Efficient Illumination for a Light-Addressable Potentiometric Sensor.

A light-addressable potentiometric sensor (LAPS) is a chemical sensor that is based on the field effect in an electrolyte-insulator-semiconductor structure. It requires modulated illumination for generating an AC photocurrent signal that responds to the activity of target ions on the sensor surface. Although high-power illumination generates a large signal, which is advantageous in terms of the signal-to-noise ratio, excess light power can also be harmful to the sample and the measurement. In this study, we tested different waveforms of modulated illuminations to find an efficient illumination for a LAPS that can enlarge the signal as much as possible for the same input light power. The results showed that a square wave with a low duty ratio was more efficient than a sine wave by a factor of about two.

Novel anchoring device for endoscopic ultrasound-guided gallbladder drainage: Secondary publication.

BACKGROUND: Recently, endoscopic ultrasound-guided gallbladder drainage has attracted much attention. However, the risk management of adverse events and techniques to avoid them are not yet mature. Difficulty dilating the fistula with a dilator or placing a stent for drainage often prolongs the procedure time, which increases the risk of peritonitis or the procedure failure rate. Therefore, the result of the procedure will be unstable, and one cause is the lack of adhesion between the gallbladder and the digestive tract walls. METHODS: We developed an anchor to fix the stomach and gallbladder walls prior to endoscopic ultrasound-guided gallbladder drainage in four live pigs using the anchor. RESULTS: The stomach and gallbladder walls were fixed in three pigs, and technical success was achieved in all three pigs. In two pigs that were dissected 17 and 34 days post-procedure, respectively, fixation occurred in one pig. In the other pig, anchoring of the gallbladder and stomach walls did not occur because the wings of the anchor in the gallbladder were damaged. CONCLUSIONS: Although issues remain regarding efficacy and safety, we plan to make improvements in this novel device and aim for clinical application.

Simultaneous In Situ Imaging of pH and Surface Roughening during the Progress of Crevice Corrosion of Stainless Steel.

Stainless steel plays an important role in industry due to its anti-corrosion characteristic. It is known, however, that local corrosion can damage stainless steel under certain conditions. In this study, we developed a novel measurement system to observe crevice corrosion, which is a local corrosion that occurs inside a narrow gap. In addition to pH imaging inside the crevice, another imaging technique using an infrared light was combined to simultaneously visualize surface roughening of the test piece. According to experimental results, the lowering of local pH propagated inside the crevice, and after that, the surface roughening started and expanded due to propagation of corrosion. The real-time measurement of the pH distribution and the surface roughness can be a powerful tool to investigate the crevice corrosion.

[Rapid response of secondary plasma cell leukemia after carfilzomib and dexamethasone therapy].

An 83-year-old man was admitted to our hospital due to a recurrence of multiple myeloma, accompanied by the appearance of plasma cells in the peripheral blood (PB). Subsequently, he was diagnosed with secondary plasma cell leukemia (sPCL). A chemotherapy regimen of carfilzomib and dexamethasone (Cd) combination therapy was selected, and 15 days later, plasma cells completely disappeared from the PB. Cd therapy was continued, and the free kappa chain levels normalized. Three months later, M-protein could not be detected using serum electrophoresis. This is a valuable report wherein Cd combination therapy was successful in treating sPCL.

Estimation of Potential Distribution during Crevice Corrosion through Analysis of I-V Curves Obtained by LAPS.

Crevice corrosion is a type of local corrosion which occurs when a metal surface is confined in a narrow gap on the order of 10 µm filled with a solution. Because of the inaccessible geometry, experimental methods to analyze the inner space of the crevice have been limited. In this study, a light-addressable potentiometric sensor (LAPS) was employed to estimate the potential distribution inside the crevice owing to the IR drop by the anodic current flowing out of the structure. Before crevice corrosion, the I-V curve of the LAPS showed a potential shift, depending on the distance from the perimeter. The shift reflected the potential distribution due to the IR drop by the anodic current flowing out of the crevice. After crevice corrosion, the corrosion current increased exponentially, and a local pH change was detected where the corrosion was initiated. A simple model of the IR drop was used to calculate the crevice gap, which was 12 µm-a value close to the previously reported values. Thus, the simultaneous measurement of the I-V curves obtained using a LAPS during potentiostatic electrolysis could be applied as a new method for estimating the potential distribution in the crevice.

