Halo Structure of the Neutron-Dripline Nucleus

The heaviest bound isotope of boron ^{19}B has been investigated using exclusive measurements of its Coulomb dissociation, into ^{17}B and two neutrons, in collisions with Pb at 220 MeV/nucleon. Enhanced electric dipole (E1) strength is observed just above the two-neutron decay threshold with an integrated E1 strength of B(E1)=1.64±0.06(stat)±0.12(sys) e^{2} fm^{2} for relative energies below 6 MeV. This feature, known as a soft E1 excitation, provides the first firm evidence that ^{19}B has a prominent two-neutron halo. Three-body calculations that reproduce the energy spectrum indicate that the valence neutrons have a significant s-wave configuration and exhibit a dineutronlike correlation.

First Observation of

The most neutron-rich boron isotopes ^{20}B and ^{21}B have been observed for the first time following proton removal from ^{22}N and ^{22}C at energies around 230 MeV/nucleon. Both nuclei were found to exist as resonances which were detected through their decay into ^{19}B and one or two neutrons. Two-proton removal from ^{22}N populated a prominent resonancelike structure in ^{20}B at around 2.5 MeV above the one-neutron decay threshold, which is interpreted as arising from the closely spaced 1^{-},2^{-} ground-state doublet predicted by the shell model. In the case of proton removal from ^{22}C, the ^{19}B plus one- and two-neutron channels were consistent with the population of a resonance in ^{21}B 2.47±0.19 MeV above the two-neutron decay threshold, which is found to exhibit direct two-neutron decay. The ground-state mass excesses determined for ^{20,21}B are found to be in agreement with mass surface extrapolations derived within the latest atomic-mass evaluations.

Nucleus

The unbound nucleus ^{26}O has been investigated using invariant-mass spectroscopy following one-proton removal reaction from a ^{27}F beam at 201 MeV/nucleon. The decay products, ^{24}O and two neutrons, were detected in coincidence using the newly commissioned SAMURAI spectrometer at the RIKEN Radioactive Isotope Beam Factory. The ^{26}O ground-state resonance was found to lie only 18±3(stat)±4(syst) keV above threshold. In addition, a higher lying level, which is most likely the first 2^{+} state, was observed for the first time at 1.28_{-0.08}^{+0.11} MeV above threshold. Comparison with theoretical predictions suggests that three-nucleon forces, pf-shell intruder configurations, and the continuum are key elements to understanding the structure of the most neutron-rich oxygen isotopes beyond the drip line.

Copolymerisation of ethylene with polar monomers by using palladium catalysts bearing an N-heterocyclic carbene-phosphine oxide bidentate ligand.

We report the synthesis and characterisation of palladium complexes bearing an N-heterocyclic carbene-phosphine oxide bidentate ligand and their use as catalysts for ethylene polymerisation and ethylene/polar monomer copolymerisation.

Determination of the prognostic significance of unscheduled cyclin A overexpression in patients with esophageal squamous cell carcinoma.

The expression of cyclin A protein was retrospectively investigated in 124 patients with human esophageal squamous cell carcinoma with immunohistochemical techniques using antibody to cyclin A protein (BF683). Of 124 tumors, 49 (39.5%) exhibited positive staining in cancer cells with this antibody. Staining was observed predominantly but not exclusively in the nucleus. A significantly higher degree of association of immunoreactivity with this antibody was detected for advanced types of tumors (stages I, II, III, and IV) than for early tumors (stage 0; P < 0.05). Patients with cyclin A immunopositivity had a significantly poorer survival rate than did other patients (P < 0.01). These findings provide the first evidence for frequent and unscheduled overexpression of cyclin A protein in human esophageal cancer and suggest the possibility that alteration of cyclin A overexpression is associated with tumor progression and patient prognosis for esophageal cancers.

Aberrant expression of p53 and retinoblastoma gene products in human esophageal squamous cell carcinoma.

