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Biomedical subjects

Shigeru Oshima

Publications and source records attributed to Shigeru Oshima.

At least 55 records · Page 3Linked to original sources

Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells.

Intestinal epithelial cell-derived interleukin (IL)-7 functions as a pleiotropic and nonredundant cytokine in the human intestinal mucosa; however, the molecular basis of its production has remained totally unknown. We here showed that human intestinal epithelial cells both constitutively and when induced by gamma interferon (IFN-gamma) produced IL-7, while several other factors we tested had no effect. Transcriptional regulation via an IFN regulatory factor element (IRF-E) on the 5' flanking region, which lacks canonical core promoter sequences, was pivotal for both modes of IL-7 expression. IRF-1 and IRF-2, the latter of which is generally known as a transcriptional repressor, were shown to interact with IRF-E and transactivate IL-7 gene expression in an IFN-gamma-inducible and constitutive manner, respectively. Indeed, tetracycline-inducible expression experiments revealed that both of these IRF proteins up-regulated IL-7 protein production, and their exclusive roles were further confirmed by small interfering RNA-mediated gene silencing systems. Moreover, these IRFs displayed distinct properties concerning the profile of IL-7 transcripts upon activation and expression patterns within human colonic epithelial tissues. These results suggest that the functional interplay between IRF-1 and IRF-2 serves as an elaborate and cooperative mechanism for timely as well as continuous regulation of IL-7 production that is essential for local immune regulation within human intestinal mucosa.

5' Untranslated Regions↗

Evaluation of salvaged myocardium after acute myocardial infarction using single photon emission computed tomography after 201Tl-glucose-insulin infusion.

BACKGROUND: GIK-201Tl imaging reportedly improves the detection of viable myocardium, so the present study evaluated whether it can detect myocardial viability after acute myocardial infarction (AMI). METHODS AND RESULTS: Resting 201Tl and 99mTc-pyrophosphate (PYP) dual single photon emission computed tomography (SPECT) and 201Tl SPECT after 201Tl with GIK (10% glucose, insulin 5 U, and KCl 10 mmol) infusion (GIK-201Tl) were performed in 25 AMI patients within 10 days of admission. GIK-201Tl SPECT images were obtained immediately and 4 h after infusion. Left ventriculography (LVG) was performed within 3 weeks and at 6 months when follow-up 201Tl SPECT was also performed. From 20 SPECT segments, both the summed defect score (RDS) and the number of defect segments (ES) were calculated. The infarcted area was defined as 99mTc-PYP uptake segments. Wall motion was estimated in 7 LVG segments. The ES of R-201Tl (5.5 +/- 2.8), immediate GIK-201Tl (4.0 +/- 2.3), and 4-h GIK-201Tl (5.6 +/- 2.7) were lower than that of 99mTc-PYP (7.5 +/- 4.1) (p<0.05), and the ES had significantly declined 6 months later on 201Tl (3.5 +/- 2.8) (p<0.05). Although the RDS of R-201Tl (11.3 +/- 7.9) and 4-h GIK-201Tl (11.2 +/- 6.3) were greater than at the 6-month 201Tl (7.1 +/- 6.5), immediate GIK-201Tl (7.4 +/- 6.5) was equivalent to follow-up 201Tl. The sensitivity of immediate GIK-201Tl was highest among the imaging methods. CONCLUSION: To detect myocardial viability after AMI, early imaging with GIK-201Tl is more useful than resting 201Tl imaging.

Aged↗

Prevalence and electrocardiographic characteristics of idiopathic ventricular arrhythmia originating in the free wall of the right ventricular outflow tract.

