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Radical surgery for advanced pure squamous cell carcinoma of the gallbladder: report of a case.

Squamous cell carcinoma (SCC) of the gallbladder is frequently detected at an advanced stage because of its tendency to infiltrate adjacent organs. In addition, more rapid growth of this type of carcinoma compared to that of adenocarcinoma, the most frequent subtype of gallbladder carcinoma, has been reported. Although it is not rare to find squamous cell carcinoma components in cases other than the usual adenocarcinoma of the gallbladder, these cases must be distinguished from those of pure squamous cell carcinoma, as diagnosed in the present case. Pure squamous cell carcinoma is characterized by a well-localized growth, no visceral metastasis, and a rarity or lack of lymph node metastasis, even when the tumor has grown to a large size locally. Prognosis of SCC of the gallbladder has generally been considered poor. Nevertheless, long-term survival after curative resection in patients with SCC of the gallbladder has been sporadically reported. We performed extended right hemihepatectomy with portal vein resection after portal vein embolization for a 55-year-old woman with advanced SCC of the gallbladder. The patient has not developed any signs of recurrence 40 months after the surgery. Although such radical surgery remains challenging, it may lead to a favorable outcome in selected patients with advanced SCC of the gallbladder

Non-missense variants of KCNH2 show better outcomes in type 2 long QT syndrome

AIMS: More than one-third of type 2 long QT syndrome (LQT2) patients carry KCNH2 non-missense variants that can result in haploinsufficiency (HI), leading to mechanistic loss-of-function. However, their clinical phenotypes have not been fully investigated. The remaining two-thirds of patients harbour missense variants, and past studies uncovered that most of these variants cause trafficking deficiency, resulting in different functional changes: either HI or dominant-negative (DN) effects. In this study, we examined the impact of altered molecular mechanisms on clinical outcomes in LQT2 patients. METHODS AND RESULTS: We included 429 LQT2 patients (234 probands) carrying a rare KCNH2 variant from our patient cohort undergoing genetic testing. Non-missense variants showed shorter corrected QT (QTc) and less arrhythmic events (AEs) than missense variants. We found that 40% of missense variants in this study were previously reported as HI or DN. Non-missense and HI-groups had similar phenotypes, while both exhibited shorter QTc and less AEs than the DN-group. Based on previous work, we predicted the functional change of the unreported variants-whether they cause HI or DN via altered functional domains-and stratified them as predicted HI (pHI)- or pDN-group. The pHI-group including non-missense variants exhibited milder phenotypes compared to the pDN-group. Multivariable Cox model showed that the functional change was an independent risk of AEs (P = 0.005). CONCLUSION: Stratification based on molecular biological studies enables us to better predict clinical outcomes in the patients with LQT2

Phosphorylation of the RSRSP stretch is critical for splicing regulation by RNA-Binding Motif Protein 20 (RBM20) through nuclear localization

RBM20 is a major regulator of heart-specific alternative pre-mRNA splicing of TTN encoding a giant sarcomeric protein titin. Mutation in RBM20 is linked to autosomal-dominant familial dilated cardiomyopathy (DCM), yet most of the RBM20 missense mutations in familial and sporadic cases were mapped to an RSRSP stretch in an arginine/serine-rich region of which function remains unknown. In the present study, we identified an R634W missense mutation within the stretch and a G1031X nonsense mutation in cohorts of DCM patients. We demonstrate that the two serine residues in the RSRSP stretch are constitutively phosphorylated and mutations in the stretch disturb nuclear localization of RBM20. Rbm20 S637A knock-in mouse mimicking an S635A mutation reported in a familial case showed a remarkable effect on titin isoform expression like in a patient carrying the mutation. These results revealed the function of the RSRSP stretch as a critical part of a nuclear localization signal and offer the Rbm20 S637A mouse as a good model for in vivo study

Imaging of radiation during impurity gas puffing in LHD

In LHD, several methods of detachment have been attempted, including impurity gaspuffing [1], and the application of an m/n=1/1 magnetic perturbation [2]. LHD is equipped with an imaging bolometer (IRVB) [3] that views the plasma from an upper port. Two scenarios are shown and compared, Ne puffing and N2 puffing. In the case of Ne puffing, radiation becomes more intense near the helical divertor X-point as the radiation increases. In the case of N2 puffing, a double stripe pattern evolves around the upper helical divertor X-point, which appears to be localized near the gas puff inlet. In addition, probe data also indicates that the drop in divertor flux with N2 is localized, while uniform with Ne

