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We investigated the expression pattern of Dkk-3, a secreted Wnt pathway inhibitor, in mouse intestinal tissue and three-dimensional cultured Caco-2 spheroids. Dkk-3 was expressed at the bottom of crypts from the mouse small intestine. Human colon adenocarcinoma Caco-2 cells expressed Dkk-3 under a semi-confluent condition, but Dkk-3 expression was seen in only some of the Caco-2 cells when the cells were sparse. Caco-2 cells formed hollow spheroids in Matrigel, and the layer-forming cells in the hollow spheroids expressed Dkk-3. Our results demonstrated that Dkk-3 might affect intestinal cells when the fate of stem cells changes.

Background: During total hip arthroplasty (THA) in lateral decubitus, perioperative radiography allows the surgeon a simple evaluation of the leg length difference (LLD) by measuring the proximal femoral length. However, the effect of femoral malpositioning on proximal femoral length measurements during the evaluation of perioperative radiographs is not adequately understood. We aimed to (1) investigate the effects of malposition on proximal femoral length using three-dimensional computer simulations and (2) verify whether a simple correction formula can improve the accuracy of LLD evaluation on perioperative radiographs., Methods: We analyzed 86 patients who underwent THA. Digitally reconstructed radiography (DRR) images were reconstructed in various limb positions (femoral abduction, adduction, and flexion), and proximal femoral length measurements in those malpositions were simulated. Additional morphological measurements of the femoral neck torsion angle in the sagittal plane were performed to elucidate the simulation findings. The malposition angle of abduction-adduction was evaluated with actual perioperative radiographs, and trigonometric correction was attempted., Results: The leg length measurement decreased as the femoral DRR image shifted from neutral to abduction and adduction, demonstrating approximately 1 mm per 10° of abduction or adduction. The leg length measurement increased as the femoral image shifted from neutral to 10° and 20° of flexion, demonstrating approximately 3 mm per 10° of flexion. With a peak at 20° of flexion, the proximal femoral length measurement decreased in the DRR images at 30°, 40°, 50° and 60° of flexion. The femoral neck torsion angle was 21.1 ± 5.6° on the operative side. The effect of coronal malposition on leg length discrepancy was so small that the difference following trigonometric correction was not statistically significant (p=0.108)., Conclusion: In the present simulation, coronal malposition had a small effect on LLD evaluation. As the femoral neck has a torsion of approximately 20°, the proximal femoral length is projected the longest when the femur is flexed 20°. With careful positioning of the limb in the coronal plane, the use of a correction formula for LLD evaluation would not be necessary. Surgeons should ensure that both lower limbs are in the same position in the sagittal plane during THA in lateral decubitus., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board of Kyushu University, Fukuoka, Japan issued approval 30-91. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kokubu et al.)

