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This study explores a novel therapeutic approach for peritoneal metastasis (PM) using AAV-mediated delivery of tumor suppressor microRNA-29b (miR-29b) to peritoneal mesothelial cells (PMC). AAV serotypes 2 and DJ demonstrate high transduction efficiency for human and murine PMC, respectively. In vitro analysis indicates that AAV vectors encoding miR-29b precursor successfully elevate miR-29b expression in PMC and their secreted small extracellular vesicle (sEV), thereby inhibiting mesothelial mesenchymal transition and reducing subsequent attachment of tumor cells. A single intraperitoneal (IP) administration of AAV-DJ-miR-29b demonstrates robust and sustained transgene expression, suppressing peritoneal fibrosis and inhibiting the development of PM from gastric and pancreatic cancers. Additionally, AAV-DJ-miR-29b enhances the efficacy of IP chemotherapy using paclitaxel, restraining the growth of established PM. While conventional gene therapy for cancer encounters challenges targeting tumor cells directly but delivering miRNA to the tumor stroma offers a straightforward and efficient means of altering the microenvironment, leading to substantial inhibition of tumor growth. AAV-mediated miR-29b delivery to peritoneum via IP route presents a simple, minimally invasive, and promising therapeutic strategy for refractory PM.

L10-FePt grains with structural inhomogeneity in a granular film was investigated, and their blocking phenomenon was simulated. It was confirmed that: 1) structure analysis reveals that both lattice distorted disordered portion at the bottom region near the interface with MgO underlayer and ordered portion at the upper region exist inside one FePt grain in a granular film and 2) simulation of blocking phenomenon for FePt grains with structural inhomogeneity which consists of a hard (order)/soft (disorder) bilayer shows that switching field ( ${H}_{\mathbf {sw}}$ ) increases steeply near the Curie temperature ( ${T}_{C}$ ) of the disorder layer with decreasing temperature. To generalize blocking phenomenon of the hard/soft bilayer structure, it was found that matching the Curie temperatures of the hard and soft layers leads to enhancement of ${H}_{\mathbf {sw}}$ near the ${T}_{C}$ , which means enhancement of robustness against thermal field in random direction. These findings are useful for the design of cap-layer for heat-assisted magnetic recording (HAMR) media to realize the high spatial resolution.

Precipitation hardening of soft magnetic stainless steel was investigated to achieve both workability (low hardness during machining) and durability (high hardness in practical use) while maintaining soft magnetic properties. NiAl intermetallic compound was used for precipitation hardening. The relationship among aging temperature, microstructure, magnetic properties, and hardness was investigated for 22 composition samples with the basic composition of 15Cr–1Si–2Mo–3Ni–1Al–0.15Ti–bal. Fe (in wt%) and varying compositions of Si, Mo, Ni, Al, and Cu. The maximum aged hardness was obtained by solution treatment at 1030 °C followed by aging at 550 °C. Soft magnetic properties were achieved with a single-phase ferrite composition ( $\delta $ : bcc structure), and the hardness level could be adjusted with the concentration of solid solution-strengthening elements. Two indices of the relationship between microstructure and magnetic properties and between solid solution strengthening elements and hardness were obtained. The soft magnetic properties obtained by solution treatment were maintained after aging despite the occurrence of nonmagnetic precipitates of NiAl intermetallic compound. This is because precipitates do not become pinning sites for the domain wall due to their small size and distance between precipitates (1/175 and 1/26 of the domain wall, respectively). As a result, a practical precipitation hardening soft magnetic stainless steel with good properties of 227 HV after solution treatment, 372 HV, and a coercive force of 64 A/m after aging treatment was realized.

Electromagnetic wave absorbers for low-frequency kHz ranges have attracted much attention due to electromagnetic wave inference problems. In this study, we fabricated co-aggregated assemblies of Fe and Fe3O4 nanoparticles (NPs) as a new candidate for electromagnetic wave shielding and absorbing materials. The co-aggregated assemblies with a mass ratio of Fe to Fe3O4 NPs of 5:5 showed a maximum magnetic loss (tan $\delta $ ) value of 0.023 at around 200 K. This can be explained by the blocking of magnetically isolated Fe NPs in the co-aggregated assembly, where the magnetostatic dipole interactions between the Fe NPs and the Fe and Fe3O4 NPs can be negligibly small.

The effect of adding carbon (C) grain boundary material (GBM) on magnetic properties and nanostructure of FePt-nitride granular films with various nitrides is reported. The saturation magnetization of FePt-nitride-C granular films shows a similar tendency with that of FePt-nitride granular films which varies almost linearly against volume averaged melting point ( ${T} _{m}^{\text {ave}}$ ) of the GBM. The values of perpendicular magnetic anisotropy and degree of order of $\text{L}1_{0}$ -FePt phase for all FePt-nitride granular films are enhanced and the amount of magnetic grains with the ${c}$ -axis parallel to the film plane is reduced when nitride is partially replaced with C. Furthermore, by replacing nitride with C, the grain-to-grain separation is promoted significantly. When the ${T} _{m}^{\text {ave}}$ of the GBM increases from around 2500 °C to 3500 °C, in general, the average cluster diameter (CD) and cluster boundary (CB) decrease from around 13 to 9 nm and from 12 to 5 nm, respectively. Considering of ${T} _{m}^{\text {ave}}$ of the GBM, these results suggest that the GBM with high ${T} _{m}^{\text {ave}}$ will solidify prior to FePt which acts as the nucleation site to reduce the CD, which is similar to CoPt-based alloy granular films.

