Publications by authors named "Takeshi Miura"

127 Publications

Oculopharyngodistal myopathy with coexisting histology of systemic neuronal intranuclear inclusion disease: Clinicopathologic features of an autopsied patient harboring CGG repeat expansions in LRP12.

Authors:
Rie Saito Hiroshi Shimizu Takeshi Miura Norikazu Hara Naomi Mezaki Yo Higuchi Akinori Miyashita Izumi Kawachi Kazuhiro Sanpei Yoshiaki Honma Osamu Onodera Takeshi Ikeuchi Akiyoshi Kakita

Acta Neuropathol Commun 2020 06 3;8(1):75. Epub 2020 Jun 3.

Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-ku, Niigata, 951-8585, Japan.

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http://dx.doi.org/10.1186/s40478-020-00945-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268649PMC
June 2020

[Attitude Survey Data on Interaction between Dietary Supplements and Medicines].

Authors:
Tomoki Ikuta Takeshi Miura Kazumasa Shinozuka

Yakugaku Zasshi 2019 ;139(11):1463-1470

Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University.

Since "Foods with Function Claims" system was established in 2015, the percentage of people taking health foods and supplements is gradually increasing. The number of people taking both dietary supplements and medicines is also increasing. Therefore, providing information on interaction between dietary supplements and medicines has become increasingly important. We have conducted a study for understanding the awareness of the consumers on the interaction of health foods and supplements with medicines. The ratio of those who do not consult with an informed opinion on the interaction between health foods and supplements with medicines was 76% and 55.2% admitted that they did not experience any side effects as a result of this interaction. In conclusion, the understanding of the interaction between health foods and medication among consumers is still limited and most of them do not consult with specialized physicians. It has been revealed that efforts to expanding the consumers understanding on the risk of interaction between supplements and medicines are necessary. It was suggested that the "Database for guiding the interaction between medicines and health foods" could be a useful tool for providing this type of information.
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http://dx.doi.org/10.1248/yakushi.19-00135DOI Listing
February 2020

The Dipterose of Black Soldier Fly ) Induces Innate Immune Response through Toll-Like Receptor Pathway in Mouse Macrophage RAW264.7 Cells.

Authors:
Muhammad Fariz Zahir Ali Takashi Ohta Atsushi Ido Chiemi Miura Takeshi Miura

Biomolecules 2019 10 31;9(11). Epub 2019 Oct 31.

Graduate School of Agriculture, Ehime University, 3-5-7, Tarumi, Matsuyama, Ehime, 790-8566, Japan.

In our study, a novel bioactive polysaccharide was identified in the larvae of the black soldier fly (BSF) () as a molecule that activates the mammalian innate immune response. We attempted to isolate this molecule, which was named dipterose-BSF, by gel-filtration and anion-exchange chromatography, followed by nitric oxide (NO) production in mouse RAW264.7 macrophage cells as a marker of immunomodulatory activity. Dipterose-BSF had an average molecular weight of 1.47 × 10 and consisted of ten monosaccharides. Furthermore, in vitro assays demonstrated that dipterose-BSF enhanced the expression of proinflammatory cytokines and interferon β (IFNβ) in RAW264.7 cells. The inhibition of Toll-like receptor 2 (TLR2) and 4 (TLR4) significantly attenuated NO production by dipterose-BSF, indicating that dipterose-BSF stimulates the induction of various cytokines in macrophages via the TLR signaling pathway. This observation was analogous with the activation of nuclear factor kappa B in RAW264.7 cells after exposure to dipterose-BSF. Our results suggest that dipterose-BSF has immunomodulatory potential through activating the host innate immune system, which allows it to be a novel immunomodulator for implementation as a functional food supplement in poultry, livestock, and farmed fish.
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http://dx.doi.org/10.3390/biom9110677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920837PMC
October 2019

Upregulation of Carbonyl Reductase 1 by Nrf2 as a Potential Therapeutic Intervention for Ischemia/ Reperfusion Injury during Liver Transplantation.

Authors:
Jae Hyun Kwon Jooyoung Lee Jiye Kim Varvara A Kirchner Yong Hwa Jo Takeshi Miura Nayoung Kim Gi-Won Song Shin Hwang Sung-Gyu Lee Young-In Yoon Eunyoung Tak

Mol Cells 2019 Sep;42(9):672-685

Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology; and Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygenglucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation.
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http://dx.doi.org/10.14348/molcells.2019.0003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776159PMC
September 2019

USP10 is a critical factor for Tau-positive stress granule formation in neuronal cells.

Authors:
Svetlana Piatnitskaia Masahiko Takahashi Hiroki Kitaura Yoshinori Katsuragi Taichi Kakihana Lu Zhang Akiyoshi Kakita Yuriko Iwakura Hiroyuki Nawa Takeshi Miura Takeshi Ikeuchi Toshifumi Hara Masahiro Fujii

Sci Rep 2019 07 22;9(1):10591. Epub 2019 Jul 22.

Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.

Tau aggregates in neurons of brain lesions is a hallmark pathology of tauopathies, including Alzheimer's disease (AD). Recent studies suggest that the RNA-binding protein TIA1 initiates Tau aggregation by inducing the formation of stress granules (SGs) containing Tau. SGs are stress-inducible cytoplasmic protein aggregates containing many RNA-binding proteins that has been implicated as an initial site of multiple pathogenic protein aggregates in several neurodegenerative diseases. In this study, we found that ubiquitin-specific protease 10 (USP10) is a critical factor for the formation of Tau/TIA1/USP10-positive SGs. Proteasome inhibition or TIA1-overexpression in HT22 neuronal cells induced the formation of TIA1/Tau-positive SGs, and the formations were severely attenuated by depletion of USP10. In addition, the overexpression of USP10 without stress stimuli in HT22 cells induced TIA1/Tau/USP10-positive SGs in a deubiquitinase-independent manner. In AD brain lesions, USP10 was colocalized with Tau aggregates in the cell body of neurons. The present findings suggest that USP10 plays a key role in the initiation of pathogenic Tau aggregation in AD through SG formation.
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http://dx.doi.org/10.1038/s41598-019-47033-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646309PMC
July 2019

Expressional regulation of gonadotropin receptor genes and androgen receptor genes in the eel testis.

Authors:
Yuichi Ozaki Erin L Damsteegt Alvin N Setiawan Takeshi Miura P Mark Lokman

Gen Comp Endocrinol 2019 09 19;280:123-133. Epub 2019 Apr 19.

Department of Zoology, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.