The aberrant expression of p53 and RB proteins was investigated by immunohistochemistry in 73 patients with esophageal SCC, who underwent esophageal resection. Fresh tumor tissues from 21 patients were also tested for p53 mutations in exons 4 through 9 by direct sequencing. Positive nuclear staining with p53 antibody in cancer cells was found in 49.3% (36/73) of the tumors. Mutations in the p53 gene were detected in 66.7% (14/21) by direct sequencing. Nuclear staining with RB antibody in cancer cells was diffuse in 11.0% (8/73) and heterogeneous in 57.5% (42/73) of cases. Ten patients with p53-positive but RB-negative tumors had a significantly higher incidence of stage IV disease than the other patients studied. In addition, 8 patients with tumors with diffuse nuclear staining for RB antibody had a significantly lower survival rate than the other patients. These findings demonstrate that aberrant expression of RB and/or p53 protein is frequent in human esophageal SCC, and is probably associated with tumor progression and unfavorable prognosis.

Resection of cancer of the thoracic esophagus without thoracotomy.

We developed a new surgical technique to manually resect the thoracic esophagus without thoracotomy and employed it in 31 patients with cancer of the esophagus who were considered poor risks for resection by traditional thoracotomy. Postoperative complications consisted of left hemothorax in seven patients, hoarseness in five, sternal osteomyelitis in three, a perforated trachea in one, and cardiorenal failure in three patients. No severe pulmonary complications occurred, and there were no hospital deaths. The long-term results of this surgical treatment have not been assessed.

Significance of the concentrated red cell and albumin priming method with particular reference to anaphylatoxin generation.

Anaphylatoxins generated by cardiopulmonary bypass were observed in basic and clinical studies (n = 120 in the latter). In vitro immunoglobulin fractions denatured by oxygen bubbling produced C4a, C3a, and C5a, but albumin identically treated did not. Therefore concentrated red cells with albumin were used to prime homologous blood for clinical application during cardiopulmonary bypass. Complement levels were compared with type of oxygenator (bubble or membrane) and the ratio of primed homologous blood to circulating autologous blood volume. With the bubble oxygenator at a low ratio of homologous to autologous blood (arbitrarily defined as less than 20%), C3a levels during cardiopulmonary bypass tended to be lower in the concentrated red cells plus albumin priming group than in the ordinary priming group (p less than 0.1, at 60 and 90 minutes of cardiopulmonary bypass). C4a and C3a levels increased less after protamine administration with concentrated red cells plus albumin priming (p less than 0.05, p less than 0.01, respectively, 90 minutes after protamine) than with ordinary priming. Such changes in the membrane oxygenator group were less remarkable. Thus C3a levels were approximately the same in both oxygenator groups primed with concentrated red cells plus albumin. The higher the homologous to autologous ratio, the steeper the C4a and C3a increase from the beginning of cardiopulmonary bypass with the bubble oxygenator. This tendency was less remarkable in the membrane oxygenator group. Early postoperative pulmonary function was improved by concentrated red cells plus albumin priming, especially in the bubble oxygenator group. In conclusion, (1) oxygenator systems primed with concentrated red cells plus albumin produced less anaphylatoxin than those with homologous blood, especially with the bubble oxygenator, and (2) our clinical results support the importance of immunoglobulin denatured by oxygen bubbling in anaphylatoxin generation (by means of the classical pathway), as shown by our in vitro study.

Determination of the prognostic significance of cyclin B1 overexpression in patients with esophageal squamous cell carcinoma.

Recent studies have identified a family of proteins referred to as cyclins, which control the cell cycle. Cyclin B1 activates cdc2, which regulates cell progression through the G2 and M phases. The main aim of this study was to examine the relationships between the cyclin B1 expression in human esophageal squamous cell carcinoma (SCC) and clinicopathological factors and prognosis of the patients. Eighty-seven cases of primary human SCC consecutively obtained at esophagectomy were immunohistochemically studied using an anti-human cyclin B1 protein antibody (2H1-H6). The relationship between cyclin B1 expression and clinicopathological factors, including prognosis, were also statistically assessed. Positive immunostaining of cancer cells, mainly in the cytoplasm, was detected in 72.4% (63/87): heterogeneous pattern in 37.9% (33/87) and homogeneous pattern in 34.5% (30/87). The prevalence of cyclin B1 expression was significantly higher in cases with invasion deeper than the muscularis propria (P<0.005) and with venous invasion (P<0.01) than in other cases. Patients whose SCCs expressed high levels of cyclin B1 protein had a significantly poorer prognosis than did the other patients (P<0.05). Multivariate analysis demonstrated that cyclin B1 status was an important factor affecting survival (P<0.05). These findings demonstrated that overexpression of cyclin B1 protein is associated with tumor behavior and prognosis for patients with human esophageal SCC.

