Publications by authors named "Takashi Kondo"

620 Publications

CTCF looping is established during gastrulation in medaka embryos.

Genome Res 2021 Jun 18;31(6):968-980. Epub 2021 May 18.

Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033 Japan.

Chromatin looping plays an important role in genome regulation. However, because ChIP-seq and loop-resolution Hi-C (DNA-DNA proximity ligation) are extremely challenging in mammalian early embryos, the developmental stage at which cohesin-mediated loops form remains unknown. Here, we study early development in medaka (the Japanese killifish, ) at 12 time points before, during, and after gastrulation (the onset of cell differentiation) and characterize transcription, protein binding, and genome architecture. We find that gastrulation is associated with drastic changes in genome architecture, including the formation of the first loops between sites bound by the insulator protein CTCF and a large increase in the size of contact domains. In contrast, the binding of the CTCF is fixed throughout embryogenesis. Loops form long after genome-wide transcriptional activation, and long after domain formation seen in mouse embryos. These results suggest that, although loops may play a role in differentiation, they are not required for zygotic transcription. When we repeated our experiments in zebrafish, loops did not emerge until gastrulation, that is, well after zygotic genome activation. We observe that loop positions are highly conserved in synteny blocks of medaka and zebrafish, indicating that the 3D genome architecture has been maintained for >110-200 million years of evolution.
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http://dx.doi.org/10.1101/gr.269951.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168583PMC
June 2021

Deterioration of modern concrete structures and asphalt pavements by respiratory action and trace quantities of organic matter.

PLoS One 2021 13;16(5):e0249761. Epub 2021 May 13.

Green Consultant Co. Ltd., Eniwa, Japan.

In concrete structures (concrete), damage from cracks, deterioration, amorphization, and delamination occur in some structures, causing disaggregation (concrete changed to very fine particles) and hollowing out of the concrete. In concrete pavements, damage from large amounts of pop-out of aggregate occurs from the surface of the concrete pavement 4-5 hours after spraying of snow melting agent on the surface of the pavement. The damage from disaggregation, blistering, cracks, and peeling-off of a surface course have also been observed in asphalt runways and highways. The damage from disaggregation, cracks and pop-out of aggregate in asphalt pavements and concrete structures have long been seen as strange and unexpected and have defied explanation. As a result of examinations in various experiments, it was concluded that all of the unexplained kinds of damage of both asphalt pavements and concrete structures were caused by Trace Quantities of Organic Matter (TQOM), Air Entrained (AE) water reducing agent in air and/or cement, and surfactant in snow melting agent. The emission sources of TQOM and these organic substances were also identified by chemical analysis for these unexpected and unexplained phenomena. The TQOM includes phthalate compounds (phthalates in the following), amine compounds, phosphate compounds, snow melting agent and Sodium Polyoxyethylene Nonyl phenyl Ether Sulfate (SPNES). SPNES is a surfactant in windshield washer fluid for automobiles. We found that the water content and content of organic matter in damaged asphalt pavements and concrete structures are also important indicators for the damage. Further, a new evaluation method for amorphization was proposed in this study and it appears suitable for evaluating the safety of concrete structures along roads which were exposed to TQOM in severely air-polluted environments.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249761PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118311PMC
May 2021

Prediction of blood pressure change during surgical incision under opioid analgesia using sympathetic response evoking threshold.

Sci Rep 2021 May 5;11(1):9558. Epub 2021 May 5.

Department of Anesthesiology and Critical Care, Hiroshima University, 1-2-3 Kasumi, Minami, Hiroshima, 734-8551, Japan.

Opioid inhibition of nociceptive stimuli varies in individuals and is difficult to titrate. We have reported the vascular stiffness value (K) as a standard monitor to quantify sympathetic response with high accuracy. On the contrary, among individuals, a considerable variation in the rate of change in K for constant pain has been observed. In this study, we proposed a new index, the minimum stimulus intensity value that evoked the response on K (MEC: Minimum Evoked Current of K), and evaluated its accuracy in predicting sympathetic response to nociceptive stimuli under constant opioid administration. Thirty patients undergoing open surgery under general anesthesia were included. After anesthetic induction, remifentanil was administered at a constant concentration of 2 ng/ml at the effect site followed by tetanus stimulation. MEC was defined as the minimal current needed to produce a change in K. MEC significantly (P < 0.001) correlated with the rate of change of systolic blood pressure during skin incision (ROC). Bland-Altman plot analysis using the predicted ROC calculated from MEC and the measured ROC showed that the prediction equation for ROC was highly accurate. This study showed the potential of MEC to predict blood pressure change during surgical incision under opioid analgesia.Clinical trial registration Registry: University hospital medical information network; Registration number: UMIN000041816; Principal investigator's name: Satoshi Kamiya; Date of registration: July 9th, 2019.
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http://dx.doi.org/10.1038/s41598-021-87636-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100133PMC
May 2021

Effect of Instruction on Preventing Delayed Bleeding after Colorectal Polypectomy and Endoscopic Mucosal Resection.

J Clin Med 2021 Mar 1;10(5). Epub 2021 Mar 1.

Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.

Background: The frequency of delayed bleeding after colorectal polypectomy has been reported as 0.6-2.8%. With the increasing performance of polypectomy under continuous use of antithrombotic agents, care is required regarding delayed post-polypectomy bleeding (DPPB). Better instruction to educate endoscopists is therefore needed. We aimed to evaluate the effect of instruction and factors associated with delayed bleeding after endoscopic colorectal polyp resection.