A sputtered tape that uses a CoPtCr-based granular recording layer consisting of magnetic grains and grain boundary oxides was developed for practical applications in next-generation large-capacity magnetic tapes. The role of oxides in CoPtCr-oxide composite targets in forming nanostructures for the granular layer was investigated under the distinctive conditions of a roll-to-roll sputtering system. It was confirmed that: 1) increasing the amount of Co3O4 in the CoPtCr-SiO2-Co3O4 composite target improved the magnetic isolation between magnetic grains and the magnetic anisotropy of the granular recording layer due to diffusion of Si and Cr from within magnetic grains to oxide grain boundaries by oxidation; 2) this magnetic isolation led to 3.6 dB improvement in the broadband signal-to-noise ratio (BB-SNR) at a linear density of 353 kfci through suppression of noise; and 3) overlaying CoPtCrB alloy layer to this sample as a cap layer brought the higher BB-SNR of 2.3 dB than that for the sample reported by us in TMRC2017. Applying the latest track-following technology, this SNR improvement was estimated to have the potential to achieve an areal density of 375 Gb/in2.

Technical developments and operational experiences that have been achieved by Taiheiyo Cement Corporation of Japan in recycling household waste incineration ash are explained. The recycling efforts are part of a program named 'Zero Emission framework in Saitama Prefecture.' How Taiheiyo refined preprocessing and desalination measures for flyash is also discussed.

A method for managing the volatile components of alternative materials in cement manufacturing in Japan is presented. The introduction of the chlorine bypass system has solved the problem of chlorine content in such materials. Extraction of the potassium salt from the material has also been found to solve the problem.

The frequency of tumor cell dissemination in the peritoneal cavity is critically related to the progression of peritoneal metastases (PM). Recently, flow cytometry (FCM) has been successfully used to detect tumor cells in malignant effusions. A total of 143 single cell suspensions derived from ascites or peritoneal lavages from patients with advanced gastric cancer (GC) were stained with monoclonal antibodies to CD45 and to CD326 as well as 4,6‐diamidino‐2‐phenylindole (DAPI) and FVS780. Using FCM, tumor‐leukocyte ratio (TLR) were calculated from CD45(−)CD326(+) tumor cell counts/ CD45(+)CD326(+) leukocyte counts in DAPI (+) FVS780(−) gated area. In 54 patients, the ratios of CD11b(+), CD4(+) and CD8(+) cells in CD45(+) leukocytes were evaluated in parallel. TLR of 69 patients with PM were significantly higher than those of 74 without PM (p< .001) and log(TLR) showed strong correlation with peritoneal cancer index scores in 51 PM (+) patients (r= 0.439). TLR in PM (+) patients also correlated with the ratio of CD11b (+) myeloid cells (r= 0.547), and correlated inversely with those of CD4(+) (r= −0.490) and CD8(+) T cells (r= −0.648). In PM (−) patients who underwent gastrectomy, TLR never exceeded 0.1% in patients with primary GC without serosal involvement (

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

Patients with esophageal cancer and a history of gastrectomy or concurrent gastric cancer undergo not only esophagectomy but also total gastrectomy. The goal of this study is to evaluate the postoperative quality of life (QOL) and dysfunction of these patients using two postoperative questionnaires.

ABSTRACTLung cancer is the leading cause of cancer-related deaths worldwide with over 1 million deaths each year. The overall prognosis of lung cancer patients remains unsatisfactory, with a 5-year overall survival rate of less than 15%. Although most lung cancers are a result of smoking, approximately 25% of lung cancer cases worldwide are not attributable to tobacco use. Notably, more than half of the lung cancer cases in women occur in non-smokers. Among non-small-cell lung cancer (NSCLC) cases, cigarette-smokers have a greater association with squamous cell carcinoma than adenocarcinoma, which is more common in non-smokers. These findings imply that specific molecular and pathological features may associate with lung adenocarcinoma arising in non-smoker female patients.Over the past decade, whole genome sequencing and other ‘-omics’ technologies led to the discovery of pathogenic mutations that drive tumor cell formation. These technological developments may enable tailored patient treatments throughout the course of their disease, potentially leading to improved patient outcomes. Some clinical and laboratory studies have shown success outcomes using epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) in patients with EGFR mutations and ALK rearrangements, respectively. In fact, these 2 mutations are predominantly present in female non-smokers with adenocarcinoma. Immunotherapy has also recently emerged as a major therapeutic modality in NSCLC.In this review, we summarize the current understanding of NSCLC biology and new therapeutic molecular targets, focusing on the pathogenesis of non-smoker female NSCLC patients.

The blocking temperature (TB) and blocking temperature distribution (ΔTB) of magnetic grains were evaluated for L10-type FePt granular films with various grain boundary materials (GBMs). TBand ΔTBwere measured from remanent magnetization. The relationship between the degree of order and Curie temperature (TC) for the L10-type FePt phase was separately evaluated using alloy films. According to actual measurements, the obtained mean TB, mean TB/TCand ΔTBfor granular films were 620 K, 0.83 K, and 200 K, respectively, for SnO GBM film and 450 K, 0.61 K, and 260 K, respectively, for TiO2GBM film. Based on these values, mean TB, mean TB/TC, and ΔTBwere calculated assuming that τ= 2 × 10−7s, which is the relaxation time, corresponds to the HAMR writing time. These were 737 K, 0.98 K, and 24 K, respectively, for SnO GBM film and 685 K, 0.93 K, and 72 K, respectively, for TiO2GBM film. These results for granular films can be useful for designing a hard disk drive with HAMR.

In this study, post-annealing under NH3gas atmosphere was conducted in order to promote the two-phase separation of FePt-BN granular films. Magnetic properties and structural analysis for the Fe50Pt50–30 vol% BN granular films revealed that (1) saturation magnetization (Ms) of the granular film increased from 500 to 650 emu cm-3with increasing post-annealing time from 0 to 10 min, (2) the orientation of FePt grains changes from (002) to (111) and fully ordered with increasing post-annealing time up to 30 min, (3) the unit cell volume of FePt grains in the granular film decreased from 55.91 to 55.55 Å3with increasing post-annealing time from 0 to 10 min, which suggests dissolve and eject of solid solution element. From the above, Msreduction for the FePt-BN granular films is considered to be caused by the solid solution of B in the FePt grains.

Magnetic properties and nanostructure for FePt-30vol%TiN deposited while flowing N2gas are investigated. When N2gas addition of 3%–5% are introduced, compared with that of without N2gas, reduction in the lattice constant ratio and the unit cell volume, the increase in the degree of order of the granular film are observed. These indicate the segregation of Ti into grain boundaries as the result of the N2gas addition through nitridization of Ti dissolved in the FePt grains which lead to the enhancement of saturation magnetization, perpendicular magnetic anisotropy, and magnetic anisotropy field of the granular film. Therefore, magnetic decoupling in the FePt-TiN similar to the FePt-BN granular films is promoted by the segregation of nitrides formed by nitridization of metal element solidly soluble in FePt magnetic grains due to nitrogen deficiency.

Metallic silver with a nanofilament morphology was directly formed on electrodes with a combination of electrochemical processes and a silver halide photography development reaction. Metallic silver was first electrodeposited on a substrate electrode, and then converted to silver iodide through a combined electrochemical/chemical process. The silver iodide on the electrode was then treated with a photographic developer solution, giving metallic silver with the nanofilament morphology. The use of carbon paper as the substrate electrode gave superior adhesive stability of the nanofilaments for future functionalization.Metallic silver with a nanofilament morphology was directly formed on an electrode through combination of electrochemical processes and a silver halide photography development reaction. Metallic silver was first electrodeposited on a substrate electrode, and converted to silver iodide through a combined electrochemical/chemical process. The silver iodide was then treated with a photographic developer solution, giving metallic silver with nanofilament morphology on the electrode.

In this study, we investigated the effects of the sheet texture of the Mo underlayer on the c-axis texture of the high-rate-sputtered Nd2Fe14B phase. The magnetic properties revealed that the squareness of the Nd–Fe–B magnetic layer did not depend on the sheet texture of the Mo underlayer but on the substrate temperature: large squareness was obtained when the magnetic layer was sputtered at high substrate temperature above 500 °C. In-plane X-ray diffraction measurements indicated that the intensity of diffraction from the Nd2Fe14B (410) plane did not depend on the sheet texture of the Mo underlayer but on the substrate temperature: high intensity was obtained when the magnetic layer was sputtered at above 500 °C, which was consistent with magnetic properties. These results support that the c-axis texture of the high-rate-sputtered magnetic layer was driven by the cplane with the lowest surface energy among the crystal planes in the Nd2Fe14B phase.

The double-stapling technique (DST) for esophagojejunostomy using the transorally inserted anvil (OrVil; Covidien Japan, Tokyo, Japan) is one of the reconstruction methods used after laparoscopy-assisted total gastrectomy (LATG). This technique has potential advantages in terms of less invasive surgery without the need to create a complicated intraabdominal anastomosis.From 2008 to 2011, 262 patients with gastric cancer underwent total gastrectomy and reconstruction with a Roux-en-Y anastomosis, and 52 patients underwent LATG with DST. A retrospective analysis then was performed comparing the patients who experienced postoperative stenosis after LATG-DST (positive group) and the patients who did not (negative group). A comparative analysis was performed among patients comparing conventional open total gastrectomy and LATG, and multivariate analysis was performed to evaluate risk factors for the development of anastomotic stenosis.A minor leak was found in 1 patient (1.9 %), and 11 patients experienced anastomotic stenosis (21 %) after LATG with DST. Among the patients with anastomotic stenosis, three (3/4, 75 %) anastomoses were performed with the 21-mm end-to-end anastomosis (EEA) stapler, and eight anastomoses were performed (8/47, 17 %) with the 25-mm EEA stapler. The median interval to the diagnosis of anastomotic stenosis was 43 days after surgery. The patients with stenosis needed endoscopic balloon dilation an average of four times, and the rate of perforation after dilation was 13 %. The clinical and operative characteristics did not differ between the two groups. Anastomotic stenosis after open total gastrectomy occurred in two cases (0.98 %). Multivariate analysis showed that the size of the EEA stapler and the use of DST were risk factors for anastomotic stenosis.Esophagojejunostomy using DST with OrVil is useful in performing a minimally invasive procedure but carries a high risk of anastomotic stenosis.