Intraoperative detection of embedded coronary arteries in MIDCAB using a color Doppler microprobe.

Intraoperative detection of deeply embedded coronary arteries is difficult, especially in minimally invasive coronary artery bypass grafts. This report describes an effective method to identify embedded coronary arteries by using a color Doppler microprobe. Five embedded left anterior descending coronary arteries were successfully identified by intraoperative ultrasonography. We believe that the color Doppler microprobe is helpful for surgeons in this difficult situation.

A histological study of surgical landmarks for the specialized atrioventricular conduction system, with particular reference to the papillary muscle.

Surgical landmarks of the conduction system were histologically evaluated in 29 cardiac specimens. The distribution of the system was grossly inherent to the type of ventricular septal defect as classified by Soto and coworkers, although it varied individually. The relationship of the right bundle branch (RBB) to the papillary muscles was of surgical interest. In defects unrelated to maldevelopment of the septum of the conus, the RBB passed beneath or slightly anterior to upper accessory papillary muscles (AcPMs) and posterior to the medial papillary muscle (MPM), regardless of the subtype of defect. In defects caused by maldevelopment, such as tetralogy of Fallot, it passed anterior to the MPM. Such data support the hypothesis that the RBB descends beneath or anterior to embryological upper AcPMs, whatever the morphological role may be, because of the supposedly independent developmental origin of the MPM and AcPMs. The relationship between the RBB and upper AcPMs appeared further modified by the attitude of the trabecula septomarginalis. Our improved clinical results have demonstrated that such information offers a gross but practical guide for prevention of conduction disturbances.

Complement activation in cardiopulmonary bypass, with special reference to anaphylatoxin production in membrane and bubble oxygenators.

Complement activation by cardiopulmonary bypass (CPB) was studied in 82 patients divided into membrane (MOG) and bubble oxygenator groups (BOG). The influence of primed homologous to circulating autologous blood volume (H/A) ratio was also evaluated. C4a increased very slowly during CPB in both groups, maintaining slightly higher levels in the BOG than in the MOG, with the exception of a marked initial rise in the BOG with a high H/A ratio (greater than or equal to 20%). Anaphylatoxin C3a levels increased more steeply in the BOG than in the MOG. An obvious rise in anaphylatoxin C5a production was observed in the BOG alone. The influence of high H/A ratio perfusion on complement activation was milder in the MOG than in the BOG. In 20 monkeys (Macaca fascicularis), continuous intraaortic infusion with bubbled autologous blood increased C4a and C3a levels, while autologous blood extracorporeally contacted with nylon increased C3a levels alone. In vitro studies revealed that human immunoglobulin fractions denatured by oxygen bubbling produced C4a, C3a, and C5a in a dose-dependent manner, although human albumin treated identically as human immunoglobulin did not produce these complements. It was thus inferred that (1) during CPB, complement is predominantly activated via the classical pathway in the BOG and via the alternative pathway in the MOG; (2) higher anaphylatoxin levels in the BOG than in the MOG are related to mode and grade of blood trauma; (3) anaphylatoxin level differences in both groups tend to increase with high H/A perfusion; and (4) immunoglobulin-free sera may reduced classical pathway activation.

Assessment of internal thoracic artery graft with intraoperative color Doppler ultrasonography.

