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Aims Reactive atrial-based anti-tachycardia pacing (rATP) in pacemakers (PMs) and cardiac resynchronization therapy defibrillators (CRT-Ds) has been reported to prevent progression of atrial fibrillation, and this reduced progression is expected to decrease the risk of complications such as stroke and heart failure (HF). This study aimed to assess the cost-effectiveness of rATP in PMs and CRT-Ds in the Japanese public health insurance system. Methods and results We developed a Markov model comprising five states: bradycardia, post-stroke, mild HF, severe HF, and death. For devices with rATP and control devices without rATP, we compared the incremental cost-effectiveness ratio (ICER) from the payer's perspective. Costs were estimated from healthcare resource utilisation data in a Japanese claims database. We evaluated model uncertainty by analysing two scenarios for each device. The ICER was 763 729 JPY/QALY (5616 EUR/QALY) for PMs and 1,393 280 JPY/QALY (10 245 EUR/QALY) for CRT-Ds. In all scenarios, ICERs were below 5 million JPY/QALY (36 765 EUR/QALY), supporting robustness of the results. Conclusion According to a willingness to pay threshold of 5 million JPY/QALY, the devices with rATP were cost-effective compared with control devices without rATP, showing that the higher reimbursement price of the functional categories with rATP is justified from a healthcare economic perspective.

Objective We compared the incidence rates of hospitalized infections (HIs) between tocilizumab (TCZ) and other biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in adults aged ≥75 years with rheumatoid arthritis (RA). Methods We used a Japanese claims database from Medical Data Vision Co., Ltd (Tokyo, Japan) to perform a retrospective longitudinal population-based study in patients with RA who were prescribed b/tsDMARDs between 2014 and 2019. We calculated adjusted risk ratios (aRRs) for HIs in three age groups ( Results Of 5506 patients, 2265 (41.1%) were Conclusion In patients with RA aged ≥75 years, b/tsDMARDs have a similar risk of HIs to tocilizumab except for etanercept.

Methylglyoxal (MGO) produced during glycolysis is known to react with arginine residues on proteins to generate advanced glycation end products, such as Nδ-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine (MG-H1). Since the production of MGO is increased during hyperglycemia or metabolic disorders in vivo, it is considered that the measurement of MG-H1 is useful for evaluating abnormalities in carbohydrate metabolism. Thus, we prepared a monoclonal antibody against MG-H1 to develop a conventional measurement system for MG-H1. Reactivity and specificity of the antibody to MGO-modified protein were confirmed by enzyme-linked immunosorbent assay and western blotting, respectively. The measurement of MG-H1 content by the antibody was positively correlated with that by electrospray ionization-liquid chromatography-tandem mass spectrometry and the ratio of modified arginine residues by amino acid analysis. Our results demonstrated that immunochemical methods could be useful for the estimation of MG-H1 content in modified proteins.

Objective To assess the cost-effectiveness of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in rheumatoid arthritis. Methods We conducted three analyses: a lifetime analysis with a cohort model (Study A) and two short-term analyses (Studies B and C). Study A evaluated the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained from costs of standard treatments. Study B evaluated yearly costs per person achieving American College of Rheumatology (ACR) response (ACR20, ACR50, and ACR70), and Study C evaluated costs per person achieving previously defined claims-based effectiveness (equivalent to 28-joint Disease Activity Score ≤ 3.2). The proportion of ACR responders to the drugs of interest were determined by mixed treatment comparisons. Studies B and C estimated costs using a claims database. Results In Study A, ICERs of all b/tsDMARDs were lower than 5.0 million Japanese yen (JPY) per QALY. In Study B, yearly costs per person with ACR50 response were lower for subcutaneous tocilizumab (TCZ-SC; 1.9 million JPY) and SC abatacept (2.3 million JPY). In Study C, costs per person were lower for TCZ-SC (1.3 million JPY) and intravenous TCZ (1.6 million JPY) and effectiveness rates were higher for intravenous TCZ (45.3%) and infliximab (43.0%). Conclusion The b/tsDMARDs with lower prices showed higher cost-effectiveness.

