Search

Most structural health monitoring systems estimate the overall behavior by measuring the acceleration response, which cannot directly measure the stress or damage state of individual structural members. An alternative approach is to use strain measurements; however, methods for analyzing and utilizing strain data for actual steel buildings have not been established. In this study, highly precise semiconductor strain gauges were applied to an actual building. The accelerations and strains measured during earthquake loading were used to calculate the ratio of the bending moment at the beam or column sections to the displacement at the top of the building, which was defined as the "local stiffness." This physical index represents the stiffness of structural elements near the measurement location and can be easily predicted through simple static frame analysis. The measured local stiffness was comparable to the analytical local stiffness values for the beams but was larger than that for the columns. This indicates that nonstructural members may exhibit a certain degree of restoring force and that the measured local stiffness may be strongly affected by nonstructural elements that are not considered during the structural design stage. Conversely, the measured local stiffness can be used to estimate the behavior of nonstructural components. The measured dominant frequency and local stiffness of the beams and columns showed a dependency on amplitude, but opposite trends were observed for the beams and columns. This indicates that the amplitude dependency of the dominant frequency is not due to the behavior of the beams and columns but to other reasons such as nonstructural components or changes in mass. [ABSTRACT FROM AUTHOR]

We have studied the critical parameters of Micheletti's glycoluril synthesis starting from urea and glyoxal on a statistical and multivariate analysis basis [12]. The process is potentially highly useful for scaling-up glycoluril production, and needs to be optimized. We have come to a conclusion that H3PO4 could be used as well as P4O10 giving high yields at temperature around 95°C, using glyoxal without prior purification. All reactions have been completed in less than 25 min with the yield as high as 80% under the optimized conditions. [ABSTRACT FROM AUTHOR]

Purpose: Radiation-induced oral mucositis is the most common side effect of radiotherapy in head and neck cancer; however, effective modalities for its prevention have not been established. In this study, we evaluated the effectiveness of Hangeshashinto (TJ-14), a Japanese herbal medicine, for preventing radiation-induced mucositis and elucidated its effect on inflammatory responses, including inflammatory cell chemotaxis and cyclooxygenase-2 (COX2) expression, in an animal model. Methods: Syrian hamsters, 8-9 weeks old, were enrolled in this study. Animals were irradiated with a single 40 Gy dose to the buccal mucosa. Hamsters freely received a treatment diet mixed with 2% TJ-14 or a normal diet daily. The therapeutic effect was determined based on the visual mucositis score, body weight, and histological examination of infiltrated neutrophils and COX2 expression. Results: TJ-14 significantly reduced the severity of mucositis. The percentage with severe mucositis (score ≥3) was 100% in the untreated group and 16.7% in the TJ-14 group ( P < 0.05). There was no difference in body weight change between the groups; however, weight gain in the untreated group tended to be suppressed compared to that in the TJ-14 group during the peak period of mucositis. In addition, TJ-14 inhibited the infiltration of neutrophils and COX2 expression in irradiated mucosa ( P < 0.05). Conclusions: TJ-14 reduced the severity of mucositis in an animal model by suppressing the inflammatory response. Because TJ-14 is inexpensive and its safety is established, it is a promising candidate for the standard treatment of radiation-induced mucositis in cancer patients. [ABSTRACT FROM AUTHOR]

In the present study, we report the SERS effect of rhodamine 6G (Rh6G) and 4-4 ′ bipyridine (Bipy) molecules on the surface of gold nanohole (AuNh) arrays fabricated by the interference lithography (IL) technique. It was observed an enhancement of the main bands of Rh6G and 4-4′ Bipy molecules, when deposited over the surface of AuNh, in comparison when that was deposited on the surface of 5-nm flat gold film. Our study indicates that metallic nanostructures fabricated by IL technique have the potential for high impact on biochemical sensing, such as DNA and bacterial detection, real time glucose sensing for diabetes, and in situ identification of reaction products. [ABSTRACT FROM AUTHOR]

High-resolution estimation of thermodynamic properties in the atmosphere can help to predict and mitigate meteorological disasters, such as local heavy rainfall and tornadic storms. For the purposes of short-term forecasting and nowcasting of severe storms, we propose a novel ground-based measurement system, which observes the intensity of atmospheric radiation in the microwave range. Our multi-band receiver system is designed to identify a rapid increase in water vapor before clouds are generated. At frequencies between 20 and 30 GHz, our system simultaneously measures water vapor as a broad absorption peak at 22 GHz as well as cloud liquid water. Another band at 50-60 GHz provides supplementary information from oxygen radiation to give vertical profiles of physical temperature. For the construction of this cold receiver system, novel technologies originally developed for observations of cosmic microwave background radiation were applied. The input atmospheric signal is amplified by a cold low-noise amplifier maintained below 10 K, while the spectrum of this amplified signal is measured using a signal analyzer under ambient conditions. The cryostat also contains a cold black body at 40 K to act as a calibration signal. This calibration signal is transported to each of the receivers via a wire grid. We can select either the atmospheric signal or the calibration signal by changing the orientation of this wire. Each receiver can be calibrated using this setup. Our system is designed to be compact ( $$<$$ 1 m $$^{3}$$ ), with low power consumption ( $$\sim $$ 1.5 kW). Therefore, it is easy to deploy on top of high buildings, mountains, and ship decks. [ABSTRACT FROM AUTHOR]

