Measurements of Strong-Interaction Effects in Kaonic-Helium Isotopes at Sub-eV Precision with X-Ray Microcalorimeters.

We have measured the 3d→2p transition x rays of kaonic ^{3}He and ^{4}He atoms using superconducting transition-edge-sensor microcalorimeters with an energy resolution better than 6 eV (FWHM). We determined the energies to be 6224.5±0.4(stat)±0.2(syst) eV and 6463.7±0.3(stat)±0.1(syst) eV, and widths to be 2.5±1.0(stat)±0.4(syst) eV and 1.0±0.6(stat)±0.3(stat) eV, for kaonic ^{3}He and ^{4}He, respectively. These values are nearly 10 times more precise than in previous measurements. Our results exclude the large strong-interaction shifts and widths that are suggested by a coupled-channel approach and agree with calculations based on optical-potential models.

Spectroscopy of Pionic Atoms in

We observed the atomic 1s and 2p states of π^{-} bound to ^{121}Sn nuclei as distinct peak structures in the missing mass spectra of the ^{122}Sn(d,^{3}He) nuclear reaction. A very intense deuteron beam and a spectrometer with a large angular acceptance let us achieve a potential of discovery, which includes the capability of determining the angle-dependent cross sections with high statistics. The 2p state in a Sn nucleus was observed for the first time. The binding energies and widths of the pionic states are determined and found to be consistent with previous experimental results of other Sn isotopes. The spectrum is measured at finite reaction angles for the first time. The formation cross sections at the reaction angles between 0° and 2° are determined. The observed reaction-angle dependence of each state is reproduced by theoretical calculations. However, the quantitative comparison with our high-precision data reveals a significant discrepancy between the measured and calculated formation cross sections of the pionic 1s state.

Fast Heating of Imploded Core with Counterbeam Configuration.

A tailored-pulse-imploded core with a diameter of 70 µm is flashed by counterirradiating 110 fs, 7 TW laser pulses. Photon emission (>40 eV) from the core exceeds the emission from the imploded core by 6 times, even though the heating pulse energies are only one seventh of the implosion energy. The coupling efficiency from the heating laser to the core using counterirradiation is 14% from the enhancement of photon emission. Neutrons are also produced by counterpropagating fast deuterons accelerated by the photon pressure of the heating pulses. A collisional two-dimensional particle-in-cell simulation reveals that the collisionless two counterpropagating fast-electron currents induce mega-Gauss magnetic filaments in the center of the core due to the Weibel instability. The counterpropagating fast-electron currents are absolutely unstable and independent of the core density and resistivity. Fast electrons with energy below a few MeV are trapped by these filaments in the core region, inducing an additional coupling. This might lead to the observed bright photon emissions.

Candidate Resonant Tetraneutron State Populated by the

A candidate resonant tetraneutron state is found in the missing-mass spectrum obtained in the double-charge-exchange reaction ^{4}He(^{8}He,^{8}Be) at 186 MeV/u. The energy of the state is 0.83±0.65(stat)±1.25(syst) MeV above the threshold of four-neutron decay with a significance level of 4.9σ. Utilizing the large positive Q value of the (^{8}He,^{8}Be) reaction, an almost recoilless condition of the four-neutron system was achieved so as to obtain a weakly interacting four-neutron system efficiently.

Measurement of Excitation Spectra in the

Excitation spectra of ^{11}C are measured in the ^{12}C(p,d) reaction near the η^{'} emission threshold. A proton beam extracted from the synchrotron SIS-18 at GSI with an incident energy of 2.5 GeV impinges on a carbon target. The momenta of deuterons emitted at 0° are precisely measured with the fragment separator (FRS) operated as a spectrometer. In contrast to theoretical predictions on the possible existence of deeply bound η^{'}-mesic states in carbon nuclei, no distinct structures are observed associated with the formation of bound states. The spectra are analyzed to set stringent constraints on the formation cross section and on the hitherto barely known η^{'}-nucleus interaction.

Treatment of pressure ulcers in patients with declining renal function using arginine, glutamine and ß-hydroxy-ß-methylbutyrate.

The aim of this study is to examine the efficacy on healing pressure ulcers (PU) of using a supplement combination containing arginine, glutamine and ß-hydroxy-ß-methylbutyrate, which was given to two elderly patients with renal dysfunction. The PU was surgically opened, decompressed and treated by drugs. A half quantity of the defined dose of the supplement combination, with an enteral nutrition product, was administered to the patients twice a day. This combination improved the PUs, with no effect on renal function. This novel finding may provide a nutritional rationale of arginine, glutamine and ß-hydroxy-ß-methylbutyrate for PUs associated with renal dysfunction.

Clinicopathological significance of laminin-5γ2 chain expression in superficial esophageal cancer.

The glycoprotein laminin 5γ2 chain (LN-5γ2) has recently become a focus of increased interest and investigation as a marker of invasion in gastrointestinal malignancies. We investigated the significance of LN-5γ2 expression as a prognostic factor in superficial esophageal cancer. The study population consisted of 87 patients who had undergone a transthoracic esophagectomy and three-field lymphadenectomy for the treatment of superficial esophageal cancer at Tokai University Hospital. Formalin-fixed, paraffin-embedded sections of the resected specimens were examined using immunohistochemical staining and hematoxylin and eosin staining to assess the correlations between the LN-5γ2 expression pattern and the clinicopathological factors (age, sex, T-factor, N-factor, ly-factor, v-factor, degree of differentiation, infiltrative growth pattern, tumor node metastasis classification of malignant tumors [TNM] stage, etc.) and the patient outcome. The expression pattern of LN-5γ2 was classified into an extracellular type (E type), characterized by the staining of extracellular matrix such as the basement membrane and the stroma (31 cases, 35.6%), and a cytoplasmic type (C type), characterized by the staining of the cytoplasm in the cancer cells (56 cases, 64.6%). The expression pattern was not correlated with any of the clinicopathological factors that were assessed. However, univariate analyses of the survival analysis data showed that the N-factor (P = 0.011), TNM stage (P = 0.011), and LN-5γ2 C type (P = 0.017) were prognostic factors. A multivariate analysis revealed that the N-factor (P = 0.049) and LN-5γ2 C type (P = 0.048) were prognostic factors. In the survival analysis, a univariate analysis of the 75 T1b cases also showed that the N-factor (P = 0.048), TNM stage (P = 0.048), and LN-5γ2 C type (P = 0.029) were prognostic factors, while a multivariate analysis showed that the LN-5γ2 C type (P = 0.035) was a prognostic factor. The C type expression of LN-5γ2, i.e. confined to the cytoplasm, was correlated with an unfavorable outcome among the patients with superficial esophageal cancer in the present series. Observation of the LN-5γ2 expression pattern may be useful for the diagnosis of highly malignant tumors.

Safety and Feasibility of a Pancreaticoduodenectomy with Total Meso-Pancreatoduodenum Excision: Analysis in Various Periampullary Disorders.

BACKGROUND/AIMS: This study aimed to evaluate the safety and feasibility of a pancreaticoduodenectomy with total meso-pancreatoduodenum excision (tMPDe) as an new anatomical concept. METHODOLOGY: A total of 90 patients underwent PD for various periampullary diseases. Of these, 52 patients received a conventional PD (cPD), while 38 patients underwent a tMPDe. Surgical outcomes were compared between the two study groups. RESULTS: Operative time was equivalent in the two groups; however, the estimated blood loss (cPD, 1360 ml; tMPDe, 995 ml; median, P = 0.026) and blood transfusion rate (cPD, 63%; tMPDe, 31% ; P = 0.001) were significantly decreased in tMPDe. Morbidity had no significant difference between cPD and tMPDe, and tMPDe showed no characteristic complications. With regard to oncological aspects, tMPDe was superior to cPD. Risk factors analysis revealed the operative time (P = 0.003), estimated blood loss (P < 0.001), and blood transfusion (P < 0.001) to be significant predictive risk factors for postoperative morbidity but not tMPDe procedure (P = 0.794). CONCLUSIONS: tMPDe is safe and superior to cPD because it is a bloodless operation with a good oncological outcome: We concluded that tMPDe should be adaptable to various periampullary diseases, including benign and low-grade malignant disorders.

Distal pancreatectomy utilizing a flexible stapler closure eliminates the risk of pancreas-related factors for postoperative pancreatic fistula.