BACKGROUND: The prevalence and ECG characteristics of idiopathic ventricular arrhythmia originating in the free wall of the right ventricular outflow tract (RVOT) require further clarification, which was the aim of the present study of 110 patients with idiopathic ventricular tachycardia (n=34) or premature ventricular contraction (n=76; OT-VT/PVC) who underwent successful catheter ablation at the RVOT. METHODS AND RESULTS: Ten OT-VT/PVCs (9%) were ablated successfully at the free wall (FW-VT/PVC); the remaining 100 (91%) were ablated at the RVOT septum (Sep-VT/PVC). R wave amplitudes in the inferior leads were significantly smaller in FW-VT/PVC than in Sep-VT/PVC (p<0.01). An RR' pattern in the inferior leads was observed significantly more often in FW-VT/PVC than in Sep-VT/PVC (p<0.001). QS-wave amplitude in each of leads V(1) to V(3) was significantly deeper in FW-VT/PVC than in Sep-VT/PVC (p<0.001). ECG criteria requiring an RR' pattern in all inferior leads as well as an S-wave amplitude of at least 3.0 mV in lead V(2) differentiated FW-VT/PVC from Sep-VT/PVC with high sensitivity, specificity, and predictive accuracy. CONCLUSIONS: Although FW-VT/PVC has a relatively low prevalence, it has several distinctive ECG characteristics and detailed ECG analysis can differentiate it from Sep-VT/PVC.

Adult↗

Factors predicting success in cryoablation of the pulmonary veins in patients with chronic atrial fibrillation.

BACKGROUND: This study was designed to investigate the factors predicting maintenance of sinus rhythm (SR) in patients with chronic atrial fibrillation (AF) undergoing cryoablation of the pulmonary veins (PV-cryo) during cardiac surgery. METHODS AND RESULTS: Seventy-seven patients with AF undergoing PV-cryo were recruited and divided into 2 groups based on whether they were able to maintain SR at discharge. The duration of AF (AF-D), left atrial dimension (LAd), and the average of the peak left atrial appendage outflow velocities (LAA-V) before surgery were determined for both groups. Group SR consisted of 54 patients (70%), and group AF consisted of 23 patients (30%). All patients with an AF-D 40 cm/s were in group SR and all those with an AF-D >10 years and LAd >or=65 mm were in group AF. Only 71% of patients with a LAA-V <or=20 cm/s were in group AF. CONCLUSIONS: Restoration of AF to SR by PV-cryo can be predicted from a knowledge of the AF-D, LAd and LAA-V.

Aged↗

[Does cardiac resynchronization therapy improve nitric oxide concentration in exhaled gas?].

OBJECTIVES: Cardiac resynchronization therapy (CRT) is widely known to improve cardiac function in patients with chronic heart failure, especially those with increased intraventricular conduction delay. However, whether vascular endothelial cell function is improved remains unknown. Capability of nitric oxide (NO) production is a good marker to evaluate endothelial cell function. Therefore, NO output was measured in exhaled air in patients with chronic heart failure after CRT. METHODS: Six patients with chronic heart failure and dilated cardiomyopathy (mean age 62.0 +/- 11.3 years, left ventricular ejection fraction 22.8 +/- 11.6%) received CRT. Pacing leads were lodged at the right atrium, the apex of the right ventricle and at the mid portion of the postero-lateral branch of the coronary sinus. One month after CRT, endtidal NO concentration was evaluated with and without pacing using the chemiluminescence method. RESULTS: Left ventricular ejection fraction improved from 22.8% to 28.8% after the procedure. Endtidal NO was significantly (p = 0.038) increased from 64.7-13.2 ppb without pacing to 69.1-14.1 ppb with pacing. Respiratory rate (with pacing: 19.7-5.7 n/min, without pacing: 20.3-4.8 n/min), tidal volume (with pacing: 523.2-122.7 ml, without pacing: 516.2-160.3 ml) and minute ventilation were not changed. CONCLUSIONS: CRT did not affect respiratory rate, tidal volume or minute ventilation, so increased endtidal NO did not result from enhanced production from tracheal and/or bronchial epithelial cells. Therefore, endtidal NO increased because chronic heart failure increased pulmonary perfusion and so raised vascular shear stress. CRT for patients with dilated cardiomyopathy can improve vascular endothelial cell function.

Aged↗

Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis.

The IL-7/IL-7R-dependent signaling pathway plays a crucial role in regulating the immune response in intestinal mucosa. Here we demonstrate the pivotal role of this pathway in the development and treatment of chronic colitis. T cells expressing high levels of IL-7R were substantially infiltrated in the chronic inflamed mucosa of TCR alpha-chain knockout mice and IL-7 transgenic mice. Transfer of mucosal T cells expressing high levels of IL-7R, but not T cells expressing low levels of IL-7R, from these mice into recombinase-activating gene-2(-/-) mice induced chronic colitis. Selective elimination of T cells expressing high levels of IL-7R by administrating small amounts of toxin-conjugated anti-IL-7R Ab completely ameliorated established, ongoing colitis. These findings provide evidence that therapeutic approaches targeting mucosal T cells expressing high levels of IL-7R are effective in the treatment of chronic intestinal inflammation and may be feasible for use in the therapy of human inflammatory bowel disease.

Adoptive Transfer↗

Superoxide radical generation and Mn- and Cu-Zn superoxide dismutases activities in human leukemic cells.

Mn- and Cu-Zn superoxide dismutase (SOD) activities and generation of superoxide radicals (O(2) (-)) were assessed in leukemic cells from 10 patients with acute myeloid or monocytic leukemia (AML) and 10 patients with acute lymphoblastic leukemia (ALL), using a sensitive, specific chemiluminescence method. Leukemic cells were classified according to the French-American-British classification. M4 AML cells from two patients produced some O(2) (-) upon stimulation with opsonized zymosan (OZ), phorbol myristate acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (FMLP), but less than normal granulocytes or monocytes. M5b AML cells from one patient produced as much O(2) (-) in response to these stimulants as normal monocytes. No O(2) (-) generation was induced in other types of leukemic cells. Total SOD activity in AML cells was significantly greater in normal granulocytes, but was only half of the activity in ALL cells. Mn-SOD in AML cells was very low or undetectable. These results suggest that except in M5b cells, decreased O(2) (-) production may contribute to susceptibility to infections in AML patients. Decreased Mn-SOD activity in AML cells may predispose them to oxidative stress.

Adult↗

Delayed recovery of left ventricular regional work after coronary angioplasty in patients with opposite wall old myocardial infarction.

To evaluate the changes in left ventricular (LV) regional function during acute ischemia in patients with opposite wall old myocardial infarction (OMI), we examined LV regional work during percutaneous transluminal coronary angioplasty (PTCA) of the left anterior descending artery (LAD) in patients with a posterior OMI. Twelve patients with normal LV contraction (group A) and six patients with posterior OMI (group B) who were scheduled to undergo PTCA were enrolled in this study. All patients had single-vessel coronary artery disease and no collateral circulation. Sixty-second inflation was performed, and data were collected every 10 s. The regional work was calculated from the relationship between the mean wall stress and area strain. Regional work of the interventricular septum decreased after balloon inflation and was at its minimum at the end of inflation (group A: 0.6 +/- 0.3 mJ/cm(3); group B: 0.8 +/- 0.4 mJ/cm(3)). After balloon deflation, the septal regional work increased in both groups, and recovered to baseline at 40 s in group A and at 60 s in group B. Regional work of the posterior wall increased in group A after balloon inflation, but not in group B. The recovery of LV regional work after PTCA is delayed in patients with opposite-wall OMI.

Adult↗

Sulfonated human immunoglobulin enhances CD16-linked CD11b expression on human neutrophils.

