Two-Proton Radioactivity of

In an experiment with the BigRIPS separator at the RIKEN Nishina Center, we observed two-proton (2p) emission from ^{67}Kr. At the same time, no evidence for 2p emission of ^{59}Ge and ^{63}Se, two other potential candidates for this exotic radioactivity, could be observed. This observation is in line with Q value predictions which pointed to ^{67}Kr as being the best new candidate among the three for two-proton radioactivity. ^{67}Kr is only the fourth 2p ground-state emitter to be observed with a half-life of the order of a few milliseconds. The decay energy was determined to be 1690(17) keV, the 2p emission branching ratio is 37(14)%, and the half-life of ^{67}Kr is 7.4(30) ms.

Hepatic arterial complications in adult living donor liver transplant recipients: a single-center experience of 673 cases.

BACKGROUND: Hepatic arterial reconstruction during living donor liver transplantation (LDLT) is a very delicate and technically complicated procedure. Post-LDLT hepatic arterial complications are associated with significant morbidity and mortality. METHODS: We retrospectively analyzed the details of post-operative hepatic arterial complications in 673 consecutive adult LDLT recipients between January 1996 and September 2009. RESULTS: Hepatic arterial complications occurred in 43 of 673 adult recipients (6.4%) within a median of 13 post-transplant days (range, 1-63). These included hepatic artery thrombosis (including anastomotic stenosis) in 33 cases, anastomotic bleeding in seven cases, and rupture of anastomotic aneurysm in three cases. To treat these complications, surgical re-anastomosis was performed in 26 cases, while the other 17 cases underwent conservative therapies, including four angioplasties by interventional radiology. Biliary complications after hepatic arterial complications occurred in 17 cases. The overall survival rate after LDLT was significantly lower in the hepatic arterial complication group compared with that in the non-complication group (60.7% vs. 80.1% at one yr, 44.3% vs. 74.2% at five yr, respectively; p < 0.001). Multivariate analysis showed that the extra-anatomical anastomosis (p = 0.011) was the only independent risk factor for hepatic arterial complications. CONCLUSION: Because hepatic arterial complications after LDLT are associated with poor patient survival, early diagnosis and immediate treatment are crucial. The anatomical anastomosis may be the first choice for the hepatic arterial reconstruction to the extent possible.

A novel organ preservation for small partial liver transplantations in rats: venous systemic oxygen persufflation with nitric oxide gas.

The prognosis for recipients of small liver grafts is poor. The aim of this study was to determine the impact of venous systemic oxygen persufflation (VSOP) with nitric oxide (NO) gas for 30% partial liver preservation and transplantation in rats. After we determined optimal NO concentration as 40 ppm in vitro with the isolated perfused rat liver model, we assessed liver injury and regeneration in vivo at 1, 3, 24 and 168 h after transplantation in the following three groups after 3 h-cold storage (n = 20 per group): control group = static storage; VSOP group = oxygen persufflation and VSOP+NO group = oxygen with NO persufflation. The liver graft persufflation was achieved with medical gas via the suprahepatic vena cava; In comparison with control group after transplantation, VSOP+NO preservation (1) increased portal circulation, (2) reduced AST and ALT release, (3) upregulated hepatic endothelial NO synthase, (4) reduced hepatocyte and bileductule damage and (5) improved liver regeneration. These results suggest that gaseous oxygen with NO persufflation is a novel and safe preservation method for small partial liver grafts, not only alleviating graft injury but also improve liver regeneration after transplantation.

Impact of sarcopenia on survival in patients undergoing living donor liver transplantation.