Lamps that emit 222 nm short-wavelength ultraviolet (UV) radiation can be safely used for sterilization without harming human health. However, there are few studies on the effects of 222 nm UVC (222-UVC) radiation exposure on plants compared with the effects of germicidal lamps emitting primarily 254 nm UVC (254-UVC) radiation. We investigated the growth inhibition and cell damage caused by 222-UVC exposure to Arabidopsis plants, especially mitochondrial dynamics, which is an index of damage caused by UVB radiation. Growth inhibition resulted from 254-UVC or 222-UVC exposure depending on the dose of UVC radiation. However, with respect to the phenotype of 222-UVC-irradiated plants, the leaves curled under 1 kJ m−2 and were markedly bleached under 10 kJ m−2 compared with those of plants irradiated with 254-UVC. The cellular state, especially the mitochondrial dynamics, of epidermal and mesophyll cells of Arabidopsis leaves exposed to 254-UVC or 222-UVC radiation was investigated using Arabidopsis plants expressing mitochondrial matrix-targeted yellow fluorescent protein (MT-YFP) under the control of Pro35S to visualize the mitochondria. 222-UVC (1 or 5 kJ m−2) severely damaged the guard cells within the epidermis, and YFP signals and chloroplast autofluorescence in guard cells within the epidermis exposed to 222-UVC (1 or 5 kJ m−2) were not detected compared with those in cells exposed to 254-UVC radiation. In addition, 222-UVC irradiation led to mitochondrial fragmentation in mesophyll cells, similar to the effects of 254-UVC exposure. These results suggest that 222-UVC severely damages guard cells and epidermal cells and that such damage might have resulted in growth inhibition.

Methylglyoxal (MGO) produced during glycolysis is known to react with arginine residues on proteins to generate advanced glycation end products, such as N

This study aims to investigate the feasibility of using convolutional neural networks to predict an accurate and high resolution dose distribution from an approximated and low resolution input dose.Sixty-six patients were treated for prostate cancer with VMAT. We created the treatment plans using the Acuros XB algorithm with 2 mm grid size, followed by the dose calculated using the anisotropic analytical algorithm with 5 mm grid with the same plan parameters. U-net model was used to predict 2 mm grid dose from 5 mm grid dose. We investigated the two models differing for the training data used as input, one used just the low resolution dose (D model) and the other combined the low resolution dose with CT data (DC model). Dice similarity coefficient (DSC) was calculated to ascertain how well the shape of the dose-volume is matched. We conducted gamma analysis for the following: DVH from the two models and the reference DVH for all prostate structures.The DSC values in the DC model were significantly higher than those in the D model (p 0.01). For the CTV, PTV, and bladder, the gamma passing rates in the DC model were significantly higher than those in the D model (p 0.002-0.02). The mean doses in the CTV and PTV for the DC model were significantly better matched to those in the reference dose (p 0.0001).The proposed U-net model with dose and CT image used as input predicted more accurate dose.

In this CyberKnife® dose verification study, we investigated the effectiveness of the novel potential error (PE) concept when applied to the determination of a robust measurement point for targeting errors. PE was calculated by dividing the differences between the maximum increases and decreases in dose distributions by the original distribution after obtaining the former by shifting the source-to-axis and off-axis distances of each beam by ±1.0 mm. Thus, PE values and measurement point dose heterogeneity were analyzed in 48 patients who underwent CyberKnife radiotherapy. Sixteen patients who received isocentric dose delivery were set as the control group, whereas 32 who received non-isocentric dose delivery were divided into two groups of smaller PE (SPE) and larger PE (LPE) by using their median PE value. The mean dose differences (± standard deviations) were 1.0 ± 0.9%, 0.5 ± 1.4% and 4.1 ± 2.8% in the control, SPE and LPE groups, respectively. We observed significant correlations of the dose difference with the PE value (r = 0.582, P

Understanding the mechanisms of adaptation of alpine aquatic organisms to the alpine environment, one of the ecosystems most vulnerable to climate change, would help us predict how those organisms would respond to the upcoming climate change. Here, we examined how one of Japan's endemic crustaceans, Daphnia tanakai, which has been found only in alpine lakes and pools in high mountain moors, is adapted to the alpine environment and what restricts its distribution only to the alpine environment. Lab experiments on UVB tolerance and growth rate under different pH and temperature based on the field survey for pools in mountain moors revealed that D. tanakai was differentiated from two low-altitude species (Daphnia dentifera and Daphnia pulicaria) by its tolerance to low pH such as 4.5, which is equal to the mean pH of pools in the high mountain moors occupied by D. tanakai. The growth rate at pH 4.5 was, however, significantly lower than that at higher pH, suggesting that low pH was not necessarily an optimal condition, and that other factors restrict the distribution to alpine lakes. Vulnerability to invertebrate predators such as Chaoborus was suggested as such a factor by additional experiments on swimming activity and predation and the fact that D. tanakai has only been found in pools without Chaoborus. Because it is known that the pH of alpine lakes is tightly linked with temperature, global warming may diminish the advantage of D. tanakai and allow invasion of alpine lakes by unwelcome predators and competitors from lower altitudes.

