Mayumi Ito, Ph.D.

Coordinated activation of wnt in epithelial and melanocyte stem cells initiates pigmented hair regeneration
Rabbani, Piul; Takeo, Makoto; Chou, Weichin; Myung, Peggy; Bosenberg, Marcus; Chin, Lynda; Taketo, M Mark; Ito, Mayumi
2011 Jun 10;145(6):941-955, Cell
Melanocyte stem cells (McSCs) intimately interact with epithelial stem cells (EpSCs) in the hair follicle bulge and secondary hair germ (sHG). Together, they undergo activation and differentiation to regenerate pigmented hair. However, the mechanisms behind this coordinated stem cell behavior have not been elucidated. Here, we identified Wnt signaling as a key pathway that couples the behavior of the two stem cells. EpSCs and McSCs coordinately activate Wnt signaling at the onset of hair follicle regeneration within the sHG. Using genetic mouse models that specifically target either EpSCs or McSCs, we show that Wnt activation in McSCs drives their differentiation into pigment-producing melanocytes, while EpSC Wnt signaling not only dictates hair follicle formation but also regulates McSC proliferation during hair regeneration. Our data define a role for Wnt signaling in the regulation of McSCs and also illustrate a mechanism for regeneration of complex organs through collaboration between heterotypic stem cell populations. PAPERFLICK:
— id: 134458, year: 2011, vol: 145, page: 941, stat: Journal Article,

Hair cycling and wound healing: to pluck or not to pluck?
Stojadinovic, Olivera; Ito, Mayumi; Tomic-Canic, Marjana
2011 Feb;131(2):292-294, Journal of investigative dermatology
The incidence of nonhealing wounds (diabetic foot, pressure, venous, and arterial ulcers) is reaching epidemic proportions, underscoring the need for new treatment modalities. Understanding hair follicle biology and its potential to accelerate wound healing may offer new treatment strategies. In this issue, Ansell et al. show that wounds on anagen skin heal faster than those on telogen skin, suggesting that hair cycle stages may influence healing outcome
— id: 120529, year: 2011, vol: 131, page: 292, stat: Journal Article,

Removal of lead compounds from polyvinylchloride in electric wires and cables using cation-exchange resin
Tsunekawa, Masami; Ito, Mayumi; Yuta, Sasaki; Tomoo, Sakai; Hiroyoshi, Naoki
2011 Jul 15;191(1-3):388-392, Journal of hazardous materials
Recycling treatment of cable insulation resin generated from electric wires and cables was investigated. Conventional insulation PVC contains a lead component, tribase, as a thermal stabilizer and lead removal is necessary to recycle this PVC as insulation resin. This paper describes a solid surface adsorption method using ion exchange resin to remove the fine lead containing particles from PVC dissolved solution. Low lead concentration in the recovered PVC, complying with the requirements of RoHS, was achieved
— id: 137830, year: 2011, vol: 191, page: 388, stat: Journal Article,

Defining the hair follicle stem cell (Part I)
Myung, Peggy; Andl, Thomas; Ito, Mayumi
2009 Sep;36(9):1031-1034, Journal of cutaneous pathology
— id: 115710, year: 2009, vol: 36, page: 1031, stat: Journal Article,

Defining the hair follicle stem cell (Part II)
Myung, Peggy; Andl, Thomas; Ito, Mayumi
2009 Oct;36(10):1134-1137, Journal of cutaneous pathology
— id: 115709, year: 2009, vol: 36, page: 1134, stat: Journal Article,

Efficient in vivo targeting of epidermal stem cells by early gestational intraamniotic injection of lentiviral vector driven by the keratin 5 promoter
Endo, Masayuki; Zoltick, Philip W; Peranteau, William H; Radu, Antoneta; Muvarak, Nidal; Ito, Mayumi; Yang, Zaixin; Cotsarelis, George; Flake, Alan W
2008 Jan;16(1):131-137, Molecular therapy
At the present time, no efficient in vivo method for gene transfer to skin stem cells exists. In this study, we hypothesized that early in gestation, specific epidermal stem cell populations may be accessible for gene transfer. To test this hypothesis, we injected lentiviral vectors encoding the green fluorescence protein marker gene driven by either the cytomegalovirus promoter or the keratin 5 (K5) promoter into the murine amniotic space at early developmental stages between embryonic days 8 and 12. This resulted in sustained green fluorescent protein (GFP) expression in both basal epidermal stem cells and bulge cells in the hair follicles of the skin. Transduction of stem cell populations was dependent on the developmental stage, and confirmed by the prolonged duration of GFP expression in all skin elements into adulthood. In addition, transduced stem cell populations responded to regenerative signals after wounding and actively participated in wound healing. Finally, we quantified the fraction of epidermal stem cells transduced, and the distribution of transduction related to the promoters utilized, confirming improved efficiency with the K5 promoter. This simple approach has possible biological applications in our study of gene functions in skin, and perhaps future clinical applications for treatment of skin based disorders
— id: 81149, year: 2008, vol: 16, page: 131, stat: Journal Article,