Single crystal Ge layers were successfully fabricated on the buried oxide layer of a silicon-on-insulator wafer using a combined technique of two-step selective epitaxial growth and Ge condensation. X-ray diffraction measurements revealed that the single crystal Ge layer formed on the buried oxide layer had a tensile strain of 0.07% on the $\langle 110\rangle$ lattice plane in a large unpatterned area. Furthermore, a steep photoluminescence spectrum was obtained from Ge stripes fabricated on the buried oxide layer, and a red shift in the photoluminescence peak was observed due to tensile strain with a wavelength of 1620 nm. The peak intensity of a 10-mm-wide Ge stripe on the buried oxide layer was three times higher than that on a Ge stripe on an Si substrate, which was achieved by improving the crystallinity and carrier confinement within the Ge stripes. These results indicate that this combined technique efficiently improves the performance of Ge light-emitting devices.

Abstract: Background: To decrease the incidence of internal hernia after laparoscopic gastric bypass, current recommendations include closure of mesenteric defects. Laparoscopic gastric resection is used increasingly for the treatment of gastric cancer, but the incidence of internal hernia in the treated patients has not been studied. Methods: This study retrospectively reviewed 173 patients who underwent laparoscopic resection for gastric cancer at one institution, including distal and total gastric resections with antecolic Roux-en-Y reconstruction. Results: An internal hernia occurred in 4 (7%) of 58 patients whose jejunojejunal mesenteric defect was not closed a mean of 326 days after surgery. All the patients underwent reoperation with reduction and repair of the hernia. In 115 subsequent cases, with closure of the mesenteric defect, internal hernias did not occur (0/115 cases; p < 0.05). Conclusion: Based on the current recommendations for patients undergoing bariatric surgery, closure of this potential hernia defect is mandatory after laparoscopic gastrectomy with a Roux-en-Y reconstruction for gastric cancer.

Quantum mechanical electron tunneling has potential applications in both science and technology, such as flash memories in modern LSI technologies and electron transport chains in biosystems. Although it is known that one-dimensional quantum electron tunneling lacks temperature dependence, the behavior of electron tunneling between different dimensional systems is still an open question. Here, we investigated the electron tunneling between a two-dimensional electron gas (2DEG) and zero-dimensional Si quantum dots and discovered an unexpected temperature dependence: At high temperature, the gate voltage necessary for electron injection from 2DEG to Si quantum dots becomes markedly small. This unusual tunneling behavior was phenomenologically explained by considering the geometrical matching of wave functions between different dimensional systems. We assumed that electron tunneling would occur within a finite experimental measurement time. Then, the observed electron tunneling is explained only by the contributions of wave packets below the quantum dot with a finite lifetime rather than the ordinary thermal excited states of 2DEG.

A novel DNA microarray method to detect one line of genetically modified (GM) soybean and five lines of GM maize was developed using multiplex PCR coupled with primer extension on a plastic plate. Multiplex PCR products were applied on an extension primer-immobilized plate and the spots corresponding to the DNA sequences were visualized. This method is a rapid and simple way to detect GM soybean and GM maize optically.

In order to open a way to realize ultra high density hard disk (HD) drives with fast operation speed utilizing a spin nano-technology, precisely controlled fabrication technology with nano-scale for head and media according to the required properties is essential from material, processes, and physical view point. In the present paper, correlation between process parameter of ultra clean (UC) dry-process proposed by us and structure and physical property for ferro/antiferro interface, magnetic tunnel junctions and perpendicular magnetic recording media will be widely discussed.

In this report, we have developed a novel quantitative RT-PCR protocol in which the procedure including mRNA purification can be performed in an all-in-one tube. To simplify gene expression analysis, oligo-dT30immobilized PCR tubes were used serially to capture mRNA, synthesize solid-phase cDNA, and amplify specific genes. The immobilized oligo-dT30can efficiently capture mRNA directly from crude human cell lysates. The captured mRNA is then amplified by one-step reverse transcription PCR (RT-PCR) with initial cDNA synthesis followed by PCR. In RT-PCR, this new reusable PCR tube device can be employed for multiple PCR amplifications with different primer sets from a solid-phase oligo-dT30primed cDNA library. This paper introduces a novel and highly reliable all-in-one tube method for rapid cell lysis, followed by quantitative preparation and expression analysis of target mRNA molecules with small amounts of sample. This procedure allows all steps to be carried out by sequential dilution in a single tube, without chemical extraction. We demonstrate the utility of this novel method by quantification of two housekeeping genes, β-actin and GAPDH, in HeLa cells. We believe this new PCR device can be useful as a platform for various mRNA expression analyses, including basic research, drug screening, and molecular toxicology, as well as for molecular pathological diagnostics.

A new real-time PCR method using capturing oligo-immobilized PCR tubes is described. This method was used to detect specific genes for soybean and genetically modified (GM) soybean in food matrices. In a standard reaction using soybean genomic DNA and a capturing oligo for the lectin gene (Le1) immobilized on the tube, we examined the effects of such hybridization conditions as the location, length, and amount of the capturing oligo, and the incubation time and temperature. Under optimized conditions, the copy number of Le1was determined in a concentration-dependent manner from soybean genomic DNA and soybean lysate (DNA 10–1000 ng, r=0.99; lysate 1–100%, r=0.99). The copy number of a Roundup Ready soybean (RRS) gene was also successfully detected in a concentration-dependent manner (1–100%, r=0.99) from GM soybean lysate, using PCR tubes with an immobilized capturing oligo for the transgene. Our data indicate that this is a rapid and simple method to determine specific genes for soybean and GM soybean in food matrices.