Receptors for follicle-stimulating hormone (Fshr), luteinizing hormone (Lhcgr1 and Lhcgr2) and androgens (Ara and Arb) transduce the hormonal signals that coordinate spermatogenesis, but the factors that regulate the abundance of these transducers in fish testes remain little-understood. To mend this paucity of information, we first determined changes in transcript abundance for these receptors (fshr, lhcgr1, ara and arb) during spermatogenesis induced by human chorionic gonadotropin (hCG) injection in the eel, Anguilla australis. We related our findings to testicular production of the fish androgen, 11-ketotestosterone (11-KT), and to the levels of the transcripts encoding steroidogenic acute regulatory protein (star) and 11β-hydroxylase (cyp11b), and subsequently evaluated the effects of hCG or 11-KT on mRNA levels of these target genes in vitro. Testicular 11-KT production was greatly increased by hCG treatment, both in vivo and in vitro, and associated with up-regulation of star and cyp11b transcripts. In situ hybridization indicated that testicular fshr mRNA levels were higher in the early stages of hCG-induced spermatogenesis, while lhcgr1 transcripts were most abundant later, once spermatids were observed. In vitro experiments further showed that hCG and its steroidal mediator 11-KT significantly increased fshr transcript abundance. These data provide new angles on the interactions between gonadotropin and androgen signaling during early spermatogenesis. Increases in levels of 11-KT following hCG injection elevated testicular fshr mRNA levels augmenting Fsh sensitivity in the testis. This evidence is suggestive of a positive feedback loop between gonadotropins and 11-KT that may be key to regulating early spermatogenesis in fish.
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http://dx.doi.org/10.1016/j.ygcen.2019.04.020DOI Listing
September 2019

Replacement of Fish Meal by Defatted Yellow Mealworm () Larvae in Diet Improves Growth Performance and Disease Resistance in Red Seabream ().

Authors:
Atsushi Ido Atsushi Hashizume Takashi Ohta Takayuki Takahashi Chiemi Miura Takeshi Miura

Animals (Basel) 2019 Mar 19;9(3). Epub 2019 Mar 19.

Graduate School of Agriculture, Ehime University, 3-5-7, Tarumi, Matsuyama, Ehime 790-8566, Japan.

Yellow mealworm () larvae are a potential alternative animal protein source for sustainable aquaculture. However, reports on the successful complete substitution of fish meal with yellow mealworm larvae in an aquaculture diet have been limited. In this study, we conducted a feeding trial with red seabream () being fed diets with partial or complete replacement of fish meal with yellow mealworm larvae defatted with a hexane⁻ethanol solution. Feed intake in red seabream increased in accordance with yellow mealworm larvae inclusion, and diets including 65% defatted mealworm larvae (complete replacement of fish meal) showed significant growth promotion. The addition of the oil fraction from mealworm larvae to diets resulted in growth reduction, despite meeting the nutritional requirements of red seabream. Moreover, the survival rate of red seabreams fed diets with partial replacement of fish meal with mealworm larvae was significantly higher in a challenge test with pathogenic bacteria. The present study demonstrated that yellow mealworm larvae are not merely an alternative animal protein, but have potential as functional feed ingredients for aquaculture production.
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http://dx.doi.org/10.3390/ani9030100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466227PMC
March 2019

Evaluation of Black Soldier Fly () Larvae and Pre-Pupae Raised on Household Organic Waste, as Potential Ingredients for Poultry Feed.

Authors:
Kiyonori Kawasaki Yuka Hashimoto Akihiro Hori Toshiya Kawasaki Hirofumi Hirayasu Shun-Ichiro Iwase Atsushi Hashizume Atsushi Ido Chiemi Miura Takeshi Miura Satoshi Nakamura Tomohiro Seyama Yoshiki Matsumoto Koji Kasai Yasuhiro Fujitani

Animals (Basel) 2019 Mar 19;9(3). Epub 2019 Mar 19.

Research Institute of Environment, Agriculture and Fisheries, Osaka Prefecture, Shakudo 442, Habikino, Osaka 583-0862, Japan.

Black soldier fly (BSF) larvae and pre-pupae could be satisfactorily raised on household organic waste and used as poultry feed, offering a potential sustainable way to recycle untapped resources of waste. The present study was conducted to determine if whole (non-defatted) BSF larvae and pre-pupae raised on experimental household waste could substitute soybean meal and oil as ingredients for laying hen diets. While no significant differences in feed intake and the egg-laying rate of hens were observed throughout the experiment, egg weight and eggshell thickness were greater in the pre-pupae-fed group than in the other groups. Moreover, although diversity of the cecal microbiota was significantly higher in the pre-pupae-fed than in the control group, no significant differences in bacterial genera known to cause food poisoning were observed when comparing the treatment groups. Nonetheless, and populations were significantly lower in the treatment than in the control group. Fat content in BSF was possibly related with the changes in the cecal microbiota. Hence, since BSF fat was deficient in essential fatty acids, special attention should be paid to the fat content and its fatty acid composition in the case of regular inclusion of BSF larvae and pre-pupae oil as an ingredient in poultry diets.
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http://dx.doi.org/10.3390/ani9030098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466380PMC
March 2019

Cooperative regulation of mouse aldose reductase (AKR1B3) gene transcription by Nrf2, TonEBP, and c-jun.

Authors:
Toru Nishinaka Kahori Shimizu Takeshi Miura Chihiro Yabe-Nishimura Tomoyuki Terada

Chem Biol Interact 2019 Apr 29;302:36-45. Epub 2019 Jan 29.

Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan.

Aldose reductase (AR), a member of aldo-keto reductase family, is the rate-limiting enzyme in the polyol pathway, and is known to play a key role in the pathogenesis of diabetic complications. AR also catalyzes the reduction of reactive aldehydes, thereby detoxifying endogenous as well as xenobiotic aldehydes in various tissues. The transcription of the AR gene was previously shown to be augmented by various stimuli including osmotic and oxidative stresses. A highly conserved region composed of an antioxidant response element (ARE), AP-1 site, and tonicity responsive enhancer (TonE) has been identified within the 5'-flanking region of the AR genes of humans, rats, and mice, which we designated as the multiple stress response region (MSRR). We previously showed that the transcription factor Nrf2 activated AR transcription via ARE within MSRR. In the present study, we examined the interactions among Nrf2, c-Jun, and the TonE-binding protein (TonEBP) in the regulation of AR gene transcription. In gene reporter assays using luciferase reporter constructs containing the MSRR of the mouse AR (AKR1B3) gene with HepG2 cells, the forced expression of Nrf2 or TonEBP significantly increased promoter activity. The synergistic augmentation of promoter activity was observed when Nrf2 and TonEBP were co-introduced. On the other hand, the co-expression of c-Jun repressed promoter activation by Nrf2 and TonEBP. The mutation of the AP-1 site within MSRR did not affect the repressive effects of c-Jun, while the introduction of truncated c-Jun proteins lacking the leucine zipper domain no longer suppressed Nrf2-or TonEBP-mediated transactivation, suggesting that c-Jun repressed promoter activity independently of the AP-1 site and that interactions with protein factors via the leucine zipper domain were necessary for its negative effects on Nrf2 and TonEBP. These results indicate that AR promoter activity is cooperatively regulated by multiple transcription factors via MSRR.
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http://dx.doi.org/10.1016/j.cbi.2019.01.024DOI Listing
April 2019

Duplication and deletion upstream of in autosomal dominant adult-onset leukodystrophy.

Authors:
Naomi Mezaki Takeshi Miura Kotaro Ogaki Makoto Eriguchi Yuri Mizuno Kenichi Komatsu Hiroki Yamazaki Natsuki Suetsugi Sumihiro Kawajiri Ryo Yamasaki Takanobu Ishiguro Takuya Konno Hiroaki Nozaki Kensaku Kasuga Yasuyuki Okuma Jun-Ichi Kira Hideo Hara Osamu Onodera Takeshi Ikeuchi

Neurol Genet 2018 Dec 7;4(6):e292. Epub 2018 Dec 7.

Department of Molecular Genetics (N.M., T.M., T. Ishiguro, K. Kasuga, T. Ikeuchi) and Department of Neurology (N.M., T.M., T. Ishiguro, T.K., O.O.), Brain Research Institute, Niigata University; Department of Neurology (K.O., S.K., Y.O.), Juntendo University Shizuoka Hospital; Division of Neurology, Department of Internal Medicine (M.E., N.S., H.H.), Faculty of Medicine, Saga University; Department of Neurology (Y.M., R.Y., J.-I.K.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University; Department of Neurology (K. Komatsu, H.Y.), Kitano Hospital, The Tazuke Kofukai Medical Research Institute; and Medical Technology (H.N.), Graduate School of Health Sciences, Niigata University.

Objective: To characterize the genetic and clinical features of patients with autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) carrying duplication and deletion upstream of lamin B1 ().

Methods: Ninety-three patients with adult-onset leukoencephalopathy of unknown etiology were genetically analyzed for copy numbers of and its upstream genes. We examined expression by reverse transcription-qPCR using total RNA extracted from peripheral leukocytes. Clinical and MRI features of the patients with ADLD were retrospectively analyzed.

Results: We identified 4 patients from 3 families with duplication. The duplicated genomic regions were different from those previously reported. The mRNA expression level of in patients with duplication was significantly increased. The clinical features of our patients with duplication were similar to those reported previously, except for the high frequency of cognitive impairment in our patients. We found 2 patients from 1 family carrying a 249-kb genomic deletion upstream of . Patients with the deletion exhibited relatively earlier onset, more prominent cognitive impairment, and fewer autonomic symptoms than patients with duplication. The presence of cerebellar symptoms and lesions may be characteristic in our patients with the deletion compared with the previously reported family with the deletion. Magnetic resonance images of patients with the deletion exhibited a widespread distribution of white matter lesions including the anterior temporal region.

Conclusions: We identified 4 Japanese families with ADLD carrying duplication or deletion upstream of . There are differences in clinical and MRI features between the patients with the duplication and those with the deletion upstream of .
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http://dx.doi.org/10.1212/NXG.0000000000000292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340331PMC
December 2018

Post-treatment with JP-1302 protects against renal ischemia/reperfusion-induced acute kidney injury in rats.

Authors:
Takaomi Shimokawa Hidenobu Tsutsui Takeshi Miura Masashi Takama Kohei Hayashi Toru Nishinaka Tomoyuki Terada Kozo Yoneda Masayo Yamagata Tokihito Yukimura

J Pharmacol Sci 2019 Mar 31;139(3):137-142. Epub 2018 Dec 31.

Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka, 584-8540, Japan.

Ischemia/reperfusion injury is the most common cause of acute kidney injury. We previously revealed that pre-treatment with yohimbine or JP-1302 attenuated renal ischemia/reperfusion injury by inhibition of α2C-adrenoceptor antagonist. The aim of the present study is to investigate the effects of post-treatment with JP-1302 on renal ischemia/reperfusion injury in rats. Male Sprague Dawley rats were randomly divided into four groups: sham operation, ischemia/reperfusion, pre-treatment with JP-1302 (3.0 mg/kg) and post-treatment with JP-1302 groups. In ischemia/reperfusion injury, renal functional parameters, such as blood urea nitrogen, plasma creatinine and creatinine clearance, deteriorated after reperfusion. Renal venous norepinephrine concentrations, as well as inflammatory molecules in the kidney increased after reperfusion. Both pre- and post-treatment with JP-1302 improved renal dysfunction, tissue damage, renal venous norepinephrine concentrations and inflammatory molecules expression in the kidney. In conclusion, these results suggest that post-treatment with JP-1302 protects on ischemia/reperfusion-induced acute kidney injury by suppressing cytokine upregulation via α2C-adrenoceptors.
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http://dx.doi.org/10.1016/j.jphs.2018.12.008DOI Listing
March 2019

Globular glial tauopathy Type II: Clinicopathological study of two autopsy cases.

Authors:
Hidetomo Tanaka Shinobu Kawakatsu Yasuko Toyoshima Takeshi Miura Naomi Mezaki Atsushi Mano Kazuhiro Sanpei Ryota Kobayashi Hiroshi Hayashi Koichi Otani Takeshi Ikeuchi Osamu Onodera Akiyoshi Kakita Hitoshi Takahashi

Neuropathology 2019 Apr 15;39(2):111-119. Epub 2019 Jan 15.

Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.

Globular glial tauopathies (GGTs) are four-repeat tauopathies characterized by the presence of two types of tau-positive globular glial inclusions (GGIs): globular oligodendrocytic and astrocytic inclusions (GOIs and GAIs). GGTs are classified into three different neuropathological subtypes: Types I, II and III. We report two patients with GGTs - a 76-year-old woman and a 70-year-old man - in whom the disease duration was 5 and 6 years, respectively. Both patients exhibited upper and lower motor neuron signs and involuntary movements, and the latter also had dementia with frontotemporal cerebral atrophy evident on magnetic resonance imaging. Neuropathologically, in both cases, the precentral gyrus was most severely affected, and at the gray-white matter junction there was almost complete loss of Betz cells and occurrence of GOIs and coiled bodies with numerous neuropil threads. Both patients also showed neuronal loss and GGIs (mostly GOIs) in many other central nervous system regions, including the basal ganglia. Apart from the degree of regional severity, the distribution pattern was essentially the same in both cases. However, GAIs were not conspicuous in any of the affected regions. Based on the morphology and distribution pattern of the GGIs, we diagnosed the present two patients as having GGT Type II. Electron microscopic and biochemical findings in the former were consistent with the diagnosis. Type II cases are reported to be characterized by pyramidal features reflecting predominant motor cortex and corticospinal tract degeneration. The present observations suggest that a variety of neurological features, including dementia, can occur in GGT Type II reflecting widespread degeneration beyond the motor neuron system.
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http://dx.doi.org/10.1111/neup.12532DOI Listing
April 2019

Inhibition of α2C-adrenoceptors ameliorates cisplatin-induced acute renal failure in rats.

Authors:
Hidenobu Tsutsui Takaomi Shimokawa Takeshi Miura Masashi Takama Toru Nishinaka Tomoyuki Terada Masayo Yamagata Tokihito Yukimura

Eur J Pharmacol 2018 Nov 7;838:113-119. Epub 2018 Sep 7.

Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka 584-8540, Japan.