Intravenous human immunoglobulin therapy infrequently results in excessive inflammatory responses in vivo; these effects are not fully understood. We assessed whether sulfonated human immunoglobulin (SHIG) or polyethylene glycol-treated human immunoglobulin (PHIG) enhanced expression of inflammatory receptors on peripheral blood neutrophils in vitro, such as alphaMbeta2 (CD11b/CD18) and Fc gamma receptor type III (FcgammaRIII). CD11b and CD16 expression on neutrophils was measured by fluorescence flow cytometry. Various cytokines were assessed using a highly sensitive fluorescence microsphere system. SHIG enhanced/induced CD11b expression and partial aggregations on neutrophils, but PHIG did not. No detection of aggregation IgG was observed in SHIG and PHIG. SHIG-induced CD11b expression was inhibited by treatment of corticosteroid (dexamethasone) and by anti-CD16 monoclonal antibody. Concentrations of various cytokines such as interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, RANTES, tumor necrosis factor (TNF)-alpha, and interferon (INF)-gamma in culture supernatant were not significantly changed by SHIG or PHIG. SHIG and PHIG did not enhance CD16 on neutrophils. SHIG enhanced CD16-linked CD11b expression on neutrophils in vitro. CD11b induction was inhibited by dexamethasone and by anti-CD16 antibody. These in vitro results suggest that aggregations and enhancement of CD11b on neutrophils by SHIG may induce excessive inflammatory responses in vivo.

Antibodies↗

Nitric oxide exhalation correlates with ventilatory response to exercise in patients with heart disease.

AIMS: It is controversial whether or not pulmonary nitric oxide (NO) production, reflected in the end-tidal alveolar NO concentration, is diminished in patients with heart failure. Since pulmonary perfusion is regulated by NO production, decreased NO production in the pulmonary vasculature is assumed to result in diminished lung perfusion and further increases in ventilation-perfusion mismatch. The aim of this study is to investigate whether exhaled NO correlates with both exercise-induced hyperpnea and exercise tolerance in patients with heart disease. METHODS AND RESULTS: Forty-two patients with heart disease were enrolled (history of prior myocardial infarction (n=19), dilated cardiomyopathy (n=2), hypertensive heart disease (n=5) and prior open-heart surgery (n=16)). During cardiopulmonary exercise testing, exhaled air was collected and end-tidal NO (ETNO) was measured using a chemiluminescent method. Peak ETNO was found to correlate positively with both ventilatory anaerobic threshold (r=0.468) and peak VO(2) (r=0.562). The VE-CO(2) slope, which reflects the ventilatory response to exercise, correlated negatively with peak ETNO (r=-0.588). CONCLUSION: These data indicate that NO exhalation correlates, inversely, with the ventilatory response to exercise and directly with exercise intolerance, although the weakness of the correlation coefficient suggests there may be other possible mechanisms.

Exercise↗

Development and validation of an ECG algorithm for identifying the optimal ablation site for idiopathic ventricular outflow tract tachycardia.

INTRODUCTION: Idiopathic ventricular outflow tract tachycardia or premature ventricular contractions (OT-VTs) can originate from several different sites in the outflow tract, including the left ventricular (LV) endocardium and epicardium. The aims of this study were (1) to develop an ECG algorithm to predict the origin of OT-VT and (2) to test prospectively the accuracy of the algorithm. METHODS AND RESULTS: An algorithm was developed by correlating the 12-lead ECG findings with the catheter ablation site in 80 patients with OT-VT. The ECG characteristics of the QRS complex during the arrhythmia were analyzed. The catheter sites were verified by multi-plane fluoroscopy. The outflow tract was classified into six subdivisions: right ventricular (RV) septum, RV free wall, RV near the His-bundle region, LV endocardium, left sinus of Valsalva (LSV), and LV epicardium remote from the LSV. An OT-VT originating from the LV epicardium remote from the LSV was defined as an OT-VT in which the earliest ventricular activation was recorded at the LSV and radiofrequency ablation from the LSV failed. This algorithm subsequently was tested prospectively in 88 patients. Overall sensitivity was 88% and specificity was 95%. The positive and negative predictive values were 88% and 96%, respectively. CONCLUSION: We describe a new ECG algorithm having a high sensitivity and specificity to identify the optimal ablation site for idiopathic ventricular outflow tachycardia or premature ventricular contractions.

Adolescent↗

Failure to raise blood pressure during exercise is a poor prognostic sign in patients with hypertrophic non-obstructive cardiomyopathy.

Sudden cardiac death is a well-documented complication of hypertrophic cardiomyopathy and additionally, failure to raise blood pressure (BP) during exercise has been associated with a poor outcome. The present study group comprised 58 patients with hypertrophic non-obstructive cardiomyopathy (HNCM) who were receiving beta-blocker therapy. All patients underwent submaximal exercise radionuclide ventriculography (RNVG) to evaluate left ventricular (LV) function at both rest and peak exercise. Patients were divided into 2 groups based on the increase in systolic BP during exercise (ie, group A <30% or group N >/=30% of resting systolic BP) and were involved in long-term follow-up (10.4+/-4.0 years). Group A comprised 29% of the subjects. Age and workload at peak exercise were similar in the 2 groups. LV end-diastolic dimension was smaller and the interventricular septum was thicker in group A. LV ejection fraction on RNVG was similar in the 2 groups at rest and at peak exercise. During the follow-up period, more patients in group A than group N suffered syncopal attack (29% vs 5%, p<0.05) and cardiac sudden death (24% vs 2%, p<0.05). Patients with HNCM whose BP fails to rise during exercise have a poor prognosis.

Adrenergic beta-Antagonists↗

Segmental pulmonary vein isolation for paroxysmal atrial fibrillation improves quality of life and clinical outcomes.

The purpose of this study was to clarify the change in the quality of life (QOL) and clinical outcomes following segmental pulmonary vein (PV) isolation for paroxysmal atrial fibrillation (AF) in 50 patients with drug-refractory, paroxysmal AF. The left superior, left inferior, and right superior PVs were targeted for isolation in all patients, and the right inferior PV was isolated in 4 patients. AF recurred in 22 of 50 patients, and these patients were treated with class I or class III antiarrhythmic drugs that had been ineffective before the ablation procedure. The symptom severity and frequency was scored and the QOL was assessed using the Short-Form-36 questionnaire (SF-36) before the PV isolation and at the end of the follow-up period (6.0+/-3.0 months). PV isolation resulted in a reduction in the symptom severity (p<0.001) and symptom frequency (p<0.001) scores as compared with the pre-ablation values. Ninety percent of the patients had a >90% reduction in the frequency of symptomatic episodes of AF after the ablation procedure. The mean SF-36 physical and mental component summary scores also significantly improved after PV isolation as compared with the pre-ablation values (both for p<0.001). With a segmental isolation approach that targets at least 3 PVs, satisfactory improvement in the symptoms and QOL can be achieved in patients with drug-refractory, paroxysmal AF.

Aged↗

Effectiveness of thrombectomy before stent implantation in acute myocardial infarction.

Percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) may cause distal embolization, with deterioration of distal flow and further extension of the infarct. The purpose of the present study was to evaluate the effectiveness of pretreatment by thrombectomy on myocardial salvage after stent implantation in patients with AMI. From January 2000 to July 2002, 209 consecutive patients with AMI successfully underwent emergency stent implantation. They were divided into 2 groups: those treated in the year before the introduction of the thrombectomy device (Group A; n=109), and those treated the year after introduction of the device (Group B; n=100). Follow-up quantitative coronary angiography (QCA) and left ventriculography were carried out 6 months after PCI. Microvascular circulation after revascularization was assessed by Thrombolysis in myocardial infarction (TIMI) flow grade analysis, the maximum creatine kinase concentration was recorded, and the follow-up left ventricular ejection fraction and ST segment score were assessed on the 12-lead electrocardiography just before revascularization and on return to the coronary care unit. The QCA data, rate of restenosis (% restenosis) and rate of target lesion revascularization were also compared between the 2 groups. The results demonstrated that the introduction of thrombectomy had increased the number of patients who displayed blush-3 after primary angioplasty, which suggests that thrombectomy before stent implantation has the potential to minimize myocardial ischemic insult, presumably by protecting the coronary microvasculature.

Aged↗

Macrophage-derived IL-18 targeting for the treatment of Crohn's disease.

Crohn's disease is an inflammatory bowel disease associated with several changes in the immune system, including an increased number of infiltrating macrophages. These macrophages release a variety of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha, macrophage infiltrating factor (MIF), interleukin (IL)-6, IL-12 and IL-18, which are critically involved in the onset and the development of Crohn's disease. We here focus on the role of macrophages, especially macrophage-derived IL-18 in both patients with Crohn's disease and a murine model of Crohn's disease.

Animals↗

Impedance cardiography and quantitative tissue Doppler echocardiography for evaluating the effect of cardiac resynchronization therapy: a case report.

An 83-year-old woman presented with dilated cardiomyopathy. Cardiac resynchronization therapy was performed. Two weeks later, cardiac output and ventricular wall motion were estimated using impedance cardiography and tissue Doppler echocardiography with and without pacing. Cardiac output increased from 3.5 to 4.5 l/min during biventricular pacing with a 120 msec atrioventricular interval. Intraventricular phase difference for contraction decreased from 190 to 150 msec. When the atrioventricular interval was 180 msec, cardiac output and phase difference became 4.6 l/min and 170 msec. These assessments were performed rapidly and non-invasively. New impedance cardiography and tissue Doppler echocardiography are useful to evaluate the effect of cardiac resynchronization therapy.

Aged↗

Efficacy of carvedilol treatment on cardiac function and cardiac sympathetic nerve activity in patients with dilated cardiomyopathy: comparison with metoprolol therapy.

UNLABELLED: Carvedilol and metoprolol have been reported to be effective in the treatment of patients with chronic heart failure. However, to our knowledge, there have been no studies comparing the effects of the 2 drugs on cardiac function, including cardiac sympathetic nerve activity. METHODS: We compared 15 patients with dilated cardiomyopathy (DCM) who were receiving carvedilol (group A) with 15 patients with DCM who were receiving metoprolol (group B). Before and after 1 y of treatment, cardiac (123)I-metaiodobenzylguanidine ((123)I-MIBG) uptake was assessed using the total defect score (TDS) and the heart-to-mediastinum (H/M) activity ratio from the delayed images. The New York Heart Association (NYHA) class and echocardiographic left ventricular ejection fraction (LVEF) also were assessed. RESULTS: In both groups, the TDS decreased (in group A, from 25 +/- 14 to 16 +/- 14, P < 0.01; in group B, from 27 +/- 9 to 19 +/- 10, P < 0.01), the H/M increased (in group A, from 1.67 +/- 0.31 to 2.01 +/- 0.36, P < 0.01; in group B, from 1.68 +/- 0.21 to 1.93 +/- 0.32, P < 0.01), the LVEF increased (in group A, from 31% +/- 10% to 48% +/- 10%, P < 0.01; in group B, from 28% +/- 9% to 47% +/- 15%, P < 0.01), and the NYHA functional class improved (in group A, from 2.9 +/- 0.3 to 1.7 +/- 0.5, P < 0.01; in group B, from 2.8 +/- 0.6 to 1.7 +/- 0.6, P < 0.01). The change in LVEF was mildly correlated with the change in the TDS in group A (r = 0.41) as well as in group B (r = 0.53). In the patients with a favorable response in the TDS or H/M, the NYHA class improved more than in the patients without a favorable response (P < 0.05). CONCLUSION: Carvedilol treatment can improve cardiac function, symptoms, and cardiac sympathetic nerve activity in patients with DCM to a similar extent as metoprolol treatment. The improvement of cardiac function and symptoms is related to the improvement of cardiac sympathetic nerve activity.

3-Iodobenzylguanidine↗