Publications by authors named "Akira Matsuda"

407 Publications

Canine mast cell tumour cells regulate tryptophan catabolism via the expression of indoleamine 2,3-dioxygenase.

Res Vet Sci 2021 Jul 30;137:159-162. Epub 2021 Apr 30.

Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.

Indoleamine 2,3-deoxygenase (IDO) produced by cancer cells catabolizes tryptophan (TRP) to kynurenine (KYN) in the environment, resulting induction of cancer immune escape through induction of T cell anergy and enhancement of regulatory T cells. Recently, inhibition of IDO has been recognized as one of therapeutic strategies for human neoplastic diseases. However, there have been few reports about IDO-expressing cancers in dogs. In this study, we attempted to examine whether canine mast cell tumour (MCT) cells express IDO and modulate the concentration of TRP and KYN in the environment. BR, MPT-1.2, and MPT-3 cells were used as canine MCT cells. Expression of IDO was examined with RT-PCR and western blotting. Concentrations of TRP and KYN in the culture medium after incubation with canine MCT cells were detected with liquid chromatography-tandem mass spectrometry. The expression of mRNA and protein of IDO were confirmed in all samples extracted from canine MCT cells. TRP concentration in the culture medium was decreased and that of KYN was increased on incubation with canine MCT cells. The ratio of KYN/TRP, widely considered to represent IDO activity, was also significantly elevated. Moreover, treatment with an IDO inhibitor L-1-methyl-tryptophan (L-1MT) clearly diminished the elevation of KYN/TRP ratio induced by the incubation with canine MCT cells. Our results indicate that canine MCT cells could directly regulate the concentrations of TRP and KYN through expressing IDO, suggesting that canine MCT have an immune escape ability. Therefore, inhibition of IDO might be a novel strategy for the treatment of dogs with MCT.
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http://dx.doi.org/10.1016/j.rvsc.2021.04.030DOI Listing
July 2021

Amyloid beta cleavage by ANA-TA9, a synthetic peptide from the ANA/BTG3 Box A region.

Alzheimers Dement (N Y) 2021 31;7(1):e12146. Epub 2021 Mar 31.

O-Force Co., Ltd Hata-gun Kochi Japan.

Introduction: We recently discovered a short synthetic peptide derived from the ANA/BTG3 protein Box A region called ANA-TA9 (SKGQAYRMI), which possesses catalytic activity. Herein we demonstrated the proteolytic activity of ANA-TA9 against amyloid beta 42 (Aβ42).

Methods: The proteolytic activity of ANA-TA9 against both the authentic soluble form Aβ42 (-Aβ42) and the solid insoluble form Aβ42 (-Aβ42) was analyzed by high-performance liquid chromatography and mass spectrometry. Plasma clearance, brain uptake, and cell viability were examined.

Results: ANA-TA9 cleaved not only -Aβ42 but also -Aβ42. Proteolytic activity was partially inhibited by 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride, a serine protease inhibitor. Plasma clearance was very rapid, and the brain concentration indicated efficient brain delivery of ANA-TA9 via nasal application. Cell viability analysis indicated that ANA-TA9 did not display toxicity.

Discussion: ANA-TA9 is an attractive potential candidate for the development of novel peptide drugs in Alzheimer's disease treatment.
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http://dx.doi.org/10.1002/trc2.12146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012241PMC
March 2021

A Case of Canine Polyglandular Deficiency Syndrome with Diabetes Mellitus and Hypoadrenocorticism.

Vet Sci 2021 Mar 7;8(3). Epub 2021 Mar 7.

Earth Animal Hospital, 4-3-43 Hokushin-cho, Kitami, Hokkaido 090-0052, Japan.

This report describes the first clinical case, to our knowledge, of a dog with polyglandular deficiency syndrome with diabetes mellitus and hypoadrenocorticism. A six-year-old female Cavalier King Charles Spaniel presented with a history of lethargy and appetite loss. The dog was diagnosed with diabetic ketoacidosis based on hyperglycemia and renal glucose and ketone body loss. The dog's condition improved on intensive treatment of diabetes mellitus; daily subcutaneous insulin detemir injection maintained an appropriate blood glucose level over half a year. However, the dog's body weight gradually decreased from day 207, and on day 501, it presented with a decreased appetite; the precise cause could not be determined. Based on mild hyponatremia and hyperkalemia, hypoadrenocorticism was suggested; the diagnosis was made using an adrenocorticotropic hormone stimulation test. Daily fludrocortisone with low-dose prednisolone oral administration resulted in poor recovery of the blood chemistry abnormalities; however, monthly desoxycorticosterone pivalate (DOCP) subcutaneous injection with daily low-dose prednisolone oral administration helped in the significant recovery of the abnormalities. Therefore, clinicians should consider the possibility of coexistence of hypoadrenocorticism in dogs with diabetes mellitus presenting with undifferentiated weight loss. Additionally, DOCP (not fludrocortisone) may be useful in treating dogs with diabetes mellitus complicated with hypoadrenocorticism.
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http://dx.doi.org/10.3390/vetsci8030043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000634PMC
March 2021

Structure, solubility, and permeability relationships in a diverse middle molecule library.

Bioorg Med Chem Lett 2021 Apr 9;37:127847. Epub 2021 Feb 9.

Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Science, Hokkaido University, Kita 12, Nishi 6, Kita ku, Sapporo 060 0812, Japan; Global Station for Biosurfaces and Drug Discovery, Hokkaido University, Kita 12, Nishi 6, Kita ku, Sapporo 060 0812, Japan. Electronic address:

To develop methodology to predict the potential druggability of middle molecules, we examined the structure, solubility, and permeability relationships of a diverse library (HKDL ver.1) consisting of 510 molecules (359 natural product derivatives, 76 non-natural products, 46 natural products, and 29 non-natural product derivatives). The library included peptides, depsipeptides, macrolides, and lignans, and 476 of the 510 compounds had a molecular weight in the range of 500-2000 Da. The solubility and passive diffusion velocity of the middle molecules were assessed using the parallel artificial membrane permeability assay (PAMPA). Quantitative values of solubility of 471 molecules and passive diffusion velocity of 287 molecules were obtained, and their correlations with the structural features of the molecules were examined. Based on the results, we propose a method to predict the passive diffusion characteristics of middle molecules from their three-dimensional structural features.
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http://dx.doi.org/10.1016/j.bmcl.2021.127847DOI Listing
April 2021

Clonal hematopoiesis in adult pure red cell aplasia.

Sci Rep 2021 Jan 26;11(1):2253. Epub 2021 Jan 26.

Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan.

Idiopathic pure red cell aplasia (PRCA) and secondary PRCA associated with thymoma and large granular lymphocyte leukemia are generally considered to be immune-mediated. The PRCA2004/2006 study showed that poor responses to immunosuppression and anemia relapse were associated with death. PRCA may represent the prodrome to MDS. Thus, clonal hematopoiesis may be responsible for treatment failure. We investigated gene mutations in myeloid neoplasm-associated genes in acquired PRCA. We identified 21 mutations affecting amino acid sequences in 11 of the 38 adult PRCA patients (28.9%) using stringent filtering of the error-prone sequences and SNPs. Four PRCA patients showed 7 driver mutations in TET2, DNMT3A and KDM6A, and 2 PRCA patients carried multiple mutations in TET2. Five PRCA patients had mutations with high VAFs exceeding 0.3. These results suggest that clonal hematopoiesis by stem/progenitor cells might be related to the pathophysiology of chronic PRCA in certain adult patients.
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http://dx.doi.org/10.1038/s41598-021-81890-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838416PMC
January 2021

miR103a-3p in extracellular vesicles from FcεRI-aggregated human mast cells enhances IL-5 production by group 2 innate lymphoid cells.

J Allergy Clin Immunol 2021 May 17;147(5):1878-1891. Epub 2021 Jan 17.

Allergy and Immunology Research Project Team, Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan; Center for Allergy, Nihon University Itabashi Hospital, Tokyo, Japan; Center for Medical Education, Nihon University School of Medicine, Tokyo, Japan. Electronic address:

Background: Mast cells (MCs) are key regulators of IgE-mediated allergic inflammation. Cell-derived extracellular vesicles (EVs) contain bioactive compounds such as microRNAs. EVs can transfer signals to recipient cells, thus using a novel mechanism of cell-to-cell communication. However, whether MC-derived EVs are involved in FcεRI-mediated allergic inflammation is unclear.

Objective: We sought to investigate the effect of EVs derived from FcεRI-aggregated human MCs on the function of human group 2 innate lymphoid cells (ILC2s).

Methods: Human cultured MCs were sensitized with and without IgE for 1 hour and then incubated with anti-IgE antibody, IL-33, or medium alone for 24 hours. EVs in the MC supernatant were isolated by using ExoQuick-TC.

Results: Coculture of ILC2s with EVs derived from the FcεRI-aggregated MCs significantly enhanced IL-5 production and sustained upregulation of IL-5 mRNA expression in IL-33-stimulated ILC2s, but IL-13 production and IL-13 mRNA expression were unchanged. miR103a-3p expression was upregulated in IL-33-stimulated ILC2s that had been cocultured with EVs derived from anti-IgE antibody-stimulated MCs. Transduction of an miR103a-3p mimic to ILC2s significantly enhanced IL-5 production by IL-33-stimulated ILC2s. miR103a-3p promoted demethylation of an arginine residue of GATA3 by downregulating protein arginine methyltransferase 5 (PRMT5) mRNA. Reduction of protein arginine methyltransferase 5 expression in ILC2s by using a small interfering RNA technique resulted in upregulation of IL-5 production by IL-33-stimulated ILC2s. Furthermore, the level of miR103a-3p expression was significantly higher in EVs from sera of patients with atopic dermatitis than in EVs from nonatopic healthy control subjects.

Conclusion: Eosinophilic allergic inflammation may be exacerbated owing to ILC2 activation by MC-derived miR103a-3p.
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http://dx.doi.org/10.1016/j.jaci.2021.01.002DOI Listing
May 2021

Operative Complications of Glaucoma Drainage Implant Tube Insertion Through the Sulcus for Pseudophakic Eye.

J Glaucoma 2021 Apr;30(4):e169-e174

Department of Ophthalmology, Juntendo University School of Medicine.

Precis: Malposition of the tube through the ciliary sulcus is more frequently observed with the Ahmed glaucoma valve (AGV) than the Baerveldt drainage implant (BDI) due to the weaker rigidity of the Ahmed tube.

Purpose: To report intraoperative and early postoperative complications of ciliary sulcus tube insertion of glaucoma drainage implants (GDIs).

Patients And Methods: We performed retrospective analysis of 104 eyes of 94 patients with GDI tube insertion through the ciliary sulcus were performed. The rigidities of tubes were also examined using a microcompression tester.

Results: The mean observation period was 20.0 (range, 6 to 60) months. Thirteen eyes were treated with the BDI and 91 were with the AGV. The mean age of the patients was 69.3 (34 to 90) years. The mean intraocular pressure was 27.9 mm Hg before surgery and 12.9 mm Hg after surgery (P<0.01). Upon tube insertion 42/91 eyes (46%) with the AGV required reinsertion of the tube due to malpositioning, whereas only 1/13 (8%) eyes with BDI did (P<0.01). Transient hyphema (12 eyes) and hypotony (12 eyes) were observed as early postoperative complications with the AGV. Seven eyes with hypotony were treated by proline stenting of the tube. We could not accomplish sulcus insertions in 4 eyes. Microcompression analysis of the tubes showed that the BGI tube was more rigid than that of the AGV.

Conclusions: Ciliary sulcus insertion of the tube is an effective method to control intraocular pressure. The tube of the AGV was more difficult to insert through the sulcus than the BDI due to its weaker rigidity.
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http://dx.doi.org/10.1097/IJG.0000000000001783DOI Listing
April 2021

Role of oncostatin M in the pathogenesis of vernal keratoconjunctivitis: focus on tissue remodeling.