Skeletal muscle depletion, referred to as sarcopenia, predicts morbidity and mortality in patients undergoing digestive surgery. However, the impact on liver transplantation is unclear. The present study investigated the impact of sarcopenia on patients undergoing living donor liver transplantation (LDLT). Sarcopenia was assessed by a body composition analyzer in 124 adult patients undergoing LDLT between February 2008 and April 2012. The correlation of sarcopenia with other patient factors and the impact of sarcopenia on survival after LDLT were analyzed. The median ratio of preoperative skeletal muscle mass was 92% (range, 67-130%) of the standard mass. Preoperative skeletal muscle mass was significantly correlated with the branched-chain amino acids to tyrosine ratio (r = -0.254, p = 0.005) and body cell mass (r = 0.636, p < 0.001). The overall survival rate in patients with low skeletal muscle mass was significantly lower than in patients with normal/high skeletal muscle mass (p < 0.001). Perioperative nutritional therapy significantly increased overall survival in patients with low skeletal muscle mass (p = 0.009). Multivariate analysis showed that low skeletal muscle mass was an independent risk factor for death after transplantation. In conclusion, sarcopenia was closely involved with posttransplant mortality in patients undergoing LDLT. Perioperative nutritional therapy significantly improved overall survival in patients with sarcopenia.

Pediatric liver transplantation using reduced and hyper-reduced left lateral segment grafts: a 10-year single-center experience.

Few studies have examined the long-term outcomes and prognostic factors associated with pediatric living living-donor liver transplantation (LDLT) using reduced and hyper-reduced left lateral segment grafts. We conducted a retrospective, single-center assessment of the outcomes of this procedure, as well as clinical factors that influenced graft and patient survival. Between September 2000 and December 2009, 49 patients (median age: 7 months, weight: 5.45 kg) underwent LDLT using reduced (partial left lateral segment; n = 5, monosegment; n = 26), or hyper-reduced (reduced monosegment grafts; n = 18) left lateral segment grafts. In all cases, the estimated graft-to-recipient body weight ratio of the left lateral segment was more than 4%, as assessed by preoperative computed tomography volumetry, and therefore further reduction was required. A hepatic artery thrombosis occurred in two patients (4.1%). Portal venous complications occurred in eight patients (16.3%). The overall patient survival rate at 1, 3 and 10 years after LDLT were 83.7%, 81.4% and 78.9%, respectively. Multivariate analysis revealed that recipient age of less than 2 months and warm ischemic time of more than 40 min affected patient survival. Pediatric LDLT using reduced and hyper-reduced left lateral segment grafts appears to be a feasible option with acceptable graft survival and vascular complication rates.

Effect of portal haemodynamics on liver graft and intestinal mucosa after small-for-size liver transplantation in swine.

BACKGROUND: After small-for-size graft (SFSG) transplantation, elevated portal venous pressure (PVP) may lead to postoperative liver damage. Herein we evaluated the impact of portocaval shunt (PCS) to control PVP on liver grafts and intestine following SFSG transplantation. METHODS: Nineteen SFSG transplantations were performed with 30% of native liver in swine. Swine were divided into 3 groups: a high-flow shunt group (HS: n = 7), in which portal venous flow (PVF) was reduced with a 10-mm diameter PCS; a low-flow shunt group (LS: n = 6), in which PVF was reduced with a 5-mm diameter PCS, and a no-shunt group (NS: n = 6), in which no PCS was placed. RESULTS: Seven-day survivals were 83.3% in NS, 100% in LS and 0% in HS (p = 0.0088). PVP was significantly higher in the NS group (p = 0.0001; mean ± SEM NS/LS/HS: 20.5 ± 0.7/14.0 ± 1.2/11.6 ± 0.5 mm Hg). The LS group exhibited the highest compliance (PVF/PVP; NS/LS/HS 42.7 ± 10.9/44.6 ± 4.9/37.7 ± 8.3 ml/min/mm Hg; p = 0.009), the lowest aspartate aminotransferase (NS/LS/HS 562 ± 18/370 ± 55/720 ± 130 IU/l; p = 0.0493), and suppressed deleterious alternations of the hepatic parenchyma and intestinal mucosa. CONCLUSIONS: Portal hypertension after SFSG transplantation impaired liver and intestinal mucosa; however, inadequate portal flow impaired not only the liver, but also survival.