Nephrotoxicity is a major adverse reaction of the anticancer drug, cisplatin. We investigated the renoprotective effects of the α2-adrenoceptor antagonist, yohimbine and selective α2C-adrenoceptor antagonist, JP-1302, in cisplatin-treated Sprague Dawley rats. Rats were given a single intravenous dose of 7.5 mg/kg cisplatin and then yohimbine or JP-1302 was administered intraperitoneally at 0.1 or 3 mg/kg/day, respectively, for four days. Renal functional parameters, such as blood urea nitrogen, plasma creatinine, creatinine clearance and renal venous norepinephrine concentrations were measured. Kidney tissue damage and tumour necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) mRNA levels were assessed after the animals were euthanized. Cisplatin treatment aggravated the kidney functional parameters of blood urea nitrogen, plasma creatinine and creatinine clearance. Renal venous norepinephrine concentrations were also elevated after cisplatin administration. Treatment with yohimbine or JP-1302 clearly ameliorated kidney function and cell apoptosis. These treatments suppressed elevated renal plasma norepinephrine, TNF-α, MCP-1 and cleaved caspase 3 expressions which occurred after administration of cisplatin. These results suggest that yohimbine can prevent cisplatin-induced renal toxicity associated with acute kidney injury by suppressing cytokine expression through α2C-adrenoceptors.
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http://dx.doi.org/10.1016/j.ejphar.2018.09.010DOI Listing
November 2018

Identification and functional characterization of novel mutations including frameshift mutation in exon 4 of CSF1R in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia.

Authors:
Takeshi Miura Naomi Mezaki Takuya Konno Akio Iwasaki Naoyuki Hara Masatomo Miura Michitaka Funayama Yuki Unai Yuichi Tashiro Kenji Okita Takeshi Kihara Nobuo Ito Yoichi Kanatsuka David T Jones Norikazu Hara Takanobu Ishiguro Takayoshi Tokutake Kensaku Kasuga Hiroaki Nozaki Dennis W Dickson Osamu Onodera Zbigniew K Wszolek Takeshi Ikeuchi

J Neurol 2018 Oct 22;265(10):2415-2424. Epub 2018 Aug 22.

Department of Molecular Genetics, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-ku, Niigata, 951-8585, Japan.

Objective: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is caused by mutations in CSF1R. Pathogenic mutations in exons 12-22 including coding sequence of the tyrosine kinase domain (TKD) of CSF1R were previously identified. We aimed to identify CSF1R mutations in patients who were clinically suspected of having ALSP and to determine the pathogenicity of novel CSF1R variants.

Methods: Sixty-one patients who fulfilled the diagnostic criteria of ALSP were included in this study. Genetic analysis of CSF1R was performed for all the coding exons. The haploinsufficiency of CSF1R was examined for frameshift mutations by RT-PCR. Ligand-dependent autophosphorylation of CSF1R was examined in cells expressing CSF1R mutants.

Results: We identified ten variants in CSF1R including two novel frameshift, five novel missense, and two known missense mutations as well as one known missense variant. Eight mutations were located in TKD. One frameshift mutation (p.Pro104LeufsTer8) and one missense variant (p.His362Arg) were located in the extracellular domain. RT-PCR analysis revealed that the frameshift mutation of p.Pro104LeufsTer8 caused nonsense-mediated mRNA decay. Functional assay revealed that none of the mutations within TKD showed autophosphorylation of CSF1R. The p.His362Arg variant located in the extracellular domain showed comparable autophosphorylation of CSF1R to the wild type, suggesting that this variant is not likely pathogenic.

Conclusions: The detection of the CSF1R mutation outside of the region-encoding TKD may extend the genetic spectrum of ALSP with CSF1R mutations. Mutational analysis of all the coding exons of CSF1R should be considered for patients clinically suspected of having ALSP.
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http://dx.doi.org/10.1007/s00415-018-9017-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182692PMC
October 2018

Sex-changing patterns of Akoya pearl oyster ().

Authors:
Jeane Siswitasari Mulyana Toshiharu Iwai Masaharu Takahashi Achmad Farajallah Yusli Wardiatno Chiemi Miura Takeshi Miura

Zoological Lett 2018 5;4:11. Epub 2018 Jun 5.

2Laboratory of Fish Reproductive Physiology, Graduate School of Agriculture, Ehime University, Matsuyama, Ehime Japan.

Background: Pearl production by transplantation in Akoya pearl oyster is a biotechnology developed in Japan that skillfully utilizes the pearl-forming ability of oysters. In this method, cultured pearls are formed from a pearl nucleus and a small piece of mantle transplanted into the gonads of recipient pearl oysters. In this study, we hypothesized that the sex of the recipient pearl oyster might affect the quality of pearl produced. While some previous studies have examined the sex of Akoya pearl oyster, detailed information is lacking.

Results: To investigate sex in Akoya pearl oyster, we collected small gonadal fragments from 1-year-old pearl oysters by biopsy. Using the collected gonad fragment, the sex of the oysters was determined by microscopic observation, and the remaining samples were stored for gene expression analyses. All oysters were labeled to distinguish each individual for serial samplings every four months over the 2-year study period. At the start of experiment, nearly all of the pearl oysters were male, but the male:female ratio ofmale decreased over the course of the experiment. Interestingly, the number of males increased after spring, during the breeding season. This suggests that, in pearl oyster, sex is affected by season. Expression analysis of sex-related genes () indicated that all genes were expressed in all individuals and all periods.

Conclusions: These results suggest that Akoya pearl oysters are hermaphroditic, and that females appear as necessary, such as during the breeding season. These findings could contribute to higher efficiency and quality of pearl cultivation.
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http://dx.doi.org/10.1186/s40851-018-0098-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987639PMC
June 2018

The silkrose of Bombyx mori effectively prevents vibriosis in penaeid prawns via the activation of innate immunity.

Authors:
Muhammad Fariz Zahir Ali Indri Afriani Yasin Takashi Ohta Atsushi Hashizume Atsushi Ido Takayuki Takahashi Chiemi Miura Takeshi Miura

Sci Rep 2018 06 11;8(1):8836. Epub 2018 Jun 11.

Graduate School of Agriculture, Ehime University, 3-5-7, Tarumi, Matsuyama, Ehime, 790-8566, Japan.

We previously identified novel bioactive polysaccharides from Bactrocera cucurbitae and Antheraea yamamai that activate innate immunity in RAW264 murine macrophages. However, in terms of potential applications in the cultivation of prawns, there were problems with the availability of these insects. However, we have now identified a polysaccharide from Bombyx mori that activates innate immunity in RAW264 cells and penaeid prawns. This purified polysaccharide, termed silkrose of B. mori (silkrose-BM), has a molecular weight of 1,150,000 and produces a single symmetrical peak on HPLC. Eight of nine constitutive monosaccharides of silkrose-BM are concomitant with dipterose of B. cucurbitae (dipterose-BC) and silkrose of A. yamamai (silkrose-AY). The major differences are found in the molar ratios of the monosaccharides. Silkrose-BM is approximately 500-fold less potent than silkrose-AY (EC: 2.5 and 0.0043 μg/mL, respectively) in a nitrite oxide (NO) production assay using RAW264 cells. However, the maximum NO production for silkrose-BM and AY were comparable and higher than that of the lipopolysaccharide of Escherichia coli. The survival of penaeid prawns (Litopenaeus vannamei and Marsupenaeus japonicus) after infection with Vibrio penaecida was significantly improved by both dietary silkrose-BM and B. mori pupae. This suggests that silkrose-BM effectively prevents vibriosis in penaeid prawns via the activation of innate immunity.
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http://dx.doi.org/10.1038/s41598-018-27241-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995915PMC
June 2018

Effect of monoamine oxidase inhibitors on ischaemia/reperfusion-induced acute kidney injury in rats.

Authors:
Hidenobu Tsutsui Takaomi Shimokawa Takeshi Miura Masashi Takama Toru Nishinaka Tomoyuki Terada Masayo Yamagata Tokihito Yukimura

Eur J Pharmacol 2018 Jan 12;818:38-42. Epub 2017 Oct 12.

Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka 584-8540, Japan.

Increases in renal sympathetic nerve activity during ischaemia and renal venous norepinephrine levels after reperfusion play important roles in the development of ischaemia/reperfusion-induced acute kidney injury. In the present study, we examined the effect of isatin, an endogenous monoamine oxidase inhibitor, on renal venous norepinephrine levels, superoxide production after reperfusion, and ischaemia/reperfusion-induced acute kidney injury. Ischaemia/reperfusion-induced acute kidney injury was accomplished by clamping the left renal artery and vein for 45min, followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal superoxide production and norepinephrine overflow were elevated and significant renal tissue damage was observed following ischaemia/reperfusion injury. Intravenous injection of isatin (10mg/kg) at 5min before ischaemia increased the renal venous plasma norepinephrine level after reperfusion and aggravated ischaemia/reperfusion-induced renal dysfunction and histological damage. The excessive superoxide production after reperfusion was significantly suppressed by isatin administration, indicating that the inhibition of oxidative deamination effectively suppressed superoxide production. These data suggest that the exacerbation effect of isatin is associated, at least in part, with increased norepinephrine levels but not with superoxide production. To the best of our knowledge, this is the first report of isatin involvement in the pathogenesis and/or development of acute kidney injury.
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http://dx.doi.org/10.1016/j.ejphar.2017.10.021DOI Listing
January 2018

A novel frameshift GRN mutation results in frontotemporal lobar degeneration with a distinct clinical phenotype in two siblings: case report and literature review.

Authors:
Takashi Hosaka Kazuhiro Ishii Takeshi Miura Naomi Mezaki Kensaku Kasuga Takeshi Ikeuchi Akira Tamaoka

BMC Neurol 2017 Sep 15;17(1):182. Epub 2017 Sep 15.

Department of the Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Ten'noudai, Tsukuba, Ibaraki, 305-8575, Japan.

Background: Progranulin gene (GRN) mutations are major causes of frontotemporal lobar degeneration. To date, 68 pathogenic GRN mutations have been identified. However, very few of these mutations have been reported in Asians. Moreover, some GRN mutations manifest with familial phenotypic heterogeneity. Here, we present a novel GRN mutation resulting in frontotemporal lobar degeneration with a distinct clinical phenotype, and we review reports of GRN mutations associated with familial phenotypic heterogeneity.

Case Presentation: We describe the case of a 74-year-old woman with left frontotemporal lobe atrophy who presented with progressive anarthria and non-fluent aphasia. Her brother had been diagnosed with corticobasal syndrome (CBS) with right-hand limb-kinetic apraxia, aphasia, and a similar pattern of brain atrophy. Laboratory blood examinations did not reveal abnormalities that could have caused cognitive dysfunction. In the cerebrospinal fluid, cell counts and protein concentrations were within normal ranges, and concentrations of tau protein and phosphorylated tau protein were also normal. Since similar familial cases due to mutation of GRN and microtubule-associated protein tau gene (MAPT) were reported, we performed genetic analysis. No pathological mutations of MAPT were identified, but we identified a novel GRN frameshift mutation (c.1118_1119delCCinsG: p.Pro373ArgX37) that resulted in progranulin haploinsufficiency.

Conclusion: This is the first report of a GRN mutation associated with familial phenotypic heterogeneity in Japan. Literature review of GRN mutations associated with familial phenotypic heterogeneity revealed no tendency of mutation sites. The role of progranulin has been reported in this and other neurodegenerative diseases, and the analysis of GRN mutations may lead to the discovery of a new therapeutic target.
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http://dx.doi.org/10.1186/s12883-017-0959-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603021PMC
September 2017

Cognitive dysfunction and symptoms of movement disorders in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia.

Authors:
Takeshi Ikeuchi Naomi Mezaki Takeshi Miura

Parkinsonism Relat Disord 2018 Jan 16;46 Suppl 1:S39-S41. Epub 2017 Aug 16.

Department of Molecular Genetics, Brain Research Institute, Niigata University, Japan.

Adult-onset leukoencephalopathies are clinically and genetically heterogeneous disorders that affect predominantly the cerebral white matter of the central nervous system. Clinical and neuroimaging-based approaches have been developed to improve diagnostic processes for adult-onset leukoencephalopathies. However, the differential diagnosis is often challenging. Recently, knowledge of the genetic basis of leukoencephalopathies has been accumulated rapidly, which provides powerful diagnostic approaches. The article provides an overview of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), focusing on the clinical presentations of cognitive impairment and symptoms of movement disorders. ALSP is a subtype of dominantly inherited leukoencephalopathy caused by CSF1R mutations. ALSP typically develop in adulthood, with cognitive decline, psychiatric symptoms, and motor symptoms of movement disorders. Cognitive symptoms in ALSP are characterized by frontal lobe dysfunctions such as executive dysfunction, attention deficits and indifference. The cardinal motor symptoms of movement disorders ALSP were gait disturbance and bradykinesia, which may appear as the initial symptoms. Thus, ALSP should be recognized as both a cognitive disorder and a movement disorder.
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http://dx.doi.org/10.1016/j.parkreldis.2017.08.018DOI Listing
January 2018

Effect of the squid viscera hydrolysate on growth performance and digestion in the red sea bream Pagrus major.

Authors:
Fumitaka Kondo Takashi Ohta Toshiharu Iwai Atsushi Ido Chiemi Miura Takeshi Miura

Fish Physiol Biochem 2017 Dec 4;43(6):1543-1555. Epub 2017 Jul 4.

Research Group for Reproductive Physiology, Graduate School of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, 790-8566, Japan.

