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We experienced a case of mass-forming intrahepatic cholangiocarcinoma which could not been diagnosed accurately without pathologic findings. A 78-year-old Japanese woman with no particular symptoms was admitted for changes in liver function tests. Ultrasonography revealed a solid liver tumor. When there are no typical imaging features, no pathognomonic clinical findings and no obvious risk factors for any specific hepatic tumor, it may be difficult to make an accurate diagnosis before surgical resection. The lesion was resected on the basis of a high degree of suspicion for malignancy and submitted for pathologic evaluation. Microscopically, the neoplasm was a moderately differentiated adenocarcinoma with abundant fibrous stroma, consistent with a mass-forming cholangiocarcinoma. This case exemplifies the importance of considering the various tumorous and non-tumorous diseases in the differential diagnosis of a liver mass with atypical features, especially when malignancy cannot be excluded.

The rationale for fusing dendritic cells (DCs) with whole tumor cells to generate anticancer vaccines resides in the fact that the former operate as potent antigen-presenting cells, whereas the latter express a constellation of tumor-associated antigens (TAAs). Although the administration of DC/malignant cell fusions to cancer patients is safe and this immunotherapeutic intervention triggers efficient tumor-specific T-cell responses in vitro, a limited number of objective clinical responses to DC/cancer cell fusions has been reported thus far. This review discusses novel approaches to improve the immunogenicity of DC/malignant cell fusions as anticancer vaccines.

Tumor-derived transforming growth factor β1 (TGFβ1) generally abrogates the immunogenicity of dendritic cells (DCs) fused to whole cancer cells. We have recently revealed that ethanol-treated neoplastic cells fused to DCs exposed to 2 Toll-like receptor agonists efficiently induce cytotoxic T lymphocytes via TGFβ1 blockade and the production of interleukin-12.

Listeria monocytogenes is a foodborne pathogen that causes the potentially life-threatening illness listeriosis. Previously, a few clones of L. monocytogenes persisting in a cold-smoked fish processing plant were isolated from the plant's products continuously. To evaluate the role of biofilms in the persistence of L. monocytogenes strains specific to this plant, the abilities of the persistent strain (PS) and transient strain (TS) of L. monocytogenes found in this plant to form biofilms were compared, as was resistance to the sanitizing effects of benzalkonium chloride (BC). The PS produced more biofilm than the TS in 48 h. The half-maximal effective concentration (EC50), the BC concentration at which the ATP bioluminescence of each bacterial strain decreased by 50 % relative to its maximum activity, was about 150-fold higher in the PS than in the TS. In contrast, when these values were measured in organisms in a planktonic state, the EC50 of the PS was only 2.2-fold higher than that of the TS. Extracellular polymeric substances (EPS) were extracted from biofilms, and the glucose content of these biofilms was determined with the phenol-sulfuric acid method to estimate the quantity of EPS. The total amount of EPS in the PS biofilm was higher than that in the TS biofilm. These findings suggest that the PS produces greater amounts of biofilm and EPS than the TS, which results in greater resistance of the PS to disinfectants. The persistence of the strain in the fish processing plant might be attributable to these properties.

The induction of antitumor immune responses by dendritic cell (DC)/tumor cell fusions can be modulated by their activation status. Our recent work reveals that the combination of Toll-like receptor 2 (TLR2) and TLR4 agonists promotes the immunogenicity of DC/tumor cell fusions, allowing them to overcome the immunosuppressive effects of transforming growth factor β1.

The therapeutic efficacy of fusion cell (FC)-based cancer vaccine generated with whole tumor cells and dendritic cells (DCs) requires the improved immunogenicity of both cells. Treatment of whole tumor cells with ethanol resulted in blockade of immune-suppressive soluble factors such as transforming growth factor (TGF)-β1, vascular endothelial growth factor, and IL-10 without decreased expression of major histocompatibility complex (MHC) class I and the MUC1 tumor-associated antigen. Moreover, the ethanol-treated tumor cells expressed "eat-me" signals such as calreticulin (CRT) on the cell surface and released immunostimulatory factors such as heat shock protein (HSP)90α and high-mobility group box 1 (HMGB1). A dual stimulation of protein-bound polysaccharides isolated from Coriolus versicolor (TLR2 agonist) and penicillin-inactivated Streptococcus pyogenes (TLR4 agonist) led human monocyte-derived DCs to produce HSP90α and multiple cytokines such as IL-12p70 and IL-10. Interestingly, incorporating ethanol-treated tumor cells and TLRs-stimulated DCs during the fusion process promoted fusion efficiency and up-regulated MHC class II molecules on a per fusion basis. Moreover, fusions of ethanol-treated tumor cells and dual TLRs-stimulated DCs (E-tumor/FCs) inhibited the production of multiple immune-suppressive soluble factors including TGF-β1 and up-regulated the production of IL-12p70 and HSP90α. Most importantly, E-tumor/FCs activated T cells capable of producing high levels of IFN-γ, resulting in augmented MUC1-specific CTL induction. Collectively, our results illustrate the synergy between ethanol-treated whole tumor cells and dual TLRs-stimulated DCs in inducing augmented CTL responses in vitro by FC preparations. The alternative system is simple and may provide a platform for adoptive immunotherapy.

Various strategies have been developed to deliver tumor-associated antigens (TAAs) to dendritic cells (DCs). Among these, the fusion of DCs and whole cancer cells can process a broad array of TAAs, including hitherto unidentified molecules, and present them in complex with MHC Class I and II molecules and in the context of co-stimulatory signals. DC-cancer cell fusions have been shown to stimulate potent antitumor immune responses in animal models. In early clinical trials, however, the antitumor effects of DC-cancer cell fusions are not as vigorous as in preclinical settings. This mini-review summarizes recent advances in anticancer vaccines based on DC-cancer cell fusions.

Aim: In the digestive tract, endoscopic band ligation (EBL) has been routinely used for the treatment of variceal bleeding and superficial malignancies. In recent years, endoscopic treatments for duodenal varices, adenoma, and cancer have also actively incorporated EBL. Although there have been a number of reports on the risks associated with the use of EBL in the esophagus, stomach, and colon, few studies have focused on EBL in the duodenum. We performed EBL procedures to evaluate the risks associated with the use of EBL in the duodenum., Material and Methods: Overall, EBLs were performed at nine sites in duodenum sampled from a pig immediately after sacrifice. Submucosal saline injections were placed in three of the nine studied sites., Results: Regardless of saline injection, the full thickness of the duodenal wall was ligated in all attempts., Conclusions: Routine EBL is not recommended in the duodenum because the risk of perforation is unacceptably high.