BACKGROUND: Intraoperative ultrasonography has the potential to provide anatomic and functional information about internal thoracic artery (ITA) graft, but this potential has been hindered by the relatively large standard probe. In this study, we used a color Doppler microprobe to evaluate ITA grafts. METHODS: The subjects were 15 consecutive patients who underwent elective coronary artery bypass grafting either with cardiopulmonary bypass (n = 14) or without (n = 1). All patients underwent anastomosis of the left ITA to the left anterior descending artery. The ITA graft was assessed before the chest was closed, with the microprobe placed directly on the graft. RESULTS: A good-quality color Doppler image of the ITA graft was easily obtained in all 15 patients within a few minutes. The ITA graft function was assessed by analyzing the shape of the pulsed Doppler wave. All ITA grafts were patent, and the mean graft diameter was 1.8 +/- 0.04 mm. The peak systolic velocity, peak diastolic velocity, and mean velocity were 52.0 +/- 14.9 cm/s, 58.3 +/- 22.4 cm/s, and 36.5 +/- 10.9 cm/s, respectively. The ratio of peak diastolic velocity to peak systolic velocity was 1.24 +/- 0.66. The ITA graft seemed to function well when the biphasic diastolic predominant flow appeared. The mean blood flow was 55.1 +/- 22.0 mL/min. CONCLUSIONS: Intraoperative ultrasonography using the microprobe provides adequate anatomic and hemodynamic information regarding ITA grafts. As the Doppler flow evaluation has high sensitivity and specificity, we suggest that intraoperative ultrasonography is useful for the assessment of these grafts.

Effect of administration of nucleosides and nucleotides on protein turnover and the hypoxic myocardium.

Nucleotides and nucleosides have effects on improving energy metabolism and enhancing immune function. Under a surgical stress, requirement of nucleotides are increased as well as nitrogen. A well-balanced nucleoside solution (OG-VI) was developed for parenteral administration and its effect was examined in animals. The OG-VI solution contained 3.11% of nucleosides which was composed of inosine, guanosine monophosphate, cytidine, uridine and thymidine of 4:4:4:3:1 in molar ratio. The whole body protein turnover increased significantly in rats received total parenteral nutrition (TPN) with OG-VI after 70% hepatectomy and enhanced the fractional protein synthesis rates of the muscle and liver. Also myocardial contractility (%segment shortening, %SS) in dogs after occlusion of left anterior descending artery (LAD) was recovered to 70% after reperfusion in the OG-VI group. The creatine phosphate (PCr) / inorganic phosphate (Pi) was maintained the baseline level and did not decrease after hypoxia in the OG-VI group while PCr/ Pi was decreased after hypoxia in normal rat. These data suggested that the nucleoside-nucleotide (OG-VI) improved nitrogen metabolism and might stimulate synthesis of high-energy phosphate in recovery after severe surgical stress.

Interrelationship between the expression of h-ras p21, C-myc and p53 proteins, and the infection of high-risk human papillomaviruses in Japanese patients with esophageal squamous-cell carcinoma.

The presence and distribution of increased expression of H-ras p21 protein, c-myc protein and p53 protein, or of human papillomavirus (HPV) DNA were investigated in 42 Japanese patients with esophageal squamous cell carcinoma (SCC) by immunohistochemical techniques using each protein antibody, and by in situ hybridization with fluorescein isothiocyanate (FITC)-labelled DNA. probes for HPV-16 and HPV-18. Eighteen cases were positive with H-ras p21 antibody, but only one with c-myc protein antibody. Positive reaction of the cancer cell nuclei with p53 antibody was found in 14 cases. Among these positive cases with H-ras p21 or p53 antibody, 7 were double positive. In addition, we found positive results in 7 cases with HPV-16, and 8 cases with HPV-18, including 2 double positive cases. Among them, 6 cases were also positive with H-ras p21. Only HPV infection or p53 overexpression was detected each in 7 cases. All of HPV-positive tumors were negative with p53 antibody. Moreover, among the cases with the expression of I-I-ins p21, combined cases with overexpressed p53 protein or HPV infection counted for more than 50%. Statistically, these combined cases showed worse survival rate than only H-ras p21 positive ones. Judging from these results obtained in the present study, the increased expression of H-ras p21 protein as well as p53 and/or HPV may be involved in the carcinogenesis of this kind of disease, and become apparent, when the function of p53 as a tumor suppressor gene is inhibited with overexpressed p53 protein or HPV oncoprotein, resulting in a poor prognostic indicator.

New multi-disciplinary treatment modality with RALS for patients with esophageal cancer.

