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Ichiro Watanabe

Publications and source records attributed to Ichiro Watanabe.

17 recordsLinked to original sources
PubMed2003

A study to survey susceptible genetic factors responsible for troglitazone-associated hepatotoxicity in Japanese patients with type 2 diabetes mellitus.

BACKGROUND AND OBJECTIVE: Troglitazone is a 2,4-thiazolidinedione antidiabetic agent with insulin-sensitizing activities. This agent had been used efficiently in a large number of patients but was withdrawn from the market in March 2000 because of its association with idiosyncratic hepatotoxicity. To address the susceptible genetic factors responsible for the hepatotoxicity associated with this agent, we performed a genetic polymorphic analysis by a target gene approach in troglitazone-treated Japanese patients with type 2 diabetes mellitus. METHODS: One hundred ten patients treated with troglitazone were recruited into this study. The case patients (n = 25) were recruited through medical professionals who had previously reported abnormal increases in the levels of ALT or AST among their patients. The control patients (n = 85) were recruited through physicians prescribing troglitazone. For statistical accuracy, efforts were made to maximize the size of the case group. Genotype analysis was performed in 68 polymorphic sites of 51 candidate genes related to drug metabolism, apoptosis, roduction and elimination of reactive oxygen species, and signal transduction pathways of peroxisome proliferator-activated receptor gamma 2 and insulin. RESULTS: The strong correlation with transaminase elevations was observed in the combined glutathione-S-transferase GSTT1-GSTM1 null genotype (odds ratio, 3.692; 95% confidence interval, 1.354-10.066; P =.008). CONCLUSIONS: The double null mutation of GSTT1 and GSTM1 might influence troglitazone-associated abnormal increases of liver enzyme levels.

Aged↗
PubMed2003

Effect of 60 minutes of rapid atrial pacing on atrial action potential duration in the in-situ canine heart.

Right atrial monophasic action potentials were recorded before and after 60 minutes of rapid atrial pacing (pacing cycle length (CL); 127 +/- 10 ms) in 12 closed-chest dogs. The right atrial (RA) monophasic action potential (MAP) duration at 90% repolarization (RAMAPD) was measured at CLs of 400 ms and 250 ms. CL-dependent changes in RAMAPD (CL 400 ms - 250 ms) before and after rapid atrial pacing were 24 +/- 1 ms and 16 +/- 5 ms, respectively (p < 0.02). RAMAP was recorded at each atrial pacing CL starting at 240 ms decreasing by 10-ms increments. RAMAPD alternans was observed in 10 of 12 dogs at a CL of 163 +/- 17 ms before and in 10 of 12 dogs at s CL of 198 +/- 29 ms (p < 0.01) after rapid atrial pacing. Sustained atrial fibrillation (AF) (>5 minutes) was induced in 1 of 12 dogs at a pacing CL of 130 ms before rapid atrial pacing and in 4 of 12 dogs at a pacing CL of 135 +/- 17 ms after rapid atrial pacing. Onset of AF was always preceded by the RAMAPD alternans. Sixty minutes of rapid atrial pacing leads to diminution of rate adaptation of atrial action potential duration (APD) and appearance of APD alternans of greater magnitude at longer CL, both of which may contribute to the initiation and perpetuation of AF during its early phase.

Action Potentials↗
PubMed2003

Intravenous administration of class I antiarrhythmic drug induced T wave alternans in an asymptomatic Brugada syndrome patient.

A 53-year-old man with an abnormal ECG was referred to the Nihon University School of Medicine. The 12-lead ECG showed right bundle branch block and saddleback-type ST elevation in leads V1-V3 (Brugada-type ECG). Signal-averaged ECG showed positive late potentials. Double ventricular extrastimuli (S1: 500 ms, S2: 250 ms, S3: 210 ms) induced VF. Amiodarone (200 mg/day) was administered for 6 months and programmed ventricular stimulation was repeated. VF was induced again by double ventricular stimuli (S1: 600 ms, S2: 240 ms, S3: 170 ms). Intravenous administration of class Ic antiarrhythmic drug, pilsicainide (1 mg/kg), augmented ST-T elevation in leads V1-V3, and visible ST-T alternans that was enhanced by atrial pacing was observed in leads V2 and V3. Visible ST-T wave alternans disappeared in 15 minutes. However, microvolt T wave alternans was present during atrial pacing at a rate of 70/min without visible ST-T alternans.