Experimental observations and modelling of radiation asymmetries during N2 seeding in LHD

N2 gas has been seeded in the Large Helical Device (LHD) to reduce the divertor heat load through enhanced radiation. Radiation is observed by two imaging bolometers, viewing the same poloidal cross-section from top and bottom ports, at a location which is 36° toroidally removed from the N2 gas puff nozzle located at the bottom of the machine. During N2 seeding, these measurements both confirm that additional radiation from the outboard side is coming exclusively from the top of the cross-section, indicating up/down asymmetry, which is also reproduced by modelling with EMC3-EIRENE using a half torus model. In addition, a toroidally localized, magnetic field direction-dependent radiation enhancement is observed with N2 seeding, but is not reproducible by the model

Development of impurity seeding and radiation enhancement in the helical divertor of LHD

Impurity seeding to reduce the divertor heat load was conducted in the large helical device (LHD) using neon (Ne) and krypton (Kr) puffing. Radiation enhancement and reduction of the divertor heat load were observed. In the LHD, the ratio between the total radiated power and the heating power, f rad = Prad/Pheating, is limited up to around 30% in hydrogen plasmas even for high density plasma just below the radiative collapse (ne, bar  >  1   ×   1020 m−3), where ne, bar is the line averaged density. With Ne seeding, the ratio could be raised to 52% at ne, bar ~ 1.3   ×   1019 m−3, albeit with a slight reduction in confinement. f rad ~ 30% could be sustained for 3.4 s using multi-pulse Ne seeding at ne, bar ~ 4   ×   1019 m−3. The localized supplemental radiation was observed along the helical divertor X-points (HDXs) which is similar to the estimated structure by the EMC3-EIRENE code. Kr seeding was also conducted at ne, bar ~ 3.1   ×   1019 m−3. f rad ~ 25% was obtained without a significant change in stored energy. The radiation enhancement had a slower time constant. The supplemental radiation area of the Kr seeded plasma moved from the HDXs to the core plasma. Highly charged states of Kr ions are considered to be the dominant radiators from the plasma core region

Pitavastatin suppresses diethylnitrosamine-induced liver preneoplasms in male C57BL/KsJ-db/db obese mice

<p>Abstract</p> <p>Background</p> <p>Obesity and related metabolic abnormalities, including inflammation and lipid accumulation in the liver, play a role in liver carcinogenesis. Adipocytokine imbalances, such as decreased serum adiponectin levels, are also involved in obesity-related liver tumorigenesis. In the present study, we examined the effects of pitavastatin - a drug used for the treatment of hyperlipidemia - on the development of diethylnitrosamine (DEN)-induced liver preneoplastic lesions in C57BL/KsJ-<it>db/db </it>(<it>db/db</it>) obese mice.</p> <p>Methods</p> <p>Male <it>db/db </it>mice were administered tap water containing 40 ppm DEN for 2 weeks and were subsequently fed a diet containing 1 ppm or 10 ppm pitavastatin for 14 weeks.</p> <p>Results</p> <p>At sacrifice, feeding with 10 ppm pitavastatin significantly inhibited the development of hepatic premalignant lesions, foci of cellular alteration, as compared to that in the untreated group by inducing apoptosis, but inhibiting cell proliferation. Pitavastatin improved liver steatosis and activated the AMPK-α protein in the liver. It also decreased free fatty acid and aminotransferases levels, while increasing adiponectin levels in the serum. The serum levels of tumor necrosis factor (TNF)-α and the expression of <it>TNF-α </it>and <it>interleukin-6 </it>mRNAs in the liver were decreased by pitavastatin treatment, suggesting attenuation of the chronic inflammation induced by excess fat deposition.</p> <p>Conclusions</p> <p>Pitavastatin is effective in inhibiting the early phase of obesity-related liver tumorigenesis and, therefore, may be useful in the chemoprevention of liver cancer in obese individuals.</p