Esophageal cancer is frequently found when it is already in the advanced stage and curative surgery for such cases is consequently difficult to perform. The new multi-disciplinary treatment for esophageal cancer presented here was, therefore, conceived to improve both the survival rate and quality of life of these patients. This combined treatment modality consists of limited surgery, external irradiation, intracavitary irradiation with remote-controlled after-loading system (RALS) and peri-operative chemotherapy. In the present series, 45 patients with esophageal cancer received esophagectomy and on another 11 patients bypass operation was performed. All patients were treated with this multi-disciplinary treatment after operation. A 3 cm-wide thin gastric tube was made from the greater curvature of the stomach of the patient using an autosuture apparatus (PLC55 or GIA). In the bypass operation, the jejunum was anastomosed to the original esophagus in the Roux-en Y fashion and jejunostomy was performed on the oral side of the Roux loop. A silastic tube of 9 mm inner diameter was inserted from the jejunostomy and placed into the original esophagus for the purpose of postoperative intracavitary irradiation with RALS. For the patients receiving esophagectomy, a similar silastic tube was also placed in the posterior mediastinum for intracavitary irradiation with RALS. The indication of the bypass operation was i) a tumor length longer than 9 cm on the X-ray film and/or ii) direct invasion to the aortic wall evident by CT or MRI examination. Two weeks after the operation, external irradiation to the mediastinum with Linac 10 MV X-ray, and to the bilateral cervical regions with Linac 15 MeV electron beam, was started. The irradiation doses were 30 Gy (2 Gy/day, 5 times/ week) and 48 Gy (4 Gy/day, 3 times/week), respectively. The intracavitary irradiation with RALS was started shortly before the end of the external irradiation period and was delivered from a 60Co source. The total dose was 24 Gy (6 Gy/day, once a week) for the esophagectomized cases, and 18 Gy for the bypassed cases. Two or three weeks after the termination of the radiotherapy, chemotherapy with cisplatinum and 5-fluorouracil was performed and repeated every 6 months for 2 years. All patients could eat normally and were discharged after finishing the first chemotherapy session. The overall 5-year survival rate was 49% for the esophagectomized cases and 11% for the bypassed cases. The longest survival time in the bypassed cases was 5 years and 4 months. Neither operative death nor severe complications were experienced during the treatment period. The results indicate that this newly developed multi-disciplinary treatment with RALS can improve the prognosis and the quality of life not only in the esophagectomized patients but also in the bypassed patients with advanced esophageal cancer.

Immunohistochemical characterization of p57KIP2 expression in human esophageal squamous cell carcinoma.

Functional defects in the CIP/KIP family of cyclin-dependent kinase inhibitors (CDKIs) have been shown to be associated with human malignancies. We immunohistochemically examined p57KIP2 (p57) expression in 92 patients with human esophageal squamous cell carcinoma (SCC) to determine the relationship between this expression and those of cyclin D1 and E. The p57 labeling index (LI) (defined as the percentage of p57-positive cells) in esophageal SCC was 43.3 +/- 3.2% (mean +/- standard error of the mean). In non-neoplastic esophageal epithelium, p57 staining was more frequently observed in the basal and parabasal cells than in surface layer cells. Immunostaining for cyclin D1 and E was observed in 28.2% (28/92) and 32.6% (30/92) of tumors, respectively. The median p57 LI in cyclin D1-positive cases was 66.2, and significantly higher than that in negative cases (31.9%) (p = 0.0009). There was no significant relationship between p57 LI and cyclin E expression (p = 0.147). As determined using Kaplan-Meier's method, loss of p57 immunoreactivity was not a prognostic factor for esophageal SCC (p = 0.548). Our in vivo findings suggested that p57 protein expression was positively correlated with cyclin D1 expression and that loss of p57 protein expression alone does not affect progression of esophageal SCC.

Effects of OG-VI, a nucleoside-nucleotide mixture, on ischemic myocardial metabolism in dogs.

