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Biomedical subjects

Go Watanabe

Publications and source records attributed to Go Watanabe.

At least 91 records · Page 5Linked to original sources

The effects of a specific neutrophil elastase inhibitor (ONO-5046) in pulmonary ischemia-reperfusion injury.

Ischemia-reperfusion injury is a significant problem in lung transplantation. Polymorphonuclear elastase derived from neutrophils plays a major mechanistic role in this process. Hence, we have investigated the effects of ONO-5046, a neutrophil elastase inhibitor, on ischemia-reperfusion injury. Fifteen rabbits were divided into three groups: 2 h of single left-lung perfusion (control group, n=3); 2 h of ischemia followed by 2 h of reperfusion (ischemic group, n=6); and drip intravenous administration of ONO-5046 during the 2 h of ischemia and 2 h of reperfusion (ONO-5046 group, n=6). Hemodynamic parameters were determined and a histopathological examination of the lung was performed. In the ONO-5046 group, arterial oxygen pressure, cardiac output, and tissue blood perfusion were higher and pulmonary vascular resistance was lower than in the ischemic group. The ONO-5046 group also showed large decreases in neutrophil infiltration, pulmonary edema, and intra-alveolar hemorrhage. Treatment with ONO-5046 improves lung function in a rabbit-lung ischemia-reperfusion model.

Animals↗

Doxycycline treatment in a model of early abdominal aortic aneurysm.

PURPOSE: To evaluate the effects doxycycline (Dox) in animal models of early abdominal aortic aneurysm. METHODS: Of 43 male Wistar rats, 33 underwent intraluminal perfusion of the abdominal aorta with thioglycolate plus plasmin to reproduce early aortic aneurysm. These rats then were treated for 7 days with subcutaneous injections of Dox or saline. The 10 remaining rats underwent intra-aortic perfusion with saline and were injected subcutaneously with saline. On day 7, the rats were killed after abdominal aortic diameters were measured. Some aortic specimens were examined microscopically after elastica van Gieson (EVG) and hematoxylin-eosin (H&E) staining. In other specimens, the matrix metalloproteinase (MMP) activity in tissue extracts was evaluated by gelatin zymography. RESULTS: Among the thioglycolate plus plasmin-perfused rats, the degree of aortic dilation was less in Dox-treated than in saline-treated rats. EVG staining indicated that Dox maintained a nearly normal pattern of elastic lamellae and normal medial elastin thickness. The aortic inflammatory response was not suppressed by Dox in H&E staining. In gelatin zymography, Dox reduced the MMP-9 activity, but did not significantly change either MMP-2 or the percentage of activated MMP-2. CONCLUSIONS: Dox inhibited experimental aneurysmal dilation by preserving medial elastin. This effect involved the suppression of MMP-9 but not of the MMP-2 activity.

Animals↗

Beating heart coronary artery bypass grafting: results from 402 patients and the usefulness of gastroepiploic artery composite grafting.

OBJECTIVES: We have studied the results of 402 consecutive cases of beating heart coronary artery bypass grafting (CABG) and evaluated the usefulness of gastroepiploic artery (GEA) composite grafts. METHODS: Between March 1993 and August 2001, 402 patients underwent beating heart CABG. They were 321 male and 81 female patients, aged 17 to 88 (mean 66) years. Beating heart CABG was facilitated by mechanical stabilization with a doughnut stabilizer, a newly designed sternal retractor and a new coronary perfusion system. Minimally invasive direct coronary artery bypass (MIDCAB) was performed in 206 patients (the MIDCAB Group), and beating heart CABG with median sternotomy (OPCAB) was performed in 196 patients (the OPCAB Group). RESULTS: Definite off-pump CABG was accomplished in 381 patients. 21 patients (5%) were converted to on-pump beating heart CABG using percutaneous cardiopulmonary system via femoral vessels because of hemodynamic instability. There was 1 operative mortality (0.2%). There was perioperative myocardial infarction in 2 (0.5%), and cerebral infarction in 3 (0.7%). The rate of complete revascularization was 78% in the MIDCAB Group and 97% in the OPCAB Group. The mean number of anastomoses was 1.6 in the MIDCAB Group and 3.3 in the OPCAB Group. The early graft patency was 99.1% in a left internal thoracic artery graft, 97.0% in a right internal thoracic artery graft, 96.5% in GEA, 98.2% in a radial artery graft, and 94.2% in a vein graft. A GEA composite graft was used in 55 of the 168 patients who received GEA grafting. The mean number of anastomoses for the GEA composite graft was 1.6 +/- 0.6 per patient. The graft patency rate was 94.6% (53/56) for GEA and 98.6% (72/73) for the radial artery used as a composite graft. CONCLUSION: A consecutive series of beating heart CABG was performed safely and effectively with a low mortality rate and low morbidity rate. Beating heart CABG could be performed in all patients, and definite off-pump CABG was accomplished in 95% of them. In order to aim for complete revascularization, GEA composite graft was found to be effective since it required a low mean number of 1.6 anastomoses and a satisfactory patency rate at the same time.

