A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder.

Background: S-288310, a cancer peptide vaccine composed of two HLA-A*24:02-restricted peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder. Patients and methods: Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1 mg or 2 mg/peptide subcutaneously once a week to evaluate safety and tolerability. In the phase II, 32 patients were randomized to receive either 1 mg or 2 mg to evaluate the difference in cytotoxic T lymphocytes (CTL) induction and safety. Results: S-288310 was safe and well tolerated in the phase I. Of 27 patients evaluable for immune responses in the phase II, there was no difference in CTL induction rate between the 1 mg (100%) and 2 mg (80.0%) groups. Of 32 patients receiving S-288310 in the phase II, the most frequent drug-related AE was the injection site reaction that was observed in 29 patients (90.6%), but none of the patients discontinued administration due to these reactions and no dose relationship in the frequency and severity was observed. The objective response rate of the 32 patients was 6.3% and the disease control rate was 56.3%. The median overall survival (OS) rates for patients vaccinated with S-288310 after one regimen of chemotherapy, 2 regimens, or 3 or more were 14.4, 9.1 and 3.7 months, respectively, and 32.2% of patients post first-line treatment were alive at 2 years. OS of patients who showed CTL induction to both peptides was longer than that of those with CTL induction to no or one peptide. Conclusion: S-288310 was well-tolerated and effectively induced peptide-specific CTLs, which were correlated with longer survival for patients with UC of the bladder. Trial registration ID: JapicCTI-090980.

Search for Two-Photon Interaction with Axionlike Particles Using High-Repetition Pulsed Magnets and Synchrotron X Rays.

We report on new results of a search for a two-photon interaction with axionlike particles (ALPs). The experiment is carried out at a synchrotron radiation facility using a "light shining through a wall (LSW)" technique. For this purpose, we develop a novel pulsed-magnet system, composed of multiple racetrack magnets and a transportable power supply. It produces fields of about 10 T over 0.8 m with a high repetition rate of 0.2 Hz and yields a new method of probing a vacuum with high intensity fields. The data obtained with a total of 27 676 pulses provide a limit on the ALP-two-photon coupling constant that is more stringent by a factor of 5.2 compared to a previous x-ray LSW limit for the ALP mass ≲0.1 eV.

FTIR spectroscopy of three fundamental bands of H2F+.

The ν1, ν2, and ν3 bands of H2F(+) were observed with a Fourier transform absorption spectroscopic technique in the 3 and 7 µm regions. The ion was produced with a hollow cathode discharge in a F2, He, and H2 gas mixture. A simultaneous analysis of FT data combined with laser spectroscopic data was carried out using the Watson's A-reduced Hamiltonian to determine molecular constants in vibrationally excited states. The effect of the vibration-rotation interaction between the ν1 and ν3 states was found to be small compared with the case of H2O. The vibration-rotation transitions of the ν2 band were first identified and analyzed to obtain molecular constants in the ν2 state, and the band origin was determined to be 1370.5236 (7) cm(-1) with one standard deviation in parentheses. Determined molecular constants can be used to derive the re structure of H2F(+) as re(H-F) = 0.9608(6) Å, ∠e(H-F-H) = 112.2(2)° with the error corresponding to the uncertainty of the assumed vibration rotation constant γ2(a) and the range of the values derived from three pairs of rotational constants.

Face, content and concurrent validity of the Mimic® dV-Trainer for robot-assisted endoscopic surgery: a prospective study.

OBJECTIVE: The aim of this study was to determine whether any correlation exists between the performance of the Mimic® dV-Trainer (Mimic Technologies, Seattle, Wash., USA) and the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, Calif., USA). METHODS: Twelve participants were recruited, ranging from residents to consultants. We used four training tasks, consisting of 'Pick and Place', 'Peg Board', 'Thread the Rings' and 'Suture Sponge', from the software program of the Mimic dV-Trainer. The performance of the participants was recorded and measured. Additionally, we prepared the same tasks for the da Vinci Surgical System. All participants completed the tasks using the da Vinci Surgical System and were assessed according to time, the Objective Structured Assessment of Technical Skill checklist and the global rating score for endoscopic suturing assessed by two independent blinded observers. After performing these tasks, the participants completed a questionnaire that evaluated the Mimic dV-Trainer's face and content validity. The final results for each participant for the Mimic dV-Trainer and the da Vinci Surgical System were compared. RESULTS: All participants ranked the Mimic dV-Trainer as a realistic training platform that is useful for residency training. There was a significant relationship between the Mimic dV-Trainer and the da Vinci Surgical System in all four tasks. We verified the reliability of the assessment of the checklist and the global rating scores for endoscopic suturing assessed by the two blinded observers using Cronbach's alpha test (r = 0.803, 0.891). CONCLUSIONS: We evaluated the concurrent validity of the Mimic dV-Trainer and the da Vinci Surgical System. Our results suggest the possibility that training using the Mimic dV-Trainer may therefore be able to improve the operator's performance during live robot-assisted surgery.