Influence of Helicobacter pylori eradication on reflux esophagitis in Japanese patients.

The relationship between Helicobacter pylori eradication and reflux esophagitis is controversial. We analyzed the development of reflux esophagitis and the change in the grade of pre-existing reflux esophagitis after eradication. Enrolled were 559 Japanese patients who received eradication therapy for H. pylori. The grade of reflux esophagitis by endoscopy before and after therapy was evaluated retrospectively. No esophagitis was present before eradication in 526 patients. H. pylori was and was not eradicated in 429 and 97, respectively. Reflux esophagitis developed in 40 of the eradication group and in three of the treatment failure group, with prevalence higher with successful eradication (P = 0.04). Successful eradication and hiatus hernia were significant risk factors for reflux esophagitis development. Twenty-seven of 33 patients with pre-existing reflux esophagitis had successful eradication and six treatment failure. The reflux esophagitis grade worsened in two (Los Angeles classification from A to B) and improved in 14 patients after eradication. With treatment failure, reflux esophagitis worsened in none and improved in three patients. There showed no significant change in the grade of pre-existing reflux esophagitis after H. pylori eradication but the sample size was too small to evaluate the difference. In conclusion, the eradication of H. pylori increases the prevalence of reflux esophagitis, and hiatus hernia was a significant risk factor for the development of reflux esophagitis.

Epigenetics: the DNA methylation profile of tissue-dependent and differentially methylated regions in cells.

Methylation of DNA, which occurs at cytosines of CpG sequences, is a unique chemical modification of the vertebrate genome. Methylation patterns can be copied to daughter DNA after mitosis; thus DNA methylation has been suggested to act as a "cellular memory of the genome function". Genome-wide analysis of DNA methylation revealed that there are numerous tissue-dependent differentially methylated regions (T-DMRs) in unique sequences of the mammalian genome. There are T-DMRs in both CpG-rich and -poor sequences. Methylation of T-DMRs is responsible for gene-silencing and chromatin structure change. Each tissue/cell type has a unique DNA methylation profile that consists of methylation patterns of numerous loci in the genome. DNA methylation profiles are not associated with bulk DNA, which is mainly comprised of repetitive sequences. Disruption of DNA methylation profiles putatively produce abnormal cells and tissues. Cloned mice produced by somatic nuclear transfer are associated with aberrant DNA methylation profiles. Tissue/cell type-specific DNA methylation profiles can provide a novel viewpoint for understanding normal and aberrant development, in terms of both differentiation and reproduction.

Satisfaction with bispectral index monitoring of propofol-mediated sedation during endoscopic submucosal dissection: a prospective, randomized study.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is one of the most complex and lengthy endoscopic procedures, so deep sedation during ESD is indispensable. Our study aims were to determine whether bispectral index (BIS) monitoring is useful in titrating and reducing the dose of the sedative propofol during ESD, and to measure the satisfaction of patients and endoscopists involved in this complex and lengthy endoscopic therapy. PATIENTS AND METHODS: We performed a prospective, randomized clinical trial from July 2006 to February 2008. A total of 156 patients, with gastric neoplasm to be treated using ESD, were randomized to two groups. The BIS group (n = 78) was monitored for propofol sedation using BIS, and the no-BIS group (n = 78) was monitored by standard methods only. The two groups were compared by evaluating the doses of propofol administered to patients and the satisfaction scores (scale of 0 - 10) of patients and endoscopists. RESULTS: Although there were no significant differences between the two groups in the mean dose of propofol used (BIS group vs. no-BIS group, 5.32 mg/kg/hour vs. 4.85 mg/kg/hour; P = 0.10), the satisfaction scores of the patients (9.15 vs. 7.94; P < 0.01) and endoscopists (8.53 vs. 6.42; P < 0.001) were significantly higher with BIS monitoring. CONCLUSIONS: Monitoring with BIS during the ESD procedure did not lead to a reduction in the dose of propofol required, but did lead to higher satisfaction scores from the patients and endoscopists. A complicated and prolonged endoscopic treatment such as ESD can be carried out with optimal safety, control, and comfort by using BIS to monitor propofol sedation.