Far-upstream element-binding protein-interacting repressor (FIR) is a transcription factor that inhibits c-Myc expression and has been shown to have antitumor effects in some malignancies. Here, we evaluated the antitumor effects of FIR using fusion gene-deleted Sendai virus (SeV/ΔF) as a nontransmissible vector against head and neck squamous cell carcinoma (HNSCC). Using in vitro and in vivo xenograft mouse models, we observed efficient expression of green fluorescent protein (GFP) following transduction with the SeV/ΔF vector encoding GFP (GFP-SeV/ΔF) into HNSCC cells. In vitro and in vivo studies revealed that administration of the FIR-encoded SeV/ΔF (FIR-SeV/ΔF) vector exerted significant antitumor effects, suppressed c-Myc expression and induced apoptosis in HNSCC. Additionally, the antitumor effects of FIR or the expression of GFP following administration of the FIR- or GFP-SeV/ΔF vector, respectively, were dependent on the multiplicity of infection or titer. Furthermore, the SeV/ΔF vector itself had no cytotoxic effects. Therefore, the SeV/ΔF vector may be safe and useful for the treatment of HNSCC, allowing for high-titer SeV/ΔF vector administration for anticancer gene therapy. In addition, SeV/ΔF vector-mediated FIR gene therapy demonstrated effective tumor suppression in HNSCC, suggesting that this therapy may have the potential for clinical use as a novel strategy for HNSCC treatment. [ABSTRACT FROM AUTHOR]

Background: Epithelial-to-mesenchymal transition (EMT) is a fundamental process governing not only morphogenesis in multicellular organisms, but also cancer progression. During EMT, epithelial cadherin (E-cadherin) is downregulated while neural cadherin (N-cadherin) is upregulated, referred to as 'cadherin switch'. This study aimed to investigate whether cadherin switch promotes cancer progression in cholangiocarcinoma (CC).Methods: CC cell lines were examined for migration, invasion, and morphological changes with typical EMT-induced model using recombinant TGF-β1. The changes in E-cadherin and N-cadherin expression were investigated during EMT. We also examined E-cadherin and N-cadherin expression in resected specimens from extrahepatic CC patients (n=38), and the associations with clinicopathological factors and survival rates.Results: TGF-β1 treatment activated cell migration, invasion, and fibroblastic morphological changes, especially in extrahepatic CC HuCCT-1 cells. These changes occurred with E-cadherin downregulation and N-cadherin upregulation, that is, cadherin switch. Patients with low E-cadherin expression had a significantly lower survival rate than patients with high E-cadherin expression (P=0.0059). Patients with decreasing E-cadherin and increasing N-cadherin expression had a significantly lower survival rate than patients with increasing E-cadherin and decreasing N-cadherin expression (P=0.017).Conclusion: Cadherin switch promotes cancer progression via TGF-β-induced EMT in extrahepatic CC, suggesting a target for elucidating the mechanisms of invasion and metastasis in extrahepatic CC. [ABSTRACT FROM AUTHOR]

Purpose: Differences in efficacy and toxicity between UDP-glucuronosyltransferase (UGT) 1A1*1/*1 and *1/*6 or *1/*28 genotypes remain unclear in Japanese patients.Methods: Patients with advanced colorectal cancer who received irinotecan combined with 5-fluorouracil plus l-leucovorin (FOLFIRI) as first-line therapy were divided into two groups: those with UGT1A1*1/*1 genotype and those with UGT1A1*1/*6 or *1/*28 genotype. Efficacy and toxicity were compared between these groups retrospectively.Results: Forty-two patients (24 *1/*1 and 18 *1/*6 or *1/*28) were evaluated. The response rate was 48% in *1/*1 group and 56% in *1/*6 or *1/*28 group (P = 0.847). Median progression-free survival was 8.6 months in *1/*1 group and 8.5 months in *1/*6 or *1/*28 group (P = 0.888). No hematologic or non-hematologic toxic effects were clearly related to UGT1A1*1/*6 or *1/*28 during the first cycle or throughout the entire course of chemotherapy.Conclusions: There were no significant differences in the efficacy or toxicity of FOLFIRI between patients with UGT1A1*1/*1 genotype and those with UGT1A1*1/*6 or *1/*28 genotype. Our results suggest that patients with the latter genotypes can receive FOLFIRI at the same dose of irinotecan as those with the UGT1A1*1/*1 genotype receive. [ABSTRACT FROM AUTHOR]

Background: a fibroblast growth factor 2 (FGF2)-targeted adenoviral system can alter viral tropism and allow for improved transduction and reduced systemic toxicity. This study is to investigate if the FGF2-targeted adenoviral mutant Nijmegen breakage syndrome 1 (FGF2-Ad-NBS1) gene transfer can enhance cisplatin chemosensitisation not only by targeting DNA repair, but also through the induction of antiangiogenesis, whereas at the same time reducing toxicities in treating head and neck squamous cell carcinoma (HNSCC).Methods: the human HNSCC cell line was treated in vitro and in a nude mouse xenograft model. We conducted verification of binding ability of mutant NBS1 and downregulation of MRN complex, evaluation of transduction efficiency and combined antitumour activities. The antiangiogenesis mechanism was also investigated. Finally, we estimated the distribution of adenoviral vector in the liver.Results: the mutant NBS1 protein retains the binding ability and effectively suppresses the expression level of the MRN in infected cells. Transduction efficiency in vitro and cisplatin chemosensitisation were upregulated. The FGF2-Ad-NBS1 also showed detargeting the viral vectors away from the liver. The downregulation of NF-κB expression was supposed to correlate with increased antiangiogenesis.Conclusions: FGF2-targeted adenoviral system enhances the cisplatin chemosensitisation of mutant NBS1 and may avoid viral-associated liver toxicities. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease, known to be associated with a markedly increased risk of colorectal carcinoma development.Methods: Using proteomic analysis with two-dimensional gel electrophoresis and mass spectrometry, differentially expressed proteins were assessed between UC-associated cancer and sporadic colon cancer cell lines. Western blot and immunostaining were performed for confirming the expression.Results: Heat-shock protein of 47 kDa (HSP47) was identified as one of the proteins expressed more highly in UC-associated cancer cell lines, and an immunohistochemical examination confirmed significantly higher levels of HSP47 in UC-associated colon cancers than in sporadic counterparts, the expression increasing with a progression of neoplastic lesions. Heat-shock protein of 47 kDa was further found to be coexpressed with type I collagen in the cytoplasm, and both HSP47 and type I collagen were released from cultured cells into the culture medium.Conclusion: These results suggest that overexpression of HSP47 is a unique characteristic of UC-associated carcinoma related to type I collagen synthesis, with possible clinical applications. [ABSTRACT FROM AUTHOR]

Background: Recently, preoperative chemoradiation therapy (CRT) for rectal cancer has been increasingly used as a neoadjuvant treatment. In the present study, the relation between histological response to CRT and immunohistochemical markers in biopsy specimens was investigated.Methods: Biopsy specimens from a total of 60 patients were collected before preoperative CRT with S-1 and irinotecan, and liniac 45 Gy. Immunohistochemical staining for Ki67, Mcm3, Bax, Bcl-2, ssDNA, Grp78, thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), CD34, vascular endothelial growth factor, nestin, and L-type amino-acid transporter 1 was performed to allow comparison of the Ki67 labelling index (LI), Bax score, TS score, DPD score, microvessel density by CD34, and Grp78 score with cancer regression.Results: When the cases were divided into responders (Dworak grades 3 and 4) and non-responders (grades 1 and 2) groups, good correlations were evident with Ki67 LI, Bax, Grp78, and TS expression. On multiple logistic regression analysis, Ki67 LI, Bax, and TS scores were found to be independent factors. With their use in a logistic model, P-values could predict responder cases with a sensitivity of 82.8% and a specificity of 83.9%.Conclusion: Using this system, treatment strategy for locally advanced rectal cancers can be determined before chemoradiation. [ABSTRACT FROM AUTHOR]

The relationships between serum level of testosterone (T) and prostate cancer (PCa) are complex. The present study evaluated whether presence of PCa alters serum T levels. Subjects were 125 patients with clinically localized PCa treated using radical prostatectomy (RP), for whom pretreatment T levels were recorded. We investigated clinical and pathological factors such as pretreatment serum T level, age, pretreatment prostate-specific antigen, Gleason score and pathological stage. Serum T and human luteinizing hormone (LH) levels before and after RP were then compared in 118 of the 125 patients. Mean pretreatment T level was significantly higher in patients with organ-confined PCa (pT2; 4.03±1.50 ng ml−1) than in patients with nonorgan-confined cancer (pT3; 3.42±1.06 ng ml−1; P=0.0438). No association existed between pretreatment serum T level and pathological Gleason score. After RP, serum T level (5.60±1.90 ng ml−1) was significantly elevated compared to preoperative level (3.89±1.43 ng ml−1; P<0.0001). In parallel, significant increases were seen in postoperative serum LH level (6.86±3.64 ng ml−1) compared to preoperative level (5.11±2.47 ng ml−1; P=0.0001). In contrast, differences in serum T levels according to pathological stage disappeared postoperatively (P=0.5513). Significant increases in serum T and LH levels were seen after RP, compared to preoperative levels in parallel. This study suggests that serum T levels are altered by the presence of PCa, supporting the possibility that PCa may inhibit serum T levels with negative feedback in the hypothalamic–pituitary axis.Prostate Cancer and Prostatic Diseases (2009) 12, 78–82; doi:10.1038/pcan.2008.35; published online 3 June 2008 [ABSTRACT FROM AUTHOR]

E2Fs are key regulators of cell-cycle progression, and their transcriptional activities are regulated by histone acetyltransferases (HATs). Retinoblastoma (Rb) family proteins (pRb, p107 and p130) bind to E2Fs and inhibit their transcriptional activities by disrupting HAT binding and recruitment of histone deacetylases. In this study, we show that IκB kinases (IKKα or IKKβ) activation inhibits cell growth and E2F-dependent transcription in normal human fibroblasts. The inhibition of E2F by IKKs was not observed in cells lacking nuclear factor (NF)-κB/p65; however, it was observed in cells lacking three Rb family genes. p65 disrupted the physical interaction between activator E2Fs (F2F1, E2F2 and E2F3) and the HAT cofactor transactivation/transformation-domain associated protein, resulting in a reduction in E2F-responsive gene expression. Furthermore, IKKα and IKKβ directly phosphorylated E2F4, resulting in nuclear accumulation and enhanced DNA binding of the E2F4/p130 repressor complex. Our study describes a novel growth inhibitory system that functions by Rb-independent suppression of E2Fs by the IKK/NF-κB signaling pathway.Oncogene (2008) 27, 5696–5705; doi:10.1038/onc.2008.184; published online 9 June 2008 [ABSTRACT FROM AUTHOR]

Recent advances in laparoscopic surgery have made various abdominal surgeries possible. To avoid wound infection, mesh repair of abdominal incisional hernias is performed laparoscopically. Here we present a new procedure to fix mesh to the abdominal wall. Four anchoring sutures are made using a suture-grasping device; the additional transabdominal sutures are then made with a modified double-needle device. Additional circumferential fixation with tacks is not necessary. This new mesh fixation method involves simple suturing techniques and is less time consuming than the conventional procedure. [ABSTRACT FROM AUTHOR]

Background: When we perform laparoscopic lymph node dissection around the inferior mesenteric artery (IMA), we preserve the left colic artery (LCA) to maintain the blood supply to the proximal sigmoid colon. In this study, we present our laparoscopic D2 and D3 lymph node (LN) dissection technique and evaluate its applicability and safety.Methods: We performed LN dissection on 23 rectal and lower sigmoid colon cancer cases from April 2002 to December 2004. For D3 LN dissection, the incision to the mesosigmoid extends to just before the root of the IMA, which is exposed with an ultrasonic cutting and coagulating surgical device to avoid bleeding. Then, the arterial wall is exposed with a dissecting electrocautery spatula down to the LCA, at least 2 cm of which is exposed. Adipose tissue surrounding the IMA and inferior mesenteric vein is dissected. For D2 LN dissection, we partially expose the IMA to confirm the location of the LCA.Results: The mean times taken for D2 and D3 LN dissections were 36.2 and 68.2 min, respectively. Both procedures took longer in male patients. There was a trend for the procedure overall to take less time in female patients. However, D2 dissection took significantly longer in male than female patients (p < 0.05). In women, D3 dissection took significantly longer than D2 (p < 0.05), but this trend was not seen in men. Increased experience among surgeons with this procedure was associated with significantly faster LN dissections in men (p < 0.05), but not in women (p = 0.493). Pearson product moment analysis identified a relationship between body mass index (BMI) and the time taken for D2 LN dissection (r = 0.765), but not D3 LN dissection (r = 0.158). There was no treatment-related morbidity with this technique.Conclusions: This method was safe and feasible for all patients in this series, but takes longer to perform in male patients. [ABSTRACT FROM AUTHOR]

To assess the possibility of gene therapy for recurrent laryngeal nerve (RLN) injury, we examined functional and histological recovery after glial cell line-derived neurotrophic factor (GDNF) gene transfer in a rat RLN crush model. Adenoviral vector encoding β-galactosidase gene (AxCALacZ) or human GDNF gene (AxCAhGDNF) was injected into the crush site of the RLN. Neurons in the nucleus ambiguus on the crushed side were labeled with X-gal or GDNF immnohistochemistry after AxCALacZ or AxCAhGDNF injection. Reverse transcription-polymerase chain reaction analysis revealed expression of human GDNF mRNA transcripts in brainstem tissue containing the nucleus ambiguus on the crushed side after AxCAhGDNF injection. Animals injected with AxCAhGDNF displayed significantly improved motor nerve conduction velocity of the RLN and recovery rate of vocal fold movement at 2 and 4 weeks after treatment as compared to controls. AxCAhGDNF-injected animals showed a significantly larger axonal diameter and improved remyelination in crushed RLN as compared to controls. Adenoviral GDNF gene transfer may thus promote laryngeal function recovery after RLN injury. Inoculation of adenoviral vector containing the GDNF gene at the site of damage soon after nerve injury may assist patients with laryngeal paralysis caused by nerve injury during head and neck surgery.Gene Therapy (2006) 13, 296–303. doi:10.1038/sj.gt.3302665; published online 27 October 2005 [ABSTRACT FROM AUTHOR]

Monoclonal antibody E5/G6 recognized a linear epitope common to hantavirus nucleocapsid proteins. Using synthetic peptides, we identified epitope E5/G6 as the 9 mer YEDVNGIRK (NP 165-173), in which D167, G170, I171, and R172 are indispensable. Furthermore, all the peptides synthesized using various hantavirus sequences bound MAb E5/G6 consistently, despite the existence of several amino acid variations in this region. These results indicate that MAb E5/G6 is a useful tool for detecting hantavirus antigen in rodent or patient tissues using Western blotting or other immunohistochemical assays. [ABSTRACT FROM AUTHOR]

Objective. To clarify the involvement of cytochrome P450 (CYP) 3A4 in the metabolism of etizolam. Methods. The effects of itraconazole, a potent and specific inhibitor of CYP3A4, on the single oral dose pharmacokinetics and pharmacodynamics of etizolam were examined. Twelve healthy male volunteers received itraconazole (200 mg/day) or placebo for 7 days in a double-blind randomized crossover manner, and on the 6th day they received a single oral 1-mg dose of etizolam. Blood samplings and evaluation of psychomotor function using the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 24 h after etizolam dosing. Plasma concentration of etizolam was measured by means of high-performance liquid chromatography. Results. Itraconazole treatment significantly increased the total area under the plasma concentration–time curve (AUC; 213±106 ng⁃h/ml versus 326±166 ng⁃h/ml, P<0.001) and the elimination half-life (12.0±5.4 h versus 17.3±7.4 h, P<0.01) of etizolam. The 90% confidence interval of the itraconazole/placebo ratio of the total AUC was 1.38–1.68, indicating a significant effect of itraconazole. No significant change was induced by itraconazole in the two pharmacodynamic parameters. Conclusion. The present study suggests that itraconazole inhibits the metabolism of etizolam, providing evidence that CYP3A4 is at least partly involved in etizolam metabolism. [ABSTRACT FROM AUTHOR]

Japanese R&D activities in photovoltaics (PV) and our R&D activities with III–V compound multijunction (MJ) solar cells are presented. We have realized high-efficiency InGaP/InGaAs triple-junction solar cells with an efficiency of 36.5–37% (AM1.5G, 200 suns) and concentrator triple-junction solar cell modules with an outdoor efficiency of 27% as a result of designing a grid structure, developing low optical loss Fresnel lens and homogenizers, and designing low thermal conductivity modules. Our challenge now is to develop low-cost and high output power concentrator MJ solar cell modules with an output power of 400W/m2 for terrestrial applications. © 2004 MAIK “Nauka / Interperiodica”. [ABSTRACT FROM AUTHOR]

Summary. To investigate age-dependent differences in hantavirus-specific CD8+ T-cell responses, mice were inoculated with 0.1 50% newborn mouse lethal dose of Hantaan virus (HTNV) at 0, 3, 7, 14, or 35 days after birth. HTNV-specific CD8+ T cells producing gamma interferon (IFN-γ) were measured on day 30 after HTNV inoculation. Although no IFN-γ-producing HTNV-specific CD8+ T cells were detected in most of the mice inoculated with HTNV on day 0 after birth, most mice inoculated at 3, 7, 14, or 35 days had HTNV-specific CD8+ T cells. The production of tumor necrosis factor alpha (TNF-α) by IFN-γ-producing CD8+ T cells and the cytotoxic activity against HTNV-infected target cells were similar in immature and adult mice. However, the number of IFN-γ-producing HTNV-specific CD8+ T cells was significantly less in mice inoculated with HTNV at 3 days than in older mice. In addition, a strong correlation between HTNV persistence and a lack of HTNV-specific CD8+ T cells was observed. These results suggest that mice over 7 days old have the ability to induce functional HTNV-specific CD8+ T-cell responses that are indistinguishable from the responses of adult mice, and that HTNV-specific CD8+ T cells are important for clearance of HTNV. [ABSTRACT FROM AUTHOR]

Summary Peroxidase-labeled staphylococcal protein A, streptococcal protein G, and antibodies directed against Mus musculus (mouse), Rattus norvegicus (rat), Mesocretus auratus (hamster), and Peromyscusleucopus were examined for their reactivity with immunoglobulin G (IgG) from various rodent species. The purpose of this study was to identify the optimal secondary antibodies or reagents for specific serodiagnosis of hantavirus infection in various rodent species. Using ELISA, a total of 65 sera from 29 rodent species of the family Muridae and one serum sample from family Octodontidae were compared for IgG reactivity with the six different reagents. The results demonstrate that the reactivities of the secondary antibodies and reagents to the sera varied, even among sera from rodents of the same genus. Hantavirus-specific antibody ELISA revealed that hantavirus-infected rodent sera obtained from M. musculus, R. norvegicus, Apodemus agrarius, A. peninsulae, and Bandicota indica bound to the six different conjugates in a similar pattern as that detected in IgG ELISA. These results indicate that the applicability of secondary antibodies and protein A and G should be carefully evaluated before use for serodiagnosis in different rodent species. [ABSTRACT FROM AUTHOR]

Twenty-two patients with malignant melanoma were treated with boron neutron capture therapy (BNCT) using10B- p-boronophenylalanine (BPA). The estimation of absorbed dose and optimization of treatment dose based on the pharmacokinetics of BPA in melanoma patients is described. The doses of γ-rays were measured using small TLDs of Mg2SiO4 (Tb) and thermal neutron fluence was measured using gold foil and wire. The total absorbed dose to the tissue from BNCT was obtained by summing the primary and capture γ-ray doses and the high LET radiation doses from10B(n,α)7Li and14N(n,p)14C reactions. The key point of the dose optimization is that the skin surrounding the tumour is always irradiated to 18 Gy−Eq, which is the maximum tolerable dose to the skin, regardless of the10B-concentration in the tumor. The neutron fluence was optimized as follows. (1) The10B concentration in the blood was measured 15−40 min after the start of neutron irradiation. (2) The10B-concentration in the skin was estimated by multiplying the blood10B value by a factor of 1.3. (3) The neutron fluence was calculated. Absorbed doses to the skin ranged from 15.7 to 37.1 Gy−Eq. Among the patients, 16 out of 22 patients exhibited tolerable skin damage. Although six patients showed skin damage that exceeded the tolerance level, three of them could be cured within a few months after BNCT and the remaining three developed severe skin damage requiring skin grafts. The absorbed doses to the tumor ranged from 15.7 to 68.5 Gy−Eq and the percentage of complete response was 73% (16/22). When BNCT is used in the treatment of malignant melanoma, based on the pharmacokinetics of BPA and radiobiological considerations, promising clinical results have been obtained, although many problems and issues remain to be solved. [ABSTRACT FROM AUTHOR]

Summary. Seoul virus is a hantavirus that causes hemorrhagic fever with renal syndrome (HFRS). The virion has a tripartite (S, M, and L) negative-stranded RNA genome, which is characteristic of the family Bunyaviridae. However, the molecular basis of virus replication is not well known. We established a Northern blot hybridization (NB) procedure using digoxygenin-labeled RNA probes, to quantitate the hantaviral plus- and minus-strand RNAs separately. Virus RNA replication was analyzed in infected Vero E6 cells. When the Vero E6 cells were infected with Seoul virus strain KI-83-262 (KI) at m.o.i. = 0.25, the plus-strand RNA was detected within 1 h post-infection (hpi), and the minus-strand RNA was detected subsequently. Using laser confocal microscopy, the nucleocapsid protein (NP) was detected within 2 hpi, and accumulated as scattered granules in the cytoplasm until 24 hpi. In contrast, the G2 protein first appeared at 8 hpi, was immediately transported to the Golgi, and accumulated in the Golgi until 24 hpi. Infectious virus particles were released into the medium at 24 h hpi. These findings indicate that hantavirus RNA replication starts with the appearance of NP at 2 hpi, glycoproteins then accumulate gradually in the Golgi, and virion formation is initiated once the viral RNAs and proteins have accumulated. [ABSTRACT FROM AUTHOR]

Summary. Hemorrhagic fever with renal syndrome (HFRS) is endemic in East Asia and Europe. The disease is caused by several viruses belonging to the genus Hantavirus, including the Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava Belgrade virus (DOBV), and Puumala virus (PUUV). Recently, HTNV-related viruses, Amur (AMR) and Far East (FE) genotypes were identified as causative agents of HFRS in Far Eastern Russia. To investigate the epidemiology of HFRS and virus transmission, we collected sera from 17 acute and 32 convalescent patients who were clinically diagnosed with HFRS in the Khabarovsk region of Far Eastern Russia, and detected anti-hantavirus antibodies using an ELISA that can differentiate the infected virus serotype using truncated hantavirus nucleocapsid protein antigen. Sixteen of the 17 acute phase patients had antibodies to hantavirus, and all the positive sera had higher optical densities for HTNV-specific antigen than for SEOV-, DOBV-, or PUUV-specific antigens. The partial M segment of the viral genome was amplified from blood clots from three acute patients by PCR. The nucleotide sequences had closer identities to the FE genotype (>96%) than to the prototype HTNV (88 to 89%) or AMR genotype (81 to 83%). A phylogenetic analysis found that the virus sequences from the patients clustered with the FE type, and were distinct from the AMR type. Thirty-one of 32 convalescent patient sera had antibodies to HTNV-specific antigen. These data suggest that our ELISA system can detect HTNV-specific antibodies to the FE type, which may be responsible for most of the HFRS in Khabarovsk. [ABSTRACT FROM AUTHOR]

