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Understanding radioactive Cs contamination has been a central issue at Fukushima Daiichi and other nuclear legacy sites; however, atomic-scale characterization of radioactive Cs in environmental samples has never been achieved. Here we report, for the first time, the direct imaging of radioactive Cs atoms using high-resolution high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM). In Cs-rich microparticles collected from Japan, we document inclusions that contain 27 - 36 wt% of Cs (reported as Cs 2 O) in a zeolite: pollucite. The compositions of three pollucite inclusions are (Cs 1.86 K 0.11 Rb 0.19 Ba 0.22 ) 2.4 (Fe 0.85 Zn 0.84 X 0.31 ) 2.0 Si 4.1 O 12 , (Cs 1.19 K 0.05 Rb 0.19 Ba 0.22 ) 1.7 (Fe 0.66 Zn 0.32 X 0.41 ) 1.4 Si 4.6 O 12 , and (Cs 1.27 K 0.21 Rb 0.29 Ba 0.15 ) 1.9 (Fe 0.60 Zn 0.32 X 0.69 ) 1.6 Si 4.4 O 12 (X includes other cations). HAADF-STEM imaging of pollucite, viewed along the [111] zone axis, revealed an array of Cs atoms, which is consistent with a simulated image using the multi-slice method. The occurrence of pollucite indicates that locally enriched Cs reacted with siliceous substances during the Fukushima meltdowns, presumably through volatilization and condensation. Beta radiation doses from the incorporated Cs are estimated to reach 10 6 - 10 7 Gy, which is more than three orders of magnitude less than typical amorphization dose of zeolite. The atomic-resolution imaging of radioactive Cs is an important advance for better understanding the fate of radioactive Cs inside and outside of nuclear reactors damaged by meltdown events., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Due to the increasing of industrial plastic waste and its refractory characteristics, it is extremely urgent to develop new degradation technology and environmentally friendly catalyst for industrial plastic waste. Manganese oxides are one of the most promising candidates for the catalytic degradation of plastic wastes. However, an improved understanding of the structural properties affecting their catalytic activity is required for high-efficient wastewater treatment. We herein report the surface reactivity effects of δ-MnO 2 structural defects with regards to Bisphenol A (BPA) degradation/probe in the presence of peroxymonosulfate (PMS). Four δ-MnO x samples with different Mn(III) contents (different Mn(III)-deficient sample) were prepared and their structural properties as well as surface reactivity were characterized by batch test, ESR and XAFS analysis. For the Mn(III)-deficient sample, BPA removal was principally affected by direct electron transfer, with the adsorbed BPA degraded following hydroxylation. In contrast, a small fraction of Mn(III) substitution in δ-MnO 2 could significantly encouraged the activation of PMS to produce SO 4 - ☐and ☐OH, and a BPA degradation via beta scission. Moreover, the Mn(III)-rich δ-MnO 2 demonstrate a high BPA removal rate even with a low sample load, which performed well following a reuse of five times. Our results provide a new way for the improvement of δ-MnO 2 activity for the use of industrial plastic wastes treatment., Competing Interests: Declaration of competing interest 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., (Copyright © 2022. Published by Elsevier Inc.)

Boron carbide control rods remain in the fuel debris of the damaged reactors in the Fukushima Daiichi Nuclear Power Plant, potentially preventing re-criticality; however, the state and stability of the control rods remain unknown. Sensitive high-resolution ion microprobe analyses have revealed B-Li isotopic signatures in radioactive Cs-rich microparticles (CsMPs) that formed by volatilization and condensation of Si-oxides during the meltdowns. The CsMPs contain 1518-6733 mg kg -1 of 10+11 B and 11.99-1213 mg kg -1 of 7 Li. The 11 B/ 10 B (4.15-4.21) and 7 Li/ 6 Li (213-406) isotopic ratios are greater than natural abundances (~4.05 and ~12.5, respectively), indicating that 10 B(n,α) 7 Li reactions occurred in B 4 C prior to the meltdowns. The total amount of B released with CsMPs was estimated to be 0.024-62 g, suggesting that essentially all B remains in reactor Units 2 and/or 3 and is enough to prevent re-criticality; however, the heterogeneous distribution of B needs to be considered during decommissioning., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The brain is organized into anatomically distinct structures consisting of a variety of projection neurons. While such evolutionarily conserved neural circuit organization underlies the innate ability of animals to swiftly adapt to environments, they can cause biased cognition and behavior. Although recent studies have begun to address the causal importance of projection-neuron types as distinct computational units, it remains unclear how projection types are functionally organized in encoding variables during cognitive tasks. This review focuses on the neural computation of decision making in the prefrontal cortex and discusses what decision variables are encoded by single neurons, neuronal populations, and projection type, alongside how specific projection types constrain decision making. We focus particularly on "over-representations" of distinct decision variables in the prefrontal cortex that reflect the biological and subjective significance of the variables for the decision makers. We suggest that task-specific over-representation in the prefrontal cortex involves the refinement of the given decision making, while generalized over-representation of fundamental decision variables is associated with suboptimal decision biases, including pathological ones such as those in patients with psychiatric disorders. Such over-representation of the fundamental decision variables in the prefrontal cortex appear to be tightly constrained by afferent and efferent connections that can be optogenetically intervened on. These ideas may provide critical insights into potential therapeutic targets for psychiatric disorders, including addiction and depression., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

This study contributes toward developing measures for the disposal of radiocesium-contaminated sewage sludge ash (SSA). Here, we prepared two types of solidified bodies containing 30 wt% radiocesium-bearing SSA. The material used for the two solidified bodies were alkaline-reacted metakaolinite (geopolymer) and ordinary Portland cement (OPC). Cement has been used for solidification of low-level radioactive wastes, and geopolymer is a candidate of cement alternative materials. The characteristics of these solidified bodies were investigated by various aspects including mechanical strength, transformation of SSA components during solidification, and radiocesium confinement ability by leaching test. The compressive strength of geopolymer- and OPC-solidified bodies at 30 wt% SSA content was more than 40 MPa. After static leaching test at 60 °C, 137 Cs was hardly leached out from the geopolymer-solidified bodies containing SSA at 30 wt% to ultrapure water (<0.1%), whereas more than 30% 137 Cs was leached from the OPC-solidified bodies containing SSA at 30 wt% even though only ~9% of 137 Cs in the SSA is soluble. These results strongly indicate that geopolymer is far superior to OPC for solidifying radiocesium-bearing SSA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A contaminated zone elongated toward Futaba Town, north-northwest of the Fukushima Daiichi Nuclear Power Plant (FDNPP), contains highly radioactive particles released from reactor Unit 1. There are uncertainties associated with the physio-chemical properties and environmental impacts of these particles. In this study, 31 radioactive particles were isolated from surface soils collected 3.9 km north-northwest of the FDNPP. Two of these particles have the highest particle-associated 134+137 Cs activity ever reported for Fukushima (6.1 × 10 5 and 2.5 × 10 