In most cases, hot metal dephosphorization slag is saturated with dicalcium-silicate that forms complete solid solution with tricalciumphosphate; the partition ratio of phosphorous between C2S and liquid slag is large. In order to utilize the effect of C2S phase for the improvement of reaction efficiency, the optimum route of the slag composition change during dephosphorization should be clarified. The results of the fundamental experiments about the phosphorous partition between C2S and liquid slag from the viewpoints of equilibrium and kinetics are reported.

Magnetic resonance imaging (MRI) can clearly visualize both the ossification centers and surrounding cartilage of growing bones and enable a three-dimensional analysis of their positional relationships by using overlapping images. The calcaneal position was evaluated based on five newly proposed parameters of magnetic resonance images in 30 clubfeet of 18 infants with the bimalleolar and lower leg axes as reference lines. Sixteen unaffected feet in the unilateral cases were analyzed as normal feet. MRI showed that the calcaneus in clubfoot rotated internally, medially and posteriorly with reference to the bimallelar axis and that it took an equinus and a varus position with reference to the lower leg axis as compared with the normal foot. These five parameters and their normal values on the calcaneal position should be useful for the evaluation of infantile clubfeet.

Acute effect of Mao-Bushi-Saishin-To(Ma-Huang-Fu-Zi-Xi-Xin-Tangin Chinese: MBS) on histamine release was investigated. The IgE-mediated anaphylaxic response in Wistar rats was significantly suppressed by MBS and Mao. However, Saishinand Bushihad no or little effect on the antigen-mediated anaphylaxic reaction. Maoas well as MBS but not Saishinnor Bushiinhibited IgE-mediated histamine release from rat basophilic leukemia (RBL-2H3) cells. Consistently, MBS and Maobut not Bushinor Saishinincreased cAMP levels in RBL-2H3 cells. However, ephedrine, methylephedrine, and pseudoephedrine, the main components in Mao, did not affect histamine release. From these results, increase of cAMP levels may account for the inhibitory effect of Maoon histamine release. Furthermore, these inhibitory actions of MBS were mainly due to Maowith an ingredient(s) different from ephedrines.

Purpose:To report a rare case of choroiditis in association with systemic lupus erythematosus (SLE).

Purpose To predict future glaucomatous sensitivity loss using a perimetric color saturation test (PCST) that measures the color saturation discrimination threshold for six hues (red, yellow, green, green-blue, blue, and purple) at 9° in horizontal and 3° in vertical extrafoveal points. Methods This new test was carried out on 31 patients (31 eyes) with early glaucoma or ocular hypertension. The sensitivity loss at the four points approximately 9.5° apart from the fixation point was prospectively evaluated annually for 3 years using the Humphrey Field Analyzer (HFA) program central 30-2. The initial results of PCST and the total deviation (TD) in the follow-up HFA results were compared. Results Twenty-seven patients (27 eyes) were followed up for 3 years. The color saturation threshold for six hues was correlated with the TD of HFA results at 108 points in the 27 eyes. The TD was −4 dB or better at the baseline measurement in 91 out of the 108 points. The averaged TD in the second and the third year in the follow-up period decreased below −4 dB in 10 of these 91 points, which were categorized as progression points in relation to the 81 nonprogression points. In the initial PCST, only the saturation threshold for purple was higher in the progression points when compared with the nonprogression points ( P = .0004, Mann-Whitney U -test). Conclusion Future sensitivity loss is most likely at the points where the threshold of color saturation discrimination is increased for purple in eyes with early glaucoma or ocular hypertension.

We investigated the viscoelastic effects on the early stage spinodal decomposition (SD) in semi-dilute polymer solutions where the coupling between stress and diffusion plays an important role. The so-called viscoelastic length, ξve, within which the stress suppresses the growth of the concentration fluctuations, was quantitatively evaluated experimentally. The evaluated value was found out to be about 10 times larger than the radius of gyration of polymer. We measured the interdiffusion coefficient, the cooperative diffusion coefficient, the zero-shear viscosity, and the plateau modulus in the one phase region and evaluated ξveindependently from the SD experiment. The value ξveobtained in the early stage SD agrees well with that estimated from the diffusion and viscoelasticity measurements, confirming the validity of the Doi–Onuki theory.

The production of ascorbate radical (A·-) was investigated in tissues of rats intoxicated with paraquat (PQ) to know the protective role of antioxidant ascorbate (AH·-) in tissues. The electron spin resonance (ESR) method is applied to observe A·-. To eliminate increased biosynthesis of ascorbic acid (AH2) by PQ intoxication, ODS rats were chosen and fed with or without 250 ppm PQ in the diet. The radical A·- was detected only in the lung and spleen homogenates of both intoxicated and control rats at the beginning of ESR measurement. The radical levels of intoxicated rat lung and spleen were increased rapidly to twice the initial level after 3 h and decreased to 0.2-0.6 times the initial level after 24 h, whereas those of control rats were increased slowly to 1.1 times the initial level after 4 h and decreased slowly to 0.7 times the initial level after 24 h at 4°C. In other organs such as liver, kidney, heart and testis, A·- was not detected initially but detected afterwards. Higher A·- level was observed in the intoxicated rat liver than the control but no appreciable differences of A·- levels were observed between the intoxicated kidney, heart and testis and the respective controls. In the intoxicated rat lung the concentration of AH2 is only half but that of A·- is twice as high as that of the control. Larger amounts of A·- produced in the intoxicated rats decayed more quickly than those in the control rats. The simple addition of PQ to the control organ enhanced neither A·- production nor A·- quenching. These facts suggest that the tissues damaged by PQ require larger amounts of AH- to detoxicate harmful oxidants, resulting in concomitant production of A·-.

