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  • 1
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1005, No. 1 ( 2003-11), p. 440-448
    Abstract: A bstract : Type 1 diabetes is an organ‐specific autoimmune disease characterized by T cell‐mediated destruction of pancreatic β cells. In Japanese population, the incidence of type 1 diabetes in children is very low compared to European countries. However, there are more patients with type 1 diabetes in adults, including latent autoimmune diabetes in adults (LADA). The circulating autoantibodies to multiple islet autoantigens including GAD, insulin, and IA‐2 are the important immunological features of type 1 diabetes. The prevalences of anti‐islet autoantibodies in patients with Japanese type 1 diabetes are 60‐70% for GAD autoantibodies, 45‐50% for insulin autoantibodies (IAA), and 60‐65% for IA‐2 autoantibodies at disease onset, which are similar to those reported in Caucasian patients. With combinatorial analysis of these autoantibodies, 90% of patients express at least one of these autoantibodies and are classified as type 1A diabetes. Although the majority of patients with type 1 diabetes are young, lean, and ketosis‐prone, there are a number of patients with type 1 diabetes initially diagnosed as having type 2 diabetes at disease onset called LADA. These patients with LADA often progress toward an insulin‐deficient state within several years after diagnosis. High levels of GAD autoantibodies have a high predictive value for future insulin deficiency in LADA. Further, epitope analysis of GAD65 autoantibodies may be helpful to predict future insulin dependency in LADA patients. In conclusion, Japanese patients with type 1 diabetes are clinically heterogeneous and the determination of immunological features are helpful to clarify the characteristics of the Japanese type 1 diabetic syndrome.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2003
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  • 2
    In: Cancer Science, Wiley, Vol. 110, No. 8 ( 2019-08), p. 2667-2675
    Abstract: Multicellular structures, such as tumor buddings and poorly differentiated clusters ( PDC ), exist at the invasive front of colorectal cancers ( CRC ). Although it has been reported that CRC with PDC showed frequent lymph node metastases with a worse prognosis, the molecular markers of PDC that are responsible for prognosis have not been identified. We here noticed for the first time that Ezrin, a regulator of the actin cytoskeleton, is expressed in the corner cells of PDC . We then aimed to verify whether heterogeneous Ezrin expression in PDC predicts the prognosis of CRC patients. We immunohistochemically analyzed Ezrin expression in PDC of 184 patients with completely resected stages I‐III CRC . We established the Ezrin corner score ( ECS ), which quantifies the tendency of Ezrin‐positive cells to accumulate at the corners of PDC . On the basis of ECS values, 2 indices, the mean ECS and the number of PDC with high ECS , were obtained. Both indices were significantly higher in CRC with lymphatic invasion, higher PDC grade, and presence of micropapillary ( MP ) PDC . The mean ECS ‐high group showed shorter recurrence‐free survival than the mean ECS ‐low group but without significance. The other index, the number of ECS ‐high PDC , was significantly associated with recurrence‐free survival. These results suggest that Ezrin is involved in PDC progression and lymphatic invasion, and that ECS may be a marker for aggressive PDC .
    Type of Medium: Online Resource
    ISSN: 1347-9032 , 1349-7006
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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  • 3
    In: Cancer Science, Wiley, Vol. 110, No. 1 ( 2019-01), p. 356-365
    Abstract: We previously identified a novel nanomagnetic particle, N , N ′ ‐ bis(salicylidene)ethylenediamine iron [Fe(Salen)]. Fe(Salen) not only shows antitumor effects but also magnetic properties. We found that Fe(Salen) can be used for magnet‐guided drug delivery and visualization of accumulated drug by magnetic resonance imaging (MRI) because of its magnetism. In addition, Fe(Salen) can generate heat by itself when exposed to an alternating current magnetic field (AMF), resulting in a hyperthermia effect. Herein, we partly elucidated the antitumor mechanism of Fe(Salen) and carried out an i.v. repeated dose toxicity study to decide the therapeutic amount. Furthermore, we evaluated the antitumor effect of selective intra‐arterial injection or i.v. injection of Fe(Salen) by catheter and the hyperthermia effect of Fe(Salen) when exposed to AMF in vivo. We used a rabbit model grafted with VX2 cells (rabbit squamous cell carcinoma) on the right leg. Intra‐arterial injection of Fe(Salen) showed a greater antitumor effect than did i.v. injection. The combination of Fe(Salen) intra‐arterial injection and AMF exposure showed a greater antitumor effect than did either Fe(Salen) or methotrexate (MTX) without AMF exposure, suggesting that AMF exposure greatly enhanced the antitumor effect of Fe(Salen) by arterial injection by catheter. This is the first report that the effectiveness of Fe(Salen) was evaluated in the point of administration route; that is, selective intra‐arterial injection by catheter. Taken together, these results indicate a new administration route; that is, selective arterial injection of Fe(Salen) by catheter, and the development of a new strategy of simultaneous hyperthermia‐chemotherapy in the future.
    Type of Medium: Online Resource
    ISSN: 1347-9032 , 1349-7006
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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  • 4
    Online Resource
    Online Resource
    Wiley ; 2014
    In:  Journal of the American Oil Chemists' Society Vol. 91, No. 11 ( 2014-11), p. 1885-1890
    In: Journal of the American Oil Chemists' Society, Wiley, Vol. 91, No. 11 ( 2014-11), p. 1885-1890
    Abstract: Oleic acid esters of phytosterols (PSs) and triterpene alcohols (TAs), derived from rice bran, were synthesized using lipases under mild conditions. Some lipases, especially from Candida rugosa , type VII, showed very high substrate specificity towards both PSs and TAs, when a mixture of PS and TA (PS/TA mixture) was used as the substrate source. The maximum yield of PS esters was ca. 80 % in each case; however, the maximum yield of TA esters was much lower when the reaction was continued for 7 days. Due to the difficulty in purifying the esters obtained when the PS/TA mixture was used as source of substrate, free PSs and TAs were separated from the PS/TA mixture by silica‐gel and reverse‐phase chromatography prior to esterification. The pure PSs or TAs were esterified with oleic acid to obtain the corresponding esters with high purity. Differential scanning calorimetric analysis of the resulting esters revealed that their melting points ranged from 7.0 to 42 °C. These values were at least 100 °C lower than those of the free PSs and TAs.
    Type of Medium: Online Resource
    ISSN: 0003-021X , 1558-9331
    Language: English
    Publisher: Wiley
    Publication Date: 2014
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  • 5
    In: Food Science & Nutrition, Wiley, Vol. 11, No. 6 ( 2023-06), p. 2776-2786
    Abstract: The aging process is affected by various stressors. An increase in oxidative stress is related to the impairment of physiological functions and enhancement of glycative stress. Food‐derived bioactive peptides have various physiological functions, including antioxidant activities. Dipeptides comprising Leu and Lys (LK and KL, respectively) have been isolated from foods; however, their physiological properties remain unclear. In this study, we investigated the antioxidant/antiglycation activity of dipeptides and their antiaging effects using Caenorhabditis elegans ( C .  elegans ). Both dipeptides showed antioxidant activities against several reactive oxygen species (ROS) in vitro. In particular, the scavenging activity of LK against superoxide radicals was higher than KL did. Moreover, dipeptides suppressed advanced glycation end products (AGEs) formation in the BSA–glucose model. In the lifespan assays using wild‐type C .  elegans , both LK and KL significantly prolonged the mean lifespan by 20.9% and 11.7%, respectively. In addition, LK decreased intracellular ROS and superoxide radical levels in C .  elegans . Blue autofluorescence, an indicator of glycation in C .  elegans with age, was also suppressed by LK. These results suggest that dipeptides, notably LK, show an antiaging effect by suppressing oxidative and glycative stress. Our findings suggest that such dipeptides can be used as a novel functional food ingredient. Food‐derived dipeptide Leu–Lys (LK) and Lys–Leu (KL) exert antioxidant and antiglycation activity in vitro. Treatment with LK prolonged the mean lifespan and maximum lifespan of C .  elegans more than that of KL. Intracellular ROS and blue autofluorescence levels (indicator of aging) were suppressed by LK.
    Type of Medium: Online Resource
    ISSN: 2048-7177 , 2048-7177
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 6
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1005, No. 1 ( 2003-11), p. 344-347
    Abstract: A bstract : Type 1 diabetes is a heterogeneous autoimmune disease and is frequently associated with other organ‐specific autoimmune diseases, including autoimmune thyroid disease (AITD). Type 1 diabetic patients with AITD are known to show distinct clinical and immunological features from patients without AITD. This study investigated whether interleukin‐10 (IL‐10) gene promoter region polymorphisms are associated with susceptibility to type 1 diabetes and AITD. The frequency of −1082G/A, −819C/T, and −592C/A polymorphisms was analyzed in 54 type 1 diabetic patients with AITD, 74 type 1 diabetic patients without AITD, 124 nondiabetic patients with AITD, and 107 healthy subjects in a case‐control study. No significant differences on the allele and genotype frequencies of three polymorphisms were found not only in type 1 diabetic patients with AITD compared with normal controls, but also between nondiabetic patients with AITD and healthy controls. The distribution of IL‐10 gene haplotypes was also similar between both patient groups and normal controls. These results suggest that IL‐10 gene promoter region polymorphisms are not associated with genetic susceptibility to type 1 diabetes and AITD.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2003
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    SSG: 11
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  • 7
    In: Cancer Science, Wiley, Vol. 109, No. 11 ( 2018-11), p. 3483-3493
    Abstract: We previously reported the efficacy of anti‐cancer therapy with hyperthermia using an alternating magnetic field ( AMF ) and a magnetic compound. In the course of the study, unexpectedly, we found that an AMF enhances the cytotoxicity of Compound C, an activated protein kinase ( AMPK ) inhibitor, although this compound is not magnetic. Therefore, we examined the cellular mechanism of AMF ‐induced cytotoxicity of Compound C in cultured human glioblastoma ( GB ) cells. An AMF (280 kH z, 250 Arms) for 30 minutes significantly enhanced the cytotoxicity of Compound C and promoted apoptosis towards several human GB cell lines in vitro. The AMF also increased Compound C‐induced cell‐cycle arrest of GB cells at the G2 phase and, thus, inhibited cell proliferation. The AMF increased Compound C‐induced reactive oxygen species production. Furthermore, the AMF decreased ERK phosphorylation in the presence of Compound C and suppressed the protective autophagy induced by this compound. The application of an AMF in cancer chemotherapy may be a simple and promising method, which might reduce the doses of drugs used in future cancer treatment and, therefore, the associated side effects.
