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Six postlingually deaf patients using multi-channel cochlear implants were examined by positron emission tomography (PET) using 15O-labeled water. Changes in regional cerebral blood flow (rCBF) were measured during different sound stimuli. The stimulation paradigms employed consisted of two sets of three different conditions; (1) no sound stimulation with the speech processor of the cochlear implant system switched off, (2) hearing white noise and (3) hearing sequential Japanese sentences. In the primary auditory area, the mean rCBF increase during noise stimulation was significantly greater on the side contralateral to the implant than on the ipsilateral side. Speech stimulation caused significantly greater rCBF increase compared with noise stimulation in the left immediate auditory association area (P < 0.01), the bilateral auditory association areas (P < 0.01), the posterior part of the bilateral inferior frontal gyri; the Broca's area (P < 0.01) and its right hemisphere homologue (P < 0.05). Activation of cortices related to verbal and non-verbal sound recognition was clearly demonstrated in the current subjects probably because complete silence was attained in the control condition.

Introduction: Adult patients with WHO grade 2 low-grade glioma (LGG) have a significant risk of tumor progression despite treatment with surgery or surgery followed by radiation therapy (RT) and /or chemotherapy, and most patients eventually die of the disease. High-risk subsets of these LGG patients display astrocytoma or oligoastrocytoma histology plus any one of the following conditions: 1) age ≥40 with any extent resection; 2) age 18-39 with incomplete resection; or 3) age 18-39 with neurosurgeon-defined gross total resection with tumor size ≥ 4 cm in diameter. These patients have as high as an 89% risk of recurrence by 5 years following surgery. Methods: Based on encouraging data from a phase I vaccine study targeting multiple glioma-associated antigen (GAA) epitopes in adult high-grade glioma (HGG) patients, we initiated a bi-institutional pilot study of subcutaneous vaccinations of subcutaneous vaccinations with synthetic peptides for GAA epitopes emulsified in Montanide-ISA-51 every 3 weeks for 8 courses, and intramuscular administration of poly-ICLC in HLA-A2+ patients with: newly diagnosed high-risk LGG without prior RT (Cohort 1); newly diagnosed high-risk LGG with prior RT (Cohort 2), or recurrent LGG (Cohort 3). Primary endpoints were safety and CD8+ T-cell responses against vaccine-targeted GAAs, assessed by Enzyme-Linked Immuno-SPOT (ELISPOT) assays. Treatment response was evaluated clinically and by MR imaging. Targeted GAAs were EphA2, interleukin (IL)-13 receptor-α2, survivin, and WT1. As these GAAs are expressed not only in a subset of LGG cells but even at higher levels in HGG cells, our vaccine approach may offer both immunotherapeutic and immunoprophylactic potential to reduce the risk of tumor recurrence. Results: To date, 13, 1 and 10 patients have been enrolled in Cohorts 1, 2 and 3, respectively. No dose-limiting non-CNS toxicity has been encountered except for one case with Grade 3 fever (Cohort 1). ELISPOT assays, completed in 7 and 1 patients in Cohorts 1 and 2, respectively, demonstrated robust and sustained interferon (IFN)-γ (type-1) responses against at least 3 of the GAA epitopes in all cases, while IL-5 (type-2) responses were absent or transient in all cases. The magnitude of the IFN-γ ELISPOT responses in the current study was significantly higher than that observed in our previous phase I/II study in HGG patients (Okada H et al. 2011). Although evaluation of progression-free survival would require a longer observation period, among 9, 1 and 7 patients who completed the 8 vaccinations spanning 24 weeks, 6, 1 and 3 patients in Cohorts 1, 2 and 3, respectively, are currently with stable disease. Conclusion: Our preliminary results demonstrate that the regimen in these patients is well tolerated, and induces robust type-1 anti-GAA T-cell responses. These data suggest that patients with LGG are suitable for vaccine therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-135. doi:1538-7445.AM2012-LB-135