Methods: This single-center, retrospective study was performed to assess instruction in checking complete hemostasis and risk factors for onset of DPPB. The incidence of delayed bleeding, comorbidities, and medications were evaluated from medical records. Characteristics of historical control patients and patients after instruction were compared.

Results: A total of 3318 polyps in 1002 patients were evaluated. The control group comprised 1479 polyps in 458 patients and the after-instruction group comprised 1839 polyps in 544 patients. DPPB occurred in 1.1% of polyps in control, and 0.4% in after-instruction. Instruction significantly decreased delayed bleeding, particularly in cases with antithrombotic agents. Hot polypectomy, clip placement, and use of antithrombotic agents were significant independent risk factors for DPPB even after instruction.

Conclusion: The rate of delayed bleeding significantly decreased after instruction to check for complete hemostasis. Even after instruction, delayed bleeding can still occur in cases with antithrombotic agents or hot polypectomy.
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http://dx.doi.org/10.3390/jcm10050928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957812PMC
March 2021

Malignant hyperthermia in a 16-day-old infant with congenital diaphragmatic hernia: a case report.

J Anesth 2021 04 24;35(2):311-314. Epub 2021 Feb 24.

Department of Anesthesiology, Hiroshima Prefectural Rehabilitation Center, Higashi-Hiroshima, 739-0036, Japan.

Malignant hyperthermia (MH) is a severe hypermetabolic disorder associated with dysregulation of calcium homeostasis and is triggered by inhalational anesthetics (isoflurane, sevoflurane, desflurane) and a depolarizing muscle relaxant (succinylcholine). We report the case of a 16-day-old infant undergoing laparoscopic surgery. The patient developed hyperthermia and hypercarbia with muscle rigidity. After the diagnosis of MH, dantrolene was administered with sufficient hydration. The patient was transferred to the pediatric intensive care unit for monitoring and treatment of acute renal injury due to myoglobinuria. Subsequently, two variants of the ryanodine receptor 1 (RYR1) gene were identified in the patient as the mutation point at c.1589G > A p.Arg530His and c.1841G > T p.Arg614Leu, which are known to be associated with MH. This was a rare case of MH in a 16-day-old infant that might be related to two RYR1 mutations inherited from the parents.
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http://dx.doi.org/10.1007/s00540-021-02902-2DOI Listing
April 2021

Verifying the applicability of SWAT to simulate fecal contamination for watershed management of Selangor River, Malaysia.

Sci Total Environ 2021 Jun 3;774:145075. Epub 2021 Feb 3.

Research Center for Environmental Quality Management, Graduate School of Engineering, Kyoto University, 1-2 Yumihama, Otsu 520-0811, Japan.

The Soil and Water Assessment Tool (SWAT) ecohydrological model was utilized to simulate fecal contamination in the 1937 km Selangor River Watershed in Malaysia. The watershed conditions posed considerable challenges owing to data scarcity and tropical climate conditions, which are very different from the original conditions that SWAT was developed and tested for. Insufficient data were compensated by publicly available data (e.g., land cover, soil, and weather) to run SWAT. In addition, field monitoring and interviews clarified representative situations of pollution sources and loads, which were used as input for the model. Model parameters determined by empirical analyses in the USA (e.g., surface runoff, evapotranspiration, and temperature adjustment for bacteria die-off) are thoroughly discussed. In particular, due consideration was given to tropical climate characteristics such as intense rainfall, high potential evapotranspiration, and high temperatures throughout the year. As a result, the developed SWAT successfully simulated fecal contamination ranging several orders of magnitude along with its spatial distribution (i.e., Nash-Sutcliffe Efficiency (NSE) = 0.64, Root Mean Square Error-Observations Standard Deviation Ratio (RSR) = 0.64 at six mainstem sites, and NSE = 0.67 and RSR = 0.57 at 12 major tributaries). Moreover, mitigation countermeasures for future worsening of fecal contamination (i.e., E.coli concentration > 20,000 CFU/100 mL for 690 days during nine years at a raw water intake point for Kuala Lumpur [KL] residents) were analyzed through scenario simulations, thereby contributing to discussing effective watershed management. The results propose improving decentralized sewage treatment systems and treating chicken manure with effective microorganisms in order to guarantee water safety for KL residents (i.e., E.coli concentrations <20,000 CFU/100 mL throughout the period, considering Malaysian standards). Accordingly, this study verified the applicability of SWAT to simulate fecal contamination in areas that are difficult to model and suggests solutions for watershed management based on quantitative evidence.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145075DOI Listing
June 2021

Intraoperative responses of motor evoked potentials to the novel intravenous anesthetic remimazolam during spine surgery: a report of two cases.

JA Clin Rep 2020 Dec 9;6(1):97. Epub 2020 Dec 9.

Department of Anesthesiology and Critical Care, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Background: Remimazolam is a novel short-acting benzodiazepine characterized by metabolism independent from organ function. We report intraoperative MEP responses of two patients who underwent spine surgery under general anesthesia using remimazolam.

Case Presentation: In case 1, MEP monitoring was successfully performed with the use of a fixed dose of remimazolam at 0.5 mg/kg/h and remifentanil at 0.2 μg/kg/min. In case 2, an increasing dose of remimazolam from 0.5 to 1.5 mg/kg/h during the operation did not affect MEP signals. In both cases, remimazolam was titrated to maintain the values of entropy electroencephalogram (EEG) monitoring at 40-60.

