Emission of low-energy positronium from alkali-metal coated single-crystal tungsten surfaces.

We have measured the time-of-flight of ortho-positronium emitted from Cs-, Na- and Li-coated single-crystal tungsten surfaces. The data obtained after the coating show a new positronium energy component with a specific energy loss in addition to the component whose emission energy is simply determined by the positron and the electron work functions. We suggest that this new component is attributed to the formation of positronium accompanied by inter-band transition and/or surface plasmon excitation at the surfaces.

Structure determination of the rutile-TiO2(110)-(1 × 2) surface using total-reflection high-energy positron diffraction (TRHEPD).

The exact structure of the rutile-TiO2(110)-(1 × 2) surface, which had been under debate over the past 30 years, was investigated using the newly developed technique of total-reflection high-energy positron diffraction (TRHEPD), which is a positron counterpart of reflection high-energy electron diffraction (RHEED). The rocking-curves for the 00-spot obtained from the experimental diffraction patterns were compared to the curves for various models calculated with a full-dynamical theory. It was found that the rocking-curves matched those for a surface consisting of a Ti2O3 configuration, originally suggested by Onishi and Iwasawa [H. Onishi and Y. Iwasawa, Surf. Sci., 1994, 313, L783], but with a further modification of atomic positions close to the ones proposed by Wang et al. [Q. Wang, A. R. Oganov, Q. Zhu and X. F. Zhou, Phys. Rev. Lett., 2014, 113, 266101]. This result demonstrates that TRHEPD can distinguish between the existence and absence of the oxygen atoms on the topmost surface, and between the Ti atoms residing in positions at the interstitial-vertical sites and those at interstitial-horizontal sites.

S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial).

BACKGROUND: S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur-uracil plus leucovorin (UFT/LV). PATIENTS AND METHODS: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120 mg/day on days 1-28 every 42 days; four courses) or UFT/LV (UFT: 300-600 mg/day and LV: 75 mg/day on days 1-28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years. RESULTS: A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70-1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups. CONCLUSION: Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer. CLINICALTRIALSGOV: NCT00660894.

Safety of UFT/LV and S-1 as adjuvant therapy for stage III colon cancer in phase III trial: ACTS-CC trial.

BACKGROUND: The Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) is a phase III trial designed to validate the non-inferiority of S-1 to UFT/leucovorin (LV) as postoperative adjuvant chemotherapy for stage III colon cancer. We report the results of a planned safety analysis. METHODS: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive UFT/LV (UFT, 300 mg m(-2) per day as tegafur; LV, 75 mg per day on days 1-28, every 35 days, 5 courses) or S-1 (80, 100, or 120 mg per day on days 1-28, every 42 days, 4 courses). Treatment status and safety were evaluated. RESULTS: Of 1535 enrolled patients, a total of 1504 (756 allocated to S-1 and 748 to UFT/LV) were analysed. The completion rate of protocol treatment was 77% in the S-1 group and 73% in the UFT/LV group. The overall incidence of adverse events (AEs) were 80% in S-1 and 74% in UFT/LV. Stomatitis, anorexia, hyperpigmentation, and haematological toxicities were common in S-1, whereas increased alanine aminotransferase and aspartate aminotransferase were common in UFT/LV. The incidences of grade 3 AEs were 16% and 14%, respectively. CONCLUSION: Although AE profiles differed between the groups, feasibility of the protocol treatment was good. Both S-1 and UFT/LV could be safely used as adjuvant chemotherapy.

Molecular cloning of a novel CC chemokine, interleukin-11 receptor alpha-locus chemokine (ILC), which is located on chromosome 9p13 and a potential homologue of a CC chemokine encoded by molluscum contagiosum virus.

