A cytokine mixture of GM-CSF and IL-3 that induces a neuroprotective phenotype of microglia leading to amelioration of (6-OHDA)-induced Parkinsonism of rats

Dopamine (DA) agonists are widely used as primary treatments for Parkinson's disease. However, they do not prevent progressive degeneration of dopaminergic neurons, the central pathology of the disease. In this study, we found that subcutaneous injection of a cytokine mixture containing granulocyte macrophage colony-stimulating factor and interleukin-3 (IL-3) markedly suppressed dopaminergic neurodegeneration in 6-hydroxydopamine-lesioned rats, an animal model of Parkinson's disease. The cytokine mixture suppressed the decrease of DA content in the striatum, and ameliorated motor function in the lesioned rats. In response to the cytokine injection, dopaminergic neurons in the substantia nigra pars compacta increased expression of the antiapoptotic protein Bcl-xL. Microglial activation in the pars compacta was evident in both the saline- and cytokine-injected rats. However, the cytokine mixture suppressed expression of the proinflammatory cytokines IL-1β and tumor necrosis factors α, and upregulated the neuroprotective factors insulin-like growth factor-1 and hepatocyte growth factor. Similar responses were observed in cultured microglia. Detailed morphometric analyses revealed that NG2 proteoglycan-expressing glial cells increased in the cytokine-injected rats, while astrocytic activation with increased expression of antioxidative factors was evident only in the saline-injected rats. Thus, the present findings show that the cytokine mixture was markedly effective in suppressing neurodegeneration. Its neuroprotective effects may be mediated by increased expression of Bcl-xL in dopaminergic neurons, and the activation of beneficial actions of microglia that promote neuronal survival. Furthermore, this cytokine mixture may have indirect actions on NG2 proteoglycan-expressing glia, whose role may be implicated in neuronal survival

The Optical/Near-Infrared Light Curves of SN 2002ap for the First 1.5 Years after Discovery

Late-time BVRIJHK photometry of the peculiar Type Ic SN 2002ap, taken between 2002 June 12 and 2003 August 29 with the MAGNUM telescope, is presented. The light curve decline rate is derived in each band and the color evolution is studied through comparison with nebular spectra and with SN 1998bw. Using the photometry, the OIR bolometric light curve is built, extending from before light maximum to day 580 after explosion. The light curve has a late-time shape strikingly similar to that of the hypernova SN 1998bw. The decline rate changes from 0.018 mag/day between day 130 and 230 to 0.014 mag/day between day 270 and 580. To reproduce the late-time light curve, a dense core must be added to the 1-D hypernova model that best fits the early-time observations, bringing the ejecta mass from 2.5 Msun to 3 Msun without much change in the kinetic energy, which is 4 times 10^51 ergs. This is similar to the case of other hypernovae and suggests asymmetry. A large H-band bump developed in the spectral energy distribution after about day 300, probably caused by strong [Si I] 1.646 micron and 1.608 micron emissions. The near-infrared flux contribution increased simultaneously from 50% at day 580. The near-infrared light curves were compared with those of other Type Ib/c supernovae, among which SN 1983I seems similar to SN 2002ap both in the near-infrared and in the optical.Comment: 24pages, 9 figures, ApJ in press (10 June 2006, v644 1 issue). Acknowledgements update

The structure of the Antarctic cyclones which cause blizzards to Syowa Station

第3回極域科学シンポジウム/第35回極域気水圏シンポジウム 11月30日（金） 国立国語研究所 ２階多目的

骨盤前傾および後傾座位での傾斜反応における内腹斜筋，多裂筋の筋活動の変化

研究報告Original articles〔目的〕本研究は，骨盤前傾および後傾座位での傾斜反応における内腹斜筋，多裂筋の筋活動の変化について検討した．〔対象〕健常成人男性8 名，平均年齢28.4 ± 3.2 歳であった．〔方法〕骨盤前傾および後傾座位にて右側方傾斜時の左右の内腹斜筋，多裂筋の筋電図積分値を測定し，安静時の筋電図積分値を100% として比較を行った．〔結果〕筋電図積分相対値は，骨盤後傾座位では有意差を示さなかったが，骨盤前傾座位において右内腹斜筋は，10°右側方傾斜時と比べ20°右側方傾斜時に有意に増加した．左内腹斜筋は，安静時に比べ10°右側方傾斜時に有意に増加した．右多裂筋は，有意差がなかったが，左多裂筋は安静時に比べて10°右側方傾斜，20°右側方傾斜で有意に増加した．〔結論〕座位で体幹筋群の筋活動を高める傾斜反応の誘導は，骨盤前傾座位にて誘導することが重要であることが示された．Purpose：We investigated the activity of the internal abdominal oblique and multifidus muscles during forward and backward pelvic tilting in different seated positions. Subjects：The study included 8 young males（ mean age, 28.4 ± 3.2 years）. Methods：We obtained the integral values of electromyography signals for the right and left internal abdominal oblique and multifidus muscles when the body was seated at rest and titled to the right in the forward and backward pelvic tilting positions. Results：All integral values for both muscles did not show any significant differences when obtained during backward pelvic tilting. With regard to the forward pelvic tilting position, the values for the right internal abdominal oblique muscle were significantly higher during right-sided tilting at 20° than during right-sided tilting at 10°. The values for the left internal abdominal oblique muscle were significantly higher during right-sided tilting at 10° than at rest.Although the values for the right multifidus muscle were not significantly different between positions, those for the left multifidus muscle were significantly higher during right-sided tiltingat 10° and 20° than at rest. Conclusion：The results indicate that guidance during forward pelvic tilting is important increasing the activity of trunk muscles in the seated position

