at tyrosine and serine is significantly suppressed by the direct binding to STAT5 with NDRG2 leading to the inhibition of STAT5 downstream gene expression. Furthermore, NDRG2 binds to STAT5B with alanine replacement of Y699 (Y699A), but only weakly associates with S193A, suggesting that NDRG2 is directly involved in serine phosphorylation through the recruitment of serine/threonine protein phosphatase 2A to STAT5. Because S193 A remarkably induces reduced phosphorylation of Y699 and subsequent transcriptional activity, the induction of serine phosphorylation through the loss of NDRG2 expression is dispensable for STAT5 tyrosine phosphorylation and activity. Since the loss of NDRG2 expression is essential factor to maintenance of ATL cells by STAT5 activity through phosphorylation of serine and tyrosine, targeting STAT5 becomes a feasible and effective strategy in NDRG2-deficient ATL.

Humans↗
PubMed2007

Effects of photodynamic therapy using 5-aminolevulinic acid on cultured human adenomyosis-derived cells.

OBJECTIVE: To evaluate the potential of photodynamic therapy with aminolevulinic acid (ALA) on human adenomyosis-derived cells compared with endometrial stromal cells. DESIGN: In vitro study. SETTING: Department of Obstetrics and Gynecology, Tohoku University Hospital. PATIENT(S): Women with adenomyosis attending the University hospital. INTERVENTION(S): Photodynamic treatment. MAIN OUTCOME MEASURE(S): Cell survival rates. RESULT(S): Treatment with both ALA and irradiation caused significantly decreased survival of cells derived from human adenomyosis compared with ALA or irradiation alone. The combination of irradiation and ALA led to 79.3%, 68.0%, and 59.5% cell survival at 1.6, 4, and 8 J/cm2, respectively, whereas ALA and irradiation alone caused 92.8% and 97% survival, respectively. CONCLUSION(S): Photodynamic therapy using ALA caused extensive death of cells derived from human adenomyosis. Photodynamic treatment using ALA may be a new treatment for patients with adenomyosis uteri in the future.

Adult↗
PubMed2006

Small numbers of residual tumor cells at the site of primary inoculation are critical for anti-tumor immunity following challenge at a secondary location.

Luciferase-transduced B16 murine melanoma cells (luc-B16) inoculated in ear skin do not form tumors but prevent tumor formation by luc-B16 cells injected into the footpad. To determine the requirements for such immunity, we followed the fate of luc-B16 cells following ear injection. Surprisingly, small numbers of viable luc-B16 cells were detected in tumor-free mouse skin for up to 60 days post-inoculation. After 1 week, the number of Foxp3(+)CD4(+)CD25(+) T cells (along with foxp3 mRNA expression) increased rapidly in the injected ear skin. Residual tumor cells in ears were reduced in mice treated with anti-CD25 mAb and in CD4-deficient mice, but increased in CD8-deficient mice. Strikingly, the loss of luc-B16 cells in the ear skin, either spontaneously or following amputation of the injected ear, resulted in significantly enhanced tumor formation by parental and luciferase-expressing B16 cells after footpad injection. These studies suggest that small numbers of tumor cells (possibly regulated by CD4(+)CD25(+) regulatory T cells expressing Foxp3) are required for effective host anti-tumor responses at alternate inoculation sites.

Animals↗
PubMed2006

Use of sphingosine-1-phosphate 1 receptor agonist, KRP-203, in combination with a subtherapeutic dose of cyclosporine A for rat renal transplantation.

