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A 77-year-old woman with Sjögren's syndrome has been followed for mild interstitial pneumonia. A 2-cm pulmonary nodule was incidentally found in the left lower lobe, and positron emission tomography-computed tomography showed (18)F-fluorodeoxyglucose uptake with a maximum standardized uptake value of 8.78 in this nodule. Although this suggested a malignant disease, transbronchial biopsy of the nodule revealed that it was cholesterol granuloma. It is known that some benign inflammatory diseases show an increased uptake of (18)F-fluorodeoxyglucose, particularly granulomatous lesions like tuberculosis. To our knowledge, this is the first report of (18)F-fluorodeoxyglucose-positron emission tomography findings for cholesterol granuloma. We speculate that increased (18)F-fluorodeoxyglucose uptake with cholesterol granuloma occurs through cellular infiltration and macrophage proliferation, resulting in the activation of glycolysis-like tuberculosis.

The effect of radiation on the intestine has been studied for more than one hundred years. It remains unclear, however, whether this organ uses specific defensive mechanisms against ionizing radiation. The infection with Pseudomonas aeruginosa (PA14) in Caenorhabditis elegans induces up-regulation of innate immune response genes. Here, we found that exposure to ionizing radiation also induces certain innate immune response genes such as F49F1.6 (termed mul-1), clec-4, clec-67, lys-1 and lys-2 in the intestine. Moreover, pre-treatment with ionizing radiation before seeding on PA14 lawn plate significantly increased survival rate in the nematode. We also studied transcription pathway of the mul-1 in response to ionizing radiation. Induction of mul-1 gene was highly dependent on the ELT-2 transcription factor and p38 MAPK. Moreover, the insulin/IGF-1 signal pathway works to enhance induction of this gene. The mul-1 gene showed a different induction pattern from the DNA damage response gene, ced-13, which implies that the expression of this gene might be triggered as an indirect effect of radiation. Silencing of the mul-1 gene led to growth retardation after treatment with ionizing radiation. We describe the cross-tolerance between the response to radiation exposure and the innate immune system.

Conclusion: We conclude that intra-arterially injected cisplatin passed via lymph flow into sentinel nodes (SNs) as the platinum concentration in the SNs was higher than that in the non-sentinel nodes (NSNs). It is possible that preoperative intra-arterial chemotherapy targeting primary cancer also has a therapeutic effect on subclinical metastatic SNs., Objectives: Intra-arterial chemoradiotherapy has been reported to be effective against not only primary tumors but also nodal metastases. We considered the hypothesis that intra-arterially injected cisplatin passed via lymph flow into regional nodes. This study aimed to investigate intra-arterially injected cisplatin distribution to regional nodes by comparing platinum concentrations in SNs and NSNs., Methods: Five patients with T1-2 N0 tongue cancer were treated with preoperative intra-arterial chemotherapy (cisplatin, 100 mg/m(2)) targeting primary cancer. Partial glossectomy together with SN biopsy and elective neck dissection were performed 2 weeks after intra-arterial chemotherapy. Platinum concentrations in the lymph nodes were measured using a Zeeman atomic absorption spectrometer., Results: Thirteen SNs were harvested together with eight NSNs from the areas adjacent to the SNs. Platinum concentrations were then measured, revealing a significant difference in platinum concentration between the SNs and the NSNs (mean ± SD, 0.682 ± 0.246 µg/g vs 0.506 ± 0.274 µg/g; p = 0.049).

Concomitant radiotherapy and superselective arterial infusion of cisplatin for laryngeal cancer has shown excellent therapeutic outcomes. It is expected to be a reasonable treatment option for laryngeal cancer, especially in locally advanced cases.

This retrospective study aimed to compare the accuracy of two nodal evaluation criteria using computed tomography after intra-arterial chemoradiation in node-positive head and neck squamous cell carcinomas. Computed tomography was used to evaluate radiographic nodal response 4-8 weeks after intra-arterial chemoradiation. We compared the accuracy of two different criteria: criterion 1 (radiographic complete response was recorded in the absence of focal abnormalities and if the maximum diameter of the metastatic node was less than 15 mm), and criterion 2 (radiographic complete response was recorded in the absence of focal abnormalities and if the minimum diameter of metastatic nodes was less than 7 mm in level II and if the minimum diameter of metastatic nodes in the rest of the neck was less than 6 mm). Positive predictive values were criterion 1: 69.2%, criterion 2: 47.8%; negative predictive values were criterion 1: 88.5%, criterion 2: 90.5%. Positive likelihood ratios were criterion 1: 7.50, criterion 2: 3.06. The difference between each criteria was statistically significant using McNemar's test (p = 0.0016). Computed tomography evaluation accuracy of nodal response after intra-arterial chemoradiation was comparable to recent reports, and it was feasible to perform salvage neck dissection by computed tomography evaluation for nodal response. We recommend using criterion 1 because of its simplicity and reliability.

Sclerosing mesenteritis is a rare inflammatory and fibrosing disorder of unknown etiology, while IgG4-related disease (IgG4-RD) consists of mass-forming, fibroinflammatory lesions characterized by high serum IgG4 levels and tissue infiltration of many IgG4-positive plasma cells; obliterative phlebitis is common. This report describes a case of sclerosing mesenteritis that was considered a manifestation of IgG4-RD. A 53-year-old man underwent right hemicolectomy because of an ileocecal mass that did not improve with conservative therapy. The ill-defined fibroinflammatory lesion extended in the mesentery with storiform fibrosis, obliterative phlebitis, and infiltration of many IgG4-positive plasma cells. The ratio of IgG4-positive/IgG-positive cells was 64%, and the ratio of forkhead box protein 3 (FOXP3)-positive/CD4-positive cells was elevated (13%). It is likely that at least some cases of sclerosing mesenteritis are a manifestation of IgG4-RD. It is important to investigate this relationship because steroid therapy may benefit such cases., (© 2012 The Authors. Pathology International © 2012 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.)

Tardigrades are tiny (less than 1 mm in length) invertebrate animals that have the potential to survive travel to other planets because of their tolerance to extreme environmental conditions by means of a dry ametabolic state called anhydrobiosis. While the tolerance of adult tardigrades to extreme environments has been reported, there are few reports on the tolerance of their eggs. We examined the ability of hydrated and anhydrobiotic eggs of the tardigrade Ramazzottius varieornatus to hatch after exposure to ionizing irradiation (helium ions), extremely low and high temperatures, and high vacuum. We previously reported that there was a similar pattern of tolerance against ionizing radiation between hydrated and anhydrobiotic adults. In contrast, anhydrobiotic eggs (50% lethal dose; 1690 Gy) were substantially more radioresistant than hydrated ones (50% lethal dose; 509 Gy). Anhydrobiotic eggs also have a broader temperature resistance compared with hydrated ones. Over 70% of the anhydrobiotic eggs treated at either -196°C or +50°C hatched successfully, but all the hydrated eggs failed to hatch. After exposure to high-vacuum conditions (5.3×10(-4) Pa to 6.2×10(-5) Pa), the hatchability of the anhydrobiotic eggs was comparable to that of untreated control eggs.

To clarify the relative biological effectiveness (RBE) values of carbon ion (C) beams in normal brain tissues, a rat organotypic slice culture system was used. The cerebellum was dissected from 10-day-old Wistar rats, cut parasagittally into approximately 600-µm-thick slices and cultivated using a membrane-based culture system with a liquid-air interface. Slices were irradiated with 140 kV X-rays and 18.3 MeV/amu C-beams (linear energy transfer = 108 keV/µm). After irradiation, the slices were evaluated histopathologically using hematoxylin and eosin staining, and apoptosis was quantified using the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. Disorganization of the external granule cell layer (EGL) and apoptosis of the external granule cells (EGCs) were induced within 24 h after exposure to doses of more than 5 Gy from C-beams and X-rays. In the early postnatal cerebellum, morphological changes following exposure to C-beams were similar to those following exposure to X-rays. The RBEs values of C-beams using the EGL disorganization and the EGC TUNEL index endpoints ranged from 1.4 to 1.5. This system represents a useful model for assaying the biological effects of radiation on the brain, especially physiological and time-dependent phenomena.

In this study, a three-dimensional finite-element model of the passive human cochlea was created. Dynamic behavior of the basilar membrane caused by the vibration of the stapes footplate was analyzed considering a fluid-structure interaction with the cochlear fluid. Next, the effects of a perilymphatic fistula (PLF) on the vibration of the cochlea were examined by making a small hole on the wall of the cochlea model. Even if a PLF existed in the scala vestibuli, a traveling wave was generated on the basilar membrane. When a PLF existed at the basal end of the cochlea, the shape of the traveling wave envelope showed no remarkable change, but the maximum amplitude became smaller at the entire frequency range from 0.5 to 5kHz and decreased with decreasing frequency. In contrast, when a PLF existed at the second turn of the cochlea, the traveling wave envelope showed a notch at the position of the PLF and the maximum amplitude also became smaller. This model assists in elucidating the mechanisms of hearing loss due to a PLF from the view of dynamics., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The treatment of base of tongue (BOT) cancer is highly controversial with differing options according to individual institutions, or the primary surgical or radiation therapy bias. We aimed to determine patient outcomes and discuss technical aspects following treatment with concurrent radiation therapy and targeted cisplatin chemotherapy (RADPLAT). We utilized RADPLAT for the definitive treatment of patients with BOT cancers. The 5-year local control and overall survival rate was 92.3% and 90.9% for all patients, respectively, and all surviving patients achieved normal swallowing without a feeding-tube and normal speech without tracheostoma after treatment. Our study found that RADPLAT gave excellent survival rates and organ functions for patients with BOT cancers. We consider that BOT cancer is a good indication for RADPLAT and that the angiographic technique and patient selection are keys to success., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The movements of 28 adult chum salmon, Oncorhynchus keta (Walbaum) tagged with electromyogram (EMG) transmitters were tracked along the Toyohira river, Hokkaido, Japan, in October of 2007 and 2008 to investigate and evaluate the upstream migratory behavior through the protection bed and fishway of ground sills. The approach time of fish that ascended successfully through the protection bed and fishway was shorter than that of unsuccessful fish. The unsuccessful fish were observed to swim in currents with high water velocity and shallow water depth at swimming speeds that exceeded their critical swimming speed (U (crit)) during the approach to these structures. In consequence, unsuccessful fish frequently alternated between burst and maximum sustained speeds without ever ascending the fishway, and eventually became exhausted. It is important that fishway are constructed to enable chum salmon to find a passage way easily, so that they can migrate upstream rapidly without wasting excessive energy.

Background: The number of older adults is growing rapidly. This fact, combined with the high rates of suicide in later life, indicates that many more older adults will die by their own hands before rigorous trials can be conducted to fully understand the best approaches to prevent late life suicide., Aims: To disseminate key considerations for interventions addressing senior suicidal behavior., Methods: An international expert panel has reviewed and discussed key considerations for interventions against suicide in older adults based on existing evidence, where available, and expert opinion., Results: A set of new key considerations is divided into: universal, selective, and indicated prevention as well as a section on general considerations., Conclusions: The suggestions span a wide range and are offered for consideration by local groups preparing new interventions, as well as large scale public health care planning.

Anhydrobiotic chironomid larvae can withstand prolonged complete desiccation as well as other external stresses including ionizing radiation. To understand the cross-tolerance mechanism, we have analyzed the structural changes in the nuclear DNA using transmission electron microscopy and DNA comet assays in relation to anhydrobiosis and radiation. We found that dehydration causes alterations in chromatin structure and a severe fragmentation of nuclear DNA in the cells of the larvae despite successful anhydrobiosis. Furthermore, while the larvae had restored physiological activity within an hour following rehydration, nuclear DNA restoration typically took 72 to 96 h. The DNA fragmentation level and the recovery of DNA integrity in the rehydrated larvae after anhydrobiosis were similar to those of hydrated larvae irradiated with 70 Gy of high-linear energy transfer (LET) ions ((4)He). In contrast, low-LET radiation (gamma-rays) of the same dose caused less initial damage to the larvae, and DNA was completely repaired within within 24 h. The expression of genes encoding the DNA repair enzymes occurred upon entering anhydrobiosis and exposure to high- and low-LET radiations, indicative of DNA damage that includes double-strand breaks and their subsequent repair. The expression of antioxidant enzymes-coding genes was also elevated in the anhydrobiotic and the gamma-ray-irradiated larvae that probably functions to reduce the negative effect of reactive oxygen species upon exposure to these stresses. Indeed the mature antioxidant proteins accumulated in the dry larvae and the total activity of antioxidants increased by a 3-4 fold in association with anhydrobiosis. We conclude that one of the factors explaining the relationship between radioresistance and the ability to undergo anhydrobiosis in the sleeping chironomid could be an adaptation to desiccation-inflicted nuclear DNA damage. There were also similarities in the molecular response of the larvae to damage caused by desiccation and ionizing radiation.

