A novel laser melting sampler for discrete, sub-centimeter depth-resolved analyses of stable water isotopes in ice cores

We developed a novel laser melting sampler (LMS) for ice cores to measure the stable water isotope ratios (δ18O and δD) as temperature proxies at sub-centimeter depth resolutions. In this LMS system, a 2 mm diameter movable evacuation nozzle holds an optical fiber through which a laser beam irradiates the ice core. The movable nozzle intrudes into the ice core, the laser radiation meanwhile melts the ice cylindrically, and the meltwater is pumped away simultaneously through the same nozzle and transferred to a vial for analysis. To avoid isotopic fractionation of the ice through vaporization, the laser power is adjusted to ensure that the temperature of the meltwater is always kept well below its boiling point. A segment of a Dome Fuji shallow ice core (Antarctica), using the LMS, was then demonstrated to have been discretely sampled with a depth resolution as small as 3 mm: subsequent analysis of δ18O, δD, and deuterium excess (d) was consistent with results obtained by hand segmentation within measurement uncertainties. With system software to control sampling resolution, the LMS will enable us to identify temperature variations that may be detectable only at sub-centimeter resolutions in ice cores

破壊過程における断層幾何の重要性

京都大学0048新制・課程博士博士(理学)甲第8161号理博第2183号新制||理||1154(附属図書館)UT51-2000-F65京都大学大学院理学研究科地球惑星科学専攻(主査)教授 尾池 和夫, 教授 竹本 修三, 教授 安藤 雅孝学位規則第4条第1項該当Doctor of ScienceKyoto UniversityDA

Correlation between elevation of serum antinuclear antibody titer and decreased therapeutic efficacy in the treatment of Behçet's disease with infliximab

Background: Infliximab, an anti-TNF-α monoclonal antibody, administered to Behçet's disease (BD) patients in Japan with refractory intraocular inflammation, has shown excellent clinical results. However, some patients demonstrate a decreased response to infliximab during the course of the treatment. In the present study, we investigated the correlation between this reduced therapeutic effect and elevation of the serum antinuclear antibody (ANA) titers in patients with BD who were undergoing infliximab therapy. Methods: Seventeen patients (14 males and 3 females) with uveitis in BD who were undergoing treatment with infliximab for 2 years or longer were enrolled. Their blood test results and clinical histories were obtained from medical records. Results: One patient (5.9%) was ANA-positive prior to the initiation of infliximab, and 11 patients (64.7%) developed positive ANA during the therapy. The appearance of ANA was observed 6 months after the initiation of the infliximab therapy, and its titres gradually increased. None of the patients showed lupus symptoms. Five patients (29.4%) have suffered from ocular inflammatory attacks since 6th month from the initiation of infliximab treatment and all of them were ANA-positive. In contrast, 4 patients (23.5%) who were ANA-negative experienced no ocular attacks during the follow-up period. Conclusions: Here we report the positive conversion and subsequent elevation of serum ANA titres in some patients with BD after the initiation of infliximab therapy. Since all recurrences of uveitis were shown only in the ANA-positive patients, serum ANA titre may be a helpful biomarker for predicting the recurrence of ocular attacks in BD patients treated with anti-TNF-α antibody therapies

An Fc Gamma Receptor-Mediated Upregulation of the Production of Interleukin 10 by Intravenous Immunoglobulin in Bone-Marrow-Derived Mouse Dendritic Cells Stimulated with Lipopolysaccharide In Vitro

Intravenous immunoglobulin (IVIG), a highly purified immunoglobulin fraction prepared from pooled plasma of several thousand donors, increased anti-inflammatory cytokine IL-10 production, while decreased proinflammatory cytokine IL-12p70 production in bone-marrow-derived mouse dendritic cells (BMDCs) stimulated with lipopolysaccharide (LPS). The changes of cytokine production were confirmed with the transcription levels of these cytokines. To study the mechanisms of this bidirectional effect, we investigated changes of intracellular molecules in the LPS-induced signaling pathway and observed that IVIG upregulated ERK1/2 phosphorylation while downregulated p38 MAPK phosphorylation. Using chemical inhibitors specific to protein kinases involved in activation of Fc gamma receptors (FcγRs), which mediate IgG signals, we found that hyperphosphorylation of ERK1/2 and Syk phosphorylation occurred after stimulation of BMDC with LPS and IVIG, and the increasing effect on IL-10 production was abolished by these inhibitors. Furthermore, an antibody specific to FcγRI, one of FcγRs involved in immune activation, inhibited IVIG-induced increases in IL-10 production, but not IL-12p70 decreases, whereas the anti-IL-10 antibody restored the decrease in IL-12p70 induced by IVIG. These findings suggest that IVIG induced the upregulation of IL-10 production through FcγRI activation, and IL-10 was indispensable to the suppressing effect of IVIG on the production of IL-12p70 in LPS-stimulated BMDC

Tyrosinase gene family and Vogt-Koyanagi-Harada disease in Japanese patients.

PURPOSE: The aim of the present study was to examine the genetic background of Vogt-Koyanagi-Harada (VKH) disease in a Japanese population by analyzing the tyrosinase gene family (TYR, TYRP1, and dopachrome tautomerase (DCT)). METHODS: 87 VKH patients and 122 healthy controls were genotyped using seven microsatellite markers on the candidate loci. We analyzed microsatellite (MS) polymorphisms at regions within tyrosinase gene family loci. In addition, the haplotype frequencies were also estimated and statistical analysis was performed. HLA-DRB1 genotyping was performed by the PCR-restriction fragment length polymorphism (RFLP) method. RESULTS: No significant evidence for an association was found. HLA-DRB1*0405 showed a highly significant association with VKH disease compared with the healthy controls (Pc=0.000000079), as expected. CONCLUSIONS: We concluded that there is no genetic susceptibility or increased risk attributed to the tyrosinase gene family. Our results suggest the need for further genetic study and encourage a search for novel genetic loci and predisposing genes in order to elucidate the genetic mechanisms underlying VKH disease

Alterations of choroidal circulation and vascular morphology in a patient with chronic myeloid leukemia before and after chemotherapy

Background Chronic myeloid leukemia (CML) is known to cause leukemic retinopathy due to leukemia cell invasion into the choroid; however, details of the circulatory dynamics and morphological changes in the choroid are unknown. The aim of this study was to present a case of leukemic retinopathy and examine choroidal circulatory and structural analyses using laser speckle flowgraphy (LSFG) and optical coherence tomography with a binarization method, respectively. Case presentation A 15-year-old male diagnosed with CML complained of blurred vision in his right eye. He was ophthalmologically diagnosed with leukemic retinopathy due to retinal hemorrhage in both eyes. Tyrosine kinase inhibitors achieved complete cytogenetic remission and resolution of retinal hemorrhages at 6 months after treatment. After the treatment, the best-corrected visual acuity had recovered from 0.1 to 1.2 oculus dexter (OD) and remained at 1.5 oculus sinister (OS). The rate of change in macular blood flow assessed by the mean blur rate on LSFG was 18.3% increase OD and 25.2% decrease OS 19 months after treatment. The central choroidal thickness showed 0.4 and 3.1% reductions OD and OS, respectively. The binarization technique demonstrated that the rate of luminal areas in choroidal areas exhibited 3.2% increase OD but 4.8% decrease OS. Conclusion Choroidal blood flow improved OD after treatment for CML, while it deteriorated OS, together with choroidal thinning due to reduction of luminal areas. The degrees of leukemia cell invasion into the choroidal tissue and tissue destruction might be different between the eyes in this case