Jpn J Ophthalmol 2021 Jan 6;65(1):144-153. Epub 2021 Jan 6.

Department of Ophthalmology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba, Japan.

Purpose: Vernal keratoconjunctivitis (VKC) is a severe and recurrent allergic conjunctivitis, the mechanism of which is not well understood. In this study, we investigated the role of oncostatin M (OSM) in the pathogenesis of VKC, with a focus on tissue remodeling.

Study Design: Clinical and experimental.

Patients And Methods: The OSM concentrations in tear fluid samples obtained from VKC patients and healthy controls were measured using ELISA, and the expression of OSM mRNA and protein in giant papillae resected from VKC patients was investigated using RT-PCR and immunohistochemistry, respectively. In cultured human conjunctival epithelial cells (HconEpiCs), expression of OSM receptor β (OSMRβ) was detected using immunocytochemical and FACS analyses. Finally, we investigated whether recombinant OSM activated STAT1 and STAT3 to induce the expression of various genes related to tissue remodeling in HconEpiCs, by using Western blot analysis, microarray analysis, and RT-PCR.

Results: The OSM concentration was higher in the tear fluid of VKC patients than in that of the healthy controls, and strong expression of OSM mRNA was found in the giant papillae. We also detected T cells expressing OSM in the giant papillae. In addition, HconEpiCs showed surface expression of OSMRβ. Recombinant human OSM strongly activated both STAT1 and STAT3 in HconEpiCs and induced various tissue remodeling-related genes, including MMP-1, MMP-3, IL-24, IL-20, serpinB3, S100A7, tenascin C, and SOCS3.

Conclusion: Our results suggest that OSM is one of the key molecules involved in remodeling of giant papillae in VKC.
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http://dx.doi.org/10.1007/s10384-020-00791-8DOI Listing
January 2021

Prognostic impact of peripheral blood mRNA expression levels in response to azacytidine in MDS: A single-centre analysis.

Leuk Res Rep 2021 8;15:100231. Epub 2020 Dec 8.

Department of Haemato-Oncology, Saitama International Medical Centre, Saitama Medical University, Hidaka, Saitama, Japan.

To determine the impact of peripheral blood (PB) () mRNA levels in patients with primary myelodysplastic syndromes (MDS), we analysed the relationships between several clinical variables at the time of diagnosis and the haematological response of patients treated with azacytidine. We observed overall responses in 20 (63%) patients; there were no significant differences in clinical variables, including bone marrow blast counts, IPSS scores and IPSS-R risk scores, between responders and non-responders. The responders' PB mRNA levels were significantly lower than those of non-responders ( = 0.03). PB mRNA expression could be a marker for predicting the response to azacytidine in patients with MDS.
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http://dx.doi.org/10.1016/j.lrr.2020.100231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744716PMC
December 2020

EVALUATION OF ORGAN DOSE BASED ON PATIENT DATA IN EAST ASIAN DESCENT PEDIATRIC HEAD CT EXAMINATIONS.

Radiat Prot Dosimetry 2020 Dec;192(3):335-340

Division of Clinical Radiology Service, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku Kyoto 606-8507, Japan.

The purpose of this study was to investigate other indices estimating absorbed dose for eye lens and brain, using clinical images of East Asian pediatric patients. We simulated head computed tomography (CT ) examinations in 104 pediatric patients. Effective diameter (deff) and water equivalent diameter (dw) were measured on clinical images. Various size metrics and age were compared with absorbed dose normalised by CTDIvol (nD). The nD was estimated for eye and brain. The nD tended to decrease with advancing age. R2 between age and nD were 0.38 and 0.31 for eye and brain, respectively. Increasing head diameters decreased each nD. R2 between deff and dw, and nD were 0.20-0.24 and 0.51-0.53 for eye and brain, respectively. Head sizes allowed us to estimate absorbed dose in brain CT on East Asian pediatric patients. Scanning parameters for pediatric head CT may need to be based on individual patient information.
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http://dx.doi.org/10.1093/rpd/ncaa200DOI Listing
December 2020

Eltrombopag in Combination with Rabbit Anti-thymocyte Globulin/Cyclosporine A in Immunosuppressive Therapy-naïve Patients with Aplastic Anemia in Japan.

Intern Med 2021 Apr 23;60(8):1159-1168. Epub 2020 Nov 23.

Department of Hematology, Kanazawa University Institute of Medical Pharmaceutical and Health Sciences, Japan.

Objective In Japan, immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG), and cyclosporine A (CsA) is the standard of care in patients with aplastic anemia (AA) who are not indicated for stem-cell transplantation, although some patients may experience relapse. This study assessed the efficacy and safety of eltrombopag in combination with rabbit-ATG/CsA in IST-naïve patients with non-severe or severe AA in Japan. Methods In this non-randomized, open-label, single-arm, phase II study, rabbit-ATG/CsA and eltrombopag were initiated on Days 1 and 15 (±3 days), respectively, and continued for ≥26 weeks; rabbit-ATG was given for 5 days (Days 1 to 5). The primary endpoint was the overall response rate (ORR) at Week 26. Patients Patients with AA who were IST-naïve and ≤70 years old or between 71 and 75 years old based on the recommendation of the investigator were enrolled in Japan. Results Of the 11 enrolled patients, 10 started treatment with eltrombopag. The ORRs at Weeks 26 and 52 were 70.0% and 60.0%, respectively. The ORR at Week 26 was 100% (all 3 patients) in patients with non-severe AA and 57.1% (4/7) in patients with severe AA. Among transfusion-dependent patients, 66.7% (4/6) and 62.5% (5/8) became red blood cell- and platelet-transfusion independent, respectively. The most common adverse events were nausea and headache. No deaths or hematologic malignancies were reported. A cytogenetic abnormality was reported in one patient. Conclusion This study confirmed the clinical benefit of eltrombopag plus rabbit-ATG/CsA in IST-naïve patients with non-severe or severe AA in Japan.
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http://dx.doi.org/10.2169/internalmedicine.6063-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112980PMC
April 2021

Experimental Mouse Models of Ragweed- and Papain-Induced Allergic Conjunctivitis.

Methods Mol Biol 2021 ;2223:133-149

Laboratory of System Biology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Mouse models of allergic conjunctivitis mimic various aspects of human allergic conjunctivitis. They are useful as acute models of allergic conjunctivitis to study immunological aspects of this condition. In this chapter, we will describe ragweed-pollen-induced experimental allergic conjunctivitis (mostly driven by adaptive immunity), and papain-soaked contact lens-induced experimental allergic conjunctivitis (mostly driven by innate immunity). Giemsa staining of histological sections is used for quantification of the number of infiltrating eosinophils, which is useful to evaluate the severity of the allergic inflammation. Immunohistochemical staining and quantitative PCR are used to clarify spatiotemporal expression of proinflammatory molecules in the conjunctival tissue. Flow cytometric analysis of conjunctival tissue is used for the detection of innate lymphoid cell type 2 (ILC2) in the ocular surface tissues.
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http://dx.doi.org/10.1007/978-1-0716-1001-5_10DOI Listing
March 2021

Antitumor Effect of Sugar-Modified Cytosine Nucleosides on Growth of Adult T-Cell Leukemia Cells in Mice.

Vaccines (Basel) 2020 Nov 5;8(4). Epub 2020 Nov 5.

Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.

Adult T-cell leukemia (ATL) is a CD4 T-cell neoplasm caused by human T-cell leukemia virus type I. As the prognosis for patients with ATL remains extremely poor due to resistance to conventional chemotherapy regimens, introduction of novel therapeutic agents is needed. Previous studies have reported that nucleosides 2'-deoxy-2'-methylidenecytidine (DMDC) and its derivative 2'-deoxy-2'-methylidene-5-fluorocytidine (FDMDC) exhibit antitumor activities in T-cell acute lymphoblastic leukemia (T-ALL) and solid tumor cell lines. Another nucleoside, 1-(2-azido-2-deoxy-β-D-arabinofuranosyl)cytosine (cytarazid), is considered a therapeutic drug with antitumor activity in human solid tumors. In this study, we investigated the effects of these nucleosides on cell growth in vitro and in vivo using relevant leukemia cell lines and NOD/Shi-, (NOG) mice, respectively. The nucleosides demonstrated significant cytotoxic effects in ATL and T-ALL cell lines. Intraperitoneal administration of FDMDC and DMDC into tumor-bearing NOG mice resulted in significant suppression of tumor growth without lethal side effects. Our findings support a therapeutic application of these nucleosides against tumor progression by targeting DNA polymerase-dependent DNA synthesis in patients with ATL.
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http://dx.doi.org/10.3390/vaccines8040658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712840PMC
November 2020

Efficacy and safety of romiplostim in refractory aplastic anaemia: a Phase II/III, multicentre, open-label study.

Br J Haematol 2021 01 5;192(1):190-199. Epub 2020 Nov 5.

Division of Transfusion Medicine, Kanazawa University Hospital, Kanazawa, Japan.

A previous dose-finding study has suggested that romiplostim is effective in patients with refractory aplastic anaemia (AA) and 10 µg/kg once weekly was recommended as a starting dose. In this Phase II/III, multicentre, open-label study, romiplostim was administered subcutaneously at a fixed dose of 10 µg/kg once weekly for 4 weeks (weeks 1-4) followed by weekly doses (5, 10, 15 and 20 µg/kg) titrated by platelet response for up to 52 weeks (weeks 5-52). A total of 31 patients with AA who were refractory to immunosuppressive therapy (IST) and thrombocytopenia (platelet count of ≤30 × 10 /l) were enrolled. The primary efficacy endpoint of the proportion of patients achieving any haematological (platelet, neutrophil and erythrocyte) response at week 27 was 84% [95% confidence interval (CI) 66-95%]. Trilineage response was 39% (95% CI 22-58%) at week 53. The most common treatment-related adverse events (AEs) were headache and muscle spasms (each 13%). All AEs were mild or moderate except for three patients with Grade 3 hepatic AEs; no AEs necessitated romiplostim discontinuation. Two patients developed cytogenetic abnormalities, of whom one returned to normal karyotype at last follow-up. High-dose romiplostim is effective and well tolerated in the treatment of patients with AA refractory to IST.
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http://dx.doi.org/10.1111/bjh.17190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821109PMC
January 2021

Usefulness of model-based iterative reconstruction in low-dose lumbar spine CT after spine surgery with metal implant: a phantom study.

Acta Radiol 2020 Oct 5:284185120961424. Epub 2020 Oct 5.

Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Background: The major problems of computed tomography (CT) imaging include radiation exposure and severe artifacts caused by operative implants.

Purpose: To evaluate the usefulness of the metal artifact reduction algorithm and model-based iterative reconstruction (MBIR) in postoperative low-dose (LD) spine CT.

Material And Methods: A CT torso phantom was scanned at standard-dose (SD) and LD settings. The CT images were reconstructed by three methods: hybrid iterative reconstruction (HIR); metal artifact reduction; and MBIR. The radiation dose of the phantom imaging was evaluated by volume CT dose index (mGy), dose length product (DLP, mGy × cm), and effective dose (mSv). The image quality of the six images was visually evaluated and analyzed using Scheffe's paired comparison method. The average preference of each method was calculated based on the comparative scores. The task transfer function (TTF) and noise power spectrum for HIR and MBIR were also measured.

Results: The respective radiation-dose-related parameters of the SD and LD conditions were: volume CT dose index = 10.2 and 1.2 mGy; DLP = 277.9 and 33.9 mGy × cm; and effective dose = 4.2 and 0.5 mSv. The average preference for diagnostic acceptability of MBIR at LD was not significantly different from the other reconstructions of SD data. MBIR successfully reduced metal artifacts in the LD condition. The 10% TTF was higher for HIR at SD and higher for MBIR at LD.

Conclusion: MBIR is useful for LD spine CT after spine surgery with metal implant.
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http://dx.doi.org/10.1177/0284185120961424DOI Listing
October 2020

Critical role of IL-33, but not IL-25 or TSLP, in silica crystal-mediated exacerbation of allergic airway eosinophilia.

Biochem Biophys Res Commun 2020 12 22;533(3):493-500. Epub 2020 Sep 22.

Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima, 739-8528, Japan; Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama, 332-0012, Japan. Electronic address:

Silica crystals (silica), which are a major mineral component of volcanic ash and desert dust, contribute to the pathogenesis of pulmonary disorders such as asthma and fibrosis. Although administration of silica or sand dust to rodents exacerbates development of ovalbumin-induced or house dust mite-induced asthma-like airway inflammation, the detailed mechanisms remain unclear. Here, using murine models, we found that silica can induce IL-33 expression in pulmonary epithelial cells. IL-33, but not IL-25 or TSLP, and type 2 cytokines such as IL-5 and IL-13 were critically involved in silica's exacerbation of OVA-induced airway eosinophilia in mice. Innate lymphoid cells (ILCs), but not T, B or NKT cells, were also involved in the setting. Moreover, a scavenger receptor that recognized silica was important for silica's exacerbating effect. These observations suggest that IL-33 induced in epithelial cells by silica activates ILCs to produce IL-5 and/or IL-13, contributing to silica's exacerbation of OVA-induced airway eosinophilia in mice. Our findings provide new insight into the underlying mechanisms of exacerbation of pulmonary disorders such as asthma following inhalation of silica-containing materials such as volcanic ash and desert dust.
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http://dx.doi.org/10.1016/j.bbrc.2020.09.046DOI Listing
December 2020

Alteration of gene expression in mice after glaucoma filtration surgery.

Sci Rep 2020 09 14;10(1):15036. Epub 2020 Sep 14.

Laboratory of Ocular Atopic Diseases, Department of Ophthalmology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan.

To clarify the early alterations of gene expression using a mouse model of glaucoma filtration surgery, we carried out microarray expression analysis. Using BALB/c mice, a filtration surgery model was made by incision of the limbal conjunctiva, followed by the insertion of a 33G needle tip into the anterior chamber, and 11-0 nylon sutures. Subgroups of mice were treated intraoperatively with 0.4 mg/ml mitomycin-C (MMC). At day 3 after surgery the bleb was maintained. The bleb region tissue was sampled 3 days after the filtration surgery, and gene expression analysis was carried out using a mouse Agilent 8 × 60 K array. We found 755 hyperexpressed transcripts in the bleb region compared to control conjunctiva. The hyperexpressed transcripts included epithelial cell metaplasia-related (Il1b, Krt16, Sprr1b), inflammation-related (Ccl2, Il6) and wound healing-related (Lox, Timp1) genes. We also found downregulation of a goblet cell marker gene (Gp2) in the bleb conjunctiva. MMC treatment suppressed elastin (Eln) gene expression and enhanced keratinization-related gene expression (Krt1, Lor) in the bleb region. Our results suggest the importance of epithelial wound healing after filtration surgery, and this filtration surgery model will be a useful tool for further pathophysiological analysis.
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http://dx.doi.org/10.1038/s41598-020-72036-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490364PMC
September 2020

Establishment and characterization of a canine sebaceous epithelial cell line derived from an eyelid mass.

J Vet Med Sci 2020 Nov 11;82(11):1577-1584. Epub 2020 Sep 11.

Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoinooka, Imabari, Ehime 794-8555, Japan.

Little is known about the pathological roles of sebaceous glands in canine skin diseases, as most examinations have been conducted with cultured human sebaceous epithelial cell lines. To our knowledge, there is no available canine sebaceous epithelial cell line. The purpose of this study was to establish a canine sebaceous epithelial cell line and characterize it. An eyelid mass in a dog was surgically resected for treatment, and it was histologically diagnosed as sebaceous epithelioma. Collected tissue was conducted for culture, and the growing epithelial-like cells were passaged. The cells showed continuous proliferation for over 6 months. After 40 passages, the cells were named CMG-1. Lipid droplets in the cytoplasm of CMG-1 cells were confirmed by Oil Red O staining. As reported in studies with human sebaceous epithelial cell lines, lipogenesis in CMG-1 cells was promoted by linoleic acid, whereas transforming growth factor-β (TGF-β) suppressed it. Additionally, real-time PCR revealed that the expression levels of chemokines and cytokines, including CC chemokine ligand (CCL)-2, CCL-20, CXCL-10, Tumor necrosis factor-α (TNF-α), Interleukin (IL)-1α, IL-1β, and IL-8, were significantly increased in CMG-1 cells following treatment with lipopolysaccharide. In conclusion, we successfully established a new canine sebaceous epithelial cell line. Our data indicated that lipogenesis and inflammatory responses were quantitatively evaluable in this cell line. CMG-1 cells could be useful for the pathological analysis of sebaceous gland diseases in dogs.
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http://dx.doi.org/10.1292/jvms.20-0179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719885PMC
November 2020

Assessment of dysplasia in bone marrow smear with convolutional neural network.

Sci Rep 2020 09 7;10(1):14734. Epub 2020 Sep 7.

Department of Hemato-Oncology, International Medical Center, Saitama Medical University, Saitama, Japan.

In this study, we developed the world's first artificial intelligence (AI) system that assesses the dysplasia of blood cells on bone marrow smears and presents the result of AI prediction for one of the most representative dysplasia-decreased granules (DG). We photographed field images from the bone marrow smears from patients with myelodysplastic syndrome (MDS) or non-MDS diseases and cropped each cell using an originally developed cell detector. Two morphologists labelled each cell. The degree of dysplasia was evaluated on a four-point scale: 0-3 (e.g., neutrophil with severely decreased granules were labelled DG3). We then constructed the classifier from the dataset of labelled images. The detector and classifier were based on a deep neural network pre-trained with natural images. We obtained 1797 labelled images, and the morphologists determined 134 DGs (DG1: 46, DG2: 77, DG3: 11). Subsequently, we performed a five-fold cross-validation to evaluate the performance of the classifier. For DG1-3 labelled by morphologists, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 91.0%, 97.7%, 76.3%, 99.3%, and 97.2%, respectively. When DG1 was excluded in the process, the sensitivity, specificity, PPV, NPV, and accuracy were 85.2%, 98.9%, 80.6%, and 99.2% and 98.2%, respectively.
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http://dx.doi.org/10.1038/s41598-020-71752-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477564PMC
September 2020

Proline-assisted Tube Insertion Through Sulcus in Ahmed Valve.

J Glaucoma 2020 09;29(9):e106-e107

Department of Ophthalmology, Juntendo University School of Medicine, Tokyo.

To prevent corneal endothelial cell loss, ciliary sulcus tube insertion is preferred for the pseudophakic eye. However, we sometimes encounter technical difficulties when inserting the tube through the sulcus. Even in cases in which we are able to insert a 23-G needle through the sulcus into the space between the iris and intraocular lens, the tube of Ahmed valve may stray into the vitreous cavity or under Elschnig pearls. To remedy such conditions, we developed a new tube insertion method using a 4-0 proline stent as a guide to insert the tube in the appropriate position.
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http://dx.doi.org/10.1097/IJG.0000000000001602DOI Listing
September 2020

Leukotriene B receptors as therapeutic targets for ophthalmic diseases.

Biochim Biophys Acta Mol Cell Biol Lipids 2020 09 11;1865(9):158756. Epub 2020 Jun 11.

Department of Biochemistry, Juntendo University Graduate School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, Japan. Electronic address:

Leukotriene B (LTB) is an inflammatory lipid mediator produced from arachidonic acid by multiple reactions catalyzed by two enzymes 5-lipoxygenase (5-LOX) and LTA hydrolase (LTAH). The two receptors for LTB have been identified: a high-affinity receptor, BLT1, and a low-affinity receptor, BLT2. Our group identified 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (12-HHT) as a high-affinity BLT2 ligand. Numerous studies have revealed critical roles for LTB and its receptors in various systemic diseases. Recently, we also reported the roles of LTB, BLT1 and BLT2 in the murine ophthalmic disease models of mice including cornea wound, allergic conjunctivitis, and age-related macular degeneration. Moreover, other groups revealed the evidence of the ocular function of LTB. In the present review, we introduce the roles of LTB and its receptors both in ophthalmic diseases and systemic inflammatory diseases. LTB and its receptors are putative novel therapeutic targets for systemic and ophthalmic diseases.
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http://dx.doi.org/10.1016/j.bbalip.2020.158756DOI Listing
September 2020

Indolent T-cell lymphoproliferative disorder of the stomach successfully treated by radiotherapy.

J Clin Exp Hematop 2020 ;60(1):7-10

Department of Hematology, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Hidaka, Saitama, Japan.

Successful treatment of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (ITLPDGI) by chemotherapy is rare and watchful waiting is often performed for asymptomatic patients. We report a case of ITLPDGI successfully treated by involved field radiotherapy (IFRT). The patient presented with slow ITLPDGI localised to the stomach with mild symptoms. IFRT (30 Gy/20f) was administered, after which endoscopy revealed resolution of lesions and blood vessel appearance, and absence of proliferating abnormal lymphocytes was confirmed by biopsy. The patient remains lymphoma-free 1 year post-treatment. Although long-term follow-up and additional cases are essential for the evaluation of IFRT as a treatment option for localised ITLPDGL, complete remission after relatively low-dose IFRT is promising, particularly as this has been rarely achieved by chemotherapy.
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http://dx.doi.org/10.3960/jslrt.19022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187675PMC
January 2021

The Gene Is Activated to Alleviate Mutagenesis by an Oxidized Deoxynucleoside.

Front Microbiol 2020 25;11:263. Epub 2020 Feb 25.

Department of Chemistry, Bioscience and Environmental Technology, Centre for Organelle Research, Faculty of Science and Technology, University of Stavanger, Stavanger, Norway.

The cellular methyl donor -adenosylmethionine (SAM) and other endo/exogenous agents methylate DNA bases non-enzymatically into products interfering with replication and transcription. An important product is 3-methyladenine (mA), which in is removed by mA-DNA glycosylase I (Tag) and II (AlkA). The gene is constitutively expressed, while is induced by sub-lethal concentrations of methylating agents. We previously found that AlkA exhibits activity for the reactive oxygen-induced thymine (T) lesion 5-formyluracil (fU) . Here, we provide evidence for AlkA involvement in the repair of oxidized bases by showing that the adenine (A) ⋅ T → guanine (G) ⋅ cytosine (C) mutation rate increased 10-fold in wild-type and cells exposed to 0.1 mM 5-formyl-2'-deoxyuridine (fdU) compared to a wild-type specific reduction of the mutation rate at 0.2 mM fdU, which correlated with gene induction. G⋅C → A⋅T alleviation occurred without induction (at 0.1 mM fdU), correlating with a much higher AlkA efficiency for fU opposite to G than for that to A. The common keto form of fU is the AlkA substrate. Mispairing with G by ionized fU is favored by its exclusion from the AlkA active site.
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http://dx.doi.org/10.3389/fmicb.2020.00263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051996PMC
February 2020

Peripheral T-cell lymphoma with gastrointestinal involvement and indolent T-lymphoproliferative disorders of the gastrointestinal tract.

Leuk Res 2020 04 29;91:106336. Epub 2020 Feb 29.

Departments of Haematology, International Medical Centre, Saitama Medical University, Hidaka, Saitama, Japan.

The 2017 WHO classification includes a new provisional entity of indolent T-lymphoproliferative disorders of the gastrointestinal tract (ITLPD-GIT). We investigated GI involvement of peripheral T-cell lymphoma (PTCL). Eighty-two patients were diagnosed with PTCL during 2007-2017. Eleven patients (13 %) had histologically-confirmed GI tract involvement {3 monomorphic epitheliotropic intestinal lymphoma (MEITL), 3 extranodal NK-/T-cell lymphoma nasal type (ENKL), 2 PTCL, not otherwise specified, 1 adult T-cell leukemia-lymphoma, 2 ITLPD-GIT}. Three patients each had lesions in the small intestine and multiple lesions, two each in the stomach and colon, and one in the duodenum. Six of the 11 patients remained alive. No perforation/stenosis was observed after chemo-radiotherapy, although one patient with ENKL developed gastric bleeding during chemotherapy. One patient with ITLPD-GIT (CD4/CD8/Ki67) with a colonic lesion showing diffuse edema and multiple aphtha by endoscope and diarrhea, initially diagnosed with MEITL, had active but stable disease after various chemotherapies for 1 year and no therapy for the next 5 years. Another patient with ITLPD-GIT (CD4/CD8/Ki67) with a localized gastric lesion and slight epigastralgia was in remission for 1 year after radiation. In conclusion, about 10 % of PTCLs were complicated by GI tract lesions and most had a poor prognosis. ITLPD-GIT should be considered as a differential diagnosis based on histology and clinical course. Local complications after chemo/radiotherapy in PTCL with GI involvement were not frequent.
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http://dx.doi.org/10.1016/j.leukres.2020.106336DOI Listing
April 2020

Repair of DNA damage induced by the novel nucleoside analogue CNDAG through homologous recombination.

Cancer Chemother Pharmacol 2020 04 18;85(4):661-672. Epub 2020 Feb 18.

Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77054, USA.

Purpose: We postulate that the deoxyguanosine analogue CNDAG [9-(2-C-cyano-2-deoxy-1-β-D-arabino-pentofuranosyl)guanine] likely causes a single-strand break after incorporation into DNA, similar to the action of its cytosine congener CNDAC, and that subsequent DNA replication across the unrepaired nick would generate a double-strand break. This study aimed at identifying cellular responses and repair mechanisms for CNDAG prodrugs, 2-amino-9-(2-C-cyano-2-deoxy-1-β-D-arabino-pentofuranosyl)-6-methoxy purine (6-OMe) and 9-(2-C-cyano-2-deoxy-1-β-D-arabino-pentofuranosyl)-2,6-diaminopurine (6-NH). Each compound is a substrate for adenosine deaminase, the action of which generates CNDAG.

Methods: Growth inhibition assay, clonogenic survival assay, immunoblotting, and cytogenetic analyses (chromosomal aberrations and sister chromatid exchanges) were used to investigate the impact of CNDAG on cell lines.

Results: The 6-NH derivative was selectively potent in T cell malignant cell lines. Both prodrugs caused increased phosphorylation of ATM and its downstream substrates Chk1, Chk2, SMC1, NBS1, and H2AX, indicating activation of ATM-dependent DNA damage response pathways. In contrast, there was no increase in phosphorylation of DNA-PKcs, which participates in repair of double-strand breaks by non-homologous end-joining. Deficiency in ATM, RAD51D, XRCC3, BRCA2, and XPF, but not DNA-PK or p53, conferred significant clonogenic sensitivity to CNDAG or the prodrugs. Moreover, hamster cells lacking XPF acquired remarkably more chromosomal aberrations after incubation for two cell cycle times with CNDAG 6-NH, compared to the wild type. Furthermore, CNDAG 6-NH induced greater levels of sister chromatid exchanges in wild-type cells exposed for two cycles than those for one cycle, consistent with increased double-strand breaks after a second S phase.

Conclusion: CNDAG-induced double-strand breaks are repaired mainly through homologous recombination.
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http://dx.doi.org/10.1007/s00280-020-04035-xDOI Listing
April 2020

A case series of adult T-cell leukemia-lymphoma, associated with human T-cell leukemia virus type-1, at a single center in a non-viral-endemic metropolitan area.

J Clin Exp Hematop 2019 ;59(3):108-111

We examined 13 patients with adult T-cell leukemia-lymphoma (ATL) diagnosed between 2007 and 2018 at a single center in a metropolitan area non-endemic for human T-cell leukemia virus type I (HTLV-1). The median age of the patients (eight male, five female) was 65 years (range, 48-83). The time from onset of symptoms to referral to our center was relatively short (median, 2 months; range, 1-9 months). Upon referral, all patients were suspected to have lymphoma, five were examined for soluble IL-2 receptor and two were examined for anti-HTLV-1 antibody. In ten of the 13 (77%), the patient themselves or their relatives were born in Kyushu. The birth places of the remaining three patients were unknown. Three patients (23%) had family histories of lymphoma. They all exhibited aggressive ATL (five acute, eight lymphoma type); however, the disease status was generally stable, with relatively stable performance status and low scores for prognostic indices. After combination chemotherapy, eight (62%) achieved remission. However, long-term remission was achieved in only one patient with localized lymphoma-type ATL and one young patient after allogeneic hematopoietic stem cell transplantation. In conclusion, at a center in a metropolitan and HTLV-1 non-endemic area in Japan, patients with ATL were relatively young and mainly presented with aggressive subtypes. At initial referral to our center, all 13 patients were suspected of having lymphoma but only two of having ATL. For centers in similar areas of Japan, prompt diagnosis and appropriate treatment of ATL patients will become increasingly necessary following the recent migration of HTLV-1 carriers to non-endemic areas.
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http://dx.doi.org/10.3960/jslrt.19001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798142PMC
February 2020

Nucleoside analogs as a radiosensitizer modulating DNA repair, cell cycle checkpoints, and apoptosis.

Nucleosides Nucleotides Nucleic Acids 2020 27;39(1-3):439-452. Epub 2019 Sep 27.

Laboratory of Radiation Biology, Department of Applied Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.