This retrospective study aimed to assess the role of salvage surgery for local recurrence in hypopharyngeal cancer (HPC) patients who had received radiotherapy (RT) or concomitant chemoradiotherapy (CRT) as an initial treatment. The local recurrence rate, salvage rate after local recurrence and overall survival rate were investigated in 104 HPC patients who received treatment between 1991 and 2005. Local recurrence in the primary site was observed in 41 patients (rate, 39.4%) of whom only 12 could undergo further salvage surgery. Disease control was achieved in seven of these patients (successful salvage rate, 17.1%). The 5-year overall survival rate was 40.6% in the RT/CRT patient group and successful salvage rates for T1, T2, T3 and T4 primary disease were 33.3% (1/3), 20.0% (4/20), 16.7% (2/12) and 0% (0/6), respectively. Severe postoperative complications such as pharyngo-cutaneous fistula were seen in six patients (50.0%). Prognosis of patients with locally recurring HPC after RT/CRT is poor at any primary T-stage and the incidence of postoperative complication is relatively high. This should be taken into consideration when the initial treatment plan is decided and the choice of salvage surgery for such recurrent cases should be carefully determined.

Inflammatory pseudotumor is an idiopathic granuloma characterized by infiltrative proliferation of inflammatory cells and myofibroblastic cells, as well as locally aggressive features, clinically and radiologically mimicking a neoplastic process. The occurrence of inflammatory pseudotumor in the head and neck area is uncommon, especially in the parapharyngeal space. The case of a 54-year-old female with inflammatory pseudotumor of the parapharyngeal space is presented. The patient initially complained of hoarseness, dysarthria, aspiration, and hearing impairment. MRI disclosed an expansive soft mass in the parapharyngeal space encompassing the carotid arteries. Histopathologically, the lesions were composed of numerous plasma cells, lymphocytes, histiocytes, and spindle myofibroblastic cells, showing perineural infiltration of inflammatory cells. The patients' symptoms, including conductive hearing loss, improved dramatically with reduction in lesion size after corticosteroid treatment., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Comorbidity has an impact on survival in laryngeal cancer in several reports. However, the importance of comorbidity in hypopharyngeal cancer (HPC) has not been reported., Methods: A retrospective medical record review of 156 patients with HPC treated between 1995 and 2005 was performed. Comorbid illness was measured by the Adult Comorbidity Evaluation-27. A Cox proportional hazards model was used to determine the factors related to overall survival., Results: Comorbidity was absent in 55 (35.2%) of the patients, mild in 39 (25%), moderate in 28 (17.9%), and severe in 34 (21.8%). There were statistically significant differences between the survival rates in accord with age, stage, subsite, and comorbidity (45.1% for none or mild vs 27.7% for moderate or severe; p = .0073). Age, stage, and comorbidity were identified as independent prognostic factors in the multivariate analysis., Conclusion: Comorbidity, along with the clinical stage, should be considered in treatment planning for patients with HPC., (Copyright 2009 Wiley Periodicals, Inc.)

The study of radiation effect in Caenorhabditis (C.) elegans has been carried out over three decades and now allow for understanding at the molecular, cellular and individual levels. This review describes the current knowledge of the biological effects of ionizing irradiation with a scope of the germ line, aging and behavior. In germ cells, ionizing radiation induces apoptosis, cell cycle arrest and DNA repair. Lots of molecules involved in these responses and functions have been identified in C. elegans, which are highly conserved throughout eukaryotes. Radiosensitivity and the effect of heavy-ion microbeam irradiation on germ cells with relationship between initiation of meiotic recombination and DNA lesions are discussed. In addition to DNA damage, ionizing radiation produces free radicals, and the free radical theory is the most popular aging theory. A first signal transduction pathway of aging has been discovered in C. elegans, and radiation-induced metabolic oxidative stress is recently noted for an inducible factor of hormetic response and genetic instability. The hormetic response in C. elegans exposed to oxidative stress is discussed with genetic pathways of aging. Moreover, C. elegans is well known as a model organism for behavior. The recent work reported the radiation effects via specific neurons on learning behavior, and radiation and hydrogen peroxide affect the locomotory rate similarly. These findings are discussed in relation to the evidence obtained with other organisms. Altogether, C. elegans may be a good "in vivo" model system in the field of radiation biology.

Background: In addition to implementing a depression screening program, conducting a survey beforehand might contribute to suicide risk reduction for the elderly., Aims: This study evaluates outcomes of a community-based program to prevent suicide among individuals aged 60 and over, using a quasiexperimental design with an intervention region (41,337 residents, 35.1% aged 60 and over) and a neighboring reference region., Methods: Our 2-year intervention program included an anonymous survey by random sample in the entire intervention region and, in the second year, a depression screening with follow-up by a psychiatrist in the higher-risk districts. Changes in the risk of completed suicide were estimated by the incidence-rate ratio (IRR)., Results: The risk for men in the intervention region was reduced by 61% (age-adjusted IRR = 0.39; 90% CI = 0.18-0.87), whereas there was a (statistically insignificant) 51% risk reduction for women in the intervention region, and no risk reduction for either men or women in the reference region. The ratio of the crude IRR for elderly men in the intervention region to that for all elderly men in Japan was estimated at 0.42 (90% CI = 0.18-0.92), showing that the risk reduction was greater than the national change., Conclusions: The management of depression through a combination of an initial survey and subsequent screening holds clear promise for prompt effectiveness in the prevention of suicide for elderly men, and potentially for women.

Purpose: Recently carbon-ion beams have been reported to be remarkably effective for controlling various cancers with less toxicity and are thought to be a promising modality for cancer treatment. However, the biological effect of carbon-ion beams arising on normal neuron remains unknown. Therefore, this study was undertaken to investigate the effect of carbon-ion beams on neurons by using both morphological and functional assays., Materials and Methods: Dorsal root ganglia (DRG) and sympathetic ganglion chains (SYMP) were isolated from day-8 and day-16 chick embryos and cultured for 20 h. Cultured neurons were exposed to carbon-ion beams and X-rays. Morphological changes, apoptosis and cell viability were evaluated with the Growth Cone Collapse (GCC), Terminal deoxynucleotidyl Transferase (TdT)-mediated deoxyUridine TriPhosphate (dUTP) nick End Labeling [TUNEL] assay and 4-[3-(4-iodophenyl)- 2-(4-nitrophenyl)- 2H-5-tetrazolio]- 1,3-benzenedisulfonate [WST-1] assays, respectively., Results: Irradiation caused GCC and neurite destruction on a time- and irradiation dose-dependent manner. Changes in morphological characteristics were similar following either irradiation. Morphological and functional assays showed that day-8 neurons were more radiosensitive than day-16 neurons, whereas, radiosensitivity of DRG was comparable to that of SYMP. The dose-response fitting curve utilising both GCC and TUNEL labeling index showed higher relative biological effectiveness (RBE) values were associated with lower lethal dose (LD) values, while lower RBE was associated with higher LD values., Conclusion: Exposure to high-linear energy transfer (LET) irradiation is up to 3.2 more efficient to induce GCC and apoptosis, in early developed neuronal cells, than low-LET irradiation. GCC is a reliable method to assess the radiobiological response of neurons.