端座位および直立位における足趾圧迫力とアーチ高率との関係：臨床的な足部の機能と構造の評価の検討

研究報告Original Articles〔目的〕本研究は，端座位と直立位における足趾圧迫力とアーチ高率を測定し，足趾圧迫力とアーチ高率の関係性について調査した．〔対象〕対象は，平均年齢31.0±4.5歳の若年成人男性11名であった．〔方法〕方法は，端座位と直立位での足趾圧迫力とアーチ高率を測定した．〔結果〕足趾圧迫力は，端座位と比べ直立位において有意に増加した．一方でアーチ高率は端座位と比べ直立位において有意に低下した．直立位における足趾圧迫力は，アーチ高率と有意な正の相関を示した．〔結論〕臨床において直立位における足趾機能や足部構造の評価の必要性が示された．[Purpose] We measured the force generated by toe pressure and the arch ratio, both in sitting and standing positions, and investigated the differences in and relations among these data.[Subjects] Subjects were 11 young males (mean age. 31.0 ± 4.5 years ).[Method] Measurement items comprised the force generated by toe pressure and the arch ratio, both in sitting and standing positions.[Results] Force generated by toe pressure in the standing position was greater than that in the sitting position, but the arch ratio in the standing position was lower than that in the sitting position. Force generated by toe pressure in the standing position significantly correlated with the arch ratio in both positions.[Conclusion] The study shows importance of assessing the function and structure of the toes and feet in the standing position in a clinical setting

Fuzzy Rolling Control of High-speed Catamaran

The high-speed catamaran boat used by this study has attached trim tabs to the stern both sides as the antirolling device for reducing the rolling. A PD control was initially employed in the system, and the observed data from the instrument showed the anti-rolling effect. However no significant improvement was observed for passengers although instrumental data showed good results. Therefore, it is not evaluated highly as the anti-rolling device. In this paper, fuzzy control system is applied to the anti-rolling device of a high-speed catamaran boat in order to improve the passenger comfort. Measurements of rolling data using the real ship were carried out. From the analysis results of the frequency analysis, the presented fuzzy control system suppressed the rolling of ship about 60% in maximum peak than the PD control. Also, crews have felt the anti-rolling effect of the fuzzy control, and it showed that this system provided good comfort ride.本研究で扱う高速双胴船には,横揺れの低減のためのアンチ・ローリング装置として,両側の船尾にト リムタブが取り付けられている.この装置の制御にはPD制御が用いられており,計測器から得られるデー タより,減揺効果がある程度認められている.しかし,実際の乗客の体感としては,さほど効果が得られ ておらず,減揺装置としては高い評価が得られていない.そこで本論文では,乗客の乗り心地を改善する ために,高速双胴船のアンチ・ローリング装置の制御にファジィ制御を用いる.実船における実験より, ローリングデータを計測し,周波数分析を行った.分析結果より,最大ピーク時でファジィ制御の方がPD 制御より約60%揺動が抑制されていた.また,ファジィ制御の揺動抑制効果は乗組員によっても体感する ことができ,スムーズな制御を感じることができた

Binary Formation with Different Metallicities: Dependence on Initial Conditions

The fragmentation process in collapsing clouds with various metallicities is studied using three-dimensional nested-grid hydrodynamics. Initial clouds are specified by three parameters: cloud metallicity, initial rotation energy and initial cloud shape. For different combinations of these parameters, we calculate 480 models in total and study cloud evolution, fragmentation conditions, orbital separation and binary frequency. For the cloud to fragment during collapse, the initial angular momentum must be higher than a threshold value, which decreases with decreasing metallicity. Although the exact fragmentation conditions depend also on the initial cloud shape, this dependence is only modest. Our results indicate a higher binary frequency in lower-metallicity gas. In particular, with the same median rotation parameter as in the solar neighbourhood, a majority of stars are born as members of binary/multiple systems for < 10^-4 Z_sun. With initial mass < 0.1 M_sun, if fragments are ejected in embryo from the host clouds by multi-body interaction, they evolve to substellar-mass objects. This provides a formation channel for low-mass stars in zero- or low-metallicity environments.Comment: Accepted for publication in MNRAS. High resolution figures are available at http://www2-tap.scphys.kyoto-u.ac.jp/~machidam/astro-ph/metallicity.pd