Fluoroquinolones (FQs) have been detected in aquatic environments in several countries. Long-term exposure to low levels of antimicrobial agents provides selective pressure, which might alter the sensitivity of bacteria to antimicrobial agents in the environment. Here, we examined FQ levels and the resistance of Escherichia coli (E. coli) to FQs by phenotyping and genotyping. In the aquatic environment in Osaka, Japan, ciprofloxacin, enoxacin, enfloxacin, lomefloxacin, norfloxacin, and ofloxacin were detected in concentrations ranging from 0.1 to 570 ng L(-1). FQ-resistant E. coli were also found. Although no obvious correlation was detected between the concentration of FQs and the presence of FQ-resistant E. coli, FQ-resistant E. coli were detected in samples along with FQs, particularly ciprofloxacin and ofloxacin. Most FQ-resistant E. coli carried mutations in gyrA, parC, and parE in quinolone resistance-determining regions. No mutations in gyrB were detected in any isolates. Amino acid changes in these isolates were quite similar to those in clinical isolates. Six strains carried the plasmid-mediated quinolone resistance determinant qnrS1 and expressed low susceptibility to ciprofloxacin and nalidixic acid: the minimum inhibitory concentrations ranged from 0.25 μg mL(-1) for ciprofloxacin, and from 8 to 16 μg mL(-1) for nalidixic acid. This finding confirmed that plasmids containing qnr genes themselves did not confer full resistance to quinolones. Because plasmids are responsible for much of the horizontal gene transfer, these genes may transfer and spread in the environment. To our knowledge, this is the first report of plasmid-mediated quinolone resistance determinant qnrS1 in the aquatic environment, and this investigation provides baseline data on antimicrobial resistance profiles in the Osaka area., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The local structure and dynamic behaviour of a benzene molecular assembly confined within the nano-cavities of a zinc-based metal-organic framework, [Zn(4)O(CO(2)C(6)H(4)CO(2))(3)](n) (IRMOF-1), were investigated by means of molecular dynamics (MD) simulations. The local structure of the confined benzene molecules was evaluated using radial distribution functions. The sites for adsorption of benzene in IRMOF-1 were well defined by the simulation. The diffusion coefficients at ambient temperature suggested that the mobility of the confined benzene was high, comparable to the bulk fluid. Decreasing the temperature gave rise to the aggregation of benzene in the IRMOF-1 frameworks. Molecular aggregation was attributed to the localization of benzene in the large and the small cavities of IRMOF-1, respectively. Both the translational diffusion coefficient and the trajectory of benzene provided evidence that the localization of benzene in the large and the small cavities takes place at ca. 200 K. Furthermore, at high benzene loading, the migration of benzene in the small cavities was prevented (frozen) below 135 K. Thus, the translational degree of freedom of the benzene molecules changed drastically, depending on the temperature.

Background: Optimal management of metastatic brain disease requires precise detection and detailed characterization of all intracranial lesions., Methods: We analyzed an experience with 3200 brain MRI investigations performed at 1.5 T and 3.0 T for identification and/or evaluation of intracranial metastases. Usually axial T1- and T2-weighted images and contrast-enhanced T1-weighted images in axial and coronal and/or sagittal projections were obtained. Fluid-attenuated inversion recovery and diffusion-weighted imaging were sometimes used as well. Routinely, 0.2 mmol/kg of gadoteridol (ProHance®) was administered intravenously, but the dose was reduced to 0.1 mmol/kg in elderly patients or in patients with mild renal dysfunction., Findings: Magnetic resonance imaging (MRI) provided excellent information on tumor location; interrelations with functionally important intracranial structures; type of growth; vascularity; recent, old or multiple hemorrhages within or in the vicinity of the mass; presence of peritumoral edema; necrotic changes; subarachnoid dissemination; meningeal carcinomatosis. However, without administration of gadoteridol or without contrast enhancement, small metastatic tumors could not be reliably distinguished from brain lacunes. Some metastases (malignant melanoma, thyroid cancer, endocrine carcinoma, small cell lung carcinoma) may demonstrate specific neuroimaging features. Non-metastatic -multiple brain lesions caused by vascular, inflammatory, demyelinative or lymphoproliferative diseases require a thorough differential diagnosis with metastatic brain tumors based not only on neuroimaging but on additional analysis of various clinical data., Conclusion: Contemporary MRI techniques provide excellent options for detection, detailed characterization, and differential diagnosis of metastatic brain tumors, which is extremely important when choosing the optimal treatment strategy, particularly with Gamma Knife radiosurgery.

The availability of advanced computer-aided robotized devices for the Gamma Knife (i.e., an automatic positioning system and PerfeXion) resulted in significant changes in radiosurgical treatment strategy. The possibility of applying irradiation precisely and the significantly improved software for treatment planning led to the development of the original concept of robotic Gamma Knife microradiosurgery, which is comprised of the following: (1) precise irradiation of the lesion with regard to conformity and selectivity; (2) intentional avoidance of excessive irradiation of functionally important anatomical structures, particularly cranial nerves, located both within the target and in its vicinity; (3) delivery of sufficient radiation energy to the tumor with a goal of shrinking it while keeping the dose at the margins low enough to prevent complications. Realization of such treatment principles requires detailed evaluation of the microanatomy of the target area, which is achieved with an advanced neuroimaging protocol. From 2003, we applied the described microradiosurgical concept in our clinic for patients with benign skull base tumors. Overall, 75 % of neoplasms demonstrated shrinkage, and 47 % showed ≥50 % and more volume reduction. Treatment-related complications were encountered in only 6 % of patients and were mainly related to transient cranial nerve palsy. Just 2 % of neoplasms showed regrowth after irradiation. In conclusion, applying the microradiosurgical principles based on advanced neuroimaging and highly precise treatment planning is beneficial for patients, providing a high rate of tumor shrinkage and a low morbidity rate.

Fusobacterium varium is an elusive pathogenic factor in ulcerative colitis (UC); conventional methods of fecal culture rarely recover F. varium. We have developed a nested culture method to recover Fusobacterium and we used it to investigate whether F. varium could be isolated from UC patients. We enrolled 50 consecutive patients in this study; 26 received combination antibiotic therapy that included amoxicillin, tetracycline, and metronidazole (ATM) for 2 weeks and were thus assigned to the ATM group, and the remaining 24 were assigned to the non-ATM group and did not receive any antibiotics. Stool samples were added to 10 ml of GAM broth that contained neomycin and crystal violet. The samples were vortexed and incubated under anaerobic conditions. The preincubated broth was streaked onto a Fusobacterium-selective agar plate and then incubated under anaerobic conditions. The species of the colonies isolated were identified using the Vitek Automated system and PCR analysis. We recoverd F. varium from 7 of the 24 non-ATM patients (29.2%) and none from the ATM patients (0%) (P = 0.0035). All of the F. varium isolates were susceptible to ATM. This study suggests that the recovery of F. varium is related to UC, which aligns with results from previous studies that used mucosal culture, immunostaining, real-time PCR, and serological studies.

From 1993 to 2011, a total of 3,095 patients with brain metastases underwent Gamma Knife radiosurgery (GKS) at Tokyo Women's Medical University. Follow-up information on 2,283 of these patients was available for retrospective analysis. The cases were separated into three groups according to the treatment period, the model of the Gamma Knife used, main goals of treatment, and technical nuances of radiosurgery. In the latest cohort of patients treated with the Leksell Gamma Knife model 4C with automatic positioning system, an optimized treatment strategy was applied. It was based on highly selective dose planning, with the use of multiple small isocenters located within the bulk of the mass, which was done for prevention of the excessive irradiation of the perilesional brain and avoidance of its posttreatment edema. In cases of large cystic tumors, selective coverage of the contrast-enhancing capsule with chain-like application of multiple small isocenters was done. Introduction of the new treatment strategy did not affect the 1-year tumor control rate, which was consistently >90 %. However, it did result in a statistically significant reduction of severe posttreatment peritumoral brain edema (from 15.5 % to 6.3 %; P < 0.0001). In conclusion, recent technical and methodological achievements of GKS seemingly do not affect its high efficacy in cases of brain metastasis with regard to tumor control. However, it may result in a prominent reduction of treatment-associated -morbidity, which is particularly important in patients with large and/or critically located neoplasm.

Background: Gamma Knife radiosurgery (GKS) is currently performed with 0.1 mm preciseness, which can be designated microradiosurgery. It requires advanced methods for visualizing the target, which can be effectively attained by a neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state (CISS) images., Methods: Since 2003, the following thin-sliced images are routinely obtained before GKS of skull base lesions in our practice: axial CISS, gadolinium-enhanced axial CISS, gadolinium-enhanced axial modified time-of-flight (TOF), and axial computed tomography (CT). Fusion of "bone window" CT and magnetic resonance imaging (MRI), and detailed three-dimensional (3D) delineation of the anatomical structures are performed with the Leksell GammaPlan (Elekta Instruments AB). Recently, a similar technique has been also applied to evaluate neuroanatomy before open microsurgical procedures., Results: Plain CISS images permit clear visualization of the cranial nerves in the subarachnoid space. Gadolinium-enhanced CISS images make the tumor "lucid" but do not affect the signal intensity of the cranial nerves, so they can be clearly delineated in the vicinity to the lesion. Gadolinium-enhanced TOF images are useful for 3D evaluation of the interrelations between the neoplasm and adjacent vessels. Fusion of "bone window" CT and MRI scans permits simultaneous assessment of both soft tissue and bone structures and allows 3D estimation and correction of MRI distortion artifacts., Conclusion: Detailed understanding of the neuroanatomy based on application of the advanced neuroimaging protocol permits performance of highly conformal and selective radiosurgical treatment. It also allows precise planning of the microsurgical procedures for skull base tumors.

Induction of antitumor immunity by dendritic cell (DC)-tumor fusion cells (DC/tumor) can be modulated by their activation status. In this study, to address optimal status of DC/tumor to induce efficient antigen-specific cytotoxic T lymphocytes (CTLs), we have created various types of DC/tumor: 1) un-activated DC/tumor; 2) penicillin-killed Streptococcus pyogenes (OK-432; TLR4 agonist)-activated DC/tumor; 3) protein-bound polysaccharides isolated from Coriolus versicolor (PSK; TLR2 agonist)-activated DC/tumor; and 4) Combined OK-432- and PSK-activated DC/tumor. Moreover, we assessed the effects of TGF-β1 derived from DC/tumor on the induction of MUC1-specific CTLs. Combined TLR2- and TLR4-activated DC/tumor overcame immune-suppressive effect of TGF-β1 in comparison to those single activated or un-activated DC/tumor as demonstrated by: 1) up-regulation of MHC class II and CD86 expression on DC/tumor; 2) increased fusion efficiency; 3) increased production of fusions derived IL-12p70; 4) activation of CD4(+) and CD8(+) T cells that produce high levels of IFN-γ; 5) augmented induction of CTL activity specific for MUC1; and 6) superior efficacy in inhibiting CD4(+)CD25(+)Foxp3(+) T cell generation. However, DC/tumor-derived TGF-β1 reduced the efficacy of DC/tumor vaccine in vitro. Incorporating combined TLRs-activation and TGF-β1-blockade of DC/tumor may enhance the effectiveness of DC/tumor-based cancer vaccines and have the potential applicability to the field of adoptive immunotherapy.

A number of intracranial tumors demonstrate some degree of enlargement after stereotactic radiosurgery (SRS). It necessitates differentiation of their regrowth and various treatment-induced effects. Introduction of low-dose standards for SRS of benign neoplasms significantly decreased the risk of the radiation-induced necrosis after -management of schwannomas and meningiomas. Although in such cases a transient increase of the mass volume within several months after irradiation is rather common, it usually followed by spontaneous shrinkage. Nevertheless, distinguishing tumor recurrence from radiation injury is often required in cases of malignant parenchymal brain neoplasms, such as metastases and gliomas. The diagnosis is frequently complicated by histopathological heterogeneity of the lesion with coexistent viable tumor and treatment-related changes. Several neuroimaging modalities, namely structural magnetic resonance imaging (MRI), diffusion-weighted imaging, diffusion tensor imaging, perfusion computed tomography (CT) and MRI, single-voxel and multivoxel proton magnetic resonance spectroscopy as well as single photon emission CT and positron emission tomography with various radioisotope tracers, may provide valuable diagnostic information. Each of these methods has advantages and limitations that may influence its usefulness and accuracy. Therefore, use of a multimodal radiological approach seems reasonable. Addition of functional and metabolic neuroimaging to regular structural MRI investigations during follow-up after SRS of parenchymal brain neoplasms may permit detailed evaluation of the treatment effects and early prediction of the response. If tissue sampling of irradiated intracranial lesions is required, it is preferably performed with the use of metabolic guidance. In conclusion, differentiation of tumor progression and radiation-induced effects after intracranial SRS is challenging. It should be based on a complex evaluation of the multiple clinical, radiosurgical, and radiological factors.

Background: Gamma Knife surgery (GKS) should be considered a standard treatment option for small and medium-sized vestibular schwannomas (VSs). It results in a tumor control rate similar to that seen with microsurgery and provides better preservation of facial nerve function and hearing., Methods: From December 2002 to April 2011, a total of 260 patients with VS underwent GKS using Leksell Gamma Knife model 4C with an automatic positioning system. There were 30 Koos stage I tumors, 112 stage II, 100 stage III, and 18 stage IV. All patients were treated with the use of high-resolution magnetic resonance imaging; creation of the highly precise conformal and selective multi-isocenter dose planning with small collimators, carefully sparing adjacent cranial nerves of any excessive irradiation; and creation of a wide 80 % isodose area within the tumor while applying a low marginal dose (mean 11.9 Gy) at the 50 % isodose line., Results: Among 182 patients who were followed for more than 3 years after treatment, the tumor control and shrinkage rates were 98.4 % and 76.4 %, respectively. Volume reduction of >50 % was marked in 54.9 % of VSs. Preservation of facial nerve function and hearing at the pretreatment level was noted in 97.8 % and 87.9 %, respectively. There was marked improvement of facial nerve function and hearing after GKS in 2.2 % and 3.8 %, respectively. There was no major morbidity., Conclusion: Due to contemporary technological and methodological achievements GKS can be focused not only on growth control but on shrinking the VS, with possible reversal of the neurological deficit.

For some plant species, DNA extraction and downstream experiments are inhibited by various chemicals such as polysaccharides and polyphenols. This short communication proposed an organic-solvent free (except for ethanol) extraction method. This method consists of an initial washing step with STE buffer (0.25 M sucrose, 0.03 M Tris, 0.05 M EDTA), followed by DNA extraction using a piece of glass fiber filter. The advantages of this method are its safety and low cost. The purity of the DNA solution obtained using this method is not necessarily as high as that obtained using the STE/CTAB method, but it is sufficient for PCR experiments. These points were demonstrated empirically with two species, Japanese speedwell and common dandelion, for which DNA has proven difficult to amplify via PCR in past studies.

We describe a case of a non-invasive precursor of minimal deviation adenocarcinoma (MDA) of the uterine cervix, associated with Peutz-Jeghers syndrome (PJS). A 27-year-old woman, who had been followed for PJS, was referred to the gynecology clinic. Colposcopic examination demonstrated a small polypoid lesion in the transformation zone. Microscopic examination of the biopsy specimen demonstrated papillary proliferation of the mucinous epithelium with bland nuclear morphology. Conization revealed lobular endocervical glandular hyperplasia (LEGH) with distinct nuclear anaplasia, as well as papillary proliferation of the mucinous epithelium with mild to moderate nuclear abnormalities. This case suggests that the incipient phase of PJS-associated MDA is related to atypical LEGH ("MDA in situ"), and indicates the importance of early screening and surveillance by gynecologists in cases of PJS to detect cervical adenocarcinomas., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Purpose: To assess outcomes of carbon ion radiotherapy for diffuse astrocytomas in adults., Methods and Materials: Between October 1994 and February 2002, 14 patients with diffuse astrocytoma, identified as eligible for carbon ion radiotherapy, were enrolled in a phase I/II clinical trial. Carbon ion radiotherapy was administered in 24 fractions over 6 weeks. The normal tissue morbidity was monitored carefully, and the carbon ion dose was escalated from 50.4 Gy equivalent (GyE) to 55.2 GyE. Patients were divided into two groups according to their carbon ion doses: a low-dose group in which 2 patients were irradiated with 46.2 GyE and 7 patients were irradiated with 50.4 GyE, and a high-dose group in which 5 patients were irradiated with 55.2 GyE., Results: Toxicities were within acceptable limits, and none of the patients developed Grade 3 or higher acute or late reactions. The median progression-free survival (PFS) time was 18 months for the low-dose group and 91 months for the high-dose group (p = 0.0030). The median overall survival (OS) time was 28 months for the low-dose group and not reached for the high-dose group (p = 0.0208)., Conclusion: High-dose group patients showed significant improvement in PFS and OS rates compared to those in the low-dose group, and both dose groups showed acceptable toxicity., (Copyright © 2012 Elsevier Inc. All rights reserved.)

During the 2009-2010 season, a significant numerical increase of genotype GII.2 norovirus (NoV)-associated outbreaks was observed in Osaka City, Japan. The most common genotype in that season was GII.2 (44.6%), followed by GII.4 (39.2%). Mostly, GII.2 strains were associated with outbreaks in children and with person-to-person contact. The National Infectious Disease Surveillance Center reported that GII.2 NoV infections were widespread in Japan in that season. Comparative phylogenetic analysis of RNA-dependent RNA polymerase (RdRp) and capsid sequences revealed that this GII.2 epidemic resulted from two genetic strains. The first, GII.2p2 strains, had an identical genotype in the RdRp and capsid genes. GII.2p2 strains in the 2009-2010 season were a different genetic cluster from the strains of spring 2004, the previous epidemic of GII.2 NoV, but showed no unique amino acid change. The second, GII.2 chimera virus (GII.2p16), had GII.16 RdRp and GII.2 capsid genotypes, suggesting prior recombination at the junction of ORF1 and ORF2. GII.2p16 strains had four significant amino acid changes in the P2 subdomain, suggesting antigenic changes. Before the 2009-2010 season, GII.2 chimera viruses had been observed only sporadically. This spreading of GII.2p16 strains in the 2009-2010 season might be the first epidemic of GII.2 chimera virus. This study revealed that the NoV epidemic in the 2009-2010 season differed considerably from the prior season, when GII.4 was predominant. Furthermore, GII.2 strains persisted in human populations by drastic recombination and gradual accumulation of mutations, indicating a prevalent pattern of non-GII.4 genotypes with genetic evolution., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: As many invertebrate species have multipotent cells that undergo cell growth and differentiation during regeneration and budding, many unique and interesting homeostatic factors are expected to exist in those animals. However, our understanding of such factors and global mechanisms remains very poor. Single zooids of the tunicate, Polyandrocarpa misakiensis, can give off as many as 40 buds during the life span. Bud development proceeds by means of transdifferentiation of very limited number of cells and tissues. TC14-3 is one of several different but closely related polypeptides isolated from P. misakiensis. It acts as a cytostatic factor that regulates proliferation, adhesion, and differentiation of multipotent cells, although the molecular mechanism remains uncertain. The Polycomb group (PcG) genes are involved in epigenetic control of genomic activity in mammals. In invertebrates except Drosophila, PcG and histone methylation have not been studied so extensively, and genome-wide gene regulation is poorly understood., Results: When Phe(65) of TC14-3 was mutated to an acidic amino acid, the resultant mutant protein failed to dimerize. The replacement of Thr(69) with Arg(69) made dimers unstable. When Glu(106) was changed to Gly(106), the resultant mutant protein completely lost Ca(2+) binding. All these mutant proteins lacked cytostatic activity, indicating the requirement of protein dimerization and calcium for the activity. Polyandrocarpa Eed, a component of PcG, is highly expressed during budding, like TC14-3. When wild-type and mutant TC14-3s were applied in vivo and in vitro to Polyandrocarpa cells, only wild-type TC14-3 could induce Eed without affecting histone methyltransferase gene expression. Eed-expressing cells underwent trimethylation of histone H3 lysine27. PmEed knockdown by RNA interference rescued cultured cells from the growth-inhibitory effects of TC14-3., Conclusion: These results show that in P. misakiensis, the cytostatic activity of TC14-3 is mediated by PmEed and resultant histone modification, and that the gene expression requires both the protein dimerization and Ca(2+)-binding of TC14-3. This system consisting of a humoral factor, PcG, and histone methylation would contribute to the homeostatic regulation of cell growth and terminal differentiation of invertebrate multipotent cells.

Stance instability is seen in late stage Parkinson's disease (PD). Stabilometer-based center-of-pressure (COP) evaluation is an easy, routine method for measuring postural control ability. Most of the stabilometer- and force plate-based studies on upright postural control have discussed horizontal COP component control. Previous studies on vertical component control have been few, and no fractal analysis-based study on the component has been reported. We aimed to show the influence of neurological changes and aging on the vertical component and the difference in fluctuation pattern behavior in healthy young and elderly subjects as well as Parkinsonian patients. Detrended fluctuation analysis was used to study characteristics of fluctuation of vertical ground reaction force. In the three groups, all scaling exponents (α, α1, α2), which are time-correlated data of vertical ground reaction force, had a value >0 and <0.5 (0<α<0.5). Additionally, α and α2 were significantly different between PD and the other groups. Significant differences were observed between PD and the other groups regarding RMS, maximum peak value, and coefficient of variance. We demonstrated statistically significant differences in vertical ground reaction force between Parkinsonian patients and the other groups, suggesting that a neurological influence with PD may be markedly reflected in the vertical ground reaction force., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Availability of modern computer-aided robotized devices, such as the Automatic Positioning System (APSTM; Elekta Instruments AB, Stockholm, Sweden) and PerfexionTM (Elekta Instruments AB), allowed us to develop the original concept of robotic gamma knife microradiosurgery, which is based on the very precise irradiation of the lesion with regard to conformity and selectivity; intentional avoidance of the excessive irradiation of functionally-important anatomical structures, particularly cranial nerves, located both within and in the vicinity of the target; and delivery of sufficient irradiation energy to the tumor with the intention to attain lesion shrinkage, while keeping the marginal dose sufficiently low for prevention of possible complications. The results of such treatment strategy were evaluated retrospectively in 120 patients with benign cavernous sinus neoplasms (pituitary adenomas, meningiomas, schwannomas, and hemangiomas), who were followed up from 24 to 78 months (mean 47 months) after radiosurgery. Tumor growth control and shrinkage rates were 98% and 68%, respectively. More than 50% volume reduction was noted in 25% of lesions. The most prominent volumetric tumor response was observed in hemangiomas, followed by schwannomas, pituitary adenomas, and meningiomas. Treatment-related complications were marked in 7% of cases, and were mainly related to transient isolated cranial neuropathy appearing within several months after radiosurgery. Major morbidity was limited to one patient (0.8%). Application of microradiosurgical treatment principles provides effective and safe management of benign cavernous sinus tumors and is associated with high probability of lesion shrinkage and minimal risk of complications.

Here we report the case of a 72-year-old woman with nodular bronchiectatic Mycobacterium avium complex (MAC) disease. Chest computed tomography on admission revealed multiple micronodular and branching opacities in both lobes with segmental distribution; bronchiectasis and bronchial wall thickening were observed in the middle lobe and lingula. The patient consented to and underwent thoracoscopic lung biopsy; epithelioid granulomas were occasionally observed, but follicular bronchiolitis was widespread. While bronchial lesions from nontuberculous mycobacterial infection generally present as epitheliod granulomas, the present case suggests that follicular bronchiolitis can also be a histological counterpart to nodular opacities in nodular bronchiectatic MAC disease.

Objective: Renal fibrosis is a common cause of renal dysfunction with chronic kidney disease. We previously investigated the renoprotective effects of the antifibrotic agent pirfenidone in a rat model of subtotal nephrectomy. Here, we further evaluated the antifibrotic effects of pirfenidone in rat proximal tubular epithelial cells., Methods: NRK52E cells were incubated in a medium containing either transforming growth factor (TGF)-β1 (3 ng/mL) or platelet-derived growth factor (PDGF)-BB (5 Ang/mL) or both, with or without pirfenidone (0.1-1 mmol/L), for 24 h to assess mRNA expression, for 48 h to assess protein production, and for 1 h or various time (5-120 min) to assess phosphorylation of signal kinase., Results: TGF-β1, a key mediator in renal fibrosis, induced increases in the mRNA expression of various profibrotic factors and extracellular matrix, including plasminogen activator inhibitor type 1 (PAI-1), fibronectin, type 1 collagen, and connective tissue growth factor (CTGF)-increases which pirfenidone significantly inhibited. Specifically, pirfenidone potently inhibited TGF-β1-induced increases in the mRNA expression and protein secretion of PAI-1, an effect mediated, at least in part, via the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling. Further, PDGF-BB, which has been implicated in renal interstitial fibrosis, potently activated PAI-1 expression under TGF-β1 stimulation, and pirfenidone significantly inhibited TGF-β1- and PDGF-BB-induced increases in PAI-1 expression., Conclusions: Taken together, these results suggest that TGF-β1 closely correlates with renal fibrosis in cooperation with several fibrosis-promoting molecules, such as PAI-1 and PDGF, in rat proximal tubular epithelial cells, and pirfenidone inhibits TGF-β1-induced fibrosis cascade and will therefore likely exert antifibrotic effects under pathological conditions.

The objective of the present study was the evaluation of outcome in 130 patients with essential trigeminal neuralgia, who were treated using Leksell Gamma Knife model C with automatic positioning system and followed at least 24 months thereafter. Radiosurgery was guided by fused thin-sliced magnetic resonance (MR) and "bone window" computed tomographic (CT) images. In all cases, retrogasserian part of the trigeminal nerve at the level of trigeminal incisura was selected as a target, and one 4-mm collimator was used for delivery of the maximum irradiation dose of 90 Gy. The coordinates of the isocenter were adjusted for positioning of the nerve in the center of 80% isodose area, and were corrected in each individual case with regard to presence of distortion artifacts on MR images. Initial relief of the typical paroxysmal facial pain was marked in 127 patients (98%) within a median interval of 3 weeks after treatment. However, in 23 patients the pain re-appeared later on. Overall, at the time of the last follow-up 112 patients (86%) were pain-free, including 86 who remained both pain- and medication-free after initial radiosurgery. In 31 cases (24%), treatment was complicated by facial hypesthesia and/or paresthesia. In conclusion, radiosurgery of essential trigeminal neuralgia results in a high rate of initial pain relief, but pain recurrences and associated complications are not uncommon. The outcome may be influenced by various technical nuances; therefore, treatment should be preferably done in specialized clinical centers with sufficient expertise in the management of this disorder.

