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Involvement of autotaxin in the pathophysiology of elevated intraocular pressure in Posner-Schlossman syndrome

Nozomi Igarashi, Megumi Honjo, Reiko Yamagishi, Makoto Kurano, Yutaka Yatomi, Koji Igarashi, Toshikatsu Kaburaki, Makoto Aihara
2020 Scientific Reports  
To examine whether autotaxin (ATX) in the aqueous humor causes elevated intraocular pressure (IOP) in patients with Posner-Schlossman syndrome (PSS). ATX and transforming growth factor beta (TGF-β) in the aqueous humor were quantified in PSS patients. The expression of ATX and TGF-β in cytomegalovirus (CMV)-infected-human trabecular meshwork (hTM) cells was examined. Biological changes in hTM cells and monkey Schlemm's canal endothelial (SCE) cells cultured in the conditioned medium of
more » ... ted hTM cells were analyzed. The expression of ATX and TGF-β1 was upregulated in the aqueous humor of CMV-positive PSS patients, and the level of ATX in the aqueous humor was positively correlated with IOP. CMV infection upregulated ATX and TGF-β1 in hTM cells. The conditioned medium induced fibrotic changes in hTM cells and reduced SCE permeability, which was attenuated by an ATX inhibitor, a lysophosphatidic acid receptor antagonist, and a Rho kinase inhibitor. ATX in the aqueous humor induced by CMV infection may trigger elevated IOP. Modulating ATX activity may be a novel treatment modality for PSS.
doi:10.1038/s41598-020-63284-1 pmid:32286414 pmcid:PMC7156668 fatcat:dmkxnjskx5arrpxti6sz4emtcy

Studied under the Drinking Behaviors about Parents and Children

Matsuko Harada, Aiko Higashi, Chiyoko Shimokawa, Noriko Sekiguchi, Eiko Kato, Reiko Saito, Masue Igarashi, Reiko Mitsuishi
2000 Journal for the Integrated Study of Dietary Habits  
We used female students(junior high,high school,and college)and their parents as subjects and assessed the eating behavior of the parents and children by investigating the passing down of drinking behavir(in the broad sense),preferences and drinking behavior (in the narrow sense:drinks or does not drink beverages),food habits(skipping breakfast/between meal types),degree of obesity,awareness of obesity,symptoms,and number of bottles ingested,and the following results were obtained. 1)Beverages
more » ... ften drunk by both parents and children consisted of green tea,oolong tea,and milk,while sweet beverages,i.e.,fruit juice beverages,lactobacillus beverages, coffee,black tea(suger added),cola,carbonated beverages,and isotonic beverages were drunk in the following order:mothersfather,2)sweet beverages and isotonic drinks,for junior high school students, high school students,and college students:child>father and mother,and in every instance the differences were significant. 3)The results for the junior high school students showed that the parents and children drank several types of beverages within the home,and the proportion of all of the mothers who drank cola and black tea(with/without suger)at home because they enjoyed them was high.The beverages that were drunk by each of the age brackets at home and
doi:10.2740/jisdh.11.223 fatcat:3lyzjb7fubdktfs3ak7yakmpgm

Studied under the Drinking Behaviors about Parents and Children

Matsuko Harada, Noriko Sekiguchi, Eiko Kato, Aiko Higashi, Reiko Saito, Chiyoko Shimokawa, Masue Igarashi, Toshiko Soegima, Reiko Mitsuishi, Hirofumi Takagi
1997 Journal for the Integrated Study of Dietary Habits  
Masue Igarashi Similarities and differences between parents and children in beverage drinking behavior and preferences were investigated using female college students and their parents as subjects, yielding  ... 
doi:10.2740/jisdh.8.3_48 fatcat:vrgtwn2gtrhx7npelto5ufplxy

A Studied on Drinking Behaviors about Parents and Chidren

Noriko Sekiguchi, Matsuko Harada, Aiko Higashi, Reiko Saito, Eiko Kato, Chiyoko Shimokawa, Masue Igarashi, Toshiko Soegima, Reiko Mitsuishi, Hirofumi Takagi
1998 Journal for the Integrated Study of Dietary Habits  
The actual status of beverage drinking behavior and preferences was investigated in female senior high school students and their parents,and the similarities and differences between parents and children were assessed.The results are outlined below. A high percentage of all three,i.e.,the student and both parents,drink green tea/oolong tea and milk.The female senior high school students drink much more fruit juices,lactic acid bacteria beverages,cola drinks/carbonated beverages,coffee/tea (with
more » ... ugar),isotonic beverages,and dietary fiber beverages.They also drink a greater volume per day and usually drink several different kinds of beverages.In addition,they drink these beverages inside and outside the home; often drinking lactic acid bacteria beverages and fruit juices at mealtime,and cola drinks/carbonated beverages and isotonic beverages at any time during the day,at mealtimes and at other times.In terms of preferences,the female senior high school students often liked beverages other than vegetable juices more,and many more cited "preference,"preference,""physiology,""custom,"and
doi:10.2740/jisdh.9.39 fatcat:tuuablizkbfehgk5aj5wcizofm

A Study on Drinking Behaviors about Parents and Children

Eiko Kato, Matsuko Harada, Noriko Sekiguchi, Aiko Higashi, Reiko Saito, Chiyoko Shimokawa, Masue Igarashi, Toshiko Soegima, Reiko Mitsuishi, Hirofumi Takagi
1998 Journal for the Integrated Study of Dietary Habits  
doi:10.2740/jisdh.9.52 fatcat:ztz4g3mkarhyvhp7266nl7knr4

Crosstalk between transforming growth factor β-2 and Autotaxin in trabecular meshwork and different subtypes of glaucoma

Nozomi Igarashi, Megumi Honjo, Reiko Yamagishi, Makoto Kurano, Yutaka Yatomi, Koji Igarashi, Toshikatsu Kaburaki, Makoto Aihara
2021 Journal of Biomedical Science  
Expression levels of COL1A1, fibronectin, and α-SMA were enhanced upon ATX stimulation, and these changes were significantly suppressed by treatment with either TGF-β inhibitor or ATX inhibitor (D, E, and F) Igarashi  ... 
doi:10.1186/s12929-021-00745-3 pmid:34140021 fatcat:ngjsgyq5tfgvtjoh7zkd3rujfi

Infant-directed speech as a window into the dynamic nature of phonology

Reiko Mazuka, Yosuke Igarashi, Andrew Martin, Akira Utsugi
2015 Laboratory Phonology  
Igarashi et al.'  ...  Analyses To test this prediction, Igarashi et al. (2013) analyzed speech from 21 of 22 mothers in R-JMICC.  ... 
doi:10.1515/lp-2015-0009 fatcat:obji26hep5ahbfeoha2lcezl5u

Whipple disease mimicking inflammatory bowel disease

Maiko Tatsuki, Takashi Ishige, Yoshiko Igarashi, Reiko Hatori, Akira Hokama, Junko Hirato, Aleixo Muise, Takumi Takizawa, Hirokazu Arakawa
2020 Intestinal Research  
Whipple disease is a systemic chronic infection caused by Tropheryma whipplei. Although chronic diarrhea is a common gastrointestinal symptom, diagnosis is often difficult because there are no specific endoscopic findings, and the pathogen is not detectable by stool culture. We present a female patient with Whipple disease who developed chronic bloody diarrhea and growth retardation at the age of 4 years. Colonoscopy showed a mildly edematous terminal ileum and marked erythema without vascular
more » ... atterns throughout the sigmoid colon and rectum. Subsequently, a primary diagnosis of ulcerative colitis was made. Histopathological analysis of the terminal ileum showed the presence of foamy macrophages filled with periodic acidSchiff-positive particles. Polymerase chain reaction using DNA from a terminal ileum biopsy sample amplified a fragment of 16S rRNA from T. whipplei. Antibiotic treatment relieved the patient's symptoms. There was no evidence of immunodeficiency in the present case. Since Whipple disease worsens after anti-tumor necrosis factor inhibitor therapy, considering this infection in the differential diagnosis may be important in patients with inflammatory bowel disease, especially before initiation of immunotherapy.
doi:10.5217/ir.2019.09177 pmid:32610889 pmcid:PMC7873397 fatcat:id6t2a7mgzekpnada2ux5o4k7y

Novel Betacellulin Derivatives

Takashi Itoh, Mitsuyo Kondo, Yoko Tanaka, Masayuki Kobayashi, Reiko Sasada, Kouichi Igarashi, Masato Suenaga, Nobuyuki Koyama, Osamu Nishimura, Masahiko Fujino
2001 Journal of Biological Chemistry  
Betacellulin (BTC) is a member of the epidermal growth factor family. It has two biological activities: mitogenic activity in fibroblasts and vascular smooth muscle cells, and differentiation activity for the differentiation of pancreatic acinar AR42J cells into insulinsecreting cells. The previous finding that recombinant BTC promotes the neogenesis of ␤-cells in a mouse model supports the possibility that BTC is a therapeutic protein. However, the mitogenic activity of BTC may not be needed
more » ... r differentiation into ␤-cells and may cause a side effect in clinical use. We prepared several derivatives of BTC to segregate the two activities, to decrease the mitogenic activity, and to maintain the differentiation activity. We succeeded in obtaining BTC derivatives segregated by the two biological activities by preparing truncated-type derivatives. A derivative of BTC, BTC24 -76, with a truncated N-terminal 23 amino acids and C-terminal 4 amino acids, was 2.5-fold more active in differentiation and had one-tenth of the mitogenic activity. The derivatives described in the present study should be helpful in future applications as therapeutic proteins and in basic research for discovery of a BTCspecific receptor.
doi:10.1074/jbc.m106603200 pmid:11522793 fatcat:hkorrp6hkfdyjllpjvcz6m635u

The establishment of IL-2 producing cells by genetic engineering

Reiko Sasada, Haruo Onda, Koichi Igarashi
1987 Cell Structure and Function  
Expression plasmids containing human interleukin-2(IL-2) cDNA under the control of viral promoters (SV40 early region, MuLV LTR, HTLV-I LTR, and ASV(Y73) LTR) were introduced into TK-mouse L cells and human FL cells to establish IL-2 producing cells. The highest levels of IL-2 producing clones were obtained in TK+ mouse L cells transformed with a recombinant plasmid having MuLV LTR as a promoter, whereas transformed cells of human FL cells (G418r) were revealed to produce IL-2 at the highest
more » ... el when the cells were transfected with a plasmid containing HTLV LTR as a promoter. These results suggest that these promoter/enhancer regions possess different cell specificities in gene expression. To obtain higher levels of IL-2 production using gene amplification, the hybrid plasmids containing the hamster DHFR and human IL-2 genes were constructed and transfected into DHFR-CHO cells. DHFR+ colonies produced IL-2 at about the same level as that produced by TK+ L cells transformed with the recombinants containing MuLV LTR. Selection of methotrexate-resistant cells resulted in a 5-to 30-fold increase of IL-2 production. These cells produced IL-2 stably for at least 3 months, even in the absence of methotrexate. 205
doi:10.1247/csf.12.205 fatcat:6gnk7lnnubf37o2xplg2gaif4a

Cloning and expression of cDNA encoding human basic fibroblast growth factor

Tsutomu Kurokawa, Reiko Sasada, Makoto Iwane, Koichi Igarashi
1987 FEBS Letters  
A cDNA encoding human basic fibroblast growth factor (bFGF) was isolated from a human foreskin fibroblast cDNA library. The cDNA, 4 kilobases in size, had a coding sequence, 5' and 3' untranslated regions, and a poly(A) chain. Isolation of additional cDNA clones that had a short 3' untranslated region suggested the presence of multiple mRNA forms. By Northern blot analysis, at least five bFGF mRNA species were detected in cultured fibroblast cells. Transfection of the cDNA to COS cells resulted
more » ... in the detection of mitogenic activity in the culture medium of the transfected cells, suggesting that a part of the synthesized protein might be secreted from cells despite its unusual short signal sequence.
doi:10.1016/0014-5793(87)81489-8 pmid:2435575 fatcat:nj4fdfucgvdnlkj2qj3zev6p2u

A case of herpes zoster oticum

Kimiyo Tsutsui, Reiko Igarashi
1957 The Journal of Kansai Medical University  
doi:10.5361/jkmu1956.9.3_158 fatcat:6ccukqv75zd6nhm5u6ddr4p244

Characterization of the glycoproteins of bat-derived influenza viruses

Junki Maruyama, Naganori Nao, Hiroko Miyamoto, Ken Maeda, Hirohito Ogawa, Reiko Yoshida, Manabu Igarashi, Ayato Takada
2016 Virology  
Recently found bat-derived influenza viruses (BatIVs) have hemagglutinin (HA) and neuraminidase (NA) gene segments distinct from those of previously known influenza A viruses. However, pathogenicities of these BatIVs remain unknown since infectious virus strains have not been isolated yet. To gain insight into the biological properties of BatIVs, we generated vesicular stomatitis viruses (VSVs) pseudotyped with the BatIV HA and NA. We found that VSVs pseudotyped with BatIV HAs and NAs
more » ... y infected particular bat cell lines but not those derived from primates, and that proteolytic cleavage with a trypsin-like protease was necessary for HA-mediated virus entry. Treatment of the susceptible bat cells with some enzymes and inhibitors revealed that BatIV HAs might recognize some cellular glycoproteins as receptors rather than the sialic acids used for the other known influenza viruses. These data provide fundamental information on the mechanisms underlying the cellular entry and host restriction of BatIVs.
doi:10.1016/j.virol.2015.11.002 pmid:26605499 pmcid:PMC7126434 fatcat:lrlnb3ok25f47nv3omzwtk6noq

Discovery of an antibody for pan-ebolavirus therapy

Wakako Furuyama, Andrea Marzi, Asuka Nanbo, Elaine Haddock, Junki Maruyama, Hiroko Miyamoto, Manabu Igarashi, Reiko Yoshida, Osamu Noyori, Heinz Feldmann, Ayato Takada
2016 Scientific Reports  
During the latest outbreak of Ebola virus disease in West Africa, monoclonal antibody therapy (e.g., ZMapp) was utilized to treat patients. However, due to the antigenic differences among the five ebolavirus species, the current therapeutic monoclonal antibodies are only effective against viruses of the species Zaire ebolavirus. Although this particular species has indeed caused the majority of human infections in Central and, recently, West Africa, other ebolavirus species (e.g., Sudan
more » ... us and Bundibugyo ebolavirus) have also repeatedly caused outbreaks in Central Africa and thus should not be neglected in the development of countermeasures against ebolaviruses. Here we report the generation of an ebolavirus glycoprotein-specific monoclonal antibody that effectively inhibits cellular entry of representative isolates of all known ebolavirus species in vitro and show its protective efficacy in mouse models of ebolavirus infections. This novel neutralizing monoclonal antibody targets a highly conserved internal fusion loop in the glycoprotein molecule and prevents membrane fusion of the viral envelope with cellular membranes. The discovery of this highly cross-neutralizing antibody provides a promising option for broad-acting ebolavirus antibody therapy and will accelerate the design of improved vaccines that can selectively elicit cross-neutralizing antibodies against multiple species of ebolaviruses. Ebolaviruses, members of the family Filoviridae, cause severe hemorrhagic fever in humans and nonhuman primates, with human case fatality rates of up to 90% 1,2 . As proven by the latest epidemic of Ebola virus disease (EVD) in West Africa, ebolaviruses pose a significant public health concern. However, no effective prophylaxis or treatment for EVD is as yet commercially available. Five distinct species are known in the genus Ebolavirus, Zaire ebolavirus, Sudan ebolavirus, Taï forest ebolavirus, Bundibugyo ebolavirus, and Reston ebolavirus, represented by Ebola virus (EBOV), Sudan virus (SUDV), Taï forest virus (TAFV), Bundibugyo virus (BDBV), and Reston virus (RESTV), respectively 3 . Of these, EBOV, SUDV, and BDBV have caused EVD outbreaks with increased frequency in Central and West Africa in the last decade 1, 2, 4 . Ebolaviruses express a single transmembrane glycoprotein (GP) that is responsible for both receptor binding and membrane fusion, and thus the only known target of neutralizing antibodies. GP undergoes proteolytic cleavage by host proteases such as furin, resulting in the two subunits, GP1 and GP2, which are linked by a disulfide bond 5, 6 . The GP1 subunit (amino acids 33-501) contains the core of the glycoprotein, receptor binding domain (RBD), a glycan cap, and a large mucin-like domain which extends around the RBD 7 . The GP2 (amino acids 502-676) subunit contains the internal fusion loop (IFL), heptad repeats 1 and 2 (HR1 and HR2), the transmembrane region (TM), and the cytoplasmic tail (CT) 8 . During the transport of ebolavirus particles to late endosomes, low pH leads to proteolytic processing of GPs by host cysteine proteases such as cathepsins 9 , and the exposed receptor binding site of the proteolytically digested GP is thought to interact with a host receptor, Niemann Pick C1, followed by membrane fusion 8, 10, 11 . Several studies have demonstrated that administration of EBOV GP-specific antibodies protects nonhuman primates from lethal EBOV infection and may constitute a leading treatment option for EVD in humans [12] [13] [14] [15] [16] . During the West African EVD outbreak, EBOV GP-specific monoclonal antibody (MAb) cocktails (e.g., ZMapp) 12 , were used to treat several patients [17] [18] [19] [20] . However, most of characterized therapeutic MAbs to date are EBOV GP-specific and cross-neutralizing activity against any other ebolavirus species (e.g., SUDV and
doi:10.1038/srep20514 pmid:26861827 pmcid:PMC4748290 fatcat:25ce7z4chjetbfxtysp33coef4

Predicting the Antigenic Structure of the Pandemic (H1N1) 2009 Influenza Virus Hemagglutinin

Manabu Igarashi, Kimihito Ito, Reiko Yoshida, Daisuke Tomabechi, Hiroshi Kida, Ayato Takada, Robert Belshaw
2010 PLoS ONE  
The pandemic influenza virus (2009 H1N1) was recently introduced into the human population. The hemagglutinin (HA) gene of 2009 H1N1 is derived from "classical swine H1N1" virus, which likely shares a common ancestor with the human H1N1 virus that caused the pandemic in 1918, whose descendant viruses are still circulating in the human population with highly altered antigenicity of HA. However, information on the structural basis to compare the HA antigenicity among 2009 H1N1, the 1918 pandemic,
more » ... and seasonal human H1N1 viruses has been lacking. By homology modeling of the HA structure, here we show that HAs of 2009 H1N1 and the 1918 pandemic virus share a significant number of amino acid residues in known antigenic sites, suggesting the existence of common epitopes for neutralizing antibodies cross-reactive to both HAs. It was noted that the early human H1N1 viruses isolated in the 1930s-1940s still harbored some of the original epitopes that are also found in 2009 H1N1. Interestingly, while 2009 H1N1 HA lacks the multiple N-glycosylations that have been found to be associated with an antigenic change of the human H1N1 virus during the early epidemic of this virus, 2009 H1N1 HA still retains unique three-codon motifs, some of which became N-glycosylation sites via a single nucleotide mutation in the human H1N1 virus. We thus hypothesize that the 2009 H1N1 HA antigenic sites involving the conserved amino acids will soon be targeted by antibody-mediated selection pressure in humans. Indeed, amino acid substitutions predicted here are occurring in the recent 2009 H1N1 variants. The present study suggests that antibodies elicited by natural infection with the 1918 pandemic or its early descendant viruses play a role in specific immunity against 2009 H1N1, and provides an insight into future likely antigenic changes in the evolutionary process of 2009 H1N1 in the human population.
doi:10.1371/journal.pone.0008553 pmid:20049332 pmcid:PMC2797400 fatcat:kjzpmmgpirdq3oe5jpeuiirgxa
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