Molluscum contagiosum virus (MCV) encodes a CC chemokine MC148R which is likely to have been acquired from the host. By a homology search employing MC148R as a probe, we have identified a novel CC chemokine whose gene exists next to the IL-11 receptor alpha (IL-11Ralpha) gene in both humans and mice. Thus, this chemokine maps to chromosome 9p13 in humans where IL-11Ralpha has been assigned. We term this novel chemokine IL-11Ralpha-locus chemokine (ILC). ILC has the highest homology to MC148R among the known human CC chemokines. Furthermore, ILC is strongly and selectively expressed in the skin where infection of MCV also takes place. Thus, ILC is likely to be the original chemokine of MC148R.

Ultrastructural studies on the formation and distribution of lipid droplets in the lung capillary endothelial cells in patients with sarcoidosis.

BACKGROUND AND AIM OF THE WORK: We previously reported the presence of definite morphological alterations in the capillary endothelium of sarcoid lung. The aim of this study was to examine ultrastructural changes and distribution of lipid droplets in the endothelium of lung capillaries of patients with sarcoidosis. METHODS: Tissue specimens were obtained by transbronchial lung biopsy or open lung biopsy from 16 patients with sarcoidosis and 13 controls. Biopsies were evaluated by electron microscopy following lead citrate and uranyl acetate staining. RESULTS: Typical lipid droplets were observed in pulmonary capillaries of 11 out of 16 sarcoid patients (69%); the droplet frequency was higher in sarcoid patients than in control specimens. Lipid droplets were characterized by biphasic density: most droplets contained eccentrically located vacuoles (saturated fatty acids) others were characterized by low density areas (unsaturated fatty acids). Biphasic droplets were covered by large lysosomal granules and were mainly distributed in the endothelium and pericytes. Interestingly, in the latter, vacuoles increased in size while small amounts of lysosomal granules were detectable. CONCLUSION: Our findings suggest that biphasic droplets increase in number in pulmonary capillaries of patients with sarcoidosis with a characteristic distribution pattern from the endothelium to pericytes.

Endothelial cell damage in sarcoidosis and neurosarcoidosis: autoantibodies to endothelial cells.

Damage to the vascular system, of which endothelial cells are the main constituent, may occur in sarcoidosis. Evidence of blood-brain barrier (BBB) disruption is shown in sarcoidosis with central nervous system (CNS) involvement by means of magnetic resonance imaging or computed tomography. We investigated the presence of antiendothelial cell antibodies by culture of endothelial cells derived from human umbilical cord vein and from human brain using an enzyme-linked immunosorbent assay, and the presence of circulating immune complexes using a Raji cell assay, in the sera of patients with sarcoidosis. The patients with sarcoidosis displayed significantly high levels of immunoglobulin G (IgG) binding to endothelial cells after blocking Fc receptor compared to controls (p < 0.01). The sera of neurosarcoid patients with CNS involvement still showed significantly increased levels of IgG binding to brain endothelial cells after blocking Fc receptor compared to controls and those of pulmonary sarcoidosis (p < 0.001 and p < 0.01 respectively). These results suggest that the presence of autoantibodies to endothelial cells may be involved in endothelial cell damage, including BBB disruption.

[Capillary endothelial cells in sarcoidosis--electron microscopic findings].

The distribution of von Willebrand (vW) factor, thrombomodulin (TM) and fibronectin (FN) in the capillary endothelial cells of the lung of patients with sarcoidosis was investigated using their monoclonal or polyclonal antibodies. The vW factor showed strong reaction with exudation towards outside and irregular dilatation or occlusion in the capillary walls surrounded sarcoid granulomas and capillaries in the remote area. The area showing alveolitis disclosed also strong reaction with exudation by vW factor. TM having a anti-coagulating function showed a very low reactivity in the lung tissues with or without of granulomas in sarcoidosis at light microscopic level, but in electron microscopically, strong reaction and broad distribution in capillary endothelial cells, involving luminal occlusion and reaction in subendothelial region. FN showed new and many capillaries formation in the growing collagenous tissues between the old sarcoid granulomas suggesting neocapillarization originating from endothelial cells. These findings suggest that the capillary endothelial cells participate strongly in formal genesis of sarcoid granulomas.

Pulmonary vascular involvement in sarcoidosis: granulomatous angiitis and microangiopathy in transbronchial lung biopsies.

