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Biomedical subjects

Hiroshi Inoue

Publications and source records attributed to Hiroshi Inoue.

At least 55 records · Page 3Linked to original sources
PubMed2006

Bradycardia-dependent ECG changes in Brugada syndrome.

BACKGROUND: In patients with Brugada syndrome (BS), ventricular fibrillation (VF) occurs mainly during sleep; therefore, not only vagal activity but also bradycardia dependent changes in ECG may relate to the nighttime occurrence of VF. The present study aimed to examine the difference in bradycardia-dependent changes in the ECG of symptomatic and asymptomatic BS patients. METHODS AND RESULTS: Twenty-one patients with BS were categorized into symptomatic (n = 9) and asymptomatic (n = 12) groups. During the electrophysiologic study, the ECG changes were evaluated at RR intervals of 400, 600, 750, 1,000 and 1,100 ms during extrastimulation from the right atrium. The ST levels in V2, and the QT interval in both V2 and V5 were measured. Along with an increase in the RR interval from 400 to 1,100 ms, the ST levels in V2 increased in both groups; the increase did not differ between the 2 groups. In both leads V2 and V5, the prolongation of the QT interval along with an increase in the RR interval from 400 to 1,100 ms was significantly smaller and the QT intervals at an RR interval of 1,100 ms were significantly shorter in the symptomatic than in the asymptomatic group. CONCLUSIONS: In patients with BS, the ST elevation was augmented during bradycardia to a similar extent in both symptomatic and asymptomatic patients. However, a inhibited prolongation of the QT interval during bradycardia was characteristic of symptomatic patients. These unique repolarization dynamics could relate to the nighttime occurrence of VF during bradycardia in patients with BS.

Adult↗
PubMed2006

Brief episode of myocardial ischemia before prolonged ischemia attenuates cardiac sympathetic nerve injury.

BACKGROUND: The aim of this study was to investigate the effects of brief ischemia before prolonged ischemia on cardiac sympathetic neural function. Brief ischemia inhibits the sympathetic neural release of norepinephrine (NE) during subsequent sustained ischemia. However, whether it can attenuate the neural function after sustained ischemia remains unknown. METHODS AND RESULTS: Sympathetic neural function was assessed using 123I-metaiodobenzylguanidine (MIBG) in patients who with (Group I) or without angina (Group II) within 3 days prior to acute myocardial infarction. In the rat experiment, cardiac interstitial NE (iNE) with or without pretreatment of 5-min coronary ligation was determined during a 30-min occlusion. Differences between MIBG and Thallium-201 for the total defect score were significantly greater in Group II than in Group I (6.1 +/- 4.0 vs 0.4 +/- 4.4). Levels of iNE were less in rats with a 5-min pretreatment (7.3 +/- 2.3 vs 18.6 +/- 5.9 x 10(3) pg/ml, p < 0.01) and MIBG uptake of ischemic region was greater (0.061 +/- 0.029 vs 0.031 +/- 0.011 %kg dose/g, p < 0.05) compared with rats without the pretreatment. CONCLUSION: A brief episode of ischemia attenuates the sympathetic neural injury caused by subsequent prolonged ischemia and this protective effect is associated with attenuation of NE release during the prolonged ischemia.

3-Iodobenzylguanidine↗
PubMed2006

Rate control and quality of life in patients with permanent atrial fibrillation: the Quality of Life and Atrial Fibrillation (QOLAF) Study.

BACKGROUND: The present study aimed to determine whether quality of life (QOL) in permanent atrial fibrillation (AF) patients would be improved by monotherapy with beta-blocker (BB) or calcium antagonist (CAA) as compared with digitalis. METHODS AND RESULTS: Twenty-nine patients with permanent AF under digitalis were randomized into BB (bisoprolol, atenolol or metoprolol) or CAA (verapamil) monotherapy treatment group. Twenty-five were men and the mean age was 67+/-8 years. After the assigned monotherapy, 12 patients received the other monotherapy in a cross-over fashion. Under each treatment, efficacy of rate control was determined by Holter electrocardiogram (ECG), treadmill testing and QOL questionnaire (Short Form-36 (SF-36) and Quality of Life of Atrial Fibrillation (AFQLQ)), and compared with the baseline digitalis treatment. CAA significantly increased mean and minimum heart rate (HR) in Holter ECG as compared with digitalis, whereas BB increased only minimum HR. Exercise duration in treadmill testing was significantly prolonged by CAA treatment, although it only tended to be prolonged by BB treatment. CAA but not BB improved role function-physical score of SF-36, and frequency and severity of symptoms of AFQLQ. CONCLUSION: These results indicate that CAA is preferable to digitalis when monotherapy is selected for short-term improvement of QOL and exercise tolerance in patients with permanent AF.