Henoch-Schönlein Purpura After Living Donor Liver Transplantation: Report of the First Case.

Henoch-Schönlein purpura (HSP) is a systemic vasculitis affecting the small vessels that mainly presents in children and young adults. It is characterized by tissue deposition of immunoglobulin A (IgA) immune complexes with the classic manifestations of purpura, arthritis, arthralgia, and gastrointestinal and renal involvements. We report a case of HSP nephritis that occurred 2 years after living-donor liver transplantation (LDLT). After pulse steroid administration, the patient's symptoms disappeared and blood markers normalized. To the best of our knowledge, this is the first HSP case to be reported in a liver transplant recipient.

Coexistent End-stage Nonalcoholic Steatohepatitis and Colon Cancer: Should We Do Liver Transplantation?

BACKGROUND: Colon cancer accompanying decompensated liver cirrhosis is a rare clinical condition. Usually, treatment of colon cancer is prioritized, with cirrhosis dealt with later. CASE REPORT: We present a case of end-stage liver disease due to nonalcoholic steatohepatitis evaluated for living donor liver transplant. During the pretransplant examination, an ascending colon cancer was detected. Liver function was too poor to perform colon resection first. Simultaneous living donor liver transplant and colonic resection were carried out. The patient developed left lung metastasis at 2 different times during the first postoperative year, and both of them were resected. The patient received the standard chemoradiotherapy. Now, the patient is alive at 42 months postprocedure and recurrence-free at 31 months postoperatively. CONCLUSION: Simultaneous liver transplantation and colon resection are possible with acceptable long-term outcomes. Immunosuppressive therapy after transplantation increases the risk for cancer recurrence. So the patient should undergo close surveillance.

Case Report of Extensive Isolated Spontaneous Celiac Trunk Dissection After Liver Transplantation.

Arterial dissection is a rare complication after liver transplantation (LT). We report a case of extensive isolated spontaneous celiac trunk dissection (ISCTD) up to the proper hepatic artery, left gastric artery, and splenic artery after living donor liver transplantation. A 48-year-old woman with cryptogenic liver cirrhosis underwent living donor liver transplantation. Intraoperative and postoperative Doppler ultrasound revealed sufficient flow in the hepatic artery, portal vein, and hepatic vein. On postoperative day (POD) 10, Doppler ultrasound showed reduction of hepatic arterial flow. On POD 16, a contrast-enhanced computed tomography scan showed that the ISCTD extended to the proper hepatic artery, left gastric artery, and splenic artery with an entry tear on the proximal side of the celiac trunk. Although the computed tomography scan showed ischemia of a small part of the liver, blood flow to the liver was kept to some extent. Because all false lumens were occluded by thrombi and the liver enzyme levels normalized, we chose conservative therapy with antiplatelet agents. The patient was discharged on POD 53. She remains well without any liver dysfunction after 18 months with reduction in all false lumens and a patent hepatic artery. Several cases of ISCTD have been reported apart from LT, most of which were treated with conservative therapy. We conclude that conservative therapy could be the first choice in ISCTD even after LT.

Global tuning of local molecular phenomena: an alternative approach to bionanoelectronics.

We have applied simultaneous horizontal and vertical bias to a single molecule (2 nm(2)) in an ordered and disordered matrix to virtually isolate and tune its property without taking it out physically from its environment. Using a dedicated electrode system, we have locally tuned nanoscale properties vertically by STM, while stabilizing its environment by applying a global electric field horizontally. Using this technique, we report tuning of molecular conformations in room temperature, whose evolution of states has been statistically investigated. We have also shown control on switching of a few selected conformations by applying dual bias simultaneously. As we avoid any direct injection of charge into the system via electrode contact, this technique could be used as a generalized method to tune phenomena evolved in an environment of weak interaction from a large distance without destroying the property.