We investigated the effectiveness of fosfomycin combined with other antibiotics, such as piperacillin, cefepime, ceftazidime, imipenem, meropenem, aztreonam, gentamicin, or levofloxacin, against 30 Pseudomonas aeruginosa strains, including multidrug-resistant strains, isolated from clinical specimens, using the efficacy time index (ETI) assay. The assay refers to the result of pharmacokinetics obtained from adult men volunteers, and yields an ETI to evaluate the effect of a combination of antimicrobial agents. With the ETI, based on serum concentration 3 h after the administration of two antimicrobial agents, the effectiveness of antimicrobial combinations was evaluated as follows: poor, ETI < 0.5; fair, 0.5 ≤ ETI < 1; good, 1 ≤ ETI < 8; and excellent, ETI ≥ 8. The combination of fosfomycin and cefepime (efficacy rate [excellent plus good], 76.7%) and fosfomycin/aztreonam (efficacy rate, 76.7%) appeared to be the most effective, followed by fosfomycin/meropenem (efficacy rate, 76.6%), fosfomycin/imipenem (efficacy rate, 73.3%), fosfomycin/ceftazidime (efficacy rate, 70%), fosfomycin/gentamicin (efficacy rate, 70%), fosfomycin/piperacillin (efficacy rate, 66.7%), and fosfomycin/levofloxacin (efficacy rate, 66.7%). Fosfomycin/cefepime, fosfomycin/aztreonam, and fosfomycin/meropenem may be clinically useful in selected patients, particularly for P. aeruginosa. The ETI assay provided information on the minimum inhibitory concentration (MIC) of many pairs of combined antimicrobial agents simultaneously. The ETI assay may be a useful technique with which to investigate the effect of combinations of antimicrobial agents against P. aeruginosa, including multidrug-resistant strains. [ABSTRACT FROM AUTHOR]

The activities of the enzymes related to the malate–aspartate shuttle, which convert cytosolic NADH into mitochondrial NADH, were measured in red and white blood cells from thoroughbred horses undergoing continuous training (race horses) and compared with those in blood cells from riding horses. The activities of malate dehydrogenase (MDH), a rate-limiting enzyme for the malate-aspartate shuttle, were significantly elevated in the white blood cells (WBC) from race horses compared with those from riding horses. There were no significant differences in the activities of the enzymes in the red blood cells between race horses and riding horses. This increase in the MDH activity in their WBC is considered to reflect the increased metabolic activity in the race horses resulting from the training. [ABSTRACT FROM AUTHOR]

The regeneration mechanism of injured rat colonic mucosa with 1% acetic acid was certified in this study. The injured colons were studied periodically on experimental days 1, 3, 5, 7, 15, and 20 with light and scanning electron microscopy. Specimens were examined in paraffin sections stained with hematoxylin and eosin; crypts were isolated with the HCl digestion method; and three-dimensional stromal collagen tissue was prepared with the NaOH cell maceration method. Damage to the mucosal and submucosal layers peaked between the 1st and 3rd days with edema, regeneration, necrosis, and inflammation. The edema and inflammation subsided, and mucosal atrophy and crypt reduction remained at around 1 week. At 2 weeks the mucosa became thick, and crypts showed many branches in their lower two-thirds; and by 3 weeks the mucosa had recovered to almost normal. The ratio of number of crypts at the base and surface was almost 1.5 on the 15th day and 1.0 on the 20th day, suggesting that each branch progresses upward to create an independent crypt. We believe that the fission mechanism plays an important role in crypt repair after acetic acid injury of the colonic mucosa. As the proliferative zone of the colonic crypt is localized at the crypt base, fission of the crypt starting at the base and progressing up to the surface is the most reasonable and efficient mechanism for repair by increasing the number of crypts. [ABSTRACT FROM AUTHOR]

To clarify the prognostic factors in patients with submucosal carcinoma of the oesophagus, we examined the results of surgical treatment for 78 cases over the last decade. The clinicopathological factors including age, sex, location of the tumour, length of the tumour, histological differentiation, subclassification of depth, lymphatic or blood vessel invasion, intramural metastasis and lymph node metastasis were all analysed. Then the correlation between these factors and prognosis was investigated. As a result, significant differences were observed in the survival rates between the groups regarding lymphatic vessel invasion (P = 0.0003), intramural metastasis (P = 0.0051) and lymph node metastasis (P = 0.0026). According to a multivariate analysis, intramural metastasis (P = 0.0038, relative risk 9.17), vessel invasion (P = 0.0033, relative risk 6.25) and lymph node metastasis (P = 0.0187, relative risk 3.62) were found to be independent prognostic factors. The prognosis of the patients with at least one of these factors was significantly poorer than that without. The five-year survival rate of the patients without these factors was as good as that with mucosal carcinoma of the oesophagus. Based on our findings, vessel invasion, intramural metastasis and lymph node metastasis are thus considered to be significant prognostic factors in patients with submucosal carcinoma of the oesophagus. [ABSTRACT FROM AUTHOR]

In order to search for the relationship between the structure and the function of the nervous system, the spinal cord provides suitable material. We devised a procedure for isolation of large ventral and small dorsal horn neurons. Then we examined the γ-aminobutyric acid (GABA) system in both neurons isolated using our procedure. Glutamic decarboxylase (GAD) activity in dorsal horn neurons was much higher than that in ventral horn neurons. Further, GABA uptake activity by the dorsal horn neurons was also somewhat higher than that by the ventral horn neurons, although some properties of GABA uptake were found to be almost the same in both neuronal fractions. However, we could not find any difference of GABA-α-ketoglutarate transaminase (GABA-T) activity between the dorsal and ventral horn neurons. These results suggest that GAD and GABA uptake may be indicators for cell specificity to some extent. [ABSTRACT FROM AUTHOR]