6  Bq per particle after decay-correction to March 2011). The new, highly-radioactive particle labeled FTB1 is an aggregate of flaky silicate nanoparticles with an amorphous structure containing ~0.8 wt% Cs, occasionally associated with SiO 2 and TiO 2 inclusions. FTB1 likely originates from the reactor building, which was damaged by a H 2 explosion, after adsorbing volatilized Cs. The 134+137 Cs activity in the other highly radioactive particle labeled FTB26 exceeded 10 6  Bq. FTB26 has a glassy carbon core and a surface that is embedded with numerous micro-particles: Pb-Sn alloy, fibrous Al-silicate, Ca-carbonate or hydroxide, and quartz. The isotopic signatures of the micro-particles indicate neutron capture by B, Cs volatilization, and adsorption of natural Ba. The composition of the micro-particles on FTB26 reflects the composition of airborne particles at the moment of the H 2 explosion. Owing to their large size, the health effects of the highly radioactive particles are likely limited to external radiation during static contact with skin; the highly radioactive particles are thus expected to have negligible health impacts for humans. By investigating the mobility of the highly radioactive particles, we can better understand how the radiation dose transfers through environments impacted by Unit 1. The highly radioactive particles also provide insights into the atmospheric conditions at the time of the Unit 1 explosion and the physio-chemical phenomena that occurred during reactor meltdown., Competing Interests: Declaration of competing interest 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Traces of Pu have been detected in material released from the Fukushima Daiichi Nuclear Power Plant (FDNPP) in March of 2011; however, to date the physical and chemical form of the Pu have remained unknown. Here we report the discovery of particulate Pu associated with cesium-rich microparticles (CsMPs) that formed in and were released from the reactors during the FDNPP meltdowns. The Cs-pollucite-based CsMP contained discrete U(IV)O 2 nanoparticles, <~10 nm, one of which is enriched in Pu adjacent to fragments of Zr-cladding. The isotope ratios, 235 U/ 238 U, 240 Pu/ 239 Pu, and 242 Pu/ 239 Pu, of the CsMPs were determined to be ~0.0193, ~0.347, and ~0.065, respectively, which are consistent with the calculated isotopic ratios of irradiated-fuel fragments. Thus, considering the regional distribution of CsMPs, the long-distance dispersion of Pu from FNDPP is attributed to the transport by CsMPs that have incorporated nanoscale fuel fragments prior to their dispersion up to 230 km away from the Fukushima Daiichi reactor site., Competing Interests: Declaration of competing interest 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Low-level radioactive wastes are commonly immobilized in cementitious materials, where cement-based material can incorporate radionuclides into their crystal structure. Specifically, ettringite (Ca 6 Al 2 (OH) 12 (SO 4 ) 3 ∙26H 2 O) is known to stabilize anionic species, which is appealing for waste streams with radioactive iodine ( 129 I) that persists as iodide (I-) and iodate (IO 3 -) in the cementitious nuclear waste repository. However, the structural information and immobilization mechanisms of iodine species in ettringite remain unclear. The present results suggested minimal I- incorporation into ettringite (0.05 %), whereas IO 3 - exhibited a high affinity for ettringite via anion substitution for SO 4 2- (96 %). The combined iodine K-edge extended X-ray absorption fine structure (EXAFS) spectra and first-principles calculations using density functional theory (DFT) suggested that IO 3 - was stabilized in ettringite by hydrogen bonding and electrostatic forces. Substituting IO 3 - for SO 4 2- was energetically favorable by -0.41 eV, whereas unfavorable substitution energy of 4.21 eV was observed for I- substitution. Moreover, the bonding charge density analysis of the substituted IO 3 - and I- anions into the ettringite structure revealed the interaction between intercalated ions with the structural water molecules. These results provided valuable insight into the long-term stabilization of anionic iodine species and their migration in cementitious nuclear waste repository or alkaline environments., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Scans without evidence of dopaminergic deficits (SWEDDs) in dopamine transporter single-photon emission computed tomography (DAT-SPECT) are found in 3.6-19.6% of patients with clinically suspected Parkinson's disease (PD). We investigated whether combined use of 123 I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy would be helpful to differentiate PD among SWEDDs patients., Patients and Methods: 145 patients with clinically suspected PD underwent both DAT-SPECT and MIBG myocardial scintigraphy. Striatal binding ratio (SBR) of DAT-SPECT and heart-to-mediastinal (H/M) ratio and washout rate (WR) of MIBG myocardial scintigraphy were calculated., Results: Among 18 SWEDDs patients (12.4%), 11 were finally diagnosed with PD based on follow-up for at least two years after the DAT-SPECT and MIGB myocardial scintigraphy scans. Among the latter group, 8 patients showed an H/M ratio of less than 2.2, and 9 showed WR above 30%., Conclusion: Our results indicate that the combination of low H/M ratio and high WR of MIBG myocardial scintigraphy of SWEDDs patients may be helpful for detection of PD patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Adsorption of cesium (Cs) on phyllosilicates has been intensively investigated because natural soils have strong ability of immobilizing Cs within clay minerals resulting in difficulty of decontamination. The objectives of present study are to clarify how Cs fixation on vermiculite is influenced by structure change caused by Cs sorption at different loading levels and how Cs desorption is affected by various replacing cations induced at different treating temperature. As a result, more than 80% of Cs was readily desorbed from vermiculite with loading amount of 2% saturated Cs (5.49×10 -3 mmolg -1 ) after four cycles of treatment of 0.01M Mg 2+ /Ca 2+ at room temperature, but less than 20% of Cs was desorbed from saturated vermiculite. These distinct desorption patterns were attributed to inhibition of Cs desorption by interlayer collapse of vermiculite, especially at high Cs loadings. In contrast, elevated temperature significantly facilitated divalent cations to efficiently desorb Cs from collapsed regions. After five cycles of treatment at 250°C with 0.01M Mg 2+ , ∼100% removal of saturated Cs was achieved. X-ray diffraction analysis results suggested that Cs desorption was completed through enhanced diffusion of Mg 2+ cations into collapsed interlayer space under hydrothermal condition resulting in subsequent interlayer decollapse and readily release of Cs + ., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The migration and dispersion of radioactive Cs (mainly (134)Cs and (137)Cs) are of critical concern in the area surrounding the Fukushima Daiichi Nuclear Power Plant (FDNPP). Considerable uncertainty remains in understanding the properties and dynamics of radioactive Cs transport by surface water, particularly during rainfall-induced flood events to the ocean. Physical and chemical properties of unique estuary sediments, collected from the Kuma River, 4.0km south of the FDNPP, were quantified in this study. These were deposited after storm events and now occur as dried platy sediments on beach sand. The platy sediments exhibit median particle sizes ranging from 28 to 32μm. There is increasing radioactivity towards the bottom of the layers deposited; approximately 28 and 38Bqg(-1) in the upper and lower layers, respectively. The difference in the radioactivity is attributed to a larger number of particles associated with radioactive Cs in the lower part of the section, suggesting that radioactive Cs in the suspended soils transported by surface water has decreased over time. Sequential chemical extractions showed that ~90% of (137)Cs was strongly bound to the residual fraction in the estuary samples, whereas 60~80% of (137)Cs was bound to clays in the six paddy soils. This high concentration in the residual fraction facilitates ease of transport of clay and silt size particles through the river system. Estuary sediments consist of particles <100μm. Radioactive Cs desorption experiments using the estuary samples in artificial seawater revealed that 3.4±0.6% of (137)Cs was desorbed within 8h. More than 96% of (137)Cs remained strongly bound to clays. Hence, particle size is a key factor that determines the travel time and distance during the dispersion of (137)Cs in the ocean., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: To investigate the clinical characteristics and therapeutic outcomes of patients who underwent surgery for stage III thymoma in Japan., Methods: Using the Japanese nationwide database, which contains the records of 2,835 patients with thymic epithelial tumors who underwent treatment between 1991 and 2010, we extracted and analyzed the records of those who underwent surgery for stage III thymoma., Results: A total of 310 patients (170 males, 140 females; median age, 58 years) were analyzed. Involved sites were the lung in 194 (62.6%), the pericardium in 151 (48.7%), the great vessels in 126 (40.6%), the phrenic nerve in 84 (27.1%), and the chest wall in 7 (2.3%). Complete resection (R0) was achieved in 247 (79.7%) cases. Induction therapies were administered to 42 (13.5%) patients, and postoperative therapies were administered to 147 (47.4%). In R0 cases, 68 (27.5%) experienced recurrence. The pleural space was the most frequent site of recurrence (46; 18.6%). The 10-year overall and disease-free (in R0) survival rates were 80.2% and 51.6%, respectively. Multivariate analyses revealed that age (p = 0.002), male sex (p = 0.017), induction therapy (p < 0.001), and type B histology (p = 0.037) were independent adverse predictors for overall survival. Chest wall invasion was the only independent adverse predictor for disease-free survival, although the factor analysis was marginal for overall survival., Conclusions: The outcomes of surgery for patients with stage III thymoma were favorable unless chest wall invasion was present; however, the role of complete resection and appropriate multimodal treatment plan require further investigation., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We investigated the effectiveness of glucagon-like peptide-2 (GLP-2) on memory impairment in lipopolysaccharide (LPS)-treated mice, and anxiety-like behavior in adrenocorticotropic hormone (ACTH)-treated mice. In the Y-maze test, LPS (10 µg/mouse, i.c.v.) significantly decreased spontaneous alternation, which was prevented by pretreatment with GLP-2 (0.01-0.3 µg/mouse, i.c.v.). The GLP-2 treatment just before the Y-maze test also improved LPS-induced memory impairment. Continuous treatment with GLP-2 (3 µg/mouse, i.c.v.) had no effect on the open-field test in saline-treated or ACTH-treated mice. Chronic ACTH treatment did not cause anxiogenic effects in the elevated plus-maze test. GLP-2 showed weak anxiolytic-like effects in the elevated plus-maze test in ACTH-treated, but not saline-treated mice. Moreover, GLP-2 increased 5-HT, but not 5-HIAA and tryptophan hydroxylase 2 levels in the amygdala of ACTH-treated mice. Pharmacological depletion of 5-HT prevented the anxiolytic effects of GLP-2. These results suggest that GLP-2 protected and improved memory function in LPS-treated mice, and also had anxiolytic effects due to changes in the 5-HT system., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To compare postcontrast T1-weighted imaging (T1WI+) with precontrast T1-weighted (T1WI-), T2-weighted (T2WI), and proton density-weighted imaging (ProWI) in depiction of the anterior disc displacement (ADD) in temporomandibular disorders (TMDs)., Study Design: A total of 120 joints with TMD were included in this study. Qualitatively, Receiver operating characteristic analysis was performed. Quantitatively, the ratio of the intensity in the retrodiscal tissue to intensity in the disc (intensity ratio) was measured., Results: One reader achieved superior performance in visualization of ADD with T1WI+ than with the other sequences. The other reader showed superiority with T1WI+ rather than T2WI or T1WI-. The intensity ratio on T1WI+ was significantly higher than the intensity ratio on other sequences. On T1WI,+ the intensity ratio in the joints with ADD was significantly higher than that in the joints without ADD., Conclusion: Postcontrast T1-weighted imaging can improve the visualization of ADD in TMDs.

We have previously identified a Galpha(i/o)-protein-coupled receptor (TG1019/OXE) using 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) as its ligand. We investigated signal transduction from TG1019 following stimulation with 5-oxo-ETE and role of TG1019 in 5-oxo-ETE-induced chemotaxis, using Chinese hamster ovary cells expressing TG1019 (CHO/TG1019 cells). 5-Oxo-ETE induced intracellular calcium mobilization and rapid activation of MEK/ERK and PI3K/Akt pathways in CHO/TG1019 cells. CHO/TG1019 cells stimulated with 5-oxo-ETE and other eicosanoids exhibited chemotaxis with efficacies related to agonistic activity of each eicosanoid for TG1019. Pretreatment of the cells with pertussis toxin, a phospholipase C (PLC) inhibitor (U73122) or a PI3K inhibitor (LY294002), markedly suppressed 5-oxo-ETE-induced chemotaxis, whereas pretreatment with a MEK inhibitor (PD98059) had no significant effect on the chemotaxis. Our results show that TG1019 mediates 5-oxo-ETE-induced chemotaxis and that signals from TG1019 are transduced via Galpha(i/o) protein to PLC/calcium mobilization, MEK/ERK, and PI3K/Akt, among which PLC and PI3K would play important roles in the chemotaxis.

Objective: The purposes of this study were (1) to assess functional and pain outcomes after arthroscopic surgery on patients with temporomandibular joint disorders (TMD); (2) to evaluate postsurgical changes in disk position, mobility, and morphology on magnetic resonance imaging (MRI); and (3) to measure the association between changes in disk position, mobility, and morphology on MRI and clinical outcomes., Study Design: A retrospective analysis was conducted of temporomandibular joints with internal derangement and osteoarthritis that were refractory to nonsurgical treatments and underwent arthroscopic surgery and on which MRI was performed within 1 month after the initial visit and 1 year after arthroscopic surgery. Clinical findings were assessed on the basis of mandibular range of motion and joint pain level on a visual analog scale at the initial visit and 1 year after arthroscopic surgery. The disk position, mobility, and morphology on MRI were compared with clinical findings and were statistically analyzed before and after arthroscopic surgery. The treatment outcome was judged according to our success criteria. The associations between changes in disk position, mobility, and morphology and clinical outcomes after arthroscopic surgery were statistically analyzed., Results: Forty-three joints of 43 patients who underwent arthroscopic surgery were assessed in this study. After arthroscopic surgery, mandibular range of motion and visual analog scale results improved statistically. According to the criteria for clinical resolution, 32 surgeries were successful and 11 were unsuccessful. Preoperative and postoperative MRI showed that most joints had anterior disk displacement (ADD) without reduction. Postoperative MRI revealed that, statistically, the number of mobile disks had increased and deformity of the disks had progressed. In the successful group, postoperative MRI revealed that all joints had mobile disks. In both groups, most joints had ADD without reduction before and after arthroscopic surgery, and, statistically, deformity of the disks progressed after arthroscopic surgery., Conclusions: Arthroscopic surgery was an effective treatment for TMD refractory to nonsurgical treatments. This study provides important information of clinical significance. Disk position remained ADD without reduction, disk mobility increased, and deformity of the disks progressed after arthroscopic surgery.

This investigation was performed to assess the importance of interaction in the bindings of selective and nonselective alpha(1)-antagonists to alpha(1)-adrenergic receptor (alpha(1)-AR) subtypes using molecular modeling. The alpha(1)-antagonists used in this study were prazosin, tamsulosin and KMD-3213. Molecular modeling was performed on Octane 2 workstation (Silicon Graphics) using Discover/Insight II software (Molecular Simulations Inc.). Through molecular modeling, possible binding sites for these drugs were suggested to lie between transmembrane domains (TM) 3, 4, 5 and 6 of the alpha(1)-AR subtypes. In prazosin, the 4-amino group, 1-nitrogen atom and two methoxy groups of quinazoline ring possibly interact with the amino acids in TM3, TM5 and TM6 of alpha(1)-ARs. In tamsulosin, amine group of ethanyl amine chain, methoxy group of benzene ring and sulfonamide nitrogen of benzene ring interacts in TM3, TM4 and TM5 of alpha(1)-ARs. In KMD-3213, amine of ethyl amine chain and indoline nitrogen of this compound possibly interact within TM3 and TM5 of alpha(1)-ARs. Amide nitrogen of KMD-3213 also interacts within TM4 of alpha(1A)-AR. The results of the present study suggested that prazosin has similar binding sites in all the alpha(1)-AR subtypes while tamsulosin interacts at higher number of sites with alpha(1D)-subtype than other alpha(1)-AR subtypes. KMD-3213 being an alpha(1A)-AR selective ligand, binds to higher number of sites of alpha(1A) subtype than to other subtypes. All these amino acids are located near the extracellular loop. These findings are consistent with the previous studies that antagonists bind higher in the pocket closer to the extracellular surface unlike agonist binding.

Distraction osteogenesis with the shortening and lengthening method is a well-established procedure for repairing extremities. We used this technique for reconstruction after mandibular segmental resection. A 74-year-old woman underwent distraction osteogenesis with an intraoral device, initially shortening the mandible after a 20-mm-long segmental resection, followed by lengthening at a rate of 0.8 mm per day for 21 days. Eight weeks after the distraction, the device was removed and a dental implant was placed at the site of distraction. Radiographic observation showed new bone formation, and the implant was completely osseointegrated. Although the follow-up period is relatively short, the clinical course was uneventful. Distraction osteogenesis with the shortening and lengthening method seems to be a feasible option for reconstruction after segmental resection of the mandible.

The structure-activity relationships of bopindolol and its two metabolites (18-502 and 20-785) and their beta-blocking potencies in the human beta2-adrenoceptor (AR) were assessed using molecular modeling on an INDIGO2 workstation (SGI Co., Ltd.) and DISCOVER/INSIGHT II (Biosym Co., Ltd.). Through modeling, possible binding sites for these agents were hypothesized to involve the 3rd, 4th, 5th and 6th helices of the beta2-AR, and these shared a common interaction site at Asp113 in helix 3. The different chemical structure of these three agents, however, showed binding to different binding sites (amino acids). This study therefore suggests that different beta-blocking potencies of these agents may be due to different chemical structure.

Production of blood cells is regulated by the interplay of various cytokines and bone marrow stromal cells. Recently, a ligand for the orphan receptor Mpl was identified as thrombopoietin (TPO), which specifically regulates megakaryocyte differentiation, and it was reported to be expressed mainly in liver and kidney. As it was found that thrombopoietin is also produced in bone marrow stromal cells, we studied further the roles of bone marrow stromal cells on megakaryocytopoiesis and platelet formation. The stromal cells stimulated growth and maturation of bone-marrow-derived megakaryocytes in the presence of thrombopoietin, and also supported growth of BaF3 cells expressing exogenous Mpl without thrombopoietin. Thrombopoietin induces drastic morphological change of megakaryocytes in bone marrow cells in vitro, ie, the formation of lengthy beaded cytoplasmic processes (proplatelet formation). However, when the purified megakaryocytes were cocultured with the stromal cells with or without thrombopoietin, most of the megakaryocytes adhered to the stromal cells and remained unchanged, while free megakaryocytes induced proplatelet formation. These observations indicated that the stromal cells in a hematopoietic microenvironment in bone marrow secrete thrombopoietin and stimulate proliferation and maturation of megakaryocytes, but the interaction of megakaryocytes with the stromal cells may suppress proplatelet formation.

Thrombopoietin (Tpo) is a specific cytokine which regulates megakaryocyte differentiation and maturation. We isolated a truncated mouse Tpo cDNA, the product of which turned out to function neither as an active Tpo variant nor as an antagonist. To define the functional domains of the Tpo molecule further, various truncated and point-mutated Tpo molecules were prepared and their biological activity was assayed. It was found that deletion of the amino terminal side of a potential proteolytic cleavage site, Arg-Arg motif, caused complete loss of Tpo's activity, and that point-mutants lacking one of four conserved cysteine residues lost Tpo activity. We also noticed that Tpo activity was inhibited by the reducing agent. Thus, it was concluded that the amino terminal half of the Tpo is sufficient for Tpo activity, and that the cysteine residues, especially the last cysteine residue located two amino acids away from the Arg-Arg motif, are critical for this activity.

We have previously isolated the rat serotonin (5-HT)1A receptor gene (G21Y2) and now report the expression and characterization of this receptor. The BamHI/Xbal fragment of this gene was cloned into Rc/RSV and stably transfected into HeLa cells by the calcium phosphate method. For determination of specific 5-HT1A receptor binding, [3H]8OH-DPAT was used as the radioligand and incubated with HeLa cell membranes. The cells expressed specific and saturable binding of [3H]8OH-DPAT with a Kd value of 0.3 nM and a Bmax value of 2 pmol/mg protein. GTP (50 microM) added to the incubation mixture increased the Kd value to 3 nM indicating that the expressed receptor is coupled to a G protein. The specific binding was inhibited by selective 5-HT1A partial agonists, such as buspirone, ipsapirone, gepirone, tandospirone, zalospirone and SUN8399 with Ki values of 1-30nM, whereas other neurotropic drugs except for spiperone (Ki = 46 nM) and nemonapride (Ki = 2.3 nM) were effective only at concentrations of more than 100 microM. The potencies of these compounds to inhibit [3H]8OH-DPAT from its specific binding sites were similar to their affinities determined in rat hippocampus binding studies. These data suggest that the expressed receptor is a 5-HT1A-type similar to 5-HT1A receptors in the rat hippocampus.