Using heavy-ion microbeam, we report target irradiation of selected compartments within the diapause-terminated egg and its mutational consequences in the silkworm, Bombyx mori. On one hand, carbon-ion exposure of embryo to 0.5-6 Gy increased the somatic mutation frequency, suggesting targeted radiation effects. On the other, such increases were not observed when yolk was targeted, suggesting a lack of nontargeted bystander effect.

Objective: To determine patient-perceived voice-related quality of life in patients treated with various methods based on the results of Voice-Related Quality of Life (VRQOL) and Voice Handicap Index-10 (VHI-10) questionnaires., Design: The VRQOL and VHI-10 questionnaires., Setting: University hospital., Patients: One hundred thirty-seven patients who had received definitive treatment of laryngeal cancer were followed-up at Hokkaido University Hospital, Sapporo, Japan, and were alive with no evidence of malignancy at the time of the survey., Main Outcome Measure: Patient-perceived voice-related quality of life based on the results of the VRQOL and VHI-10 questionnaires., Results: The mean VRQOL scores for patients who had undergone radiotherapy (n = 63), chemoradiotherapy (n = 29), laser surgery (n = 14), or total laryngectomy (n = 27) as final treatment of laryngeal cancer were 92.6, 92.9, 85.5, and 68.4, respectively; the mean VHI-10 scores were 2.87, 2.34, 5.43, and 11.26, respectively., Conclusion: The VRQOL and VHI-10 questionnaires are important in judging the overall effectiveness of treatment options for laryngeal cancer.

Cells exposed to genotoxic stress, such as ionizing radiation and DNA damaging reagents, either arrest the cell cycle to repair the genome, or undergo apoptosis, depending on the extent of the DNA damage. DNA damage also has been implicated in various differentiation processes. It has been reported that gamma-ray exposure or treatment with DNA-damaging agents could induce myogenic differentiation in Drosophila Schneider cells. However, the mechanism underlying this process has been poorly understood. In this study, exposure of Schneider cells to X-rays or energetic carbon ion beams caused increase of TUNEL-positive cells and conversion of round-shaped cells to elongated cells. Both upregulation of genes related to myogenesis and increase of myosin indicate that the radiation-induced morphological changes of Schneider cells were accompanied with myogenic differentiation. Because the intracellular ceramide was increased in Schneider cells after exposure to X-ray, we examined whether exogenous ceramide could mimic radiation-induced myogenic differentiation. Addition of membrane-permeable C(2)-ceramide to Schneider cells increased apoptosis and expression of myogenic genes. These results suggest that ceramide plays important roles in both apoptosis and the radiation-induced myogenic differentiation process.

In order to study the radiobiological effects of low dose radiation, microbeam irradiation facilities have been developed in the world. This type of facilities now becomes an essential tool for studying bystander effects and relating signaling phenomena in cells or tissues. This review introduces you available microbeam facilities in Japan and in China, to promote radiobiology using microbeam probe and to encourage collaborative research between radiobiologists interested in using microbeam in Japan and in China.

Objectives: To evaluate the risk factors for perioperative complications among patients undergoing craniofacial resection for the treatment of skull base tumors., Design: Retrospective analysis., Participants: The study group comprised 29 patients with skull base tumors (22 malignant and 7 benign) who underwent 30 craniofacial resections at Hokkaido University Hospital between 1989 and 2006. Of these cases, 21 had undergone prior treatment by radiation (16 cases), surgery (7 cases), or chemotherapy (1 case). Moreover, 19 needed extended resection involving the dura (11 cases), brain (5 cases), orbit (12 cases), hard palate (5 cases), skin (3 cases), or cavernous sinus (2 cases)., Main Outcome Measures: Perioperative complications and risk factor associated with their incidence., Results: Perioperative complications occurred in 12 patients (40%; 13 cases). There was a significant difference between complication rates for cases with and without prior therapy (52.4% vs. 11.1%). The complication rate for dural resection cases was 81.8%. There was a significant difference between complication rates for cases with and without dura resection. No postoperative mortality was reported., Conclusions: Craniofacial resection is a safe and effective treatment for skull base tumors. However, additional care is required in patients with extended resection (especially dural) and those who have undergone prior therapy.

Locomotory behavior (motility) and mechanosensation are of vital importance in animals. We examined the effects of ionizing radiation (IR) on locomotory behavior and mechanosensation using a model organism, the nematode Caenorhabditis elegans. Bacterial mechanosensation in C. elegans induces the dopamine-mediated slowing of locomotion in the presence of bacteria (food), known as the basal slowing response. We previously reported an IR-induced reduction of locomotory rate in the absence of food. In the present study, we observed a similar IR-induced reduction of locomotory rate in the cat-2 mutant, which is defective in bacterial mechanosensation. The dose response pattern of the locomotory rate in the presence of food was relatively flat in wild-type animals, but not in cat-2 mutants. This suggests that the dopamine system, which is related to bacterial mechanosensation in C. elegans, might have a dominant effect on locomotory rate in the presence of food, which masks the effects of other stimuli. Moreover, we found that the behavioral responses of hydrogen peroxide-exposed wild-type animals are similar to those of IR-exposed animals. Our findings suggest that the IR-induced reduction of locomotory rate in the absence of food is mediated by a different pathway from that for bacterial mechanosensation, at least partially through IR-produced hydrogen peroxide.

Recently, SJL/J mice have been used as an animal model in studies of dysferlinopathy, a spectrum of muscle diseases caused by defects in dysferlin protein. In this study we irradiated muscle fibers isolated from skeletal muscle of SJL/J mice with heavy-ion microbeam, and the ultrastructural changes were observed by electron microscopy. The plasma membrane of heavy-ion beam irradiated areas showed irregular protrusions and invaginations. Disruption of sarcomeric structures and the enhancement of autophagy were also observed. In addition, many vesicles of varying size and shape were seen to be accumulated just beneath the plasma membrane. This finding further supports the recent hypothesis that dysferlin functions as a membrane fusion protein in the wound healing system of plasma membrane, and that the defect in dysferlin causes insufficient membrane fusion resulting in accumulation of vesicles.

