全身性強皮症患者におけるGERD症状および逆流性食道炎の検討

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 山本 一彦, 東京大学教授 瀬戸 泰之, 東京大学准教授 池田 均, 東京大学准教授 門野 岳史, 東京大学講師 丸山 稔之University of Tokyo(東京大学

Long-term Follow-up of Orthodontic Patient with Cervical Lymphangioma

Aim: To report a treatment case of mandibular deviation caused by congenital cervical lymphangioma with traditional orthodontic techniques, following-up by 10-year retention. Background: Lymphangiomas, developmental anomalies, can induce various disturbances of swallowing, mastication, speech, breathing, and skeletal deformities as well as psychological stress and anxiety for the patient and their family. Lymphangiomas are benign with virtually no possibility of turning into a malignant lesion, so clinical management aims to treat the patient functionally. Case description: A girl, aged 6 years and 4 months, complained about facial asymmetry and anterior crossbite caused by congenital cervical lymphangioma. Her facial profile was the straight type with an adequate lip position. Anterior and right-side posterior crossbites were observed. On the frontal cephalogram, the menton shifted 3.0 mm to the right. A functional appliance with an expander was placed to correct her dental midline deviation and posterior crossbite. After 2-year treatment, the anterior and right-side posterior crossbites were improved. Multibracket treatment began after the growth spurt. After 44-month active treatment, a functional occlusion, including a Class I molar relationship with a proper interincisal relationship, was achieved. A functional occlusion was maintained during a 10-year retention period, while a mandibular downward growth was observed through the retention period. Conclusion: Conventional orthodontic techniques enable functional and stable occlusion even in patients with mandibular deviation caused by congenital cervical lymphangioma, although only using early orthodontic management by itself may have some limitations. Clinical significance: The hybrid technique combining functional appliance and intermaxillary elastics proves to be an effective therapy for correcting occlusal cant and mandibular deviation caused by cervical lymphangioma

An OFDM Receiver with Frequency Domain Diversity Combined Impulsive Noise Canceller for Underwater Network

In order to explore marine natural resources using remote robotic sensor or to enable rapid information exchange between ROV (remotely operated vehicles), AUV (autonomous underwater vehicle), divers, and ships, ultrasonic underwater communication systems are used. However, if the communication system is applied to rich living creature marine environment such as shallow sea, it suffers from generated Impulsive Noise so-called Shrimp Noise, which is randomly generated in time domain and seriously degrades communication performance in underwater acoustic network. With the purpose of supporting high performance underwater communication, a robust digital communication method for Impulsive Noise environments is necessary. In this paper, we propose OFDM ultrasonic communication system with diversity receiver. The main feature of the receiver is a newly proposed Frequency Domain Diversity Combined Impulsive Noise Canceller. The OFDM receiver utilizes 20–28 KHz ultrasonic channel and subcarrier spacing of 46.875 Hz (MODE3) and 93.750 Hz (MODE2) OFDM modulations. In addition, the paper shows Impulsive Noise distribution data measured at a fishing port in Okinawa and at a barge in Shizuoka prefectures and then proposed diversity OFDM transceivers architecture and experimental results are described. By the proposed Impulsive Noise Canceller, frame bit error rate has been decreased by 20–30%

Intraoperative hand strength as an indicator of consciousness during awake craniotomy: a prospective, observational study

握力が覚醒下開頭手術中の覚醒度の指標となる. 京都大学プレスリリース. 2022-01-11.Awake craniotomy enables mapping and monitoring of brain functions. For successful procedures, rapid awakening and the precise evaluation of consciousness are required. A prospective, observational study conducted to test whether intraoperative hand strength could be a sensitive indicator of consciousness during the awake phase of awake craniotomy. Twenty-three patients who underwent awake craniotomy were included. Subtle changes of the level of consciousness were assessed by the Japan Coma Scale (JCS). The associations of hand strength on the unaffected side with the predicted plasma concentration (Cp) of propofol, the bispectral index (BIS), and the JCS were analyzed. Hand strength relative to the preoperative maximum hand strength on the unaffected side showed significant correlations with the Cp of propofol (ρ =  − 0.219, p = 0.007), the BIS (ρ = 0.259, p = 0.002), and the JCS (τ =  − 0.508, p = 0.001). Receiver operating characteristic curve analysis for discriminating JCS 0–1 and JCS ≥ 2 demonstrated that the area under the curve was 0.76 for hand strength, 0.78 for Cp of propofol, and 0.66 for BIS. With a cutoff value of 75% for hand strength, the sensitivity was 0.76, and the specificity was 0.67. These data demonstrated that hand strength is a useful indicator for assessing the intraoperative level of consciousness during awake craniotomy