Significance of lymph node micrometastasis in pN0 hilar bile duct carcinoma.

AIMS: To examine micrometastasis in node-negative hilar bile duct carcinoma (HBDC) using an immunohistochemical method and evaluated the clinical significance. METHODS: Four hundred and twenty three regional lymph nodes from 28 patients with node-negative HBDC who had undergone a resection were immunostained with an antibody against cytokeratins eight and 18 (CAM 5.2). RESULTS: Lymph node micrometastasis was detected in 11 of the 28 patients and 14 of the 423 lymph nodes. Lymph node micrometastasis was significantly correlated with the pT classification (p=0.03), the histopathological grading (p=0.01) and venous invasion (p=0.05). The 5-year survival rate of the patients with lymph node micrometastasis was 21.8%, as opposed to 66.5% in the patients without micrometastasis. Patients with micrometastasis showed a significantly poorer survival rate than those without micrometastasis (p=0.02). CONCLUSION: The results suggest that immunohistochemically detected lymph node micrometastasis has an impact on the outcome in HBDC.

Anticancer efficacy in vivo and in vitro, synergy with 5-fluorouracil, and safety of recombinant methioninase.

The elevated exogenous-methionine dependency of tumors for growth has been observed in all major cancer cell types. We have previously cloned a methioninase (rMETase) from Pseudomonas putida to deplete methionine. Growth inhibition followed by apoptotic cell death was induced by treatment of tumor cells with rMETase in vitro. A single i.p. injection of 300 units of rMETase can lower the serum methionine level in the mice from 70 microM to less than 1 microM within 2 h and maintain this depleted level for 8 h. Repeated dosing of rMETase of tumor-bearing mice could be administered without acute immune-hypersensitivity. rMETase treatment demonstrated growth inhibitory activity against human tumors in nude mice, including those which were multiple drug-resistant. No body weight loss or hematotoxicity, except a slight anemia, was found throughout the therapy. The combined treatment of the Lewis lung carcinoma with a fixed rMETase dose and increasing doses of 5-fluorouracil (5-FU) resulted in a dose-dependent enhanced antitumor efficacy for survival as well as tumor growth inhibition. Thus, methionine depletion by rMETase potentiates the antitumor efficacy of 5-FU. The data presented in this report thus indicate that rMETase is active alone, is synergistic in combination with 5-FU, and has negligible toxicity suggesting a novel clinical approach for effective cancer therapy.

Effects of insulin on vasoconstrictive responses to norepinephrine and angiotensin II in rabbit femoral artery and vein.

To determine whether insulin has a vasodilator action on the artery and vein, the effects of insulin at varying concentrations (120 microU/ml, 1.2 mU/ml, 12 mU/ml, and 120 mU/ml) on vasoconstriction by norepinephrine (NE) and angiotensin II (ANG II) were studied in the isolated rabbit femoral artery and vein. Helical strips were suspended in an organ bath filled with modified Krebs solution (pH 7.4), were gassed with 95% O2/5% CO2 at 36 degrees C, and isotonic contractions were measured. Insulin significantly and dose dependently inhibited the vasoconstriction induced by NE (10(-8) M for the artery and 10(-7) M for the vein) at greater than or equal to 1.2 mU/ml for both the artery and vein and the vasoconstriction induced by ANG II (3 x 10(-10) M for the artery and 3 x 10(-9) M for the vein) at greater than or equal to 1.2 mU/ml for the artery and greater than or equal to 12 mU/ml for the vein. The results indicate that insulin has an inhibitory effect on NE- and ANG II-induced contraction in both the artery and vein, and this appeared to be a contributory factor in the hypotensive effect observed in diabetic patients treated with insulin.

Identification of a commonly deleted region at 17p13.3 in leukemia and lymphoma associated with 17p abnormality.