Plants have evolved various mechanisms that protect against the harmful effects of UV-B radiation (280–315 nm) on growth and development. Cyclobutane pyrimidine dimer (CPD) photolyase, the repair enzyme for UV-B-induced CPDs, is essential for protecting cells from UV-B radiation. Expression of the CPD photolyase gene (PHR) is controlled by light with various wavelengths including UV-B, but the mechanisms of this regulation remain poorly understood. In this study, we investigated the regulation of PHR expression by light with various wavelengths, in particular low-fluence UV-B radiation (280 nm, 0.2 µmol m–2 s –1), in Arabidopsis thaliana seedlings grown under light–dark cycles for 7 d and then adapted to the dark for 3 d. Low-fluence UV-B radiation induced CPDs but not reactive oxygen species. AtPHR expression was effectively induced by UV-B, UV-A (375 nm) and blue light. Expression induced by UV-A and blue light was predominantly regulated by the cryptochrome-dependent pathway, whereas phytochromes A and B played a minor but noticeable role. Expression induced by UV-B was predominantly regulated by the UVR8-dependent pathway. AtPHR expression was also mediated by a UVR8-independent pathway, which is correlated with CPD accumulation induced by UV-B radiation. These results indicate that Arabidopsis has evolved diverse mechanisms to regulate CPD photolyase expression by multiple photoreceptor signaling pathways, including UVR8-dependent and -independent pathways, as protection against harmful effects of UV-B radiation.

Understanding the thermal properties of methane hydrate (MH)-bearing sediments is important to develop future energy resources. Thus, in this study, we measured the thermal properties of synthetic hydrate-bearing sediment samples comprising sand, water, methane, and MH using the hot-disk transient plane source technique. The melting heat of MH possibly affects the measurements; thus, the experiments were performed at supercooled conditions during MH formation in the sediment pores. The results show that thermal conductivity and diffusivity of the samples slightly increased as hydrate saturation increased from 0 to 0.3. We also performed thermal conductivity calculations using simple thermophysical models. The distribution model (geometric mean model) shows a relatively good agreement with the experimental data; however, it underestimates the thermal conductivity of the four-component sample. Thus, better prediction models are required to accurately determine the thermal properties of four-component systems.

AIM We aimed to investigate the correlation between biochemical recurrence (BCR) and the pretreatment apparent diffusion coefficient (ADC) ratio of tumor to normal prostate tissue in patients with prostate cancer who underwent intensity-modulated radiotherapy (IMRT). PATIENTS AND METHODS Retrospective analyses were performed for 101 patients diagnosed with localized prostate cancer who underwent IMRT at a dose of 70-78 Gy to the prostate gland and medial part of the seminal vesicles. Before treatment, all patients underwent magnetic resonance imaging including diffusion-weighted imaging of the prostate. BCR was defined as a rising prostate-specific antigen level (the Phoenix criterion). RESULTS The median follow-up for all patients was 29 months, and BCR occurred in 10 patients (9.9%). ADC ratios and Gleason scores were significant independent prognostic factors of BCR by multivariate analysis. CONCLUSION The pretreatment ADC ratio was an independent prognostic factor for BCR in patients with prostate cancer who underwent IMRT.

We have retrospectively analyzed the outcomes of high-dose-rate (HDR) brachytherapy as a salvage therapy for vaginal recurrence of endometrial cancer.From 1997 to 2012, salvage HDR brachytherapy was performed in 43 patients. The median age was 64 years (range, 41-88 years). HDR brachytherapy was performed by interstitial brachytherapy in 34 patients (79%) and by intracavity brachytherapy in nine patients (21%). Seventeen (40%) of the 43 patients were treated with external beam radiotherapy. The median followup period was 58 months (range, 6-179 months).The 5-year overall survival (OS), progression-free survival (PFS), and local control rates (LC) were 84%, 52%, and 78%, respectively. Patients who received brachytherapy with external beam radiotherapy experienced no nodal recurrence (0 of 17 patients), whereas 23% of the patients (6 of 26 patients) who received brachytherapy alone experienced nodal recurrence (p = 0.047). The pathologic grade at the time of initial surgery (G1-2 vs. G3) was found to be a significant prognostic factor for both OS and PFS. The respective 5-year OS was 96% vs. 40% (p 0.01), and the 5-year PFS was 58% vs. 0% (p 0.01). Age (≥60 vs.60) and modality (interstitial brachytherapy vs. intracavity brachytherapy) were significant prognostic factors for LC. The respective 5-year LC was 74% vs. 100% (p = 0.020) and 85% vs. 56% (p = 0.035).HDR brachytherapy is effective and feasible in patients with isolated vaginal recurrence of endometrial cancer. Pathologic grade, age, and modality were significant prognostic factors.

The taste and extractive components of boiled dorsal muscle and broth prepared from half-smooth golden puffer Lagocephalus spadiceus caught in Japan and from those imported from China were compared. In the sensory test, the first taste, elasticity, and saltiness of boiled muscle from Japanese (domestic) fish were higher than those of the imported fish, whereas the orthonasal fishy smell of the imported fish was higher than that of the domestic fish. The first taste, aftertaste, retronasal fishy smell, sweetness, saltiness, and umami of the broth prepared from dorsal muscle of the domestic fish were higher than those of the imported fish, whereas orthonasal fishy smell and bitterness of the imported fish were higher than those of the domestic fish. Most panelists preferred the overall taste of the domestic fish to that of the imported fish. The concentration of trimethylamine in the trichloroacetic acid extracts from boiled muscle and broth of the imported fish was higher than that of the domestic fish, suggesting that this substance contributes to the orthonasal fishy smell of the imported fish.

Wabula is a small coastal settlement in the south of Buton Island, Southeast Sulawesi Province, Indonesia. Its residents are at the periphery of contemporary Butonese society, which focuses on the district capital of Bau-Bau, immediately adjacent to an historic walled precinct widely represented as the centre of a Butonese kingdom and sultanate that existed from the fourteenth century until 1960. Locally published accounts of the realm's history scarcely refer to Wabula. However, Wabula people narrate a unique account of Buton in which Wabula has a leading role as the place of origin of the Butonese kingdom. In Wabula the account is known as ‘True History’. This paper describes this historical narrative focusing on a local trek that takes place as part of Wabula's annual cycle of agricultural-calendric rituals. The paper reflects on the manner in which context is inseparable from embedding historical narrative in the spatial and temporal character of the Wabula social world.

Buton Kingdom is supposed to have been founded in the thirteenth century on Buton Island in Southeast Sulawesi; the kingdom existed until 1960. The purpose of this paper is to investigate the historical process of the formation of the Buton Kingdom through the sixteenth to the seventeenth centuries. Written materials such as official letters of the VOC (the Dutch East India Company) and the English East India Company, diaries of foreign sailors, and other historical monographs will be investigated.In the sixteenth century, the Buton Kingdom was socially and symbolically situated at the periphery of the Maluku World and was regarded as the “child” of a “father-like” Ternate Kingdom and the “brother” of other kingdoms of the Maluku World. The Buton Kingdom accepted Islam under the strong influence of the Ternate Kingdom in the latter half of the sixteenth century.At the beginning of the seventeenth century, because of its strategic location as a trading port and its possession of various kinds of commodities, the English East India Company and the VOC showed interest in Buton Kingdom/Island and made contact several times with some of the sultans of Buton. However, the entities did not form a maritime trade center on the island. Throughout the seventeenth century, the Buton Kingdom was involved in keen competition among the Gowa-Talloq' United Kingdom in Makassar, the VOC, and the Ternate Kingdom, each of which was eager to grasp the maritime network and to establish authority over the sea areas in Eastern Indonesia. Under such a situation, the “father-son” relationship between Ternate and Buton was kept, and Buton offered tribute to Ternate to receive protection from its “father”. In the middle of the seventeenth century, Ternate was subordinated to the VOC. The Buton Kingdom, at the time, was on the side of the VOC and Ternate as they faced the menace of Makassar. In the latter half of the seventeenth century, the united forces of the VOC —which were made up of Ternate, Bone, Buton, and the like— defeated Gowa-Talloq' United Kingdom in the Makassar War.The decline of Gowa and Talloq' led to the further expansion of the VOC, and eventually to the decay of the Ternate Kingdom under its subordination to the VOC. Buton lost the protection from its “father”, and thereafter the VOC interfered intermittently in the domestic affairs of the Buton Kingdom.

By cloning and sequencing cDNA, the primary structure of a mycelial aggregate-specific lectin of Pleurotus cornucopiae was determined. The amino acid sequence was novel and elucidated unique properties of this lectin: It was composed of 373 amino acids, 33 of which constitute a signal sequence. The sequence of the mature lectin consisted of two homologous regions having five glycosylation recognition signals and six cysteine residues. However, the distribution of these elements in the two regions was biased. Expression of cDNA in Escherichia coli and Pichia pastoris revealed the requirement of glycosylation to produce the functional lectin. Gel filtration followed by gel electrophoretic analyses of the purified lectin showed that the active component moved faster than the bulk of the protein, suggesting that the most active lectin formed an oligomer of subunits through disulfide bonds. From these observations, a model for the structure of the active form of this lectin is proposed. Southern hybridization using the cDNA as a probe revealed the presence of several genes. The lectin gene was composed of five exons and five introns.

The polymerization ofe-caprolactone (e-CL) with a combination of tert-butyllithium ( t-BuLi ) and bis(2,6-di-t-butylphenoxy)methylaluminum [MeAl(ODBP) 2 ] in toluene at 0°C proceeded in a living manner to give polymers with narrow molecular weight distributions ( MWD ) within a few minutes, while the polymerization with t-BuLi alone gave a polymer with much broader MWD. The yield of the polymer did not reach 100 % at the Al / Li ratio of 5, because the excess MeAl(ODBP) 2 coordinates with e-CL to protect it from the attack by the propagating species. The polymerization with t-BuLi / EtAl(ODBP) 2 gave polymers in quantitative yields regardless of Al / Li ratio, and also narrower MWD even for higher molecular weight polymers.

Two endogenous ligands for cannabinoid receptors, anandamide (arachidonylethanolamide) and 2-arachidonoylglycerol, lose their biological activities by enzymatic hydrolysis. A cDNA for a rat liver enzyme hydrolyzing anandamide as well as oleamide was overexpressed in COS-7 cells. When the particulate fraction was allowed to react with 2-arachidonoylglycerol, arachidonic acid was produced. In contrast, this hydrolytic reaction did not occur with the control cells. The hydrolysis of 2-arachidonoylglycerol proceeded about 4-fold faster than the anandamide hydrolysis with a Km value as low as 6 μM and an optimal pH of 10. Phenylmethylsulfonyl fluoride and methyl arachidonyl fluorophosphonate inhibited the hydrolysis of both anandamide and 2-arachidonoylglycerol in parallel. Furthermore, the hydrolysis of [14C]2-arachidonoylglycerol was inhibited by anandamide dose-dependently. These results suggest that anandamide and 2-arachidonoylglycerol can be inactivated by the same enzyme.

Panax ginseng hairy root cultures were established by infecting petiole segments with Agrobacterium rhizogenes strain 15834. Hairy root segments including root tips placed onto phytohormone-free 1/2 Murashige and Skoog solid medium and stored at 4 °C in the dark for 4 months, resumed elongation when the temperature was raised to 25 °C in the dark. For cryopreservation, a vitrification method was applied. Root tips precultured with 0.1 mg/l 2,4-D for 3 days and dehydrated with PVS2 solution for 8 minutes prior to immersion into liquid nitrogen had a survival rate of 60 % and could regenerate. The hairy roots regenerated from cryopreserved root tips grew well and showed the same ginsenoside productivity and patterns as those of the control hairy roots cultured continuously at 25 °C. The conservation of T-DNAs in the regenerated hairy roots was proved by PCR analysis.

