Aberrant HS1 molecule in a patient with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the activation of autoreactive B lymphocytes, which are supposed to carry aberrant signal transduction after the stimulation of B-cell receptor (BCR). To investigate abnormalities in BCR-mediated signaling pathway in lupus B lymphocytes, we analyzed HS1, a molecule downstream of BCR, in 80 Japanese SLE patients. We identified 37 amino acid deletion of HS1 in a 25-year-old female patient, and the aberrant HS1 lacked a part of a functional motif. Analysis of genomic DNA revealed that the aberrant HS1 was caused by exon skipping. Family study showed that the patient as well as her father and sister are heterozygous for the abnormality. WEHI-231 cell, a mouse B cell line, transfected with the aberrant HS1 displayed a significantly increased cell death upon cross-linking of BCR. Additionally, peripheral B lymphocytes from the patient exerted increased apoptosis after BCR stimulation compared to those from control SLE patients. These data suggest that the aberrant HS1 molecule may transmit an accelerated signal after BCR stimulation and may play a role in the activation of autoreactive B lymphocytes.

Treatment of myelodysplastic syndromes.

The IPSS scoring system is useful to establish the appropriate treatment plan in MDS. Growth factors may alleviate both anemia and neutropenia in some MDS patients. Serum Epo levels and need for transfusion serve as good predictors of the erythroid response to the combination of Epo and G-CSF. Subgroups of MDS patients may respond favorably to immunosuppressive therapies such as CyA and ATG. Low-dose chemotherapy may also improve peripheral blood counts. Platelet counts, bone marrow cellularity, chromosome aberrations, and ringed sideroblasts combine to create a model predicting the response to low-dose ara-C. High-dose chemotherapy may lead to complete remission in about half of MDS patients, but the duration of remission is often short. The only proven curative therapy for MDS is allogeneic stem cell transplantation, resulting in an overall disease-free survival rate of about 40%. Only a minority of patients, however, can undergo allogeneic transplantation, both because of patient age and the availability of suitable donors. Autologous stem cell transplantation may be an option for selected patients who are unable to find allogeneic donors. Because the clinical features of patients with MDS are quite heterogeneous, the development of more accurate predictive models may be necessary to improve the efficacy of treatment.

Ticlopidine-Associated thrombotic thrombocytopenic purpura with an IgG-type inhibitor to von Willebrand factor-cleaving protease activity.

A 41-year-old Japanese man complained of a left-sided visual disturbance. Imaging by magnetic resonance angiography revealed a narrowing of the left internal cervical artery. Thus, ticlopidine (Tc) administration was started at a daily dose of 300 mg. However, 2 weeks later, severe thrombocytopenia, fever, nausea, and psychiatric symptoms developed; Tc was therefore discontinued. Based on the diagnostic hallmark of 5 clinical signs, the patient's disease was diagnosed as thrombotic thrombocytopenic purpura (TTP). Daily plasmapheresis was performed for the first 4 days, and the patient's clinical signs gradually improved. Von Willebrand factor-cleaving protease (vWF-CPase) activity in his plasma was less than 3% of that of the control sample at diagnosis, but that value recovered steadily following plasmapheresis. In addition, immunoglobulin G purified from the patient plasma inhibited vWF-CPase activity in normal plasma with a specific activity of 0.8 Bethesda units/mg. No sign of TTP relapse has been noted following cessation of Tc. Thus, it was concluded that the patient developed TTP by producing an inhibitory autoantibody against vWF-CPase activity that was presumably triggered by Tc administration.

MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes.

AML1-MTG8 chimeric oncogene is generated in acute myelogenous leukemia with t(8;21), and seems to be responsible for the pathogenesis of the disease. However, the role of MTG8 is ambiguous. Here we found that MTG8 interacted with the regulatory subunit of type II cyclic AMP-dependent protein kinase (PKA RIIalpha). The binding site of MTG8 was NHR3 domain, and that of RIIalpha was the N-terminus for interacting with PKA anchoring proteins (AKAPs). NHR3 contains a putative alpha-amphipathic helix which is characteristic in binding of AKAPs with RII. Indirect immunofluorescence microscopy showed that MTG8 and RIIalpha were overlapped at the centrosome-Golgi area in lymphocytes. These findings suggest that MTG8 may function as an AKAP at the centrosome-Golgi area in lymphocytes.

[European-American-type hairy cell leukemia without splenomegaly, treated successfully with deoxycoformycin].

A 55-year-old Japanese man was hospitalized on October 5, 1999, because of high fever. Physical examination revealed neither lymphadenopathy nor hepato-splenomegaly. Laboratory data on admission showed a white blood cell count of 1,580/microliter, a hemoglobin level of 9.1 g/dl, and a platelet count of 113 x 10(3)/microliter. A small percentage of abnormal mononuclear cells were present in the peripheral blood. A bone marrow biopsy specimen demonstrated myelofibrosis and diffuse infiltration of abnormal monoculear cells with a mature B cell phenotype. A bone marrow aspirate showed 29% abnormal mononuclear cells, which had an indented or folded nucleus and reticular nuclear chromatin. Moderate to strong tartarate-resistant acid phosphatase activity was detected in these cells. Although the cytoplasmic projections were poorly preserved in specimens stained with May-Giemsa, fresh preparations showed numerous slender cytoplasmic projections by phase-contrast microscopy. The hairy cells had the phenotype CD5-, CD10-, CD11c+, CD19+, CD20+, CD25+, lambda. The patient was diagnosed as having European-American-type hairy cell leukemia (HCL) without splenomegaly, which is quite rare in Japan. The value of phase-contrast microscopy for recognition of the hairy cells was emphasized. The patient was treated successfully with deoxycoformycin (DCF).

Entrapment of a guide wire by the Chiari network in a patient with ablated idiopathic ventricular tachycardia.

Using a guide wire before insertion of a sheath is a common procedure with infrequent complications. We report an unusual case of a guide wire having been entrapped by the Chiari network prior to an intended radiofrequency ablation procedure, and which could be observed using intracardiac echocardiography. Using transthoracic echocardiography prior to ablation, this patient had been shown to have a relatively large Chiari network. We caution against using a long guide wire in patients with a large Chiari network.

Primary chronic myelofibrosis: clinical and prognostic evaluation in 336 Japanese patients.

We retrospectively analyzed 336 patients with primary chronic myelofibrosis from 203 medical institutes in Japan. Notwithstanding their heterogeneous treatments, the median survival in 298 patients that could be evaluated was 10.0 years. Average age at onset was 60.7 years. Men were affected 1.4 times more frequently than women. The factors associated with shorter survival included anemia, leukocytosis/leukocytopenia, thrombocytopenia, and increased blasts in the peripheral blood, and sex (male), age (>60), and the presence of symptoms. A new scoring system based on the peripheral blood findings (hemoglobin [Hb] level, platelet count, and rate of blast formation) at initial diagnosis clearly correlated with survival rate. Accordingly, patients could be categorized into 3 groups by severity grading. Through stepwise multivariate survival analysis, the significant prognostic factors were identified as the severity grading based on the new scoring system (P = .0002), age (P = .0024), sex (P = .0153), and Hb (P = .0198). Chromosomal abnormalities were found in 58 of 154 patients (38%), although these did not influence survival.

Intracellular cytokine profile of CD14 positive cells in patients with hematologic malignancies and solid tumors during hematologic recovery phase after intensive chemotherapy designed to mobilize peripheral blood stem cells.

We studied intracellular cytokines in monocytes by flow cytometry from 28 patients with hematologic malignancies and solid tumors to analyze the role of monokines in the hematologic recovery phase for peripheral blood stem cell harvest. The patients were divided into three groups: the first group, A, had a documented infection; the second group, B, had fever of unknown origin; and the third group, C, was afebrile. We found an increase in intracellular IL-1alpha, IL-6, IL-8 and TNF-alpha positive monocytes as CD14 positive gated cells cultured with lipopolysaccharide in all groups, but no increase was found with medium only when cultured for 4 h. We also found an increase in intracellular IL-1a, IL-6, IL-8 and TNF-alpha positive monocytes cultured with autologous serum for 4 h, but only in group A. The rate of intracellular cytokine positive cells was higher in monocytes cultured with only autologous serum from group A patients compared to those cells from the other groups; the data concerning IL-1a, IL-6 and TNF-alpha reached statistical significance (P < 0.05). However, increasing intracellular cytokine levels in the control group of patients exhibiting only infectious disease were observed. Thus, it appear that pro-inflammatory intracellular cytokine levels in monocytes are only related to microbial infections.

Alterations in electrical and mechanical activity in Langendorff-perfused guinea pig hearts exposed to decreased external sodium concentration with or without hypotonic insult.