The improvement in feed efficiency is one of the most important subjects in fish culture. The development of feed, in terms of good intake, high growth performance, and high feed efficiency is needed. Squid viscera are one of the candidates for alternative material in improving feed efficiency in fish culture. In the present study, we described the dietary effect of the squid viscera hydrolysate (SVH) on the growth performance of the red sea bream. The addition of SVH to feed caused significant increases in feed intake, fork length, and body weight and produced a marked improvement in feed conversion after 4 weeks of feeding. Furthermore, the results of this feeding revealed that low dietary levels of SVH promote growth performance in the red sea bream. We physiologically analyzed digestion and appetite in fish fed diet containing SVH. SVH promoted the activity of hepatic trypsin and lipase, gene expression of stomach pepsin, hepatic lipase, and pyloric caeca trypsin, thereby improving the nutrient availability in red sea bream. Moreover, the mRNA expression of appetite regulating factor, such as brain NPY and stomach ghrelin was significantly improved by dietary SVH. Our current results indicate that dietary SVH as alternative material produced excellent effects on growth performance, which is dependent on the promoting effect on digestion and appetite in red sea bream.
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http://dx.doi.org/10.1007/s10695-017-0391-yDOI Listing
December 2017

Human carbonyl reductase 1 participating in intestinal first-pass drug metabolism is inhibited by fatty acids and acyl-CoAs.

Authors:
Akira Hara Satoshi Endo Toshiyuki Matsunaga Ossama El-Kabbani Takeshi Miura Toru Nishinaka Tomoyuki Terada

Biochem Pharmacol 2017 08 24;138:185-192. Epub 2017 Apr 24.

Faculty of Pharmacy, Osaka Ohtani University, Osaka 584-8540, Japan.

Human carbonyl reductase 1 (CBR1), a member of the short-chain dehydrogenase/reductase (SDR) superfamily, reduces a variety of carbonyl compounds including endogenous isatin, prostaglandin E and 4-oxo-2-nonenal. It is also a major non-cytochrome P450 enzyme in the phase I metabolism of carbonyl-containing drugs, and is highly expressed in the intestine. In this study, we found that long-chain fatty acids and their CoA ester derivatives inhibit CBR1. Among saturated fatty acids, myristic, palmitic and stearic acids were inhibitory, and stearic acid was the most potent (IC 9µM). Unsaturated fatty acids (oleic, elaidic, γ-linolenic and docosahexaenoic acids) and acyl-CoAs (palmitoyl-, stearoyl- and oleoyl-CoAs) were more potent inhibitors (IC 1.0-2.5µM), and showed high inhibitory selectivity to CBR1 over its isozyme CBR3 and other SDR superfamily enzymes (DCXR and DHRS4) with CBR activity. The inhibition by these fatty acids and acyl-CoAs was competitive with respect to the substrate, showing the K values of 0.49-1.2µM. Site-directed mutagenesis of the substrate-binding residues of CBR1 suggested that the interactions between the fatty acyl chain and the enzyme's Met141 and Trp229 are important for the inhibitory selectivity. We also examined CBR1 inhibition by oleic acid in cellular levels: The fatty acid effectively inhibited CBR1-mediated 4-oxo-2-nonenal metabolism in colon cancer DLD1 cells and increased sensitivity to doxorubicin in the drug-resistant gastric cancer MKN45 cells that highly express CBR1. The results suggest a possible new food-drug interaction through inhibition of CBR1-mediated intestinal first-pass drug metabolism by dietary fatty acids.
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http://dx.doi.org/10.1016/j.bcp.2017.04.023DOI Listing
August 2017

Vasodilatory effect of nitroglycerin in Japanese subjects with different aldehyde dehydrogenase 2 (ALDH2) genotypes.

Authors:
Takeshi Miura Toru Nishinaka Tomoyuki Terada Kazuya Yonezawa

Chem Biol Interact 2017 Oct 23;276:40-45. Epub 2017 Mar 23.

Department of Clinical Research, National Hospital Organization Hakodate Hospital, 18-16, Kawahara, Hakodate, Hokkaido 041-8512, Japan.

The functional genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) influences the enzymatic activities of its wild type (Glu504 encoded by ALDH2*1) and mutant type (Lys504 encoded by ALDH2*2) proteins. The enzymatic activities of mutant-type ALDH2 are limited compared with those of the wild type. ALDH2 has been suggested as a critical factor for nitroglycerin-mediated vasodilation by some human studies and in vitro studies. Currently, there is no research on direct observations of the vasodilatory effect of nitroglycerin sublingual tablets, which is the generally used dosage form. In the present study, the contribution of ALDH2 to the vasodilatory effect of nitroglycerin sublingual tablets was investigated among three genotype groups (ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2) in Japanese. The results by direct assessments of in vivo nitroglycerin-mediated dilation showed no apparent difference in vasodilation among all genotypes of ALDH2. Furthermore, to analyze the effect of other factors (age and flow-mediated dilation), multiple regression analysis and Pearson's correlation coefficient analysis were carried out. These analyses also indicated that the genotypes of ALDH2 were not related to the degree of vasodilation. These results suggest the existence of other predominant pathway(s) for nitroglycerin biotransformation, at least with regard to clinical nitroglycerin (e.g., a sublingual tablet) in Japanese subjects.
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http://dx.doi.org/10.1016/j.cbi.2017.03.012DOI Listing
October 2017

Inhibitory Effect of Fruit Juices on the Doxorubicin Metabolizing Activity of Carbonyl Reductase 1.

Authors:
Takeshi Miura Katsutoshi Nagai Shingo Kaneshiro Ayako Taketomi Toshikatsu Nakabayashi Hiroki Konishi Toru Nishinaka Tomoyuki Terada

Drug Metab Lett 2017 11;11(1):48-52

Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka 584-8540, Japan.

Background And Objective: Doxorubicin, an anthracycline anti-cancer drug, is effective for breast cancer and childhood lymphoma. Chronic cardiotoxicity has been known as a critical adverse effect of doxorubicin and is attributed to its metabolite doxorubicinol produced by carbonyl reductase 1 (CBR1, SDR21C1). Some flavonoids have been reported to act as inhibitors for CBR1, therefore, commercially available juices containing flavonoids are likely to be applicable as a prophylactic treatment against doxorubicin-induced cardiotoxicity by suppression of doxorubicinol production. In the study, fruit juices containing flavonoids were investigated for inhibitory effects on CBR1.

Method: Recombinant CBR1 protein was subjected to in vitro enzymatic assays with/without juices. An apple juice and a grapefruit juice were selected in the present study as candidates capable of inhib-iting CBR1.

Results: The enzymatic assays revealed that both juices potently inhibit the CBR1-mediated metabolic conversion of doxorubicin to doxorubicinol in concertation-dependent manner. The concentrations required for obtaining 50% inhibition (IC50) were 0.0012% (v/v) and 0.0014% (v/v) for apple and grapefruit juices, respectively. Additionally, it is worth noting that these juices showed inhibitory effects on doxorubicin metabolism by CBR1 even at very low concentrations (0.0001% (v/v)).

