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1.
Nature ; 529(7584): 54-8, 2016 Jan 07.
Article in English | MEDLINE | ID: mdl-26738590

ABSTRACT

How black holes accrete surrounding matter is a fundamental yet unsolved question in astrophysics. It is generally believed that matter is absorbed into black holes via accretion disks, the state of which depends primarily on the mass-accretion rate. When this rate approaches the critical rate (the Eddington limit), thermal instability is supposed to occur in the inner disk, causing repetitive patterns of large-amplitude X-ray variability (oscillations) on timescales of minutes to hours. In fact, such oscillations have been observed only in sources with a high mass-accretion rate, such as GRS 1915+105 (refs 2, 3). These large-amplitude, relatively slow timescale, phenomena are thought to have physical origins distinct from those of X-ray or optical variations with small amplitudes and fast timescales (less than about 10 seconds) often observed in other black-hole binaries-for example, XTE J1118+480 (ref. 4) and GX 339-4 (ref. 5). Here we report an extensive multi-colour optical photometric data set of V404 Cygni, an X-ray transient source containing a black hole of nine solar masses (and a companion star) at a distance of 2.4 kiloparsecs (ref. 8). Our data show that optical oscillations on timescales of 100 seconds to 2.5 hours can occur at mass-accretion rates more than ten times lower than previously thought. This suggests that the accretion rate is not the critical parameter for inducing inner-disk instabilities. Instead, we propose that a long orbital period is a key condition for these large-amplitude oscillations, because the outer part of the large disk in binaries with long orbital periods will have surface densities too low to maintain sustained mass accretion to the inner part of the disk. The lack of sustained accretion--not the actual rate--would then be the critical factor causing large-amplitude oscillations in long-period systems.

2.
Clin Exp Hypertens ; 44(1): 72-82, 2022 Jan 02.
Article in English | MEDLINE | ID: mdl-34724868

ABSTRACT

BACKGROUND: The intake of Saccharina japonica (SJ), a widely consumed brown seaweed, has been reported to decrease blood pressure (BP) in hypertensive rats. It has been suggested that this effect is related to an increase in fecal sodium excretion (SE) by alginate (Alg) to the gastrointestinal tract; however, the mechanism is still unclear. This study investigated how different seaweeds with different amounts of Alg suppressed BP increase and enhanced fecal SE in 2-kidney, 1-clip renovascular hypertensive (2K1C) rats given SJ diet. METHODS: Rats with 2K1C or sham operation were fed a normal-/high-salt diet with some kinds of seaweeds (5.0%, w/w) or SJ extract with different Alg contents for 6 weeks. We measured systolic BP every week and mean arterial pressure at the end, and measured the total and molecular weights of Alg in each seaweed. Then, we evaluated the relationship of the Alg amount in each seaweed with the suppression of BP increase in 2K1C rats. Finally, urinary and fecal SE for 24 h was measured. RESULTS: The intake of SJ, SJ extract, Saccharina ochotensis (SO) blades and SO roots suppressed BP increase in 2K1C rats, but the strength was not proportional to the amounts of Alg contained in the seaweeds. Although SJ intake increased fecal SE in 2K1C rats fed a high-salt diet, the fecal SE was much less than urinary SE. CONCLUSION: The sodium excretion in feces by Alg in SJ may not be one of the major mechanisms by which SJ intake attenuates hypertension in 2K1C rats.


Subject(s)
Hypertension, Renovascular , Hypertension , Seaweed , Alginates/pharmacology , Animals , Blood Pressure , Hypertension/drug therapy , Kidney , Rats , Surgical Instruments
3.
Pathol Int ; 69(3): 172-176, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30737997

ABSTRACT

Recently, a new entity "myoepithelioma-like tumor of the vulvar region (MELTVR)" was proposed as a rare mesenchymal neoplasm arising in vulvar regions of adult women. While MELTVRs morphologically resemble soft tissue myoepitheliomas and extraskeletal myxoid chondrosarcomas, they have a unique immunohistochemical profile (positive for epithelial membrane antigen and estrogen receptor, negative for S100 protein and glial fibrillary acidic protein, and loss of INI1/SMARCB1 expression), and lack EWSR1 and NR4A3 gene rearrangement, as seen by fluorescence in situ hybridization. MELTVRs are usually well-demarcated tumors, with no reports of extensive infiltrative growth. In the current report, we present an unusual case of MELTVR showing infiltrative growth and harboring only a few estrogen receptor-positive cells, which might indicate a variation in this rare tumor.


Subject(s)
Biomarkers, Tumor/genetics , Gene Rearrangement/genetics , Myoepithelioma/pathology , Receptors, Estrogen/metabolism , Calmodulin-Binding Proteins/genetics , Humans , Immunohistochemistry/methods , Mucin-1/immunology , Myoepithelioma/diagnosis
4.
Int J Clin Oncol ; 20(2): 262-7, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25652907

ABSTRACT

Whilst estrogen receptor (ER)-positive breast cancers are preferentially treated with hormone therapy, approximately one-third of them relapse. The mechanisms of refractoriness have been investigated by numerous studies but have not been fully clarified. Hormonal therapy resistance, particularly aromatase inhibitor (AI) resistance, may be related to the acquisition of alternative intracellular ER signaling. We have been investing the mechanisms using cancer specimens and cell lines by monitoring the transcription activity of ERs. AI refractory specimens showed diverse ER activity in the adenovirus estrogen receptor element-green fluorescent protein (ERE-GFP) assay and varied sensitivity to anti-estrogens, indicating the existence of multiple resistant mechanisms. We established six different types of cell lines mimicking AI resistance from ERE-GFP-introduced ER-positive cell lines. They revealed that multiple and alternative ER activating pathways were involved in the resistance, such as phosphorylation-dependent or androgen metabolite-dependent mechanisms. The response to fulvestrant and mammalian target of rapamycin inhibitor also varied among individual resistant cell lines. These results indicate that further subclassification of ER-positive breast cancer is extremely important to decide the therapeutic management of not only hormonal therapy but also new molecular target therapy.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Aromatase Inhibitors/therapeutic use , Breast Neoplasms/drug therapy , Drug Resistance, Neoplasm , Receptors, Estrogen/metabolism , Breast Neoplasms/chemistry , Cell Line, Tumor , Female , Humans , Ligands , Phosphorylation , Receptors, Estrogen/analysis , Receptors, Estrogen/genetics , Signal Transduction , Transcription, Genetic
5.
Biosci Biotechnol Biochem ; 78(2): 276-8, 2014.
Article in English | MEDLINE | ID: mdl-25036681

ABSTRACT

We have reported that new N-glycans carrying the TF-antigen occurred on a major royal jelly glycoprotein, and we have identified the glycosylation site to which the antigenic N-glycan is linked, but an appropriate procedure has not been established to prepare non-labeled immunoreactive glycopeptides in large amounts for functional analysis. In this study, we developed an effective method of preparing Asn-glycopeptide bearing TF-antigen.


Subject(s)
Antigens, Tumor-Associated, Carbohydrate/metabolism , Fatty Acids/chemistry , Glycopeptides/metabolism , Glycosylation
6.
Breast Cancer Res Treat ; 137(3): 773-82, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23288347

ABSTRACT

ATP-binding cassette (ABC) transporters are membrane proteins that efflux various compounds from cells, including chemotherapeutic agents, and are known to affect multidrug resistance. Recent reports disagree on whether ABCC11 is a risk factor for breast tumorigenesis, but its expression in breast cancer is poorly investigated. We hypothesized that both frequency and expression levels of ABC transporters in breast tumors would vary by cancer subtype, and be associated with prognosis. Here, we constructed a tissue microarray breast tumor samples from 281 patients, and analyzed expressions of ABCB1, ABCC1, ABCC11, and ABCG2 immunohistochemically. Breast cancer subtypes were determined by immunohistochemistry of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Protein expression was correlated to clinicopathological characteristics, clinical follow-up, and pathological complete response to neoadjuvant chemotherapy. The tissue microarray comprised 191 luminal A (68.0 %), 17 luminal B (6.0 %), 27 HER2 (9.6 %), and 46 triple-negative (16.4 %) samples. ABCC1 and ABCC11 expressions were associated with significantly shorter disease-free survival (P = 0.027 and P = 0.003, respectively). ABCC1, ABCC11, and ABCG2, but not ABCB1, were expressed significantly more, and more frequently, in aggressive subtypes. Patients with HER2+ and triple-negative tumor subtypes that expressed high levels of ABCC11 had significantly worse disease-free survival (P = 0.017 and P < 0.001, respectively). We have shown, for the first time, that ABCC1, ABCC11, and ABCG2 are highly expressed in aggressive breast cancer subtypes, and that tumor ABCC11 expression is associated with poor prognosis.


Subject(s)
ATP-Binding Cassette Transporters/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , ATP-Binding Cassette Transporters/genetics , Aged , Aged, 80 and over , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Disease Progression , Female , Gene Expression , Genotype , Humans , Middle Aged , Multidrug Resistance-Associated Proteins/genetics , Multidrug Resistance-Associated Proteins/metabolism , Neoadjuvant Therapy , Neoplasm Staging , Prognosis
7.
Biosci Biotechnol Biochem ; 77(6): 1269-74, 2013.
Article in English | MEDLINE | ID: mdl-23748790

ABSTRACT

In our previous report (M. Okano, et al., Clin. Exp. Allergy, 34, 770-778 (2004)), we found that free plant complex type N-glycans suppressed the production of IL4 from Th2 cells of Japanese cedar pollinosis patients, suggesting that plant complex type N-glycan can be used as a leading compound for developing immuno-pharmaceuticals. Although immunoreactive plant complex type N-glycans occur ubiquitously on glycoproteins expressed in plants, an appropriate procedure has not been established to prepare non-labeled immunoreactive glycans or glycopeptides bearing structurally homologous immunoreactive glycans in large amounts. In this study, therefore, we developed a new preparative procedure for the large-scale preparation of Asn-glycopeptide bearing plant complex type N-glycan using a combination of gel-filtration and the hydrophilic partitioning method. By this new method, about 103 mg of Asn-glycopeptide bearing the antigenic N-glycans was obtained from 1.9 kg of shelled Ginkgo biloba seeds.


Subject(s)
Antigens/immunology , Asparagine/chemistry , Glycopeptides/biosynthesis , Polysaccharides/metabolism , Antigens/chemistry , Asparagine/immunology , Chromatography, Gel , Chromatography, High Pressure Liquid , Ginkgo biloba/chemistry , Ginkgo biloba/immunology , Glycopeptides/chemistry , Glycopeptides/isolation & purification , Humans , Polysaccharides/chemistry , Polysaccharides/immunology , Polysaccharides/isolation & purification , Seeds/chemistry , Seeds/immunology
8.
J Cell Sci ; 123(Pt 5): 747-55, 2010 Mar 01.
Article in English | MEDLINE | ID: mdl-20164304

ABSTRACT

Visualization and quantification of the dynamics of protein-protein interactions in living cells can be used to explore the macromolecular events involved in signal transduction processes. In this study, functional molecular imaging using a luciferase-based complementation method demonstrated how the integrin-linked kinase (ILK)-mediated protein complex controls downstream signals. The luciferase complementation assay showed that Akt1 preferentially binds to beta-parvin rather than to ILK within the complex. Moreover, photon flux from the interaction between beta-parvin and Akt1 increased following serum stimulation, and the beta-parvin-Akt1 interaction was dependent on phosphoinositide 3-kinase. Intriguingly, small interfering (si)RNA-mediated beta-parvin knockdown increased photon flux from the interaction between ILK and Akt1, leading to stabilization of hypoxia-inducible factor-1alpha and increased expression of vascular endothelial growth factor-A. These data from functional molecular imaging demonstrated that beta-parvin plays a regulatory role in the ILK-mediated Akt (also called protein kinase B) signaling cascades, suggesting that beta-parvin might be a crucial modulator of cell survival.


Subject(s)
Actinin/metabolism , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Actinin/genetics , Animals , Blotting, Western , Cell Line , Cell Survival/genetics , Cell Survival/physiology , Humans , Hypoxia-Inducible Factor 1/metabolism , Immunoprecipitation , Mice , NIH 3T3 Cells , Phosphatidylinositol 3-Kinases/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/genetics , Signal Transduction/physiology , Vascular Endothelial Growth Factor A/metabolism
9.
Am J Physiol Heart Circ Physiol ; 302(9): H1871-83, 2012 May 01.
Article in English | MEDLINE | ID: mdl-22389386

ABSTRACT

To examine whether and how heart ANG II influences the coordination between cardiomyocyte hypertrophy and coronary angiogenesis and contributes to the pathogenesis of diabetic cardiomyopathy, we used Spontaneously Diabetic Torii (SDT) rats treated without and with olmesartan medoxomil (an ANG II receptor blocker). In SDT rats, left ventricular (LV) ANG II, but not circulating ANG II, increased at 8 and 16 wk after diabetes onset. SDT rats developed LV hypertrophy and diastolic dysfunction at 8 wk, followed by LV systolic dysfunction at 16 wk, without hypertension. The SDT rat LV exhibited cardiomyocyte hypertrophy and increased hypoxia-inducible factor-1α expression at 8 wk and to a greater degree at 16 wk and interstitial fibrosis at 16 wk only. In SDT rats, coronary angiogenesis increased with enhanced capillary proliferation and upregulation of the angiogenic factor VEGF at 8 wk but decreased VEGF with enhanced capillary apoptosis and suppressed capillary proliferation despite the upregulation of VEGF at 16 wk. In SDT rats, the phosphorylation of VEGF receptor-2 increased at 8 wk alone, whereas the expression of the antiangiogenic factor thrombospondin-1 increased at 16 wk alone. All these events, except for hyperglycemia or blood pressure, were reversed by olmesartan medoxomil. These results suggest that LV ANG II in SDT rats at 8 and 16 wk induces cardiomyocyte hypertrophy without affecting hyperglycemia or blood pressure, which promotes and suppresses coronary angiogenesis, respectively, via VEGF and thrombospondin-1 produced from hypertrophied cardiomyocytes under chronic hypoxia. Thrombospondin-1 may play an important role in the progression of diabetic cardiomyopathy in this model.


Subject(s)
Angiotensin II/physiology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Cardiomyopathies/physiopathology , Hypertrophy, Left Ventricular/physiopathology , Myocytes, Cardiac/pathology , Neovascularization, Physiologic/physiology , Angiotensin Receptor Antagonists/pharmacology , Animals , Apoptosis/physiology , Diabetes Mellitus, Type 2/complications , Diabetic Cardiomyopathies/etiology , Disease Models, Animal , Hypertrophy/physiopathology , Imidazoles/pharmacology , Male , Myocytes, Cardiac/drug effects , Olmesartan Medoxomil , Rats , Rats, Mutant Strains , Rats, Sprague-Dawley , Tetrazoles/pharmacology , Thrombospondin 1/physiology , Vascular Endothelial Growth Factor A/physiology , Ventricular Dysfunction, Left/physiopathology
10.
Oncol Res ; 20(2-3): 71-9, 2012.
Article in English | MEDLINE | ID: mdl-23193913