Fluorescence in situ hybridization (FISH) was performed in 17 myeloid leukemia patients and seven lymphoid leukemia/ lymphoma patients who exhibited chromosomal abnormalities on the short arm of chromosome 17, in order to detect a commonly deleted region on chromosome band 17p13. Twenty-four leukemia/lymphoma patients studied cytogenetically at our institution over a period of 10 years had detectable 17p abnormalities such as translocation (six patients), addition (11 patients) and deletion of 17p13 (seven patients). A 17p abnormality was the only abnormality present in three patients. Most of the patients had additional complex cytogenetic abnormalities. The diagnosis was acute myeloid leukemia (AML) in 10 patients, two each with chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and myelodysplastic syndrome (MDS) and the remaining three with malignant lymphoma (ML). Seven cosmid probes (D17S34, cCI17-624, cCI17-453, D17S379, cCI17-636, cCI17-732 and TP53) which mapped on 17p13 were used to analyze the allelic deletion. Eighty percent (19 out of 24) of the informative leukemia patients exhibited allelic loss in 17p13.3 at cC17-624. The smallest region of an overlapping deletion was observed on chromosome band 17p13.3 between cCI17-624 and cCI17-453. Patients with translocation involving 17p also showed deletion at cCI17-624 and cCI17-453. We hypothesize that this region contains a novel tumor suppressor gene(s) that is involved in leukemogenesis.

Non-invasive assessment of the age related changes in stiffness of major branches of the human arteries.

The static mechanical properties of major branches of the human arteries (common carotid artery, abdominal aorta, femoral artery, and brachial artery) were studied in 39 subjects, aged 6-81 years, using an ultrasonic phase locked echo tracking system that allows continuous transcutaneous measurement of the diameter of the artery. The stiffness indices were calculated from the relation between systemic blood pressure and arterial diameter. With advancing age there was a significant increase in the diameter of all arteries with a reduction in percentage change in diameter. The stiffness index increased with age in all arteries; however, in the brachial and femoral arteries there was considerable variation in the individual values for a given age. The age associated increase in stiffness was statistically significant only in the common carotid artery and the abdominal aorta. Although the mechanical properties of the peripheral arteries were significantly influenced by the measuring environment, the calculated stiffness indices were less vulnerable to these stimuli in the central arteries. These results indicate that the stiffness indices of the peripheral muscular arteries are modified appreciably by vasoactive stimuli and that the mechanical properties of the deeper elastic arteries provide sufficiently reliable information about changes caused by aging and arteriosclerosis. The new ultrasonic method used appears to be suitable for this analysis.

Antihypertensive effect of interleukin-2 in salt-sensitive Dahl rats.

We investigated the effects of interleukin-2, which stimulates the proliferation and maturation of thymus-derived lymphocytes, on hypertension and organ injuries in genetically hypertensive rats. Interleukin-2 (5 x 10(4) U/kg body wt) was subcutaneously injected into Dahl salt-sensitive rats fed a 4% NaCl diet and spontaneously hypertensive rats once a week for 10 weeks. The effects on blood pressure, cardiovascular hypertrophy, and renal function were evaluated. Interleukin-2 treatment lowered blood pressure in Dahl salt-sensitive rats (162 versus 187 mm Hg, P < .005). This antihypertensive effect was associated with an increase in glomerular filtration rate (589 versus 428 mL/d per 100 g body weight, P < .005) and reduction in cardiac weight (268 versus 305 mg/100 g body weight, P < .05). Interleukin-2 also alleviated the marked glomerular sclerosis in Dahl salt-sensitive rats (glomerular injury score, 151 versus 220; P < .001). In contrast, interleukin-2 did not affect the development of hypertension or organ injuries in spontaneously hypertensive rats. Histologically, glomerular and arterial lesions of the kidney were much less marked in spontaneously hypertensive rats than in Dahl salt-sensitive rats. These data indicate that interleukin-2 ameliorates the development of hypertension and cardiac and renal injuries in Dahl salt-sensitive rats.