Simulation and Experiment for Electrode Coverage Evaluation by Electrochemical Impedance Spectroscopy Using Parallel Facing Electrodes.

A parallel facing electrode (PFE) structure for adherent cell monitoring by electrochemical impedance spectroscopy (EIS) was developed, and its characteristics were investigated by both computer simulation and experiment. The PFE model consists of two facing gold electrode strips separated by 40 µm, and the area of its intersection is 500 × 500 µm. Computer simulation of EIS with adherent cells showed a distinct difference in solution resistance for different cell coverage, which was confirmed by experimental results using latex beads suspension. A well-defined relationship between solution resistance and cell coverage in our PFE is promising for quantitative evaluation of cell density, morphology and fatality.

Modeling of the Return Current in a Light-Addressable Potentiometric Sensor.

A light-addressable potentiometric sensor (LAPS) is a chemical sensor with a field-effect structure based on semiconductor. Its response to the analyte concentration is read out in the form of a photocurrent generated by illuminating the semiconductor with a modulated light beam. As stated in its name, a LAPS is capable of spatially resolved measurement using a scanning light beam. Recently, it has been pointed out that a part of the signal current is lost by the return current due to capacitive coupling between the solution and the semiconductor, which may seriously affect the sensor performance such as the signal-to-noise ratio, the spatial resolution, and the sensitivity. In this study, a circuit model for the return current is proposed to study its dependence on various parameters such as the diameter of contact area, the modulation frequency, the specific conductivity of the solution, and the series resistance of the circuit. It is suggested that minimization of the series resistance of the circuit is of utmost importance in order to avoid the influence of the return current. The results of calculation based on this model are compared with experimental results, and its applicability and limitation are discussed.

Light-Addressable Potentiometric Sensors for Quantitative Spatial Imaging of Chemical Species.

A light-addressable potentiometric sensor (LAPS) is a semiconductor-based chemical sensor, in which a measurement site on the sensing surface is defined by illumination. This light addressability can be applied to visualize the spatial distribution of pH or the concentration of a specific chemical species, with potential applications in the fields of chemistry, materials science, biology, and medicine. In this review, the features of this chemical imaging sensor technology are compared with those of other technologies. Instrumentation, principles of operation, and various measurement modes of chemical imaging sensor systems are described. The review discusses and summarizes state-of-the-art technologies, especially with regard to the spatial resolution and measurement speed; for example, a high spatial resolution in a submicron range and a readout speed in the range of several tens of thousands of pixels per second have been achieved with the LAPS. The possibility of combining this technology with microfluidic devices and other potential future developments are discussed.

Safety and efficacy of treatment with liposomal amphotericin B in elderly patients at least 65 years old with hematological diseases.

The safety and efficacy of treatment with liposomal amphotericin B (L-AMB) in elderly patients has not been clarified, especially in Japanese patients. Therefore, we retrospectively analyzed 33 elderly patients with hematological diseases of at least 65 years old who received L-AMB between 2009 and 2012. Their clinical outcomes were compared to those of 21 patients who were younger than 65 years. L-AMB was administered for empirical therapy (n = 2) or target therapy for possible (n = 14) or probable/proven (n = 17) invasive fungal infection. There was no discontinuation of L-AMB due to adverse events. More than 2-fold increases from the baseline Cre, AST, and ALT values were observed in 21.2%, 39.4%, and 45.5% of the older group and 38.1%, 61.9%, and 52.4% of the younger group, respectively. The concurrent use of nephrotoxic antibiotics was the only risk factor for the development of a 2-fold increase in the serum Cre level. The duration of L-AMB was significantly longer in patients who developed grade III-IV hypokalemia. A partial or complete response was observed in 54.8% and 62.5% of the elderly and younger groups, respectively. In conclusion, L-AMB therapy appeared to be acceptably safe as empirical therapy or treatment for invasive fungal infection.

Light-Addressable Potentiometric Sensor as a Sensing Element in Plug-Based Microfluidic Devices.

A plug-based microfluidic system based on the principle of the light-addressable potentiometric sensor (LAPS) is proposed. The LAPS is a semiconductor-based chemical sensor, which has a free addressability of the measurement point on the sensing surface. By combining a microfluidic device and LAPS, ion sensing can be performed anywhere inside the microfluidic channel. In this study, the sample solution to be measured was introduced into the channel in a form of a plug with a volume in the range of microliters. Taking advantage of the light-addressability, the position of the plug could be monitored and pneumatically controlled. With the developed system, the pH value of a plug with a volume down to 400 nL could be measured. As an example of plug-based operation, two plugs were merged in the channel, and the pH change was detected by differential measurement.

[Successful treatment with azacitidine for a patient with relapsed myelodysplastic syndrome after cord blood transplantation].

A 72-year-old man visited our hospital in July 2009 with a major complaint of lightheadedness. Based on bone marrow aspiration, myelodysplastic syndrome (MDS), refractory anemia with excessive blast-2 was diagnosed. Complete remission (CR) was achieved after low-dose cytarabine and aclarubicin therapy. After two courses of low-dose cytarabine therapy, at the first CR, cord blood transplantation (CBT) was performed after reduced-intensity conditioning in January 2010. However, recurrence was found in September 2011. Azacitidine (AZA) was administered subcutaneously daily for either 7 or 5 days and repeated every 4 weeks at doses of 100 mg/day. During nine cycles of AZA treatment, no graft-versus-host disease was observed and no transfusions of red cells/platelet concentrate were required. As of 1 year after the relapse was detected, the patient remains alive with stable disease. As there are few reports on AZA treatment for patients with MDS who experience relapse after CBT, the efficacy of this approach remains unclear. Further clinical trials including dose, duration, and number of cycles of AZA for MDS patients who relapse after transplantation are required.

Generation of spatial filters by ICA for detecting motor-related oscillatory EEG.

To detect the imagined limb movement from EEG for the use in BCI, the increase (ERS) and decrease (ERD) of the band power of the EEG originated from the sensorimotor cortex are commonly used. A spatial filter using neighboring channels is generally applied to the measured EEG for detecting such brain activity related to the motor imagery. However, the configuration and location of the spatial filter have been selected by the empirical method on trial-and-error basis. In this study, we recorded the EEG during motor imagery of left hand, right hand and feet from five subjects, and the ICA (independent component analysis) was applied to discover the spatial filters for extracting event-related EEG components of the motor imagery. It was suggested that the application of ICA might offer the experimenters appropriate local spatial filters, or at least, the "initial guess" for designing or selecting custom local spatial filters.

A NIRS-based brain-computer interface system during motor imagery: system development and online feedback training.

A brain-computer interface (BCI) to detect motor imagery from cerebrum hemodynamic data measured by NIRS (near-infrared spectroscopy) was constructed and the effect of the online feedback training for subjects was evaluated. Concentrations of Oxy- and deOxy-hemoglobin in the motor cortex during motor imagery of subject's right hand was measured by 52-channel NIRS system, and the mean magnitude of measured signal near C3 in the International 10-20 System was visually fed back online to the subject. On two out of three subjects, it was shown that the ratio between the averaged value and the standard deviation over trials (S/N ratio) of Oxy-hemoglobin signal elicited by the imagery of subject's right hand was increased by the 5-day online feedback training. Detailed investigation of the effect of the online feedback training on brain activities was left for further study.

Clinicopathological features of lymphoma/leukemia patients carrying both BCL2 and MYC translocations.