Artificial selection reveals the role of transcriptional constraints in the maintenance of life history variation

This is the final version. Available on open access from Wiley via the DOI in this recordThe trade‐off between reproduction and self‐maintenance is a cornerstone of life history theory, yet its proximate underpinnings are elusive. Here, we used an artificial selection approach to create replicated lines of Japanese quail (Coturnix japonica) that differ genetically in their reproductive investment. Whole transcriptome sequencing revealed that females from lines selected for high reproductive output show a consistent upregulation of genes associated with reproduction but a simultaneous downregulation of immune genes. Concordant phenotypic differences in immune function (i.e., specific antibody response against keyhole limpet hemocyanin) were observed between the selection lines, even in males who do not provide parental care. Our findings demonstrate the key role of obligate transcriptional constraints in the maintenance of life history variation. These constraints set fundamental limits to productivity and health in natural and domestic animal populations.Universität ZürichKAKENHISchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschun

Correlation between brain functional connectivity and neurocognitive function in patients with left frontal glioma

The association between neurocognitive function (NCF) impairment and brain cortical functional connectivity in glioma patients remains unclear. The correlations between brain oscillatory activity or functional connectivity and NCF measured by the Wechsler Adult Intelligence Scale full-scale intelligence quotient scores (WAIS FSIQ), the Wechsler Memory Scale-revised general memory scores (WMS-R GM), and the Western aphasia battery aphasia quotient scores (WAB AQ) were evaluated in 18 patients with left frontal glioma using resting-state electroencephalography (EEG). Current source density (CSD) and lagged phase synchronization (LPS) were analyzed using exact low-resolution electromagnetic tomography (eLORETA). Although 2 and 2 patients scored in the borderline range of WAIS FSIQ and WMS-R GM, respectively, the mean WAIS FSIQ, WMS-R GM, and WAB AQ values of all patients were within normal limits, and none had aphasia. In the correlation analysis, lower WMS-R GM was associated with a higher LPS value between the right anterior prefrontal cortex and the left superior parietal lobule in the beta1 band (13-20 Hz, R = - 0.802, P = 0.012). These findings suggest that LPS evaluated by scalp EEG is associated with memory function in patients with left frontal glioma and mild NCF disorders

Combination of panobinostat with ponatinib synergistically overcomes imatinib-resistant CML cells

The major mechanism of imatinib (IM) resistance of CML is the reactivation of ABL kinase either through BCR-ABL gene amplification or mutation. We investigated the cytotoxicity of a pan-ABL tyrosine kinase inhibitor, ponatinib, and a pan-histone deacetylase inhibitor, panobinostat, against IM-resistant CML cells in vitro. Two different IM-resistant cell lines, K562/IM-R1 and Ba/F3/T315I were evaluated in comparison with their respective, parental cell lines, K562 and Ba/F3. K562/IM-R1 overexpressed BCR-ABL due to gene amplification. Ba/F3/T315I was transfected with a BCR-ABL gene encoding T315I-mutated BCR-ABL. Ponatinib inhibited the growth of both K562/IM-R1 and Ba/F3/T315I as potently as it inhibited their parental cells with an IC50 of 2-30 nM. Panobinostat also similarly inhibited the growth of all of the cell lines with an IC50 of 40-51 nM. This was accompanied by reduced histone deacetylase activity, induced histone H3 acetylation, and an increased protein level of heat shock protein 70, which suggested disruption of heat shock protein 90 chaperone function for BCR-ABL and its degradation. Importantly, the combination of ponatinib with panobinostat showed synergistic growth inhibition and induced a higher level of apoptosis than the sum of the apoptosis induced by each agent alone in all of the cell lines. Ponatinib inhibited phosphorylation not only of BCR-ABL but also of downstream signal transducer and activator of transcription 5, protein kinase B, and ERK1/2 in both K562/IM-R1 and Ba/F3/T315I, and the addition of panobinostat to ponatinib further inhibited these phosphorylations. In conclusion, panobinostat enhanced the cytotoxicity of ponatinib towards IM-resistant CML cells including those with T315I-mutated BCR-ABL

シュウゴウ テキ ジソンカンジョウ ケンキュウ ノ ガイヨウ

論

Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals

Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 variants at 36 genomic loci (P<5 × 10–8) including eight novel loci. Of these, missense variants of SESN2 and PNPLA3 were predicted to be damaging to the function of these proteins; another five loci—TMEM18, TM4SF4, MXD3-LMAN2, PSORS1C1-PSORS1C2, and HNF4A—are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, LINC01578, is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout