Discovery of

The new isotope ^{39}Na, the most neutron-rich sodium nucleus observed so far, was discovered at the RIKEN Nishina Center Radioactive Isotope Beam Factory using the projectile fragmentation of an intense ^{48}Ca beam at 345 MeV/nucleon on a beryllium target. Projectile fragments were separated and identified in flight with the large-acceptance two-stage separator BigRIPS. Nine ^{39}Na events have been unambiguously observed in this work and clearly establish the particle stability of ^{39}Na. Furthermore, the lack of observation of ^{35,36}Ne isotopes in this experiment significantly improves the overall confidence that ^{34}Ne is the neutron dripline nucleus of neon. These results provide new key information to understand nuclear binding and nuclear structure under extremely neutron-rich conditions. The newly established stability of ^{39}Na has a significant impact on nuclear models and theories predicting the neutron dripline and also provides a key to understanding the nuclear shell property of ^{39}Na at the neutron number N=28, which is normally a magic number.

[Knack and pitfall in valve replacement].

We choose prosthetic or bioprosthetic valves according to AHA/ACC guidelines in valve replacement. It is important to remove only the calcification and avoid over-resection to preserve the valve annulus during aortic valve replacement. We leave posterior leaflet as well as basal chordae in mitral valve replacement in case of large mitral annulus. Sutures should be tied-down after those on both adjacent sides are pulled up and the sawing cuff and annulus are firmly attached. Intra-operative transesophageal echocardiography is useful for detecting a stack valve, perivalvular leakage and remnant air in the cardiac chambers. We performed 53 cases of valve replacement in 2009. One patient (1.9%) died because of ventricular arrhythmia during hospital stay. Re-operation was required in 2 cases (3.8%) of infective endocarditis due to prosthetic valve endocarditis. No other major complication was observed.

[Tracheobronchial injury].

We studied 6 cases of tracheobronchial injury due to the blunt chest truma in our department. All patients were male of 19 to 60 years of age. Injured sites were main bronchus in 2, tracheobronchial portion in 2, cervical trachea and main bronchus in 1, cervical trachea in 1. In a case of cervical tracheal injury and 2 cases of tracheobronchial injury, emergent operation was performed on the day of accident. Other cases with the main bronchial injury underwent conservative treatment at first, but subsequent bronchoplasty was necessary for them due to the bronchial stenosis. After the surgery for 2 cases of tracheobronchial injury, mechanical ventilation with double lumen tube was continued to reduce the airway pressure for the anastomotic sites. In conclusion, early surgical treatment is recommended for the airway injury and the respiratory management using double lumen tube after surgery may be helpful in preventing trouble at the anastomosis.

The effects of a neutrophil elastase inhibitor on the postoperative respiratory failure of acute aortic dissection.

BACKGROUND: Postoperative respiratory failure is often encountered in patients suffering from acute aortic dissection (AAD) and is believed to be influenced by release of neutrophil elastase after cardiopulmonary bypass. Sivelestat is a specific neutrophil elastase inhibitor, and this study aims to evaluate the effects of sivelestat on postoperative respiratory failure due to AAD. METHODS AND RESULTS: Patients who were operated for AAD from January 2000 to April 2005 and who had less than 300 mmHg initial postoperative PaO (2)/FiO (2) were investigated retrospectively and divided into two groups. Group 1 (n = 9) received intravenous administration of sivelestat immediately after the operation, while Group II (n = 9) received no sivelestat. There were no significant differences between Group I and II with respect to patients' characteristics or background (age, body weight, operating time, cardiopulmonary bypass time, amount of bleeding, preoperative WBC number and initial PaO (2)/FiO (2)). Though patients in Group I showed a subtle improvement in certain parameters such as PaO (2)/FiO (2), A-aDO (2) and respiratory index (RI) over a 3-day observation period compared to those of Group II, there were no significant differences. Neither postoperative mechanical ventilation time nor ICU stay differed between Group I and II. However, Group I showed a significantly greater improvement in the ratio of RI to initial RI on the 3POD compared to that of Group II (61.6 +/- 44.2 % vs. 111.9 +/- 40.9 %, P = 0.02). CONCLUSION: Inhibiting the activity of the neutrophil elastase may attenuate the postoperative respiratory complications of patients with AAD.

Effects of pulmonary artery remodeling on pulmonary circulation after lung volume reduction surgery.

BACKGROUND: Significant pulmonary hypertension during exercise has been observed in patients with severe chronic obstructive pulmonary disease. Although favorable effects on pulmonary function and dyspnea symptoms have been demonstrated, the influence of lung volume reduction surgery (LVRS) on the pulmonary hypertension during exercise is still a controversial subject. METHODS: A pulmonary function test and 6-minute walking test were performed before and 3, 6, 12 and 24 months after LVRS (n = 12). Pulmonary hemodynamics at rest and during exercise was studied 6 months after operation. Morphology was examined in pulmonary arteries with external diameters of 100 - 200 micro m in the resected lung, and the wall thickness (defined as intima plus media) and percentage wall thickness (percentage wall thickness of the external diameter) of the pulmonary artery were calculated. RESULTS: LVRS improved early-phase pulmonary function and 6-minute walking distance. Although the increase in pulmonary capillary wedge pressure during exercise was significantly ameliorated, exercise pulmonary hypertension did not change after LVRS. The percent wall thickness was highly correlated with Delta Ppa (difference between mean pulmonary artery pressure at rest and mean pulmonary artery pressure during exercise) not only before, but also 6 months after LVRS. CONCLUSION: LVRS has no significant influence on exercise-induced pulmonary hypertension in patients with severe emphysema. From a histological analysis of the pulmonary artery in the resected lung, remodeling the pulmonary artery that may exist in the remaining lung is possibly one of the important factors preventing postoperative improvement in exercise pulmonary hypertension in patients with chronic obstructive pulmonary disease.

[Minimally invasive direct coronary artery bypass in a patient with idiopathic thrombocytopenic purpura; report of a reoperative case].

A 77-year-old man who had undergone coronary artery bypass grafting (CABG) to segment 3, 7 and 12-14 with saphenous vein grafts (SVG) 15 years before, and ligation of coronary arteriovenous (AV) fistula 8 years before was admitted to our hospital, and diagnosed as acute heart failure and idiopathic thrombocytopenic purpura. Coronary angiography showed multiple stenosis of three vessels, and the grafts to segment 3 and 7 were occluded. The area of left anterior descending (LAD) had no viability, but the inferior wall had viability on dobutamine load echocardiography. The platelet count was about 5.0 x 10(4)/mm3. Minimally invasive direct coronary artery bypass (MIDCAB) for right coronary artery (RCA) using right internal thoracic artery (RITA) was performed through right parasternotomy. Operative and postoperative bleeding was slight, and postoperative course was uneventful. Reoperative MIDCAB can be safely performed in a patient with idiopathic thrombocytopenic purpura, and should be considered a viable alternative for highrisk patients.

Expression of basic fibroblast growth factor and its receptor-1 in cardiac myxoma.

BACKGROUND: To clarify the significance of basic fibroblast growth factor (bFGF) in angiogenesis or proliferative activity in cardiac myxoma, the expression of bFGF and its receptor (FGFR-1) were immunohistochemically examined. METHODS: Formalin-embedded tissues of cardiac myxomas were obtained by surgical resection from 15 patients and analyzed by immunostaining of bFGF and FGFR-1. The microvessel density was measured in the 15 myxomas using platelet derived endothelial cell adhesion molecule-1. For evaluation of proliferative activity of the cardiac myxomas, proliferating cell nuclear antigen (PCNA) immunostaining was performed, and the PCNA labeling index was measured in each section. RESULTS: bFGF and FGFR-1 were observed in 73.3% and 67.7% of the myxomas, respectively. There was a close correlation between the expression of bFGF and FGFR-1. This co-expression was frequently observed in the myxoma cells around the microvessels appearing as a ring structure. Regarding possible relationships between the expression of bFGF or FGFR-1 and the clinicopathologic features, there were no parameters excluding the macroscopic type of myxoma. The microvessel density in the myxomas with bFGF or FGFR-1 expression was higher than that in myxomas without it. The PCNA labeling index in myxomas with bFGF expression was higher than that in myxomas without it, and the PCNA labeling index tended to be higher in myxomas with FGFR-1 expression than that in myxomas without it. CONCLUSIONS: bFGF and/or FGFR-1 was expressed in some of cardiac myxoma, and may be an important role for tumor angiogenesis and proliferative activity.