Amiodarone↗
PubMed2003

Advanced pancreatic ductal cancer: fibrotic focus and beta-catenin expression correlate with outcome.

INTRODUCTION: Many investigators have examined prognostic factors for advanced pancreatic ductal cancer, but it is still difficult to accurately predict the outcome of the disease. AIM: To examine correlation between histopathologic factors and outcome of advanced ductal carcinoma of the pancreas. METHODOLOGY: The subjects were 23 patients who underwent resection of pancreatic ductal cancer classified as stage III according to pTNM classification. Fibrotic focus (which is evidence of intratumoral fibroblast proliferation), tumor size and differentiation, invasion to the portal vein, and immunohistologic expression of E-cadherin and alpha-, beta- andbgr;- and gamma-catenins were evaluated. Correlation between histologic and immunohistologic data and correlation between these data and liver metastasis-free survival and overall survival were assessed by means of the Kaplan-Meier method, the log-rank test, and the Cox proportional hazards regression model (for multivariate analysis). RESULTS: The presence of fibrotic focus correlated with reduced membranous beta-catenin expression. The presence of fibrotic focus, reduced membranous beta-catenin expression, and reduced cytoplasmic alpha-catenin expression were significantly associated with shorter liver metastasis-free survival. The presence of fibrotic focus also significantly correlated with shorter survival and was the only factor significantly associated with survival in multivariate analysis. CONCLUSION: The presence of fibrotic focus and reduced beta-catenin expression closely correlated with poor survival of patients with advanced ductal carcinoma of the pancreas.

Adult↗
PubMed2003

Combined atriofascicular and fasciculoventricular connections.

A 32-year-old man with a 20-year history of palpitation showed a short PQ interval and delta wave on 12-lead ECG. An electrophysiological study showed that the atrio-His (AH) and His-ventricular intervals were not influenced by rapid right atrial pacing or by bolus injection of adenosine triphosphate (ATP). The AH interval was shortened by coronary sinus ostium (CSos) pacing. Ventricular stimulus to the atrial activation interval was not affected by ATP but shortened by para-Hisian pacing and orthodromic His bundle activation was followed by atrial activation. The tricuspid - inferior vena cava isthmus was blocked by CSos pacing, but Ith conduction existed during low lateral right atrial pacing.

Adenosine Triphosphate↗
PubMed2002

Vasculogenic mimicry and pseudo-comedo formation in breast cancer.

Tumors require a blood supply for growth and hematogenous metastases. Until recently, most research in this area has focused on the role of angiogenesis, the recruitment of new vessels into a tumor from preexisting vessels. Previously, in a study of breast cancer (IBC), in which we used established inflammatory breast cancer (IBC) xenografts (WIBC-9) originating from a patient with IBC (Shirakawa et al., Cancer Res 2001:61:445-451), we reported observing vasculogenic mimicry (VM), a condition in which bloodstreams within cancer tissue are not accompanied by a lining of endothelial cells (ECs) (Shirakawa et al., Cancer Res 2002:62:560-566). In the present study, we examined 331 surgically resected breast cancer specimens for evidence of VM, using immunohistochemistry and laser-captured microdissection (LCM) followed by nested reverse transcriptase polymerase chain reaction (RT-PCR). Surprisingly, 7.9% (26 specimens) of the 331 specimens exhibited evidence of VM. Of these 26 VM specimens, 84.6% (22 specimens) exhibited pseudo-comedo formation. RT-PCR analysis of 8 microdissected typical VM specimens revealed expression of Tie-2, Flt-1, thrombin receptor and CD31 in 63, 50, 0 and 0% of specimens, respectively. In contrast, results of RT-PCR analysis of 8 specimens from non-VM tumors were negative for expression of these genes. The 26 VM cases tended to have a higher percentage of hematogenous recurrence (p = 0.059) and a lower percentage of 5-year survival (p = 0.071) than the 305 non-VM cases. However, there were no significant differences in tumor size, lymph node metastasis, estrogen receptors or progesterone receptors between the 2 groups (p > 0.1). Our results suggest that the existence of VM increases the likelihood of hematogenous metastases and is in inverse proportion to prognosis.

Antigens, CD↗
PubMed2002

Tumor-infiltrating endothelial cells and endothelial precursor cells in inflammatory breast cancer.

Inflammatory breast cancer (IBC) is a specific type of breast tumor that generally has a poor prognosis, in spite of recent advances in treatment. In the present study, semiquantitative reverse transcriptase polymerase chain reaction examination of resected specimens showed that angiogenic factors, not lymphangiogenic factors, are overexpressed in IBC tumors, compared with non-IBC tumors. Immunohistochemical analysis of the specimens revealed a significantly higher population of tumor-infiltrating (TI) endothelial cells (ECs) or endothelial precursor cells (EPCs) in tumor-associated stroma of IBC specimens than in non-IBC specimens. In a previous study, we examined the phenotype of host cells in response to transplanted IBC cells, using an established human IBC xenograft model (WIBC-9) (Shirakawa et al., Cancer Res 2001;61:445-51). The data obtained in that study are consistent with the findings of the present study. To explore the therapeutic potential of blocking vascular endothelial growth factor (VEGF) and angiopoietin (Ang) pathways in IBC, established vectors encoding soluble Flt-1 (sFlt-1) and soluble Tie2 (sTie2) were injected directly into WIBC-9. Both vectors produced growth inhibition ratios of WIBC-9 that were significantly higher than those of a non-IBC xenograft (MC-5). Also, both vectors suppressed WIBC-9 lung metastases. The efficacy correlated with the number of TI ECs/EPCs, which was determined by fluorescence-activated cell sorting. These ECs/EPCs incorporated acetylated lipoprotein and were integrated within a HUVEC monolayer in vitro culture on day 5.

Angiopoietin-1↗
PubMed2002

Rapid accumulation and internalization of radiolabeled herceptin in an inflammatory breast cancer xenograft with vasculogenic mimicry predicted by the contrast-enhanced dynamic MRI with the macromolecular contrast agent G6-(1B4M-Gd)(256).

The rapid blood flow and perfusion of macromolecules in the inflammatory breast cancer xenograft (WIBC-9), which exhibits a "vasculogenic mimicry" type of angiogenesis without the participation of endothelial cells and expresses high levels of the HER-2/neu antigen, was evaluated in mice using 3D-micro-MR angiography using a novel macromolecular MR contrast agent [G6-(1B4M-Gd)(256)]. Herceptin, which recognizes the HER-2/neu antigen and has similar size (10 nm) to G6-(1B4M-Gd)(256), accumulated and internalized in the WIBC-9 tumors more quickly than in the control MC-5 tumors that progress with normal angiogenesis. Three dimensional micro-MRI with the G6-(1B4M-Gd)(256) macromolecular MRI contrast agent distinguishes between the different types of angiogenesis and is predictive of the rapid accumulation and internalization of Herceptin in the WIBC-9 inflammatory breast cancer xenograft.

Animals↗
PubMed2002

Cooled-tip ablation results in increased radiofrequency power delivery and lesion size in the canine heart: importance of catheter-tip temperature monitoring for prevention of popping and impedance rise.

UNLABELLED: Since myocardial lesion size during radio-frequency (RF) ablation is limited at high power by impedance rise when electrode tip temperature exceed 100 degrees C, controlling tip temperature by continuous intraelectrode saline infusion could permit generation of larger lesion. (1) Two dogs randomly received either standard or cooled tip RF ablation at 4 to 6 separate LV sites. Power output of 30 W was delivered via modified 7 Fr deflectable catheter with 4 mm tip for up to 120 sec or until impedance rise occurred. (2) Six dogs randomly received cooled tip RF ablation at power output of 20, 30, 40 W for 120 sec. (3) Three dogs randomly received cooled tip RF ablation using room temperature saline (21-25 degrees C) or chilled saline (1-4 degrees C) infusion. RESULTS: Overall, peak tip temperature was lower for cooled vs standard RF deliveries (97 +/- 17 degrees C vs. 42 +/- 8 degrees C). Lesion depth and volume were significantly larger for cooled burns. Lesion depth and volume and the incidence of abrupt impedance rise/popping did not differ between room temperature saline and chilled saline infusion. The catheter-tip temperature at the onset of popping and abrupt impedance rise was 54 +/- 5 degrees C (48-60 degrees C) and 59 +/- 10 degrees C (50-75 degrees C). CONCLUSION: Cooled tip RF current delivery at high power is associated with increased myocardial lesion size which may facilitate successful ablation of ventricular tachycardia associated with acquired structural heart disease. Catheter-tip temperature should be maintained below 45 degrees C to prevent popping and abrupt impedance rise during RF energy delivery.

