Epitope Analysis of Cerebrospinal Fluid IgG in Japanese Multiple Sclerosis Patients Using Phage Display Method

To investigate the antigen recognized by cerebrospinal fluid (CSF) high affinity IgG in patients with multiple sclerosis (MS), the phage display method was applied to the CSF from 15 MS and 10 control patients. Peptide sequences recognized by MS and control CSF IgG were individual specific, and no common motif was found. Peptide sequences frequently showed homology to various kinds of amino acid sequences of ubiquitous viruses such as epstein barr virus (EBV) and herpes simplex virus (HSV), although the frequency was not specific to MS patients. MS CSF IgG may recognize various types of ubiquitous viral antigen and may be increased by a bystander response

Seizure and Profound Hypokalemia: Unusual Presentation of Primary Hyperparathyroidism

A 68-year-old man was admitted because of tonic–clonic convulsion. He had been receiving 200 mg itraconazole for 10 days. He had hypokalaemia (2.2 mEq/l), hypercalcaemia (Cacorr 11.0 mg/dl) and elevated serum parathyroid hormone (PTH, 95 pg/ml). Ultrasound examination of the neck revealed a low echoic tumour. Cessation of itraconazole and fluid supplementation eradicated clinical symptoms and profound hypokalaemia, but serum potassium remained low normal (3.4 mEq/l) and the mild hypercalcaemia and elevated PTH were unchanged. To conclude, a small amount of itraconazole (200 mg) precipitated profound hypokalaemia and seizure in a patient with mild hyperparathyroidism and low normal serum potassium

Investigating the role of the Itoigawa-Shizuoka tectonic line towards the evolution of the Northern Fossa Magna rift basin

AbstractThe Itoigawa-Shizuoka tectonic line (ISTL) fault system is considered to have one of the highest probabilities for a major inland earthquake occurrence in the whole of Japan. It is a complex fault system with the dip directions of the local fault segments changing from north to south between an east-dipping low-angle thrust fault, a strike slip fault and a west-dipping thrust fault. The tectonic relations between the different parts of the fault system and the surrounding geological units are yet to be fully explained. This study aims to reveal the juncture of the northern and central parts of the ISTL and investigate its contribution towards the shaping of the Northern Fossa Magna rift basin. We conducted 3 deployments of 1 or 2 linear arrays of seismic stations across the central and northern ISTL regions and observed local micro-earthquakes for a period of 3 years. Each deployment recorded continuous waveform data for approximately 3 months. Using arrival times of 1193 local earthquakes, we jointly determined earthquake locations and a 3D velocity model, applying the tomography method. We were able to image the regional crustal structures from the surface to a depth of 20km with a spatial resolution of 5km. Subsequently, we used the obtained 3D velocity model to relocate the background local seismicity from 2003 to 2009. The juncture of the northern and central parts of the ISTL was well constrained by our results. The depth extension of the northern parts of the ISTL fault segments follows the bottom of the Miocene Northern Fossa Magna rift basin (NFM) and forms an east-dipping low-angle fault. In contrast, the central parts of the ISTL fault segments are estimated to lie along the eastern boundary of the Matsumoto basin forming an oblique strike slip fault (Fig. 1)

Regional Climate Model Intercomparison Project for Asia

Improving the simulation of regional climate change is one of the high-priority areas of climate study because regional information is needed for climate change impact assessments. Such information is especially important for the region covered by the East Asian monsoon where there is high variability in both space and time. To this end, the Regional Climate Model Intercomparison Project (RMIP) for Asia has been established to evaluate and improve regional climate model (RCM) simulations of the monsoon climate. RMIP operates under joint support of the Asia–Pacific Network for Global Change Research (APN), the Global Change System for Analysis, Research and Training (START), the Chinese Academy of Sciences, and several projects of participating nations. The project currently involves 10 research groups from Australia, China, Japan, South Korea, and the United States, as well as scientists from India, Italy, Mongolia, North Korea, and Russia. RMIP has three simulation phases: March 1997–August 1998, which covers a full annual cycle and extremes in monsoon behavior; January 1989–December 1998, which examines simulated climatology; and a regional climate change scenario, involving nesting with a global model. This paper is a brief report of RMIP goals, implementation design, and some initial results from the first phase studies