ABSTRACT

Breast cancer is not a single entity. This study therefore aimed to identify differences in the impacts of anticancer agents and predictive factors between different breast cancer subtypes. A total of 234 patients with luminal (n = 109), luminal-HER2 (L-H, n = 29), HER-2 (n = 35), or triple negative (TN, n = 61) breast cancer subtypes were treated with standard neoadjuvant chemotherapy consisting of an anthracycline and/or taxane. Pathological response and prognosis were examined in each subtype. Expression levels of estrogen and progesterone receptors, HER-2, nuclear grade, MIB-1, p53, topoisomerase IIalpha (topoIIalpha), cytokeratin (CK) 5/6, and epidermal growth factor receptor (EGFR) were examined in association with quasipathological complete response (QpCR). QpCR rates were 9.1% (10/109) in luminal, 45% (13/29) in L-H, 37% (13/35) in HER2, and 54.1% (33/61) in TN. Non-QpCR patients showed significantly poorer 3-year disease-free survival than QpCR patients in TN, but not in patients with other subtypes. No factors were associated with QpCR in luminal patients. Patients with higher nuclear grade were more likely to achieve QpCR in L-H. The proliferative markers MIB-1 and topoIlalpha had opposite impacts on pathological response in HER-2 and TN. The QpCR rate was significantly higher in TN lacking CK5/6 and/or EGFR expression, defined as nonbasal subtype, compared with basal subtype (p = 0.049). Cytotoxic anticancer agents were associated with different responses in different breast cancer subtypes. Identifying basal-type cancer and further subdivision of nonbasal types is important for treating TN patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/classification , Breast Neoplasms/mortality , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Adult , Aged , Aged, 80 and over , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Female , Humans , Middle Aged , Prognosis , Remission Induction , Survival Rate , Young Adult
11.
Biosci Biotechnol Biochem ; 76(10): 1996-8, 2012.
Article in English | MEDLINE | ID: mdl-23047116

ABSTRACT

We analyzed structural features of N-glycans linked to glycoproteins expressed in various seaweeds to identify new sources of biologically-important N-glycans or N-glycopeptides. Structural analysis of the N-glycans of glycopeptides prepared from pepsin digests of 15 species of seaweed revealed that only high-mannose type N-glycans occur in seaweed glycoproteins, and the Man9GlcNAc2 structure predominates in Sargassum fulvellum and Zostera marina, while no typical plant complex type N-glycans bearing ß1-2 xylosyl and α1-3 fucosyl residues present in either algae or seagrass. These results indicate that seaweeds lack the activities of several of the glycosyltransferases required for the biosynthesis of the complex type N-glycans found in terrestrial plants, and that the context of N-glycan processing in seaweeds is different from that in terrestrial plant cells.


Subject(s)
Glycoproteins/chemistry , Mannose , Polysaccharides/chemistry , Seaweed/chemistry , Gene Expression Regulation, Plant , Glycopeptides/chemistry , Glycopeptides/metabolism , Glycoproteins/metabolism
12.
PCN Rep ; 1(3): e45, 2022 Sep.
Article in English | MEDLINE | ID: mdl-38868688

ABSTRACT

Aim: Healthy older drivers may be at high risk of fatal traffic accidents. Our recent study showed that volumetric alterations in gray matter in the brain regions within the dorsal attention network (DAN) were strongly related to the risk of unsafe driving in healthy older people. However, the relationship between white matter (WM) structural connectivity and driving ability in healthy older people is still unclear. Methods: We used diffusion tensor imaging to examine the association between microstructural alterations in the DAN and the risk of unsafe driving among healthy older people. We enrolled 32 healthy older individuals aged over 65 years and screened unsafe drivers using an on-road driving test. We then determined the pattern of WM aberrations in unsafe drivers using tract-based spatial statistics. Results: The analysis demonstrated that unsafe drivers had significantly higher axial diffusivity values in nine WM clusters compared with safe drivers. These results were primarily observed bilaterally in the dorsal superior longitudinal fasciculus, which is involved in the DAN. Furthermore, correlation analyses showed that higher axial diffusivity values in the superior longitudinal fasciculus were associated with lower Trail Making Test A scores within unsafe drivers. This result suggests that functionally, WM microstructural alterations in the DAN are associated with attention problems, which may contribute to the risk of unsafe driving among healthy older people. Conclusion: Our findings may elucidate the neurobiological mechanisms underlying the increased risk of unsafe driving in healthy older people, potentially facilitating the development of new interventions to prevent fatal accidents.

13.
Biosci Biotechnol Biochem ; 75(1): 155-8, 2011.
Article in English | MEDLINE | ID: mdl-21228476

ABSTRACT

In this study, we analyzed structural features of the N-glycans linked to glycoproteins expressed in various edible beans to identify excellent sources of useful N-glycans and N-glycopeptides. Structural analysis of N-glycans of the glycopeptides prepared from the pepsin digests of bean powder that the useful high-mannose type N-glycans occur predominantly in Phaseolus and Vigna beans; tora bean for Man9GlcNAc2-Asn, dainagon bean for Man8GlcNAc2-Asn, and azuki bean for Man7GlcNAc2-Asn.


Subject(s)
Fabaceae/chemistry , Food , Glycoproteins/metabolism , Oligosaccharides/chemistry , Oligosaccharides/metabolism , Chromatography, High Pressure Liquid , Powders
14.
Biosci Biotechnol Biochem ; 74(10): 2148-50, 2010.
Article in English | MEDLINE | ID: mdl-20944402

ABSTRACT

In this study, we identified a royal jelly glycoprotein (RJG) that carries a unique complex-type N-glycans harboring the T-antigen (Galß1-3GalNAc) unit. The amino acid sequence of the tryptic glycopeptide harboring the T-antigen unit was G-E-S-L-X-K (X might be glycosylated Asn), confirmed in the major royal jelly glycoprotein 1 (MRJP1), which is also expressed in the mushroom body of the honeybee brain.


Subject(s)
Antigens/chemistry , Disaccharides , Galactans , Glycoproteins/analysis , Glycoproteins/chemistry , Nitrogen/chemistry , Polysaccharides/chemistry , Amino Acid Sequence , Glycoproteins/metabolism , Glycosylation , Molecular Sequence Data , Peptide Fragments/chemistry , Peptide Fragments/isolation & purification , Peptide Fragments/metabolism
15.
Int J Biol Macromol ; 147: 1294-1300, 2020 Mar 15.
Article in English | MEDLINE | ID: mdl-31751705

ABSTRACT

In the present study, for the discovery of uncharacterized glycan-binding receptors or lectin-like receptors in plants, we developed neoglycopolymers to which three types of N-glycopeptides are conjugated; the first with plant complex type N-glycan (M3FX), the second with high-mannose type N-glycan (M8), and the third with animal complex type N-glycan (NeuAc2Gal2GN2M3). Three types of Asn-oligosaccharide (Asn-M3FX, Asn-M8, or Asn-NeuAc2Gal2GN2M3) were prepared from storage glycoproteins of Ginkgo biloba seeds, Vigna angularis seeds, and egg yolk glycopeptides from actinase digests of each glycoproteins or glycopeptide. Neoglycopolymers were synthesized such that the α-amino groups of Asn-oligosaccharide were coupled to the carboxyl groups of poly-γ-L-glutamic acid (γ-L-PGA) with 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride n-hydrate (DMT-MM). The resulting neoglycopolymers were purified through a combination of gel-filtration and reverse-phase HPLC. The incorporation of N-glycans into γ-L-PGA (mol%) was estimated through amino acid composition analysis after acid hydrolysis. The incorporation rates of Asn-M3FX, Asn-M8, and Asn-NeuAc2Gal2GN2M3 into γ-L-PGA were 15.4%, 8.6%, and 11.1%, indicating that nearly 890, 500, and 640 molecules of N-glycans were conjugated with γ-L-PGA, respectively. Furthermore, we confirmed that the neoglycopolymer carrying the multivalent high-mannose type N-glycans is a useful tool for rapid purification of mannose-binding protein, Concanavalin A, from jack bean extract.


Subject(s)
Egg Yolk/chemistry , Glycopeptides/chemistry , Polymers/chemistry , Animals , Chromatography, Gel , Concanavalin A/chemistry , Ginkgo biloba/chemistry , Glycoproteins/chemistry , Hydrolysis , Mannose/chemistry , Oligosaccharides/chemistry , Polysaccharides/chemistry , Seeds/chemistry , Spectrometry, Mass, Electrospray Ionization , Vigna/chemistry
16.
Int J Biol Macromol ; 153: 1016-1023, 2020 Jun 15.
Article in English | MEDLINE | ID: mdl-31747570

ABSTRACT

Plant glycoproteins, especially allergenic glycoproteins such as pollen allergens, often carry antigenic N-glycans with α1-3 fucose and/or ß1-2 xylose residue(s) on the trimannosyl core structure. We previously reported that one of such antigenic free-form N-glycans, Man3Xyl1Fuc1GlcNAc2 (M3FX) suppressed IL-4 production from Th2 cells of pollinosis patients. For the molecular-level analysis of this immunoactivity, an effective and convenient procedure for large scale preparation of the immunoactive free-form N-glycan and a synthesis of glycopolymers bearing multivalent M3FX has been required. During the preparation of prebiotic oligosaccharides from several edible beans, we found that the free-form M3FX accumulates in relatively large amounts in white kidney beans. In this report, we describe a new procedure for preparation of M3FX from white kidney bean powders by a combination of ion-exchange method, gel-filtration, and hydrophilic partitioning. The high-purity of M3FX prepared by this procedure was confirmed by MS-analysis and 1H-NMR, suggesting that the free-form M3FX can be used for the synthesis of neoglycopolymer. Using this new procedure, the immunoactive oligosaccharide can be prepared without the chemical method such as hydrazinolysis and other purification steps required to exclude other type of N-glycans.


Subject(s)
Allergens/chemistry , Glycoproteins/chemistry , Glycoproteins/chemical synthesis , Oligosaccharides/chemistry , Phaseolus/chemistry , Allergens/immunology , Chemistry Techniques, Synthetic , Glycoproteins/immunology , Powders
17.
Surg Case Rep ; 6(1): 203, 2020 Aug 08.
Article in English | MEDLINE | ID: mdl-32770432

ABSTRACT

BACKGROUND: Nipple-areola complex (NAC) reconstruction is a technique used in breast reconstructive surgery, which is performed during the final stage of breast reconstruction after total mastectomy of primary breast cancer. Composite nipple grafts utilizing the contralateral NAC are common; however, to our knowledge, there are no reports of new primary invasive ductal carcinoma development within the graft. Here, we describe one such case for the first time. CASE PRESENTATION: A 54-year-old woman was referred to us by the Department of Plastic and Reconstructive Surgery in our medical center for further evaluation of right nipple erosion. She had undergone total mastectomy of the right breast following a breast cancer diagnosis 15 years ago, at which time tumor biological profiling revealed the following: estrogen receptor (ER), positive; progesterone receptor (PgR), negative; and human epidermal growth factor receptor 2 (HER2), undetermined. She received adjuvant chemotherapy and endocrine therapy. She defaulted endocrine therapy for a few years, and 7 years after surgery, she underwent autologous breast reconstruction with a deep inferior epigastric perforator (DIEP) flap. In the following year, NAC reconstruction was performed using a composite graft technique. Seven years after the NAC reconstruction, erosion appeared on the nipple grafted from its contralateral counterpart; scrape cytology revealed malignancy. The skin on the right side of her chest around the NAC and subcutaneous fat tissue consisted of transferred tissue from the abdomen, as the DIEP flap and grafted nipple were located on the graft skin. The right nipple carcinoma arose from the tissue taken from the left nipple. Magnetic resonance imaging (MRI) or computed tomography showed no malignant findings in the left breast. As the malignant lesion seemed limited to the area around the grafted right nipple on MRI, surgical resection with sufficient lateral and deep margins was performed around the right nipple. Pathological findings revealed invasive ductal carcinoma with comedo ductal components infiltrating the graft skin and underlying adipose tissue. Immunohistochemistry revealed positive for ER, PgR, and HER2. CONCLUSIONS: To our knowledge, this is the first case involving the development of invasive ductal carcinoma in a nipple graft constructed on the skin of a DIEP flap, with the origin from the contralateral breast's nipple.

18.
Front Aging Neurosci ; 12: 592979, 2020.
Article in English | MEDLINE | ID: mdl-33343333

ABSTRACT

In developed countries, the number of traffic accidents caused by older drivers is increasing. Approximately half of the older drivers who cause fatal accidents are cognitively normal. Thus, it is important to identify older drivers who are cognitively normal but at high risk of causing fatal traffic accidents. However, no standardized method for assessing the driving ability of older drivers has been established. We aimed to establish an objective assessment of driving ability and to clarify the neural basis of unsafe driving in healthy older people. We enrolled 32 healthy older individuals aged over 65 years and classified unsafe drivers using an on-road driving test. We then utilized a machine learning approach to distinguish unsafe drivers from safe drivers based on clinical features and gray matter volume data. Twenty-one participants were classified as safe drivers and 11 participants as unsafe drivers. A linear support vector machine classifier successfully distinguished unsafe drivers from safe drivers with 87.5% accuracy (sensitivity of 63.6% and specificity of 100%). Five parameters (age and gray matter volume in four cortical regions, including the left superior part of the precentral sulcus, the left sulcus intermedius primus [of Jensen], the right orbital part of the inferior frontal gyrus, and the right superior frontal sulcus), were consistently selected as features for the final classification model. Our findings indicate that the cortical regions implicated in voluntary orienting of attention, decision making, and working memory may constitute the essential neural basis of driving behavior.

19.
J Theor Biol ; 260(1): 90-7, 2009 Sep 07.
Article in English | MEDLINE | ID: mdl-19505480

ABSTRACT

Evolutionary conflict between the sexes has been studied in various taxa and in various contexts. When the sexes are in conflict over mating rates, natural selection favors both males that induce higher mating rates and females that are more successful at resisting mating attempts. Such sexual conflict may result in an escalating coevolutionary arms race between males and females. In this article, we develop simple replicator-dynamics models of sexual conflict in order to investigate its evolutionary dynamics. Two specific models of the dependence of a female's fitness on her number of matings are considered: in model 1, female fitness decreases linearly with increasing number of matings and in model 2, there is an optimal number of matings that maximizes female fitness. For each of these models, we obtain the conditions for a coevolutionary process to establish costly male and female traits and examine under what circumstances polymorphism is maintained at equilibrium. Then we discuss how assumptions in previous models of sexual conflict are translated to fit to our model framework and compare our results with those of the previous studies. The simplicity of our models allows us to consider sexual conflict in various contexts within a single framework. In addition, we find that our model 2 shows more complicated evolutionary dynamics than model 1. In particular, the population exhibits bistability, where the evolutionary outcome depends on the initial state, only in model 2.


Subject(s)
Conflict, Psychological , Models, Genetic , Sexual Behavior, Animal , Animals , Biological Evolution , Female , Male , Mating Preference, Animal
20.
Biosci Biotechnol Biochem ; 72(2): 514-22, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18256500

ABSTRACT

In this report, we describe that a salt adaptation of plant cells induces glycoform changes in N-glycoproteins. Intracellular and cell-wall glycopeptides were prepared from glycoproteins expressed in wild-type BY2 cells and salt-adapted cells. N-Glycans were liberated from those glycopeptides by hydrazinolysis, and the released oligosaccharides were N-acetylated and pyridylaminated. The structures of pyridylaminated (PA-) N-glycans were analyzed by a combination of two-dimensional sugar-chain mapping, MS analysis, and exoglycosidase digestion. In both wild-type cells and salt-adapted cells, the plant complex type structure was predominant among N-glycans expressed on glycoproteins, but we found that the Man2Xyl1Fuc1GlcNAc2 structure was significantly expressed on intracellular and cell-wall glycoproteins of the salt-adapted cells. Furthermore, enhancement of the specific activities of alpha-mannosidase and beta-N-acetylglucosaminidase was observed in the salt-adapted BY2 cells, suggesting that the glycoform changes are due to changes in glycosidase activities.


Subject(s)
Adaptation, Physiological , Glucosidases/metabolism , Nicotiana/physiology , Polysaccharides/metabolism , Sodium Chloride/metabolism , Carbohydrate Sequence , Cell Line , Chromatography, High Pressure Liquid , Molecular Sequence Data , Polysaccharides/chemistry , Spectrometry, Mass, Electrospray Ionization , Nicotiana/cytology , Nicotiana/enzymology , Nicotiana/metabolism
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