Conclusion: An apple juice and a grape fruit juice showed strong inhibitory effects on doxorubicin metabolism by CBR1 in vitro. These results suggest that the intake of flavonoid-containing juices can be a promising measure for protection against doxorubicin-induced cardiac toxicity, enabling patients to keep higher adherence with routine use in light of safety, economic performance and stable supply to market.
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http://dx.doi.org/10.2174/1872312811666170309153025DOI Listing
November 2017

Identification and characterization of functional antioxidant response elements in the promoter of the aldo-keto reductase AKR1B10 gene.

Authors:
Toru Nishinaka Takeshi Miura Kahori Shimizu Tomoyuki Terada

Chem Biol Interact 2017 Oct 20;276:160-166. Epub 2017 Feb 20.

Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka, 584-8540, Japan.

AKR1B10 is a human-type aldo-keto reductase. The up-regulation of AKR1B10 has been associated with various cancers including non-small cell lung carcinoma, viral and bacterial infections, and skin diseases. However, the mechanisms underlying AKR1B10 gene regulation are not fully understood. We previously indicated the involvement of the transcription factor Nrf2 in AKR1B10 gene regulation. There are at least five potential Nrf2-responsive consensus sequences, so-called antioxidant response elements (AREs), and several ARE-like sequences in the 5'-flanking region up to -3282 bp of the AKR1B10 gene. In the present study, we attempted to identify functional AREs by luciferase reporter analyses using various mutants for each ARE. And we found that only those between -530 and -520 bp (ARE-A), which is the closest location to the translation start site, were functional among the five ARE consensus sites examined. Furthermore, ARE-A functioned co-operatively with the neighboring AP-1 site. Since the AP-1 site resembles ARE, the tandem arrangement of these two elements may be essential for augmented responsiveness to Nrf2 and plays an important role in AKR1B10 gene regulation by various Nrf2-mediating stimuli.
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http://dx.doi.org/10.1016/j.cbi.2017.02.008DOI Listing
October 2017

Effects of Reinforcement Method of Dissection Physiology Education on the Achievement in Pharmacology.

Authors:
Tomoya Kitayama Satomi Kagota Noriko Yoshikawa Nobuyuki Kawai Kanae Nishimura Takeshi Miura Naomi Yasui Kazumasa Shinozuka Toshikatsu Nakabayashi

Yakugaku Zasshi 2016 ;136(12):1651-1656

Department of Pharmacy, School of Pharmacy and Pharmaceutical Science, Mukogawa Women's University.

The Pharmaceutical Education Support Center was established in the Department of Pharmacy at the School of Pharmacy and Pharmaceutical Science of Mukogawa Women's University in 2014. We started teaching first and second years students according to proficiency from the 2014 academic year. Students were divided into two classes: the regular class (high proficiency class) and the basic class (low proficiency class), based on achievement in several basic subjects related to the study of pharmacy. The staffs in the Pharmaceutical Education Support Center reinforce what is taught to students in the basic class. In this reinforcement method of education, the class size is small, consisting of about 15 students, a quiz to review the previous lesson is given at the beginning of each lecture, and an additional five lectures are conducted, compared to the high proficiency class, which receives 15 lectures. In this study, we evaluated the effects of the reinforcement method of physiology education on achievement in pharmacology that was not conducted in the proficiency-dependent teaching method. The students in the basic class in physiology education were chosen based on achievement levels in anatomy. Achievement levels of pharmacology students in the basic class of physiology improved compared with those of students who had the same achievement levels in physiology but were not taught according to proficiency-dependent teaching in the 2013 academic year. These results suggest that the reinforcement method for education in basic subjects in pharmacy, such as physiology, can improve achievement in more advanced subjects, such as pharmacology.
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http://dx.doi.org/10.1248/yakushi.16-00189DOI Listing
April 2017

Characteristic microglial features in patients with hereditary diffuse leukoencephalopathy with spheroids.

Authors:
Mari Tada Takuya Konno Masayoshi Tada Toshiyuki Tezuka Takeshi Miura Naomi Mezaki Ken-Ichi Okazaki Musashi Arakawa Kyoko Itoh Toru Yamamoto Hideaki Yokoo Nobuaki Yoshikura Kenji Ishihara Masao Horie Hirohide Takebayashi Yasuko Toyoshima Makoto Naito Osamu Onodera Masatoyo Nishizawa Hitoshi Takahashi Takeshi Ikeuchi Akiyoshi Kakita

Ann Neurol 2016 10 4;80(4):554-65. Epub 2016 Sep 4.

Department of Pathology, Brain Research Institute, Niigata University, Niigata.

Objective: To clarify the histopathological alterations of microglia in the brains of patients with hereditary diffuse leukoencephalopathy with spheroids (HDLS) caused by mutations of the gene encoding the colony stimulating factor-1 receptor (CSF-1R).

Methods: We examined 5 autopsied brains and 1 biopsy specimen from a total of 6 patients with CSF-1R mutations. Detailed immunohistochemical, biochemical, and ultrastructural features of microglia were examined, and quantitative analyses were performed.

Results: In layers 3 to 4 of the frontal cortex in HDLS brains, microglia showed relatively uniform and delicate morphology, with thin and winding processes accompanying knotlike structures, and significantly smaller areas of Iba1 immunoreactivity and lower numbers of Iba1-positive cells were evident in comparison with control brains. On the other hand, in layers 5 to 6 and the underlying white matter, microglia were distributed unevenly; that is, in some areas they had accumulated densely, whereas in others they were scattered. Immunoblot analyses of microglia-associated proteins, including CD11b and DAP12, revealed that HDLS brains had significantly lower amounts of these proteins than diseased controls, although Ki-67-positive proliferative microglia were not reduced. Ultrastructurally, the microglial cytoplasm and processes in HDLS showed vesiculation of the rough endoplasmic reticulum and disaggregated polyribosomes, indicating depression of protein synthesis. On the other hand, macrophages were immunonegative for GLUT-5 or P2ry12, indicating that they were derived from bone marrow.

Interpretation: The pathogenesis of HDLS seems to be associated with microglial vulnerability and morphological alterations. Ann Neurol 2016;80:554-565.
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http://dx.doi.org/10.1002/ana.24754DOI Listing
October 2016

A high-molecular-weight, alkaline, and thermostable β-1,4-xylanase of a subseafloor Microcella alkaliphila.

Authors:
Koki Kuramochi Kohsuke Uchimura Atsushi Kurata Tohru Kobayashi Yuu Hirose Takeshi Miura Noriaki Kishimoto Ron Usami Koki Horikoshi

Extremophiles 2016 Jul 30;20(4):471-8. Epub 2016 May 30.

Research & Development Center for Marine Biosciences, Japan Agency for Marine-Earth Science and Technology (JAMSTEC), 2-15 Natsushima, Yokosuka, Kanagawa, 237-0061, Japan.