The combination of low dose of radiation and an anticancer drug is a potent strategy for cancer therapy. Nucleoside analogs are known to have a radiosensitizing effects via the inhibition of DNA damage repair after irradiation. Certain types of nucleoside analogs have the inhibitory effects on RNA synthesis, but not DNA synthesis, with multiple functions in cell cycle modulation and apoptosis. In this review, the most up-to-date findings regarding radiosensitizing nucleoside analogs will be discussed, focusing especially on the mechanisms of action.
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http://dx.doi.org/10.1080/15257770.2019.1670839DOI Listing
September 2020

Optimal Cutoff Value of Fractional Flow Reserve Derived From Coronary Computed Tomography Angiography for Predicting Hemodynamically Significant Coronary Artery Disease.

Circ Cardiovasc Imaging 2019 08 1;12(8):e008905. Epub 2019 Aug 1.

Department of Cardiovascular Medicine (Y.M.-N., H.S., K. Kitano, M.Y., H.W., J.T., T. Kato, N.S., S.S., K.O., T. Kimura), Kyoto University Graduate School of Medicine, Japan.

Background: The optimal cutoff value of fractional flow reserve (FFR) derived from coronary computed tomography angiography (FFR) remains unclear.

Methods: The current study population consisted of 93 patients with 139 vessels, who had suspected coronary artery disease by computed tomography angiography and underwent invasive FFR. We evaluated diagnostic performance of FFR according to different FFR cutoff values and FFR ranges with invasive FFR ≤0.80 as the reference standard.

Results: In per-vessel analysis, median invasive FFR was 0.85 (interquartile range, 0.75-0.90), and 57 out of 139 vessels (41%) showed hemodynamically significant stenosis (≤0.80). Median FFR was 0.77 (interquartile range, 0.66-0.84; mean difference [invasive FFR-FFR], 0.06±0.11). Per-vessel accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 73%, 95%, 59%, 61%, and 94% for the cutoff value of FFR ≤0.80, 81%, 86%, 78%, 73%, and 89% for FFR ≤0.75, and 83%, 74%, 89%, 82%, and 83% for FFR ≤0.70, respectively. Per-vessel accuracy across the different ranges of FFR ≤0.60, 0.61 to 0.70, 0.71 to 0.80, 0.81 to 0.90, and >0.90 with the cutoff value of FFR ≤0.80 were 95%, 74%, 32%, 93%, and 100%, respectively. Setting a gray zone of FFR 0.71 to 0.80 provided high positive predictive value (82%; n=42/51) in the range of FFR ≤0.70 and high negative predictive value (94%; n=48/51) in FFR >0.80.

Conclusions: This study suggested that referral to invasive coronary angiography should be considered individually in the range of FFR 0.71 to 0.80, whereas dichotomous decision could be made in FFR ≤0.70 and >0.80. Future prospective studies evaluating clinical outcomes are needed to establish optimal FFR-based diagnostic algorithm.
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http://dx.doi.org/10.1161/CIRCIMAGING.119.008905DOI Listing
August 2019

Survival of Alpha and Intrinsically Photosensitive Retinal Ganglion Cells in NMDA-Induced Neurotoxicity and a Mouse Model of Normal Tension Glaucoma.

Invest Ophthalmol Vis Sci 2019 09;60(12):3696-3707

Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

Purpose: We assess if α retinal ganglion cells (αRGCs) and intrinsically photosensitive retinal ganglion cells (ipRGCs) survive in mouse models of glaucoma.

Methods: Two microliters of N-methyl-D-aspartate (NMDA; 1 mM) or PBS were injected intraocularly 7 days before sacrifice. Immunohistochemical analyses of the retina were performed using antibodies against RNA-binding protein with multiple splicing (RBPMS), osteopontin, and melanopsin. Immunohistochemical analyses also were performed in adult mice with glutamate/aspartate transporter (GLAST) deletion (GLAST knockout [KO] mice), a mouse model of normal tension glaucoma.

Results: NMDA-induced loss of RBPMS-positive total RGCs was 58.4% ± 0.4% compared to PBS-treated controls, whereas the loss of osteopontin-positive αRGCs was 5.0% ± 0.6% and that of melanopsin-positive ipRGCs was 7.6% ± 1.6%. In GLAST KO mice, the loss of total RGCs was 48.4% ± 0.9% compared to wild-type mice, whereas the loss of αRGCs and ipRGCs was 3.9% ± 0.4% and 9.3% ± 0.5%, respectively. The distribution of survived total RGCs, αRGCs, and ipRGCs was similar regardless of the location of the retina.

Conclusions: These results suggest that αRGC and ipRGC are highly tolerant to NMDA-induced neurotoxicity and NTG-like neurodegeneration in GLAST KO mice.
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http://dx.doi.org/10.1167/iovs.19-27145DOI Listing
September 2019

The roles of omega-3 fatty acids and resolvins in allergic conjunctivitis.

Curr Opin Allergy Clin Immunol 2019 10;19(5):517-525

Department of Ophthalmology.

Purpose Of Review: Lipids are one of the most important constituents in our body. Advances of lipidomics are elucidating the new roles of various lipid molecules in allergic diseases. For example, some reports showed anti-inflammatory effects of omega-3 fatty acids (FAs), such as docosahexaenoic acid, eicosapentaenoic acid, and their metabolites, on allergic diseases. Here, we introduce the role of lipid mediators in allergic conjunctivitis mouse model.

Recent Findings: Lipidomics using liquid chromatography-tandem mass spectrometry can profile numerous lipid molecules from small tissue samples such as conjunctival specimens. Lipidomics analysis showed that various inflammatory lipid mediators are produced in the conjunctival tissue of allergic conjunctivitis mouse model. Dietary omega-3 FAs reduced these inflammatory lipid mediators in the conjunctiva and alleviated allergic conjunctivitis symptoms in mouse models. In addition, the roles of specialized proresolving lipid mediators (SPMs) have been reported for allergic inflammation.

Summary: Lipid mediators have important roles for the pathophysiology of the allergic diseases including allergic conjunctivitis. Omega-3 FAs and SPMs are expected as new treatment tools for allergic conjunctivitis.
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http://dx.doi.org/10.1097/ACI.0000000000000561DOI Listing
October 2019