• Background: The purpose of the investigation was to ascertain the prevalence of dry eye in new outpatients. • Methods: A total of 2127 consecutive new outpatients seen in eight Japanese centers from April 1992 to January 1993 underwent comprehensive examinations, including double vital staining and measurement of tear film break-up time, basal tear secretion, and tear clearance. Dry eye was diagnosed if patients had abnormalities of both the tear film and the ocular surface. • Results: Three hundred fifty-nine patients (17%) had dry eye. There was no seasonal pattern for dry eye. The condition was significantly more common in Tokyo than in suburban areas ( P < 0.01). The prevalence of dry eye in visual display terminal (VDT) users and contact lens (CL) wearers was significantly higher than in non-VDT users and non-CL wearers ( P < 0.05 and P < 0.02, respectively). • Conclusion: Our findings suggest that dry eye is one of the most common ocular disorders encountered by physicians. Furthermore, if patients use VDTs or wear CLs, the likelihood of dry eye occurring is higher. [ABSTRACT FROM AUTHOR]

We report a 27-year-old male with Crohn's disease (CD) of the small and large intestine, whose peripheral blood lymphocytes (PBL) showed increased cell-mediated cytotoxicity (CTL). Autologous and allogeneic effector cells from PBL and intestinal lymph nodes (LN) were isolated on a Ficoll-Hypaque gradient. Colonic cells were prepared as the target and were incubated for 6h with effector cells, after being labeled with Na(2)51CrO4. The CTL activity [effector/target (E/T) ratio, 100:1] of PBL for autologous targets was increased by 38% compared with that in normal subjects (< 10%), while that shown by LN was not increased (14%). The CTL activity of allogeneic PBL prepared from three of four other CD patients was also increased. Anti-major histocompatibility (MHC) class I and II and CD4 and CD8 monoclonal antibodies (50 micrograms/ml) significantly inhibited CTL activity. Complement-mediated depletion of CD2+ cells significantly reduced CTL activity. These results suggest that MHC-restricted CTL may play a role in mucosal damage in some patients with Crohn's disease. [ABSTRACT FROM AUTHOR]

In a reversed micellar n-decane solution, a spiropyran derivative 3′,3′-dimethyl-1′-octadecyl-6-nitrospiro(2H-benzopyran-2,2′-indoline) (PC18) showed normal photochromism, and the reversed micelles provided polar microenvironment increasing stability of a zwitterionic merocyanine (MC) form of PC18. Though the reversed micelles of tetraethyleneglycol dodecylether (TEGDE) alone in n-decane had relatively low ability to extract amino acid from aqueous solutions, the PC18-incorporated TEGDE reversed micelles in n-decane showed good photo-controlled extraction of zwitterionic amino acid under UV-irradiation and release under VIS-irradiation. Extent of the extracted amino acid was higher for tryptophane (Trp) bearing hydrophobic side chain than alanine (Ala), showing amino acid selectivity. Photo-driven active transport of amino acid across a liquid membrane was attained by the PC18-incorporated TEGDE reversed micellar carrier in a water/ n-decane/water three-phase system, where one side of an aqueous/organic interface was irradiated by the UV-light and the other side by the VIS-light. When Trp and Ala were present in the aqueous solution, Trp was selectively transported. [ABSTRACT FROM AUTHOR]

There is increasing evidence that 1,25 dihydroxyvitamin D3 acts directly to differentiate and activate cells of mononuclear phagocyte lineage (MNP). However, it seems possible that in bone marrow this hormone may modulate the differentiation of MNP via the factor elaborated by the stromal cells or the macrophages. We tested this hypothesis using two separate culture systems of bone marrow cells from vitamin D-replete (D+) and -deficient (D-) rats. The animals were maintained from the third day of lactation on D+ or D- diet for up to 105 days. In vivo studies showed that the long-term D- state resulted in a depletion of acid phosphatase-positive macrophagelike cells and osteoclasts in bones. After a 14 day incubation period, cultures of D- bone marrow cells contained an increased number of fibroblastoid cell colonies and a reduced number of macrophages attached to fibroblastoid cells, compared with the controls. When D+ bone marrow cells were cultured for 4 days in the presence of supernatants obtained from 14 day cultures of D- bone marrow (marrow adherent cell-conditioned medium, MACCM), the differentiation of MNP into macrophages was inhibited. Impaired differentiation was almost complete in D- bone marrow cell cultures to which D- MACCM was added. These cultures consisted of only 6.6% macrophages compared with 53.9% in the control cultures. However, when D- bone marrow cells were cultured with D+ MACCM, differentiation was restored and 75.4% of the cells were macrophages. These results suggest that a paucity of macrophages and osteoclasts in D- rats is in part, if not entirely, a result of a failure of stromal cells and/or macrophages in the bone marrow to release a factor(s) necessary for differentiation of MNP and osteoclast precursors. [ABSTRACT FROM AUTHOR]

Ribavirin at concentrations from 1 to 10 μg/ml exihibited inhibitory effects on transcription of Borna disease virus (BDV) in persistently infected cells. Our present study indicates that ribavirin is a candidate anti-BDV drug. [ABSTRACT FROM AUTHOR]