Background: This study assessed the hip survival rate and patient-reported outcome measures (PROMs) of transtrochanteric curved varus osteotomy (CVO) for osteonecrosis of the femoral head (ONFH) compared with those of conservative management., Methods: The CVO group comprised 32 consecutive patients (39 hips) who underwent CVO for ONFH between 2000 and 2011. The conservative group consisted of 36 consecutive patients (37 hips) who were managed conservatively for at least 1 year after collapse and who had ONFH classified by the Japanese Investigation Committee of Health and Welfare as type B or C1, for which CVO is indicated. Kaplan-Meier analysis of hip survival used any ONFH-related therapeutic surgery as the endpoint. PROMs were evaluated for all patients with surviving hips and radiographs available at the latest follow-up., Result: The 10-year hip survival rate in the CVO group was 86.7%, which was significantly higher than the 51.0% 5-year survival rate in the conservative group (p < 0.0001). The Oxford Hip Score and UCLA Activity Score were significantly better in the CVO group without joint space narrowing than in the conservative group, with no significant differences between the CVO group with joint space narrowing and the conservative group., Conclusion: CVO could preserve hip joints more effectively than conservative follow-up after collapse, although the presence of joint space narrowing could reduce satisfaction levels even in patients with long-term hip survival., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: In the natural course of osteonecrosis of the femoral head, sclerotic changes at the boundary of necrotic lesion gradually occur until femoral head collapse. This study aims to examine the effects of bone mineral density at the lateral boundary of necrotic lesion on a subsequent femoral head collapse., Methods: We developed patient-specific finite element models of 9 hips with subsequent collapse and 10 hips without subsequent collapse. Cubic regions of interest were selected at both subchondral areas of the lateral boundary and the adjacent necrotic lesion. Bone mineral density values of the regions of interest were quantitatively measured, and a ratio of bone mineral density values (lateral boundary/necrotic lesion) was calculated. Stress values at the lateral boundary were also evaluated., Findings: The ratio of bone mineral density values was significantly higher in hips with subsequent collapse than that without subsequent collapse (p = 0.0016). The median equivalent stress and shear stress were significantly higher in hips with subsequent collapse than that without subsequent collapse (p = 0.0071, and p = 0.0143, respectively). The ratio of bone mineral density values showed a promising value in predicting the occurrence of subsequent femoral head collapse (AUC = 0.97)., Interpretation: Our results indicated that bone mineral density value at the lateral boundary of necrotic lesion may be associated with the occurrence of subsequent femoral head collapse in pre-collapse stage osteonecrosis of the femoral head., Competing Interests: Declaration of Competing Interest Each author certifies that he or she has no commercial associations that might pose a conflict of interest in connection with the submitted article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Articular surface irregularities are often observed in collapsed femoral heads with osteonecrosis, while the effects of the degree of collapse on the articular surface are poorly understood. We first macroscopically assessed the articular surface irregularities on 2-mm coronal slices obtained using high-resolution microcomputed tomography of 76 surgically resected femoral heads with osteonecrosis. These irregularities were observed in 68/76 femoral heads, mainly at the lateral boundary of the necrotic region. The mean degree of collapse was significantly larger for femoral heads with articular surface irregularities than for those without (p < 0.0001). Receiver operating characteristic analysis showed that the cutoff value for the degree of collapse in femoral heads with articular surface irregularities at the lateral boundary was 1.1 mm. Next, for femoral heads with <3-mm collapse (n = 28), articular surface irregularities were quantitatively assessed based on the number of automatically counted negative curvature points. Quantitative evaluation showed that the degree of collapse was positively correlated with the presence of articular surface irregularities (r = 0.95, p < 0.0001). Histological examination of articular cartilage above the necrotic region (n = 8) revealed cell necrosis in the calcified layer and abnormal cellular arrangement in the deep and middle layers. In conclusion, articular surface irregularities of the necrotic femoral head depended on the degree of collapse, and articular cartilage was already altered even in the absence of macroscopically determined gross irregularities., (© 2023 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

A flow-diverter (FD) device is a well-established tool for the treatment of unruptured intracranial aneurysms. Time-of-flight (TOF) MR angiography (MRA) is widely used for postoperative assessment after the treatment with FD; however, it cannot fully visualize intra-aneurysmal and intrastent flow signals due to the magnetic susceptibility from the FD. Recently, the utility of MRA with ultra-short TE (UTE) sequence and arterial spin labeling technique in assessing the therapeutic efficacy of intracranial aneurysms treated with metallic devices has been reported, but long image acquisition time is one of the drawbacks of this method. Herein, we introduce a novel UTE MRA using the subtraction method that enables the reduction in susceptibility artifacts with a short image acquisition time.

Chromosome aberrations have been one of the most sensitive and reliable biomarkers of exposure to ionizing radiation. Using the multiplex fluorescence in situ hybridization (M-FISH) technique, we compared the changes, over time, in the frequencies of translocations and of dicentric chromosomes in the splenic lymphocytes from specific pathogen-free (SPF) C3H/HeN female mice continuously exposed to 0.05 mGy/day (18.25 mGy/year) gamma rays for 125 to 700 days (total accumulated doses: 6.25-35 mGy) with age-matched non-irradiated controls. Results show that the frequencies of translocations and of dicentric chromosomes increased significantly over time in both irradiated and non-irradiated control mice, and that the frequencies were significantly lower, not higher, in the irradiated mice, which differs from our previous reports of increased chromosome aberration frequencies at higher radiation dose rates of 1 mGy/day and 20 mGy/day. These results will be useful when considering the radiation risk at very low-dose rates comparable to regulatory dose limits., (©2022 by Radiation Research Society. All rights of reproduction in any form reserved.)

Objective: Excessive pelvic tilt has been reported to impair the biomechanical loading of the hip joint. However, the influence of pelvic tilt in osteonecrosis of the femoral head (ONFH) remains unclear. This study aims to assess whether sagittal pelvic posture in the standing position correlates with progression of femoral head collapse in post-collapse stage ONFH., Methods: This is a single-center retrospective study. We investigated 107 patients (107 hips; 73 males and 34 females; mean age, 48 years) diagnosed with Association of Research Circulation Osseous (ARCO) stage III ONFH at the first visit and who subsequently underwent surgical treatment in our institution from July 2016 to December 2020. The sagittal pelvic posture in the standing position before surgery was quantified as the angle formed by the anterior pelvic plane and the vertical z-axis in the sagittal view (APP angle). An APP angle <0° indicated posterior pelvic tilt. Progression of femoral head collapse was calculated as collapse speed. The following factors potentially associated with collapse speed were evaluated by exploratory data analysis followed with multiple linear regression analysis: sex, age, BMI, etiology, pelvic incidence, contralateral hip condition, time interval between the first visit and surgery, size of necrotic lesion, location of necrotic lesion, and APP angle., Results: As ONFH progressed from ARCO stage IIIA to stage IV, APP angle decreased significantly and continuously (stage IIIA, -0.2° ± 5.5°; stage IIIB, -3.7° ± 5.8°; stage IV, -7.1° ± 6.4°). The factors significantly associated with collapse speed were size of necrotic lesion (p = 0.0079), location of necrotic lesion (p = 0.0190), and APP angle (p < 0.0001). APP angle showed a negative correlation with collapse speed (r = -0.40, p < 0.0001). After stratifying by size of necrotic lesion (<50% and ≥50% involvement) and location of necrotic lesion (JIC type C1 and C2), a significant negative correlation was observed between APP angle and collapse speed in each group (JIC type C1 with <50% involvement, r = -0.69, p < 0.0001; JIC type C1 with ≥50% involvement, r = -0.58, p = 0.0475; JIC type C2 with <50% involvement, r = -0.51, p = 0.0124; JIC type C2 with ≥50% involvement, r = -0.39, p = 0.0286)., Conclusions: Our results suggest that posterior pelvic tilt in the standing position occurred as ONFH progressed from ARCO stage IIIA to stage IV, which might be associated with progression of femoral head collapse in ONFH., (© 2022 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Since the Fukushima Dai-ichi Nuclear Power Plant (FDNNP) accident in 2011, 134Cs had been detected in atmospheric deposition samples collected in Rokkasho and Aomori in Japan, located ~400-km north of the FDNNP, during March 2011-May 2015. To study the distribution of radiocesium (134, 137Cs) in a Japanese black pine tree forest, we measured the activity concentration of 134, 137Cs in whole black pine trees, including roots collected during 2017-19 along with soil samples in 2015 and 2017-19. The results show that most of the deposited 134Cs was retained in the forest floor in 2015, with depth distribution different from that of the weapon testing fallout. Proportions of the weapon fallout 137Cs in trunks, branches, needles and roots were 44, 17, 13 and 26%, respectively, indicating that >50% of 137Cs in above-ground part existed in the trunks. The total inventories of 134Cs and 137Cs in the forest were estimated to be 8.9 and 2.5·103 Bq m-2, respectively, and ~4.8% of 137Cs inventory was originated from the accident. Inventory of 134Cs in the forest-including the black pine trees-was 1.6 times larger than cumulative deposition outside of the forest due to the canopy effect., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: In total hip arthroplasty (THA) for patients with previous femoral osteotomy, we hypothesized that a tapered cone stem may be an option due to the altered morphology of the proximal femur. The purpose of this study was to assess the short-term results of THA after femoral osteotomy using a tapered cone stem, and to identify issues that require further attention., Methods: Twenty-two hips in 21 consecutive patients who underwent THA after femoral osteotomy using a Wagner Cone tapered cone stem were retrospectively reviewed, with a mean follow-up period of 34.4 (range, 24-50) months. Clinical information was obtained from medical records. On preoperative radiographs, the Dorr type was classified based on the anteroposterior cortical index. On postoperative radiographs, the degree of stem subsidence and the stem location with the highest canal fill ratio were assessed., Results: The mean Harris hip score significantly improved from 55.2 at baseline to 84.8 at final follow-up. Radiologically, stem subsidence (>3 mm) was observed in seven hips, and it stabilized within 1 year after THA in all cases. In five of seven hips with stem subsidence, the highest postoperative canal fill ratio was observed in the distal third of the stem. The proportions of males and Dorr type A were significantly higher among hips with stem subsidence than among those without. During the follow-up period, no hips showed implant loosening or required revision surgery., Conclusions: The occurrence of stem subsidence should be noted when using Wagner Cone stems for Dorr type A femurs after femoral osteotomy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

There is very little information on the transgenerational or genetic effects of low dose-rate ionizing radiation. We report the detection of the transgenerational effects of chronic low dose-rate irradiation in mice, at the molecular level in the whole genome, using array comparative genomic hybridization technology. We observed that the number of the mice with de novo copy number variations (specifically, deletions) was significantly increased in the offspring of C57BL/6J male mice exposed to 20 mGy/day gamma-rays for 400 days (total dose: 8000 mGy), as compared to non-irradiated controls. We did not detect any difference in the size of the de novo deletions between the irradiated and the non-irradiated groups. An analysis of the life span of the offspring suggested a possibility that de novo copy-number variations may be associated with shorter life spans.

The effects of radiation exposure on germ cells and the gonads have been well studied at acute high-dose exposures, but the effects of chronic low-dose-rate (LDR) irradiation, particularly relevant for radiation protection, on germ cells and the gonads are largely unknown. Our previous study revealed that chronic exposure of mice to medium-dose-rate (MDR, 200 or 400 mGy/day) gamma-rays in utero for the entire gestation period (18 days) induced only a mild degree of general growth retardation, but with very drastic effects on the gonads and germ cells. In the current study, we further investigated the histomorphological changes in the gonads and the number of germ cells from gestation day (GD) 18 fetuses irradiated with MDR throughout the entire gestation period. The germ cells in the testes and ovaries of the MDR-irradiated fetuses were almost obliterated. Gestation day 18 fetuses exposed to LDR (20 mGy/day) radiation for the entire gestation period showed decreases in the number of the germ cells, which were not statistically significant or only marginally significant at most. Further investigations on the effects of LDR irradiation in utero using more sensitive methods are necessary., (©2021 by Radiation Research Society. All rights of reproduction in any form reserved.)

Large areas of Fukushima's forests were contaminated with radiocesium ( 137 Cs) after the Fukushima Dai-ichi Nuclear Power Plant accident. Most of the contaminated forests have not been decontaminated, and bioavailable 137 Cs is likely to circulate within the forest environment's food web. Nephila clavata (Nephilidae: Arachnida) is a top predator in the forest arthropod community, and this web-building spider potentially consumes many arthropod species presented in the grazing and detrital food chains. We tested whether 137 Cs in the spider could serve as a proxy for 137 Cs contamination of these arthropod communities. We also examined whether N. clavata could serve as a proxy for soil bioavailable 137 Cs. Nephila clavata was similarly or more contaminated with 137 Cs compared with lower-trophic-level arthropods such as herbivores and other predators at the same trophic level. Thus, the 137 Cs activity of N. clavata could represent the extent to which the arthropod community was contaminated with 137 Cs. Data from nine 137 Cs-contaminated sites in Fukushima showed a significant positive correlation between soil bioavailable 137 Cs and N. clavata's 137 Cs activity05 but the coefficient of determination was only moderate (R 2  = 0.43), suggesting that N. clavata is only a weak proxy of soil bioavailable 137 Cs. Our results also showed that the bioavailable fraction of 137 Cs in Fukushima was strongly correlated with the total inventory and that the K and Na contents of the soil determined the soil-to-spider transfer factor for 137 Cs and the 137 Cs activity in N. clavata, respectively. These results improve our understanding of 137 Cs transfer from the soil to arthropod species., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Calorie restriction is known to influence several physiological processes and to alleviate the late effects of radiation exposure such as neoplasm induction and life shortening. However, earlier related studies were limited to acute radiation exposure. Therefore, in this study we examined the influence of chronic low-dose-rate irradiation on lifespan. Young male B6C3F1/Jcl mice were divided randomly into two groups, which were fed either a low-calorie (65 kcal/ week) or high-calorie (95 kcal/week) diet. The latter is comparable to ad libitum feeding. The animals in the irradiated group were continuously exposed to gamma rays for 400 days at 20 mGy/day, resulting in a total dose of 8 Gy. Exposure and calorie restriction were initiated at 8 weeks of age and the diets were maintained for life. The life-shortening effects from chronic whole-body irradiation were compared between the groups. Body weights were reduced in calorie-restricted mice irrespective of radiation treatment. Radiation induced a shortened median lifespan in both groups, but to a greater extent in the calorie-restricted mice. These results suggest that calorie restriction may sensitize mice to chronic low-dose-rate radiation exposure to produce a life-shortening effect rather than alleviating the effects of radiation.

Purpose: To identify the influence of susceptibility artifact caused by commonly used trans-catheter embolic devices for vascular lesions in the body on the images of various magnetic resonance angiography (MRA) techniques as an aid to patient screening after endovascular embolization., Materials and Methods: We constructed vascular phantoms in which three embolic materials; platinum coil, Inconel coil, and vascular plug, were placed. Each phantom was imaged with three types of MRA techniques as follows: ultra-short echo time magnetic resonance imaging (UTE), three-dimensional fast advanced spin echo (3D-FASE), time-resolved contrast MRA with key hole technique (Key hole). For each embolic material, four reviewers compared the visual capabilities of the vessel lumen and surrounding area of each MRA technique by using a four-point visual scoring system. The quantitative values of susceptibility artifacts generated from each embolic material were compared between each MRA technique., Results: For all MRA techniques, the platinum coil showed the highest visual score (median=four-point) among all the embolic materials (p<0.05). In the platinum coil, the MR signal in the coil was clearly depicted in UTE. For all MRA technique, the quantitative values of the susceptibility artifacts were the lowest in platinum coil among all the embolic materials (p<0.05)., Conclusion: UTE is less susceptible to susceptibility artifact of embolic materials.

Our previous studies revealed that REIC/Dkk-3 was expressed various tissues, including skin keratinocytes. The aim of the present study was to identify the factors that regulate the expression of the dickkopf Wnt signaling pathway inhibitor 3 (REIC/Dkk‑3) tumor suppressor gene in normal human skin keratinocytes (NHKs). Several growth factors and cytokines that have previously been reported to be involved in the growth and differentiation of keratinocytes were screened as potential regulators. Western blot analysis was performed using protein from NHKs cultured with/without various factors including the epidermal growth factor, tumor necrosis factor‑α, transforming growth factor‑β, interleukin (IL)‑1F9, IL‑6, IL‑8 and Ca2+. The results indicated that only TNF‑α downregulated REIC/Dkk‑3 expression in NHKs. Subsequently, TNF‑α was confirmed to reduce the expression levels of REIC/Dkk‑3 in mouse skin tissue and hair culture models. TNF‑α‑mediated downregulation of REIC/Dkk‑3 expression in NHKs was abrogated by the addition of a TNF‑α‑specific antibody. In conclusion, the results indicate that TNF‑α downregulates REIC/Dkk‑3 expression in normal skin keratinocytes.

We investigated whether local-scale decontamination (removal of the litter layer, superficial soil layer, and understory) in a secondary forest contaminated by the Fukushima nuclear power plant accident reduced 137 Cs contamination of the soil and litter. We also measured 137 Cs concentrations in plants and in the web-building spider Nephila clavata (Nephilidae: Arachnida), as an indicator species, to examine 137 Cs contamination in arthropods. One month after decontamination, the total 137 Cs contamination (soil + litter) was reduced by 20% (100 kBq·m -2 ) relative to that in an adjacent untreated (i.e., contaminated) area, which was however not statistically significant. Four months after decontamination, 137 Cs in the decontaminated area had increased to a level similar to those in the untreated area, and the air radiation dose in the decontaminated area was about 2.1 μSv·h -1 , significantly higher than that in the untreated area (1.9 μSv·h -1 ). This may have been attributed to a torrential rain event. Although no statistically significant reduction was observed, most spiders had a lower 137 Cs contamination than that before the decontamination. This implied that the decontamination may have reduced 137 Cs transfer from soil via litter to N. clavata through the detrital food chains, but may not have reduced the amount of 137 Cs transfer through grazing food chains because the concentration of 137 Cs in living tree leaves was not reduced by the decontamination. In autumn, about 2 kBq·m -2 of 137 Cs was supplied from foliage to the ground by litterfall. The results suggested that removal of the litter and superficial soil layers in a contaminated forest may be ineffective. The present study suggests that the local-scale decontamination in a secondary forest had no effect on the reduction of 137 Cs contamination in the treated area., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The accident at the Fukushima Dai-ichi nuclear power plant seriously contaminated a large area in northeast Japan with a large amount of radioactive material. Consequently, various organisms, including arthropods, in the ecosystem have been contaminated with radiocesium ((137)Cs) through the food chain. We previously showed that the web spider Nephila clavata was contaminated with (137)Cs and that the level of contamination, which varied among spider individuals, was independent of the amount of prey consumed. The present study aimed to clarify the mechanisms that could determine the level of (137)Cs contamination in N. clavata. We first demonstrated the patterns of contents of over 30 elements in N. clavata that were collected at two forest sites (PS and ES) in Fukushima and then focused on the relationships between the contents of the alkali metals Li, Na, K, and Rb and the accumulation of (137)Cs in the spiders; Cs is an alkali metal and is expected to act similarly to Li, Na, K, and Rb. We also focused on the content of the non-alkali element, Cu, which is an essential element for oxygen transport in spiders. We found that Na content correlated positively with (137)Cs accumulation at both sites, which suggested that (137)Cs accumulation in N. clavata was related with the dynamics of Na. The K-, Rb-, and Cu-(137)Cs relationships were site specific; the relationships were significant at site PS, but not significant at site ES. Factors causing the site specific relationships and the probable pathway for (137)Cs transfer from soil to plants and then to higher trophic levels are discussed in terms of the transfer processes of the alkali metals., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We measured the concentrations of radiocesium ((134)Cs and (137)Cs) in a large web spider, Nephila clavata L. Koch (Nephilidae: Arachnida), collected at three sites at different distances from the Fukushima Dai-ichi Nuclear Power Plant about 1.5 y after the accident in March 2011. The radiocesium concentrations in spiders were highest in a streamside secondary forest 33 km northwest of the power plant: mean ± a standard deviation of 2.401 ± 1.197 Bq g(-1) dry for (134)Cs and 3.955 ± 1.756 Bq g(-1) dry for (137)Cs. In a hillside secondary forest 37 km northwest of the power plant, the mean concentrations of (134)Cs and (137)Cs were 0.825 ± 0.247 Bq g(-1) dry and 1.470 ± 0.454 Bq g(-1) dry, respectively. In a pine forest 62 km west of the power plant, very low radiocesium concentrations were detected, but in only a few individuals. The concentrations of (134)Cs and (137)Cs in spiders collected at each site tended to be correlated with the air radiation dose rate at each site. Since spiders are key components of food webs in forests, the high concentrations in this species at contaminated sites suggested that the radiocesium from the accident has transferred through food chains and reached to higher trophic level of the food chains., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Transcutaneous immunization (TCI) is an attractive alternative vaccination route compared to the commonly used injection systems. We previously developed a dissolving microneedle array for use as a TCI device, and reported that TCI with the dissolving microneedle array induced an immune response against model antigens. In the present study, we investigated the vaccination efficacy against tetanus and diphtheria, malaria, and influenza using this vaccination system. Our TCI system induced substantial increases in toxoid-specific IgG levels and toxin-neutralizing antibody titer and induced the production of anti-SE36 IgG, which could bind to malaria parasite. On influenza HA vaccination, robust antibody production was elicited in mice that provided complete protection against a subsequent influenza virus challenge. These findings demonstrate that TCI using a dissolving microneedle array can elicit large immune responses against infectious diseases. Based on these results, we are now preparing translational research for human clinical trials., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Because insect herbivores generally suffer from high mortality due to their natural enemies, reducing the risk of being located by natural enemies is of critical importance for them, forcing them to develop a variety of defensive measures. Larvae of leaf-mining insects lead a sedentary life inside a leaf and make conspicuous feeding tracks called mines, exposing themselves to the potential risk of parasitism. We investigated the defense strategy of the linear leafminer Ophiomyia maura Meigen (Diptera: Agromyzidae), by focusing on its mining patterns. We examined whether the leafminer could reduce the risk of being parasitized (1) by making cross structures in the inner area of a leaf to deter parasitoids from tracking the mines due to complex pathways, and (2) by mining along the edge of a leaf to hinder visually searching parasitoids from finding mined leaves due to effective background matching of the mined leaves among intact leaves. We quantified fractal dimension as mine complexity and area of mine in the inner area of the leaf as interior mine density for each sample mine, and analyzed whether these mine traits affected the susceptibility of O. maura to parasitism. Our results have shown that an increase in mine complexity with the development of occupying larvae decreases the probability of being parasitized, while interior mine density has no influence on parasitism. These results suggest that the larval development increases the host defense ability through increasing mine complexity. Thus the feeding pattern of these sessile insects has a defensive function by reducing the risk of parasitism.