In a previous study, we speculated that the early phase of hematopoietic recovery after PBSC transplantation (PBSCT) is rapid because of the increased production of endogenous cytokines by cotransfused monocytes and lymphocytes (Kawano Y, et al. Blood 81:856, 1993). To clarify this point, the serum level of G-CSF was measured using an ELISA, and various other cytokines, including GM-CSF, macrophage-CSF (M-CSF), SCF, IL-6, IFN-gamma, and soluble IL-2 receptor (IL-2R), were tested for comparison in children receiving conventional or high-dose chemotherapy and autologous transplantation with unmanipulated or purified PBSC. Serum G-CSF levels in patients receiving conventional chemotherapy (n = 21) or PBSCT without exogenous G-CSF treatment (n = 19) increased to 1245 +/- 2337 pg/ml and 2741 +/- 2331 pg/ml, respectively. Likewise, the peak level of G-CSF in patients who did not receive G-CSF was statistically equivalent to the trough level in those who did. There was no significant difference in the speed of hematopoietic recovery with or without G-CSF treatment in both the conventional chemotherapy and PBSCT cohorts. In addition, no meaningful change was observed in the kinetics of other tested factors in either conventional therapy or PBSCT settings, regardless of whether the patient did or did not receive G-CSF. Endogenously produced serum peak G-CSF levels after PBSCT with purified CD34+ cells were identical to those after the same procedure with unmanipulated cells. These results confirm that children receiving intense chemotherapy followed by autologous PBSCT produce a high level of G-CSF during the cytopenic period that is not due to the infusion of a large amount of facilitating cells capable of producing G-CSF.

We investigated the ground state of the infinite dimensional Hubbard model for both attractive and repulsive interactions by applying Gutzwiller type variational wave functions. Our variational wave functions have lower energies than the simple BCS wave function for the attractive case, and lower energies than the Brinkman-Rice state for the repulsive case. We found that the system has several phases depending on the density of electrons and the interaction strength. Investigated phases include antiferromagnetic, Fermi liquid, superconducting, charge density wave, and supersolid phases. The last one is a coexistence phase of superconducting and charge density wave states.

A tax reform influences households in many ways. Income tax reform influences the disposable income of households, and a reform of indirect tax influences the prices of goods and services. Furthermore, the changes in disposable income or in prices are thought to influence the consumption behavior of households. When a tax reform is enacted, one must not only evaluate the impact of the reform ex post facto but also must analyze it ex ante facto. It is likely that such an analysis will stimulate debate over the reform and lead to a more desirable reform. A series of simulation analyses that Homma (1986) attempted in the tax reform project of the Policy Design Forum was conducted with this thought in mind.

Sintering anisotropy in slip-cast SiC-whisker/Si3N4-powder compacts was studied at 1750°C in 0.1 MPa N2 or at 1825°C in 1.0 MPa N2. It was shown that whiskers oriented parallel to the mould surface and nearly 1.5-dimensionally along the slip flow direction when the whisker content was 10 wt%. Linear shrinkage was largest perpendicular to the mould surface and smallest perpendicular to the whisker alignment. It was shown that the retardation of densification by whiskers is due to the formation of a rigid network along the whisker alignment, which is in accordance with percolation theory. The addition of up to 20 wt% whisker did not affect sintering kinetics but lowered sinterability by 2-dimensional alignment of the whiskers. The anisotropy in fracture toughness is related to the orientation of the whiskers.

A toxin isolated from marine sponge, mycalolide‐B, inhibited smooth muscle contractions without changing cytosolic Ca2+levels. It also inhibited Ca2+‐induced contraction in permeabilized smooth muscles. In native actomyosin prepared from chicken gizzard, mycalolide‐B inhibited superprecipitation and Mg2+‐ATPase activity stimulated by Ca2+without changing myosin light chain phosphorylation. In the permeabilized muscle and native actomyosin preparation thiophosphorylated with ATPγS, mycalolide‐B inhibited ATP‐induced contraction and Mg2+‐ATPase activity, respectively, in the absence of Ca2+. Mycalolide‐B also inhibited Mg2+‐ATPase activity of skeletal muscle native actomyosin. Mycalolide‐B had no effect on calmodulin‐stimulated (Ca2+–Mg2+)‐ATPase activity of erythrocyte membranes. These results suggest that mycalolide‐B selectively inhibits actin—myosin interaction.

