抗T細胞性急性白血病活性を示す新規シード化合物の探索

学位の種別: 課程博士審査委員会委員 : （主査）東京大学准教授 合山 進, 東京大学教授 内丸 薫, 東京大学教授 松田 浩一, 東京大学教授 山梨 裕司, 東京大学准教授 今井 陽一University of Tokyo(東京大学

DIHS/DRESS患者における血清中HHV6B microRNAの変化

博士（医学）・甲第699号・平成31年3月15日Copyright © 2018. Acta Dermato-Venereologica. All rights reserved.This is an open access article under the CC BY-NC license(http://creativecommons.org/licenses/by-nc/4.0/)

FDG-PET/CT is useful in the diagnosis of early phase Takayasu's arteritis : A case report

A 60-year-old female patient was admitted to our hospital in April, 2010 because of low-grade fever and malaise for several months. Physical examination on admission revealed no abnormalities except for a body temperature of 37.2℃. Blood examinations showed moderate anemia and a high erythrocyte sedimentation rate. There were no other specific abnormal findings. A systemic CT scan study disclosed diffuse thickening of the artery wall through the ascending, descending and abdominal aorta to the bilateral iliac arteries. In order to evaluate the quality of the vessel lesions, a FDG-PET/CT study was performed and revealed abnormal accumulation of 18F-FDG in the thickened wall, suggesting an inflammatory process in the lesion. Taking all these findings into consideration, we made the diagnosis of Takayasu's arteritis, and treated the patient with prednisolone. The treatment was effective and her symptoms improved. A later CT scan revealed that the artery wall became somewhat thinner. Takayasu's arteritis is a disease whose diagnosis is difficult to make because there are neither specific signs nor diagnostic laboratory findings in its early stage. We found that FDG-PET/CT was helpful in the diagnosis and evaluation of lesions in a patient with Takayasu's arteritis

エキスパートナースが大切にする実践

To clarify the practical approaches of nurses in cancer chemotherapy, semi-structured interviews were conducted with 10 nurses certified for cancer chemotherapy in Tokushima Prefecture. The interview data were classified into the following categories : [not neglecting any step, as failure is unacceptable], [accurately predicting the symptoms of chemotherapy, rather than simply waiting for patients to report them], [making efforts to fulfill patients' desire to live], [bearing a heavy responsibility for handling toxic drugs], and [playing a role in generalizing chemotherapy]. The results suggest that the practical approaches of nurses in cancer chemotherapy three features place importance on “achieving positive effects while minimizing risks”, “not narrowing down the scope of life”, and “reducing resistance to chemotherapy”

Changes in lipoprotein lipase and endothelial lipase mass in familial hypercholesterolemia during three-drug lipid-lowering combination therapy.

Background: This study was performed to compare the effects of three different lipid-lowering therapies (statins, ezetimibe, and colestimide) on lipoprotein lipase and endothelial lipase masses in pre-heparin plasma (pre-heparin LPL and EL mass, respectively) from patients with familial hypercholesterolemia (FH). FH is usually treated by coadministration of these three drugs. Methods: The pre-heparin LPL and EL masses were measured in fresh frozen plasma drawn and stored at various time points during coadministration of the three drugs from patients with heterozygous FH harboring a single mutation in the LDL receptor (n = 16, mean age 63 years). The patients were randomly divided into two groups based on the timing when ezetimibe was added. Results: Plasma LPL mass concentration was significantly reduced by rosuvastatin at 20 mg/day (median = 87.4 [IQR: 71.4-124.7] to 67.5 [IQR: 62.1-114.3] ng/ml, P < 0.05). In contrast, ezetimibe at 10 mg/day as well as colestimide at 3.62 g/day did not alter its level substantially (median = 67.5 [IQR: 62.1-114.3] to 70.2 [IQR: 58.3-106.2], and to 74.9 [IQR: 55.6-101.3] ng/ml, respectively) in the group starting with rosuvastatin followed by the addition of ezetimibe and colestimide. On the other hand, the magnitude in LPL mass reduction was lower in the group starting with ezetimibe at 10 mg/day before reaching the maximum dose of 20 mg/day of rosuvastatin. Plasma EL mass concentration was significantly increased by rosuvastatin at 20 mg/day (median = 278.8 [IQR: 186.7-288.7] to 297.0 [IQR: 266.2-300.2] ng/ml, P < 0.05), whereas other drugs did not significantly alter its level. Conclusion: The effects on changes of LPL and EL mass differed depending on the lipid-lowering therapy, which may impact the prevention of atherosclerosis differently. © 2016 Tada et al