Is the hair follicle necessary for normal wound healing?
Ito, Mayumi; Cotsarelis, George
2008 May;128(5):1059-1061, Journal of investigative dermatology
The hair follicle contributes cells to the interfollicular epidermis after wounding, but the functional role of these cells has not been resolved. To address this question, Langton et al. (this issue, 2008) take advantage of the Edaradd mutant mouse, which lacks hair follicles on its tail. They discover an initial sluggish response of the hairless tail epidermis to wounding that is rapidly compensated for by recruitment of epidermal cells from outside the normally responsive area. This suggests that the hair follicle is important but not necessary for normal wound healing
— id: 81150, year: 2008, vol: 128, page: 1059, stat: Journal Article,

Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding
Ito, Mayumi; Yang, Zaixin; Andl, Thomas; Cui, Chunhua; Kim, Noori; Millar, Sarah E; Cotsarelis, George
2007 May 17;447(7142):316-320, Nature
The mammalian hair follicle is a complex 'mini-organ' thought to form only during development; loss of an adult follicle is considered permanent. However, the possibility that hair follicles develop de novo following wounding was raised in studies on rabbits, mice and even humans fifty years ago. Subsequently, these observations were generally discounted because definitive evidence for follicular neogenesis was not presented. Here we show that, after wounding, hair follicles form de novo in genetically normal adult mice. The regenerated hair follicles establish a stem cell population, express known molecular markers of follicle differentiation, produce a hair shaft and progress through all stages of the hair follicle cycle. Lineage analysis demonstrated that the nascent follicles arise from epithelial cells outside of the hair follicle stem cell niche, suggesting that epidermal cells in the wound assume a hair follicle stem cell phenotype. Inhibition of Wnt signalling after re-epithelialization completely abrogates this wounding-induced folliculogenesis, whereas overexpression of Wnt ligand in the epidermis increases the number of regenerated hair follicles. These remarkable regenerative capabilities of the adult support the notion that wounding induces an embryonic phenotype in skin, and that this provides a window for manipulation of hair follicle neogenesis by Wnt proteins. These findings suggest treatments for wounds, hair loss and other degenerative skin disorders
— id: 81145, year: 2007, vol: 447, page: 316, stat: Journal Article,

Sodium D2 resonance radiation in single-pass sum-frequency generation with actively mode-locked Nd:YAG lasers
Saito, Norihito; Akagawa, Kazuyuki; Ito, Mayumi; Takazawa, Akira; Hayano, Yutaka; Saito, Yoshihiko; Ito, Meguru; Takami, Hideki; Iye, Masanori; Wada, Satoshi
2007 Jul 15;32(14):1965-1967, Optics letters
We report on a sodium D(2) resonance coherent light source achieved in single-pass sum-frequency generation in periodically poled MgO-doped stoichiometric lithium tantalate with actively mode-locked Nd:YAG lasers. Mode-locked pulses at 1064 and 1319 nm are synchronized with a time resolution of 37 ps with the phase adjustment of the radio frequencies fed to acousto-optic mode lockers. An output power of 4.6 W at 589.1586 nm is obtained, and beam quality near the diffraction limit is also achieved in a simple design
— id: 81146, year: 2007, vol: 32, page: 1965, stat: Journal Article,

CD34 expression by hair follicle stem cells is required for skin tumor development in mice
Trempus, Carol S; Morris, Rebecca J; Ehinger, Matthew; Elmore, Amy; Bortner, Carl D; Ito, Mayumi; Cotsarelis, George; Nijhof, Joanne G W; Peckham, John; Flagler, Norris; Kissling, Grace; Humble, Margaret M; King, Leon C; Adams, Linda D; Desai, Dhimant; Amin, Shantu; Tennant, Raymond W
2007 May 1;67(9):4173-4181, Cancer research
The cell surface marker CD34 marks mouse hair follicle bulge cells, which have attributes of stem cells, including quiescence and multipotency. Using a CD34 knockout (KO) mouse, we tested the hypothesis that CD34 may participate in tumor development in mice because hair follicle stem cells are thought to be a major target of carcinogens in the two-stage model of mouse skin carcinogenesis. Following initiation with 200 nmol 7,12-dimethylbenz(a)anthracene (DMBA), mice were promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 20 weeks. Under these conditions, CD34KO mice failed to develop papillomas. Increasing the initiating dose of DMBA to 400 nmol resulted in tumor development in the CD34KO mice, albeit with an increased latency and lower tumor yield compared with the wild-type (WT) strain. DNA adduct analysis of keratinocytes from DMBA-initiated CD34KO mice revealed that DMBA was metabolically activated into carcinogenic diol epoxides at both 200 and 400 nmol. Chronic exposure to TPA revealed that CD34KO skin developed and sustained epidermal hyperplasia. However, CD34KO hair follicles typically remained in telogen rather than transitioning into anagen growth, confirmed by retention of bromodeoxyuridine-labeled bulge stem cells within the hair follicle. Unique localization of the hair follicle progenitor cell marker MTS24 was found in interfollicular basal cells in TPA-treated WT mice, whereas staining remained restricted to the hair follicles of CD34KO mice, suggesting that progenitor cells migrate into epidermis differently between strains. These data show that CD34 is required for TPA-induced hair follicle stem cell activation and tumor formation in mice
— id: 81144, year: 2007, vol: 67, page: 4173, stat: Journal Article,