As type-1 T cells have been shown to mediate effective anti-tumor immune response, we sought to identify microRNA (miRs) differentially regulated between type-1 and type-2 T cells, and determine how the expression of such miRs are regulated. We performed miR microarray analyses on in vitro differentiated murine T helper type-1 (Th1) and T helper type-2 (Th2) cells to identify differentially expressed miRs. We used RT-PCR to confirm the differential expression levels. WST-1, ELISA, and flow cytometry were used to evaluate the survival, function and phenotype of cells, respectively. Lastly, we employed mice transgenic for the identified miRs to determine the biological impact of the miR expression in T cells. Our miR microarray analyses revealed that the miR-17-92 cluster is one of the most significantly over-expressed miR in murine Th1 cells compared with Th2 cells. RT-PCR confirmed that the miR-17-92 cluster expression was consistently higher in Th1 cells than Th2 cells. Disruption of the IL-4 signaling through either IL-4 neutralizing antibody or knockout of signal transducer and activator of transcription (STAT)6 reversed the miR-17-92 cluster suppression in Th2 cells. Furthermore, T cells from tumor bearing mice and glioma patients had decreased levels of miR-17-92 compared with cells from non-tumor bearing counterparts. CD4+ T cells derived from miR-17-92 transgenic mice demonstrated superior type-1 phenotype with increased IFN-γ production and very late antigen (VLA)-4 expression when compared with counterparts derived from wild type mice. Finally Jurkat T cells ectopically expressing increased levels of miR-17-92 cluster members demonstrated increased IL-2 production and resistance to activation-induced cell death (AICD). Collectively, our data suggest that the type-2-skewing tumor microenvironment can induce the down-regulation of miR-17-92 expression in T cells, thereby diminishing the persistence of tumor-specific T cells and tumor destruction. Genetic engineering of T cells to express miR-17-92 may prove to be a promising approach for cancer immunotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4786.

Our previous preclinical studies have demonstrated that intramuscular (i.m.) administration of a Toll-like receptor 3 ligand poly-ICLC remarkably enhances induction of type-1 cytotoxic T-lymphocytes (CTLs) and improves therapeutic efficacy of vaccinations against glioma-associated antigen (GAA)-derived CD8+ T cell epitopes. The primary objectives of this phase I/II study were to evaluate the safety and immunogenicity of vaccinations with Type-1 α dendrititc cells (αDC1) loaded with glioma associated antigen (GAA) epitopes and administration of poly-ICLC in patients with recurrent malignant gliomas. Human leukocyte Antigen (HLA)-A2+ participants with recurrent malignant glioma received intra-lymph-node injections of type-1 dendritic cells (DCs) loaded with HLA-A2 binding GAA-peptides EphA2 (883-891), IL-13Ralpha2 (345-353:1A9V), YKL-40 (202-211) and GP100 (209-217: 2M) at two-week intervals. Participants also received twice weekly i.m. injections of 20 µg/kg poly-ICLC. Participants who demonstrated positive radiological response or stable disease without major adverse events were allowed to receive booster vaccines. Primary endpoints were assessments of safety and immunological responses by ELISPOT and tetramer assays. Clinical and radiological responses were also evaluated. To date, 19 participants (12 with glioblastoma multiforme [GBM], 4 with anaplastic astrocytoma [AA] and 3 anaplastic oligodendroglioma [AO]) have received at least 4 vaccinations with no major adverse events. Increased CD8+ cells reactive to EphA2- or IL-13Rα2-tetramers were detected in post-vaccine peripheral blood mononuclear cells (PBMC) in 9 of 11 participants evaluated. Some of these patients also demonstrated up-regulation of a chemokine receptor CXCR3 on CD8+ PBMC following vaccines, indicating that the vaccine regimen induced type-1 CTL responses. Six patients achieved progression free at 6 months (3 GBM, 2AA and 1 AO). Among these, 3 patients are currently progression free at 23 (AA), 20 (AA) or 9 (GBM) months after the first vaccine, and receiving booster vaccines every 3 months. Although the trial enrolled mixed tumor types, Fisher's exact test indicated an association between positive tetramer response and 6-month progression-free survival, suggesting a possible correlation between antigen-specific responses and clinical response. These interim data demonstrate preliminary safety, immunological and clinical activity of poly-ICLC-assisted type-1 DC-based vaccines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4754.

37.4 ± 3.5 vs 38.4 ± 1.8 (P = 0.006); rate of preterm birth < 34 wks: 11 cases vs 4 cases (P < 0.001); SGA: 32 cases vs 17 cases (P < 0.001). At the logistic regression the abnormal UtA was the only variable significantly releated with adverse outcome. An abnormal UtA Doppler is significantly related to PE, preterm birth below 34 weeks and rate of newborns SGA. At the logistic regression the abnormal UtA Doppler remained the only variable statistically releated with severe pregnancy complications. The PPV of the method is 61% with a sensitivity of 57% and a specificity of 82%. Conclusions: Unless these results are unsatisfactory for a screening test this method permain an useful predicting test if compared with the only previous clinical history (10%); in fact patients with an abnormal test have a risk to develop severe complications of pregnancy 6 times higher than patients with a normal Doppler.

The use of soft lasers in dental therapy has increased dramatically in recent years. However, there is a dearth of reports in the literature of controlled in vivo and in vitro studies of soft laser effectiveness with respect to dentinal pain. The purpose of this study was to assess the analgesic effects of soft laser treatment by the following five studies: (1) Clinical evaluation of soft laser irradiation of hypersensitive dentin. (2) Morphological study of dentinal surfaces following soft laser irradiation. (3) Study of the effect of soft laser irradiation on dentinal fluid movement. (4) Study of the effect of soft laser irradiation on the jaw opening reflex (JOR) in rats. (5) Study of thermal changes on the internal wall of pulp chamber with soft laser irradiation. After soft laser treatment of 3 min to hypersensitive dentin, patients experiences diminished sensitivity in 46 of 55 teeth (83.6%). In model experiment with extracted human teeth, the energy levels of this laser were too low to produce any morphological changes on the surface of exposed dentin, and dentinal fluid movements induced by air blasts for 15 sec to exposed dentin were not affected by laser irradiation to the dentin for 3 min. Moreover, there was an immediate 0.7 degree C increase in the temperature of the internal wall of the pulp chamber by laser irradiation to the tooth surface. In experimental rats, the digastric EMG induced by 1.3 x T (T: threshold value producing the JOR) was reduced by 3 min soft laser irradiation to teeth or Ho-ku points, but not at 2.0 x T. These results suggest that soft lasers have an analgesic effect, but the latter is affected by the degree of stimuli-elicited pain, and may be due in addition to descending inhibition in the central nervous system.

The root apex values given in the manufacturers' introductions of 5 electronic measuring devices were compared with the mean values measured by each device in the following cases: a) The tip of file was at the apical constriction in the experimental tooth model. b) The tip of file was between 0 mm and -2.0 mm from the root apex in the vital teeth and the pulpless teeth. In the experimental tooth model, when the tip of file was at the apical constriction, the mean values measured by each device except EM were lower than the root apex values given in the manufacturers' introductions of each device. In the case of the vital tooth, when the tip of file was between 0 mm and -2.0 mm from the root apex, the mean values measured by EM-S II and EM were similar to the values given in the manufacturers' introductions of these devices, but not to those obtained by the other devices. Measurements of the pulpless tooth by each device revealed mean values lower than the values given in manufacturers' introductions for the root apex.

Japanese and Korean are typologically quite similar, so a linguistic phenomenon in one language often has a counterpart in the other. The papers in this volume are intended to further collective and collaborative research in both languages. The contributors discuss aspects of language acquisition, discourse, syntax, semantics, pragmatics, phonology, morphology, typology, sociolinguistics, and psycholinguistics. The papers were presented at the Southern California Japanese/Korean Linguistics Conference in September 1991. Contributors to this volume are Patricia M. Clancy, Seiko Yamaguchi Fujii, Shoichi Iwasaki, Kyu-hyun Kim, Yoshiko Matsumoto, Shigeko Okamoto, Sung-Ock S. Sohn, Kyung-Hee Suh, Eunjoo Han, Jongho Jun, Ongmi Kang, David James Silva, Noriko Akatsuka, Shoji Azuma, Soonja Choi, Bruce L. Derwing, Yeo Bom Yoon, Sook Whan Cho, Tsuyoshi Ono, Hiroko Yamashita, Laurie Stowe, Mineharu Nakayama, Ruriko Kawashima, Masanori Nakamaura, Shin Watanabe, Dong-In Cho, Stanley Dubinsky, Hiroto Hoshi, Yasua Ishii, Hisatsugu Kitahara, Masatoshi Koizumi, Jae Hong Lee, Sookhee Lee, Young-Suk Lee, and Shigeo Tonoike.