In order to examine electrical and mechanical effects of hyponatremia and hypotonicity, relevant to those in patients with 'water intoxication' syndrome, Langendorff-perfused guinea pig hearts were exposed to reduced NaCl concentrations (hypotonic [NaCl](0)-reduction) under the monitoring of left ventricular developed pressure (LVDP) and epicardial ECG. In some hearts, hyponatremia (from 140 to 80 mEq/l) was compensated for by adding mannitol to maintain osmolarity at a constant level (isotonic [NaCl](0)-reduction) or tetraethylammonium chloride to maintain both osmolarity and chloride concentrations at a constant level (isotonic [Na(+)](0)-reduction). Progressive isotonic [NaCl](0)-reduction increased LVDP, which was abolished in the presence of KB-R7943, a novel inhibitor of Na(+)/Ca(2+)-exchange. LVDP was reduced in hypotonic [NaCl](0)-reduction in which myocardial water content was increased. PQ interval and QRS duration were prolonged with both hypotonic and isotonic [NaCl](0)-reduction and these changes tended to be more pronounced with hypotonic than with isotonic [NaCl](0)-reduction. Similar ECG changes were also evident with isotonic [Na(+)](0)-reduction. Gd(3+) (1-5 µM), a blocker of stretch-activated nonspecific cation channels, had no substantial effects on the electrical or mechanical changes seen with hypotonic [NaCl](0)-reduction. In conclusion, isotonic [NaCl](0)-reduction produced a positive inotropism by modulating Na(+)/Ca(2+)-exchange, whereas hypotonic [NaCl](0)-reduction led to negative inotropism, due in part to hypotonic myocardial swelling. In addition, [Na(+)](0)-reduction, irrespective of the concomitant [Cl(-)](0) or osmotic changes, depressed atrioventricular as well as intraventricular conduction.

Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia.

Aberrant hypermethylation of tumor suppressor genes plays an important role in the development of many tumors. Recently identified new DNA methyltransferase (DNMT) genes, DNMT3A and DNMT3B, code for de novo methyltransferases. To determine the roles of DNMT3A, DNMT3B, as well as DNMT1, in the development of leukemia, competitive polymerase chain reaction (PCR) assays were performed and the expression levels of DNMTs were measured in normal hematopoiesis, 33 cases of acute myelogenous leukemia (AML), and 17 cases of chronic myelogenous leukemia (CML). All genes were constitutively expressed, although at different levels, in T lymphocytes, monocytes, neutrophils, and normal bone marrow cells. Interestingly, DNMT3B was expressed at high levels in CD34(+) bone marrow cells but down-regulated in differentiated cells. In AML, 5.3-, 4.4-, and 11.7-fold mean increases were seen in the levels of DNMT1, 3A, and 3B, respectively, compared with the control bone marrow cells. Although CML cells in the chronic phase did not show significant changes, cells in the acute phase showed 3.2-, 4.5-, and 3.4-fold mean increases in the levels of DNMT1, 3A, and 3B, respectively. Using methylation-specific PCR, it was observed that the p15(INAK4B) gene, a cell cycle regulator, was methylated in 24 of 33 (72%) cases of AML. Furthermore, AML cells with methylated p15(INAK4B) tended to express higher levels of DNMT1 and 3B. In conclusion, DNMTs were substantially overexpressed in leukemia cells in a leukemia type- and stage-specific manner. Up-regulated DNMTs may contribute to the pathogenesis of leukemia by inducing aberrant regional hypermethylation. (Blood. 2001;97:1172-1179)

Outside-to-inside signal through the membrane TNF-alpha induces E-selectin (CD62E) expression on activated human CD4+ T cells.