Conclusions: General anesthesia using remimazolam and remifentanil can be a valuable alternative for spine surgery with MEP monitoring by EEG to assess the optimal dose.
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http://dx.doi.org/10.1186/s40981-020-00401-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726079PMC
December 2020

Evaluation of Muscle Cramp Associated with Liver Cirrhosis with a Focus on the Liver Function and Nutritional Status.

Intern Med 2021 May 7;60(9):1343-1348. Epub 2020 Dec 7.

Department of Gastroenterology & Hepatology, Nagoya University Graduate School of Medicine, Japan.

Objective We investigated the muscle cramp status of patients with liver cirrhosis by focusing on the degree of liver damage, skeletal muscle mass, and nutritional status. Methods All enrolled patients completed a questionnaire about muscle cramps. The degree of liver damage was examined using the Child-Pugh classification and the albumin-bilirubin (ALBI) grade. The nutritional status and skeletal muscle mass were examined using the Controlling Nutritional Status (CONUT) method and the psoas muscle index (PMI). Results Among the respondents, 55.7% of the patients reported experiencing muscle cramps. An analysis of the two patient groups-those who experienced muscle cramps and those who did not-revealed significant differences in Child-Pugh classification (muscle cramp-positive vs. muscle cramp-negative: A/B/C, 54.1%/32.4%/13.5% vs. 90.0%/10.0%/0.0%; p=0.004), ALBI grade (1/2/3, 20.5%/71.8%/7.7% vs. 54.8%/38.7%/6.5%; p=0.011), modified ALBI grade (1/2a/2b/3, 20.5%/20.5%/51.3%/7.7% vs. 54.8%/22.6%/16.1%/6.5%; p=0.008), CONUT score (normal/mild/moderate/severe, 25.6%/28.2%/41.0%/5.1% vs. 22.6%/61.3%/12.9%/3.2%; p=0.024), and PMI (3.85±1.13 cm/m vs. 4.94±1.86 cm/m; p=0.012). Conclusion Our findings suggest that muscle cramps occur more frequently in patients with liver cirrhosis due to their decreased liver function and poorer nutritional status.
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http://dx.doi.org/10.2169/internalmedicine.6231-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170239PMC
May 2021

Eosinophil-associated microinflammation in the gastroduodenal tract contributes to gastric hypersensitivity in a rat model of early-life adversity.

Am J Physiol Gastrointest Liver Physiol 2021 02 11;320(2):G206-G216. Epub 2020 Nov 11.

Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan.

Gastric hypersensitivity is a major pathophysiological feature of functional dyspepsia (FD). Recent clinical studies have shown that a large number of patients with FD present with gastroduodenal microinflammation, which may be involved in the pathophysiology of FD. However, no animal model reflecting this clinical characteristic has been established. The underlying mechanism between microinflammation and FD remains unknown. In this study, using a maternal separation (MS)-induced FD model, we aimed to reproduce the gastroduodenal microinflammation and reveal the interaction between gastroduodenal microinflammation and gastric hypersensitivity. The MS model was established by separating newborn Sprague-Dawley rats for 2 h a day from to . At 7-8 wk of age, electromyography was used to determine the visceromotor response to gastric distention (GD) and immunohistochemistry was performed to detect distension-associated neuronal activation as well as immunohistological changes. Our results demonstrated that MS-induced FD rats underwent gastric hypersensitivity with GD at 60 and 80 mmHg, which are related to increased p-ERK1/2 expression in the dorsal horn of T9-T10 spinal cords. Eosinophils, but not mast cells, were significantly increased in the gastroduodenal tract, and the coexpression rate of CD11b and major basic protein significantly increased in MS rats. Treatment with dexamethasone reversed gastric hypersensitivity in MS-induced FD rats by inhibiting eosinophil infiltration. These findings indicated that neonatal MS stress induces eosinophil-associated gastroduodenal microinflammation and gastric hypersensitivity in adulthood in rats. Microinflammation contributes to gastric hypersensitivity; therefore, anti-inflammatory therapy may be effective in treating patients with FD with gastroduodenal microinflammation. We showed for the first time that neonatal MS stress-induced FD rats undergo gastroduodenal eosinophil-associated microinflammation in adulthood. Suppression of microinflammation attenuated gastric hypersensitivity in MS rats. These findings established a functional link between microinflammation and gastric hypersensitivity, which may provide a potential clue for the clinical treatment of FD.
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http://dx.doi.org/10.1152/ajpgi.00313.2020DOI Listing
February 2021

[Clinical Efficacy of Monotherapy with Immune Checkpoint Inhibitors for Advanced Non-Small Cell Lung Cancer].

Gan To Kagaku Ryoho 2020 Oct;47(10):1443-1447

Dept. of Chest Surgery, Tohoku Medical and Pharmaceutical University Faculty of Medicine.

Objective: To retrospectively assess data on immune checkpoint inhibitors(ICIs)in an actual clinical setting, examine the factors that contribute to response and survival using real-world data, and compare the effectiveness of the 3 types of ICIs for patients with non-small cell lung cancer(NSCLC).

Methods: A retrospective analysis of 127 patients with NSCLC treated with ICIs at our hospital was conducted.

Results: Nivolumab(56 patients)showed a 3-year survival rate of 21.6% and a disease control rate of 57.1%. These results are consistent with the clinical trials of Nivolumab. Pembrolizumab(36 patients) showed a 2-year survival rate of 60.3%, a response rate of 50.0%, and a disease control rate of 63.9%. Atezolizumab(35 patients)displayed a particularly low response rate with a 1-year survival rate of 58.4%, response rate of 8.6%, and disease control rate of 25.7%. The treatment results for recurrence after surgery for lung cancer were comparable to those for unresectable lung cancer.

Conclusion: Anti-PD-1 antibody displayed better therapeutic results than anti-PD-L1 antibody. The efficacy of ICI administration for postoperative recurrent lung cancer was also shown in this study.
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October 2020

Evaluation of a new face mask concept for oxygen administration: a crossover study in healthy volunteers.

J Anesth 2020 12 8;34(6):950-952. Epub 2020 Oct 8.

Department of Anesthesiology and Critical Care, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

We developed a new face mask concept for oxygen administration using non-woven textiles. The aim of this study was to evaluate whether the new mask improves acceptability without compromising O delivery and CO elimination. 10 healthy adult volunteers were randomized to either the conventional plastic face mask-first group or the new face mask-first group. Participants were asked to wear the assigned mask with O at 3 L/min for 10 min while seated. End tidal O concentration (et-O) and end tidal CO concentration (et-CO) were measured via a sampling tube located at the mouth. After a 10-min rest period, the other mask was tested in the same manner. Mask discomfort was evaluated using a 100 mm visual analog scale (VAS) where 0, comfortable and 100, uncomfortable. The results showed that use of the new mask caused less discomfort than the conventional mask (new, 11; conventional, 33) (P = 0.002). Median et-O with the new mask was 33%, compared with 30% with the conventional mask (P = 0.008). There were no significant differences in et-CO by mask type (new, 32 mmHg; conventional, 30 mmHg). In conclusion, the new mask was more comfortable and provided higher et-O than the conventional mask.
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http://dx.doi.org/10.1007/s00540-020-02861-0DOI Listing
December 2020

Small size gold nanoparticles enhance apoptosis-induced by cold atmospheric plasma via depletion of intracellular GSH and modification of oxidative stress.

Cell Death Discov 2020 10;6:83. Epub 2020 Sep 10.

Department of Radiology, Graduate School of Medicine and Pharmaceutical Sciences University of Toyama, Toyama, Japan.

Gold nanoparticles (Au-NPs) have attracted attention as a promising sensitizer owing to their high atomic number (Z), and because they are considered fully multifunctional, they are preferred over other metal nanoparticles. Cold atmospheric plasma (CAP) has also recently gained attention, especially for cancer treatment, by inducing apoptosis through the formation of reactive oxygen species (ROS). In this study, the activity of different sized Au-NPs with helium-based CAP (He-CAP) was analyzed, and the underlying mechanism was investigated. Treating cells with only small Au-NPs (2 nm) significantly enhanced He-CAP-induced apoptosis. In comparison, 40 nm and 100 nm Au-NPs failed to enhance cell death. Mechanistically, the synergistic enhancement was due to 2 nm Au-NPs-induced decrease in intracellular glutathione, which led to the generation of intracellular ROS. He-CAP markedly induced ROS generation in an aqueous medium; however, treatment with He-CAP alone did not induce intracellular ROS formation. In contrast, the combined treatment significantly enhanced the intracellular formation of superoxide (O) and hydroxyl radical (OH). These findings indicate the potential therapeutic use of Au-NPs in combination with CAP and further clarify the role of Au-NPs in He-CAP-aided therapies.
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http://dx.doi.org/10.1038/s41420-020-00314-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483448PMC
September 2020

Alteration of Colonic Mucosal Permeability during Antibiotic-Induced Dysbiosis.

Int J Mol Sci 2020 Aug 25;21(17). Epub 2020 Aug 25.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa, Nishinomiya 663-8501, Japan.

Although dysbiosis is likely to disturb the mucosal barrier system, the mechanism involved has remained unclear. Here, we investigated alterations of colonic mucosal permeability and tight junction (TJ) molecules in mice with antibiotic-induced dysbiosis. Mice were orally administered vancomycin or polymyxin B for 7 days, and then fecal samples were subjected to microbial 16S rRNA analysis. The colonic mucosal permeability was evaluated by chamber assay. The colonic expression of TJ molecules and cytokines was examined by real-time RT-PCR, Western blotting, and immunohistochemistry. Caco2 cells were stimulated with cytokines and their transepithelial electric resistance (TEER) was measured. Vancomycin-treated mice showed significantly lower gut microbiota diversity than controls, and the same tendency was evident in polymyxin B-treated mice. The colonic mucosal permeability was significantly elevated in both vancomycin- and polymyxin B-treated mice. The expression of claudin 4 in the colonic mucosa was decreased in both vancomycin- and polymyxin B-treated mice. Colonic expression of and/or was significantly increased in mice that had been administered antibiotics. TNF-α and IFN-γ stimulation dose-dependently decreased TEER in Caco2 cells. Antibiotic-induced dysbiosis is correlated with the enhancement in colonic tissue permeability, accompanied by a reduction in claudin 4 expression and enhancement in and/or expression in mice.
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http://dx.doi.org/10.3390/ijms21176108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504080PMC
August 2020

Propagule Powder of Japanese Yam (Dioscorea Japonica) Reduces High-Fat Diet-Induced Metabolic Stress in Mice through the Regulation of Hepatic Gene Expression.

Mol Nutr Food Res 2020 09 5;64(17):e2000284. Epub 2020 Aug 5.

Group for Food functionality Assessment, Kanagawa Institute of Industrial Science and Technology, Life Science & Environment Research Center (LiSE) 4F C-4, 3-25-13 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-0821, Japan.

Scope: Japanese yam propagules are supposed to have high potential as a functional food. However, there are almost no studies examining their physiological function. This study aims to elucidate the physiological function of Japanese yam propagules that are heated, freeze-dried, and powdered.