Can sedation reduce the cardiac stress during gastrointestinal endoscopy? A study with non-invasive automated cardiac flow measurement by color Doppler echocardiography.

BACKGROUND: Upper gastrointestinal endoscopy (UGIE) may cause some cardiac stress. The effect of sedation on hemodynamics during UGIE has not been fully studied, and therefore the aim of this study was to clarify whether or not sedation can reduce cardiac stress dufing UGIE. METHODS: Eight normal male volunteers undergoing UGIE with sedation (0.1 mg/kg of midazolam) and without it (two endoscopies per volunteer in random order) were monitored throughout the procedure by means of electrocardiogram, blood pressure and peripheral oxygen saturation (SpO2). Cardiac output was measured at six points before, during and after endoscopy from automated cardiac flow measurement by color Doppler echocardiography. Serum norepinephrine, epinephrine, dopamine and ACTH concentrations were measured before and after the examination. RESULTS: No significant differences in heart rate, systolic blood pressure, rate-pressure product, cardiac output and left ventricular work index were observed between the sedated and non-sedated groups. SpO2 hardly changed during endoscopy in the non-sedated group, but decreased slightly in the sedated group (P = 0.075). Although all serum catecholamine concentration changes were within normal limits in both groups, after endoscopy only epinephrine concentration was significantly lower in the sedated group than in the non-sedated group (P = 0.0027). CONCLUSIONS: Conscious sedation with midazolam does not reduce the cardiac stress during UGIE.

Differences and relationships of thymidine phosphorylase expression in tumor-associated macrophages and cancer cells in squamous cell carcinoma of the esophagus.

Thymidine phosphorylase (TP), which has been shown to be identical to platelet-derived endothelial cell growth factor, is expressed in tumor-associated macrophages (TAMs) as well as cancer cells. The aim of this study was to clarify the differences or relationships of TP expression in TAMs and cancer cells in esophageal squamous cell carcinoma (SCC). Tissues samples were taken from 56 patients with esophageal SCC after curative surgery. The expression of TP in TAMs or SCC cells was examined using a monoclonal antibody to TP (clone 654-1). Microvessels in SCC that stained positively for Factor VIII-related antigen were counted (microvessel density, MVD). Macrophages in SCC that stained positively for CD68 antigen were counted (monocytic count). Ki-67 antigen was immunostained with MIB-1, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling was performed, and Ki-67 labeling index (LI) and apoptotic index were calculated. The expression of TP in stromal cells and cancer cells was observed in 43 (76.8%) and 33 patients (58.9%), respectively. There were significant correlations between TP expression in stromal cells (TAMs) as well as in cancer cells and venous invasion, distant metastasis, or MVD. There was a correlation between TP expression in cancer cells and lymph node metastasis, and there were correlations between TP expression in TAMs and monocytic count or Ki-67 LI; however, there was no correlation between TP expression in TAMs and lymph node metastasis. On the other hand, in SCCs with TP expression in both TAMs and cancer cells, higher frequencies of venous invasion and distant metastasis, higher MVD and lower apoptotic index were observed than in other SCCs. The 5-year survival rate in patients with TP expression in both TAMs and cancer cells was poorer than that in patients with TP expression in neither TAMs and cancer cell. In conclusion, these results suggest that co-expression of TP in TAMs and cancer cells is strongly associated with angiogenic promotion and distant metastasis. However, other effects of TP, such as promotion of tumor growth and lymph node metastasis, may be different depending on whether these are expressed in TAMs or cancer cells in esophageal SCCs. Patients with coexpression of TP in TAMs and cancer cells may be associated with a poor prognosis.

Recurrence of thymoma: clinicopathological features, re-operation, and outcome.

BACKGROUND: Even after complete resection, recurrence of thymoma is not infrequently observed, and treatment of recurrent thymoma remains controversial. STUDY DESIGN: One hundred and twenty-six patients underwent surgically complete resection for thymoma, and 24 of them had a recurrence. Surgical treatment of recurrent thymoma was attempted in 15 patients for a total of 18 times. In the present study, the relevance of clinicopathological features and the re-operation on the survival rate after the recurrence were determined. RESULTS: The most frequent recurrent type was pleural dissemination (92%), with local recurrence observed in 5%. Overall 5- and 10-year survivals after recurrence were 37 and 16%, respectively. Disease-free interval after initial operation and complication of myasthenia gravis had no significant effect on postrecurrent survival. The use of postoperative mediastinal irradiation had no effect on reducing the recurrence rate or improving survival after recurrence. Two of 15 patients who underwent re-operation died of major complications after It. pleuropneumonectomy for severe pleural dissemination. In the present study, the re-operation was not significantly effective for prolongation of postrecurrence survival. CONCLUSION: Our study showed that re-operation should not be attempted for all patients with recurrent thymoma. Because effect of subtotal resection for severe pleural recurrence is disappointing, total resection for minimal pleural dissemination or small local recurrence will be undertaken to improve postrecurrent survival. Careful follow-up for > 10 years will increase the chance of the total resection of the recurrent thymoma.

Comparative study of glycosyltransferase activities in Caco-2 cells before and after enterocytic differentiation using lectin-affinity high-performance liquid chromatography.

Human colonic adenocarcinoma Caco-2 cells differentiate into enterocytes by induction with sodium butyrate after confluence. Our previous studies have shown that there are high levels of H type 1 blood group antigen and core 2 structure present in O-glycans of the glycoproteins from these differentiated cells and these O-glycans appear to be indispensable for the process of differentiation of the cells (J. Amano and M. Oshima, 1999, J. Biol. Chem. 274, 21209-21216). Here, we have determined the glycosyltransferase activities using lectin-affinity HPLC because the method enabled easy separation and identification of mixtures of isomeric oligosaccharide structures due to the high resolution and reproducibility. The activities of beta 3-galactosyltransferase, alpha 2-fucosyltransferase, which are responsible for H type 1 antigen biosynthesis, and core 2 beta 6-N-acetylglucosaminyltransferase in differentiated Caco-2 cells were higher than those in undifferentiated cells. These results demonstrate that an increase in specific glycosyltransferase activities brought on a change of the O-glycan structures during differentiation.

Intestinal epithelial cells express and secrete the CD43 glycoform that contains core 2 O-glycans.

Several glycoforms of CD43 are known to regulate cellular interactions in the immune system. One such glycoform, the CD43 that bears core 2 O-glycans, is also known to be expressed on T lymphocytes and natural killer cells, but only after their activation. Previous studies have also shown that when Caco-2 cells, which are derived from human colon carcinoma, differentiate into enterocytes, they also express core 2 O-glycans, though proteins bearing this glycan are unknown. To examine whether CD43 glycosylation is altered during enterocytic differentiation of Caco-2 cells, we conducted immunocytochemical studies with a monoclonal antibody, 1D4, that recognizes a glycoform of CD43 bearing core 2 O-glycans. We found that 1D4 could bind to intracellular granules but not the cell surface of differentiated Caco-2 cells, whereas hematopoietic cells expressed 1D4 epitope on the cell surface as previously shown. The reactivity with this antibody increased as the degree of cell differentiation progressed as shown by the activity of the apical enzyme marker, dipeptidyl peptidase IV. 1D4-reactive CD43 was also found in the culture medium of differentiated Caco-2 cells, suggesting this molecule may be stored and secreted. The production and secretion of this CD43 glycoform by enterocyte-like Caco-2 cells was enhanced, and most 1D4 epitope converted to a soluble form when bacterial lipopolysaccharide was present. These observations strongly support the possibility that core 2 O-glycans on mucins such as CD43 are important to primary defense on the intestinal epithelium against infection.

Pulmonary epithelioid hemangioendothelioma coexistent with pulmonary metastasis of thyroid cancer.

We report a 45-year-old man with epithelioid hemangioendothelioma (EH) and simultaneous pulmonary metastasis of thyroid cancer in his lung. Thyroid cancer, and multiple small nodules in both lungs were noted. He underwent total thyroidectomy followed by radiotherapy with 131I. However, 131I scintigraphy showed poor uptake of radionuclide in the nodules, and the size of the nodules remained unchanged. The diagnostic thoracoscopic biopsy showed two types of nodules, some were positive for thyroglobulin and cytokeratin, and others were reactive for factor VIII. The former nodules were diagnosed as pulmonary metastases of thyroid cancer, and the latter EH.

Bifidobacterium longum as a delivery system for gene therapy of chemically induced rat mammary tumors.

A fundamental obstacle in cancer gene therapy is the specific targeting of therapy directly to a solid tumor, and no systemic delivery system yet exists. A strain of domestic bacteria, Bifidobacterium longum, which is nonpathogenic and anaerobic, selectively localized to and proliferated in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors after systemic application. We further ascertained the tumor specificity of genetically engineered, as well as wild-type, Bifidobacterium longum. This is the first demonstration that Bifidobacterium longum can be utilized as a specific gene delivery vector for gene therapy on solid breast tumors.

Hepatic resection for large hepatocellular carcinoma.

BACKGROUND: Long-term survival and prognostic factors after hepatic resection for large hepatocellular carcinoma (HCC) remain to be proved. METHODS: The surgical outcome in 133 consecutive patients with HCC in diameter of > or = 5 cm (large HCC; L group) undergoing hepatic resection was retrospectively clarified and compared with that of 253 patients with HCC in diameter of < 5 cm (small HCC; S group). Postresection prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model. RESULTS: The disease-free 3- and 5-year survival rates between L group and S group were 26% versus 42% and 20% versus 25%, respectively (P = 0.0032). The overall 3- and 5-year survival rates between L group and S group were 38% versus 67% and 28% versus 47%, respectively (P < 0.0001). Multivariate analysis revealed that large amount of intraoperative blood transfusion was an independently significant factor of poor disease-free and overall survivals. CONCLUSIONS: Long-term survival in patients with large HCC remains unsatisfactory compared with that in patients with non-large HCC. Restriction of intraoperative blood transfusion may play an important role in the improvement of survival and recurrence in such patients.

Tranilast inhibits cardiac allograft vasculopathy in association with p21(Waf1/Cip1) expression on neointimal cells in murine cardiac transplantation model.

Cardiac allograft vasculopathy is a major complication after cardiac transplantation, often limiting long-term recipient survival. N-(3,4-Dimethoxycinnamoyl)anthranilic acid (tranilast) inhibits cyclin-dependent kinase activity through p21(Waf1/Cip1) induction and arrests vascular smooth muscle cell proliferation in vitro. We tested a hypothesis that tranilast inhibits the vasculopathy characterized by diffuse intimal thickening in a murine heart transplantation model. Hearts from DBA/2 mice were heterotopically transplanted into B10.D2 mice as allografts. Oral administration of tranilast started 3 days before transplantation at doses of 550 or 1040 mg/kg per day until the animals were killed. Cardiac allograft vasculopathy was defined as luminal stenosis caused by neointimal formation. The percentage of luminal stenosis and cardiac rejection were analyzed 14 and 28 days after transplantation. Tranilast administration was associated with a marked reduction in luminal occlusion but with no significant effect on cardiac rejection. Immunohistochemical study of the tranilast-treated graft coronary arteries revealed enhancement of p21(Waf1/Cip1) and decreased expression of proliferating cell nuclear antigen in the neointima. The significant reduction in allograft vasculopathy concomitant with the enhancement of p21(Waf1/Cip1) indicates that tranilast has an antiproliferative effect that could be applicable to clinical treatment of cardiac allograft vasculopathy.

Coexpression of vascular endothelial growth factor and p53 protein in squamous cell carcinoma of the esophagus.