Background and Purpose: Overexpression of Bcl-2 is frequent in human cancers and has been associated with radioresistance. Here we investigated the potential impact of heavy ions on Bcl-2 overexpressing tumors., Materials and Methods: Bcl-2 cells (Bcl-2 overexpressing HeLa cells) and Neo cells (neomycin resistant gene-expressing HeLa cells) exposed to gamma-rays or heavy ions were assessed for the clonogenic survival, apoptosis and cell cycle distribution., Results: Whereas Bcl-2 cells were more resistant to gamma-rays (0.2keV/microm) and helium ions (16.2keV/microm) than Neo cells, heavy ions (76.3-1610keV/microm) yielded similar survival regardless of Bcl-2 overexpression. Carbon ions (108keV/microm) decreased the difference in the apoptotic incidence between Bcl-2 and Neo cells, and prolonged G(2)/M arrest that occurred more extensively in Bcl-2 cells than in Neo cells., Conclusions: High-LET heavy ions overcome tumor radioresistance caused by Bcl-2 overexpression, which may be explained at least in part by the enhanced apoptotic response and prolonged G(2)/M arrest. Thus, heavy-ion therapy may be a promising modality for Bcl-2 overexpressing radioresistant tumors.

This is the first study to demonstrate that the small-molecule Bcl-2 inhibitor HA14-1 renders human cervical cancer cells and their Bcl-2 overexpressing radioresistant counterparts, but not normal fibroblasts, more susceptible to heavy ions. Thus, Bcl-2 may be an attractive target for improving the efficacy of heavy-ion therapy.

A systematic review was undertaken to quantify the effect of community-based depression screening (CDS) with follow-up on the completed suicide risk for residents aged 65 and over. Five quasi-experimental studies in Japanese regions with high suicide rates were included in the meta-analysis. Combined incidence rate ratios (95% confidence intervals) by the Mantel-Haenszel method and by the DerSimonian-Laird method in two homogenous studies implementing the follow-up conducted by psychiatrists were 0.30 (0.13-0.68) and 0.33 (0.14-0.80) in men, and 0.33 (0.19-0.58) and 0.33 (0.19-0.60) in women, respectively; and those in three homogenous studies implementing the follow-up conducted by general practitioners were 0.73 (0.45-1.18) and 0.74 (0.45-1.23) in men, and 0.36 (0.21-0.60) and 0.39 (0.22-0.66) in women, respectively. There are very few studies included, however, to demonstrate an association between CDS and the reduced risk, suggesting gender difference in the effectiveness.

Here, we investigated the cell killing effectiveness of heavy-ion radiation in Bcl-2 overexpressing radioresistant tumor cells. First, irradiated cells underwent primary colony formation. Radioresistance decreased with increasing linear energy transfer (LET), indicating that heavy ions may be a promising therapeutic modality for Bcl-2 overexpressing tumors. Second, cells in primary colonies were reseeded for secondary colony formation. The incidence of delayed reproductive death increased with LET irrespective of Bcl-2 overexpression, suggesting that Bcl-2 overexpression may not facilitate heavy ion-induced genomic instability.

Histological analyses of glioblastoma cells after carbon-ion exposure are still limited and ultrastructural characteristics have not been investigated in detail. Here we report the results of morphological and morphometric analyses of a human glioblastoma cell line, CGNH-89, after ionizing radiation to characterize the effect of a carbon-beam on glioblastoma cells. Using CGNH-89 cells exposed to 0-10 Gy of X-ray (140 kVp) or carbon-ions (18.3 MeV/nucleon, LET=108 keV/microm), we performed conventional histology and immunocytochemistry with MIB-1 antibody, transmission electron microscopy, and computer-assisted, nuclear size measurements. CGNH-89 cells with a G to A transition in codon 280 in exon 8 of the TP53 gene had nuclei with pleomorphism, marked nuclear atypia and brisk mitotic activity. After carbon-ion and X-ray exposure, living cells showed decreased cell number, nuclear condensation, increased atypical mitotic figures, and a tendency of cytoplasmic enlargement at the level of light microscopy. The deviation of the nuclear area size increased during 48 h after irradiation, while the small cell fraction increased in 336 h. In glioblastoma cells of the control, 5 Gy carbon-beam, and 10 Gy carbon-beam, and MIB-1 labeling index decreased in 24 h (12%, 11%, 7%, respectively) but increased in 48 h (10%, 20%, 21%, respectively). Ultrastructurally, cellular enlargement seemed to depend on vacuolation, swelling of mitochondria, and increase of cellular organelles, such as the cytoskeleton and secondary lysosome. We could not observe apoptotic bodies in the CGNH-89 cells under any conditions. We conclude that carbon-ion irradiation induced cell death and senescence in a glioblastoma cell line with mutant TP53. Our results indicated that the increase of large cells with enlarged and bizarre nuclei, swollen mitochondria, and secondary lysosome occurred in glioblastoma cells after carbon-beam exposure.

Evidence has accumulated that ionizing radiation induces biological effects in non-irradiated bystander cells having received signals from directly irradiated cells; however, energetic heavy ion-induced bystander response is incompletely characterized. Here we performed microarray analysis of irradiated and bystander fibroblasts in confluent cultures. To see the effects in bystander cells, each of 1, 5 and 25 sites was targeted with 10 particles of carbon ions (18.3 MeV/u, 103 keV/microm) using microbeams, where particles traversed 0.00026, 0.0013 and 0.0066% of cells, respectively. diated cells, cultures were exposed to 10% survival dose (D), 0.1D and 0.01D of corresponding broadbeams (108 keV/microm). Irrespective of the target numbers (1, 5 or 25 sites) and the time (2 or 6h postirradiation), similar expression changes were observed in bystander cells. Among 874 probes that showed more than 1.5-fold changes in bystander cells, 25% were upregulated and the remainder downregulated. These included genes related to cell communication (PIK3C2A, GNA13, FN1, ANXA1 and IL1RAP), stress response (RAD23B, ATF4 and EIF2AK4) and cell cycle (MYCN, RBBP4 and NEUROG1). Pathway analysis revealed serial bystander activation of G protein/PI-3 kinase pathways. Instead, genes related to cell cycle or death (CDKN1A, GADD45A, NOTCH1 and BCL2L1), and cell communication (IL1B, TCF7 and ID1) were upregulated in irradiated cells, but not in bystander cells. Our results indicate different expression profiles in irradiated and bystander cells, and imply that intercellular signaling between irradiated and bystander cells activate intracellular signaling, leading to the transcriptional stress response in bystander cells.

Classical studies on root hydrotropism have hypothesized the importance of columella cells as well as the de novo gene expression, such as auxin-inducible gene, at the elongation zone in hydrotropism; however, there has been no confirmation that columella cells or auxin-mediated signaling in the elongation zone are necessary for hydrotropism. We examined the role of root cap and elongation zone cells in root hydrotropism using heavy-ion and laser microbeam. Heavy-ion microbeam irradiation of the elongation zone, but not that of the columella cells, significantly and temporarily suppressed the development of hydrotropic curvature. However, laser ablation confirmed that columella cells are indispensable for hydrotropism. Systemic heavy-ion broad-beam irradiation suppressed de novo expression of INDOLE ACETIC ACID 5 gene, but not MIZU-KUSSEI1 gene. Our results indicate that both the root cap and elongation zone have indispensable and functionally distinct roles in root hydrotropism, and that de novo gene expression might be required for hydrotropism in the elongation zone, but not in columella cells.