The membrane TNF-alpha is known to serve as a precursor of the soluble form of TNF-alpha. Although it has been reported the biological functions of the membrane TNF-alpha as a ligand, the outside-to-inside (reverse) signal transmitted through membrane TNF-alpha is poorly understood. Here we report a novel function mediated by outside-to-inside signal via membrane TNF-alpha into the cells expressing membrane TNF-alpha. Activation by anti-TNF-alpha Ab against membrane TNF-alpha on human T cell leukemia virus (HTLV) I-infected T cell line, MT-2, or PHA-activated normal human CD4(+) T cells resulted in the induction of an adhesion molecule, E-selectin (CD62E), on the cells with the peak of 12-24 h, which completely disappeared by 48 h. When wild-type or mutant membrane TNF-alpha (R78T/S79T) resistant to proteolytic cleavage was introduced into Jurkat or HeLa cells, E-selectin was induced by the treatment with anti-TNF-alpha Ab with the similar kinetics. Membrane TNF-alpha-expressing Jurkat cells also up-regulated E-selectin when brought into cell-to-cell contact with TNF receptor-expressing HeLa cells. Northern blot analysis and RT-PCR analysis showed that the membrane TNF-alpha-mediated E-selectin expression was up-regulated at the level of transcription. These results not only confirmed our previous findings of reverse signaling through membrane TNF-alpha, but also presented evidence that E-selectin was inducible in cell types different from endothelial cells. It is strongly suggested that membrane TNF-alpha is a novel proinflammatory cell surface molecule that transmits bipolar signals in local inflammation.

Immunosuppressive therapy for patients with refractory anemia.

Trials of immunosuppressive therapy have been reported in some case reports of hypoplastic myelodysplastic syndrome (MDS). In this study, we gave immunosuppressive therapies to eight patients with normo- or hyperplastic MDS of refractory anemia subtype without karyotypic abnormalities and analyzed the HLA-DRB1 type or the presence of paroxysmal nocturnal hemoglobinuria (PNH) neutrophils in these patients. Cyclosporin A (CyA) therapy was effective for improving cytopenia in four of the eight MDS patients. While the side effects of CyA were mostly mild and transient, one patient demonstrated karyotypic abnormality following CyA therapy and accelerated to refractory anemia with an excess of blasts. Additional antithymocyte globulin (ATG) therapy was effective in one of three nonresponders to CyA therapy. One patient died due to leukemic transformation after ATG therapy. When we analyzed the correlation between the response to CyA therapy and the HLA-DRB1 type, there were more responders with DRB1*1501 (three of four patients) than without (one of four patients), but a statistically significant difference was not evident between the two groups. In addition, the presence of PNH neutrophils was not correlated with the response to CyA and/or ATG therapy. These results indicate the usefulness of immunosuppressive therapies even for normo- or hyperplastic MDS patients. Further trials using more patients with a long follow-up period would be worthwhile in order to clarify the possibility of disease progression and in order to predict the response of patients.

Subthreshold stimulation in three types of reentrant supraventricular tachycardia: correlation with the results of catheter ablation.

The effects of subthreshold stimulation (STS) by direct current were investigated in 20 patients with atrioventricular nodal reentrant tachycardia (AVNRT), 27 with atrioventricular reentrant tachycardia (AVRT) and 3 with idiopathic atrial reentrant tachycardia (IART) STS was delivered to each eligible site for ablation prior to radiofrequency application. STS was defined as 'positive' if it could terminate the tachycardia or disrupt the conduction of accessory pathways without myocardial capture and defined as 'negative' if it could not. Radiofrequency ablation was performed irrespective of a positive or negative result from STS and was successful in all 50 patients. Among the 50 successful ablation sites, STS was positive at 26 sites (11 sites in AVNRT, 12 in AVRT and 3 in IART). STS was positive at 4 sites where ablation failed in 3 patients with AVRT and was negative at 8 sites where ablation was successful in 4 patients with AVNRT and 4 with AVRT. The positive and negative predictive value of STS for the detection of the optimal ablation site were, respectively, 100% and 74% in AVNRT, 73% and 72% in AVRT, and both 100% in IART STS-guided mapping is a specific method to predict the successful catheter ablation of reentrant supraventricular tachycardia.

Identification and characterization of two novel mutations (Q421 K and R123P) in congenital factor XII deficiency.

The factor XII genes of two unrelated factor XII-deficient Japanese families were screened, and two novel mutations were identified. A heterozygous mutation (Q421K) was identified in the gene of a cross-reacting material (CRM)-negative patient with reduced FXII activity (entitled Case 1). No mutations were discovered in the other allele. Case 2 was a CRM-negative patient with severe FXII deficiency. In this case, a homozygous mutation (R123P) was discerned. Expression studies in Chinese Hamster Ovary (CHO) cells demonstrated accumulation of mutant Q421 K factor XII in the cell, and insufficient secretion, while the R123P mutant showed lower levels of accumulation than wild-type, and no evidence of secretion in culture supernatant. In the presence of proteasome inhibitor, all types of FXII (wild-type. Q421K, R123P) accumulated in the cells. Protease protection experiments using the microsomal fraction of these cell lines demonstrated that while 20% wild-type FXII (total wild-type:100%) and 10% R123P mutant (total R123P-type: 40%) were resistant to treatment with trypsin, 50% Q421K-type FXII (total Q421K-type:130%) remained resistant to digestion. From these results, we conclude that Q421K is less susceptible to proteasome degradation than wild-type, but is unable to exit the ER efficiently, resulting in insufficient secretion phenotype. In contrast, R123P is susceptible to proteasome degradation and is not secreted.