Sequence analysis of the VP7 gene was performed on twenty-one human isolates of serotype 3 related-rotavirus in China and Japan. The five Chinese isolates were found to be not similar to the 16 Japanese isolates and to SA11 (simian rotavirus). The Chinese isolates, especially CHW2 and CH-32, were different from the major serotype 3 human isolates. AU-1 and 02/92 which previously showed a wider spacing between RNA segments 10 and 11 by RNA polyacrylamide gel electrophoretic analysis, were more closely related to each other and could be differentiated from the other Chinese and Japanese isolates. For these reasons, serotype 3 viruses were considered to be intra-serotypically more heterologous than serotype 1, 2 and 4 viruses. [ABSTRACT FROM AUTHOR]

Murine rotavirus was isolated in primary monkey kidney cells. Electrophoretic pattern of genome RNA of murine rotavirus was different from that of human rotaviruses. Oral administration of cultured murine rotavirus caused mild diarrhea in newborn BALB/C mice. [ABSTRACT FROM AUTHOR]

A new system for high-speed and continuous 3D measurement is presented. It is based on the slit-ray projection method. The key component is the image plane constructed by a position-sensitive device (PSD) array that is horizontally un segmented and linear, but vertically numbered. All PSD row elements are attached to their respective analog signal processors. The analog signals are multiplexed and digitized by multiplexers and A/D converters at appropriate sampling intervals and stored in memory. By virtue of this configuration of the image plane, basis data for 3D measurement are acquired during only one scan of the slit ray at high speed in the form of memory addresses and data. Moreover, if we use large capacity and/or dual port memories, we can continuously obtain 3D range data for as many scenes as needed. The trial system has been implemented with a newly designed 128-channel PSD array and has verified our method, enabling us to obtain successive 3D range data at video rates with an error within±0.3%. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

The temperature dependence of the elastic constants in Tb3Ga5O12 was measured and analysed with a simple crystal field model. The magneto-elastic coupling constants have been deduced from this experiment. The coupling constant gΓ5, related to the c44 mode, is anomalously large. These coupling constants are important for the interpretation of the phonon Hall effect. [ABSTRACT FROM AUTHOR]

AML is a genetically heterogeneous disease and understanding how different co-occurring mutations cooperate to drive leukemogenesis will be crucial for improving diagnostic and therapeutic options for patients. MIR142 mutations have been recurrently detected in IDH-mutated AML samples. Here, we have used a mouse model to investigate the interaction between these two mutations and demonstrate a striking synergy between Mir142 loss-of-function and IDH2R140Q, with only recipients of double mutant cells succumbing to leukemia. Transcriptomic analysis of the non-leukemic single and leukemic double mutant progenitors, isolated from these mice, suggested a novel mechanism of cooperation whereby Mir142 loss-of-function counteracts aberrant silencing of Hoxa cluster genes by IDH2R140Q. Our analysis suggests that IDH2R140Q is an incoherent oncogene, with both positive and negative impacts on leukemogenesis, which requires the action of cooperating mutations to alleviate repression of Hoxa genes in order to advance to leukemia. This model, therefore, provides a compelling rationale for understanding how different mutations cooperate to drive leukemogenesis and the context-dependent effects of oncogenic mutations. [ABSTRACT FROM AUTHOR]

We investigated levels of p53 protein expression in Japanese patients with oesophageal squamous cell carcinoma. A significantly larger proportion of heavy alcohol drinkers and cigarette smokers was evident in the p53-positive group. The combination of drinking and smoking was associated with a high frequency of p53 protein accumulation. [ABSTRACT FROM AUTHOR]

Presents a summary of the fifth Triennial International Symposium on Fluid Control Measurement and Visualization, which was held from September 1 to 4, 1997 in Hayama, Japan. Sponsors; Participants; Registration; Numbers of sessions and papers in each research field.

Marked fluctuations in mobility, known as the on-off phenomenon, frequently emerge during the course of chronic treatment with levodopa in patients with Parkinson's disease. Similar fluctuations in mobility and mental status have been observed in a 10-year-old Japanese girl with tetrahydrobiopterin deficiency (BH4 deficiency) while receiving neurotransmitter and biopterin supplement. In order to define the underlying mechanisms for the phenomenon in our patient, we studied the temporal relationship between plasma levodopa levels and clinical status during oral (2.0 mg/kg per day) and continuous intravenous (2.0 mg/kg per 12 h) administration of the drug. Following each oral levodopa dose, the plasma concentration of levodopa peaked at 60-90 ng/ml within 60 min and fell to 5-15 ng/ml within 2 h. The clinical state of the patient varied acutely in parallel with the plasma levodopa concentrations. The clinical swings completely disappeared when the plasma levodopa concentrations were stabilized between 120-150 ng/ml by continuous infusion. Paradoxically, on awakening from sleep, she was invariably ambulatory despite very low plasma levodopa levels (less than 10 ng/ml). These observations indicate that the on-off phenomenon in our patient reflect the fluctuations of plasma levodopa levels as demonstrated in Parkinson's disease, but there may be substantial differences in levodopa transport across the blood-brain barrier and/or striatal dopamine-receptor interaction between Parkinson's disease and BH4 deficiency. [ABSTRACT FROM AUTHOR]

Probable serotypes of faecal adenoviruses 40, 41, 31, 2 and 1 were found in the Tokyo area by rapid DNA restriction endonuclease analyses directly of stool specimens or after primary culture in Graham 293 cells. Some variations were found in both adenoviruses 40 and 41 by this method. [ABSTRACT FROM AUTHOR]

Colloidal clay in water suspensions are known to exhibit a multitude of bulk phases depending on initial colloidal concentration and ionic strength, and examples of this include repulsive Wigner colloidal glasses at low ionic strength and attractive gels at higher ionic strength due to screened electrostatic forces by the electrolyte. From confocal Raman microscopy combined with elasticity measurements, we infer that clay trapped at quasi two-dimensional interfaces between oil and water also exhibit confined glass-like or gel-like states. The results can be important for the preparation of particles stabilized colloidal emulsions or colloidal capsules, and a better understanding of this phenomenon may lead to new emulsion or encapsulation technologies. [ABSTRACT FROM AUTHOR]