Studies on the ability of multicellular organisms to tolerate specific environmental extremes are relatively rare compared to those of unicellular microorganisms in extreme environments. Tardigrades are extremotolerant animals that can enter an ametabolic dry state called anhydrobiosis and have high tolerance to a variety of extreme environmental conditions, particularly while in anhydrobiosis. Although tardigrades have been expected to be a potential model animal for astrobiological studies due to their excellent anhydrobiotic and extremotolerant abilities, few studies of tolerance with cultured tardigrades have been reported, possibly due to the absence of a model species that can be easily maintained under rearing conditions. We report the successful rearing of the herbivorous tardigrade, Ramazzottius varieornatus, by supplying the green alga Chlorella vulgaris as food. The life span was 35 +/- 16.4 d, deposited eggs required 5.7 +/- 1.1 d to hatch, and animals began to deposit eggs 9 d after hatching. The reared individuals of this species had an anhydrobiotic capacity throughout their life cycle in egg, juvenile, and adult stages. Furthermore, the reared adults in an anhydrobiotic state were tolerant of temperatures of 90 degrees C and -196 degrees C, and exposure to 99.8% acetonitrile or irradiation with 4000 Gy (4)He ions. Based on their life history traits and tolerance to extreme stresses, R. varieornatus may be a suitable model for astrobiological studies of multicellular organisms.

An enormous amount of nitrile hydratase (NHase) is inducibly produced by Pseudomonas chlororaphis B23 after addition of methacrylamide as the sole nitrogen source to a medium. The expression pattern of the P. chlororaphis B23 NHase gene cluster in response to addition of methacrylamide to the medium was investigated. Recently, we reported that the NHase gene cluster comprises seven genes (oxdA, amiA, nhpA, nhpB, nhpC, nhpS, and acsA). Sequence analysis of the 1.5-kb region upstream of the oxdA gene revealed the presence of a 936-bp open reading frame (designated nhpR), which should encode a protein with a molecular mass of 35,098. The deduced amino acid sequence of the nhpR product showed similarity to the sequences of transcriptional regulators belonging to the XylS/AraC family. Although the transcription of the eight genes (nhpR, oxdA, amiA, nhpABC, nhpS, and acsA) in the NHase gene cluster was induced significantly in the P. chlororaphis B23 wild-type strain after addition of methacrylamide to the medium, transcription of these genes in the nhpR disruptant was not induced, demonstrating that nhpR codes for a positive transcriptional regulator in the NHase gene cluster. A reverse transcription-PCR experiment revealed that five genes (oxdA, amiA, nhpA, nhpB, and nhpC) are cotranscribed, as are two other genes (nhpS and acsA). The transcription start sites for nhpR, oxdA, nhpA, and nhpS were mapped by primer extension analysis, and putative -12 and -24 sigma(54)-type promoter binding sites were identified. NhpR was found to be the first transcriptional regulator of NHase belonging to the XylS/AraC family.

Learning impairment following ionizing radiation (IR) exposure is an important potential risk in manned space missions. We previously reported the modulatory effects of IR on salt chemotaxis learning in Caenorhabditis elegans. However, little is known about the effects of IR on the functional relationship in the nervous system. In the present study, we investigated the effects of gamma-ray exposure on the relationship between locomotion and salt chemotaxis learning behavior. We found that effects of pre-learning irradiation on locomotion were significantly correlated with the salt chemotaxis learning performance, whereas locomotion was not directly related to chemotaxis to NaCl. On the other hand, locomotion was positively correlated with salt chemotaxis of animals which were irradiated during learning, and the correlation disappeared with increasing doses. These results suggest an indirect relationship between locomotion and salt chemotaxis learning in C. elegans, and that IR inhibits the innate relationship between locomotion and chemotaxis, which is related to salt chemotaxis learning conditioning of C. elegans.

Ionizing radiation-induced bystander effects have been documented for a multitude of endpoints such as mutations, chromosome aberrations and cell death, which arise in nonirradiated bystander cells having received signals from directly irradiated cells; however, energetic heavy ion-induced bystander response is incompletely characterized. To address this, we employed precise microbeams of carbon and neon ions for targeting only a very small fraction of cells in confluent fibroblast cultures. Conventional broadfield irradiation was conducted in parallel to see the effects in irradiated cells. Exposure of 0.00026% of cells led to nearly 10% reductions in the clonogenic survival and twofold rises in the apoptotic incidence regardless of ion species. Whilst apoptotic frequency increased with time up to 72 h postirradiation in irradiated cells, its frequency escalated up to 24h postirradiation but declined at 48 h postirradiation in bystander cells, indicating that bystander cells exhibit transient commitment to apoptosis. Carbon- and neon-ion microbeam irradiation similarly caused almost twofold increments in the levels of serine 15-phosphorylated p53 proteins, irrespective of whether 0.00026, 0.0013 or 0.0066% of cells were targeted. Whereas the levels of phosphorylated p53 were elevated and remained unchanged at 2h and 6h postirradiation in irradiated cells, its levels rose at 6h postirradiation but not at 2h postirradiation in bystander cells, suggesting that bystander cells manifest delayed p53 phosphorylation. Collectively, our results indicate that heavy ions inactivate clonogenic potential of bystander cells, and that the time course of the response to heavy ions differs between irradiated and bystander cells. These induced bystander responses could be a defensive mechanism that minimizes further expansion of aberrant cells.

Ionizing radiation (IR) is known to impair learning by suppressing adult neurogenesis in the hippocampus. However, in a mature nervous system, IR-induced functional alterations that are independent of neurogenesis remain largely unknown. In the present study, we analyzed the effects of IR on a food-NaCl associative learning paradigm of adult Caenorhabditis elegans that does not undergo neurogenesis. We observed that a decrease in chemotaxis toward NaCl occurs only after combined starvation and exposure to NaCl. Exposure to IR induced an additional decrease in chemotaxis immediately after an acute dose in the transition stage of the food-NaCl associative learning. Strikingly, chronic irradiation induced negative chemotaxis in the exposed animals, i.e., the primary avoidance response. IR-induced additional decreases in chemotaxis after acute and chronic irradiation were significantly suppressed in the gpc-1 mutant, which was defective in GPC-1 (one of the two gamma subunits of the heterotrimeric G-protein). Chemotaxis to cAMP, but not to lysine and benzaldehyde, was influenced by IR during the food-NaCl associative learning. Our novel findings suggest that IR behaves as a modulator in the food-NaCl associative learning via C. elegans GPC-1 and a specific neuronal network and may shed light on the modulatory effect of IR on learning.

Research concerning cellular responses to low dose irradiation, radiation-induced bystander effects, and the biological track structure of charged particles has recently received particular attention in the field of radiation biology. Target irradiation employing a microbeam represents a useful means of advancing this research by obviating some of the disadvantages associated with the conventional irradiation strategies. The heavy-ion microbeam system at JAEA-Takasaki, which was planned in 1987 and started in the early 1990's, can provide target irradiation of heavy charged particles to biological material at atmospheric pressure using a minimum beam size 5 mum in diameter. A variety of biological material has been irradiated using this microbeam system including cultured mammalian and higher plant cells, isolated fibers of mouse skeletal muscle, silkworm (Bombyx mori) embryos and larvae, Arabidopsis thaliana roots, and the nematode Caenorhabditis elegans. The system can be applied to the investigation of mechanisms within biological organisms not only in the context of radiation biology, but also in the fields of general biology such as physiology, developmental biology and neurobiology, and should help to establish and contribute to the field of "microbeam biology".

Ionizing radiation-induced genomic instability has been demonstrated in a variety of endpoints such as delayed reproductive death, chromosome instability and mutations, which occurs in the progeny of survivors many generations after the initial insult. Dependence of these effects on the linear energy transfer (LET) of the radiation is incompletely characterized; however, our previous work has shown that delayed reductions in clonogenicity can be most pronounced at LET of 108 keV/microm. To gain insight into potential cellular mechanisms involved in LET-dependent delayed loss of clonogenicity, we investigated morphological changes in colonies arising from normal human diploid fibroblasts exposed to gamma-rays or energetic carbon ions (108 keV/microm). Exposure of confluent cultures to carbon ions was 4-fold more effective at inactivating cellular clonogenic potential and produced more abortive colonies containing reduced number of cells per colony than gamma-rays. Second, colonies were assessed for clonal morphotypic heterogeneity. The yield of differentiated cells was elevated in a dose- and LET-dependent fashion in clonogenic colonies, whereas differentiated cells predominated to a comparable extent irrespective of radiation type or dose in abortive colonies. The incidence of giant or multinucleated cells was also increased but much less frequent than that of differentiated cells. Collectively, our results indicate that carbon ions facilitate differentiation more effectively than gamma-rays as a major response in the progeny of irradiated fibroblasts. Accelerated differentiation may account, at least in part, for dose- and LET-dependent delayed loss of clonogenicity in normal human diploid cells, and could be a defensive mechanism that minimizes further expansion of aberrant cells.

An analysis of ionizing radiation-induced damage in peripheral lymphocytes has been employed to predict the prognosis of radiotherapy in terms of toxicity in normal tissues. Therefore, understanding the sensitivity of lymphocytes to high linear energy transfer (LET)-charged particles would be indispensable for utilizing charged particle therapy in veterinary medicine. However, the availability of such information is very limited. This study aimed to compare the radiosensitivity of feline T lymphocytes to gamma-rays (0.2 keV/microm) and 4 different types of charged particles with LET values ranging from 2.8 to 114 keV/microm. It was observed that the relative biological effectiveness, inactivation cross-section, and isodose-induced apoptosis increased in an LET-dependent manner. On the other hand, no difference in apoptosis frequency was observed in the cells exposed to an isosurvival dose of all the radiation types tested. This is the first study that demonstrates the LET dependence of cell killing and apoptosis induction in feline T lymphocytes. Our results suggest that lymphocytes can be effectively used to predict the prognosis of charged-particle therapy in cat patients.

High tolerance against various extreme environments exhibited by some anhydrobionts might be due to being almost completely desiccated, a state where little or no chemical reactions occur. We have shown that anhydrobiotic larvae of Polypedilum vanderplanki have higher tolerance against both high- and low-linear energy transfer (LET) radiation than hydrated larvae. It is of great interest to know how the desiccating larvae gain radiation tolerance. We therefore examined effects of high-LET radiation on four kinds of larvae: (1) normal hydrated (intact) larva, (2) intermediates between the anhydrobiotic and normal hydrated state, (3) almost completely dehydrated (anhydrobiotic) larvae, and (4) immediately rehydrated larvae that are assumed to have a similar molecular profile to anhydrobiotic larvae. The intermediates and immediately rehydrated larvae survived longer after high-LET radiation than intact larvae, indicating that radiation tolerance could be enhanced even in hydrated larvae. Physiological changes toward anhydrobiosis, e.g. accumulation of protectants or increasing damage repair capacity, correlate with improved radiation tolerance in hydrated larvae. In addition, almost complete desiccation further enhanced radiation tolerance, possibly in a different way from the hydrated larvae.

To carry out the radio-microsurgery study using silkworm, Bombyx mori, we have already developed the specific irradiation systems for eggs and third to fifth instar larvae. In this study, a modified application consisting of the first instar silkworm larvae was further developed using heavy-ion microbeams. This system includes aluminum plates with holes specially designed to fix the first instar silkworm larvae during irradiation, and Mylar films were used to adjust energy deposited for planning radiation doses at certain depth. Using this system, the suppression of abnormal proliferation of epidermal cells in the knob mutant was examined. Following target irradiation of the knob-forming region at the first instar stage with 180-mum-diameter microbeam of 220 MeV carbon (12C) ions, larvae were reared to evaluate the effects of irradiation. The results indicated that the knob formation at the irradiated segment was specially suppressed in 5.9, 56.4, 66.7 and 73.6% of larvae irradiated with 120, 250, 400 and 600 Gy, respectively, but the other knob formations at the non-irradiated segments were not suppressed in either irradiation. Although some larva did not survive undesired non-targeted exposure, our present results indicate that this method would be useful to investigate the irradiation effect on a long developmental period of time. Moreover, our system could also be applied to other species by targeting tissues, or organs during development and metamorphosis in insect and animals.

