リアルタイムイメージングによる栄養チューブ内における流動食残渣と微生物増殖の検出

Background: Enteral nutrition (EN) residues that persist in feeding tubes provide substrates for microorganisms to proliferate and occlude the tubes. Visible EN residues in tubes are easily identified, but smaller residues can persist. We developed a new imaging technique to visualize EN residues and proliferation of microorganisms in feeding tubes. Materials and Methods: Feeding tubes containing EN labelled with fluorescent dye and EN with or without various types or amounts of thickeners were flushed once with water and then the tubes were seeded with Pseudomonas aeruginosa Xen5 with recombinant luciferase DNA. Because EN fluoresces intrinsically, EN in the feeding tubes without fluorescent dye was repeatedly flushed until the intrinsic fluorescence levels reached background levels. Fluorescent images of EN residues and bioluminescent images of microorganisms were acquired using an optical imaging system. Results: Fluorescence images showed that the amount of EN residues increased at various sites in tubes depending on EN viscosity and the thickening agent, and bioluminescence images showed that microorganism proliferation was associated with a commensurate increase in EN residues. The intrinsic fluorescence of EN also enabled the detection of EN residues in tubes even in the absence of fluorescence dye. Higher EN viscosity required more flushes to reach undetectable levels. Conclusion: EN residues and microorganism proliferation in enteral feeding tubes were detected on fluorescence and bioluminescence images, respectively. This simplified approach allowed the real-time visualization of EN residues and microorganisms in feeding tubes

リアルタイムイメージングによる栄養チューブ内における流動食残渣と微生物増殖の検出

Background: Enteral nutrition (EN) residues that persist in feeding tubes provide substrates for microorganisms to proliferate and occlude the tubes. Visible EN residues in tubes are easily identified, but smaller residues can persist. We developed a new imaging technique to visualize EN residues and proliferation of microorganisms in feeding tubes. Materials and Methods: Feeding tubes containing EN labelled with fluorescent dye and EN with or without various types or amounts of thickeners were flushed once with water and then the tubes were seeded with Pseudomonas aeruginosa Xen5 with recombinant luciferase DNA. Because EN fluoresces intrinsically, EN in the feeding tubes without fluorescent dye was repeatedly flushed until the intrinsic fluorescence levels reached background levels. Fluorescent images of EN residues and bioluminescent images of microorganisms were acquired using an optical imaging system. Results: Fluorescence images showed that the amount of EN residues increased at various sites in tubes depending on EN viscosity and the thickening agent, and bioluminescence images showed that microorganism proliferation was associated with a commensurate increase in EN residues. The intrinsic fluorescence of EN also enabled the detection of EN residues in tubes even in the absence of fluorescence dye. Higher EN viscosity required more flushes to reach undetectable levels. Conclusion: EN residues and microorganism proliferation in enteral feeding tubes were detected on fluorescence and bioluminescence images, respectively. This simplified approach allowed the real-time visualization of EN residues and microorganisms in feeding tubes

cDNA cloning of rat proteasome subunit RC1, a homologue of RING10 located in the human MHC class II region

AbstractThe nucleotide sequence of a cDNA that encodes a new subunit, named RC1, of rat proteasomes (multicatalytic proteinase complexes) has been determined. The polypeptide predicted from the open reading frame consisted of 208 amino acid residues with a calculated molecular mass of 23,130, which is consistent with the size obtained by electrophoretic analysis of purified RC1. The partial amino acid sequences of several fragments of RC1, obtained by protein chemical analyses, were found to be in excellent accordance with those deduced from the cDNA sequence. Surprisingly, the overall structure of RC1 was found to be almost identical to that of recently isolated RING10, whose gene is located in the class II region of the human MHC gene cluster. This finding suggests that RC1 is a homologue of human RING10, supporting the proposal that proteasomes are involved in the antigen processing pathway

Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression

Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improve the clinical outcome of STS patients. We previously revealed that the tumor-specific, replication-competent oncolytic adenovirus OBP-301 kills human sarcoma cells. In this study, we investigated the radiosensitizing effect of OBP-301 in human STS cells. The in vitro antitumor effect of OBP-301 and ionizing radiation in monotherapy or combination therapy was assessed using highly radiosensitive (RD-ES and SK-ES-1) and moderately radiosensitive (HT1080 and NMS-2) STS cell lines. The expression of markers for apoptosis and DNA damage were evaluated in STS cells after treatment. The therapeutic potential of combination therapy was further analyzed using SK-ES-1 and HT1080 cells in subcutaneous xenograft tumor models. The combination of OBP-301 and ionizing radiation showed a synergistic antitumor effect in all human STS cell lines tested, including those that show different radiosensitivity. OBP-301 was found to enhance irradiation-induced apoptosis and DNA damage via suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1), which was expressed at higher levels in moderately radiosensitive cell lines. The combination of OBP-301 and ionizing radiation showed a more profound antitumor effect compared to monotherapy in SK-ES-1 (highly radiosensitive) and HT1080 (moderately radiosensitive) subcutaneous xenograft tumors. OBP-301 is a promising antitumor reagent to improve the therapeutic potential of radiotherapy by increasing radiation-induced apoptosis in STS

ストレプトゾトシン誘導性糖尿病ラットにおける腎Cyp24a1遺伝子発現上昇と血漿1,25-ジヒドロキシビタミンD濃度低下との関連

Decreases in plasma vitamin D concentrations have been reported in diabetes, although the mechanism involved in this decrease is unclear. Here, we investigated the association between Cyp24a1, a vitamin D catabolic enzyme, and abnormalities in vitamin D metabolism in streptozotocin-induced diabetes rats, an animal model of type 1 diabetes. Plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] levels were significantly lower in streptozotocin-induced diabetes rats and renal Cyp24a1 mRNA expression levels were increased. Western blotting analysis of streptozotocin-induced diabetes rats kidney tissues with anti-CYP24A1 antibody showed a strong signal around 40 kDa, which differs from the predicted 50–55 kDa molecular weight for full-length Cyp24a1 and could represent the Cyp24a1-splicing variant that lacks exons 1 and 2. We observed high levels of renal Cyp24a1-splicing variant mRNA expression in streptozotocin-induced diabetes rats. We also confirmed transcriptional up-regulation of endogenous Cyp24a1 mRNA expression through glucocorticoid receptors by glucocorticoid in opossum kidney proximal cells. Taken together, our results indicated that high Cyp24a1 expression levels may play a role in the decrease of plasma 1,25(OH)2D levels in streptozotocin-induced diabetes rats. High plasma corticosterone levels in diabetes may affect transcriptional regulation to promote increases in Cyp24a1 expression

A novel PCOS rat model and an evaluation of its reproductive, metabolic, and behavioral phenotypes

Background: Although animal models of PCOS have been used in many studies, none of them can reproduce both the reproductive and metabolic phenotypes of PCOS. In addition, behavioral parameters have not been evaluated in PCOS animal models. Purpose: We tried to produce an improved rat model of PCOS, and the reproductive, metabolic, and behavioral phenotypes of the model rats were evaluated. Methods: Female rats were implanted with silicon tubes containing oil-dissolved dihydrotestosterone (Oil-DHT) as a new PCOS model. Their phenotypes were compared with those of conventional PCOS model rats (DHT), into which tubes containing crystalline DHT were implanted, and non-DHT-treated rats (control). Results: Both the Oil-DHT and DHT rats showed greater body weight gain, food intake, and fat depot weight than the control rats. Furthermore, these groups showed fewer estrous stages and increased numbers of cystic follicles. The DHT rats exhibited lower ovarian and uterine weights than the control rats, whereas no such changes were observed in the Oil-DHT rats. The Oil-DHT and DHT rats showed less locomotor activity in the light phase than the control rats. Conclusions: Our proposed PCOS model reproduced both the reproductive and metabolic phenotypes of PCOS and may have potential for PCOS research

Androgen’s effects in female

The metabolic effects of androgens and their underlying mechanisms in females have been revealed by recent studies. An excess of androgens can have adverse effects on feeding behavior and metabolic functions and induce metabolic disorders / diseases, such as obesity, insulin resistance, and diabetes, in women and experimental animals of reproductive age. Interestingly, these effects of androgens are not observed in ovariectomized animals, indicating that their effects might be dependent on the estrogen milieu. Central and peripheral mechanisms, such as alterations in the activity of hypothalamic factors, reductions in energy expenditure, skeletal muscle insulin resistance, and β-cell dysfunction, might be related to these androgens’ effects