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Interaction of Lipoplex with Albumin Enhances Gene Expression in Hepatitis Mice
Full text linkUnderstanding the in vivo fate of lipoplex, which is composed of cationic liposomes and DNA, is an important issue toward gene therapy. In disease conditions, the fate of lipoplex might change compared with the normal condition. Here, we examined the contribution of interaction with serum components to in vivo transfection using lipoplex in hepatitis mice. Prior to administration, lipoplex was incubated with serum or albumin. In the liver, the interaction with albumin enhanced gene expression in hepatitis mice, while in the lung, the interaction with serum or albumin enhanced it. In normal mice, the interaction with albumin did not enhance hepatic and pulmonary gene expression. Furthermore, hepatic and pulmonary gene expression levels of albumin-interacted lipoplex were correlated with serum transaminases in hepatitis mice. The albumin interaction increased the hepatic accumulation of lipoplex and serum tumor necrosis factor-α level. We suggest that the interaction with albumin enhanced the inflammation level after the administration of lipoplex in hepatitis mice. Consequently, the enhancement of the inflammation level might enhance the gene expression level. Information obtained in the current study will be valuable toward future clinical application of the lipoplex
Estimation of tunnel support pattern selection using artificial neural network
No full textEffective selection of tunnel support patterns is one of the key factors affecting the safety and operation cost of tunnel engineering. This study developed an artificial neural network (ANN) model for estimating tunnel support patterns ahead of tunnel face. In this respect, measure while drilling (MWD) data sets and tunnel support patterns during construction are introduced to the ANN models. The nonlinear relationship between the MWD data and the support patterns is estimated. The MWD data includes penetration rate (PR), hammer pressure (HP), rotation pressure (RP), feed pressure (FP), hammer frequency (HF), and specific energy (SE), which were collected from 97 drill holes of a high-speed railway tunnel project that is 3.88 km long in Japan. A multilayer perceptron analysis method is used based on different input sample sizes and different ANN structures. The results show that a strong correlation exists between MWD data and support patterns. It is traced that a neural network with six inputs (PR, HP, RP, FP, HF, and SE) and one hidden layer is sufficient for the estimation of the support patterns. The increase in input sample size and hidden layer node has a positive optimizing effect on the performance of the ANN. However, an input sample size more than 6000 samples and a hidden layer larger than 30 nodes do not have a significant effect on optimizing the performance of the ANN. The size of input samples of 6000 and a three-layer neural network with topology 6-30-6 were found to be optimum. The proposed ANN model is suitable for selecting support patterns in practical engineering
IgM monoclonal gammopathy with heavy-and-light-chain amyloidosis resembling fibrillary glomerulonephritis determined by tandem mass spectrometry: a case report
Full text linkBackground: Fibrillary glomerulonephritis (FGN) is distinguished from amyloidosis by thicker fibrils and the lack of staining with histochemical dyes typically reactive with amyloid. However, congophilic FGN has been proposed recently and adding laser microdissection followed by mass spectrometry (LMD/MS) to conventional pathological methods would be helpful to diagnose FGN. Here, we report a patient initially diagnosed with FGN whose final pathological diagnosis was changed to immunoglobulin heavy-and-light-chain amyloidosis (AHL) after LMD/MS. Case presentation: A 75-year-old male developed nephrotic syndrome. Protein electrophoresis showed IgM κ type M proteinemia and he was diagnosed with IgM monoclonal gammopathy. A renal biopsy was performed and pathological examination showed marked periodic acid-Schiff-positive enlargement of the mesangial region and silver stain positivity, but weak direct fast scarlet staining. Immunofluorescence analysis showed monoclonal deposition of IgM-κ chain in the glomerulus. Under electron microscopy, the fibrils were about 20 nm in diameter, which was thicker than typical amyloid fibrils. Based on these findings, the patient was diagnosed with FGN. Although cyclophosphamide and prednisolone were administered, his renal function deteriorated and progressed to end stage renal disease requiring maintenance hemodialysis. As congophilic FGN has been recognized since 2018, Congo red staining and LMD/MS were performed. The Congo red staining was positive and LMD/MS results indicated that this was a case of AHL. Conclusions: We reported a case of μ and κ chain AHL resembling FGN requiring LMD/MS for definitive diagnosis. Since FGN and amyloidosis exhibit pathological findings, even if Congo red staining is positive, LMD/MS needs to be considered in cases atypical pathological findings, such as silver stain positivity or thicker fibrils
Development of a DNA Vaccine for Melanoma Metastasis by Inhalation Based on an Analysis of Transgene Expression Characteristics of Naked pDNA and a Ternary Complex in Mouse Lung Tissues
Full text linkThe present study investigated a pulmonary delivery system of plasmid DNA (pDNA) and its application to melanoma DNA vaccines. pCMV-Luc, pEGFP-C1, and pZsGreen were used as a model pDNA to evaluate transfection efficacy after inhalation in mice. Naked pDNA and a ternary complex, consisting of pDNA, dendrigraft poly-L-lysine (DGL), and γ-polyglutamic acid (γ- PGA), both showed strong gene expression in the lungs after inhalation. The transgene expression was detected in alveolar macrophage-rich sites by observation using multi-color deep imaging. On the basis of these results, we used pUb-M, which expresses melanoma-related antigens (ubiquitinated murine melanoma gp100 and tyrosinase-related protein 2 (TRP2) peptide epitopes), as DNA vaccine for melanoma. The inhalation of naked pUb-M and its ternary complex significantly inhibited the metastasis of B16-F10 cells, a melanoma cell line, in mice. The levels of the inflammatory cytokines, such as TNF-α, IFN-γ, and IL-6, which enhance Th1 responses, were higher with the pUb-M ternary complex than with naked pUb-M and pEGFP-C1 ternary complex as control. In conclusion, we clarified that the inhalation of naked pDNA as well as its ternary complex are a useful technique for cancer vaccination
A pathological complete response after neoadjuvant triplet chemotherapy for locally advanced transverse colon cancer
Full text linkIntroduction: Perioperative chemotherapy could improve oncological outcomes for patients with advanced colon cancer. However, the effectiveness of triplet chemotherapy in the neoadjuvant setting is still unknown. Presentation of case: A 61-year-old man was referred to our hospital due to abdominal distention. Abdominal computed tomography showed a huge, 18-cm mass in the right upper abdomen. Biopsy showed well-differentiated adenocarcinoma. Locally advanced transverse colon cancer T4b N2a M0 Stage IIIC was diagnosed. Considering the extensive invasion to surrounding organs and difficulties in achieving margin-negative surgery, an emergency ileostomy was performed first. Then, neoadjuvant chemotherapy (NAC) consisting of a combination of 5-fluorouracil (5-FU), oxaliplatin, irinotecan, and leucovorin (FOLFOXIRI) was planned, followed by primary tumor resection. After 6 courses of treatment, the primary tumor shrank remarkably. Finally, laparoscopic radical extended right hemi-colectomy was performed. There were no residual tumor cells in resected specimens, including the primary tumor and surrounding lymph nodes. The pathological diagnosis was complete response. Conclusion: A case of pathological complete response after neoadjuvant treatment followed by radical resection was reported. Further research is needed to confirm the appropriate indications for neoadjuvant FOLFOXIRI therapy for patients with LACC
有限要素法を用いた、革新的な設計デザインによる空隙閉鎖ループ活性化時の矯正力による歯の移動シミュレーション
Full text link長崎大学学位論文 [学位記番号]博（医歯薬）甲第1257号 [学位授与年月日]令和2年6月3