オホーツクカイ エンガン ノトロコ ノ 2008ネン ケッピョウキ ニ オケル カイヨウ カンキョウ ト クロロフィル a ノ ドウタイ

オホーツク海は漁業資源の豊かな海として知られるが,冬季,海氷に覆われるときの調査研究例はきわめて少ない。その要因としてオホーツク海の海氷の大半は流氷であり,調査が困難であることがあげられる。そこで,本研究では定着氷に着目し,道東オホーツク沿岸域にある能取湖で2008年2月6日から3月18日にかけての結氷期に調査を実施した。本研究の結果,海氷中の積算クロロフィルa量は,2月中は海氷の成長にともない増加し,3月に減少する傾向を示した。特に2月29日から3月10日にかけては,急激に積算クロロフィルa量が減少した。一方,水柱の積算クロロフィルa量は8.7-119.1mg/m^2の範囲にあり,調査期間中増加する傾向にあった。特に3月18日には急激な増加がみられ調査期間中最大値となった。2008年の結氷期は3月10日前後を境として,海氷生成期から融解期にシフトしたと考えられる。積算クロロフィルa量は,海氷生成期には約25%は海氷中に存在し,融解期では95%以上が水柱に存在し,このシフトによって一次生産の生産構造に変化が起こったことが示唆された。海氷と水柱の値を合算した総積算クロロフィルa量は,2月6日から3月10日までの海氷生成期間には10.9-46.6mg/m^2,海氷融解期である3月18日は121.5mg/m^2であった。2007年の非結氷期の積算クロロフィルa量と比較すると,前者は8月から12月の積算クロロフィルa量の少ない期間と同程度であり,後者は4月下旬から5月上旬の比較的積算クロロフィルa量が多いときを上回る値であった。すなわち,弱光環境に適応したアイスアルジーや植物プランクトンが,能取湖の結氷期のクロロフィルa量に寄与していることが推察された。Lagoon Notoro-ko located in northeast Hokkaido, is connected to the Okhotsk Sea by an artificial channel and there are few incoming rivers. This lagoon is covered with sea ice during winter and early spring. So we conducted an investigation of temporal changing of oceanographic conditions and chlorophyll a in sea ice and water column from February 6 to March 18 in 2008. The quantity of integrated chlorophyll a in sea ice increased with the growth of sea ice during February and showed a tendency to decrease in March. Especially, the integrated quantity of chlorophyll a in sea ice sharply decreased upto March 10 (1.5mg/m^2) from February 29 (10.1mg/m^2). On the other hand, the quantity of integrated chlorophyll a of the water column tended to increase. A remarkable increase was found on March 18 (119.1mg/m^2) from March 10 (43.7mg/m^2). It is thought that the sea ice of the Lagoon Notoro-ko shifted around March 10 as the boundary for the melting phase from the product phase. The total quantity of integrated chlorophyll a was 10.9-46.6mg/m^2 for the sea ice product phase (February 6 to March 10) and 121.5mg/m^2 for the sea ice melting phase (March 18). The former was at the same level as the period with a small quantity of integrated chlorophyll a from August to December, and the latter value was more at the time when there was relatively much more integrated chlorophyll a in the beginning of May from the end of April. It was suguessed that ice algae and the phytoplankton which adapted to the low light environment contributed to the quantity of chlorophyll a in the freezing period of the Lagoon Notoro-ko

Daikenchuto accelerates the recovery from prolonged postoperative ileus after open abdominal surgery : a subgroup analysis of three randomized controlled trials

Purpose Prolonged postoperative ileus (POI) is a common complication after open abdominal surgery (OAS). Daikenchuto (DKT), a traditional Japanese medicine that peripherally stimulates the neurogenic pathway, is used to treat prolonged POI in Japan. To analyze whether DKT accelerates the recovery from prolonged POI after OAS, we conducted a secondary analysis of three multicenter randomized controlled trials (RCTs). Methods A secondary analysis of the three RCTs supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer (project numbers 39-0902, 40-1001, 42-1002) assessing the effect of DKT on prolonged POI in patients who had undergone OAS for colon, liver, or gastric cancer was performed. The subgroup included 410 patients with no bowel movement (BM) before the first diet, a DKT group (n = 214), and a placebo group (n = 196). Patients received either 5 g DKT or a placebo orally, three times a day. The primary endpoint was defined as the time from the end of surgery to the first bowel movement (FBM). A sensitivity analysis was also performed on the age, body mass index and dosage as subgroup analyses. Results The primary endpoint was significantly accelerated in the DKT group compared with the placebo group (p = 0.004; hazard ratio 1.337). The median time to the FBM was 113.8 h in the placebo group and 99.1 h in the DKT treatment group. Conclusions The subgroup analysis showed that DKT significantly accelerated the recovery from prolonged POI following OAS

Evaluation of oral immunotherapy efficacy and safety by maintenance dose dependency: A multicenter randomized study

Background Generally, oral immunotherapy (OIT) aims for daily administration. Recently, the efficacy of treatment with OIT at a low dose has been reported. However, the optimal dose and the evaluation of dose-dependent OIT outcome have not been described. Methods A multicenter, parallel, open-labeled, prospective, non-placebo controlled, randomized study enrolled 101 Japanese patients for treatment with OIT. We hypothesized that target dose OIT would induce short-term unresponsiveness (StU) earlier than reduced dose OIT. StU was defined as no response to 6200 mg whole egg, 3400 mg milk, and 2600 mg wheat protein, as evaluated by oral food challenge after 2-week ingestion cessation. To compare the two doses of OIT efficacy, the maximum ingestion doses during the maintenance phase of OIT were divided into 100%-dose or 25%-dose groups against their target StU dose, respectively. A total of 51 patients were assigned to the 100%-dose group [hen's egg (HE) = 26, cow's milk (CM) = 13, wheat = 12] and 50 to the 25%-dose group (HE = 25, CM = 13, wheat = 12). Primary outcome was established by comparing StU at 1 year. Secondary outcome was StU at 2 years and established by comparing allergic symptoms and immunological changes. Results The year 1 StU rates (%) for the 100%- and 25%-dose groups were 26.9 vs. 20.0 (HE), 7.7 vs. 15.4 (CM), and 50.0 vs. 16.7 (wheat), respectively. The year 2 StU rates were 30.8 vs. 36.0 (HE), 7.7 vs. 23.1 (CM), and 58.3 vs. 58.3 (wheat), respectively. There were no statistically significant differences in StU between years 1 and 2. The total allergic symptom rate in the 25%-dose group was lower than that in the 100%-dose group for egg, milk, and wheat. Antigen-specific IgE levels for egg-white, milk, and wheat decreased at 12 months. Conclusions Reduced maintenance dose of egg OIT showed similar therapeutic efficacy to the target dose. However, we were not able to clearly demonstrate the efficacy, particularly for milk and wheat. Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target OIT dose. Furthermore, aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT

FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters

乳がんの再発を起こす原因細胞を解明. 京都大学プレスリリース. 2023-11-16.The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain–containing ion transport regulator 3 (FXYD3), a component of the Na⁺/K⁺ pump. Accordingly, FXYD3⁺ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3⁺ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3⁺ CSCs were sensitive to senolytic Na⁺/K⁺ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3⁺ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na⁺/K⁺ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis