Paraspeckles are constructed as block copolymer micelles.

Paraspeckles are constructed by NEAT1_2 architectural long noncoding RNAs. Their characteristic cylindrical shapes, with highly ordered internal organization, distinguish them from typical liquid-liquid phase-separated condensates. We experimentally and theoretically investigated how the shape and organization of paraspeckles are determined. We identified the NEAT1_2 RNA domains responsible for shell localization of the NEAT1_2 ends, which determine the characteristic internal organization. Using the soft matter physics, we then applied a theoretical framework to understand the principles that determine NEAT1_2 organization as well as shape, number, and size of paraspeckles. By treating paraspeckles as amphipathic block copolymer micelles, we could explain and predict the experimentally observed behaviors of paraspeckles upon NEAT1_2 domain deletions or transcriptional modulation. Thus, we propose that paraspeckles are block copolymer micelles assembled through a type of microphase separation, micellization. This work provides an experiment-based theoretical framework for the concept that ribonucleoprotein complexes (RNPs) can act as block copolymers to form RNA-scaffolding biomolecular condensates with optimal sizes and structures in cells.

Severe acute respiratory syndrome coronavirus 2 prevalence in saliva and gastric and intestinal fluid in patients undergoing gastrointestinal endoscopy in coronavirus disease 2019 endemic areas: Prospective cross-sectional study in Japan.

OBJECTIVES: Gastrointestinal endoscopy (GIE) is useful for the early detection and treatment of many diseases; however, GIE is considered a high-risk procedure in the coronavirus disease 2019 (COVID-19) pandemic era. This study aimed to explore the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity in saliva and gastrointestinal fluids to which endoscopy medical staff are exposed. METHODS: The study was a single-center cross-sectional study. From June 1 to July 31, 2020, all patients who underwent GIE at Yokohama City University Hospital were registered. All patients provided 3 mL of saliva. For upper GIE, 10 mL of gastric fluid was collected through the endoscope. For lower GIE, 10 mL of intestinal fluid was collected through the endoscope. The primary outcome was the positive rate of SARS-CoV-2 in saliva and gastrointestinal fluids. We also analyzed serum-specific antibodies for SARS-CoV-2 and patients' background information. RESULTS: A total of 783 samples (560 upper GIE and 223 lower GIE samples) were analyzed. Polymerase chain reaction (PCR) on saliva samples did not show any positive results in either upper or lower GIE samples. However, 2.0% (16/783) of gastrointestinal fluid samples tested positive for SARS-CoV-2. No significant differences in age, sex, purpose of endoscopy, medication, or rate of antibody test positivity were found between PCR positive and PCR negative cases. CONCLUSIONS: Asymptomatic patients, even those with no detectable virus in their saliva, had SARS-CoV-2 in their gastrointestinal tract. Endoscopy medical staff should be aware of infection when performing procedures. The study was registered as UMIN000040587.

Involvement of Fusobacterium Species in Oral Cancer Progression: A Literature Review Including Other Types of Cancer.

Chronic inflammation caused by infections has been suggested to be one of the most important cause of cancers. It has recently been shown that there is correlation between intestinal bacteria and cancer development including metastasis. As over 700 bacterial species exist in an oral cavity, it has been concerning that bacterial infection may cause oral cancer. However, the role of bacteria regarding tumorigenesis of oral cancer remains unclear. Several papers have shown that Fusobacterium species deriving the oral cavities, especially, play a crucial role for the development of colorectal and esophageal cancer. F. nucleatum is a well-known oral bacterium involved in formation of typical dental plaque on human teeth and causing periodontal diseases. The greatest characteristic of F. nucleatum is its ability to adhere to various bacteria and host cells. Interestingly, F. nucleatum is frequently detected in oral cancer tissues. Moreover, detection of F. nucleatum is correlated with the clinical stage of oral cancer. Although the detailed mechanism is still unclear, Fusobacterium species have been suggested to be associated with cell adhesion, tumorigenesis, epithelial-to-mesenchymal transition, inflammasomes, cell cycle, etc. in oral cancer. In this review, we introduce the reports focused on the association of Fusobacterium species with cancer development and progression including oral, esophageal, and colon cancers.

2NH and 3OH are crucial structural requirements in sphingomyelin for sticholysin II binding and pore formation in bilayer membranes.

Sticholysin II (StnII) is a pore-forming toxin from the sea anemone Stichodactyla heliantus which belongs to the large actinoporin family. The toxin binds to sphingomyelin (SM) containing membranes, and shows high binding specificity for this lipid. In this study, we have examined the role of the hydrogen bonding groups of the SM long-chain base (i.e., the 2NH and the 3OH) for StnII recognition. We prepared methylated SM-analogs which had reduced hydrogen bonding capability from 2NH and 3OH. Both surface plasmon resonance experiments, and isothermal titration calorimetry measurements indicated that StnII failed to bind to bilayers containing methylated SM-analogs, whereas clear binding was seen to SM-containing bilayers. StnII also failed to induce calcein release (i.e., pore formation) from vesicles made to contain methylated SM-analogs, but readily induced calcein release from SM-containing vesicles. Molecular modeling of SM docked to the phosphocholine binding site of StnII indicated that the 2NH and 3OH groups were likely to form a hydrogen bond with Tyr135. In addition, it appeared that Tyr111 and Tyr136 could donate hydrogen bonds to phosphate oxygen, thus stabilizing SM binding to the toxin. We conclude that the interfacial hydrogen bonding properties of SM, in addition to the phosphocholine head group, are crucial for high-affinity SM/StnII-interaction.

Environmental-friendly extraction of di(2-ethylhexyl) phthalate from poly(vinyl chloride) using liquefied dimethyl ether.

Poly(vinyl chloride) (PVC) is one of the most widely used plastics. However, a major challenge in recycling PVC is that there is no economical method to separate and remove its toxic phthalate plasticizers. This research made a breakthrough by extracting PVC with liquefied dimethyl ether (DME) and successfully separating the plasticizer components. Nearly all (97.1 %) of the di(2-ethylhexyl) phthalate plasticizer was extracted within 30 min by passing liquefied DME (285 g) through PVC at 25 °C. The compatibility of PVC with organic solvents, including liquefied DME, was derived theoretically from their Hansen solubility parameters (HSP), and actual dissolution experiments were conducted to determine the optimal PVC solvents. A liquefied DME mixture was used to dissolve PVC, and the extract was diluted with ethanol to precipitate the dissolved PVC. We demonstrated that liquefied DME is a promising method for producing high quality recycled products and that the process retains the fundamental properties of plasticizers and PVC without inducing degradation or depolymerization. Because of its low boiling point, DME can be easily separated from the solute after extraction, allowing for efficient reuse of the solvent, extracted plasticizer, and PVC. DME does not require heat and produces little harmful wastewater, which significantly reduces the energy consumption of the plasticizer additive separation process.

Mechanism of Protein-PDMS Visible Particles Formation in Liquid Vial Monoclonal Antibody Formulation.

Visible particles (VPs) formation in liquid monoclonal antibody formulations is a critical quality issue. Formulations that include poloxamer 188 (PX188) as a surfactant are prone to the formation of VPs comprising aggregated complexes of protein and polydimethylsiloxane (PDMS; silicone oil) derived from primary containers. However, the mechanisms through which these VPs form are complicated and remain to be fully elucidated. This study demonstrates for the first time the dominant spot and pathway of protein-PDMS VP formation in a particular liquid vial formulation. Specifically, when a vial sealed with a PDMS-coated stopper is stored in an upright position under conditions whereby the antibody solution has become well-adhered to the stopper and an air phase exists in the vicinity, protein-PDMS aggregates form on the stopper and are then desorbed into the drug solution to be detected as VPs. Here, we evaluated the effects of several factors on VP formation: adhesion of the drug solution to the stopper, storage orientation, silicone coating on the stopper, vial material, and hydrophobicity of PX188. Remarkably, we found that changing any one of the factors could significantly affect VP formation. Our findings are instructive for better understanding the mechanisms of VP formation in vial products and can provide strategies for VP mitigation in biotherapeutics.

N-cholesteryl sphingomyelin-A synthetic sphingolipid with unique membrane properties.

A sphingomyelin chimera in which the amide-linked acyl chain was replaced with cholesterol carbamate was prepared and its properties examined. The sphingomyelin/cholesterol chimera (N-cholesterol-D-erythro-sphingomyelin) was able to form unilamellar vesicles of defined size when extruded through 200nm pore size membranes. These N-cholesteryl sphingomyelin bilayers were resistant to solubilization by Triton X-100. When N-cholesteryl sphingomyelin was added to N-palmitoyl sphingomyelin (N-palmitoyl-d-erythro-sphingomyelin) bilayers, it increased acyl chain order as determined by 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy. N-cholesteryl sphingomyelin was, however, not as good an inducer of membrane order compared to cholesterol on a molar basis. Differential scanning calorimetry studies further showed that the miscibility of N-cholesteryl sphingomyelin with N-palmitoyl-d-erythro-sphingomyelin bilayers was non-ideal, and the effect of N-cholesteryl sphingomyelin on the N-palmitoyl-d-erythro-sphingomyelin gel-fluid transition enthalpy differed from that seen with cholesterol. Together with N-palmitoyl-d-erythro-sphingomyelin, the N-cholesteryl sphingomyelin chimera was able to form sterol-enriched ordered domains in a fluid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer. N-cholesteryl sphingomyelin in the absence of N-palmitoyl-d-erythro-sphingomyelin was unable to form such sterol-enriched ordered domains in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer. However, N-cholesteryl sphingomyelin markedly increased the affinity of cholestatrienol for N-cholesteryl sphingomyelin containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayers, suggesting that N-cholesteryl sphingomyelin was able to somehow stabilize sterol interaction in fluid bilayers. Based on our results, we conclude that N-cholesteryl sphingomyelin behaved more like a cholesterol than a sphingolipid in fluid bilayer membranes. Because N-cholesteryl sphingomyelin increased bilayer order, conferred resistance against detergent solubilization, and is not degradable by phospholipases A(2), it could constitute a good lipocomplex matrix for drug delivery vehicles.

Effects of low concentration fluoride released from fluoride-sustained-releasing composite resin on the bioactivity of Streptococcus mutans.

This study aimed to determine the effects of the low concentration of fluoride sustained-released from the composite resin on properties of Streptococcus mutans (S. mutans). The proliferation, adhesion, biofilm formation, and lactic acid production of the bacterium were investigated after the treatment with fluoride from the composite resin. The activity and expression of ATPase, glucosyltransferase (GTF), and enolase were also determined by colorimetric assay and western blot analysis. Fluoride from the sustained-releasing composite resin significantly inhibited biofilm formation, adhesion, and acid production of S. mutans but did not influence the growth and ATPase activity of the bacterial strain. Fluoride-sustained-releasing composite resin inhibited adhesion, biofilm formation, and acid production of S. mutans through the suppression of GTF expression as well as the expression and activity of enolase. These resultls suggest the clinical significance of fluoride-sustained-releasing composite resin.

A familial case of periodontal Ehlers-Danlos syndrome lacking skin extensibility and joint hypermobility with a missense mutation in C1R.

Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder first described by Stewart in 1977 that is characterized by severe gingival recession and periodontitis that triggers premature loss of permanent teeth and alveolar bone absorption. It was recently shown that pEDS is caused by a heterozygous missense mutation in C1R or C1S, which encode complement 1 proteases. Here, we report a familial case of pEDS with a novel heterozygous missense mutation, c.674G>C (p.R225P), in C1R (NM_001733.4). The case exhibited pretibial hyperpigmentation and extended periodontitis but neither skin extensibility nor joint hypermobility, suggesting that this mutation will expand the definition of pEDS.

Nationwide survey for bisphosphonate-related osteonecrosis of the jaws in Japan.

PURPOSE: A nationwide retrospective cohort study was conducted by the Japanese Society of Oral and Maxillofacial Surgeons to assess the occurrence of bisphosphonate (BP)-related osteonecrosis of the jaws (BRONJ) during 2006 to 2008 and to elucidate the outcome and factors associated with remission of BRONJ. MATERIALS AND METHODS: A written questionnaire, including the clinical characteristics, management, and outcome of patients with BRONJ, was sent to 248 institutions certified as training facilities by the Japanese Society of Oral and Maxillofacial Surgeons in 2008. RESULTS: A total of 568 patients with BRONJ, including suspicious cases, were registered. Of these 568 patients, 263, including the maxilla in 81, the mandible in 160, and both in 22, met the working definition of BRONJ proposed by the American Association of Oral and Maxillofacial Surgeons. The patients included 219 women (83.3%) and 44 men (16.7%). Of these patients, 152 (57.8%) had received intravenous BPs, 104 (39.5%) had received oral BPs, and 7 (2.7%) had received both. The mean duration of administration until onset of BRONJ was 23.6 months for intravenous BPs and 33.2 months for oral BPs. BRONJ was stage 1 in 42 patients (16.0%), stage 2 in 187 (71.1%), stage 3 in 32 (12.2%), and unknown in 2. Of these patients, 34.2% had remission of BRONJ, 46.0% had persistent or progressive disease, and 19.7% died of malignancy or were lost to follow-up. Statistical analysis revealed that surgical treatment, including tooth extraction, sequestrectomy, and segmental mandibulectomy, contributed to the remission of BRONJ. In contrast, conservative treatment, concurrent anticancer drugs, poor oral hygiene, and the use of intravenous BPs did not. CONCLUSIONS: The relative ratio of BRONJ related to the use of oral BPs was greater in Japan than in the United States and European Union. Surgical treatment contributed to remission of BRONJ, and conservative treatment, concurrent anticancer drugs, poor oral hygiene, and intravenous BPs did not.

Stability of spherical vesicles in electric fields.

The stability of spherical vesicles in alternating (ac) electric fields is studied theoretically for asymmetric conductivity conditions across their membranes. The vesicle deformation is obtained from a balance between the curvature elastic energies and the work done by the Maxwell stresses. The present theory describes and clarifies the mechanisms for the four types of morphological transitions observed experimentally on vesicles exposed to ac fields in the frequency range from 500 to 2 x 10(7) Hz. The displacement currents across the membranes redirect the electric fields toward the membrane normal to accumulate electric charges by the Maxwell-Wagner mechanism. These accumulated electric charges provide the underlying molecular mechanism for the morphological transitions of vesicles as observed on the micrometer scale.

Nasolabial morphologic changes after a Le Fort I osteotomy: a three-dimensional anthropometric study.

After a Le Fort I osteotomy, nasal and labial changes are sometimes undesirable. The aim of this study was to perform a three-dimensional evaluation of the morphologic changes of the nose and lips after a Le Fort I osteotomy with a three-dimensional laser scanner.Twelve female patients who underwent a Le Fort I osteotomy with bilateral sagittal split ramus osteotomy (mean age, 24.2 y) were selected. Three-dimensional facial morphology was measured immediately after surgery and 6 months after surgery with a three-dimensional laser scanner. Analysis of the three-dimensional data was performed with three-dimensional image analyzing software. The evaluation was performed by (1) linear and angular analyses of landmarks, (2) three-dimensional curvature, and (3) visual qualitative analysis using superimposing mapping images. The results were compared control with data taken from volunteers (mean age, 24.5 y).Lateral expansion of nasal alae was commonly observed after surgery. The labial changes were mainly due to movements of the jawbone, and obvious flattening was not detected in this study. There was no relationship between the nasal changes and maxillary advancement.The nasal morphologic changes after a Le Fort I osteotomy consist mainly of a widening of the nasal alae caused by the release of the muscle insertion and their retraction. This change was not influenced by the direction of maxillary movements.

[Oral candidiasis: clinical features and control].

Candidiasis is the most commonly encountered fungal infection, and oral candidiasis is often observed as a local opportunistic infection. Oral candidiasis is clinically divided into three types: acute forms, chronic forms, and Candida-associated lesions. Candida adhesion and multiplication are largely regulated by the local and systemic factors of the host. The local factors include impairment of the oral mucosal integrity, which is usually impaired by hyposalivation, anticancer drugs/radiation for head and neck cancers, denture wearing, a decrease in the oral bacterial population, and poor oral hygiene. Among Candida species, oral candidiasis is mostly caused by Candida albicans (C. albicans), C. glabrata, or C. tropicalis. Oral Candida induces a variety of symptoms, such as oral mucosal inflammation manifesting as an uncomfortable feeling, pain, erythema, erosion, taste abnormalities, and hyperplasia of the oral mucosa. Candida overgrowth in the oral cavity may disseminate to distant organs. Therefore, in order to avoid the sequelae of systemic candidiasis, oral candidiasis should be rapidly controlled. Oral candidiasis is usually treated by the local application of antifungal drugs. However, oral candidiasis occasionally escapes the control of such local treatment due to the development of multi-drug resistant Candida strains and species or due to the suppression of salivation or cellular immune activity. When drug-resistant strains are suspected as the pathogens and when the host is generally compromised, the oral administration of combinations of antifungal drugs, enhancement of cellular immune activity, and improvement of the nutritional condition are recommended.

Metal nanoparticles-induced activation of NLRP3 inflammasome in human oral keratinocytes is a possible mechanism of oral lichenoid lesions.

The NLRP3 inflammasome has been implicated in the pathogenesis of various inflammatory diseases and is activated by particulate stimulants. Oral epithelial keratinocytes are frequently exposed to metal nanoparticles. In this study, we examined the effects of gold, silver, and palladium nanoparticles, which are frequently used for dental metal alloys on cell proliferation, cytotoxicity, autophagy, lysosomal functions, and NLRP3 inflammasome activation using the immortalized human oral keratinocyte cell line RT-7. The metal nanoparticles were agglomerated in the membrane vesicles in RT-7 cells and suppressed cell proliferation and increased lactate dehydrogenase activity as well as the proportion of apoptotic cells. Silver and palladium nanoparticles induced autophagy and lysosomal dysfunctions and all metal nanoparticles tested triggered the secretion of IL-1ß through caspase-1 activation. Furthermore, the epithelium obtained from patients with oral lichenoid lesions (OLLs) had robust NLRP3, ASC, caspase-1, and IL-1ß-positive keratinocytes and cDNA microarray showed significant elevation in the mRNA levels of NLRP3. These results suggest that internalized metal nanoparticles in oral mucosal epithelial cells activate the NLRP3 inflammasome through the induction of lysosomal damage and autophagy dysfunction. This process may be involved in the pathogenesis of OLL and suggest its potential as an alternative target for OLL therapy.

Synthesis of calcium phosphate hydrogel from waste incineration fly ash and bone powder.

Waste incineration fly ash and bone powder could be successfully recycled into calcium phosphate hydrogel, a type of fast proton conductor. Various properties of the intermediate and calcium phosphate hydrogel from them were characterized and compared with that from calcium carbonate reagent. It was found that the intermediate from the incineration fly ash and calcium phosphate glass was more brittle than that from bone powder and calcium carbonate reagent. The electric conductivity of crystallized hydrogel obtained from all raw materials increases exponentially with temperature. However, the crystallized hydrogel from incineration fly ash has lower electric conductivity and lower crystallinity than that from bone powder and the reagent. Moreover, the difference in electric conductivity between these crystallized hydrogels decreases with temperature. Compared with using the reagent as a raw material, bone powder provides a 25% reduction in the usage of H(3)PO(4) to acquire the crystallized hydrogel which has the highest conductivity. These experimental results suggest that the incineration fly ash and bone powder are useful calcium sources for the synthesis of calcium phosphate hydrogel.

Synthesis of calcium phosphate hydrogel from waste incineration fly ash and its application to fuel cell.

Waste incineration fly ash was successfully recycled to calcium phosphate hydrogel, a type of fast proton conductor. The crystallized hydrogel from incineration fly ash had a lower electric conductivity and a lower crystallinity than that from calcium carbonate reagent. However, the difference in electric conductivity between these crystallized hydrogels decreases with temperature. This was due to the presence of potassium in the incineration fly ash. The fuel cell with a membrane electrode assembly (MEA) using the calcium phosphate hydrogel membrane prepared from incineration fly ash was observed to generate electricity. The performance of this fuel cell was almost equal to that of a mixture of K(2)CO(3) and CaCO(3) reagents; further, the performance of the former was superior to the fuel cell with a perfluorosulfonic polymer membrane at temperatures greater than approximately 85 degrees C.

Wear analysis of retrieved ceramic-on-ceramic articulations in total hip arthroplasty: Femoral head makes contact with the rim of the socket outside of the bearing surface.

We investigated articular bearing surfaces retrieved from three patients with ceramic-on-ceramic total hip arthroplasties using high-quality alumina. The duration of implantation was 3.5, 3.0, and 2.5 years, respectively. Dislocation of the hip joint after implantation did not occur in any patients. The retrieved prostheses were examined by stereomicroscopy and scanning electron microscopy (SEM). In the main load-bearing area, no wear marks were seen in any sockets. However, in all three cases, stripe scars were observed at the rim of the alumina inlay under stereomicroscopy, despite the lack of indentation in the socket and the stem, which suggests impingement. Such scars were not observed on the load-bearing surface. Under SEM, the scars showed excessive wear, including material excavation, that has not been observed in conventional hip simulator experiments. These findings are similar to those of experiments in which a simulator was programmed to distract the femoral head from the socket. The present results suggest that the femoral head can separate from the socket without neck-socket impingement in vivo.

Molecular-scale observation of the surface of polystyrene particles by AFM.

The surface morphology of polystyrene particles prepared by soap-free emulsion polymerization was observed in situ using the tapping mode of an atomic force microscope (AFM). Here, the use of a cationic initiator enabled us to synthesize positively charged polystyrene, which then adsorbed electrostatically onto the negatively charged mica plate with molecular-scale smoothness. The following was found from AFM measurements in water. The surface of polystyrene particles changed from smooth to rough as the polymerization proceeded in the experimental condition, where the bulk generated tiny particles continuously, because of the heterocoagulation in the growth process between the newborn and tiny particles and the existing particles. However, it is easy to prepare the particles with smooth surfaces on the condition of rich monomers because the monomers in the bulk dissolve the polymers which form the surface morphology to be deformable and reduce the interfacial area.

TCDD disrupts posterior palatogenesis and causes cleft palate.

Dioxins (e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD) cause cleft palate at a high rate. A post-fusional split may contribute to the pathogenesis, and tissue fragility may be a concern. The objective of this study was to investigate the effects of TCDD on the palatal epithelium, bone and muscle, which contribute to tissue integrity. ICR mice (10-12 weeks old) were used. TCDD was administered on E12.5 at 40 mg/kg. Immunohistochemical staining for AhR, ER-α, laminin, collagen IV, osteopontin, Runx2, MyoD, and desmin were performed. Furthermore, western blot analysis for osteopontin, Runx2, MyoD, and desmin were performed to evaluate protein expression in the palatal tissue. Immunohistologically, there was little difference in the collagen IV and laminin localization in the palatal epithelium between control versus TCDD-treated mice. Runx2 and osteopontin immunoreactivity decreased in the TCDD-treated palatal bone, and MyoD and desmin decreased in the TCDD-treated palatal muscle. AhR and ER-α immunoreactivity were localized to the normal palatal bone, but ER-α was diminished in the TCDD-treated palate. On western blot analysis, Runx2, MyoD, and desmin were all downregulated in the TCDD-treated palate. TCDD may suppress palatal osteogenesis and myogenesis via AhR, and cause cleft palates via a post-fusional split mechanism, in addition to a failure of palatal fusion.

A multicenter phase I/II study of the BCNU implant (Gliadel(®) Wafer) for Japanese patients with malignant gliomas.

Carmustine (BCNU) implants (Gliadel(®) Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. A prospective, multicenter phase I/II study involving Japanese patients with MGs was performed to evaluate the efficacy, safety, and pharmacokinetics of BCNU implants. The study enrolled 16 patients with newly diagnosed MGs and 8 patients with recurrent MGs. After the insertion of BCNU implants (8 sheets maximum, 61.6 mg BCNU) into the removal cavity, various chemotherapies (including temozolomide) and radiotherapies were applied. After placement, overall and progression-free survival rates and whole blood BCNU levels were evaluated. In patients with newly diagnosed MGs, the overall survival rates at 12 months and 24 months were 100.0% and 68.8%, and the progression-free survival rate at 12 months was 62.5%. In patients with recurrent MGs, the progression-free survival rate at 6 months was 37.5%. There were no grade 4 or higher adverse events noted due to BCNU implants, and grade 3 events were observed in 5 of 24 patients (20.8%). Whole blood BCNU levels reached a peak of 19.4 ng/mL approximately 3 hours after insertion, which was lower than 1/600 of the peak BCNU level recorded after intravenous injections. These levels decreased to less than the detection limit (2.00 ng/mL) after 24 hours. The results of this study involving Japanese patients are comparable to those of previous studies in the United States and Europe.