OBJECTIVES: To identify the risk factors for clinically relevant pancreatic fistula after distal pancreatectomy with a flexible cartridge stapler, TL60. METHODS: Forty consecutive patients who underwent a distal pancreatectomy by the TL60 stapler were retrospectively reviewed in association with postoperative complications. RESULTS: The overall morbidity rate was 43% (17 patients), and mortality was null. Pancreatic fistula was the most frequent postoperative complication, seen in 11 patients (27.5%): grade A in 4 (10%) and grade B in 7 (17.5%). No grade C pancreatic fistula was observed. Univariate analyses of risk factors demonstrated that pancreas-related factors, including diabetes mellitus, thickness and texture of the pancreatic parenchyma, transection line for the pancreas, pancreatic duct ligation, and use of artificial patches had no impact on the occurrence of pancreatic fistula. A multivariable logistic regression analysis identified operative time (≥ 300 min) as the only notable predictor of clinically relevant pancreatic fistula (odds ratio = 3.253, 95% confidence interval 1.739-5.752; p = 0.031). CONCLUSION: Distal pancreatectomy with the use of the TL60 stapler eliminated the risk of pancreas-related factors for the occurrence of clinically relevant pancreatic fistula.

Characterization of nanoscale mechanical heterogeneity in a metallic glass by dynamic force microscopy.

We report nanoscale mechanical heterogeneity of a metallic glass characterized by dynamic force microscopy. Apparent energy dissipation with a variation of ~12%, originating from nonuniform distribution of local viscoelasticity, was observed. The correlation length of the heterogeneity was measured to be ~2.5 nm, consistent with the dimension of shear transformation zones for plastic flow. This study provides the first experimental evidence on the nanoscale viscoelastic heterogeneity in metallic glasses and may fill the gap between atomic models and macroscopic glass properties.

The involvement of calpain-dependent proteolysis of the tumor suppressor NF2 (merlin) in schwannomas and meningiomas.

Neurofibromatosis type 2 (NF2) protein, also known as merlin or schwannomin, is a tumor suppressor, and NF2 is mutated in most schwannomas and meningiomas. Although these tumors are dependent on NF2, some lack detectable NF2 mutations, which indicates that alternative mechanisms exist for inactivating merlin. Here, we demonstrate cleavage of merlin by the ubiquitous protease calpain and considerable activation of the calpain system resulting in the loss of merlin expression in these tumors. Increased proteolysis of merlin by calpain in some schwannomas and meningiomas exemplifies tumorigenesis linked to the calpain-mediated proteolytic pathway.

Anomalous electronic structure of ionic liquids determined by soft x-ray emission spectroscopy: contributions from the cations and anions to the occupied electronic structure.

Soft x-ray emission spectroscopy was used for elucidating the electronic structure of ionic liquids [C(4)mim](+)PF(6)(-) and [C(4)mim](+)OTf(-), where [C(4)mim](+) stands for methylbutylimidazolium cation and OTf(-) for the trifluoromethanesulfonate anion. Nonresonant spectra measured above N, O, and F 1s edges selectively probed the molecular orbitals (MOs) of the cation and anions. They give a clear evidence that the highest occupied molecular orbital of the [C(4)mim](+) cation contributes to the topmost occupied states of the ionic liquids [C(4)mim](+)PF(6)(-), while both cationic and anionic MOs contribute for the case of [C(4)mim](+)OTf(-). Resonant soft x-ray emission spectra at the N 1s edge of these ionic liquids revealed that the energy gap of [C(4)mim](+)PF(6)(-) is solely determined by the [C(4)mim](+) cation, in contrast to usual ionic crystals. The ionic liquids form a new class of the ionic materials from the viewpoint of the electronic structure.

Intra-operative natural sound decreases salivary amylase activity of patients undergoing inguinal hernia repair under epidural anesthesia.

BACKGROUND: The perioperative period is psychologically as well as physically stressful for patients. Although music and sound are known to reduce patients' psychological stress, a few previous studies showed an objective outcome of music. The aim of the present study was to evaluate the relaxing effect of music during epidural anesthesia, using patients' salivary amylase activity. METHODS: Thirty-two American Society of Anesthesiologists (ASA) I or II patients presenting for inguinal hernia repair under epidural anesthesia were randomly assigned to listen to sounds of a soft wind and a twitter (S group) or to have no sounds (N group). Patients' salivary amylase activity was evaluated on arrival to the operating room and at wound closure. RESULTS: Intra-operative music significantly decreased salivary amylase activity at wound closure in the S group and the activity at wound closure of the S group was significantly smaller than that of the N group. CONCLUSION: Intra-operative natural sound significantly decreased salivary amylase activity of patients undergoing inguinal hernia repair under epidural anesthesia.

Routine Referral by Urologists Increase Opportunities for Corneal Donation.

BACKGROUND: The levels of corneal donation are insufficient to meet the demand for corneal transplantation in Japan. To overcome this problem, we started to routinely mention the possibility of corneal donation to the families of patients who died in our hospital's Urology Department in February 2008. In this study, we evaluated the effectiveness of this approach. METHODS: We retrospectively reviewed the medical records of the patients who died in the Department of Urology, St. Marianna University School of Medicine Hospital, and analyzed the patients' characteristics and information about corneal donation. RESULTS: In total, 211 patients died in our department between February 2008 and March 2017, and 155 patients were medically suitable corneal donors. We mentioned the possibility of corneal donation to 129 (83.2%) families, and 29 (18.7%) families agreed. Three families subsequently withdrew their consent. Finally, 26 (16.8%) of the families that were approached about corneal donation by urologists agreed to donate their relatives' corneas. Another 2 families voluntarily offered to donate their relatives' corneas. Thus, 28 (18.1%) of 155 medically suitable donors donated their corneas for transplantation. Twenty-six (92.8%) donors were 60 years or older and all donors were affected with malignant genitourinary tumors. Fifty-four (96.4%) corneas were successfully transplanted into recipients. CONCLUSIONS: Even elderly patients who die of solid carcinoma can be an important source of corneal donors. In this study, we showed that routine referral by urologists increased corneal donation. If this approach were adopted by other departments, it might further increase the number of corneal donations.

Peptide mimics of the CTLA4-binding domain stimulate T-cell proliferation.

Phage library clones selected by a conformational epitope-recognizing and inhibitory monoclonal antibody may display moieties that mimic a receptor/ligand-like three-dimensional structure. This pseudoreceptor/ligand should be able to bind to natural ligand/receptor molecules. We tested this idea using anti-T cell costimulatory molecule antibodies and successfully isolated phage clones with costimulatory effects on T-cell proliferation. This strategy facilitates the designing of regulatory peptide molecules in the absence of precise information about the structure-function relationships in receptor/ligand interactions.

High-performance affinity beads for identifying drug receptors.

We have developed a method using novel latex beads for rapid identification of drug receptors using affinity purification. Composed of a glycidylmethacrylate (GMA) and styrene copolymer core with a GMA polymer surface, the beads minimize nonspecific protein binding and maximize purification efficiency. We demonstrated their performance by efficiently purifying FK506-binding protein using FK506-conjugated beads, and found that the amount of material needed was significantly reduced compared with previous methods. Using the latex beads, we identified a redox-related factor, Ref-1, as a target protein of an anti-NF-kappaB drug, E3330, demonstrating the existence of a new class of receptors of anti-NF-kappaB drugs. Our results suggest that the latex beads could provide a tool for the identification and analysis of drug receptors and should therefore be useful in drug development.

Autocrine growth of transitional cell carcinoma of the bladder induced by granulocyte-colony stimulating factor.

Granulocyte-colony stimulating factor (G-CSF) produced by nonhematopoietic malignant cells has been reported to be capable of inducing a leukemoid reaction in the host through intense stimulation of leukocyte production. Furthermore, this is frequently associated with aggressive tumor cell growth and a detrimental clinical outcome. In this study, we identified bladder cancer cells producing G-CSF with the expression of the functional receptor, which provides direct evidence of autocrine growth of bladder cancer cells induced by G-CSF. The cancer cells used in this study were obtained from a 76-year-old man who had a metastatic transitional cell carcinoma of the bladder and who demonstrated marked leukocytosis, his peripheral blood leukocyte count was 94,900 leukocytes/mm3, and his serum G-CSF level was 103 pg/ml. The culture medium in which the cancer cells were grown exclusively contained a significant amount of G-CSF (5560 pg/ml). Significant G-CSF mRNA expression and G-CSF receptor mRNA expression in the cultured cells were demonstrated by the reverse transcription-PCR method. In addition, binding studies with the use of radiolabeled recombinant G-CSF demonstrated the presence of high-affinity G-CSF binding receptors on the cultured cancer cells. Finally, the proliferation of the cultured cancer cells was stimulated by exogenous G-CSF administration, and this stimulation was inhibited by adding anti-G-CSF antibody, as demonstrated by both the flow cytometric bromodeoxyuridine incorporation technique and the [3H]thymidine incorporation assay. These results strongly suggest that G-CSF production by the bladder cancer cells studied augments autocrine growth. Therefore, we recommend exercising caution in the clinical use of G-CSF for bladder cancer patients.

Expression of sialyl 6-sulfo Lewis X is inversely correlated with conventional sialyl Lewis X expression in human colorectal cancer.