Lipoprotein lipase is active as a monomer

Lipoprotein lipase (LPL), the enzyme that hydrolyzes triglycerides in plasma lipoproteins, is assumed to be active only as a homodimer. In support of this idea, several groups have reported that the size of LPL, as measured by density gradient ultracentrifugation, is ∼110 kDa, twice the size of LPL monomers (∼55 kDa). Of note, however, in those studies the LPL had been incubated with heparin, a polyanionic substance that binds and stabilizes LPL. Here we revisited the assumption that LPL is active only as a homodimer. When freshly secreted human LPL (or purified preparations of LPL) was subjected to density gradient ultracentrifugation (in the absence of heparin), LPL mass and activity peaks exhibited the size expected of monomers (near the 66-kDa albumin standard). GPIHBP1-bound LPL also exhibited the size expected for a monomer. In the presence of heparin, LPL size increased, overlapping with a 97.2-kDa standard. We also used density gradient ultracentrifugation to characterize the LPL within the high-salt and low-salt peaks from a heparin-Sepharose column. The catalytically active LPL within the high-salt peak exhibited the size of monomers, whereas most of the inactive LPL in the low-salt peak was at the bottom of the tube (in aggregates). Consistent with those findings, the LPL in the low-salt peak, but not that in the high-salt peak, was easily detectable with single mAb sandwich ELISAs, in which LPL is captured and detected with the same antibody. We conclude that catalytically active LPL can exist in a monomeric state

Sex-inducing effects toward planarians widely present among parasitic flatworms

Summary Various parasitic flatworms infect vertebrates for sexual reproduction, often causing devastating diseases in their hosts. Consequently, flatworms are of great socioeconomic and biomedical importance. Although the cessation of parasitic flatworm sexual reproduction is a major target of anti-parasitic drug design, little is known regarding bioactive compounds controlling flatworm sexual maturation. Using the planarian Dugesia ryukyuensis, we observed that sex-inducing substances found in planarians are also widespread in parasitic flatworms, such as monogeneans and flukes (but not in tapeworms). Reverse-phase HPLC analysis revealed the sex-inducing substance(s) eluting around the tryptophan retention time in the fluke Calicophoron calicophorum, consistent with previous studies on the planarian Bipalium nobile, suggesting that the substance(s) is likely conserved among flatworms. Moreover, six of the 18 ovary-inducing substances identified via transcriptome and metabolome analyses are involved in purine metabolism. Our findings provide a basis for understanding and modifying the life cycles of various parasitic flatworms.journal articl

Epigenetic control of translation checkpoint and tumor progression via RUVBL1-EEF1A1 axis

Epigenetic dysregulation is reported in multiple cancers including Ewing sarcoma (EwS). However, the epigenetic networks underlying the maintenance of oncogenic signaling and therapeutic response remain unclear. Using a series of epigenetics- and complex-focused CRISPR screens, RUVBL1, the ATPase component of NuA4 histone acetyltransferase complex, is identified to be essential for EwS tumor progression. Suppression of RUVBL1 leads to attenuated tumor growth, loss of histone H4 acetylation, and ablated MYC signaling. Mechanistically, RUVBL1 controls MYC chromatin binding and modulates the MYC-driven EEF1A1 expression and thus protein synthesis. High-density CRISPR gene body scan pinpoints the critical MYC interacting residue in RUVBL1. Finally, this study reveals the synergism between RUVBL1 suppression and pharmacological inhibition of MYC in EwS xenografts and patient-derived samples. These results indicate that the dynamic interplay between chromatin remodelers, oncogenic transcription factors, and protein translation machinery can provide novel opportunities for combination cancer therapy.</p

Postoperative Course of Crohn\u27s Disease -In regard to Recurrence and Residual Disease at Anastomosis -

Twenty-seven patients with Crohn\u27s disease who were operated on at the First Department of Surgery, Nagasaki University School of Medicine and followed-up after surgery were reviewed. Involved portion of intestinal tract were 10 in small bowel only, 14 in both small and large bowels, and 3 in large bowel. Major indication for surgery were obstruction, fistula, peritonitis and intractability of medical therapy. Twenty-two patients underwent radical resection and the other 5 patients had the disease left behind at anastomosis. The recurrence rate was 25.9% (7 out of 22), and early recurrence was found in small bowel diseases with longitudinal ulcerations or multiple aphthoid ulcers. Initial recurrence occured near the suture line, which showed no wide spreading in subsequent periods. Two cases with both small and large bowel disease required reoperation over 5 years after initial surgery because of stenosis. Three out of five cases with residual disease at the intestinal resection margin had a good condition, but the other three cases with skip sigmoid disease were intractable for medical therapy. Most suture line recurrence and residual disease at anastomosis were sufficiently managed by postoperative medication for long periods of time. Long-term follow-up study showed a good quality of life in about 75% of these cases. In conclusion, conservative resection rather than the sacrifice of normal bowel should be recommended for an extended disease of small bowel