A 55-year-old man was scheduled for resection of an adrenal tumor under the diagnosis of a non-functioning adrenal tumor. He was admitted for unstable angina 58 days preoperatively, and on the second hospital day, he had an episode of ventricular tachycardia for 20 seconds following epigastric pain. Abdominal computed tomography scans revealed a retroperitoneal abscess, which was subsequently drained effectively, and a right adrenal tumor. Because of the almost normal plasma catecholamine concentration, the tumor was considered a nonfunctioning tumor. However, when the surgeon manipulated the tumor during the operation, the patient's blood pressure increased suddenly to 240/120 mmHg. The hypertensive crisis was managed with nicardipine and phentolamine. After resection of the tumor, his blood pressure decreased to 80/40 mmHg, and the patient was treated with ephedrine, phenylephrine, and noradrenaline. After surgery, the tumor was confirmed histopathologically as a pheochromocytoma. The management of patients with a hypertensive crisis under suspicion of pheochromocytoma is discussed.

We report herein the case of a 46-year-old man who developed recurrences in both the incisional laparotomy wound of the abdominal wall and the stapled anastomotic site following ileo-colonic resection for cecum cancer. The patient had initially undergone laparoscopic surgery but had converted to conventional open surgery. Intestinal reconstruction had been performed by stapled functional end-to-end anastomosis between the ileum and ascending colon. The implantation of exfoliated cancer cells during the operation may have caused recurrence.