Animals↗
PubMed2002

Relationship between polarity of the flutter wave in the surface ECG and endocardial atrial activation sequence in patients with typical counterclockwise and clockwise atrial flutter.

BACKGROUND: The relation between ECG and activation patterns within atria in typical atrial flutter (AFL) patients (pts) has not been defined due to the lack of simultaneous multisite right and left atrial mapping. METHODS: In 13 pts with AFL, a Halo catheter was positioned along tricuspid annulus and multipolar catheters were placed in right atrial appendage, His bundle region, coronary sinus (CS), proximal portion of right pulmonary artery (Bachmann's bundle region, BB) and esophagus (Eso) to record right and left atrial activation simultaneously. RESULTS: In counterclockwise (CCW) AFL (11 pts), 9 showed negative flutter wave (F) and 2 positive F in the inferior leads. CCW/negative F; CS electrograms (EGs) were proximal to distal, Eso EGs were inferior to superior and BB activation was later than CS and Eso. positive F; BB activation was earlier than CS. Eso EGs were superior to inferior or simultaneous. In clockwise (CW) AFL (7 pts), 5 showed positive F and 2 negative F. CW/positive F; BB activation preceded Eso and CS. Eso EGs were superior to inferior. CS EGs were proximal to distal (1), middle to proximal, distal (3) or proximal, distal to middle (1). negative F; CS EGs were proximal to distal. CS activation was earlier than BB or CS and BB activation were simultaneous. Eso EGs were inferior to superior. CONCLUSION: Impulse conduction to the left atrial free wall through either lower or upper interatrial connection is a major determinant of ECG morphology in AFL.

Adult↗
PubMed2002

Ectopic atrial rhythm with exit block following catheter ablation for focal atrial tachycardias in a patient with prior surgery for atrial septal defect.

The patient was a 40-year-old woman with a history of surgery for atrial septal defect and catheter ablation for typical atrial flutter. An electrophysiological study was performed because she had palpitation and syncope. She had ectopic atrial rhythm originating from low lateral RA. Two focal atrial tachycardias ([1] superior vena cava-RA junction and [2] a lowposteroseptal RA) were successfully ablated. Following catheter ablation for the second atrial tachycardia, she developed junctional rhythm because ectopic atrial rhythm showed exit block. However, atrial activation of junctional rhythm could conduct into the ectopic atrial rhythm focus and reset the rhythm when atrial activation of junctional rhythm reached the blocked line after atrial refractoriness by preceding ectopic atrial rhythm.

Adult↗
PubMed2002

Rate-dependent changes in atrial action potential duration after short- duration rapid atrial pacing in humans.

The effect of rapid atrial pacing on the rate adaptation of the atrial action potential duration was studied in humans. The right atrial monophasic action potential (RAMAP) of 5 patients was recorded before and after 30 min of rapid atrial pacing. The pacing cycle length (CL) was 146 +/- 9 ms, the shortest duration at which 1:1 capture was possible. The RAMAP duration at 90% repolarization (RMAPD) was measured. CL-dependent changes in RAMAPD (CL 600 ms-CL 300 ms) before and after rapid atrial pacing were 51.8 +/- 10.7 ms and 30.8 +/- 7.6 ms (p < 0.05), respectively.

Action Potentials↗
PubMed2002

Role of signal-averaged electrocardiograms for predicting the inducibility of ventricular fibrillation in the syndrome consisting of right bundle branch block and ST segment elevation in leads V1-V3.

Right bundle branch block and ST segment elevation (RBBB-STE) in the right precordial leads have been reported as a distinct clinical and electrocardiographic syndrome in patients prone to ventricular fibrillation (VF) in the absence of structural heart disease (Brugada syndrome). The purpose of the study was to investigate the role of signal averaged electrocardiogram (SAECG) in identifying patients at high risk among asymptomatic RBBB-STE patients. Thirteen patients with the RBBB-STE ECG were identified. Symptoms were: syncope (n=3, cases 1, 3, and 11), atypical chest pain (n=3, cases 4, 10, and 12) and palpitations (n=2, cases 6, and 7). The other 5 patients were asymptomatic. SAECG and programmed electrical stimulation (PES) were conducted in all patients. Body surface late potentials (LPs) were present in 7 of 13 patients before PES. Vf was induced in 6 of 7 LP positive patients. Vf was induced in 3 of 6 LP negative patients, but LP became positive in 2 of 3 patients in whom Vf was induced. One patient with syncope due to VF (case 1), 1 patient without symptoms who died suddenly during follow up (case 2), and 1 asymptomatic patient (case 9) showed reproducibly positive LP. In a patient (case 9) with positive LP at baseline, LP transiently became negative during follow up. In RBBB-STE patients, reproducibly positive LP is at risk for malignant ventricular arrhythmias and sudden death. Repeated SAECG recording may be useful for screening high-risk patients who should receive electrophysiological study among asymptomatic RBBB-STE patients.

Adult↗
PubMed2002

[Endocrine cell carcinoma (atypical carcinoid) of the ileocecal region adjacent to an adenocarcinoma].

An 86-year-old woman was admitted because of right lower abdominal pain. A 7 by 6 cm tumor palpable in the right lower quadrant was poorly mobile. Abdominal CT scan showed a huge tumor with a strong enhancement effect. Barium enema and colonoscopic examination revealed a submucosal tumor located from the cecum to the ascending colon on the oral side. An undifferentiated adenocarcinoma was suspected after examination of the biopsy specimen, right hemicolectomy was performed. The tumor invaded the retroperitoneal membrane. Histological examination showed a very atypical carcinoid tumor with central necrosis invading the veins. Pathohistologically, the huge tumor was diagnosed as endocrine cell carcinoma or atypical carcinoid. Furthermore, an elevated lesion, 2.5 cm in size, was revealed in the cecum closed to the huge tumor. Histological examination showed that the polypoid lesion was early moderately differentiated adenocarcinoma. There was no transition between the two tumors. The patient was discharged, but died of local recurrence 9 months after the surgery. Endocrine cell carcinoma of the large bowel is rare, in particular of the ileocecal region. Endocrine cell carcinoma of the ileocecal region adjacent to an adenocarcinoma without transition had not been reported previously in Japan.

Adenocarcinoma↗
PubMed2002

[Granulocytic sarcoma developing in lymph nodes].

A 77-year-old man was admitted to a hospital because of a left cervical tumor. He was initially diagnosed as having non-Hodgkin lymphoma, diffuse large cell type, Ann Arbor stage IV, and transferred to our hospital for chemotherapy. Flow cytometric analysis of the left axillary lymph node cells derived from a biopsy specimen showed that in addition to lymphoid surface markers (CD5, 7, 21), myeloid surface markers (CD11b, 33, 34) were also positive. The diagnosis of malignant lymphoma was therefore confirmed. The patient, was treated with THP-COP therapy, which proved very effective. Thereafter, a biopsy specimen was found to be positive for MT1 (CD43) staining but negative for myeloperoxidase and chloroacetate esterase staining on immunohistochemistry. Furthermore, no rearrangement of the IgH JH, TCR C beta 1 or TCR J gamma gene was detected by Southern blot analysis. On basis of these findings and the previous results of flow cytometry, we changed the diagnosis from malignant lymphoma to granulocytic sarcoma. THP-COP therapy was continued, and complete remission was achieved. Two months later, however, the patient developed acute myelocytic leukemia (AML M1) and received DCP therapy, but he died of pneumonia.

Aged↗