To evaluate the occurrence of granulomatous angiitis and microangiopathy in the lung with sarcoidosis, transbronchial lung biopsy specimens were examined from 174 cases with sarcoidosis. Granulomatous angiitis was seen in 72 cases, which corresponded to 53% of the cases with granulomata. Granulomatous angiitis showed venous involvement (65%), both venous and arterial involvement (24%) or arterial involvement only (11%). There was no significant difference in occurrence of granulomatous angiitis between upper and lower lobes. The cases with granulomatous angiitis in the lung had a higher frequency of ophthalmic symptoms and elevated serum angiotensin converting enzyme level. Basal lamina layering in the microvasculature was more often observed in the bronchial mucosa than in the alveolar walls and is not exclusively related to granulomata. Endothelial proliferation and basal lamina alterations in granulomatous angiitis may be closely associated with granulomas. The present study revealed coexistence of granulomatous angiitis and microangiopathy in the lung with sarcoidosis and suggests that both may participate in the development of pulmonary sarcoidosis.

Postoperative gastrointestinal hemorrhage in biliary atresia.

During the past 9 years, we have treated 23 patients with gastrointestinal hemorrhage following corrective surgery for biliary atresia. Ulcers or erosions of the stomach, duodenum or intestinal wall were observed endoscopically in 20 cases. In other 3 cases, bleeding point was not determined endoscopically, but massive bleeding was recognized frequently. Ten patients bled within 6 months of surgery, and the incidence of bleeding was also seen even after the age of 10 years. A history of cholangitis, the presence of jaundice and the use of cholagogues were related to the postoperative gastrointestinal bleeding. Serum concentrations of gastrin and gastric inhibitory polypeptide showed high values after surgery in almost half the biliary atresia patients examined, however, no clear relationship between the concentration of these factors and gastrointestinal hemorrhage was established.

Cholangiographic study of the pancreaticobiliary ductal junction in biliary atresia.

The size and arrangement of each component of pancreaticobiliary ductal junction was investigated in 28 cases with biliary atresia in which cholangiography allowed visualization of the common bile duct, pancreatic duct, and duodenum and in which relevant data were available. As controls, seven cases of neonatal hepatitis and eight cases of intrahepatic bile duct hypoplasia were also studied. The following results were obtained. (1) The diameter of the common bile duct was shortest in biliary atresia, the value corresponding to about one-third of that for neonatal hepatitis. (2) The common bile duct was visualized in 100% of cases of intrahepatic bile duct hypoplasia and 78% of cases of biliary atresia, whereas the corresponding percentage was only 43% for neonatal hepatitis. The mean length of the common channel in cases of biliary atresia and that of intrahepatic bile duct hypoplasia was about 5 mm, which was longer than that of neonatal hepatitis. (3) The pancreatic duct type, in which the pancreatic duct merged into the bile duct, was frequent in cases of biliary atresia.

Vascular lesions in the biopsied bronchus of patients with sarcoidosis changes of the endothelial cells in aggregation of eosinophils.

1) Aggregates of eosinophils closely related to the enlarged endothelial cells in the capillary vessels were recognized in 64% of 28 cases in biopsied specimens of the major bronchus of patients with sarcoidosis. 2) Electron microscopy revealed the vacuolated central cores or matrix in the specific granules of the eosinophils adjacent to the swollen vascular endothelial cells, frequent findings with attachment of the blood platelets to the damaged plasma membrane of the endothelial cells eventually becoming occluded in the lumen with platelet thrombosis, and multilayer formation of the basement membrane of the capillary vessels. 3) Sarcoidosis is suggested to be a pathological process producing both granuloma formation in each organ and vascular endothelial cell changes in the capillary vessels accompanied by aggregation of eosinophils in some periods of the disease process due to unidentified etiological factors.

Surgical limitation for biliary atresia: indication for liver transplantation.