BACKGROUND: We demonstrate the long-term effectiveness of KRP-203 treatment in combination with a subtherapeutic dose of cyclosporine A (CsA) on rat renal allografts. METHODS: We tested the effect of KRP-203 in combination with CsA using a rat skin allograft model. The Pharmacokinetic interaction between CsA and KRP-203 was evaluated. The selectivity of KRP-203 for sphingosine-1-phosphate (S1P)1 and S1P3 receptors were investigated in vitro. Heart rate alteration following bolus injection of phosphorylated KRP-203 (KRP-203-P) or FTY720 (FTY720-P) was also monitored in rats. Finally, the long-term effectiveness of KRP-203 in conjunction with a low dose of CsA was investigated in a rat renal transplantation model. RESULTS: Administration of KRP-203 with CsA prolonged skin allograft survival. KRP-203 and CsA had no effect on the pharmacokinetics of the other. While FTY720-P activated both S1P1 and S1P3 receptors, KRP-203-P selectively activated S1P1, but not the S1P3 receptor (EC50:>1000 nM). Compared to FTY720-P, a tenfold higher dose of KRP-203-P was necessary to induce transient bradycardia. With a low dose of CsA (1 mg/kg/day), KRP-203 (0.3 mg/kg/day) significantly prolonged renal allograft survival (P<0.05, survival time: 9.8 days (CsA) vs. >27.4 days (CsA+KRP)). Although a higher dose of CsA (3 mg/kg/day) alone kept recipients alive, this caused severe renal graft dysfunction. Use of KRP-203 (3 mg/kg/day) in conjunction with CsA markedly improved graft function (P<0.05, creatinine clearance: 0.41+/-0.25 ml/min [CsA] vs. 1.15+/-0.16 ml/min [CsA+KRP]). CONCLUSIONS: The selectivity of KRP-203 for S1P1 reduces the risk of bradycardia, and the combination therapy of KRP-203 with CsA represents a safe and effective strategy for use in renal transplantation.

Animals↗
PubMed2006

Successful strategy for the hysteroscopic myomectomy of a submucous myoma arising from the uterine fundus.

OBJECTIVE: To introduce a technique for hysteroscopic resection of submucous myoma arising from the uterine fundus. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 43-year-old nulliparous Japanese woman. INTERVENTION(S): An original combination technique of hysteroresectoscopy using circumferential myoma scraping, central vaporization, and intraoperative injection of prostaglandin F2alpha. MAIN OUTCOME MEASURE(S): Evaluation of clinical symptoms and imaging diagnosis. RESULT(S): Resection of a 40-mm fundal myoma was performed hysteroscopically, and the menorrhagia of the patient was remedied by the operation. CONCLUSION(S): Although large sessile fundal myomas are difficult to resect by hysteroscopic myomectomy, our original strategy may allow safe and certain surgery in such cases.

Adult↗
PubMed2006

Essential roles of sphingosine 1-phosphate/S1P1 receptor axis in the migration of neural stem cells toward a site of spinal cord injury.

Neural stem/progenitor cells (NSPCs) migrate toward a damaged area of the central nervous system (CNS) for the purpose of limiting and/or repairing the damage. Although this migratory property of NSPCs could theoretically be exploited for cell-based therapeutics of CNS diseases, little is known of the mechanisms responsible for migratory responses of NSPCs. Here, we found that sphingosine 1-phosphate (Sph-1-P), a physiological lysophospholipid mediator, had a potent chemoattractant activity for NSPCs, in which, of Sph-1-P receptors, S1P(1) was abundantly expressed. Sph-1-P-induced NSPC migration was inhibited by the pretreatment with pertussis toxin, Y-27632 (a Rho kinase inhibitor), and VPC23019 (a competitive inhibitor of S1P(1) and S1P(3)). Sph-1-P does not act as intracellular mediator or in an autocrine manner, because [(3)H]sphingosine, incorporated into NSPCs, was mainly converted to ceramide and sphingomyeline intracellularly, and the stimulation-dependent formation and extracellular release of Sph-1-P were not observed. Further, Sph-1-P concentration in the spinal cord was significantly increased at 7 days after a contusion injury, due to accumulation of microglia and reactive astrocytes in the injured area. This locally increased Sph-1-P concentration contributed to the migration of in vivo transplanted NSPCs through its receptor S1P(1), given that lentiviral transduction of NSPCs with a short hairpin RNA interference for S1P(1) abolished in vivo NSPC migration toward the injured area. This is the first report to identify a physiological role for a lipid mediator in NSPC migration toward a pathological area of the CNS and further indicates that the Sph-1-P/S1P(1) pathway may have therapeutic potential for CNS injuries.

Animals↗
PubMed2006

A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis xenografts via antiangiogenic activity in severe combined immunodeficiency mice.