    Type of Medium: Online Resource
    ISSN: 1347-9032 , 1349-7006
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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  • 8
    In: ChemInform, Wiley, Vol. 33, No. 25 ( 2010-05-21), p. no-no
    Type of Medium: Online Resource
    ISSN: 0931-7597 , 1522-2667
    Language: English
    Publisher: Wiley
    Publication Date: 2010
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  • 9
    In: ChemMedChem, Wiley, Vol. 16, No. 11 ( 2021-06-07), p. 1814-1821
    Abstract: Immunoglobulin G (IgG)‐binding peptides such as 15‐IgBP are convenient tools for the site‐specific modification of antibodies and the preparation of homogeneous antibody–drug conjugates. A peptide such as 15‐IgBP can be selectively crosslinked to the fragment crystallizable region of human IgG in an affinity‐dependent manner via the ϵ‐amino group of Lys8. Previously, we found that the peptide 15‐Lys8Leu has a high affinity ( K d =8.19 nM) due to the presence of the γ‐dimethyl group in Leu8. The primary amino group required for the crosslinking to the antibodies has, however, been lost. Here, we report the design and synthesis of a novel unnatural amino acid, 4‐(2‐aminoethylcarbamoyl)leucine (Aecl), which possesses both the γ‐dimethyl fragment and a primary amino group. A peptide containing Aecl8 (15‐Lys8Aecl) was synthesized and showed a binding affinity ten times higher ( K d =24.3 nM) than that of 15‐IgBP ( K d =267 nM). Fluorescein isothiocyanate (FITC)‐labeled 15‐Lys8Aecl with an N ‐hydroxy succinimide ester at the side chain of Aecl8 (FITC‐15‐Lys8Aecl(OSu)) successfully labeled an antibody (trastuzumab, Herceptin ® ) with the fluorophore. This peptide scaffold has both strong binding affinity and crosslinking capability, and could be a useful tool for the selective chemical modification of antibodies with molecules of interest such as drugs.
    Type of Medium: Online Resource
    ISSN: 1860-7179 , 1860-7187
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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    SSG: 15,3
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  • 10
    In: Cancer Science, Wiley, Vol. 111, No. 1 ( 2020-01), p. 160-174
    Abstract: The EP4 prostanoid receptors are one of four receptor subtypes for prostaglandin E 2 (PGE 2 ). Therefore, EP4 may play an important role in cancer progression. However, little information is available regarding their function per se, including migration and the cellular signaling pathway of EP4 in oral cancer. First, we found that mRNA and protein expression of EP4 was abundantly expressed in human‐derived tongue squamous cell carcinoma cell lines HSC‐3 and OSC‐19. The EP4 agonist (ONO‐AE1‐437) significantly promoted cell migration in HSC‐3 cells. In contrast, knockdown of EP4 reduced cell migration. Furthermore, we confirmed that knockdown of EP4 suppressed metastasis of oral cancer cells in the lungs of mice in vivo. Therefore, we focused on the mechanism of migration/metastasis in EP4 signaling. Interestingly, EP4 agonist significantly induced intracellular Ca 2+ elevation not in only oral cancer cells but also in other cells, including normal cells. Furthermore, we found that EP4 activated PI3K and induced Ca 2+ influx through Orai1 without activation of store depletion and stromal interaction molecule 1 (STIM1). Immunoprecipitation showed that EP4 formed complexes with Orai1 and TRPC1, but not with STIM. Moreover, the EP4 agonist ONO‐AE1‐437 phosphorylated ERK and activated MMP‐2 and MMP‐9. Knockdown of Orai1 negated EP4 agonist‐induced ERK phosphorylation. Taken together, our data suggested that EP4 activated PI3K and then induced Ca 2+ influx from the extracellular space through Orai1, resulting in ERK phosphorylation and promoting cell migration. Migration is regulated by EP4/PI3K/Orai1 signaling in oral cancer.
    Type of Medium: Online Resource
    ISSN: 1347-9032 , 1349-7006
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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