Adolescent↗

Myocardial ischemic preconditioning during minimally invasive direct coronary artery bypass grafting attenuates ischemia-induced electrophysiological changes in human ventricle.

OBJECTIVE: Ischemic preconditioning (IPC) has been found to protect the myocardium in animal studies. However, clinical studies have been limited and the clinical effects of IPC are still uncertain. The purpose of this study was to assess whether IPC has any protective effect on the human myocardium during minimally invasive CABG (MIDCAB), by means of epicardial electrophysiological testing. METHOD: Forty-five patients with left anterior descending artery disease who underwent a MIDCAB procedure were evaluated. In the present study, the electrical potentials which were not affected by cardio-pulmonary bypass or cardioplegia were measured. The ratio of longitudinal to transverse conduction velocity (phiL /phiT), and QT, JT dispersions were measured using plaque electrodes in the preischemic state, during a 5-minute coronary occlusion, during the subsequent 5-minute reperfusion, during 5- and 10-minute anastomosis periods, and after anastomosis. RESULT: The phiL/phiT was 2.2 +/- 0.2 at baseline. Anisotropy was exaggerated during the 5-minute coronary occlusion (2.6 +/- 0.3). During anastomosis, conduction velocities were decreased, but showed no further deterioration (2.4 +/- 0.3, and 2.4 +/- 0.3, respectively). QT and JT dispersions were improved by reperfusion. CONCLUSION: The effectiveness of IPC during the MIDCAB procedure was confirmed electrophysiologically. Anisotropy and dispersions were minimized after IPC, therefore IPC demonstrated antiarrhythmic protective effects on the human myocardium.

Aged↗

Thymic carcinoid tumor.

In this report on 3 cases of thymic carcinoid, tumors recurred in 2 patients not undergoing lymph node dissection. We review 47 cases of this disease taken from the Japanese literature, and discuss surgical procedures for reducing recurrence. In 9 of 20 cases of recurrence in encapsulated thymic carcinoid, lymph nodes were not dissected in eight. Differential diagnosis of an anterior mediastinal tumor should include thymic carcinoid, for which lymph nodes should be routinely dissected, even when the tumor is encapsulated.

Adult↗

The effects of an additive small amount of a low residual diet against total parenteral nutrition-induced gut mucosal barrier.

BACKGROUND: Total parenteral nutrition (TPN) negatively influences the gut mucosal barrier. It has been suggested that enteral nutrition is effective against the harmful influence. METHODS: Forty-eight male Donryu rats underwent placement of a central venous catheter and tube gastrostomy. They were divided into six groups, receiving isocaloric nutrients in various proportions of PN and a low residual diet (LRD) for 7 days. RESULTS: Intestinal permeability, villous height and crypt depth, and number of secretory IgA-positive cells in the villus were measured. Intestinal permeability was significantly reduced in rats receiving an LRD corresponding to more than 15% of total caloric intake. Gut morphological structure was maintained in rats receiving an LRD corresponding to more than 10%. A higher number of IgA-positive cells was observed in rats receiving an LRD corresponding to more than 15%. CONCLUSIONS: A small amount of LRD could prevent decreases in gut mucosal integrity. There was a stepwise defense mechanism in the gut mucosal barrier.

Amine Oxidase (Copper-Containing)↗

Use of the radial artery graft after transradial catheterization: is it suitable as a bypass conduit?

BACKGROUND: The suitability of the radial artery after transradial catheterization as a bypass conduit has been of great concern to surgeons. METHODS: A total of 67 patients underwent isolated coronary artery bypass grafting using the radial artery: 22 patients received preoperative transradial catheterization (group 1) and 45 patients did not receive transradial catheterization (group 2). Those patients were retrospectively reviewed. RESULTS: Patient characteristics, operative procedures, and early clinical outcome were not different between groups. The stenosis-free graft patency rates in groups 1 and 2 were 88% (16 of 18 patients) and 90% (38 of 42 patients) in the left internal thoracic artery (p = 0.87); 77% (17 of 22 patients) and 98% (48 of 49 patients) in the radial artery (p = 0.017); and 87% (13 of 15 patients) and 84% (21 of 25 patients) in the saphenous vein (p = 0.42), respectively. Intimal hyperplasia of the radial artery was observed in 68% (11 of 16 patients) in group 1 and in 39% (14 of 34 patients) in group 2 (p = 0.046). CONCLUSIONS: Transradial catheterization reduced early graft patency and caused intimal hyperplasia, although it did not affect early clinical outcomes. We suggest that the use of the radial artery as a bypass conduit after transradial catheterization should be undertaken cautiously.

Aged↗

Flow simulation of the intracoronary shunt tube for off-pump coronary artery bypass.

INTRODUCTION: To simulate blood flow provided by the intracoronary shunt tube, and to clarify whether this method is actually suitable for Off-pump coronary artery bypass (OPCAB), we investigated the efficacy of the intracoronary shunt tube in a theoretical model on the basis of fluid dynamics. METHODS: Fluid dynamics analysis was performed to simulate flow decrease after attachment on an intracoronary shunt model. RESULTS: The flow ratio in the case of turbulent flow is in proportion to the ratio of the inner diameter to the third power, and that in the case of laminar flow is in proportion to the ratio of the inner diameter to the sixth power. When this analysis is applied to commercial shunt tubes, coronary flow was estimated as approximately 2-14% of pre-attachment flow in turbulent flow, and only less than 0.1% in laminar flow. CONCLUSIONS: This result suggests that use of intracoronary shunt tubes in OPCAB may rarely contribute to maintenance of coronary flow, and they should be used carefully, especially in a jeopardized coronary artery.

Blood Flow Velocity↗

Validation of intra-operative detection of paratracheal lymph node metastasis using real-time RT-PCR targeting esophageal squamous cell carcinoma.

BACKGROUND: We previously reported that there was a significant correlation between paratracheal lymph node (LN) metastasis and cervical LN metastasis in thoracic esophageal squamous cell carcinoma (ESCC) patients. The purpose of this study was to establish an intra-operative detection method of LN micrometastasis (MM) of ESCC using hematoxylin-eosin (HE) staining, immunohistochemistry (IHC) and real-time RT-PCR with a Light Cycler technique, and to evaluate which method, or combination of methods, is most suitable for intra-operative detection of paratracheal LN MM. METHODS: Under informed consent, we obtained 33 dissected paratracheal LN samples from 22 operative patients with ESCC. Afterwards, one LN was separated into three parts by a sharp razor, and each part was checked for metastasis by HE staining, IHC with anti-cytokeratin antibody and real-time RT-PCR for SCC mRNA with a Light Cycler. RESULTS: It took 3 h for detection by real-time RT-PCR, while it took 2 h by IHC. The detection rates of MM by HE staining, IHC and real-time RT-PCR were 50.0, 33.3 and 83.3%, respectively. However, there was a case of false negative detection that was not detected by IHC or PCR. CONCLUSION: The real-time RT-PCR method was useful for intra-operative detection of paratracheal LN metastasis. However, combination analysis of HE staining, IHC and real-time RT-PCR may be desirable because there was a case of false negative detection by IHC and real-time RT-PCR.

Carcinoma, Squamous Cell↗

Protective effect of basic fibroblast growth factor against myocyte death and arrhythmias in acute myocardial infarction in rats.

The present study in rats investigated whether basic fibroblast growth factor (bFGF) plays an important role in cardioprotection against myocardial cell death and arrhythmias in acute myocardial infarction (AMI). After ligating the left coronary artery in 62 Wistar rats, 20 Eg of human recombinant bFGF was injected into the infarcted myocardium in 33 rats (group F), while saline was used for 29 control rats (group C). The development of ventricular tachyarrhythmias was assessed during the first 30 min of ischemia. After 24 h occlusion, the hearts of the surviving rats (group F: n=13, group C: n=10) were excised to assess minimum infarct wall thickness and infarct size, determine the number of TUNEL-positive cardiomyocytes and to analyze Bcl-2 and Bax expression by immunohistochemical staining and Western blotting. The incidence of ventricular tachycardia was higher in group C than in group F (p<0.05). The thinning ratio was higher in group F than in group C (p<0.05). There were fewer TUNEL-positive cardiomyocytes in the infarct border area in group F than in group C (p<.0001). Western blot analysis showed greater expression of Bcl-2 in group F than in group C (p<0.05), but similar expression of Bax in the 2 groups. In conclusion, intramyocardial administration of bFGF prevented ischemia-induced myocardial cell death and arrhythmias.

Animals↗

Cell culture in esophageal squamous cell carcinoma and the association with molecular markers.

PURPOSE: We reported previously that the patients in whom cancer cells could be cultured as continuous cell lines had a poor prognosis of esophageal squamous cell carcinoma (ESCC) patients. In this study, to evaluate additional evidence of prognostic significance and the genetic background of cell culture, we analyzed 203 ESCC patients. EXPERIMENTAL DESIGN: Culture samples were obtained from resected 203 primary ESCC (from 1986 to 1998; R0 resection). The expression of six molecular markers was evaluated retrospectively in resected primary esophageal tumors by immunohistochemical analysis, and the capability of establishing cell lines was compared. RESULTS: Thirty-five cell lines (17.2%) were established from 203 ESCC patients: group 1 (n = 35), from whom cancer cells could be cultured as continuous cell lines, and group 2 (n = 168), from whom cell lines could not be established. The cumulative survival rate of patients in group 1 was significantly lower than that of those in group 2 (P = 0.0006). Cox's proportional hazard model revealed that cell culture capability was an independent prognostic factor (risk ratio, 1.98; P = 0.007). Univariate logistic regression analysis revealed that cell culture capability had associations with the following molecular biological factors: cyclin D1, p53, murine double minute 2, p27, and fragile histidine triad gene (P < 0.05). However, multivariate logistic regression analysis revealed that p53 protein accumulation and MDM2 protein expression predict establishment of cell line in ESCC (odds ratio, 7.72 and 8.62, respectively). CONCLUSIONS: Cell culture capability is a significant prognostic factor in ESCC. p53 and MDM2 may have a crucial role in the establishment of ESCC cell lines.

Aged↗

Efficacy and adverse effects of the coronary active perfusion system--from a viewpoint of perfusional timing.

We developed a coronary active perfusion system (CAPS) to avoid myocardial ischemia during off-pump coronary artery bypass (OPCAB). The purpose of this study was to determine the optimal timing of CAPS perfusion, and to investigate any adverse effects when it is driven within the systolic phase. Twenty-four pigs were divided into four groups: (A) systolic, (B) early-diastolic, (C) middle-diastolic, and (D) late-diastolic perfusion. Myocardial blood flow (MBF), hemodynamic and mechanical data were measured during 30 minutes of CAPS perfusion. MBF in group A was lower than in the other groups (p<0.001), but no significant differences were observed among groups B to D. End-systolic pressure-volume relation (Mw) and preload recruitable stroke work relation (Ees) in group A was lower than in groups B to D (p<0.01 and p<0.05, respectively), but no significant differences were observed among groups B to D. CAPS could maintain regional MBF and left ventricular function if it was driven only within the diastolic phase and required no strict adjustment, but CAPS has an adverse effect when it is driven in the systolic phase.

Animals↗

Peripherally located occult lung cancer with AMFR expression.

A 67-year-old man was referred to our hospital because of positive sputum cytology. Despite detailed examination, the malignant cell source remained elusive. Twenty months later, CT revealed two nodules in the right S1 and S10 regions which were resected. A year following the operation, gastoendoscopy showed a stomach tumor. Total gastrectomy with lymph node dissection was performed. Histologically, this patient was diagnosed with double primary lung cancer with metastasis to the stomach. The tumors of the lung, stomach and tumor cells in the sputum showed the same immunoreactivities of autocrine motility factor receptor (AMFR). In our institution, of 38 occult lung cancers encountered during the past 10 years, four (10.5%) occurred in the peripheral region. The presented four cases of radiologically occult lung cancer in the peripheral resion revealed bad prognosis, as three out of four patients were dead within 24 months after surgery. All of the four cases showed venous invasion, though the size of the primary tumor was small. Careful follow-up, including monitoring for distant metastasis, is necessary in radiologically occult peripheral lung cancer.

Aged↗

Microsatellite instability in gastric cancer is closely associated with hMLH1 hypermethylation at the proximal region of the promoter.

Most sporadic gastric cancer with the microsatellite instability (MSI) phenotype is linked with hypermethylation (HM) of hMLH1. However, a part of gastric cancer with hMLH1 HM does not show MSI, suggesting a region-specific effect of hMLH1 promoter methylation on developing MSI. To test this possibility, we measured the methylation level in 3 distinct areas of hMLH1 promoter and compared them with MSI in 129 sporadic gastric cancer patients. Three areas of hMLH1 promoter, from distal toward proximal, were designated as hMLH1-A, hMLH1-B, and hMLH1-C, respectively. The methylation level was measured by fluorescence-based real-time methylation specific PCR. MSI status was tested using a panel of 5 microsatellite markers (BAT25, BAT26, D2S123, D5S346, and D17S250). Gastric cancers with no HM in hMLH1-A (n=105, 81.4%) also showed no HM in 2 other regions of hMLH1 promoter. On the other hand, the cancers with HM in hMLH1-A (n=24, 18.6%) showed various levels of methylation in 2 other regions. In most cases, the methylation value was the highest in hMLH1-A and the lowest in hMLH1-C. We found the MSI phenotype in 12 cancers (13%) of 92 tested cases and these cancers were all associated with HM in the region of hMLH1-C. A third of hypermethylated cancers in the hMLH1-A region did not show the MSI phenotype. The survival of the patients with HM in hMLH1-C was significantly better than that of patients without HM (P<0.05). These results suggest that HM in the proximal region of hMLH1 promoter, hMLH1-C in this study, plays a critical role in the progression of gastric cancer with MSI. The complete association between HM in hMLH1-C and MSI phenotype with gastric cancer provides an alternative diagnostic tool for detecting a favorable prognostic subgroup with MSI by using simple methylation analysis.

Adaptor Proteins, Signal Transducing↗

Spontaneous tracheal rupture associated with acquired tracheobronchomalacia.

We report here a very rare case of pneumomediastinum due to spontaneous tracheal rupture with tracheobronchomalacia. The patient was a 74-year-old woman who had suffered nocturnal dyspnea due to productive cough for five days prior to admission and had been treated with corticosteroids for five years at another hospital after being diagnosed with bronchial asthma. Computed tomographic scanning of the chest demonstrated over 1 cm longitudinal small air collections behind the upper trachea. Crescent-type tracheobronchomalacia was diagnosed by emergency bronchoscopy. At the right side of the upper trachea, a 1-cm laceration was revealed. Fibrin glue (Bolheal, Kaketsuken, Kumamoto, Japan) was sprayed on the laceration through an instrument of our design for endoscopic gluing and she was intubated for three days. Furthermore, treatment including administration of antibiotics, an antitussive agent, and a mucolytic agent, in addition to pulmonary physical therapy involving pursed lip breathing exercises and smoking cessation improved her complaints one month after admission.

Aged↗