OBJECTIVE: To investigate the effects of a selective cyclooxygenase (COX)-2 inhibitor on endometriosis xenografts in immunodeficient mice. DESIGN: Prospective placebo-controlled study. SETTING: An academic facility at a Japanese university graduate school of medicine. PATIENT(S): Eight human ovarian endometriomas from seven patients. ANIMAL(S): Twenty-three female severe combined immunodeficiency (SCID) mice. INTERVENTION(S): Human ovarian endometriomas were implanted into the peritonea of SCID mice. Vehicle alone or NS398 (a selective COX-2 inhibitor, 10 mg/kg of weight per day) were administered orally daily for 56 days after implantation. Mice were killed on the 56th day. MAIN OUTCOME MEASURE(S): Change in explants size and immunohistochemical analyses to evaluating the proliferation index, apoptosis index, microvessel density, and labeling index assessing vascular endothelial growth factor and COX-2 expression by the endometriotic lesion. RESULT(S): NS398 significantly decreased implant size in comparison to vehicle alone (NS398 [medians, with range in brackets]: 22.0% [19.0%-36.7%] vs. vehicle: 41.2% [31.0%-55.3%], P<.01). Microvessel density (85.3 per mm2 [53.9-157.0 per mm2] vs. 121.8 per mm2 [97.2-259.6 per mm2], P=.02) and the vascular endothelial growth factor (0.4 [0-1.1] vs. 0.6 [0.5-2.1], P=.03) and COX-2 (0.4 [0.4-0.5] vs. 0.6 [0.4-0.8], P=.03) labeling indices in stromal cells were significantly lower in the NS398 group than in the vehicle group. There were no differences in the proliferation or apoptosis indices between the two groups. CONCLUSION(S): Selective COX-2 inhibitors decreased the size of implants and effectively treated endometriosis.

Adult↗
PubMed2006

In vivo luminescent imaging of cyclosporin A-mediated cancer progression in rats.

BACKGROUND: Immunosuppressed individuals undergoing organ transplantation are at increased risk of recurrences of initial cancers, although how immunosuppressive therapy increases early cancer metastasis remains unclear. METHODS: The metastatic fate of luciferase-expressing rat metastatic colon cancer cells (luc-RCN-H4) injected intravenously into the liver of syngeneic and allogeneic rats was examined in the presence of the immunosuppressant cyclosporin A (CsA) by in vivo luminescent technique. With respect to potential tumor-progressing factors, contribution of chemokine receptors and transforming growth factor (TGF)-beta1 to early metastasis was evaluated using their specific signaling inhibitors. RESULTS: F344 rats injected in the liver with luc-RCN-H4 cells did not always exhibit the formation of tumors and showed a dormant state as long as 60 days after inoculation without CsA. However, CsA released early luc-RCN-H4 cells from dormancy within 2 weeks at nearly 100% in liver and preferentially promoted metastasis to the lymph nodes (approximately 40%). A similar dissemination occurred even in minor histocompatibility complex-disparate hosts. As a tumor-progressing factor, RCN-H4 cells aberrantly expressed chemokine receptors CXCR4 and CCR7. The chemokine receptor (CXC) R4-specific antagonist AMD3100 decreased early metastasis of luc-RCN-H4 cells in rats with ischemic liver conditions (P<0.05), but CsA treatment did not enhance early adhesion. Use of CsA was able to facilitate TGF-beta1 expression and the subsequent TGF-beta-mediated random migration was blocked by the use of the specific signaling inhibitor SB431542 in vitro. CONCLUSIONS: Whereas the chemokine receptor expression by cancer cells is implicated with early organotropic dissemination even under CsA-mediated immune suppression, rather, CsA enhances the late-phase progression after tumor adhesion through TGF-beta1 expression.

Adenocarcinoma↗
PubMed2006

Antitumor activity of IFN-lambda in murine tumor models.

IFN-lambda 1, -lambda 2 and -lambda 3 have been discovered as the latest members of the class II cytokine family and shown to possess antiviral activity. Murine B16 melanoma and Colon26 cancer cells were transduced with mouse IFN-lambda to determine whether IFN-lambda possesses antitumor activity. Overexpression of IFN-lambda induced cell surface MHC class I expression and Fas/CD95 Ag, induced significant caspase-3/7 activity, and increased p21(Waf1/Cip1) and dephosphorylated Rb (Ser(780)) in B16 cells in vitro. IFN-lambda expression in tumor cell lines markedly inhibited s.c. and metastatic tumor formation in vivo compared with mock transfections (p < 0.05). Moreover, IFN-lambda expression induced lymphocytic infiltrates, and an Ab-mediated immune cell depletion assay showed that NK cells were critical to IFN-lambda-mediated tumor growth inhibition. Hydrodynamic injection of IFN-lambda cDNA successfully targeted liver metastatic foci of Colon26 cells, and moderately decreased the mortality of mice with tumors. IFN-lambda overexpression in the liver increased NK/NKT cells and enhanced their tumor-killing activity, and suggested the activation of innate immune responses. Thus, IFN-lambda induced both tumor apoptosis and NK cell-mediated immunological tumor destruction through innate immune responses. These findings suggested that local delivery of IFN-lambda might prove a useful adjunctive strategy in the clinical treatment of human malignancies.

Animals↗
PubMed2006

Change from cyclosporine to combination therapy of mycophenolic acid with the new sphingosine-1-phosphate receptor agonist, KRP-203, prevents host nephrotoxicity and transplant vasculopathy in rats.

BACKGROUND: Replacement of calcineurin inhibitor (CI) with anti-metabolic agents in transplant patients with CI-induced nephrotoxicity is performed clinically and improves renal function, but increases the risk of rejection. We investigated whether the change from cyclosporine (CsA) to a limited dose of mycophenolic acid (MPA) together with a new sphingosine-1-phosphate (S1P) receptor agonist, KRP-203, is sufficient to prevent both transplant vasculopathy and CsA-induced nephrotoxicity. METHODS: Orthotopic aortic transplantation was conducted in a high-responder rat combination of Dark Agouti (DA; major histocompatibility complex [MHC] haplotype RT-1a) to Lewis (RT-1(l)). After CsA administration (15 mg/kg/day) for 2 weeks, the recipients were divided into the following treatment groups for 6 weeks: MPA (10 mg/kg); KRP-203 (KRP; 1 mg/kg); and MPA + KRP. Serum creatinine (Cr), arteriolar hyalinosis and expression of transforming growth factor (TGF)-beta1 in the recipient kidney were examined as parameters indicating nephrotoxicity. Intimal hyperplasia was assessed by vascular occlusion, and graft-infiltrated cells were semi-quantitatively evaluated histologically and then characterized immunohistochemically. RESULTS: Continuous CsA treatment attenuated intimal hyperplasia and cell infiltration (2.9 +/- 0.3% and 0.4 +/- 0.1; p < 0.01 vs vehicle), but increased Cr and hyalinosis (0.43 +/- 0.03 mg/dl and 57.2 +/- 0.4%; p < 0.01) with upregulated TGF-beta1. Replacement of CsA by MPA or KRP treatment alone improved nephrotoxicity, but worsened intimal hyperplasia and cell infiltration. Conversion to MPA + KRP treatment prevented nephrotoxicity (Cr, 0.32 +/- 0.02 mg/dl; hyalinosis, 5.6 +/- 1.3%; p < 0.01 vs CsA) and markedly suppressed intimal hyperplasia and cell infiltration (3.6 +/- 1.2% and 1.0 +/- 0.3; p = not significant vs CsA), with reduced T-cell infiltrates in the graft. CONCLUSIONS: Changing from CsA to a combined therapy of MMF with S1P agonist is a promising strategy in clinical transplantation to overcome CI-induced nephrotoxicity and chronic rejection.

Animals↗
PubMed2006

"Firefly rats" as an organ/cellular source for long-term in vivo bioluminescent imaging.

BACKGROUND: Transplantation research involving the use of stem cells demands an appropriate in vivo visualization system to monitor cellular fate over an observation period. The new field of in vivo imaging is being developed with fluorescent and luminescent biotechnology, and involves the real-time visualization of complex cellular processes in living animals. METHODS: : Following our recent development of inbred green fluorescent protein (GFP)-transgenic (Tg) rats, we created the establishment of inbred (Lewis) Tg rats with firefly luciferase. The immunogenicity against luciferase was evaluated by the skin grafting test, and the fate of grafts was monitored by in vivo luminescent technique. RESULTS: : The luciferase-Tg rats ubiquitously expressed the marker gene. Conventional skin grafting apparently showed the long-term acceptance of luciferase-Tg rat skin on wild-type rats (>100 days), compared with grafting of GFP-Tg-derived skin (<10 days). This suggests less cellular immune responsiveness against the luciferase protein than GFP. Strikingly, organ transplants with heart and small bowel, and bone marrow cell transplantation showed viability and graft acceptance, demonstrating that cells and organs from luciferase-Tg rats are transplantable and their fate can be tracked for a sufficient time. Taking advantage of less immunogenic luciferase, cellular fate of transplanted mature hepatocytes was also examined. Transplanted hepatocytes proliferated and were monitored selectively in damaged liver, but not in healthy liver, for over 60 days. CONCLUSIONS: We propose on the basis of these findings that the luciferase-Tg rat system with modern optical imaging offers a new platform for a better understanding of stem cell biology and transplantation.

Animals↗
PubMed2006

Sphingosine-1-phosphate receptor agonists suppress concanavalin A-induced hepatic injury in mice.

T cell-mediated immune responses play a critical role in a variety of liver injuries including autoimmune hepatitis. Injection of concanavalin A (Con A) into mice mimics the histological and pathological phenotype of T cell-mediated hepatitis. Recent advances in host immune control of organ transplantation include the development of sphingosine-1-phosphate (S1P) receptor agonists such as FTY720, which alter lymphocyte homing but do not suppress host general immunity. Herein we examined the effect of the new S1P receptor agonist KRP-203 on the Con A-induced liver damage model. In normal liver lymphocytes of BALB/c mice, both FTY720 and KRP203 promoted lymphocyte sequestering from the liver to secondary lymph nodes and significantly reduced the number of liver lymphocytes (p<0.05). Based on this observation, KRP203 was employed in the Con A-induced hepatitis model. KRP203 markedly reduced the number of CD4(+) lymphocytes that infiltrate Con A-treated liver (p<0.05) and successfully reduced serum transaminase elevation (p=0.017), therefore protecting mice from Con A-induced liver injury. Interestingly this homing modulation less occurs in natural hepatic T cell homing through the chemokine receptor, CXCR4. Therefore, S1P receptor agonists preferentially target CXCR4(+)CD4(+) peripheral blood T lymphocytes and suppress the occurrence of Con A-induced hepatitis, suggesting their therapeutic usefulness against T cell-mediated hepatic injury.

Animals↗
PubMed2006

Impact of weight reduction on production of platelet-derived microparticles and fibrinolytic parameters in obesity.

INTRODUCTION: Generation of platelet-derived microparticle (PMP) is implicated in cardiovascular disease (CVD). However, the influence of adiposity and weight reduction on PMP generation remains to be fully elucidated. We compared PMP generation and fibrinolytic parameters between 49 non-diabetic obese (obese group) and 37 age-matched non-obese subjects (control group), and compared the effects of weight reduction on the parameters between a 12-week calorie restricted diet and diet with aerobic exercise in obese subjects. MATERIALS AND METHODS: PMP, plasma levels of plasminogen activator inhibitor-1 (PAI-1) activity and tissue-type plasminogen activator (t-PA) antigen were measured before and after intervention. RESULTS: Before intervention, PMP, PAI-1 activity and t-PA antigen values were elevated in the obese group compared with the control group. In all 86 subjects of both groups, these three parameters correlated with body mass index, waist circumference and fat tissue mass. There was a positive correlation between plasma levels of fibrinolytic parameters and visceral fat area (VFA). PMP values correlated with subcutaneous fat area (SFA). The intervention significantly reduced PMP, PAI-1 activity and t-PA antigen levels. There was a significant correlation between percentages of changes in PMP values and those in BMI, fat tissue mass and VFA in the obese group. No additional effect of exercise on PMP or fibrinolytic parameters was observed. CONCLUSIONS: Overproduction of PMP and fibrinolytic abnormalities may be associated with excessive adipose tissue. Weight reduction by either calorie restriction with or without exercise improves fibrinolytic abnormalities and PMP overproduction, probably through reduction of adipose tissue.

Adipose Tissue↗
PubMed2006

Efficacy of mycophenolic acid combined with KRP-203, a novel immunomodulator, in a rat heart transplantation model.