UVB radiation suppresses photosynthesis and protein biosynthesis in plants, which in turn decreases growth and productivity. Here, an ultraviolet-B (UVB)-tolerant rice mutant, utr319 (UV Tolerant Rice 319), was isolated from a mutagenized population derived from 2500 M1 seeds (of the UVB-resistant cultivar ‘Sasanishiki’) that were exposed to carbon ions. The utr319 mutant was more tolerant to UVB than the wild type. Neither the levels of UVB-induced cyclobutane pyrimidine dimers (CPDs) or (6-4) pyrimidine-pyrimidone photodimers [(6-4) photoproducts], nor the repair of CPDs or (6-4) photoproducts, was altered in the utr319 mutant. Thus, the utr319 mutant may be impaired in the production of a previously unidentified factor that confers UVB tolerance. To identify the mutated region in the utr319 mutant, microarray-based comparative genomic hybridization analysis was performed. Two adjacent genes on chromosome 7, Os07g0264900 and Os07g0265100, were predicted to represent the mutant allele. Sequence analysis of the chromosome region in utr319 revealed a deletion of 45 419 bp. RNAi analysis indicated that Os07g0265100 is most likely the mutated gene. Database analysis indicated that the Os07g0265100 gene, UTR319, encodes a putative protein with unknown characteristics or function. In addition, the homologs of UTR319 are conserved only among land plants. Therefore, utr319 is a novel UVB-tolerant rice mutant and UTR319 may be crucial for the determination of UVB sensitivity in rice, although the function of UTR319 has not yet been determined.

Summary An embryogenic suspension cell line of fennel, Foeniculum vulgare Miller, directly induced from hypocotyl, was developed. The suspension cells were cold-preserved at 4 °C for up to 12 weeks and then cultured at 25 °C for 2 weeks. The packed cell volume of the cultured cells decreased as the cold-preservation period became longer. The cells, with a size of 32-82μm and having embryogenic potential, diminished suddenly with the passage of the cold-preservation period. The cells cold-preserved for 2 to 6 weeks were capable of forming normal somatic embryos that were identical to those obtained from the cells without cold-preservation. The resulting somatic embryos regenerated to develop into normal plantlets when cultured in hormone-free Murashige and Skoog medium under illumination. Esterase isozyme analysis on polyacrylamide gel electrophoresis revealed the appearance of different bands in the embryos treated with 4-week and 6-week cold-preservation, in contrast to the embryos from the cells without cold-preservation. Anethole was detected in the methanol extracts of embryos induced from the cold-preserved cells at the same level as that of embryos induced from the cells without cold-preservation.

We verified the setup error (SE) in two persons' radiation therapist's team, which consist of staff and new face. We performed the significance test for SE by the staff group and the new face group.One group consists of four staff therapists with at least 5 to 30 years of experience. The other group consists of new face radiation therapists that have 1 to 1.5 years of experience. Analyzed were 53 patients diagnosed with pelvic cancer (seven patients who underwent 3 dimensional conformal radiation therapy (3DCRT) and 46 patients who underwent intensity modulated radiation therapy (IMRT). Image verification was 1460 times. It was performed through setup verification by cone beam computed tomography (CBCT), and we measured SE of four directions (lateral, long, vertical, 3D). We performed the student's t-test to get the difference of the average error between the staff group and the new face group.The results of significance tests show that there is no difference between SE in the staff group and the new face group in radiotherapy.

Nanoscale magnetic beads coated with nerve growth factor (NGF) allow us to accumulate neurons differentiated from mouse ES cells in a selected area of the culture plate surface using a magnet. Neurons with neurite outgrowths within a particular area expressed TrkA and incorporated beads in the soma.

Nepsilon-(hexanoyl)lysine (HEL) is a potentially useful marker of oxidative stress in animals. We investigated whether HEL might be useful as a marker in rice seeds damaged by oxidative stress during storage, as well as in animals. The germination ability of rice decreased with lipid peroxidation during storage at 40 degrees C for three months. Moreover, we observed accumulation of HEL in the damaged rice. In addition, the activities of antioxidative enzymes, catalase and superoxide dismutase, significantly decreased in the rice seeds during storage at 40 degrees C. These results suggest that HEL might be a useful marker of oxidative stress in rice.

Quantification of mRNAs deriving from malignant cells is useful for estimating leukemic states. In this study, we have developed RT-PCR methods using real-time PCR detection system, a LightCycler, for quantification of bcr/abl chimerical genes in peripheral blood and bone marrow of chronic myeloid leukemia patients. Total amounts of RNA extracted were corrected using beta-actin gene as an internal standard. The coefficients of variation of intra-assay variation and inter-assay variation for each gene were within a range of 1.7-26.0% which showed more precise quantification than the competitive PCR method. The coefficients of variation of assay are within a range of 7.7-27.6% in the case of using three samples of normal subjects from blood collecting to quantification of bcr gene. Bcr/abl and WT1 genes could be measured from 10(2) to 10(8) copies and 10 to 10(5) copies with linearity, respectively. Using real-time PCR detection with LightCycler system, 2 x 10(3) K562 cells among 2 x 10(6) total cells demonstrated the bcr/abl gene, while 2 x 10(1) K562 cells among 2 x 10(6) total cells could be detected using the nested PCR method. In tests of seven clinical samples, five samples demonstrated bcr/abl and WT1 genes, while those in two other patients after bone marrow transplantation and a normal subject could not detected. This result suggests that our quantitative method reflect the clinical stages of CML patients.

The biosynthesis of prostaglandin (PG) and thromboxane (TX) is initiated by a bifunctional enzyme with oxygenase and peroxidase activities, and PGH2 is produced from arachidonic acid via PGG21. This bifunctional enzyme (prostaglandin endoperoxide synthase, E.C. 1.14.99.1) will be referred to briefly as cyclooxygenase in this chapter. There are two cyclooxygenase isozymes (COX-1 and COX-2), and COX-1 is generally known to be present in human platelets and involved in the synthesis of proaggregatory and vasoconstrictive TXA2. Since platelets have no nucleus and can not synthesize mRNA, the COX-1 protein is derived presumably from megakaryocytes which are precursor cells of platelets.

The cytosol fraction of human platelets did not convert prostaglandin (PG) H2 to PGD2. However, a homogenate of human megakaryoblastic CMK cells (precursor cells of platelets) produced PGD2 from PGH2. The PGD synthase activity was localized in the cytosol of CMK cells, and absolutely required glutathione. The catalytic properties and Western and Northern blottings indicated that the enzyme was PGD synthase of the hematopoietic type rather than the lipocalin type. When CMK cells were differentiated to megakaryocytes with phorbol ester along with induction of cyclooxygenase-1, the PGD synthase activity increased about 2-fold for 2 days and then decreased. In another human megakaryoblastic cell line, Dami, the PGD synthase increased about 10-fold by the addition of phorbol ester. Thus, the PGD synthase, which was undetectable in platelets, appeared during differentiation of megakaryoblasts to megakaryocytes.

e16018 Background: In the treatment of pharyngeal or oral cancer, surgery causes so severe deterioration of phonation, swallowing function, and cosmesis that radiation therapy is usually preferred to surgery as a primary treatment. However, after curative doses of radiation therapy are administered, surgical procedures often become difficult because of tissue fibrosis and delay of healing, hence its clinical significance is controversial. This study investigated into clinical impacts of salvage surgery on overall survival (OS) of the patients with recurrent pharyngeal or oral cancer after definitive radiation therapy. Methods: Between January 1997 and December 2007, 126 patients with pharyngeal or oral squamous cell carcinoma were treated by radiation therapy with curative intents. Ninety-four patients (75%) had stage III or IV locally-advanced diseases. In 45 patients (36%), doxorubicin- or platinum-based systemic chemotherapy was administered concurrently with radiation therapy. The median radiation dos...

The reactive site peptide bond of the eggplant inhibitor against trypsin [EC 3.4.21.4] was identified by chemical modifications with 1,2-cyclohexanedione, 2,4,6-trinitrobenzenesulfonic acid, acetic anhydride and glyoxal, and by sequential treatments with trypsin and carboxypeptidase B [EC 3.4.12.3]. The inhibitor was significantly inactivated by chemical modifications of arginine residues, but was not affected by lysine modifications. Free arginine was released from the trypsin-modified inhibitor by carboxypeptidase B digestion, accompanied by a marked loss of inhibitory activity. A serine residue was newly exposed at the N-terminal amino acid of the inhibitor after modification with trypsin. The reactive site of the inhibitor against trypsin was concluded to be an arginylseryl bond. The inhibitor was completely inactivated by full reduction of its disulfide bonds.

The thermodynamic parameters of the cytochrome c electron-transfer reaction have been estimated electrochemically using a bis(4-pyridyl)disulfide-modified gold electrode in phosphate buffer solutions (pH's 6–8) containing 0.1 M NaC104. The temperature dependence of the formal redox potential, U°′, obtained in the temperature range of 0–55°C showed biphasic behavior in an alkaline solution with an intersection point at ca. 40°C, which would be attributable to a structural change in the protein moiety of cytochrome c, while in acidic and neutral solutions a monotonous relationship between U°′ and temperature was observed. For the electron-transfer reaction entropies (ΔS°rc = S°red - S°ox) of −12.7 ± 1.6, −11.8 ± 1.1, and −10.3 ± 1.5 (below 40°C) and −41.1 ± 7.5 (above 40°C) were obtained at pH's 6, 7, and 8, respectively.

A new complex [(NH4)Cu3Cl4(C6H4O2)3⁄2·H2O] was synthesized from CuCl2, hydroquinone, and NH4Cl in an aqueous solution, and its structure was characterized on the bases of its UV, IR, and ESR spectra and TGA. On heating, this complex was stable up to 100 °C, but above 120 °C p-benzoquinone was released quantitatively. The complex was found to be a polynuclear copper(I) complex containing p-benzoquinone molecules and chlorides as ligands, and to be a charge-transfer complex in which π-electrons of the ring carbons of p-benzoquinone form coordinate bonds with Cu(I). The formation process of the complex was: 3CuCl2+3/2(C6H6O2)+H2O+NH4Cl=(NH4)Cu3Cl4(C6H4O2)3⁄2·H2O+3HCl

The crystal structure of silver (I) N,N-diethyldithiocarbamate was determined by the X-ray diffraction method. The crystals are monoclinic, with the space group P21/c, and with two hexameric molecules in a unit cell with dimensions of a=10.90±0.02, b=24.72±0.01, c=11.51±0.02 A, and β=125.8±0.1°. The structure was solved by a heavy-atom method and was refined by block-diagonal least-squares methods to a final R-value of 0.029 for 2108 observed reflections. The structure consists of hexameric molecules, [AgS2CN(C2H5)2]6. The hexameric structure was essentially consistent with Hesse’s preliminary result (1960). The terminal silver atom in one molecule is bridged by a sulfur atom to that in the adjacent hexamer, forming a chain structure along the a axis. All the silver atoms are connected to five atoms (either 1Ag and 4S or 2Ag and 3S). The dithiocarbamate ligands are classified into three types: bidentate, intra-, and inter-molecule tetradentate.

To clarify the product and the reaction pathway, anodic oxidation of acridine was investigated in acetonitrile. The voltammogram of acridine exhibited two anodic waves at 1.35 (Ia) and 2.0 (IIa) V vs. Ag/AgClO4 (0.01 M). Waves Ia and IIa were due to oxidation of acridine and protonated acridine respectively. The oxidation product was obtained by preparativescale electrolysis at 1.45 V. The results of precise analysis and electrochemical behavior of the oxidation product were somewhat complicated. The puzzling results are, finally, interpreted clearly in terms of a dication of the tetramer (on the basis of acridine) which is in equilibrium with acridyl acridinium cation radical (eqn. 1). The oxidation pathway for producing the tetramer by an ECEC mechanism (eqns. 2–5) was proposed.

Proton assignments of the cycloadducts of anhydromethylberberines with dienophiles have been made by reference to the carbon-13 nulcear magnetic resonance spectra. The correlation between the molecular geometries and the proton chemical shifts is discussed on the basis of the variable-temperature nuclear magnetic resonance spectral data.

Photolysis of 4-methyl-1-oxoanhydroberberine (9) in the presence of nitrosobenzene gives two isomeric photoadducts (11) and (12). In the presence of diethyl azodicarboxylate, 9 affords two different types of photoadduct (13) and (14). These photoadducts are considered to be formed by the photochemically allowed [2s+2s+2+s] cycloaddition reactions.

Photolysis of dihydroisoquinoline (2) in the presence of nitrosobenzene gives the epoxyimine (10), sodium borohydride reduction of which affords the aniline (14). Reaction of the dehydro compound (17) derived from 14 with performic acid followed by hydrolysis provides the diol (20). Hydrogenolysis of 20 over a palladium catalyst affords the corynoline analog (7). All compounds are formed under strictly stereoselective control.