Using indocyanine green angiography to achieve complete engraftment of pectoralis major myocutaneous flaps.

Although the pectoralis major myocutaneous (PMMC) flap is among the useful reconstructive materials following oral cancer ablation, this flap has an unstable blood circulation that could result in partial necrosis of the skin paddle. This report describes the usefulness of indocyanine green angiography (ICGA) to achieve complete engraftment of the PMMC flap. Five patients with oral cancer underwent reconstruction with a PMMC flap after cancer ablation. During the skin paddle design and flap elevation, the blood supply to the flap was assessed by ICGA. Areas of the skin paddle that showed no ICG fluorescence were excised. Consequently, prior to transfer to the recipient site, the blood supply to all flaps was confirmed with indocyanine green visible at the edge of the skin paddle, and complete engraftment was achieved without partial necrosis. Based on the results observed, ICGA would make a useful contribution to complete engraftment of the PMMC flap.

THz rotational spectrum of H2F+.

In view of recent tremendous advance in astronomical observations in the submillimeter to THz region brought by the Herschel space craft, laboratory high-resolution spectroscopic investigations in that frequency region into unstable molecules, in particular, light hydride ions, are urgently needed. As a part of such endeavor, rotational transitions of H(2)F(+) were observed in the THz-region by using a tunable far-infrared spectrometer. These newly detected lines together with the submillimeter-wave lines obtained previously and the combination differences derived from infrared vibration-rotation lines were subject to a least-squares analysis that yielded a set of molecular constants with much better accuracy. The measured and predicted THz transition frequencies should prove to be a useful probe into detection of interstellar H(2)F(+).

Correlation between docetaxel-induced skin toxicity and the use of steroids and H2 blockers: a multi-institution survey.

Steroids and H(2) blockers are commonly used as supportive care for taxane-containing chemotherapy, but they also affect docetaxel's primary metabolizer, cytochrome P(450) 3A4. This retrospective observational study was performed to better understand the effects of these compounds on docetaxel-induced skin toxicities, specifically hand-foot syndrome (HFS) and facial erythema (FE), a relationship that is currently poorly understood. Member institutions of the Japan Breast Cancer Research Group were invited to complete a questionnaire on the occurrence of grade 2 or higher HFS and FE among patients treated between April 2007 and March 2008 with docetaxel as an adjuvant or neoadjuvant chemotherapeutic treatment for breast cancer. We obtained data for 993 patients from 20 institutions. Twenty percent received H(2) blockers, and all patients received dexamethasone. Univariate and multivariate analyses revealed that H(2) blockers are associated with a significantly higher incidence of both HFS and FE. The incidence of FE was significantly higher for the docetaxel + cyclophosphamide (TC) regimen than for non-TC regimens combined. Dexamethasone usage did not affect the incidence of either HFS or FE. In conclusion, use of H(2) blockers as premedication in breast cancer patients receiving docetaxel significantly increases the risk of both HFS and FE.

Unit cell parameters of wurtzite InP nanowires determined by x-ray diffraction.

High resolution x-ray diffraction is used to study the structural properties of the wurtzite polytype of InP nanowires. Wurtzite InP nanowires are grown by metal-organic vapor phase epitaxy using S-doping. From the evaluation of the Bragg peak position we determine the lattice parameters of the wurtzite InP nanowires. The unit cell dimensions are found to differ from the ones expected from geometric conversion of the cubic bulk InP lattice constant. The atomic distances along the c direction are increased whereas the atomic spacing in the a direction is reduced in comparison to the corresponding distances in the zinc-blende phase. Using core/shell nanowires with a thin core and thick nominally intrinsic shells we are able to determine the lattice parameters of wurtzite InP with a negligible influence of the S-doping due to the much larger volume in the shell. The determined material properties will enable the ab initio calculation of electronic and optical properties of wurtzite InP nanowires.

Reduction of Alzheimer's disease amyloid-ß in plasma by hemodialysis and its relation to cognitive functions.