BACKGROUND: To explore a more effective and less toxic immunosuppressive strategy in organ transplantation, we recently developed the novel sphingosine-1-phosphate receptor agonist KRP-203. This study examined the efficacy of KRP-203 combined with mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil, in rat heart allografts. METHODS: Heterotopic heart transplantation was performed in a rat combination of DA (MHC haplotype: RT1(a)) to Lewis (RT1). The recipients were divided into 12 groups (n = 5-7): Syngeneic (Lewis to Lewis), Vehicle, KRP-203 (0.3 and 1 mg/kg), MPA (10 and 20 mg/kg), 10 mg/kg MPA with KRP-203 (0.03, 0.3, 1, and 3 mg/kg), and 20 mg/kg MPA with KRP-203 (0.3 and 1 mg/kg). MPA, KRP-203, and vehicle were given orally. RESULTS: The mean days of survival were 5.8 (vehicle), 7 and 7.9 (0.3 and 1 mg/kg KRP-203, respectively), 12.7 and >54.4 (10 and 20 mg/kg MPA), >39.6 and >30.5 (10 mg/kg MPA with 1 and 3 mg/kg KRP-203), >100 and >87.8 (20 mg/kg MPA with 0.3 and 1 mg/kg KRP-203). Histologic and immunohistochemical analysis revealed that diffuse mononuclear cell infiltration (macrophages and T cells), hemorrhage, myocardial necrosis and fibrosis, and expression of endothelin-1, transforming growth factor-beta1, monocyte chemoattractant protein-1, interleukin-8, and E-selectin were markedly diminished in the allografts treated with MPA combined with KRP-203. Pharmacokinetic experiments indicated no interaction between MPA and KRP-203, and both combination regimens were well tolerated. CONCLUSIONS: Combination therapy of MPA with KRP-203 has a therapeutic potential as a novel immunosuppressant strategy in clinical transplantation.

Animals↗
PubMed2006

Prolonged relaxant effects of vecuronium in patients with deliberate hypermagnesemia: time for caution in cesarean section.

We present two cases showing significantly prolonged action of vecuronium from magnesium treatment after general anesthesia for urgent cesarean section. The serum magnesium levels were maintained at a therapeutic range for severe eclampsia in one patient (5.6 mg.dl(-1)) and for tocolysis in another with placenta previa totalis (6.9 mg.dl(-1)). The obstetrics-specific emergency in each patient led us to proceed with general anesthesia but using reduced-dose vecuronium, which failed to prevent prolongation of the neuromuscular block. As a result, the patients received prolonged mechanical ventilation. Our cases underscore the need for anesthesiologists as well as obstetricians to be aware of the prolongation of the action of nondepolarizing muscle relaxants as a result of magnesium treatment.

Adult↗
PubMed2006

Coronary pressure measurement to identify the lesion requiring percutaneous coronary intervention in equivocal tandem lesions.

OBJECTIVES: No reliable methods are available for determining application of percutaneous coronary intervention for treatment of equivocal tandem lesions. We investigated whether coronary pressure measurement is useful for determining the lesion that requires percutaneous coronary intervention in tandem lesions. METHODS: We measured coronary pressure in 72 consecutive patients with tandem lesions. Myocardial fractional flow reserve (FFRmyo) was obtained as the ratio of coronary pressure distal to the lesion/aortic pressure under maximal hyperemia. If the FFRmyo across the tandem lesions was >or=0.75, we deferred percutaneous coronary intervention for the lesion. When the tandem lesions showed FFRmyo<0.75, percutaneous coronary intervention was performed on the lesion that showed angiographically higher stenosis. When FFRmyo was <0.75 after one-lesion percutaneous coronary intervention, this intervention was carried out on the remaining lesion. RESULTS: We deferred percutaneous coronary intervention for 26 patients (36.1%), and performed percutaneous coronary intervention in 46 patients (63.8%). We performed percutaneous coronary intervention for one lesion in 19 patients (26.4%) and for both lesions in 27 patients (37.5%). Among patients in whom percutaneous coronary intervention was deferred, only two patients (7.7%) required target lesion revascularization during the follow-up period. This rate was not higher than that in the 46 patients who underwent percutaneous coronary intervention for one or two lesions (six patients, 13.0%). Similarly, the target lesion revascularization in lesions with initially deferred percutaneous coronary intervention (5.6%, 4/71 lesions) was not higher than that in lesions with percutaneous coronary intervention (15.1%, 11/73 lesions). Major cardiac events, cardiac death and acute myocardial infarction, did not occur in patients with deferred percutaneous coronary intervention and in those with percutaneous coronary intervention during the follow-up period. CONCLUSION: Our results clearly showed that coronary pressure measurement was clinically useful for identifying equivocal tandem lesions requiring percutaneous coronary intervention.

Aged↗