BACKGROUND: OG-VI is a solution composed of 30 mmol/l inosine, 30 mmol/l sodium 5'-guanylate, 30 mmol/l cytidine, 22.5 mmol/l uridine, and 7.5 mmol/l thymidine, which is known to improve myocardial stunning. OBJECTIVE: To study the effect of OG-VI on myocardial energy and carbohydrate metabolism during ischemia. METHODS: Ischemia was induced in pentobarbital-anesthetized open-chested dogs for 3 min by left anterior descending coronary artery ligation. Saline, 1.2 mmol/kg per min OG-VI, or 12 mmol/kg per min OG-VI was infused at 0.1 ml/kg per min, starting 30 min before the onset of ischemia. The myocardium was extracted 3 min after the onset of ischemia, and used to determine the tissue levels of energy and carbohydrate metabolites. RESULTS: Ischemia decreased the levels of ATP and fructose 1,6 diphosphate significantly, and increased those of AMP, glucose 6 phosphate, fructose 6 phosphate and lactate. OG-VI infusion preserved the adenine nucleotide levels significantly in 3 min ischemic hearts, and attenuated the ischemia-induced alteration of carbohydrate metabolism. CONCLUSION: OG-VI may improve the myocardial metabolic derangement induced by ischemia.

Effects of pimobendan and EGIS 9377, cardiotonic agents, and OG-VI, a nucleoside-nucleotide mixture, administered during reperfusion after ischemia on stunned myocardium in dogs.

BACKGROUND: Pimobendan is a so-called calcium sensitizer that exerts a positive inotropic action. EGIS 9377 is synthesized as a calcium sensitizer. OG-VI is a nucleoside-nucleotide mixture that ameliorates the myocardial dysfunction (myocardial stunning) after ischemia. OBJECTIVE: To determine whether administration of these agents after the onset of reperfusion after ischemia improves the condition of stunned myocardium. METHODS: Dogs anesthetized with pentobarbital were subjected to 20 min ligation of left anterior descending coronary artery and then 60 min reperfusion. The corresponding vehicle, 0.3 and 1 mg/kg pimobendan, or 1 and 3 mg/kg EGIS 9377 was injected intravenously 30 min after the onset of reperfusion. Saline solution or 1.2 mumol/kg per min OG-VI was infused for 30 min, starting 30 min after the reperfusion. Shortening of myocardial segment was measured by sonomicrometry. The tissue levels of energy and carbohydrate metabolites in the 60 min-reperfused hearts were determined. RESULTS: Shortening of myocardial segments significantly decreased during ischemia, and returned toward preischemic level after reperfusion for all groups, although the contractile dysfunction still remained. Injections and infusion of pimobendan, EGIS 9377, and OG-VI after the onset of reperfusion ameliorated the contractile dysfunction. Systemic vascular resistance was decreased by administrations of pimobendan and OG-VI. The levels of high-energy phosphates in 60 min-reperfused heart were not changed by either treatment. CONCLUSION: Administration of pimobendan, EGIS 9377, and OG-VI ameliorate the myocardial contractile dysfunction after ischemia even when these agents are administered after the onset of reperfusion. The increase in contractile function due to these agents did not worsen the myocardial energy balance.

Effect of a nucleoside-nucleotide mixture on protein metabolism in rats after seventy percent hepatectomy.

The effect of a nucleoside-based mixture (OG-VI) on protein synthesis in partially hepatectomized rats was evaluated. Twenty male Wistar rats weighing about 200 g underwent 70% hepatectomy by Higgins and Anderson's method, and then were subjected to total parenteral nutrition (TPN) for 3 days: the control group received only standard TPN (S-TPN group) and the experiment group received standard TPN supplemented with a nucleoside-nucleotide mixture (13% W/V, OG-VI) (OG-TPN group). The rates of whole body protein turnover and protein synthesis and breakdown were determined for 3 days after hepatectomy by the method of Picou and Taylor-Roberts with [15N] glycine. The nitrogen balances on days 1 and 3 and the cumulative nitrogen balance were significantly higher in the OG-TPN group than in the control group. Moreover, the rates of protein turnover and protein synthesis were significantly higher in the OG-TPN group than in the control group. Thus, increase in protein synthesis, rather than change in protein breakdown, was concluded to be responsible for the better nitrogen balance of the OG-TPN group. These findings suggest that the nucleoside-nucleotide mixture was used for the syntheses of RNA and DNA through the salvage pathway in regenerating liver and that this resulted in enhanced protein turnover with simultaneous increase in protein synthesis.