Genes involved in the degradation of fluorene to phthalate were characterized in the fluorene degrader Terrabacter sp. strain DBF63. The initial attack on both fluorene and 9-fluorenone was catalyzed by DbfA to yield 9-fluorenol and 1,1a-dihydroxy-1-hydro-9-fluorenone, respectively. The FlnB protein exhibited activities against both 9-fluorenol and 1,1a-dihydroxy-1-hydro-9-fluorenone to produce 9-fluorenone and 2'-carboxy-2,3-dihydroxybiphenyl, respectively. FlnD is a heteromeric protein encoded by flnD1 and ORF16, being a member of the class III two-subunit extradiol dioxygenase. FlnE was identified as a serine hydrolase for the meta-cleavage products that yield phthalate.

Amiodarone is an amphiphilic, iodinated, benzofuran derivative that is known to be effective for refractory ventricular tachyarrhythmia. Amiodarone also is known to cause a variety of side effects, related to its accumulation in multiple organs. The deposition of amiodarone and its metabolite, desethylamiodarone (DA), in liver elevates liver function tests and increases liver attenuation on computed tomography (CT). Although several groups have reported increased liver attenuation in patients receiving chronic amiodarone therapy, there is still no clear statistically significant relationship between liver CT attenuation and the cumulative dose of amiodarone, or between plasma levels of amiodarone and DA. CT scans were originally performed for the evaluation of pulmonary fibrosis in 13 patients (7 men and 6 women; mean age, 69.9 years, range 35 to 86 years) receiving chronic amiodarone therapy. Liver CT attenuation tended to increase in these patients. We found no significant correlation between liver CT attenuation and the cumulative dose of amiodarone. However, the CT attenuation of the liver was correlated significantly with the plasma level of amiodarone and DA. It was also suggested that liver CT scan is a useful means of evaluating the plasma levels of amiodarone and DA, and for estimating their deposition in liver.

2-Hydroxy-6-oxo-6-(2(')-aminophenyl)-hexa-2,4-dienoate hydrolases (CarC enzymes) from two carbazole-degrading bacteria were purified using recombinant Escherichia coli strains with the histidine (His)-tagged purification system. The His-tagged CarC (ht-CarC) enzymes from Pseudomonas resinovorans strain CA10 (ht-CarC(CA10)) and Janthinobacterium sp. strain J3 (ht-CarC(J3)) exhibited hydrolase activity toward 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate as the purified native CarC(CA10) did. ht-CarC(J3) was crystallized in the space group I422 with cell dimensions of a=b=130.3A, c=84.5A in the hexagonal setting, and the crystal structure of ht-CarC(J3) was determined at 1.86A resolution. The final refined model of ht-CarC(J3) yields an R-factor of 21.6%, although the electron-density corresponding to Ile146 to Asn155 was ambiguous in the final model. We compared the known structures of BphD from Rhodococcus sp. strain RHA1 and CumD from Pseudomonas fluorescens strain IP01. The backbone conformation of ht-CarC(J3) was better superimposed with CumD than with BphD(RHA1). The side-chain directions of Arg185 and Trp262 residues in the substrate binding pockets of these enzymes were different among these proteins, suggesting that these residues may take a conformational change during the catalytic cycles.

Methylobacillus sp. strain 12S produces an exopolysaccharide (EPS), methanolan, composed of glucose, mannose and galactose. Twenty-four ORFs flanking a Tn5 insertion site in an EPS-deficient mutant were identified, and 21 genes (epsCBAKLDEFGHIJMNOPQRSTU) were predicted to participate in methanolan synthesis on the basis of the features of the primary sequence. Gene disruption analyses revealed that epsABCEFGIJNOP and epsR are required for methanolan synthesis, whereas epsKD and epsH are not essential. EpsFG and EpsE showed homology with Wzc (chain length regulator) and Wza (export protein) of group 1 capsule-producing Escherichia coli, suggesting that methanolan was synthesized via a Wzy-like biosynthesis system. This possibility was supported by the fact that the putative hydropathy profiles of EpsH and EpsM were similar to those of Wzx and Wzy, which are also involved in the flipping of the repeating unit in the cytoplasmic membrane and the polymerization of the capsule in the Wzy-dependent system. EpsBJNOP and EpsR are probably glycosyltransferases involved in the synthesis of the repeating unit onto the lipid carrier. In particular, EpsB appeared to catalyse the initial transfer of the glucose moiety. On the basis of their predicted location in the cells, it is proposed that EpsI and EpsL are involved in methanolan export to the cell surface. E. coli strains expressing EpsQ, EpsS and EpsT showed enhanced activities of GDP-mannose pyrophosphorylase, UDP-galactose 4-epimerase and UDP-glucose pyrophosphorylase, respectively, revealing that they were responsible for the production of the activated compositional sugars of methanolan. EpsU contains a conserved a lytic transglycosylase motif, indicating that it could participate in the degradation of polysaccharides. EpsA and EpsK, which have conserved DNA-binding and cAMP-binding motifs, respectively, were deduced to be transcriptional regulators. In particular, EpsA seems to positively regulate the transcription of methanolan synthesis genes, since the constitutive expression of epsA in strain 12S increased the EPS production. Interestingly, EpsD showed homology with peptidyl prolyl cis-trans isomerases that catalyse the folding of proteins following translocation across the cytoplasmic membrane.