Methods And Results: A high-fat diet with Japanese yam propagules is administered to mice for 4 weeks. High-fat loading induces a decline in respiratory quotient, and a high-fat diet with propagules reduces it more. This result suggests that propagules increase fat oxidation, indicating fat utilization. The hepatic transcriptome is analyzed using a DNA microarray. Some of the genes affected by high-fat loading are reversed by simultaneous ingestion of propagules. Such genes are mainly involved in the immune system and fat metabolism. High-fat loading induces hepatic inflammation, which is repressed by simultaneous ingestion of propagules. For lipid metabolism, propagules repress an increase in cholesterol biosynthesis and catabolism by high-fat loading. Regarding carbohydrate metabolism, propagules decrease glycolysis and glycogen synthesis and increase gluconeogenesis. Moreover, amino acids are converted into pyruvate and then used for gluconeogenesis.

Conclusion: Propagules act to delay the occurrence of hepatic disease by suppressing carbohydrate and fat metabolism disorders in high-fat loaded mice.
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http://dx.doi.org/10.1002/mnfr.202000284DOI Listing
September 2020

Hyperthermia and protein homeostasis: Cytoprotection and cell death.

J Therm Biol 2020 Jul 8;91:102615. Epub 2020 May 8.

Division of Radiation Oncology, Department of Radiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, 2630, Toyama, Japan.

Protein homeostasis or proteostasis, the correct balance between production and degradation of proteins, is an essential pillar for proper cellular function. Among the several cellular mechanisms that disrupt homeostatic conditions in cancer cells, hyperthermia (HT) has shown promising anti-tumor effects. However, cancer cells are also capable of thermoresistance. Indeed, HT-induced protein denaturation and aggregation results in the up regulation of heat shock proteins, a group of molecular chaperones with cytoprotective and anti-apoptotic properties via stress-inducible transcription factor, heat shock factor 1(HSF1). Heat shock proteins assist in the refolding of misfolded proteins and aids in their elimination if they become irreversibly damaged by various stressors. Furthermore, HSF1 also initiates the unfolded protein response in the endoplasmic reticulum (ER) to assist in the protein folding capacity of ER and also promotes the translation of pro-survival proteins' mRNA such as activating transcription factor 4 (ATF 4). Moreover, HT associated induction of microRNAs is also involved in thermal resistance of cancer cells via up-regulation of anti-apoptotic Bcl-2 proteins and down regulation of pro-apoptotic Bax and caspase 3 activities. Another cellular protection in response to stressors is Autophagy, which is regulated by the Mammalian target of rapamycin (mTOR) protein. Kinase activity in mTOR phosphorylates HSF1 and promotes its nuclear translocation for heat shock protein synthesis. Over-expression of heat shock proteins are reported to up-regulate Beclin-1, an autophagy initiator. Moreover, HT-induced reactive oxygen species (ROS) generation is sensitized by transcription factor NF-E2 related factor 2 (Nrf2) and activates the cellular expression of antioxidants and autophagy gene. Furthermore, ROS also potentiates autophagy via activation of Beclin-1. Inhibition of thermotolerance can potentiate HT-induced apoptosis. Here, we outlined that heat stress alters cellular proteins which activates cellular homeostatic processes to promote cell survival and make cancer cells thermotolerant.
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http://dx.doi.org/10.1016/j.jtherbio.2020.102615DOI Listing
July 2020

The Combination of Soy Isoflavones and Resveratrol Preserve Bone Mineral Density in Hindlimb-Unloaded Mice.

Nutrients 2020 Jul 9;12(7). Epub 2020 Jul 9.

Department of Food Function and Labeling, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan.

It is well known that physical inactivity during space flight or prolonged bed rest causes rapid bone loss. Soy isoflavones (ISOs) and resveratrol (RES) have been reported to be useful to maintain a positive balance for bone turnover. Therefore, we examined the combined effects of ISO and RES on bone loss that was induced by hindlimb-unloading in mice. Female eight-week-old ddY mice were divided into the following six groups ( = 6-8 each): normally housed mice, loading mice, hindlimb-unloading (UL) mice fed a control diet, UL mice fed a 0.16% ISO conjugates, UL mice fed a 0.15% RES diet, and UL mice fed a 0.16% ISO and 0.15% RES diet. After three weeks, femoral bone mineral density was markedly decreased in unloading mice. The combination of ISO and RES prevented bone loss and especially maintained the trabecular bone mineral density more effectively compared with cortical bones. ISO and/or RES inhibited the increase in the RANKL/OPG expression ratio in bone marrow cells in UL mice. These results suggest that the combination of ISO and RES had a preventive effect against bone loss induced by hindlimb-unloading in mice. These osteoprotective effects of ISO and RES may result from the inhibition of bone resorption.
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http://dx.doi.org/10.3390/nu12072043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400925PMC
July 2020

[Acute Megakaryoblastic Leukemia Developed after the Surgical Treatment of Mediastinal Malignant Germ Cell Tumor].

Kyobu Geka 2020 Jul;73(7):543-546

Department of Thoracic Surgery, Tohoku Medical and Pharmaceutical University, Sendai, Japan.

A 26-year-old man was admitted to our hospital for an examination of a mediastinal tumor. Chest computed tomography(CT) showed a giant anterior mediastinal tumor narrowing the trachea and right main bronchus. Although needle biopsy could not be done because of patient respiratory condition, non-seminomatous mediastinal germ cell malignant tumor was strongly suspected by high level of serum AFP without no abnormal finding in his testis. After 1 cycle of chemotherapy by cisplatin, etoposide and bleomycin, the mediastinal tumor decreased in size. Percutaneous biopsy was challenged, however, definite diagnosis could not be established and the surgical resection was performed. The tumor was pathologically diagnosed as mature teratoma with elements of a yolk-sac tumor and some sort of sarcoma. Sudden onset of back pain and thrombocytopenia were encountered 5 months after the operation. Hematologic examination confirmed acute megakaryoblastic leukemia, and remission-induction therapy and allogeneic hematopoietic stem cell transplantation were performed. Twelve months after the operation, the patient is well without recurrence of either disease.
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July 2020

Comparison of the Effects of Desflurane, Sevoflurane, and Propofol on the Glottic Opening Area during Remifentanil-Based General Anesthesia Using a Supraglottic Airway Device.

Anesthesiol Res Pract 2020 19;2020:1302898. Epub 2020 Jun 19.

Department of Anesthesia, Akane Foundation Tsuchiya General Hospital, Hiroshima, Japan.

Purpose: The aim of this study was to compare the effects of desflurane, sevoflurane, and propofol on the glottic opening area during general anesthesia using remifentanil.

Methods: Ninety patients undergoing hand and upper limb surgery combined with brachial plexus block under general anesthesia were enrolled in the study. The patients were randomized into three groups to receive desflurane (group D), sevoflurane (group S), or propofol (group P) for maintenance of anesthesia. Following induction of general anesthesia with remifentanil, continuous fiberoptic video recording around the glottis via an i-gel™ supraglottic device was started after establishing mechanical ventilation. Desflurane, sevoflurane, or propofol was administrated after video recording was started. The changes in normalized glottic opening area (n-GOA) and peak inspiratory pressure (PIP) during surgery were compared between the three groups.

Results: Intraoperative changes of n-GOA in group D showed significant differences compared with group S and group P (-0.0656 ± 0.0772 vs. -0.0076 ± 0.0499 and +0.0269 ± 0.0809, =0.005 and < 0.0001). The changes of PIP in group D showed significant differences compared with group S and group P (+3.7 ± 3.4 cmHO vs. +1.0 ± 1.3 cmHO and -0.3 ± 3.6 cmHO, =0.002 and < 0.0001). Four cases of relapsed glottic stenosis in group D were improved by changing desflurane to propofol.

Conclusions: Desflurane narrowed the n-GOA and increased the PIP compared to sevoflurane and propofol during general anesthesia with remifentanil. Clinicians should be aware of the possibility of glottic stenosis during desflurane-remifentanil anesthesia when the airway is secured by a supraglottic airway device without the use of neuromuscular blockade.
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http://dx.doi.org/10.1155/2020/1302898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321498PMC
June 2020

Current status of surgery for clinical stage IA lung cancer in Japan: analysis of the national clinical database.

Surg Today 2020 Dec 5;50(12):1644-1651. Epub 2020 Jul 5.

Department of Thoracic Surgery, Tohoku Medical and Pharmaceutical University, 1-12-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8512, Japan.

Purpose: As the number of cases of early lung cancer in Japan grows, an analysis of the present status of surgical treatments for clinical stage IA lung cancer using a nationwide database with web-based data entry is warranted.

Methods: The operative and perioperative data from 47,921 patients who underwent surgery for clinical stage IA lung cancer in 2014 and 2015 were obtained from the National Clinical Database (NCD) of Japan. Clinicopathological characteristics, surgical procedure, mortality, and morbidity were analyzed, and thoracotomy and video-assisted thoracic surgery (VATS) were compared.

Results: The patients comprised 27,208 men (56.8%) and 20,713 women (43.2%); mean age, 69.3 years. Lobectomy was performed in 64.8%, segmentectomy in 15.2%, and wedge resection in 19.8%. The surgical procedures were thoracotomy in 12,194 patients (25.4%) and a minimally invasive approach (MIA) in 35,727 patients (74.6%). MIA was divided into VATS + mini-thoracotomy (n = 13,422, 28.0%) and complete VATS (n = 22,305, 46.5%). The overall postoperative mortality rate was 0.4%, being significantly lower in the MIA group than in the thoracotomy group (0.3% vs 0.8%, P < 0.001).

Conclusions: Our analysis of data from the NCD indicates that MIA has become the new standard treatment for clinical stage IA lung cancer.
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http://dx.doi.org/10.1007/s00595-020-02063-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677152PMC
December 2020

Assessment of safety and efficacy of pine bark extract in normal and ovariectomized mice.

J Food Sci 2020 Jun 14;85(6):1956-1962. Epub 2020 May 14.

National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8636, Japan.

We evaluated the influence of pine bark extract (PBE) on organs, the cytochrome-P450 (CYP) activities in liver and estrogenic effects in normal and ovariectomized (OVX) female mice. The PBE did not affect organ weights and liver-function indexes (activities of alkaline phosphatase, aspartate amino transferase, and alanine amino transferase) at doses; 0.04%, 0.4%, and 2.0% PBE in the diet, in normal and OVX female mice. In the OVX mice, CYP1A1 activity was significantly higher in the 0.4% and 2.0% PBE groups than in the OVX control group, and in the 0.4% and 2.0% PBE groups were significantly higher than in the 0.04% PBE group. CYP1A2 and 3A4 activities were significantly higher in the 2.0% PBE group than in all other groups. The PBE did not affect uterine weight and femoral bone mineral density at all PBE doses. These results showed that the dose of PBE at the recommended human intake, had no toxic and estrogenic effects in normal female and OVX mice, however, it may need attention to use the excess intake of PBE with some drugs in postmenopausal women.
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http://dx.doi.org/10.1111/1750-3841.15160DOI Listing
June 2020

Assessment of postoperative nutritional status and physical function between open surgical aortic valve replacement and transcatheter aortic valve implantation in elderly patients.

J Med Invest 2020 ;67(1.2):139-144

Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

Background and aims : Severe aortic stenosis (AS) has been normally treated with surgical aortic valve replacement (AVR) whereas recently, transcatheter aortic valve implantation (TAVI) has been introduced as a minimally invasive operation for patients with high surgical risk and frailty. In this study, we have evaluated postoperative physical function and nutrition intake in the patients following AVR and TAVI. Methods : This prospective observational study involved 9 patients with surgical aortic valve replacement (AVR) and 7 patients with transcatheter aortic valve implantation (TAVI). Body composition was measured one day prior surgery, postoperative day (POD) 1, POD 3, POD 5 and POD 7. Hand grip strength, calf circumference and gait speed were measured one day before surgery and on the day of discharge. Results : Skeletal muscle was significantly decreased in AVR patients at postoperative day 3 and 7, while there was no change in TAVI patients. Patients with TAVI showed higher dietary intake after surgery compared to patients with AVR, and they maintained hand grip strength and calf circumference at discharge. Conclusions : In elderly patients with AS, TAVI can improve post-operative recovery maintaining nutritional status and physical function even. J. Med. Invest. 67 : 139-144, February, 2020.
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http://dx.doi.org/10.2152/jmi.67.139DOI Listing
June 2021

Mucin-Derived O-Glycans Act as Endogenous Fiber and Sustain Mucosal Immune Homeostasis via Short-Chain Fatty Acid Production in Rat Cecum.

J Nutr 2020 10;150(10):2656-2665

College of Agriculture, Academic Institute, Shizuoka University, Shizuoka, Japan.

Background: Intestinal mucins escape digestion and enter the large bowel where they are degraded by the microbiota. To what extent and how mucins impact large-bowel physiology remain unclear.

Objective: This study examined the large-bowel fermentation characteristics of mucins and mucin-derived O-glycan sugars and whether they affect gut immunity.

Methods: Mucin secretion from the terminal ileum was determined from feces of ileorectostomized male Wistar rats (age 6 wk) fed an AIN76-based control diet (CD) for 15 d (experiment 1). Normal male Wistar rats (age 6 wk; 4 wk for experiment 4) were fed CD ± porcine stomach mucin (PM) at 6 or 12 g/kg diet, equivalent to 1.5 and 3 times the daily mucin secretion, for 14 d (experiment 2); CD ± N-acetylglucosamine (GlcNAc), fucose, or N-acetylneuraminic acid at 10 g/kg diet for 14 d (experiment 3); or CD ± PM (15 g/kg diet) or GlcNAc (10 g/kg diet) for 29 d (experiment 4). SCFAs, microbial composition, and cecal O-glycan content were assessed. IgA+ plasma cells and regulatory T cells and inflammatory cytokine expression in the cecum were evaluated (experiment 4).

Results: Daily mucin secretion corresponded to 43.2 μmol of O-glycans. Cecal O-glycan contents were comparable between CD- and PM-fed rats. PM-fed rats harbored more mucin-degrading bacteria. Cecal concentrations of acetate (+37%) and n-butyrate (+73%) were higher in 12-g/kg PM diet-fed rats versus CD (P < 0.05). Among O-glycan sugars, only GlcNAc produced higher n-butyrate concentrations (+68%) versus CD (P < 0.05), with increased numbers of butyrate-producing bacteria. GlcNAc increased the abundance of IgA+ plasma cells (+29%) and regulatory T cells (+33%) versus CD, whereas PM increased IgA+ plasma cells (+25%) (all P < 0.05). GlcNAc and PM decreased expression of Tnfa (-30%, -40%) and Ifng (-30%, -70%) versus CD (all P < 0.05).

Conclusions: Mucin-derived O-glycans act as endogenous fiber and maintain mucosal immune homeostasis via large-bowel SCFA production in rats.
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http://dx.doi.org/10.1093/jn/nxaa097DOI Listing
October 2020

Crystal Systems and Lattice Parameters of CHNHPb(IBr) Determined Using Single Crystals: Validity of Vegard's Law.

Inorg Chem 2020 May 18;59(10):6709-6716. Epub 2020 Mar 18.

Department of Materials Engineering, The University of Tokyo, Tokyo, Japan.

Metal halide perovskites are promising materials for light absorbers in solar cell applications. Use of the Br/I system enables us to control band gap energy and improves the efficiency of solar cells. Precise knowledge of lattice parameters and band gap energies as functions of compositions are crucially important for developing the devices using those materials. In this study, we have determined lattice parameters and band gap energies of CHNHPb(IBr), one of the most intensively studied mix-halide perovskites, as functions of Br content . We measured accurate Br contents and lattice parameters of CHNHPb(IBr) (0 ≤ ≤ 1) using single-crystalline samples by X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) measurements, respectively. The CHNHPb(IBr) crystal system is tetragonal for ≤ 0.06 and cubic for ≥ 0.08 at 300 K. Lattice parameters of CHNHPb(IBr) strictly follow Vegard's law; i.e., they are linearly dependent on . We give linear expressions of of lattice parameters for the tetragonal and cubic phases of CHNHPb(IBr) at 300 K. We have shown that these expressions can be used for determining the Br contents of CHNHPb(IBr) polycrystalline thin-film samples based on XRD measurements and, in addition, demonstrated that XPS measurements on polycrystalline samples may be erroneous because of impure ingredients in the samples. Furthermore, we determined band gap energies of CHNHPb(IBr) (0 ≤ ≤ 1) at room temperature using absorption spectra of polycrystalline thin films taking account of excitonic effects.
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http://dx.doi.org/10.1021/acs.inorgchem.9b03421DOI Listing
May 2020

Rotational thromboelastometry-guided perioperative management of coagulation in a patient with Heyde's syndrome undergoing transcatheter aortic valve implantation.

JA Clin Rep 2019 Jan 11;5(1). Epub 2019 Jan 11.

Department of Anesthesiology and Critical Care, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Background: Changes in coagulability during the hyperacute phase within 24 h after transcatheter aortic valve implantation (TAVI) for Heyde's syndrome, or aortic stenosis complicated by gastrointestinal angiodysplasia and acquired coagulation dysfunction, have not been clarified. We evaluated perioperative changes in coagulability using rotational thromboelastometry (ROTEM).

Case Presentation: A female patient with Heyde's syndrome in her 80s underwent TAVI. ROTEM showed coagulation dysfunction before and at 6 h after surgery. Improvements in coagulation function started at 12 h after surgery. Based on ROTEM findings, oral administration of antiplatelet agents was started on the day after surgery. No hemorrhagic complications were observed in the postoperative phase.

Conclusions: Evaluation of coagulation function using ROTEM was useful for monitoring perioperative hemostasis and coagulation in this patient.
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http://dx.doi.org/10.1186/s40981-019-0224-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966723PMC
January 2019

[Pericardial Fenestration and Multidisciplinary Treatment to Improve the Prognosis of the Malignant Pericarditis Due to Lung Cancer].

Kyobu Geka 2020 Jan;73(1):63-67

Department of the Second Surgery, Tohoku Medical and Pharmaceutical University Sendai, Japan.

We experienced 3 cases in whom multidisciplinary treatment with pericardial fenestration was effective for malignant pericardial effusion associated with lung cancer. Case 1:Right upper lobectomy for lung adenocarcinoma, EGFR (-) and ALK (-) had been performed. After 34 months, malignant pericarditis occurred and left pericardial fenestration was performed. After fenestration, anticancer drugs and immune checkpoint inhibitor( ICI) were administered. He died of lung cancer in 53 months after fenestration. Case 2:Thirty-three months after left upper lobectomy for lung adenocarcinoma [EGFR (+) and ALK (-)], malignant pleuritis and pericarditis occurred and right pericardial fenestration was performed. After fenestration, anticancer drugs, EGFR-TKI and ICI were administered. He died of lung cancer in 35 months after fenestration. Case 3:Pericardial fenestration was performed for malignant pericarditis due to lung adenocarcinoma with EGFR (-), ALK (-) and PD-L1 [tumor propotion score (TPS) 0%]. After fenestration, anticancer drugs and ICI were administered. The patient died of lung cancer in 15 months after fenestration. Pericardial fenestration for malignant pericarditis is possibly useful for the management of patients, which in turns is also useful in continuing the medical treatment to prolong the prognosis.
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January 2020

Successful treatment of adult-onset type II citrullinemia with a low-carbohydrate diet and L-arginine after DNA analysis produced a definitive diagnosis.

Clin J Gastroenterol 2020 Oct 2;13(5):823-833. Epub 2020 Jan 2.

Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

A 60-year-old male, who exhibited finger tremors, obnubilation, and hyperammonemia (409 μg/dL), was admitted to our hospital. Initially, we suspected that a portosystemic shunt had caused his hyperammonemia. However, his symptoms did not improve after balloon-occluded retrograde transvenous obliteration. He was subsequently found to have some peculiar eating habits, including a fondness for bean curd and peanuts, and an aversion to alcohol and sweets. Furthermore, marked citrullinemia (454.2 nmol/mL) was revealed, which led us to suspect adult-onset type II citrullinemia (CTLN2). DNA analysis of the patient and his mother, son, and daughter confirmed that he was homozygous for the c.852_855del mutation in the SLC25A13 gene, and his relatives were heterozygous for the c.852_855del mutation, which led to a definitive diagnosis. A low-carbohydrate diet and the administration of L-arginine ameliorated his symptoms. It is important to be aware that CTLN2 can occur in elderly patients. Thus, patients who exhibit symptoms of CTLN2 should be interviewed about their dietary habits and subjected to plasma amino acid analysis.In this report, we consider the metabolic disorders seen in citrin deficiency and the associated compensatory mechanisms in relation to the clinical features and treatment of CTLN2.
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http://dx.doi.org/10.1007/s12328-019-01083-6DOI Listing
October 2020

[Association Between Juvenile Spontaneous Pneumothorax and Smoking].

Kyobu Geka 2019 Dec;72(13):1053-1056

Department of Thoracic Surgery, Tohoku Medical and Pharmaceutical University, Sendai, Japan.

We assessed the relation between smoking and pneumothorax in patients aged <40. Of 526 patients who underwent surgery for pneumothorax in 2011~2015, 311 were under the age of 40 and they were included in this study. Of 311, 54 cases( 17.4%) were diagnosed with spontaneous pneumothorax associated with emphysematous change by pathological assessment. By the multivariate analysis, 2 parameters exhibited significance for the risk of these spontaneous pneumothorax:a Brinkmann index of ≥165 and a smoking period of ≥9.5 years. It was suggested that smoking is strongly related to the onset of spontaneous pneumothorax even in the younger population less than 40 years of age.
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December 2019