BACKGROUND/AIMS: Rapid removal of plasma amyloid-ß (Aß) by blood purification may serve as a peripheral Aß sink from the brain for Alzheimer's disease therapy. We investigated the reduction of plasma Aß during hemodialysis and cognitive states. METHODS: Aß concentrations and Mini-Mental State Examinations (MMSE) were investigated in 37 hemodialysis patients (68.9 ± 4.1 years). RESULTS: The dialyzers effectively removed Aß(1-40) and Aß(1-42), 63.9 ± 14.4 and 51.6 ± 17.0% at 4 h dialysis, resulting in the reduction of Aßs in whole-body circulation by 51.1 ± 8.9 and 32.7 ± 12.0%, respectively. Although the plasma Aßs before dialysis (750.8 ± 171.3 pg/ml for Aß(1-40)) were higher than those reported for Alzheimer's disease patients, the cognitive states of hemodialysis patients were relatively normal, especially of longer dialysis vintages. CONCLUSIONS: Dialyzers effectively reduced Aßs in whole-body circulation. Repeated rapid decrease of plasma Aßs might maintain cognitive state.

Devil's staircase transition of the electronic structures in CeSb.

Solids with competing interactions often undergo complex phase transitions with a variety of long-periodic modulations. Among such transition, devil's staircase is the most complex phenomenon, and for it, CeSb is the most famous material, where a number of the distinct phases with long-periodic magnetostructures sequentially appear below the Néel temperature. An evolution of the low-energy electronic structure going through the devil's staircase is of special interest, which has, however, been elusive so far despite 40 years of intense research. Here, we use bulk-sensitive angle-resolved photoemission spectroscopy and reveal the devil's staircase transition of the electronic structures. The magnetic reconstruction dramatically alters the band dispersions at each transition. Moreover, we find that the well-defined band picture largely collapses around the Fermi energy under the long-periodic modulation of the transitional phase, while it recovers at the transition into the lowest-temperature ground state. Our data provide the first direct evidence for a significant reorganization of the electronic structures and spectral functions occurring during the devil's staircase.

Mutational analysis of the hepatitis C virus E1 glycoprotein in retroviral pseudoparticles and cell-culture-derived H77/JFH1 chimeric infectious virus particles.

Cell entry by enveloped viruses is mediated by viral glycoproteins, and generally involves a short hydrophobic peptide (fusion peptide) that inserts into the cellular membrane. An internal hydrophobic domain within E1 (aa262-290) of hepatitis C virus (HCV) may function as a fusion peptide. Retrovirus-based HCV-pseudotyped viruses (HCVpp; genotype 1a) containing Ala or Pro substitutions at conserved amino acid positions within this putative fusion peptide were generated. Mutation of conserved residues significantly reduced efficiency of HCVpp entry into Huh-7 cells. The majority of amino acid substitutions appeared to disrupt necessary interactions between E1 and E2. For some mutants, reductions in HCVpp-associated E1 were associated with the incorporation of a high molecular weight, hyperglycosylated E2 that displayed decreased CD81-binding. Other entry-deficient mutants displayed normal E1E2 incorporation into pseudoparticles and normal CD81-binding, and therefore might affect viral fusion. One mutant (S283P) consistently displayed two- to threefold higher infectivity than did wild-type. Three mutations that decreased HCVpp infectivity also reduced levels of HCVcc infectious virus production. However, the S283P mutation had a different effect in the two systems as it did not increase production of infectious HCVcc. This comprehensive mutational analysis of the putative HCV fusion peptide provides insight into the role of E1 in its interaction with E2 and in HCV entry.

Nucleotide-dependent single- to double-headed binding of kinesin.

The motility of kinesin motors is explained by a "hand-over-hand" model in which two heads of kinesin alternately repeat single-headed and double-headed binding with a microtubule. To investigate the binding mode of kinesin at the key nucleotide states during adenosine 5'-triphosphate (ATP) hydrolysis, we measured the mechanical properties of a single kinesin-microtubule complex by applying an external load with optical tweezers. Both the unbinding force and the elastic modulus in solutions containing AMP-PNP (an ATP analog) were twice the value of those in nucleotide-free solution or in the presence of both AMP-PNP and adenosine 5'-diphosphate. Thus, kinesin binds through two heads in the former and one head in the latter two states, which supports a major prediction of the hand-over-hand model.

Submucosal tunneling using endoscopic submucosal dissection for peritoneal access and closure in natural orifice transluminal endoscopic surgery: a porcine survival study.

BACKGROUND AND STUDY AIMS: Safe peritoneal access and gastric closure are the most important concerns in the clinical application of natural orifice transluminal endoscopic surgery (NOTES). We aimed to clarify the feasibility of a submucosal tunnel technique using endoscopic submucosal dissection (ESD) for transgastric peritoneal access and subsequent closure for NOTES. METHODS: Seven female pigs, each weighing about 40 kg were included in the study. The following procedures were performed: (i) after injection of normal saline into the submucosa, the mucosa was cut with a flex knife; (ii) the submucosal layer was dissected using an insulation-tipped electrosurgical knife to make a narrow longitudinal 50-mm submucosal tunnel; (iii) a small incision was made at the end of the tunnel and enlarged with a dilation balloon. After transgastric peritoneoscopy, the mucosal incision site was closed with clips. The following outcome measures were used: (a) evaluation of the technical feasibility of making a submucosal tunnel; (b) clinical monitoring for 7 days; (c) follow-up endoscopy and necropsy; and (d) peritoneal fluid culture. RESULTS: Natural orifice transluminal endoscopic peritoneoscopy with a submucosal tunnel was successfully carried out in all pigs. The pigs recovered well, without signs of peritonitis. Follow-up endoscopy showed healing of mucosal incision sites without open defects. Necropsy revealed no findings of peritonitis, confirming completeness of gastric closure; there was a thin scar in one pig and adhesion of the omentum in six pigs. Peritoneal fluid culture demonstrated no bacterial growth. CONCLUSIONS: The submucosal tunnel technique is feasible and effective for transgastric peritoneal access and closure.

FePt nanoparticles fabricated by pulsed laser ablation.

Two unique laser processes of 'PLA in low vacuum (PLALV)' and 'PLA in liquid (PLAL)' have been examined to fabricate FePt nanoparticles and the magnetic and structural properties were investigated. The particles as prepared by PLALV showed a superparamagnetic behavior with an fcc structure. The annealing temperature dependence of the transformation from fcc to fct structure was studied by the structural and magnetic properties. A large coercivity of 3.6 kOe at 300 K was obtained by the low temperature (500 C) annealing. Composition deviation due to Fe dissolution in PLAL process was successfully suppressed by Ar bubbling.

Prevalence of Helicobacter and Acanthamoeba in natural environment.

AIMS: We examined whether the presence of Helicobacter is related to that of Acanthamoeba in river and soil environments. METHODS AND RESULTS: The samples (river n = 51, soil n = 75) were collected in Sapporo City, Japan. PCR with primers for Helicobacter genus-specific and standard culture techniques were used to detect helicobacter. Prevalence of acanthamoeba was also evaluated by genus-specific PCR. The prevalence of Helicobacter genus-specific DNA in river water samples and in soil samples was 88% and 0%, respectively. No successful culture of helicobacter was achieved. The prevalence of Acanthamoeba genus-specific DNA in river samples and in soil samples was 61% and 96%, respectively. No statistical correlation between the prevalence of helicobacter and either that of acanthamoeba or water quality parameters (pH, turbidity and coliform group) except for temperature was found. CONCLUSIONS: We revealed the presence of helicobacter in river water and non-existence of helicobacter in soil. However, the distribution of helicobacter did not overlap with that of acanthamoeba in rivers. SIGNIFICANCE FOR IMPACT OF THE STUDY: The role of acanthamoeba on the survival of helicobacter might be limited as the both are coincidentally present in the environment.

A highly color-stability white organic light-emitting diode by color conversion within hole injection layer.

We demonstrated a novel-structure white organic light-emitting devices (WOLEDs) composed of a greenish blue fluorescent emitting layer and a red fluorescent dye-doped hole injection layer. The spectra of WOLEDs show no change at a wide range current density operation and long-term continuous operation. We concluded that carriers recombined inside the emitting layer in the WOLEDs to produce a greenish blue electroluminescence (EL), and a part of the EL was absorbed by the red fluorescent guest doped hole injection layer and converted into red photoluminescence (PL); the whole white emission from the device was a mixture of the greenish blue EL and red PL.

Spectral tuning of photoactive yellow protein.

We report a theoretical study on the optical properties of a small, water-soluble photosensory receptor, photoactive yellow protein (PYP). A hierarchical ab initio molecular orbital calculation accurately evaluated the optical absorption maximum of the wild-type, as well as the lambda(max) values of 12 mutants. Electronic excitation of the chromophore directly affects the electronic state of nearby atoms in the protein environment. This effect is explicitly considered in the present study. Furthermore, the spectral tuning mechanism of PYP was investigated at the atomic level. The static disorder of a protein molecule is intimately related to the complex nature of its energy landscape. By using molecular dynamics simulation and quantum mechanical structure optimization, we obtained multiple minimum energy conformations of PYP. The statistical distribution of electronic excitation energies of these minima was compared with the hole-burning experiment (Masciangioli, T. [2000] Photochem. Photobiol. 72, 639), a direct observation of the distribution of excitation energies.

Usefulness of 11C-methionine-PET for predicting the efficacy of carbon ion radiation therapy for head and neck mucosal malignant melanoma.

The aim of this study was to determine whether l-methyl-[11C]-methionine (MET) positron emission tomography (PET) allows the prediction of outcomes in patients with head and neck mucosal malignant melanoma treated with carbon ion radiation therapy (CIRT). This was a retrospective cohort study involving 85 patients who underwent a MET-PET or MET-PET/computed tomography (CT) examination before and after CIRT. MET uptake in the tumour was evaluated semi-quantitatively using the tumour-to-normal tissue ratio (TNR). Local recurrence, metastasis, and outcome predictions were studied in terms of TNR before CIRT (TNRpre), TNR after CIRT (TNRpost), and the TNR change ratio. Kaplan-Meier curves revealed significant differences between patients with higher TNRpre values and those with lower TNRpre values in regard to local recurrence, metastasis, and outcome (log-rank test P<0.0001 for all three). There were also significant differences in metastasis rates and outcomes between patients with higher and lower TNRpost values (log-rank test P=0.0105 and P=0.027, respectively). The Cox proportional hazards model revealed TNRpre to be a factor significantly influencing the risk of local recurrence (hazard ratio (HR) 29.0, P<0.001), risk of metastasis (HR 2.67, P=0.024), and the outcome (HR 6.3, P<0.001). MET-PET or MET-PET/CT is useful for predicting the outcomes of patients with head and neck mucosal malignant melanoma treated with CIRT.

Diffusion-weighted MR imaging in carotid angioplasty and stenting with protection by the reversed carotid arterial flow.

BACKGROUND AND PURPOSE: Distal embolism during carotid angioplasty with stent (CAS) can be protected by a flow-reversal device. Diffusion-weighted MR imaging was used to evaluate this protective procedure and perform a comparison with the control. METHODS: Cases of CAS with protection procedures were included in this study. Sixty-five men (68 procedures) and 5 women (5 procedures), with an average age of 68.8 years, having severe carotid stenosis were treated in our department between 2002 and 2004. Eleven cases were treated with the Parodi Anti-Emboli System, with which the internal carotid blood flow is reversed by simultaneous occlusion of the proximal common carotid artery and external carotid artery. Diffusion-weighted MR imaging was performed within 1-3 days after CAS. As controls, data from diffusion-weighted MR imaging in 26 patients who had diagnostic angiography were included. RESULTS: Diffusion-weighted MR imaging in diagnostic angiography showed 11.5% appearance of ischemic spots after procedures. In the Parodi Anti-Emboli System, this value was 18.2%. In the CAS group, ischemic lesions appeared only in the hemisphere ipsilateral to carotid stenosis. There were no ischemic lesions in the opposite carotid or vertebrobasilar territory. The appearance rate of new ischemic spots was not significantly different between the control group and the group of CAS with Parodi Anti-Emboli System (chi2 test, P = .6227, Fisher exact method). CONCLUSIONS: Protection results obtained with the Parodi system were excellent and comparable with conventional angiography.

Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro.

BACKGROUND: Somatically acquired chromosomal translocation is a common mechanism of oncogene activation in many haematopoietic tumours and sarcomas. However, very few recurrent chromosomal translocations have been reported in more common epithelial tumours such as lung carcinomas. METHODS: We established a cell line HCC2429 from an aggressive, metastatic lung cancer arising in a young, non-smoking woman, demonstrating a t(15;19)(q13.2;p13.1). The breakpoints on chromosomes 15 and 19 were cloned using long distance inverse PCR and we determined by RT-PCR that the translocation results in a novel fusion transcript in which the 3' end Brd4 on chromosome 19p is fused to the 5' end of NUT on chromosome 15q. RESULTS: In total, 128 lung cancer tissues were screened using fluorescent in situ hybridisation, but none of the tumours screened demonstrated t(15;19), suggesting that this translocation is not commonly found in lung cancer. Consistent with previous literature, ectopic expression of wild type Brd4 was shown to inhibit G(1) to S progression. However, we also found that the Brd4-NUT fusion augments the inhibition of progression to S phase compared with wild type Brd4. CONCLUSION: Alteration in cell cycle kinetics is important in tumorigenesis, although the exact role of Brd4-NUT fusion protein in the pathogenesis of lung cancers remains unclear and need to be further elucidated.