Stellettamide A (ST‐A), a novel marine toxin isolated from a marine sponge, inhibited high K+(72.7 mM)‐induced contraction in the smooth muscle of guinea‐pig taenia coli with an IC50of 88 μM.In the taenia permeabilized with Triton X‐100, ST‐A inhibited Ca2+(3 and 10 μM)‐induced contractions with an IC50of 46 μMfor 3 μMCa2+and 105 μMfor 10 μMCa2+. In the permeabilized taenia, calyculin‐A (300 nM), a potent inhibitor of type‐1 and type‐2A phosphatases, induced sustained contraction in the absence of Ca2+. ST‐A had no effect on this contraction.ST‐A inhibited Mg2+‐ATPase activity in native actomyosin prepared from chicken gizzard with an IC50of 25 μM.In a reconstituted smooth muscle contractile system containing calmodulin, myosin light chain (MLC) and MLC kinase, ST‐A inhibited MLC phosphorylation with an IC50of 152 μM. The inhibitory effect of ST‐A was antagonized by increasing the concentration of calmodulin.ST‐A inhibited calmodulin activity, assessed by Ca2+/calmodulin‐dependent enzymes, (Ca2+‐Mg2+)‐ATPase of erythrocyte membrane, with an IC50of 100 μMand phosphodiesterase prepared from bovine cardiac muscle with an IC50of 52 μM. The inhibitory effect on phosphodiesterase activity was antagonized by increasing the calmodulin concentration.Interaction between ST‐A and calmodulin was demonstrated by instantaneous quenching of the intrinsic tyrosine fluorescence of calmodulin by ST‐A (3–300 μM). Similar results were obtained in the presence or absence of Ca2+suggesting that ST‐A binds to calmodulin and that Ca2+is not essential for the binding of ST‐A to calmodulin.These results suggest that ST‐A, isolated from marine metabolites, is a novel inhibitor of calmodulin.

Purified peripheral blood hematopoietic progenitors from children in early remission from cancer respond to recombinant human interleukin-3 (IL-3), but not to granulocyte colony-stimulating factor (G-CSF). With these purified cells as a target, we studied the effect of recombinant human interferon-γ (IFN-γ) on progenitor growth, using both liquid-suspension limiting dilution assay (LDA) and regular methylcellulose culture of progenitors. We found that in LDA with IL-3, IFN-γ directly stimulated the growth of blood progenitors in a dose-dependent manner with single-hit kinetics, whereas IFN-γ suppressed the growth of G-CSF–supported progenitors obtained from bone marrow. The stimulatory effect was also observed in methylcellulose culture, but the addition of antibodies for G-CSF, granulocyte-macrophage CSF, IL-1α, IL-1β, IL-6, or tumor necrosis factor did not result in a decrease of the colony number, supporting further the possible direct effect of IFN-γ on progenitor growth. These results suggest that the inhibitory effect of IFN-γ on hematopoietic progenitors is limited to those in an advanced stage of maturation. IFN-γ may be one of the essential lymphokines upregulating the growth of human hematopoietic progenitor cells.

Endogenous production of granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-3 (IL-3), and interleukin-6 (IL-6) was investigated in 10 children who underwent a total of 12 courses of autologous peripheral blood stem cell transplant (PBSCT) by measuring their serum levels using immunoassay kits. The serum G-CSF level increased immediately following infusion of PBSC graft, peaked between days 3 and 7 posttransplant and then declined by the time the granulocyte count rose. No definitive association was found between the continuous high levels of G-CSF and infective episodes, the number of infused nucleated cells, monocytes, CFU-GM, or the number of days required to achieve greater than 0.5×109/L granulocyte, greater than 1.0 × 109/L leukocyte, or greater than 50 × 109/L platelet counts. After PBSCT, IL-6 levels tended to be elevated. No detectable serum level of GM-CSF or IL-3 (<50 pg/mL) was observed before PBSCT and 4 patients showed a transient increase in the GM-CSF level after PBSCT. No significant change was observed in the posttransplant serum levels of IL-3 or M-CSF. The role of en-dogenously secreted cytokines in early hematopoietic recovery after PBSCT needs further clarification, but, at present, routine use of exogenous G-CSF therapy is not recommended.

The present study examined the immunocytochemical localization of various intermediate filaments (IFs). 68 kDa. 160 kDa and 200 kDa neurofilament protein (NFP). cytokeratin (CK) 1, 8, 10 and 19, vimentin, and glial fibrillary acidic protein (GFAP) in the vestibular endorgans and ganglia of normal and streptomycin-treated guinea pigs. In normal animals, 68 kDa, 160 kDa and 200 kDa NFP were found in afferent nerve fibers and nerve terminals (probably nerve chalices). Fine nerve fibers (probably efferent and/or sympathetic nerve fibers) were also immunoreactive to NFP. In the vestibular ganglia, 68 kDa and 160 kDa NFP were predominantly distributed in larger cells, whereas 200 kDa NFP was also found in some small ganglion cells. Cytokeratin 8 and 19 were located in supporting cells, transitional cells, dark cells of vestibular endorgans. and the epithelial cell lining of the membranous labyrinth. Vimentin was observed in the hair cells distributed in the central region of the end organs, supporting cells, most connective tissue cells, and Schwann cells of the vestibular ganglion. Although GFAP-like immunoreactivity was evident in glial cells of the proximal vestibular nerve, no immunoreactivity was detected in the distal portion of the vestibular nerve, vestibular ganglion, or vestibular endorgans. These highly distinct staining patterns of IFs indicated that they may play different roles in the different cell types, and that they may serve as a specific marker for each cell type. In streptomycin-treated guinea pigs, immunoreactivities for NFP and vimentin (found in the hair cells) decreased after treatment, whereas immunoreactivities for the other IFs were not affected. These results suggested that neuronal cytoskeletal components are the most vulnerable IFs to this ototoxic drug.