Of 245 patients undergoing corrective operations for biliary atresia, jaundice was cleared in 113. In January 1988, 84 of them were living and free of jaundice and the other 19 were alive with jaundice. A vast majority of long-term survivors showed normal growth and development, and were leading normal lives for their respective ages. Portal hypertension, a common late complication, improved spontaneously or after sclerotherapy in jaundice-free patients. Therefore, liver transplantation is not recommended for jaundice-free patients even with esophageal varices. Patients with persistent severe jaundice (serum bilirubin over 10 mg/dL) and those with moderate jaundice (serum bilirubin 5 to 10 mg/dL) and severe esophageal varices require liver transplantation. Patients with moderate jaundice having no or slight varices should be carefully followed. When varices become worse or serum bilirubin rises, liver transplantation is indicated. Patients with mild jaundice (serum bilirubin lower than 5 mg/dL) have a possibility of improvement in their condition before the age of 15 years, and are not recommended for liver transplantation. The high value of the lowest postoperative bilirubin level suggests the necessity of liver transplantation in early childhood. Liver transplantation as the primary treatment for biliary atresia may be indicated only for patients over 120 days of age with an enlarged and hard liver.

Studies on subtype "d" biliary atresia.

Nine cases of specific type (subtype d) biliary atresia were experienced at the Tohoku University Hospital and were classified into three groups on the basis of their clinical and pathological findings. Group 1 cases were defined as cases showing obstruction on the side of the hepatic duct and cystic dilatation, communicating with the gallbladder, in the common bile duct. Group 2 cases were those showing dilatation similar to Group 1, but measuring less than 20 mm, the dilated part being covered with thick connective tissue. Group 3 cases were those showing isolated dilatation in the common hepatic duct or the common bile duct and having no communication with the gallbladder. The postoperative course was good in Group 1 patients, while jaundice was prolonged in Group 2 patients. In Group 3, jaundice disappeared in one patient who died later, while the other patient showed recurrence of slight jaundice.

Persistent jaundice after hepatic porto-jejunostomy in biliary atresia: are the patients' prognoses determined within 3 months after surgery?

Eighteen patients with biliary atresia who showed persistent jaundice after hepatic porto-jejunostomy were studied clinically. It was revealed that: 1) Patients who had abnormally high preoperative values of laboratory data showed persistent jaundice; 2) high portal pressure occurred frequently in patients with persistent jaundice; 3) most patients of persistent jaundice had a history of postoperative cholangitis; 4) in contrast to jaundice-free patients, those with persistent jaundice tended to show elevation in gamma-globulin, TTT and gamma-GTP in the early postoperative period. These results suggest that for patients showing an upward tendency in these laboratory data after surgery, carefully management should be taken, even if the serum bilirubin level continue to decrease.

Ultrastructural studies of concentric lamellar bodies in the bronchus of patients with sarcoidosis.

Biopsy specimens of the major bronchus of sixty-nine patients with sarcoidosis were investigated electronmicroscopically. 22 patients (12 males, 10 females), 32% of the cases, showed concentric lamellar or similar kinds of dense bodies in the bronchial wall. Typically, the concentric lamellar bodies were observed in various numbers, scattered in the collagen-increased tunica propria or superficial submucosal layer, where adjacent or deeply located blood capillary vessels were mostly obliterated. They were generally of 0.2 to 1.8 micron in size, but occasionally smaller ones were observed. We also found large swollen and irregular lamellated bodies greater than 2 microns in the cell cytoplasm. Six cases with particularly large numbers of these bodies in the bronchial wall showed "capped" figures, in which the concentric lamellar bodies were partly attached to other demilunar dense bodies. These figures were assumed to be the very early stage of formation of conchoidal bodies at the LM level, so-called Schaumann bodies. Two cases (5%) (chronic bronchitis, lung cancer) among 40 control patients with other diseases disclosed the same small lamellated bodies in the bronchial wall. We were unable to resolve the problem of the origin of these deposited in them, but assume that they will initially occur in the cell cytoplasm in some patients with sarcoidosis and eventually develop into typical concentric lamellar bodies.