We report the case of a 26-year-old male who presented with acute pancreatitis during the course of treatment for pancolitic ulcerative colitis (UC) with a time-dependent mesalazine formulation, prednisolone and azathioprine (AZA). Despite a review of his clinical history and various tests, the cause of pancreatitis could not be determined. Since drug-induced pancreatitis was considered possible, administration of the time-dependent mesalazine preparation and AZA was discontinued, and conservative treatment for acute pancreatitis was performed. The pancreatitis promptly improved with these treatments, but drug lymphocyte stimulation test (DLST) for both the time-dependent mesalazine formulation and AZA was negative. A pH-dependent mesalazine formulation was given for maintenance therapy of UC. Subsequently, as the pancreatitis relapsed, drug-induced pancreatitis was strongly suspected. Administration of mesalazine was discontinued, and pancreatitis was smoothly in remission by conservative treatment. According to the positive DLST result for the pH-dependent mesalazine formulation and the clinical course, a diagnosis of pH-dependent mesalazine-induced pancreatitis due to this formulation was made. During the clinical course of UC, occurrence of drug-induced pancreatitis must always be considered.

Object: The objective of the present study was analysis of results of the prospective clinical trial directed toward the evaluation of therapeutic efficacy of the administration of autologous formalin-fixed tumor vaccine (AFTV) concomitant with fractionated radiotherapy in cases of newly diagnosed glioblastoma multiforme., Methods: Twenty-four patients were enrolled into the clinical trial, while 2 cases were excluded from the final analysis of results. The treatment protocol included aggressive tumor resection, fractionated radiotherapy up to a total dose of 60 Gy, and 3 concomitant courses of AFTV administered with an interval of one week at the late stage of irradiation. Two delayed-type hypersensitivity (DTH) tests were done--one 48 hours before the initial course of vaccination (DTH-1) and one 2 weeks after the third (DTH-2). All but one of the patients received salvage therapy at the time of tumor progression. The defined primary end point was overall survival; secondary end points were progression-free survival and safety of concomitant treatment., Results: The median duration of overall survival was 19.8 [corrected] months (95% CI 13.8-31.3 months). The actuarial 2-year survival rate was 40%. The median duration of progression-free survival was 7.6 months (95% CI 4.3-13.6 months). Overall survival showed a statistically significant association with recursive partitioning analysis class (p < 0.05); progression-free survival showed a statistically significant association with p53 staining index (p < 0.05) and size of DTH-2 response (p < 0.001). AFTV injection concomitant with fractionated radiotherapy was well tolerated by all patients and in no case did treatment-related adverse effects exceed Grade 1 toxicity; adverse effects were limited to local erythema, induration, and swelling at the site of injection., Conclusions: The results of this study demonstrate that AFTV treatment concomitant with fractionated radiotherapy may be effective in patients with newly diagnosed glioblastoma. Further clinical testing is warranted.

Purpose: The aim of this study was to compare diffusion-weighted magnetic resonance imaging (DWI) and multidetector-row computed tomography (MDCT) for detection of primary pancreatic cancer by reviewing images of patients at high risk for pancreatic cancer with main pancreatic duct (MPD) dilatation shown by magnetic resonance cholangiopancreatography (MRCP)., Methods: From October 2007 to September 2009, 83 patients who had undergone both DWI and MDCT with MPD dilatation were identified and were reviewed by four readers (2 radiologists and 2 gastroenterology fellows). Diagnostic performance in pancreatic cancer detection was evaluated with 95% confidence intervals. Statistically significant differences in the detection of pancreatic cancer between DWI and MDCT were compared by receiver operating characteristics and the confidence of the diagnosis by the paired t test., Results: Thirty-two of 83 patients were diagnosed with primary pancreatic cancer by histological evaluation of 15 surgical and 2 endoscopic ultrasound-guided fine needle aspiration samples, and by the clinical course for 15 lesions. Overall average accuracies of pancreatic cancer detection by the four readers were 84% with DWI and 86% with MDCT., Conclusion: Performance of DWI and MDCT was equivocal for detection of pancreatic cancer in a high-risk population with MPD dilatation. The combination of MRCP and DWI for detection of pancreatic cancer allowed identification of a high-risk population and tumor detection with a single imaging modality with no need for contrast medium.

Neurofibromatosis type I (NF1) is one of the most common inheritable disorders and is associated with an increased risk of gastrointestinal stromal tumours (GISTs). However, the predominant location of these lesions in the small bowel makes them difficult to diagnose. We report the successful use of balloon enteroscopy in conjunction with conventional methods for clinical diagnosis of jejunal GISTs in a 70-year-old man with NF1 who presented with melaena. The importance of screening NF1 patients for GISTs and the complementary role of balloon enteroscopy with capsule endoscopy in such diagnoses is discussed.

Objective: The main goal of the present study was evaluation of proton magnetic resonance spectroscopy (¹H-MRS) in diagnosis of histopathologically aggressive intracranial meningiomas., Methods: Single-voxel ¹H-MRS of 100 intracranial meningiomas was performed before their surgical resection. Investigated metabolites included mobile lipids, lactate, alanine, N-acetylaspartate (NAA), and choline-containing compounds (Cho). According to criteria of World Health Organization (WHO) 82 meningiomas were assigned histopathological grade I, 11 grade II, and 7 grade III. The MIB-1 index varied from 0% to 27.3% (median, 1.6%). In 43 cases tight adhesion of the tumor to the pia mater or brain tissue was macroscopically identified at surgery. The consistency of 49 meningiomas was characterized as soft, 26 as hard, and 25 as mixed., Results: No one metabolic parameter had statistically significant association with histopathological grade and subtype, invasive growth, and consistency of meningioma. Univariate statistical analysis revealed greater ¹H-MRS-detected Cho content (P=0.0444) and lower normalized NAA/Cho ratio (P=0.0203) in tumors with MIB-1 index 5% and more. However, both parameters lost their statistical significance during evaluation in the multivariate model along with other clinical and radiological variables. It was revealed that non-benign histopathology of meningioma (WHO grade II/III) is mainly predicted by irregular shape (P=0.0076) and large size (P=0.0316), increased proliferative activity by irregular shape (P=0.0056), and macroscopically invasive growth by prominent peritumoral edema (P=0.0021)., Conclusion: While ¹H-MRS may be potentially used for the identification of meningiomas with high proliferative activity, it, seemingly, could not add substantial diagnostic information to other radiological predictors of malignancy in these tumors., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Reproductive interference (RI), defined as the fitness cost of interspecific sexual interactions, such as interspecific pollen transfer (IPT) in plants, is ecologically important. Theoretically, RI could result in competitive exclusion, as it operates in a frequency-dependent manner. Additionally, IPT may have a greater range than resource competition, although information about the range of IPT is lacking. In the present study, we measured the range of IPT exerted by Taraxacum officinale (an alien species) on a native dandelion, T. japonicum. We used two approaches. In one, we analyzed the RI effect on a native seed set at three spatial scales. In the second, we tracked IPT from alien to native flower heads using fluorescent pigments as markers. We estimated that pollination distances were in the order of several meters. These distances exceeded the mean distance from each native plant to the nearest alien. As hypothesized, the effect of RI reached farther than neighboring individuals. These data indicate the spatial range from which alien dandelions should be removed to allow the conservation of natives.

Cleft lip palate is a congenital anomaly that requires surgical reconstruction, and patients rarely develop tongue edema after palatoplasty. We describe a 1-year-and-8-month-old boy who underwent palatoplasty for left-sided cleft lip palate accompanied by exudative otitis media. Although previous reports have described that tongue edema usually sets in early after surgery, the symptoms of edema persisted more than 4 hours postoperatively in our case. We suggest that careful observation for edema is necessary for 24 hours at least after palatoplasty., (Copyright © 2011. Published by Elsevier B.V.)

Background/aims: The objective of the present study was the evaluation of the effectiveness of robotic microradiosurgery of skull base meningiomas using Leksell Gamma Knife model C with an automatic positioning system., Methods: The results of the management of 66 tumors were analyzed retrospectively. Their volume varied from 0.3 to 50.6 cm³ (mean = 6.6). The treatment plan was based on the use of multiple small isocenters compactly positioned within the border of the lesion with resultant improved homogeneity of high-dose distribution, increased average dose within the target and sharp dose fall outside the treated volume. The marginal dose varied from 10 to 14 Gy (mean = 12). The length of follow-up ranged from 26 to 80 months (mean = 46)., Results: The overall tumor growth control was 99%. Reduction of the mass volume was marked in 54 patients (82%), and in 15 of them it constituted ≥ 50%. In other 11 cases (17%) stabilization of the lesion growth was noted. The shrinkage rate significantly correlated with amount of radiation energy delivered per tumor volume, designated as unit energy (p = 0.007). One meningioma (1%) regrew 3.5 years after radiosurgery. The treatment-related morbidity was limited to transient abducens nerve palsy in 1 patient (1%)., Conclusion: Application of the concept of Gamma Knife robotic microradiosurgery for the management of skull base meningiomas may change the paradigm of their treatment from stabilization of growth to reduction of the volume of the neoplasm. The tumor shrinkage rate may depend on the amount of radiation energy delivered per lesion volume (unit energy)., (Copyright © 2010 S. Karger AG, Basel.)

Human rhinovirus (HRV) is a causative agent of acute respiratory tract infection (ARTI). In 2007, a novel HRV group, HRV-C, was discovered. This study, which assessed whether HRV-C is epidemic among patients with ARTI, was aimed at analyzing the seasonal prevalence of HRV-C in Osaka City, Japan. Gene amplification tests were performed to detect 10 respiratory viruses in 336 specimens collected during November 2008-October 2009. In total, 364 viruses were detected in 271 specimens. The most commonly detected virus was HRV (n = 84). For HRV-positive specimens, we conducted phylogenetic analyses using the VP4/VP2 gene region to identify the HRV species (HRV-C, 30; HRV-A, 54). Both the number and rate of HRV-C detection were highest in December. The highest numbers and the highest rate of HRV-A detection were obtained in April and June and in April, respectively. Statistical analysis showed that the most probable prevalent period of HRV-C was between September and March, and that of HRV-A was between March and November. These results suggest that HRV-C is mainly epidemic during autumn and early spring; this seasonal prevalence was different from that of HRV-A. Moreover, the HRV-C Osaka strains were scattered in many genetic clusters along with previously reported strains from different parts of the world. This result also emphasizes the worldwide circulation of HRV-C.

Background: Contemporary technological developments revolutionized management of brain tumors. The experience with information-guided surgery of gliomas, based on the integration of the various intraoperative anatomical, functional, and histological data, is reported., Methods: From 2000 to 2009, 574 surgeries for intracranial gliomas were performed in our clinic with the use of intraoperative MRI (ioMRI) with magnetic field strength of 0.3T, updated neuronavigation, neurochemical navigation with 5-aminolevulinic acid, serial intraoperative histopathological investigations of the resected tissue, and comprehensive neurophysiological monitoring. Nearly half of patients (263 cases; 45.8%) were followed more than 2 years after surgery., Findings: Maximal possible tumor resection, defined as radiologically complete tumor removal or subtotal removal leaving the residual neoplasm within the vital functionally-important brain areas, was attained in 569 cases (99.1%). The median resection rate constituted 95%, 95%, and 98%, for WHO grade II, III, and IV gliomas, respectively. Actuarial 5-year survival was significantly worse in WHO grade IV gliomas (19%), but did not differ significantly between WHO grade III and II tumors (69% vs. 87%)., Conclusions: Information-guided management of gliomas using low-field-strength ioMRI provides a good opportunity for maximal possible tumor resection, and may result in survival advantage, particularly in patients with WHO grade III neoplasms.

In water, phosphoric membrane molecule (V(-)) self-assembled to form an anionic giant vesicle, the surface of which served as a catalyst for the autocatalytic formation of V(-) from its membrane precursor (V*), and the amplified V(-) produced a new vesicle using the original vesicle as a scaffold.

Abducent nerve schwannomas are extremely rare. The authors recently performed Gamma Knife surgery (GKS) in 4 patients with such tumors and describe their experiences with these cases. The patients consisted of 3 women and 1 man whose ages varied from 31 to 60 years (mean 46 years). Two patients had no symptoms, 1 complained of slight visual disturbances, and the other 1 had abducent nerve palsy. Neurofibromatosis was not diagnosed in any case. All 4 tumors were located in the cavernous sinus: 2 of these tumors within the borders of the sinus, 1 tumor extending into the orbit, and 1 tumor extending into the prepontine cistern. The volume of the neoplasms varied from 1.7 to 4.9 cm(3) (mean 3.0 cm(3)). No patient underwent tumor resection. Treatment was delivered with the aid of a Leksell Gamma Knife model C unit and the automatic positioning system. The dose directed to the tumor margin was 12 Gy in all cases. The dose directed to the anterior visual pathways was kept below 10 Gy and that to the brainstem below 14 Gy. The length of follow-up varied between 7 and 43 months (mean 27 months). There were no acute complications or side effects. Imaging studies showed temporary enlargement of all tumors during the 1st posttreatment year, but thereafter, there was a trend toward reduction in volume. None of the neoplasms displayed regrowth. In the 3 patients who did not have abducent nerve palsy before GKS, it appeared, at least temporarily, after the procedure. Purely intracavernous neoplasms in general followed uneventful posttreatment courses, but dumbbell-shaped tumors were associated with significant morbidity. The cisternocavernous schwannoma underwent cystic degeneration 2 years after GKS, and the patient developed diplopia. After GKS, the patient treated for an orbitocavernous schwannoma experienced a significant deterioration in vision, temporary blindness in 1 eye, and late development of permanent abducent nerve palsy, which were seemingly caused by compression of neurovascular structures within the anulus of Zinn during a temporary increase in the lesion's volume after irradiation. Gamma Knife surgery controls the growth of abducent nerve schwannomas and may be effectively used to manage intracavernous neoplasms. Caution, however, should be used in cases of dumbbell-shaped tumors, particularly those extending through the superior orbital fissure.

Background and Objective: beta-Adrenoceptor-blocking agents have been used for perioperative management during anaesthesia, in which selective beta1-blockers are advantageous over nonselective beta-blockers. Apart from the different affinity for beta-adrenoceptors, beta1-blockers were differentially characterized in light of their different interaction with lipid membranes., Methods: Selective (atenolol, metoprolol and esmolol) and nonselective (alprenolol, oxprenolol and propranolol) beta1-blockers were reacted at 0.2-1 mmol l with 1,2-dipalmitoylphosphatidylcholine liposomes and biomimetic membranes consisting of phospholipids, sphingolipid and cholesterol. Their membrane interactivities were comparatively determined using the potency to modify membrane fluidity by measuring fluorescence polarization. Their relative hydrophobicities were evaluated by reversed-phase liquid chromatography., Results: The chromatographic evaluation divided the tested drugs into more hydrophobic ones containing nonselective beta-blockers and less hydrophobic ones containing selective beta1-blockers. Nonselective beta-blockers, but not selective beta1-blockers, fluidized liposomal membranes, with the potency being oxprenolol < alprenolol < propranolol. Membrane-active alprenolol preferentially acted on the hydrophobic deeper regions of phospholipid bilayers. The potency of nonselective beta-blockers to fluidize biomimetic membranes was greatest in propranolol, followed by alprenolol and oxprenolol, whereas all selective beta1-blockers were inactive., Conclusion: The membrane-fluidizing effects of beta-blockers are correlated with their relative hydrophobicities and their respective conformations to perturb the alignment of phospholipid acyl chains. The membrane-interacting characteristics differentiate beta-blockers as nonselective propranolol, alprenolol and oxprenolol vs. beta1-selective atenolol, metoprolol and esmolol. Such differentiation reflects not only the structural difference but also the beta-adrenoceptor-blocking difference. The membrane fluidization may be partly responsible for the nonselective blockade of beta-adrenoceptors.

Membranous lipid bilayers have been reconsidered as the site of action of local anesthetics (LAs). Recent understanding of biomembranes indicates the existence of lipid raft microdomains enriched in cholesterol and sphingolipids as potential platforms for channels and receptors. Based on the hypothesis that LAs may interact preferentially with lipid rafts over non-raft membranes, we compared their effects on raft model membranes and cardiolipin-containing biomimetic membranes. Liposomes were prepared with phospholipids, sphingomyelin, cerebroside, and cholesterol to have compositions corresponding to lipid rafts and cardiomyocyte mitochondrial membranes. After reacting LAs (50-200 microM) with the membrane preparations, their interactivities were determined by measuring fluorescence polarization with 1,6-diphenyl-1,3,5-hexatriene. Although bupivacaine and lidocaine acted on different raft-like liquid-ordered membranes to reduce polarization values, their effects on biomimetic less ordered membranes were much greater. LAs interacted with biomimetic membranes with the potency being R(+)-bupivacaine > racemic bupivacaine > S(-)-bupivacaine > ropivacaine > lidocaine > prilocaine, which is consistent with the rank order of pharmacotoxicological potency. However, raft model membranes showed neither structure-dependence nor stereoselectivity. The relevance of membrane lipid rafts to LAs is questionable at least in their effects on raft-like liquid-ordered membranes.

The objective of the present retrospective study was evaluation of results of "robotic microradiosurgery" of pituitary adenomas invading the cavernous sinus. Eighty-nine patients with such tumors underwent management using Leksell Gamma Knife model C with automatic positioning system. There were 77 residual and 12 recurrent neoplasms. The applied radiosurgical treatment plan was based on the use of multiple isocenters, mainly of smaller size, which were positioned compactly within the border of the lesion with resultant improved dose homogeneity, increased average dose within the target, and sharp dose fall outside the treated volume. The marginal dose varied from 12 to 25 Gy (mean, 18.2 Gy) in non-functional pituitary adenomas (43 cases), and from 12 to 35 Gy (mean, 25.2 Gy) in hormone-secreting ones (46 cases). The length of follow-up after treatment ranged from 24 to 76 months (mean, 36 months). Control of the tumor growth was attained in 86 cases (97%), whereas actual shrinkage of the lesion was marked in 57 cases (64%). In 18 out of 46 secreting neoplasms (39%), normalization of the excess of the pituitary hormone production was noted after radiosurgery. Treatment-associated morbidity was limited to transitory cranial nerve palsy in two patients (2%). No patient with either non-functional or hormone secreting tumor exhibited new pituitary hormone deficit after treatment. In conclusion, highly precise microanatomy-based Gamma Knife robotic microradiosurgery provides an opportunity for effective management of pituitary adenomas invading the cavernous sinus with preservation of the adjacent functionally important neuronal structures.

In this study, we attempted to clarify the influence of the DNA repair genes RAD54 and KU70, components of the homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways, respectively, on apoptosis induced by 1 Gy (low-dose) and 5 Gy (high-dose) irradiation. All experiments were performed using chicken B-lymphocyte DT40 cells and the DNA repair-deficient cell lines KU70(-/-), RAD54(-/-) and KU70(-/-)/RAD54(-/-). Morphological changes were detected by fluorescence methods, and the sub-G(1) fraction and the activated caspases in DT40 cells were analyzed by flow cytometry. Irradiation with 1 Gy significantly increased the level of apoptosis in cells with the defective DNA repair genes, with the maximum apoptosis occurring in double mutant cells, KU70(-/-)/RAD54(-/-), demonstrating that 1 Gy is enough to induce apoptosis in DNA repair-deficient DT40 cells, and that KU70 and RAD54 must have almost the same role in low-dose radiation-induced apoptosis. After 5 Gy, fast induction of apoptosis, within 2 h, was seen in both wild-type cells and RAD54(-/-) cells, indicating that functional KU70 must be important for the rescue of the cells from the induction of fast apoptosis.

HBoV was initially identified in patients with RTI in 2005. Since its discovery, there have been continual reports concerning HBoV detection and its prevalence. In this study of clinical specimens from young children, real-time PCR was undertaken to examine whether HBoV infection is associated with RTI and to support quantitative analysis of HBoV in these patients. In all, 376 specimens were collected from patients with RTI during April 2006-October 2008. Analyses revealed HBoV in 59 specimens (15.7%). Of HBoV-positive patients, children under the age of 3 years comprised 94.9%. Of the HBoV-positive samples, 47.5% were codetected with other respiratory viruses (dual infection, 27; triple infection, 1). During the study period, the numbers and rate of detection of HBoV were high mainly around May. Statistical analyses showed that the detection rate of HBoV during April-June was higher than during other months. Moreover, the viral load was greater in subjects with infection with HBoV alone than in subjects with mixed respiratory viral infections. Considering these results together, HBoV is probably associated with RTI in young children. However, the pathogenesis of this infection and the importance of the high rate of co-infection remain uncertain. Additional epidemiologic information and further analyses are necessary to clarify the virological characteristics and the linkage of HBoV to disease.