BACKGROUND: Lymphoid neoplasm with 18q21.3/BCL2 and 8q24/MYC translocation to immunoglobulin (IG) genes as dual-hit lymphoma/leukemia is very rare and known to have a poor clinical outcome. DESIGN AND METHODS: To clarify the clinicopathological characteristics of this malignancy, we analyzed 27 cases of cytogenetically proven dual-hit lymphoma/leukemia. RESULTS: Dual-hit lymphoma/leukemia was diagnosed at presentation in 22 cases and at relapse or disease progression in 5 cases. At the time of diagnosis of dual-hit lymphoma/leukemia, extranodal involvement was found in 25 cases (93%) and central nervous system involvement occurred in 15 cases (56%). The median survival and 1-year survival rate of the 27 cases were only 6 months and 22%, respectively, after diagnosis of the dual-hit lymphoma/leukemia. Seven cases of triple-hit lymphoma/leukemia (dual-hit lymphoma/leukemia with 3q27/BCL6 translocation) were included; the median survival of these patients was only 4 months from the diagnosis of the dual-hit lymphoma/leukemia. The duration of survival of the patients with a triple-hit malignancy was shorter than that of the other 20 cases of dual-hit lymphoma/leukemia (p=0.02). The translocation partner of MYC subdivided the dual-hit cases into two groups; 14 cases of IGH and 13 cases of IGK/L. The MIB-1 index was investigated in 14 cases with aggressive B-cell lymphoma, and was higher in the group with MYC-IGH translocation (n=7) than in the MYC-IGK/L group (n=7) (p=0.02). Overall survival was not different between the MYC-IGH translocation group (n=14) and the MYC-IGK or MYC-IGL translocation group (n=13). CONCLUSIONS: Dual-hit lymphoma/leukemia is a rare but distinct mature B-cell neoplasm with an extremely poor prognosis characterized by frequent extranodal involvement and central nervous system progression with either of the translocation partners of MYC.

A brain-computer interface (BCI) system based on auditory stream segregation.

An auditory brain-computer interface (BCI) which detected event-related potential (ERP) elicited by selective attention to one of the tone streams was proposed. Each tone in two kinds of frequency oddball tone sequences with different tone frequency range was presented alternatively to subjects, and they were perceived by subjects as two kinds of segregated streams. Event-related potentials elicited by two kinds of deviant tones were classified by linear discriminant analysis (LDA) to find which streams subjects paid selective attention. By the experiments to six subjects, it was shown that this system could realize binary selection from two kinds of segregated tone streams.

Label-free detection of protein-protein interactions at the GaAs/water interface through surface infrared spectroscopy: discrimination between specific and nonspecific interactions by using secondary structure analysis.

Here, we propose a label-free detection of protein-protein interactions that enables simultaneous qualitative analysis of target proteins by using Fourier transform infrared (FTIR) absorption spectroscopy in multiple internal reflection geometry (MIR-FTIR). Using this method, the target proteins were detected based on the peak height of the amide I and amide II bands, while discrimination of specific and nonspecific signals is made based on the secondary structure of the analytes, which is determined through second-derivative analysis of the amide I band. As a model system, an antigen peptide was immobilized on the surface of GaAs, which was transparent to mid-infrared light, and the interaction with its antibody was examined in aqueous media. We demonstrated that the binding of the antibody to the antigen immobilized on a GaAs surface selectively gave rise to beta-sheet amide I vibrations (1639 and 1690 cm-1), while no structurally related signals were induced by nonspecifically adsorbed proteins. The peak height of the beta-peak (1639 cm-1) in the amide I band linearly increased with the antiserum concentration as well as that of the amide II band. The detection limit (S/N = 3) was a 1:36 000 dilution for the amide I signal. In addition, through the use of surface-sensitive MIR-FTIR, the present sensor selectively detected the antigen-antibody interactions at the surfaces without being affected by the presence of bulk species, enabling rapid and wash-free detection. Our method provides not only rapid label-free detection of protein-protein interactions but a more accurate discrimination between specific and nonspecific interactions through the use of the secondary structure of the target proteins as a measure for the specific signals.

In situ observation of a cell adhesion and metabolism using surface infrared spectroscopy.

In this study, we report on an in situ monitoring system of living cultured cells using infrared absorption spectroscopy in the geometry of multiple internal reflections (MIR-IRAS). In order to observe living cultured cells, the temperature in the sample chamber of a FT-IR spectrometer was maintained at 37 degrees C and a humidified gas mixture containing 5% CO(2) was introduced into the sample chamber. Human breast cell line MCF-7 cultured on Si MIR prisms were placed in the sample chamber and infrared spectra of MCF-7 cells were collected for 5 h. It was found that the adhesion and metabolism of MCF-7 cells could be monitored by the absorption intensity of amide-II protein band (1,545 cm(-1)) and also by the absorption intensities of CH( x ) bands (2,700-3,100 cm(-1)). These results suggest that our system is useful for a nondestructive and non-label monitoring of cell viability. Our method based on infrared absorption spectroscopy has a potential for bioscreening application.

Reduced-intensity unrelated cord blood transplantation for patients with advanced malignant lymphoma.

We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.