Sialyl 6-sulfo Lewis X determinant has been described recently as a major ligand for L-selectin on high endothelial venules of human peripheral lymph nodes. From our investigation of its distribution in human colorectal cancer tissues and cultured colon cancer cells, the sialyl 6-sulfo Lewis X determinant was preferentially expressed in the nonmalignant colonic epithelia rather than cancer cells (P < 0.001; n = 23). This was in contrast to the distribution of conventional sialyl Lewis X, which was preferentially expressed in cancer tissues rather than nonmalignant epithelia (P = 0.007; n = 23), indicating that 6-sulfation predominantly occurs in nonmalignant tissues and is suppressed upon malignant transformation. In confirmation of this, a nonsialylated determinant 6-sulfo Lewis X was also found to be preferentially localized in the nonmalignant epithelia. Significant expression of sialyl 6-sulfo Lewis X was observed in only 2 lines, whereas 8 were positive for conventional sialyl Lewis X, among 13 cultured colon cancer cell lines. Transfection of cells with fucosyltransferase (Fuc-T) VI induced expression of sialyl 6-sulfo Lewis X, whereas transfection of Fuc-T III did not, suggesting that the determinant was synthesized mainly by Fuc-T VI in colonic epithelia. Members of the sialic acid cyclase pathway, the de-N-acetyl sialyl 6-sulfo Lewis X and cyclic sialyl 6-sulfo Lewis X determinants, were also preferentially expressed in the nonmalignant epithelia rather than colonic cancer cells (P < 0.001; n = 23). Stimulation of the sialyl 6-sulfo Lewis X-positive colon cancer cell line with a calcium ionophore ionomycin markedly reduced sialyl 6-sulfo Lewis X and induced cyclic sialyl 6-sulfo Lewis X expression. These results suggested that the metabolic conversion of sialyl 6-sulfo Lewis X into cyclic sialyl 6-sulfo Lewis X by a calcium-dependent enzyme, sialic acid cyclase, as we hypothesized for human leukocytes previously (C. Mitsuoka et al., Proc. Natl. Acad. Sci. USA, 96: 1597-1602, 1999), also occurs in nonmalignant colonic epithelia.

High-efficiency in vivo gene transfer using intraarterial plasmid DNA injection following in vivo electroporation.

A novel method for high-efficiency and region- controlled in vivo gene transfer was developed by combining in vivo electroporation and intraarterial plasmid DNA injection. A mammalian expression plasmid for the Escherichia coli lacZ gene (driven with a SV40 early promoter) was injected into the internal carotid artery of rats whose brain tumors (from prior inoculation) had been electroporated between two electrodes. The lacZ gene was efficiently transferred and expressed in the tumor cell 3 days after plasmid injection. However, neither any gene transfers nor any elevated lacZ activity was detected in tissues outside the electrodes. The plasmid was not transferred without electroporation. Human monocyte chemoattractant protein-1 cDNA was also transferred by this method, and its long-lasting (3 weeks) expression was confirmed by using the Epstein-Barr virus episomal replicon system. The expressed monocyte chemoattractant protein-1 protein was functional, as evident by the presence of a large number of monocytes in tumor tissue. This method, electrogene therapy, which does not require viral genes or particles, allows genes to be transferred and expressed in desired organs or tissues, and it may lead to the development of a new type of highly effective gene therapy.

Differential expression of two types of the neurofibromatosis type 1 (NF1) gene transcripts related to neuronal differentiation.

A 360 residue region encoded by the neurofibromatosis type 1 (NF1) gene shows significant homology to the catalytic domains of both mammalian GTPase-activating proteins (GAP) and yeast IRA proteins. This GAP-related domain of the NF1 gene (NF1-GRD), like the GAP and IRA protein, has been reported to mediate hydrolysis of Ras-bound GTP to GDP, resulting in inactivation of Ras protein. In the present study, we identified two different types of NF1-GRD cDNA. One (type I) is identical to the previously reported sequence, and the other (type II) contained an additional 63 bp insertion that encodes for a region of 21 amino acids in the center of the NF1-GRD molecule. Alternative splicing is the most likely mechanism by which these two types of transcripts arise. Our observations reveal that the type I transcript is predominantly expressed in undifferentiated cells, whereas the type II transcript predominates in differentiated cells. Furthermore, the expression pattern of type I and type II NF1-GRD mRNA immediately changed in SH-SY5Y neuroblastoma cells when neuronal differentiation programs were induced by retinoic acid treatment. We propose that the differential expression of type I and type II NF1-GRD transcripts might be an 'on/off' switch that regulates the catalytic activity of the NF1 gene product, which plays an important role in the regulation of neuronal differentiation.