Association of tumor necrosis factor receptor type II polymorphism 196R with Systemic lupus erythematosus in the Japanese: molecular and functional analysis.

OBJECTIVE: To investigate whether a polymorphism(s) or mutation(s) in the tumor necrosis factor receptor II (TNFRII) gene is involved in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: All 10 exons of the TNFRII gene were analyzed by exon-specific polymerase chain reaction-single-strand conformation polymorphism, followed by nucleotide sequencing of exons that displayed aberrant bands. To analyze the function of the TNFRII polymorphisms, the full-length TNFRII complementary DNA of each allele was transfected in HeLa cells and then studied for specific binding of 125I-TNFalpha, as well as interleukin-6 (IL-6) production and cytotoxic activity after treatment with recombinant human TNFalpha. RESULTS: We identified 4 polymorphisms, at codons 56, 181, 196, and 232. The latter 2 had amino acid substitutions M196R and E232K, respectively. Only the 196R allele was significantly associated with SLE in our 105 Japanese SLE patients, with an allele frequency of 20.5%, compared with 12.6% in 99 healthy controls (P = 0.0335). More importantly, using TNFRII-transfected HeLa cells, we demonstrated significantly increased IL-6 production by 196R TNFRII compared with 196M TNFRII. The cytotoxic activity induced by 196R TNFRII was also increased compared with that of 196M TNFRII. This increase was achieved without affecting the binding affinity of TNFalpha to TNF-RII, as demonstrated by the finding that specific TNFalpha binding to the HeLa transfectants of 196R and 196M TNFRII was similar, with Kd values of 3.12 x 10(-10)M and 4.34 x 10(-10)M, respectively. CONCLUSION: These results suggest that 196R TNFRII, which transduces the signals of TNFalpha more effectively than does 196M TNFRII, is involved in the pathogenesis of SLE.

Induction of MTG8-specific cytotoxic T-cell lines: MTG8 is probably a tumour antigen that is recognized by cytotoxic T cells in AML1-MTG8-fused gene-positive acute myelogenous leukaemia.

Several reports have demonstrated the persistent detection of AML1-MTG8 fusion products, representing minimal residual disease (MRD), in patients with t(8;21) acute myelogenous leukaemia (AML) who are in long-term remission. It is probable that immune-mediated mechanisms that are able to suppress the expansion of MRD may result in the continuance of remission. It was previously shown that some t(8;21) AML patients had high anti-MTG8 antibody titres. MTG8 expression in normal adult tissues is limited to the brain or heart in which human leucocyte antigen (HLA) class I cell-surface antigens are either not or are only faintly detectable. We hypothesized that the overexpression of the MTG8 gene in t(8;21) AML cells could act as a possible tumour antigen, which might be able to induce the immune-mediated suppression of the expansion of MRD. We were able to induce HLA-A0201-restricted cytotoxic T-lymphocyte (CTL) lines against an MTG8 peptide (MTG8b amino acids 182-191) using monocyte-derived dendritic cells from a healthy donor. T-cell receptor (TCR)Valpha17, TCRVbeta14 and 15, and TCRJbeta2.1 and 2.3 are predominantly used in these CTL lines. Our data, which suggest that the MTG8 protein could be one of the tumour antigens recognized by CTLs, may be helpful in further investigations of TCR analysis in t(8;21) AML patients with HLA-A0201 who are in long-term remission.

Tyk2 plays a restricted role in IFN alpha signaling, although it is required for IL-12-mediated T cell function.