Effects of lead nitrate (LN), a hepatic mitogen, on hepatic gene expressions of lanosterol 14alpha-demethylase (CYP51) and the sterol regulatory element binding proteins (SREBP-1a, SREBP-1c and SREBP-2), which are thought to be transcription factors for hepatic CYP51 gene, were examined by the methods of Northern blot and/or real time reverse transcriptase-polymerase chain reaction (RT-PCR). In both immature (4-week-old) and mature (7-week-old) rats, LN treatment resulted in definite increases in hepatic gene expression of CYP51 at 12 h and in the liver weight at 48 h. As for transcription factors for the CYP51 gene, enhanced gene expression of SREBP-2 was observed 6-12 h after LN treatment, whereas no enhanced gene expression of other SREBPs, SREBP-1a and SREBP-1c, was observed at any time after the treatment; for SREBP-1a, there was no significant change; for SREPB-1c, there was a drastic decrease. In addition, the serum total cholesterol level was increased 12 h after LN treatment to 7-week-old rats, and the increased level was maintained at least up to 48 h later. In the present study, we demonstrate for the first time that LN, a heavy-metal ion, activates the expression of the SREBP-2 and CYP51 genes without decreasing the serum total cholesterol level and further suggest that only SREBP-2 among SREBPs might play an important role in the LN-enhanced CYP51 gene expression.

We report the case of a 29-year old female who developed a fixed drug eruption due to ephedrine hydrochloride administered intravenously during the cesarean section. On the day of the operation a palm-sized dark brown macula with half egg-sized erosion appeared on her right lower thigh. We diagnosed her disease as fixed drug eruption and examined the causative agent among all the 14 drugs used from admission to the appearance of fixed drug eruption. Each of systemic challenge, patch test on the lesion, intradermal and subcutaneous injection on the lesion with ephedrine hydrochloride showed positive reaction. As far as we have been able to search, our case is the first one of fixed drug eruption due to ephedrine hydrochloride.

The management of postoperative rectovaginal fistula (RVF) after low anterior resection for rectal cancer is difficult and the results are often unsatisfactory. Among 140 patients with rectal cancer who underwent low anterior resection with a double-stapled anastomosis at our hospital between 1986 and 1996, 4 (2.9%) developed RVF as a postoperative complication. The RVF developed gradually from 9 to 128 days after low anterior resection. We describe herein our technique of using a modified transvaginal approach for RVF repair with a diverting colostomy. In all four patients, the RVFs were completely eradicated with reestablishment of intestinal continuity and did not recur during the mean follow-up period of 29.5 months, ranging from 12 to 67 months. This report serves to demonstrate that emerging RVFs secondary to stapled anastomosis in low anterior resection for rectal cancer must be recognized, and that a modified transvaginal approach provides an effective method of repair.

Effects of aminoguanidine (AG) on binding of glucose and pyridoxal phosphate (PLP) to albumin, and on glycation reaction of cytosolic aspartate aminotransferase (cAST) were examined in an in vitro system. AG was found to inhibit not only glycation of albumin but binding of PLP to albumin, indicating that distribution of PLP into tissues is inhibited by AG. AG bound to PLP directly to produce a new compound, and in this manner AG inhibited cAST activity. AG could also inhibit glycation of cAST and the extent of inhibition was varied with sugars used. It appears that, although AG is a useful inhibitor of glycation proteins, it may be toxic from the viewpoints of vitamin B6 as an essential nutrient and also PLP-dependent enzymes.

The analysis of kinetic rate constants in the compartment model for [18F]fluorodeoxyglucose (FDG) was undertaken. Four kinetic rate constants were determined with a least square fitting package SALS (Statistical Analysis with Least Squares), using the measured data of 18F activity as a function of time. SALS calculations were found to be easy and quick with high precision. The rate constants and the curves fitted by the k3 and the k4 models were compared in situations with various degree of cerebral glucose metabolism during positron emission tomography (PET) studies. The k4 model in the determination of cerebral metabolic rate for glucose (CMRglu) was much superior than the k3 model in any given situation as it always underestimates the metabolic rate. However, the k3 model produces less variation when the cerebral radioactivity curve shows steady rising pattern.