Contribution of high p34cdc2 kinase activity to premature chromosome condensation of injected somatic cell nuclei in rat oocytes
Ito, Junya; Hirabayashi, Masumi; Kato, Megumi; Takeuchi, Ayumu; Ito, Mayumi; Shimada, Masayuki; Hochi, Shinichi
2005 Feb;129(2):171-180, Reproduction
The present study was undertaken to clarify the relationship between the p34cdc2 kinase activity of in vitro-aged or enucleated rat oocytes and the premature chromosome condensation (PCC) of microinjected cumulus cell nuclei. Wistar rat oocytes were placed in vitro up to 120 min after the animal was killed. The p34cdc2 kinase activity of the oocytes decreased in a time-dependent manner. The incidence of PCC was higher when nuclear injection into intact oocytes was completed in 15-45 min rather than 46-120 min. When rat oocytes were enucleated for subsequent nuclear injection, the p34cdc2 kinase activity transiently increased soon after enucleation but drastically decreased after 30 min. Removal of the cytoplasm instead of the meta-phase-plate did not affect the p34cdc2 kinase activity even after 60 min. PCC occurred in intact and cytoplasm-removed oocytes but not in enucleated oocytes. In contrast, oocytes from BDF1 mice exhibited a p34cdc2 kinase level twice that of rat oocytes and supported PCC despite enucleation. The p34cdc2 kinase level of intact rat oocytes was reduced to the equivalent level of aged (120 min) or enucleated (+60 min) oocytes by a 45 min treatment with roscovitine, an inhibitor of p34cdc2 kinase. None of the roscovitine-treated oocytes supported PCC while half of the control oocytes did. When rat oocytes were treated with MG132, a proteasome inhibitor, delayed inactivation of the p34cdc2 kinase was observed in the MG132-treated oocytes. A significantly higher proportion of the MG132-treated oocytes supported PCC when compared with the control oocytes. Moreover, a higher proportion of MG132-treated and enucleated oocytes carried two pseudo-pronuclei after cumulus cell injection and developed to the two-cell stage when compared with the enucleated oocytes at the telophase-II stage. These results suggest that the decreased level of p34cdc2 kinase activity in aged or enucleated rat oocytes is responsible for their inability to support PCC of microinjected donor cell nuclei and that inhibition of p34cdc2 kinase inactivation by chemicals such as MG132 is in part effective for rat oocytes to promote PCC and further development
— id: 81133, year: 2005, vol: 129, page: 171, stat: Journal Article,

Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis
Ito, Mayumi; Liu, Yaping; Yang, Zaixin; Nguyen, Jane; Liang, Fan; Morris, Rebecca J; Cotsarelis, George
2005 Dec;11(12):1351-1354, Nature medicine
The discovery of long-lived epithelial stem cells in the bulge region of the hair follicle led to the hypothesis that epidermal renewal and epidermal repair after wounding both depend on these cells. To determine whether bulge cells are necessary for epidermal renewal, here we have ablated these cells by targeting them with a suicide gene encoding herpes simplex virus thymidine kinase (HSV-TK) using a Keratin 1-15 (Krt1-15) promoter. We show that ablation leads to complete loss of hair follicles but survival of the epidermis. Through fate-mapping experiments, we find that stem cells in the hair follicle bulge do not normally contribute cells to the epidermis which is organized into epidermal proliferative units, as previously predicted. After epidermal injury, however, cells from the bulge are recruited into the epidermis and migrate in a linear manner toward the center of the wound, ultimately forming a marked radial pattern. Notably, although the bulge-derived cells acquire an epidermal phenotype, most are eliminated from the epidermis over several weeks, indicating that bulge stem cells respond rapidly to epidermal wounding by generating short-lived 'transient amplifying' cells responsible for acute wound repair. Our findings have implications for both gene therapy and developing treatments for wounds because it will be necessary to consider epidermal and hair follicle stem cells as distinct populations
— id: 81139, year: 2005, vol: 11, page: 1351, stat: Journal Article,

Characterization of epithelial cells in the hair follicle with S100 proteins
Kizawa, Kenji; Ito, Mayumi
2005 ;289:209-222, Methods in molecular biology
S100 proteins are the largest subgroup of Ca2+ binding proteins with the EF-hand structural motif. A unique feature of this protein family is that individual members are localized in specific cellular compartments. For example, various S100 proteins are expressed in very restricted regions of the hair follicle: S100A3 and S100A6 in distinct postmitotic differentiated epithelial cells and S100A4 and S100A6 in the epithelial stem cell compartments. Characterization of epithelial cells by their S100 protein expression profiles is therefore useful for a better understanding of the dynamic cellular events associated with hair follicle development and regeneration. This chapter presents our protocols for probe preparations and histochemical analyses of S100 proteins in hair follicle tissue, including simultaneous detection procedures for pulse-labeled proliferating cells
— id: 81128, year: 2005, vol: 289, page: 209, stat: Journal Article,

Association of coronary heart disease with pre-beta-HDL concentrations in Japanese men
Hattori, Hiroaki; Kujiraoka, Takeshi; Egashira, Tohru; Saito, Eiji; Fujioka, Takayuki; Takahashi, Sadao; Ito, Mayumi; Cooper, Jackie A; Stepanova, Irina P; Nanjee, M Nazeem; Miller, Norman E
2004 Mar;50(3):589-595, Clinical chemistry
BACKGROUND: In individuals heterozygous for ABCA1 transporter mutations, defective reverse cholesterol transport (RCT) causes low HDL-cholesterol and premature coronary heart disease (CHD). However, the extent to which impaired RCT underlies premature CHD in others with low HDL-cholesterol is not known. The primary acceptors of cell cholesterol are a minor subclass of lipid-poor pre-beta-HDLs. These are generated during remodeling of alpha-HDLs, which account for almost all HDL-cholesterol. We studied the strength of the association of CHD with pre-beta-HDL concentrations in Japanese men. METHODS: Blood was collected from 42 men with clinical CHD and 44 healthy controls 40-70 years of age. Pre-beta-HDL was assayed by crossed immunoelectrophoresis. RESULTS: Cases had lower HDL-cholesterol (-23%), total apolipoprotein A-I (-26%), and pre-beta-HDL (-55%; all P <0.001) concentrations; lower pre-beta-HDL:alpha-HDL ratios (-45%; P <0.001); and higher plasma triglycerides (20%; P <0.03) than the controls. On stepwise logistic regression, CHD was associated most strongly with pre-beta-HDL concentrations. On ROC analysis, pre-beta-HDL concentration discriminated between cases and controls better than any other lipoprotein measurement. When plasma was incubated for 16 h at 37 degrees C, mean (SD) pre-beta-HDL increased by 47 (36)% in controls, but was unchanged in cases (group difference, P <0.001). CONCLUSIONS: Our results suggest that inefficient RCT, secondary to a low pre-beta-HDL concentration and production rate in plasma, contributes to premature CHD in Japanese men with low HDL-cholesterol
— id: 81120, year: 2004, vol: 50, page: 589, stat: Journal Article,

Practical use of labile protein as an index of hair
Inoue, Takafumi; Kizawa, Kenji; Ito, Mayumi; Shinkai, Masakazu; Iwamoto, Yoshimichi
2004 Nov-Dec;55(6):553-558, Journal of cosmetic science
Because of small fluctuations, it is difficult to evaluate hair damage caused by bleaching using previously utilized hair damage indexes. Application of commercial bleaching products elevates partially extractable labile hair protein amounts in the range of 0.4-1.2 mg/g of hair. Within this range, the level of labile protein fluctuates greatly, depending on the extent of bleaching. In the current study, it was found that the effects of alkaline constituents and various peptides contained in bleaching lotions on hair damage could be evaluated by measuring labile protein amounts without employing harsher bleaching conditions
— id: 81132, year: 2004, vol: 55, page: 553, stat: Journal Article,

Hair follicle stem cells in the lower bulge form the secondary germ, a biochemically distinct but functionally equivalent progenitor cell population, at the termination of catagen
Ito, Mayumi; Kizawa, Kenji; Hamada, Kazuto; Cotsarelis, George
2004 Dec;72(9-10):548-557, Differentiation
The lowermost portion of the resting (telogen) follicle consists of the bulge and secondary hair germ. We previously showed that the progeny of stem cells in the bulge form the lower follicle and hair, but the relationship of the bulge cells with the secondary hair germ cells, which are also involved in the generation of the new hair at the onset of the hair growth cycle (anagen), remains unclear. Here we address whether secondary hair germ cells are derived directly from epithelial stem cells in the adjacent bulge or whether they arise from cells within the lower follicle that survive the degenerative phase of the hair cycle (catagen). We use 5-bromo-2'-deoxyuridine to label bulge cells at anagen onset, and demonstrate that the lowermost portion of the bulge collapses around the hair and forms the secondary hair germ during late catagen. During the first six days of anagen onset bulge cells proliferate and self-renew. Bulge cell proliferation at this time also generates cells that form the future secondary germ. As bulge cells form the secondary germ cells at the end of catagen, they lose expression of a biochemical marker, S100A6. Remarkably, however, following injury of bulge cells by hair depilation, progenitor cells in the secondary hair germ repopulate the bulge and re-express bulge cell markers. These findings support the notion that keratinocytes can 'dedifferentiate' to a stem cell state in response to wounding, perhaps related to signals from the stem cell niche. Finally, we also present evidence that quiescent bulge cells undergo apoptosis during follicle remodeling in catagen, indicating that a subpopulation of bulge cells is not permanent
— id: 81131, year: 2004, vol: 72, page: 548, stat: Journal Article,

Effects of intravenous apolipoprotein A-I/phosphatidylcholine discs on paraoxonase and platelet-activating factor acetylhydrolase in human plasma and tissue fluid
Kujiraoka, Takeshi; Hattori, Hiroaki; Ito, Mayumi; Nanjee, M Nazeem; Ishihara, Mitsuaki; Nagano, Makoto; Iwasaki, Tadao; Cooke, C Justin; Olszewski, Waldemar L; Stepanova, Irina P; Egashira, Tohru; Miller, Norman E
2004 Sep;176(1):57-62, Atherosclerosis
We have previously shown that intravenous apolipoprotein (apo) A-I/phosphatidylcholine (apo A-I/PC) discs increase plasma high-density lipoprotein (HDL) concentration in humans. We have now studied the associated changes in two enzymes, paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH) that are carried in whole or in part by HDLs, and are thought to influence atherogenesis by hydrolyzing oxidized phospholipids in lipoproteins. Apo A-I/PC discs (40 mg/kg over 4 h) were infused into eight healthy males. Although plasma apo A-I and HDL cholesterol increased on average by 178 and 158%, respectively, plasma total PON and total PAF-AH concentrations did not rise. By the end of the infusion, HDL-associated PAF-AH had increased by 0.56 +/- 0.14 microg/mL (mean +/- S.D., P < 0.01), and nonHDL-associated PAF-AH had decreased by 0.84 +/- 0.11 microg/mL (P < 0.05). These changes were accompanied by an increase in the HDL-associated PAF-AH/apo A-I ratio from 0.19 to 0.35 (P < 0.05), and by a decrease in the nonHDL-associated PAF-AH/apo B ratio from 2.1 to 1.4 (P < 0.05). No changes in PON or PAF-AH concentrations were detected in prenodal lymph (tissue fluid), collected continuously from the leg. Our results show that the total concentrations of PON and PAF-AH in plasma are uninfluenced by plasma HDL concentration. PAF-AH transfers readily between HDLs and LDLs in vivo, and its distribution between them is determined partly by their relative concentrations and partly by HDL composition
— id: 81126, year: 2004, vol: 176, page: 57, stat: Journal Article,

Altered distribution of plasma PAF-AH between HDLs and other lipoproteins in hyperlipidemia and diabetes mellitus
Kujiraoka, Takeshi; Iwasaki, Tadao; Ishihara, Mitsuaki; Ito, Mayumi; Nagano, Makoto; Kawaguchi, Akito; Takahashi, Sadao; Ishi, Jun; Tsuji, Masahiro; Egashira, Tohru; Stepanova, Irina P; Miller, Norman E; Hattori, Hiroaki
2003 Oct;44(10):2006-2014, Journal of lipid research
Platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A2 associated with lipoproteins that hydrolyzes platelet-activating factor (PAF) and oxidized phospholipids. We have developed an ELISA for PAF-AH that is more sensitive than previous methods, and have quantified HDL-associated and non-HDL-associated PAF-AH in healthy, hyperlipidemic, and diabetic subjects. In healthy subjects, plasma total PAF-AH concentration was positively correlated with PAF-AH activity and with plasma total cholesterol, triacylglycerol, LDL cholesterol and apolipoprotein B (apoB) concentrations (all P < 0.01). HDL-associated PAF-AH concentration was correlated positively with plasma apoA-I and HDL cholesterol. Subjects with hyperlipidemia (n = 73) and diabetes mellitus (n = 87) had higher HDL-associated PAF-AH concentrations than did controls (P < 0.01). Non-HDL-associated PAF-AH concentration was lower in diabetic subjects than in controls (P < 0.01). Both hyperlipidemic and diabetic subjects had lower ratios of PAF-AH to apoB (P < 0.01) and higher ratios of PAF-AH to apoA-I (P < 0.01) than did controls. Our results show that the distribution of PAF-AH mass between HDLs and LDLs is determined partly by the concentrations of the lipoproteins and partly by the mass of enzyme per lipoprotein particle, which is disturbed in hyperlipidemia and diabetes mellitus
— id: 81115, year: 2003, vol: 44, page: 2006, stat: Journal Article,

Effects of intravenous apolipoprotein A-I/phosphatidylcholine discs on LCAT, PLTP, and CETP in plasma and peripheral lymph in humans
Kujiraoka, Takeshi; Nanjee, M Nazeem; Oka, Tomoichiro; Ito, Mayumi; Nagano, Makoto; Cooke, C Justin; Takahashi, Sadao; Olszewski, Waldemar L; Wong, Jinny S; Stepanova, Irina P; Hamilton, Robert L; Egashira, Tohru; Hattori, Hiroaki; Miller, Norman E
2003 Sep 1;23(9):1653-1659, Arteriosclerosis, thrombosis, & vascular biology
OBJECTIVE: We have previously shown that intravenous apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) discs increase plasma pre-beta HDL concentration and stimulate reverse cholesterol transport (RCT) in humans. We have now investigated the associated changes in the following 3 HDL components that play key roles in RCT: lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). METHODS AND RESULTS: apoA-I/PC discs (40 mg/kg over 4 hours) were infused into 8 healthy men. Samples of blood and prenodal peripheral lymph were collected for 24 to 48 hours. At 12 hours, plasma LCAT concentration had increased by 0.40+/-0.90 mg/L (+7.8%; mean+/-SD; P<0.05), plasma cholesterol esterification rate by 29.0+/-9.0 nmol/mL per h (+69.5%; P<0.01), plasma CETP concentration by 0.5+/-0.2 mg/L (+29.7%; P<0.01), and plasma PLTP activity by 1.45+/-0.67 micromol/mL per h (+23.9%; P<0.01). In contrast, plasma PLTP concentration had decreased by 4.4+/-2.7 mg/L (-44.8%; P<0.01). The changes in PLTP were accompanied by alterations in the relative proportions of large lipoproteins containing inactive PLTP and small particles containing PLTP of high specific activity. No changes were detected in peripheral lymph. CONCLUSIONS: Nascent HDL secretion may induce changes in PLTP, LCAT, and CETP that promote RCT by catalyzing pre-beta HDL production, cholesterol esterification in HDLs, and cholesteryl ester transfer from HDLs to other lipoproteins
— id: 81117, year: 2003, vol: 23, page: 1653, stat: Journal Article,

Labile proteins accumulated in damaged hair upon permanent waving and bleaching treatments
Inoue, Takafumi; Ito, Mayumi; Kizawa, Kenji
2002 Nov-Dec;53(6):337-344, Journal of cosmetic science
We previously found that certain hair proteins were soluble by means of a partial extraction method. In this study, we demonstrate that the amount of soluble proteins internally formed in permed and bleached hair, labile proteins, is a useful index for hair damage assessment. Compared to tensile property changes, this index rose in widely dynamic ranges as the time of either permanent waving or bleaching treatments increased. The amount of labile proteins was much larger than that of proteins eluted into perming and bleaching lotions. However, the labile proteins showed electrophoretic profiles similar to those of the eluted proteins. These results suggest that a portion of the stable proteins in normal hair was transformed into labile proteins upon permanent waving and bleaching treatments. Consequently, permed and bleached hair tends to release the resultant labile proteins
— id: 81111, year: 2002, vol: 53, page: 337, stat: Journal Article,

Label-retaining cells in the bulge region are directed to cell death after plucking, followed by healing from the surviving hair germ
Ito, Mayumi; Kizawa, Kenji; Toyoda, Masahiko; Morohashi, Masaaki
2002 Dec;119(6):1310-1316, Journal of investigative dermatology
Hair plucking is the most frequently used method of anagen induction within hair follicles. In this study, we found that plucking leads to the entire renewal of the follicular stem cell region of the mouse pelage follicle. Comparative histochemical analysis revealed that S100A4 protein was specifically distributed in the outer layer of the epithelial sac, which has been identified as the stem cell region of the pelage follicle, whereas the slow cycling cells that retained 5-bromo-2'-deoxyuridine label for 8 wk were located in the epithelial sac and also in the hair germ. Combined terminal deoxynucleotide transferase deoxyuridine triphosphate fluorescein nick end labeling method and immunohistochemistry revealed that positive cells were detected in the outer layer of the epithelial sac possessing both bromo-2'-deoxyuridine and S100A4 labels 4.5 h after plucking. No terminal deoxynucleotide transferase deoxyuridine triphosphate fluorescein nick end labeling signal, however, was observed in the hair germ. Serial inspection of the plucked follicle revealed that almost all regions of the epithelial sac became terminal deoxynucleotide transferase deoxyuridine triphosphate fluorescein nick end labeling positive 12 h after plucking. Terminal deoxynucleotide transferase deoxyuridine triphosphate fluorescein nick end labeling-positive cells ultimately degenerated without forming apoptotic bodies. Subsequently, the surviving label-retaining cells in the hair germ migrated upward to re-epithelialize the damaged portion. These results indicate that follicular stem cells in the epithelial sac underwent cell death after plucking. It is likely that the hair germ is responsible for the reconstruction of the stem cell region of the hair follicle
— id: 81110, year: 2002, vol: 119, page: 1310, stat: Journal Article,

Two novel missense mutations in the CETP gene in Japanese hyperalphalipoproteinemic subjects: high-throughput assay by Invader assay
Nagano, Makoto; Yamashita, Shizuya; Hirano, Ken-ichi; Ito, Mayumi; Maruyama, Takao; Ishihara, Mitsuaki; Sagehashi, Yukiko; Oka, Tomoichiro; Kujiraoka, Takeshi; Hattori, Hiroaki; Nakajima, Norimichi; Egashira, Tohru; Kondo, Masatoshi; Sakai, Naohiko; Matsuzawa, Yuji
2002 Jul;43(7):1011-1018, Journal of lipid research
Cholesteryl ester transfer protein (CETP) deficiency is one of the most important and common causes of hyperalphalipoproteinemia (HALP) in the Japanese. CETP deficiency is thought to be a state of impaired reverse cholesterol transport, which may possibly lead to the development of atherosclerotic cardiovascular disease despite high HDL-cholesterol (HDL-C) levels. Thus, it is important to investigate whether HALP is caused by CETP deficiency. In the present study, we identified two novel missense mutations in the CETP gene among 196 subjects with a marked HALP (HDL-C > or = 2.59 mmol/l = 100 mg/dl). The two missense mutations, L151P (CTC-->CCC in exon 5) and R282C (CGC-->TGC in exon 9), were found in compound heterozygous subjects with D442G mutation, whose plasma CETP levels were significantly lower when compared with those in D442G heterozygous subjects. In COS-7 cells expressing the wild type and mutant CETP, these two mutant CETP showed a marked reduction in the secretion of CETP protein into media (0% and 39% of wild type for L151P and R282C, respectively). These results suggested that two novel missense mutations cause the decreased secretion of CETP protein into circulation leading to HALP. By using the Invader assay for seven mutations, including two novel mutations of the CETP gene, we investigated their frequency among 466 unrelated subjects with HALP (HDL-C > or = 2.07 mmol/l = 80 mg/dl). Two novel mutations were rare, but L151P mutation was found in unrelated subjects with a marked HALP. Furthermore, we demonstrated that CETP deficiency contributes to 61.7% and 31.4% of marked HALP and moderate HALP in the Japanese, respectively
— id: 81108, year: 2002, vol: 43, page: 1011, stat: Journal Article,

Expansion of the cell plate in plant cytokinesis requires a kinesin-like protein/MAPKKK complex
Nishihama, Ryuichi; Soyano, Takashi; Ishikawa, Masaki; Araki, Satoshi; Tanaka, Hirokazu; Asada, Tetsuhiro; Irie, Kenji; Ito, Mayumi; Terada, Mizuya; Banno, Hiroharu; Yamazaki, Yoshiko; Machida, Yasunori
2002 Apr 5;109(1):87-99, Cell
The tobacco mitogen-activated protein kinase kinase kinase NPK1 regulates lateral expansion of the cell plate at cytokinesis. Here, we show that the kinesin-like proteins NACK1 and NACK2 act as activators of NPK1. Biochemical analysis suggests that direct binding of NACK1 to NPK1 stimulates kinase activity. NACK1 is accumulated specifically in M phase and colocalized with NPK1 at the phragmoplast equator. Overexpression of a truncated NACK1 protein that lacks the motor domain disrupts NPK1 concentration at the phragmoplast equator and cell plate formation. Incomplete cytokinesis is also observed when expression of NACK1 and NACK2 is repressed by virus-induced gene silencing and in embryonic cells from Arabidopsis mutants in which a NACK1 ortholog is disrupted. Thus, we conclude that expansion of the cell plate requires NACK1/2 to regulate the activity and localization of NPK1
— id: 81104, year: 2002, vol: 109, page: 87, stat: Journal Article,

Distribution of human plasma PLTP mass and activity in hypo- and hyperalphalipoproteinemia
Oka, Tomoichiro; Yamashita, Shizuya; Kujiraoka, Takeshi; Ito, Mayumi; Nagano, Makoto; Sagehashi, Yukiko; Egashira, Tohru; Nanjee, M Nazeem; Hirano, Ken-ichi; Miller, Norman E; Matsuzawa, Yuji; Hattori, Hiroaki
2002 Aug;43(8):1236-1243, Journal of lipid research
Plasma phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism and reverse cholesterol transport. We have recently reported that plasma PLTP concentration correlates positively with plasma HDL cholesterol (HDL-C) but not with PLTP activity in healthy subjects. We have also shown that PLTP exists as active and inactive forms in healthy human plasma. In the present study, we measured plasma PLTP concentration and PLTP activity, and analyzed the distribution of PLTP in normolipidemic subjects (controls), cholesteryl ester transfer protein (CETP) deficiency, and hypo-alphalipoproteinemia (hypo-ALP). Plasma PLTP concentration was significantly lower (0.7 +/- 0.4 mg/l, mean +/- SD, n = 9, P < 0.001) in the hypo-ALP subjects, and significantly higher (19.5 +/- 4.3 mg/l, n = 17, P < 0.001) in CETP deficiency than in the controls (12.4 +/- 2.3 mg/l, n = 63). In contrast, we observed no significant differences in plasma PLTP activity between controls, hypo-ALP subjects, and CETP deficiency (6.2 +/- 1.3, 6.1 +/- 1.8, and 6.8 +/- 1.2 micro mol/ml/h, respectively). There was a positive correlation between PLTP concentration and plasma HDL-C (r = 0.81, n = 89, P < 0.001). By size exclusion chromatography analysis, we found that the larger PLTP containing particles without PLTP activity (inactive form of PLTP) were almost absent in the plasma of hypo-ALP subjects, and accumulated in the plasma of CETP deficiency compared with those of controls. These results indicate that the differences in plasma PLTP concentrations between hypo-ALP subjects, CETP deficiency, and controls are mainly due to the differences in the amount of the inactive form of PLTP
— id: 81109, year: 2002, vol: 43, page: 1236, stat: Journal Article,

Control of plant cytokinesis by an NPK1-mediated mitogen-activated protein kinase cascade
Soyano, Takashi; Ishikawa, Masaki; Nishihama, Ryuichi; Araki, Satoshi; Ito, Mayumi; Ito, Masaki; Machida, Yasunori
2002 Jun 29;357(1422):767-775, Philosophical transactions of the Royal Society of London. Series B. Biological sciences
Cytokinesis is the last essential step in the distribution of genetic information to daughter cells and partition of the cytoplasm. In plant cells, various proteins have been found in the phragmoplast, which corresponds to the cytokinetic apparatus, and in the cell plate, which corresponds to a new cross wall, but our understanding of the functions of these proteins in cytokinesis remains incomplete. Reverse genetic analysis of NPK1 MAPKKK (nucleus- and phragmoplast-localized protein kinase 1 mitogen-activated protein kinase kinase kinase) and investigations of factors that might be functionally related to NPK1 have helped to clarify new aspects of the mechanisms of cytokinesis in plant cells. In this review, we summarize the evidence for the involvement of NPK1 in cytokinesis. We also describe the characteristics of a kinesin-like protein and the homologue of a mitogen-activated protein kinase that we identified recently, and we discuss possible relationships among these proteins in cytokinesis
— id: 81107, year: 2002, vol: 357, page: 767, stat: Journal Article,

Subulatin, an antioxidic caffeic acid derivative isolated from the in vitro cultured liverworts, Jungermannia subulata, Lophocolea heterophylla, and Scapania parvitexta
Tazaki, Hiroyuki; Ito, Mayumi; Miyoshi, Masako; Kawabata, Jun; Fukushi, Eri; Fujita, Takashi; Motouri, Mutsumi; Furuki, Tatsuo; Nabeta, Kensuke
2002 Feb;66(2):255-261, Bioscience, biotechnology, & biochemistry
The new caffeic acid derivative, subulatin (1), was isolated from in vitro cultured liverworts, Jungermannia subulata, Lophocolea heterophylla, and Scapania parvitexta. The structure of 1 involved two caffeic acids, D-glucose, and 2-carboxy-6-(1,2-dihydroxy-ethyl)-4,5-dihydroxy-5,6-dihydro-4H-pyran. The connectivity of those and the absolute stereochemistry of 1 were elucidated on the basis of spectroscopic evidence. The antioxidative activity of 1 was comparable to that of alpha-tocopherol. (2'R)-Phaselic acid (2a) and (-)-9,2''-epiphylloyl-L-malic acid (4) were also isolated from J. subulata and L. heterophylla, respectively. A chiral HPLC analysis of the p-bromobenzoyl-malic acids derived from 2a showed that 2a from J. subulata was unusual (+)-trans-caffeoyl-D-malic acid
— id: 81106, year: 2002, vol: 66, page: 255, stat: Journal Article,