An endo β-1,4-xylanase (XynE15) from a culture broth of a deep subseafloor microorganism, Microcella alkaliphila JAM-AC0309, was purified to homogeneity. The molecular mass of XynE15 was approximately 150 kDa as judged by SDS-PAGE. The optimal pH and temperature for hydrolysis of xylan were pH 8 and 65 °C. The enzyme was stable to incubation for 30 min at up to 75 °C, and the half-life at 50 °C was 48 h. XynE15 hydrolyzed arabinoxylan, oat spelt xylan, and birchwood xylan well, but not avicel, carboxymethylcellulose, or arabinan. Xylooligosaccharides were hydrolyzed to mainly xylobiose from higher than xylotetraose. The genome sequencing analysis of strain JAM-AC03039 revealed that XynE15 was composed of 1,319 amino acids with one catalytic domain and three carbohydrate-binding domains belonging to glycoside hydrolase (GH) family 10 and carbohydrate-binding module (CBM) family 4, respectively.
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http://dx.doi.org/10.1007/s00792-016-0837-7DOI Listing
July 2016

Renoprotective effect of yohimbine on ischaemia/reperfusion-induced acute kidney injury through α2C-adrenoceptors in rats.

Authors:
Takaomi Shimokawa Hidenobu Tsutsui Takeshi Miura Toru Nishinaka Tomoyuki Terada Masashi Takama Shuhei Yoshida Takao Tanba Ayumi Tojo Masayo Yamagata Tokihito Yukimura

Eur J Pharmacol 2016 Jun 31;781:36-44. Epub 2016 Mar 31.

Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nshikiori-kita, Tondabayashi, Osaka 584-8540, Japan.

Excitation of renal sympathetic nervous activity and the resulting increased levels of renal venous norepinephrine play important roles in renal ischaemia/reperfusion injury in rats. This study examined the effects of yohimbine, a non-selective α2-adrenoceptor antagonist, on renal venous norepinephrine levels and kidney function in acute kidney injury. Acute ischaemia/reperfusion-induced kidney injury was induced in rats by clamping the left renal artery and vein for 45min, followed by reperfusion, 2 weeks after a contralateral nephrectomy. Intravenous injection of yohimbine (0.1mg/kg) 5min prior to ischaemia significantly attenuated kidney injury and decreased the renal venous norepinephrine levels, as compared with vehicle-treated rats. To investigate the involvement of α2-adrenoceptor subtypes, we pre-treated with JP-1302, a selective α2C-adrenoceptor antagonist (1mg/kg). This suppressed renal venous norepinephrine levels and tumour necrosis factor-α and monocyte chemoattractant protein-1 mRNA levels after reperfusion and improved kidney function. Pre-treatment with BRL44408, a selective α2A-adrenoceptor antagonist (1mg/kg), or imiloxan, a selective α2B-adrenoceptor antagonist (1mg/kg) had no effect on renal function or tissue injury. These results suggest that yohimbine prevented ischaemia/reperfusion-induced kidney injury by inhibiting α2C-adrenoceptors and suppressing pro-inflammatory cytokine expression.
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http://dx.doi.org/10.1016/j.ejphar.2016.03.059DOI Listing
June 2016

Differences in the ability of two marine annelid species, Thalassodrilides sp. and Perinereis nuntia, to detoxify 1-nitronaphthalene.

Authors:
Katsutoshi Ito Mana Ito Toshimitsu Onduka Kohei Ohta Takaaki Torii Takeshi Hano Kazuhiko Mochida Nobuyuki Ohkubo Takeshi Miura Kazunori Fujii

Chemosphere 2016 May 15;151:339-44. Epub 2016 Mar 15.

National Research Institute of Fisheries and Environment of Inland Sea, Fisheries Research Agency, 2-17-5, Maruishi, Hatsukaichi, Hiroshima 739-0452, Japan.

Bioremediation is a promising method for remediating environmentally polluted water. We investigated the abilities of two benthic annelid species to biotransform 1-nitronaphthalene, a nitrated polycyclic aromatic hydrocarbon. We used an oligochaete, Thalassodrilides sp. (Naididae), collected from the sediment beneath a fish farm and a polychaete, Perinereis nuntia, which was obtained from a commercial source. Populations of both organisms were exposed to 1400 μg L(-1) of 1-nitronaphthalene in seawater for 3 days in the dark at 20 °C. The concentration of the pollutant decreased to 12 μg L(-1) in the seawater containing the Thalassodrilides sp. and to 560 μg L(-1) in the seawater containing P. nuntia. The 1-nitronaphthalene concentration in the bodies of the animals increased from 12 to 94 μg kg(-1) in Thalassodrilides sp. and from 0.90 μg kg(-1) to 38,000 μg kg(-1) in P. nuntia. After 3 days, 99% and 40% of the 1-nitronaphthalene had been biotransformed in the Thalassodrilides sp. and P. nuntia experimental groups, respectively. We then tested the acute toxicity of residual 1-nitronaphthalene from the same water using mummichog (fish) larvae. After the larvae had been exposed for 96 h, the percentage of apparently unaffected larvae remaining was 83.3% in Thalassodrilides sp. group but only 16.7% in the P. nuntia group. Clearly, of the two species we studied, Thalassodrilides sp. had a superior ability to convert 1-nitronaphthalene into substances that were nontoxic to mummichog larvae. Therefore, we recommend the use of this species for bioremediation of chemically polluted sediments.
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http://dx.doi.org/10.1016/j.chemosphere.2016.02.026DOI Listing
May 2016

Familial idiopathic basal ganglia calcification: Histopathologic features of an autopsied patient with an SLC20A2 mutation.

Authors:
Tadashi Kimura Takeshi Miura Kenju Aoki Shoji Saito Hiroaki Hondo Takuya Konno Akio Uchiyama Takeshi Ikeuchi Hitoshi Takahashi Akiyoshi Kakita

Neuropathology 2016 Aug 4;36(4):365-71. Epub 2015 Dec 4.

Departments of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.

Idiopathic basal ganglia calcification (IBGC), or Fahr's disease, is a neurological disorder characterized by widespread calcification in the brain. Recently, several causative genes have been identified, but the histopathologic features of the brain lesions and expression of the gene products remain unclear. Here, we report the clinical and autopsy features of a 62-year-old Japanese man with familial IBGC, in whom an SLC20A2 mutation was identified. The patient developed mild cognitive impairment and parkinsonism. A brain CT scan demonstrated abnormal calcification in the bilateral basal ganglia, thalami and cerebellum. An MRI study at this point revealed glioblastoma, and the patient died 6 months later. At autopsy, symmetric calcification in the basal ganglia, thalami, cerebellar white matter and deeper layers of the cerebral cortex was evident. The calcification was observed in the tunica media of small arteries, arterioles and capillaries, but not in veins. Immunohistochemistry using an antibody against type III sodium-dependent phosphate transporter 2 (PiT-2), the SLC20A2 product, demonstrated that astrocytic processes were labeled in several regions in control brains, whereas in the patient, reactivity in astrocytes was apparently weak. Immunoblotting demonstrated a marked decrease of PiT-2 in the patient. There are few autopsy reports of IBGC patients with confirmation of the genetic background. The autopsy features seem informative for better understanding the histogenesis of IBGC lesions.
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http://dx.doi.org/10.1111/neup.12280DOI Listing
August 2016