Janus kinases (Jaks) play an important role in signal transduction via cytokine receptors. Tyk2 is a Janus kinase, and we developed tyk2-deficient mice to study the requirement for tyk2 in vivo. Tyk2-deficient mice show no overt developmental abnormalities; however, they display a lack of responsiveness to a small amount of IFNalpha, although a high concentration of IFNalpha can fully transduce its signal even in the absence of tyk2. Furthermore, IL-12-induced T cell function is defective in these mice. In contrast, these mice respond normally to IL-6 and IL-10, both of which activate tyk2 in vitro. These observations demonstrate that tyk2 plays only a restricted role in mediating IFNalpha-dependent signaling while being required in mediating IL-12-dependent biological responses.

Low cell binding ability of HCV is closely related to interferon treatment especially in patients with HCV genotype 2a/2b. A large series prospective study on Japanese patients with chronic hepatitis C.

BACKGROUND/AIMS: We have previously shown that the quantity of antibody-free virion in the pre-treatment sera of the patients with chronic hepatitis C is a good predictive factor for the efficacy of interferon treatment. However, the biological significance of the free virion should be verified by a prospective study. METHODS: We prospectively evaluated 152 consecutive patients with chronic hepatitis C who received a standardized interferon treatment, and analyzed the free virion and the binding titers, the ability of hepatitis C virus (HCV) to bind to the human lymphocytic cell line. RESULTS: Sixty-five patients achieved a long-term sustained remission, 76 patients did not respond to the interferon therapy, and 11 patients dropped out. The sera from the patients with genotype 2a/2b had significantly lower free virion and cell binding titers than those with genotype 1b. A multivariate analysis showed three independent variables associated with the interferon response; cell binding titer <10(0.5)/ml, viral load <10(4.5) copies/50 microl, and genotype 2a/2b with odds ratios of 14.6, 11.8, and 9.8, respectively. CONCLUSIONS: The low level of in vitro cell binding ability of HCV helped to clarify the good responsiveness to interferon observed in patients especially with a high viral load of genotype 2a/2b.

Human thymic epithelial cells maintain long-term survival of clonogenic myeloid and erythroid progenitor cells in vitro.

Precursor cells that migrate into the thymus are still multipotent. Therefore, thymic epithelial cells (TECs) may provide microenvironments not only for T-cell development, but also for maintenance of multipotent precursor cells until they undergo T-cell commitment. In the present study, we performed long-term cultures of CD34+ bone-marrow (BM) cells on TEC lines that were derived from cortical epithelial cells of post-natal thymus, to investigate whether human TECs could maintain long-term nonlymphoid haematopoiesis. Haematopoietic cells maintained in direct contact with established TEC lines were able to generate clonogenic progeny to both myeloid and erythroid cells for periods in excess of 5 weeks. Their abilities to support colony-forming units of granulocytes-macrophages (CFU-GM) and burst-forming units of erythroids (BFU-E) were almost equal to those of BM stromal cells. We observed similar results by using cloned TEC lines derived by limiting dilution, as well as those by using parental TEC lines. Colony-forming activities were maintained even when haematopoietic progenitor cells were physically separated from TEC lines and cultured on microporous membrane. These observations indicate that haematopoiesis maintained in TEC-contact long-term cultures may depend on soluble factors produced by TEC lines. Our results suggest that thymic cortical epithelial cells have the ability to support not only the differentiation of haematopoietic cells, but also long-term survival of clonogenic myeloid/erythroid progenitor cells.

Influence of right atrial structure on outcome of radio-frequency catheter ablation for common atrial flutter.

Radiofrequency catheter ablation (RFCA) targeting the cavotricuspid isthmus is usually an effective treatment for common atrial flutter (AFL), except in a small subset of patients and the reason for this has yet to be elucidated. The present study investigated the relationship between the outcome of RFCA for common AFL and the anatomy of the right atrium as seen on angiography. Twenty consecutive patients who underwent RFCA for common AFL were divided into 2 groups according to the results of RFCA. Group A comprised 13 patients whose AFL was abolished, fulfilling the criteria of success by the conventional catheter approach, and group B comprised 7 patients whose AFL could not be abolished according to the criteria for success (n=4) or was abolished following an additional superior vena cava approach (n=3). On angiography, the cavotricuspid isthmus was longer (3.5+/-0.5 vs 2.2+/-0.6 cm) and deeper (0.94+/-0.35 vs 0.49+/-0.19 cm) in group B than in group A (both p<0.01). The height of the eustachian valve was also greater in group B than in group A (1.4+/-1.1 vs 0.48+/-0.48 cm, p<0.02). These results suggest that the anatomical structure of the cavotricuspid isthmus affects the outcome of RFCA for common AFL.