Naive B cells expressing IgM and IgD on their surface have no or little somatic mutations in V genes. We have demonstrated that the human IgM⁺IgD⁺B cell clone (0 – 81), which expresses nephritogenic idiotypes, produces IgM anti-DNA antibodies which show monospecificity to DNA. Using a DNA probe which specifically links to the VH gene of antibody 0 – 81, we identified the counterpart germ-line V gene of 0 – 81, V3-7, which appears to be used by pathogenic autoantibodies in humans. Clone 0 – 81, which may belong to naive B cells in terms of cell phenotype, uses a somatically mutated V3-7 gene. We further studied DNA sequences of V3-7 genes in circulating IgM⁺IgD⁺B cells from normal subjects and patients with systemic lupus erythematosus (SLE). The results revealed that rearranged V3-7 genes in IgM⁺IgD⁺B cells from patients with SLE contained somatically mutated sequences at significantly increased frequencies. These data indicate an abnormal maturation of B cells in autoimmune states that may be associated with an escape of self-reactive B cells from the elimination process in the germinal center.

A new practical method for the rapid microdetermination of hydroxyproline (Hyp) in biomedical samples, such as tissue and urine, in the presence of a definite amount of cysteine as antioxidant was established by means of the modified KISO method using flow injection analysis. This method uses no organic solvent and requires only 9 min for each sample, which can be injected every 3 min (about 5 h is sufficient for 100 samples). A good linear relationship (r=0.99996) was obtained between the concentration of Hyp (0–80μg/ml) and the absorbance (0–0.514). In biomedical samples (hydrolyzates of rat stomach tissue), the recoveries (94.8–103.7%) and the reproducibility (the mean of RSD; 0.484% for ten kinds of rat tissues) were satisfactory. The correlation between values from this method and from the conventional KISO method was shown to be good enough (r=0.966) for hydrolyzate samples (N=95), when a proper amount of cysteine solution was added to both the sample and standard solutions and the concentration of the oxidant was optimized to Hyp contents.

Peripheral blood stem cells (PBSC) were collected by two leukaphereses and cryopreserved in a 3-year-old girl with T-lymphoblastic leukemia; this was after remission was induced by an investigative regimen when she failed to respond to a first-line induction therapy. The patient received marrow-ablative chemotherapy 4.5 months after the diagnosis; this was followed by the infusion of thawed PBSC (203 x 104CFU-GM/kg). The peripheral granulocyte count reached 0.5 x 109/L by day +7 and the platelet count reached 20 x 109/L by day +9. Thereafter, the leukocyte count increased to 38 x 109/L by day + 14, with a gradual decline to normal levels. She has remained in unmaintained, complete remission 47 months after the autograft, with full school activity. This case illustrates the PBSC autograft is useful as an alternative to bonemarrow transplantation in a selected patient population, and extends the application of cure-oriented therapy to refractory childhood leukemia.

To clarify the toxicological mechanism of action of paraquat and diquat, the level of ascorbate radical, an oxidized product of ascorbic acid, was examined using the electron spin resenance (ESR) method. The ascorbate radiacal level increased to twice the normal level in sera from humans acutely intoxicated with a 1∶1 mixture of paraquat and diquat, and to more than 1.5 times the normal level in rat plasma containing moderate levels of paraquat. The dosage level for rats was 0.025% paraquat dichloride in the diet. The ascorbate radical in both intoxicated human sera and rat plasma decayed much faster than that in normal samples

To investigate the vestibular function in patients with bilateral progressive sensorineural hearing loss, we examined 5 cases using electronystagmography. Cases 1, 2 and 3 were adult type, and Cases 4 and 5 juvenile type. All patients had dizzy spells in the early stage of the disease, and showed spontaneous nystagmus. Bilateral reduction of caloric response and very low vestibulo-ocular reflex (VOR) gain on rotation testing were observed in Cases 1, 2 and 3. Case 4 showed right canal paresis upon the caloric test and left directional preponderance upon the rotation test. Case 5 showed good responses to both tests. Optokinetic afternystagmus (OKAN) in Cases 2, 3 and 5 was not brisk, and Cases 1 and 2 showed directional preponderence of OKAN. OKAN was useful for detecting directional preponderance. We believe there are two types of this disease which correlate with vestibular function. One type is associated with high grade vestibular dysfunction while, in the other, vestibular function is reasonably good.

Abstract: Effect of mineral restriction was studied to clarify which mineral in the diet is most indispensable in preventing paraquat (PQ) toxicosis. ODS rats were chosen as the experimental animal owing to the inability to synthesize vitamin C similarly to humans. Rats were fed with either mineral-adequate or restricted diets dosed with 125 ppm PQ. The mineral-adequate diet was based on the American Institute of Nutrition-76, and the restricted diet was one-half the amounts. Measurements were made on the onset day of PQ toxicosis, body weight changes during the feeding experiment, and changes of two acute phase reactant proteins – cysteine proteinase inhibitor and α1-proteinase inhibitor. The minerals tested were divided into three classes: I, largely needed, Ca, K, Na, and Mg; II, moderately needed, Mn, Fe, Zn, and Cu; and III, minutely needed, Cr and Se, respectively. Rats fed with a Mg-restricted diet showed a severe toxicosis but those with a K-restricted diet, a mild toxicosis. No appreciable effect was observed by restriction of other minerals. A synergistic effect was observed in the restriction of Mg and K.

Neuroradiological characteristics and functional outcomes of patients with intracerebral hemorrhage (ICH) during novel oral anticoagulant treatment were not well defined. We examined these in comparison with those during warfarin treatment.