Adrenergic beta-Antagonists↗
PubMed2006

Matrix metalloproteinase-1 produced by human CXCL12-stimulated natural killer cells.

Natural killer (NK) cells play a key role in inflammation and tumor regression through their ability to migrate into tissues. CXCL12 is a chemokine that promotes lymphocyte invasion and migration into tissues; however, the mechanism for this process remains incompletely understood. In this study, we show that CXCL12 significantly enhanced CD16(+)CD56(+) human peripheral NK-cell invasion into type I collagen by the catalytic activity of matrix metalloproteinase-1 (MMP-1). Confocal immunofluorescence and co-immunoprecipitation studies suggest that MMP-1 colocalized with alpha(2)beta(1) integrin on CXCL-12-stimulated NK-cell surface. The binding of pro-MMP-1 with alpha(2)beta(1) integrin required activation of G(i)-coupled pathway. However, the production of MMP-1 from CXCL12-stimulated NK cells was mediated by p38 and mitogen-activated or extracellular signal-regulation protein kinase kinase 1/2 in a manner independent of the G(i)-coupled pathway. These results suggest that CXCL12/CXCR4 interaction transduces the two signaling pathways to promote NK-cell invasion, which stimulates pericellular degradation of extracellular matrix proteins by membrane-associated MMP-1. The mechanisms would thus play a role in facilitating lymphocyte trafficking and accumulation in tissues during physiological and pathological processes.

CD56 Antigen↗
PubMed2006

Differential gene expression profiles of radioresistant pancreatic cancer cell lines established by fractionated irradiation.

Identification of the genes that are differentially-expressed between radiosensitive and radioresistant cancer cells is important to the ability to predict the clinical effectiveness of radiotherapy. We established radioresistant human pancreatic cancer cell lines using fractionated irradiation in order to identify genes that are differentially-expressed between parental lines and radioresistant cell sublines. Six pancreatic cancer cell lines (PK-1, PK-8, PK-9, T3M4, MiaPaCa2 and PANC-1) were treated with 10 Gy fractionated irradiation at approximately two-week intervals (total dose 150-180 Gy). Five radioresistant sublines (PK-1, PK-8, PK-9, T3M4, and MiaPaCa2) were successfully established. Using oligonucleotide microarrays containing 17,086 genes, we identified 73 up-regulated genes and 55 down-regulated genes common to radioresistant sublines. Subsequent analysis by quantitative RT-PCR confirmed the reliability of our microarray strategy. Up-regulated genes were associated with growth factor (example, amphiregulin), cell-cycle check point (MAPKAPK2), intracellular signaling pathway (regucalcin), and angiogenesis stimulation (angiopoietin 2). Down-regulated genes were associated with apoptosis (caspase 8), retinoid esterification (lecithin retinol acyltransferase), and electron transport (calcium-activated chloride channel 1). Some of these genes have known association with response to radiation, such as caspase 8 and MAPKAPK2, but others are novel. Global gene analysis of radioresistant sublines may provide new insights into the mechanisms underlying clinical radioresistance and to improving the efficacy of radiotherapy for pancreatic cancer.

Apoptosis↗
PubMed2006

[A questionnaire report concerning the actual situation of respiratory physicians in Japan].

A nation-wide questionnaire was carried out at the end of 2004 to elucidate the actual situation of respiratory physicians in Japan. The questionnaires were characterized by simultaneously looking into the actual situation in the departments of respiratory medicine, cardiology and gastroenterology. The number of the surveyed institution was 168, from which questionnaire replies were obtained from 79 general hospitals, 39 university hospitals and 10 hospitals mainly for tuberculosis. In general hospitals, compared to the departments of cardiology and gastroenterology, the full-time physician staff in the department of respiratory medicine per 10 inpatient beds was only 60.9% and 79.4%, while specialist staff were 54.9% and 68.4%, respectively. The numbers of deaths in the department of respiratory medicine per 10 inpatient beds were 186.9% and 132.6%, compared with in the departments of cardiology and gastroenterology, while those per full-time physicians were 271.9% and 148.5%, respectively. Thus, it was concluded that there was an obvious shortage in number of not only in respiratory specialists but also of all respiratory physicians. Furthermore, respiratory physicians were taking care of more severe patients than other colleagues.

Cardiology↗
PubMed2006

Expression of the TRAG-3 gene in human esophageal cancer: the frequent synchronous expression of MAGE-3 gene.

We previously reported some cancer testis antigens, especially for MAGE genes, to be expressed in a relatively high population of gastro-intestinal and breast cancers. TRAG-3 (Taxol resistant associated gene-3) may be another cancer testis antigen; however, its expression has still not been fully studied. The TRAG-3 expression was evaluated in a total of 57 cancer cell lines and 322 cancer samples of gastrointestinal and breast cancers by RT-PCR. TRAG-3 was expressed in 23/57 (40%) of the cell lines: the highest expression was found in gastric cancer (6/9: 67%), followed by esophageal (13/28: 46%), colon (3/11: 27%) and liver (1/4: 25%) cancers. In clinical samples, the expression was the highest in esophageal cancer (32/58: 55%), followed by liver (13/50: 26%), bile duct (5/27: 19%), gastric (5/50: 10%), breast (5/50: 10%) and colon (2/87: 2.3%) cancers. The TRAG-3 expression significantly correlated with the expression of MAGE-3 in esophageal cancer (p<0.05). As the TRAG-3 gene is located on Xq28, which is the same locus as the MAGE gene family, we found a frequent synchronous expression pattern with TRAG-3 and MAGE-3 in esophageal cancer.

Antigens, Neoplasm↗
PubMed2006

Poor outcome of patients with pulmonary adenocarcinoma showing decreased E-cadherin combined with increased S100A4 expression.

A loss or reduced expression of E-cadherin, the main cell-to-cell adhesion molecule, correlates with distant metastasis in various cancers. Recent studies have reported a close correlation between the expression of E-cadherin and that of S100A4, calcium-binding protein. In this study, we investigated the expression of E-cadherin and S100A4 status in relation to the clinicopathological parameters of pulmonary adenocarcinoma. We finely and quantitatively examined the expression of E-cadherin and S100A4 using real-time polymerase chain reaction (PCR) in a total of 92 pulmonary adenocarcinomas obtained by surgical resection. All of the pulmonary adenocarcinomas showed significant expression of E-cadherin and S100A4. Real-time PCR showed lower E-cadherin expression in 21 adenocarcinomas, while 71 adenocarcinomas expressed a higher expression of E-cadherin. Of 21 adenocarcinomas with lower-expressing E-cadherin, 12 showed a higher expression of S100A4. These 12 cases significantly showed a poorer prognosis than others (p=0.047, Kaplan-Meier, log-rank test) and significantly showed more frequent venous involvement than others (p=0.042, chi2 test). These results suggested that reduced E-cadherin expression combined with higher S100A4 expression is related to a poor prognosis through hematogenous metastasis in pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed2006

[Effects of proton pump inhibitor on airway hyperresponsiveness in asthmatics with gastroesophageal reflux].

BACKGROUND: Previous data suggest the high incidence of gastroesophageal reflux (GER) in asthmatics, although the relationship between GER and the respiratory condition in asthmatics remain unclear. We investigated the incidence of GER in asthmatics and the association between the effects of proton-pump inhibitor (PPI) on respiratory functions and esophageal pH in asthmatics with GER. METHODS: Two hundreds ninety outpatients who attended our unit with asthma received GER symptoms questionnaire used at Mayo Clinic. Twenty three of them who answered to have any GER symptom were treated with PPI (lansoprazole 30 mg/day) for eight weeks, and investigated changes in the GER symptoms and peak expiratory flow rates (PEFR) before and after treatment. Furthermore, in six of twenty three, airway hyperresponsiveness to methacholine and esophageal pH monitor for 24 hours were measured in order to evaluate the association between esophageal pH and the effect of PPI on GER during the test. Furthermore, the serum level of theophylline was analyzed for assessment of the PPI effect on theophylline metabolism. RESULTS: 150 of 290 asthmatics had answered to have any GER symptom including cough. Most of GER symptoms had improved except for cough after treatment with PPI. The airway hyperresponsiveness significantly improved after treatment with PPI (n=6, p<0.03), although PEF and FEV1 were not significantly changed. CONCLUSION: These results suggest that PPI may be an effective drug for asthmatics with GER through suppression of airway hyperresponsiveness.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2006

[Cytoprotective effects of heat shock protein-70 in bronchial epithelium against neutrophil elastase-induced cell injury].

BACKGROUND: Neutrophil releases several mediators during inflammation, including neutrophil elastase (NE) that impairs bronchial epithelial function. The stress response and stress proteins protect cells against a variety of cytotoxic conditions. Accordingly, we tested the hypothesis that bronchial epithelial heat shock protein (Hsp-70) would protect a NE-induced cell injury. METHODS: Bronchial epithelial cells (BECs) obtained by bronchial brushing under bronchoscopy were cultured and used for experiments. Expression of Hsp-70 in BECs was confirmed by Western blot and flowcytometric analysis. To test Hsp-70 in BECs, induction of Hsp-70 protein into BECs was carried out by liposome-based delivery system. Introduction of Hsp-70 into BECs were examined by direct fluorescence microscope examination and flowcytometric analysis. NE-induced cytotoxicity was evaluated by cell culture supernatant LDH assay and cell detachment assay. RESULTS: Higher expressions of Hsp-70 were observed in BECs, which were induced by sodium arsenite. Over expression of Hsp-70 in BECs reduced NE-induced cell injury. Introduction of Hsp-70 protein into BECs by liposomal delivery decreased LDH release, and inhibited necrosis and apoptosis of the cells by NE as compared to untreated control. CONCLUSION: These data suggested that Hsp-70 in BECs may inhibit NE-induced airway epithelial damage. Liposomal delivery of Hsp-70 into BECs may be a possible means of protecting bronchial epithelium against inflammatory airway diseases including acute and chronic bronchitis.

Bronchi↗
PubMed2006

[Practice and education in thoracoscopic surgery].

There are 2 vectors in training in thoracoscopic surgery. One is a paradigm in which training is patterned on education in laparoscopic surgery centered on young surgeons, and the other is a paradigm in which introduction of thoracoscopic surgery is promoted among thoracic surgeons who are already active on the front line. Although the demand, degree of need, and content of each of these paradigms differ, the ultimate goal is the same. Thus, it is important to prepare a system that combines safer operations and less invasive surgical techniques, and haste is being made to prepare a society-initiated program. Publication of thoracoscopic surgery techniques that overcomes the barriers of university and school and support of technical standards are desirable, and we think that achieving this will be linked to the standardization of techniques.

General Surgery↗
PubMed2006

Efficient induction of specific cytotoxic T lymphocytes to tumor rejection peptide using functional matured 2 day-cultured dendritic cells derived from human monocytes.

Dendritic cells (DCs) are powerful antigen-presenting cells (APCs), that have so far been applied for cancer specific immunotherapy. Recent results suggest that matured DCs derived from human monocytes have a significant impact on the outcome of vaccination. The conventional generation of mature DCs from human monocytes in vitro has been reported to require 5 days for differentiation with granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and 2 days for stimulation. We herein report a new strategy for the functional maturation of monocyte-derived DCs within only 2 days of in vitro culture and the induction of specific cytotoxic T lymphocytes (CTLs) to tumor rejection peptide. The monocytes were incubated for 1 day with GM-CSF and IL-4, followed by activation with a bacterial product, OK-432 and prostaglandin E2 (PGE2) for another 1 day (rapid DC). Rapid DC expressed mature DC surface markers as well as chemokine receptor 7 and secreted Th1-type cytokines. The DCs generated in this study mobilized Ca2+ in response to CCL21/6Ckine and SDF-1, but only marginally did so to Mip-1alpha. Moreover, when rapid DC were compared with mature conventional 7-day DCs, they were equally potent in inducing specific CTLs in vitro. These results indicate that the rapid DC is as effective as the monocyte-derived conventional DCs. The rapid DC would be a potentially useful new cancer-specific immunotherapy.

Antigens, Neoplasm↗
PubMed2006

Gene expression profiling of lymph node metastasis by oligomicroarray analysis using laser microdissection in esophageal squamous cell carcinoma.

We applied oligomicroarray analysis of 17086 genes to identify the genes related to lymph node metastasis in esophageal squamous cell carcinoma (ESCC). The samples of cancer and non-cancerous paired tissue were taken from 16 patients with ESCC who underwent esophagectomy with lymph node dissection. Total ribonucleic acid was extracted from the cancer cells obtained by using laser microdissection and was amplified by T7 based-amplification for the application to the oligomicroarray. The oligomicroarray demonstrated 43 overexpressed genes, such as cell-cycle regulators, cell adhesion related genes, anti-apoptosis related genes, and 138 suppressed genes such as cell differentiation related and apoptosis related genes in ESCC cells with lymph node metastasis. Among them, 5 overexpressed genes (SPP-1, CKS2, CCT5, STMN1, NDUFB9) and one suppressed expression gene (GJB2) were selected in the gene profiles, and then the expressions of those genes were confirmed by real-time semi-quantitative reverse transcriptional polymerase chain reaction (RT-PCR) method for confirmation of the result not only in study cases but also in additional 21 cases. The gene expression by real-time semi-quantitative RT-PCR was in accordance with the microarray data. Although we were able to extract some genes related to nodal metastasis in ESCC, further examination is necessary in other genes as well as the interaction of stromal tissues.

Aged↗
PubMed2006

[Clinical features, neuroimaging and prognosis of adult patients with clinically diagnosed acute-onset encephalitis treated at a teaching neurology center in the Toyama area of Japan].

Although acute viral encephalitis (AVE) and acute disseminated encephalomyelitis (ADEM) are etiologically and pathologically distinct, a differential diagnosis between these two disorders is often difficult, especially if the patient exhibits a disturbance in consciousness. To identify useful clinical differences enabling a differential diagnosis to be made at an early stage, we retrospectively analyzed patients who had been admitted to our hospital within the past seven years because of acute-onset encephalitis with a disturbance in consciousness. Eleven adult patients were classified as having AVE, and 8 adult patients were classified as having ADEM within this period. The clinical characteristics of the two groups were then compared. Patients with AVE exhibited a disturbance in consciousness as their first neurological sign, whereas patients with ADEM initially showed focal signs like spastic paralysis, urinary disturbance and ataxia, which were followed by a disturbance in consciousness. ADEM is usually preceded by infection or vaccination, but obtaining a medical history from patients with disturbed consciousness is often difficult Based on the present analysis, the initial manifestation of focal neurological signs may be very useful for distinguishing ADEM from AVE.

Acute Disease↗
PubMed2006

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2004)].

From October 2004 to September 2005, we collected the specimen from 319 patients with lower respiratory tract infections in 12 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 383 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 381 strains were examined. The breakdown of the isolated bacteria were: Staphylococcus aureus 87, Streptococcus pneumoniae 80, Haemophilus influenzae 78, Pseudomonas aeruginosa (non-mucoid) 35, P. aeruginosa (mucoid) 9, Klebsiella pneumoniae 15, Moraxella subgenus Branhamella catarrhalis 30, etc. Of 87 S. aureus strains, those with 2 microg/mL or less of MIC of oxacillin (methicillin-sensitive S. aureus: MSSA) and those with 4 microg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 40 (46.0%) and 47 (54.0%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all the strains at 0.063 microg/mL. Against MRSA, vancomycin showed the most potent activity and inhibited the growth of all the strains at 1 microg/mL. Arbekacin (ABK) also showed the potent activity and its MIC90 was 2 microg/mL. Carbapenems showed the most potent activities against S. pneumoniae and inhibited the growth of all the strains at 0.25-0.5 microg/mL. Cefozopran (CZOP) also had a preferable activity (MIC90: 1 microg/mL) and inhibited the growth of all the strains at 2 microg/mL. In contrast, there were high-resistant strains (MIC: 128 microg/mL or more) for ABK (2.5%), erythromycin (37.5%), and clindamycin (38.8%). Against H. influenzae, levofloxacin showed the most potent activity and inhibited the growth of all the strains at 0.125 microg/mL. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and inhibited the growth of all the strains at 2 microg/mL. Against P. aeruginosa (non-mucoid), amikacin (AMK) had the most potent activity and its MIC90 was 4 microg/mL. The activity of CZOP against the non-mucoid type also was preferable and its MIC90 was 8 microg/mL. Against K. pneumoniae, CZOP, cefmenoxime, cefpirome, flomoxef were the most potent activity and inhibited the growth of all the strains at 0.063 microg/mL. Also, all the agents generally showed a potent activity against M. (B.) catarrhalis and the MIC90 of them were 4 microg/mL or less. The approximately half the number (57.0%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 50.8% and 23.8% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (21.6%), S. pneumoniae (24.7%) and H. influenzae (20.1%). S. aureus (20.9%), S. pneumoniae (16.1%), and H. influenzae (16.1%) also were relatively frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (22.3%) and H. influenzae (25.1%). The bacteria relatively frequently isolated from the patients treated with macrolides were P. aeruginosa and the isolation frequency was 43.5%.

Aged↗