The Optical/Near-Infrared Light Curves of SN 2002ap for the First 140 Days after Discovery

Supernova (SN) 2002ap in M74 was observed in the $UBVRIJHK$ bands for the first 40 days following its discovery (2002 January 29) until it disappeared because of solar conjunction, and then in June after it reappeared. The magnitudes and dates of peak brightness in each band were determined. While the rate of increase of the brightness before the peak is almost independent of wavelength, the subsequent rate of decrease becomes smaller with wavelength from the $U$ to the $R$ band, and is constant at wavelengths beyond $I$. The photometric evolution is faster than in the well-known ``hypernovae'' SNe~1998bw and 1997ef, indicating that SN 2002ap ejected less mass. The bolometric light curve of SN 2002ap for the full period of observations was constructed. The absolute magnitude is found to be much fainter than that of SN 1998bw, but is similar to that of SN 1997ef, which lies at the faint end of the hypernova population. The bolometric light curve at the early epochs was best reproduced with the explosion of a C+O star that ejects 2.5~M_\sun with kinetic energy $E_{\rm K}=4\times 10^{51}~{\rm ergs}$. A comparison of the predicted brightness of SN 2002ap with that observed after solar conjunction may imply that $\gamma$-ray deposition at the later epochs was more efficient than in the model. This may be due to an asymmetric explosion.Comment: 15 pages, 6 figures, quality of figure1 is reduced for smaller filesize, accepted for publication in Ap

INTRODUCTION Clinical trials leading to drug approval (registra- tion trials) play a central role in the drug devel- opment process, and clinical trials in the general View and present status of personnel involved in clinical trials : a survey of particip

. Among the support staff, 36 (80% %) had more than 5 years of experience. The most common questionnaire answer selected for participation in the symposium was &quot;willing to contact staff from other medical institutions or organizations&quot; for support staff and &quot;to obtain further knowledge concerning clinical trials&quot; for medical staff. The overall view of the discussion (&quot;Was the discussion satisfactory?&quot;) was favorable for 36 (53% %) respondents. This survey revealed that the group discussion in the present symposium appears to be valuable for participants, using overall satisfaction as a surrogate. Based on the information obtained in the present study, further development of the clinical trial infrastructure, including training opportunities and career development for support staff, is required. Due to the limitations of this study, further analysis is warranted to determine the optimal strategy for training support staff. J. Med. Invest. 58 : 81-85, February, 201

Influence of istradefylline on non-motor symptoms of Parkinson\u27s disease: A subanalysis of a 1-year observational study in Japan (J-FIRST)

IntroductionThe non-motor symptoms (NMSs) of Parkinson\u27s disease (PD) significantly impact the patient\u27s health-related quality of life. This subanalysis of the J-FIRST study evaluated the effect of istradefylline, a selective adenosine A2A receptor antagonist, on NMSs in istradefylline-naïve Japanese patients with PD.MethodsPatients with PD and ≥1 NMS and ‘wearing-off’ with their current antiparkinsonian treatment were observed for up to 52 weeks. The effect of istradefylline on NMSs was measured in terms of changes in the Movement Disorder Society Unified Parkinson\u27s Disease Rating Scale (MDS-UPDRS) Part 1 total, individual sub-items scores and the 8 item PD questionnaire (PDQ-8) estimated by the marginal structural model.ResultsOverall, 732 patients were istradefylline-naïve prior to the study, of whom 171 were treated with istradefylline for ≥8 weeks during the observation period (istradefylline-treated patients). At baseline, istradefylline-treated patients were more likely to have a dyskinesia (49.7% vs 40.8%) and received a significantly higher daily dose of levodopa (462.8 mg vs 413.0 mg) than those who did not receive istradefylline (n = 561). MDS-UPDRS Part 1 total score at the end of the 52-week observational period slightly increased in patients who received istradefylline and those who did not (0.49 ± 0.41 vs 0.07 ± 0.20; P = 0.36). There were no statistically significant differences between the two groups of patients in terms of changes in the MDS-UPDRS Part 1 total score or any sub-items, or in the PDQ-8 total score.ConclusionNMSs remained generally controlled in istradefylline-treated Japanese patients with PD who exhibited wearing-off with their current antiparkinsonian treatment. Istradefylline could be a feasible treatment option for patients with advanced PD, without worsening existing NMSs