OBJECTIVE: p53 plays a role in tumor angiogenesis, and vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. The aim of the present study was to clarify how expression of p53 protein participates in angiogenesis, and whether the coexpression of VEGF and p53 protein has a significance for angiogenesis and the clinicopathological features in esophageal squamous cell carcinoma (SCC). METHODS: Tissues samples were taken from 60 patients with esophageal SCC after surgery. The expression of VEGF and p53 protein in these SCC was examined immunohistochemically. Microvessel density (MVD) was determined by counting microvessels in tumor sections stained for Factor VIII-related antigen. Ki-67 labeling index (LI) was calculated, based on Ki-67 antigen immunostaining, as a proliferative marker. Apoptotic index (AI) was calculated, based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling, to evaluate apoptosis. RESULTS: VEGF expression was observed in 58.3%, and p53 protein expression was observed in 61.7% of the 60 patients. VEGF and p53 protein were significantly coexpressed in 26 (43.4%). Histological venous invasion (p < 0.01) and distant metastasis (p < 0.05) were significantly correlated with p53 protein expression. The two parameters were more frequently observed in the SCC with VEGF/p53 coexpression than in those without the coexpression. The MVD and Ki-67 LI were significantly higher (p < 0.01 and p < 0.001), and the AI was significantly lower (p < 0.001) in the SCC with p53 protein expression than in the SCC without it. The MVD and Ki-67 LI were higher, and the AI was lower in the SCC with VEGF/p53 coexpression than in those without the coexpression. The 5-yr survival rate in patients with the coexpression was poorer than in the other patients. CONCLUSION: These results suggest that mutant p53 expression is associated with angiogenesis and distant metastasis in esophageal SCC, and that the coexpression of p53 and VEGF may play an important role in angiogenesis, and have important clinical significance.

Cavernous hemangioma of the liver with giant cyst formation: degeneration by apoptosis?

Cavernous hemangioma of the liver with cyst formation is a very rare condition. A case of cavernous hemangioma of the liver with unilocular giant cyst formation undergoing surgical removal is reported. Notably, the patient also had Budd-Chiari syndrome with an obstructing lesion in the inferior vena cava. The cystic degeneration of the hemangioma implied a relationship with apoptosis. This is the first reported case of Budd-Chiari syndrome caused by advanced cystic degeneration of hepatic cavernous hemangioma.

Early growth-response factor 1 and basic transcriptional element-binding protein 2 expression in cardiac allografts.

Early growth-response factor 1 (Egr-1) and basic transcriptional element-binding protein 2 (BTEB2) are transcriptional factors that regulate multiple genes involved in phenotypic changes of smooth muscle cells (SMCs), one of the outstanding pathologic features of chronic cardiac allograft rejection. In this study, we used a heterotopic abdominal heart transplant model in monkeys to evaluate the roles of these molecules in graft coronary vasculopathy. We demonstrated that Egr-1 and BTEB2 are induced in vascular SMCs of rejected cardiac allografts well before morphologic changes, such as intimal thickening. These findings suggest that expression of Egr-1 and BTEB2 is one of the initial events in allograft angiopathy.

Prognostic factors after hepatic resection for hepatocellular carcinoma with hepatitis C viral infection: univariate and multivariate analysis.

OBJECTIVES: Although the incidence of hepatocellular carcinoma (HCC) with hepatitis C virus (HCV) infection is higher than in patients with hepatitis B virus (HBV)-related HCC in Japan, the long-term prognosis and prognostic factors of HCV-related HCC after hepatic resection are poorly understood. METHODS: The surgical outcome of HCV-related HCC in 172 consecutive patients who underwent hepatic resection between 1989 and 1997 was retrospectively clarified. Postresection prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model. RESULTS: The overall incidence of postoperative complications was 23.2%, and 11 patients among that group had hospital deaths (6.4%) including 9 (5.2%) operative deaths. The mean and median overall survivals including hospital death after surgery were 41 months and 33 months, respectively. The 3-, 5-, and 7-yr overall survival rates after hepatic resection were 63%, 52%, and 47%, respectively. The 3-, 5-, and 7-yr disease-free survival rates after hepatic resection were 33%, 20%, and 15%, respectively. Multivariate analysis revealed that serum alpha-fetoprotein (AFP) of > or = 1000 ng/ml and the presence of vascular invasion were independent unfavorable prognostic factors affecting overall survival and that AFP of > or = 1000 ng/ml was an independently significant factor of poor disease-free survival. CONCLUSIONS: We found the postresection survival of patients with HCV-related HCC should be stratified by the high value of AFP and the presence of vascular invasion. AFP may be the most powerful predictor of the long-term prognosis and recurrence in such patients.