Purpose: To investigate the role of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) in the medium-mediated bystander effect for chromosomal aberrations induced by low-linear energy transfer (LET) X-rays and high-LET heavy ions in normal human fibroblast cells., Materials and Methods: The recipient cells were treated for 12 h with conditioned medium, which was harvested from donor cells at 24 h after exposure to 10 Gy of soft X-rays (5 keV/microm) and 20Ne ions (437 keV/microm), followed by analyses of chromosome aberrations in recipient cells with premature chromosome condensation methods. To examine the role of DNA-PKcs and nitric oxide (NO), cells were treated with its inhibitor LY294002 (LY) and its scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (c-PTIO), respectively., Results: Increased frequency of chromosome aberrations in recipient cells treated with conditioned medium from irradiated but not from un-irradiated donor cells was observed which was independent of radiation type. Bystander induction of chromosome aberrations in recipient cells was mitigated when donor cells were treated with LY before irradiation and with c-PTIO after irradiation, and was enhanced when recipient cells were treated with LY before treatment of recipient cells with conditioned medium from irradiated donor cells., Conclusion: Irradiated normal human cells secrete NO and other molecules which in turn transmit radiation signals to unirradiated bystander cells, leading to the induction of bystander chromosome aberrations partially repairable by DNA-PKcs-mediated DNA damage repair machinery, such as non-homologous end-joining repair pathways.

The effects of heavy ion microbeams on muscle fibers isolated from mouse skeletal muscles were examined by electron microscopy. The plasma membranes of heavy ion beam-irradiated areas of muscle fibers showed irregular protrusions and invaginations. In the cytoplasm, an irregular distribution of microfilaments was found near the plasma membrane. Sarcoplasmic reticula in the irradiated regions showed a distended appearance with flocculent material within the lumen. These changes were seen as early as 2 min after irradiation, and persisted until as late as 22 min after irradiation. Many autophagic vacuoles could be seen at 7 min after irradiation. At 22 min, the vacuoles became more prominent and showed more variety. These observations suggest that heavy ion beam irradiation causes disruption of the cellular architecture and the autophagy is involved in removal of this disruption.

Extracellular DNA is omnipresent in aquatic environments and is thought to be a genetic material for horizontal gene transformation between microorganisms. We studied the impact of gamma irradiation on the transformation efficiency (transformants number per ng of DNA per ml) of extracellular DNA. Plasmid pEGFP as a model extracellular DNA was irradiated by gamma rays. The transformation efficiency decreased with the increase in radiation dose. A total dose of 10Gy is normally not lethal for microorganisms but certainly affects the transformation efficiency of extracellular DNA. The decrease in the efficiency would be induced by strand breaks of extracellular DNA because the yield of both single-strand breaks (SSBs) and double-strand breaks (DSBs) increased with the increase in radiation dose. The relative transformation efficiency of SSBs and DSBs to that of covalently closed circles (CCCs) was 30.3% and 0.2%, respectively. This impact on natural transformation suggests an inability of microorganisms to acquire new characteristics which should be normally acquired.

Purpose: Anhydrobiotic larvae of Polypedilum vanderplanki are known to show an extremely high tolerance against a range of stresses. We have recently reported that this insect withstands exposure to high doses of gamma-rays (linear energy transfer [LET] 0.2 keV/microm). However, its tolerance against high LET radiation remains unknown. The aim of this study is to characterize the tolerance to high-LET radiations of P. vanderplanki., Materials and Methods: Larval survival and subsequent metamorphoses were compared between anhydrobiotic (dry) and non-anhydrobiotic (wet) samples after exposure to 1 - 7000 Gy of three types of heavy ions delivered from the azimuthally varying field (AVF) cyclotron with LET values ranging from 16.2 - 321 keV/microm. The tolerance against 4He ions was also compared among three chironomid species., Results: At all LET values measured, dry larvae consistently showed greater radiation tolerance than hydrated larvae, perhaps due to the presence of high concentrations of the disaccharide trehalose in anhydrobiotic animals, and the radiation-induced damage became evident at lower doses as development progressed. Relative biological effectiveness (RBE) values based on the median inhibitory doses reached a maximum at 116 keV/microm (12C), and the maximum RBE clearly increased as development progressed. Lower D0 (dose to reduce survival from relative value 1.00 - 0.37 on the exponential part of the survival curve), and higher Dq (quasi-threshold dose) were found in individuals exposed to 4He ions, compared to gamma-rays, and in P. vanderplanki larvae compared to non-anhydrobiotic chironomids., Conclusion: Anhydrobiosis potentiates radiation tolerance in terms of larval survival, pupation and adult emergence of P. vanderplanki exposed to high-LET radiations as well as to low-LET radiation. P. vanderplanki larvae might have more efficient DNA damage repair after radiation than other chironomid species.

Purpose: Tardigrades are known to survive high doses of ionizing radiation. However, there have been no reports about radiation effects in tardigrades under culture conditions. In this study, we investigated tolerance of the tardigrade, Milnesium tardigradum, against gamma-rays and heavy ions by determining short-term or long-term survival, and reproductive ability after irradiation., Materials and Methods: Hydrated and anhydrobiotic animals were exposed to gamma-rays (1000 - 7000 Gy) or heavy ions (1000 - 8000 Gy) to evaluate short-term survival at 2, 24 and 48 h post-irradiation. Long-term survival and reproduction were observed up to 31 days after irradiation with gamma-rays (1000 - 4000 Gy)., Results: At 48 h after irradiation, median lethal doses were 5000 Gy (gamma-rays) and 6200 Gy (heavy ions) in hydrated animals, and 4400 Gy (gamma-rays) and 5200 Gy (heavy ions) in anhydrobiotic ones. Gamma-irradiation shortened average life span in a dose-dependent manner both in hydrated and anhydrobiotic groups. No irradiated animals laid eggs with one exception in which a hydrated animal irradiated with 2000 Gy of gamma-rays laid 3 eggs, and those eggs failed to hatch, whereas eggs produced by non-irradiated animals hatched successfully., Conclusion: M. tardigradum survives high doses of ionizing radiation in both hydrated and anhydrobiotic states, but irradiation with >1000 Gy makes them sterile.

High linear energy transfer (LET) heavy charged particles have previously been applied clinically to human cancer radiotherapy because of their excellent physical properties of selective dose distribution and higher relative biological effectiveness (RBE) for human; however, such an approach has yet to be applied to cat patients. The present study investigates the biological effectiveness of low-LET gamma-rays (0.2 keV/micro m) compared to high-LET carbon ions (114 keV/micro m) in feline T- lymphocyte FeT-J cells. Clonogenic survival analysis revealed that the RBE value of carbon ions was 2.98 relative to a 10% survival dose (D(10)) by gamma-rays, and that the inactivation cross-section in cells exposed to gamma-rays and carbon ions was 0.023 and 38.9 micro m(2), respectively. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) analysis revealed that TUNEL-positive frequency in carbon-irradiation cells is higher than for gamma-irradiated cells against exposure to the same physical doses, but that very little difference in TUNEL-positive frequency is observed between cells exposed to the respective D(10) dose of gamma-rays. Our data thus indicate that carbon ions are more effective for cell killing than gamma-rays at the same physical doses, but kill cells to an extent that is comparable to gamma-rays at the same biological doses. Carbon ion radiotherapy is therefore a promising modality for cat patients.