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  1. Artikel: ABCB1 c.2677G>T/c.3435C>T diplotype increases the early-phase oral absorption of losartan.

    Shin, Hyo-Bin / Jung, Eui Hyun / Kang, Pureum / Lim, Chang Woo / Oh, Kyung-Yul / Cho, Chang-Keun / Lee, Yun Jeong / Choi, Chang-Ik / Jang, Choon-Gon / Lee, Seok-Yong / Bae, Jung-Woo

    Archives of pharmacal research

    2020  Band 43, Heft 11, Seite(n) 1187–1196

    Abstract: ... gene. ABCB1 c.2677G>T and c.3435C>T variants are known to be associated with reduced expression and ... of losartan. Thirty-eight healthy Korean volunteers with different ABCB1 diplotypes [c.2677G> T and c.3435C>T ... the concentrations of both samples were determined by HPLC method. Significant differences were observed in C ...

    Abstract Losartan has been shown to be a substrate of the drug-efflux transporter MDR1, encoded by the ABCB1 gene. ABCB1 c.2677G>T and c.3435C>T variants are known to be associated with reduced expression and function of P-glycoprotein (P-gp). We investigated the effects of ABCB1 diplotype on the pharmacokinetics of losartan. Thirty-eight healthy Korean volunteers with different ABCB1 diplotypes [c.2677G> T and c.3435C>T; carriers of GG/CC (n = 13), GT/CT (n = 12) and TT/TT (n = 13) diplotype] were recruited and administered a single 50 mg oral dose of losartan potassium. Losartan and its active metabolite E-3174 samples in plasma and urine were collected up to 10 and 8 h after drug administration, respectively, and the concentrations of both samples were determined by HPLC method. Significant differences were observed in C
    Mesh-Begriff(e) ATP Binding Cassette Transporter, Subfamily B/genetics ; ATP Binding Cassette Transporter, Subfamily B/metabolism ; Administration, Oral ; Adult ; Angiotensin II Type 1 Receptor Blockers/administration & dosage ; Angiotensin II Type 1 Receptor Blockers/pharmacokinetics ; Chromatography, High Pressure Liquid ; Gastrointestinal Absorption ; Genotype ; Humans ; Losartan/administration & dosage ; Losartan/pharmacokinetics ; Pharmacogenetics ; Pharmacogenomic Variants ; Republic of Korea ; Young Adult
    Chemische Substanzen ABCB1 protein, human ; ATP Binding Cassette Transporter, Subfamily B ; Angiotensin II Type 1 Receptor Blockers ; Losartan (JMS50MPO89)
    Sprache Englisch
    Erscheinungsdatum 2020-11-29
    Erscheinungsland Korea (South)
    Dokumenttyp Comparative Study ; Journal Article
    ZDB-ID 447623-2
    ISSN 1976-3786 ; 0253-6269
    ISSN (online) 1976-3786
    ISSN 0253-6269
    DOI 10.1007/s12272-020-01294-3
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: ABCB1 c.2677G>T/c.3435C>T diplotype increases the early-phase oral absorption of losartan

    Shin, Hyo-Bin / Jung, Eui Hyun / Kang, Pureum / Lim, Chang Woo / Oh, Kyung-Yul / Cho, Chang-Keun / Lee, Yun Jeong / Choi, Chang-Ik / Jang, Choon-Gon / Lee, Seok-Yong / Bae, Jung-Woo

    Archives of pharmacal research. 2020 Nov., v. 43, no. 11

    2020  

    Abstract: ... gene. ABCB1 c.2677G>T and c.3435C>T variants are known to be associated with reduced expression and ... of losartan. Thirty-eight healthy Korean volunteers with different ABCB1 diplotypes [c.2677G> T and c.3435C>T ... in the TT/TT group was higher than that of the GG/CC group. These results suggest that c.2677G>T/c.3435C>T ...

    Abstract Losartan has been shown to be a substrate of the drug-efflux transporter MDR1, encoded by the ABCB1 gene. ABCB1 c.2677G>T and c.3435C>T variants are known to be associated with reduced expression and function of P-glycoprotein (P-gp). We investigated the effects of ABCB1 diplotype on the pharmacokinetics of losartan. Thirty-eight healthy Korean volunteers with different ABCB1 diplotypes [c.2677G> T and c.3435C>T; carriers of GG/CC (n = 13), GT/CT (n = 12) and TT/TT (n = 13) diplotype] were recruited and administered a single 50 mg oral dose of losartan potassium. Losartan and its active metabolite E-3174 samples in plasma and urine were collected up to 10 and 8 h after drug administration, respectively, and the concentrations of both samples were determined by HPLC method. Significant differences were observed in Cₘₐₓ of losartan and losartan plus E-3174 (Lo + E) among the three diplotype groups (both P < 0.01). However, the power of the performed test is less than the desired power (0.800). The tₘₐₓ of losartan and E-3174 in three diplotype groups were also significantly different (both P < 0.01). The AUC values of Lo + E were significantly different among the three diplotype groups until 6 h after losartan administration (P < 0.01). On the contrary, AUC at the periods of 8–10 h and 10 h-infinity of Lo + E were significantly lower in the TT/TT group than in the GG/CC group. Urinary excretion of losartan until 4 h after losartan administration in the TT/TT group was higher than that of the GG/CC group. These results suggest that c.2677G>T/c.3435C>T diplotypes of ABCB1 may significantly increase the early-phase absorption of losartan, but not the total absorption.
    Schlagwörter P-glycoproteins ; absorption ; drugs ; excretion ; genes ; metabolites ; oral administration ; pharmacokinetics ; potassium ; research ; urine
    Sprache Englisch
    Erscheinungsverlauf 2020-11
    Umfang p. 1187-1196.
    Erscheinungsort Pharmaceutical Society of Korea
    Dokumenttyp Artikel
    Anmerkung NAL-AP-2-clean
    ZDB-ID 447623-2
    ISSN 1976-3786 ; 0253-6269
    ISSN (online) 1976-3786
    ISSN 0253-6269
    DOI 10.1007/s12272-020-01294-3
    Datenquelle NAL Katalog (AGRICOLA)

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  3. Artikel ; Online: Preparation of Nanoemulsions of Vitamin A and C by Microfluidization: Efficacy on the Expression Pattern of Milk-Specific Proteins in MAC-T Cells.

    Kim, Tae-Il / Kim, Tae-Gyun / Lim, Dong-Hyun / Kim, Sang-Bum / Park, Seong-Min / Hur, Tai-Young / Ki, Kwang-Seok / Kwon, Eung-Gi / Vijayakumar, Mayakrishnan / Kim, Young-Jun

    Molecules (Basel, Switzerland)

    2019  Band 24, Heft 14

    Abstract: ... of nanoemulsified vit-A and vit-C on the in vitro expression pattern of milk-specific proteins in MAC-T cells was ... In this study, we prepared stabilized vitamin A and C nanoemulsions, and investigated ... their efficacy on milk-specific proteins in bovine mammary epithelial cells (MAC-T). Emulsions of vitamin A (vit ...

    Abstract In this study, we prepared stabilized vitamin A and C nanoemulsions, and investigated their efficacy on milk-specific proteins in bovine mammary epithelial cells (MAC-T). Emulsions of vitamin A (vit-A) and C (vit-C) were prepared using Lipoid S 75 and microfluidization. The particle size and polydispersity index (PDI) of nanoemulsified vit-A and vit-C were studied. The cytotoxic effect of nanoemulsion-free and nanoemulsified vit-A and vit-C was determined by an MTT assay. In addition, the efficacy of nanoemulsified vit-A and vit-C on the in vitro expression pattern of milk-specific proteins in MAC-T cells was investigated by quantitative RT-PCR. The results showed that the efficacies of stabilized nanoemulsions of vit-A and vit-C were 100% and 92.7%, respectively. The particle sizes were around 475.7 and 225.4 nm, and the zeta potentials were around -33.5 and -21.3 mV, respectively. The expression changes of α
    Mesh-Begriff(e) Animals ; Ascorbic Acid/chemistry ; Ascorbic Acid/pharmacology ; Cattle ; Cell Line ; Drug Stability ; Emulsions ; Female ; Gene Expression Regulation/drug effects ; Mammary Glands, Animal/cytology ; Mammary Glands, Animal/drug effects ; Mammary Glands, Animal/metabolism ; Microfluidic Analytical Techniques ; Milk Proteins/drug effects ; Milk Proteins/metabolism ; Nanoparticles ; Particle Size ; Vitamin A/chemistry ; Vitamin A/pharmacology
    Chemische Substanzen Emulsions ; Milk Proteins ; Vitamin A (11103-57-4) ; Ascorbic Acid (PQ6CK8PD0R)
    Sprache Englisch
    Erscheinungsdatum 2019-07-15
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules24142566
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Identification of a rare homozygous c.790C>T variation in the TFB2M gene in Korean patients with autism spectrum disorder.

    Park, Chan Bae / Choi, Vit-Na / Jun, Jae-Bum / Kim, Ji-Hae / Lee, Youngsoo / Lee, Jinhyuk / Lim, GyuTae / Kim, Jeonghyun / Jeong, Seon-Yong / Yim, Shin-Young

    Biochemical and biophysical research communications

    2018  Band 507, Heft 1-4, Seite(n) 148–154

    Abstract: ... in any human diseases. We identified a rare homozygous c.790C>T (His264Tyr) variation in TFB2M gene in two Korean ...

    Abstract Mitochondrial dysfunction and subsequent enhanced oxidative stress is implicated in the pathogenesis of autism spectrum disorder (ASD). Mitochondrial transcription factor B2 (TFB2M) is an essential protein in mitochondrial gene expression. No reports have described TFB2M mutations and variations involved in any human diseases. We identified a rare homozygous c.790C>T (His264Tyr) variation in TFB2M gene in two Korean siblings with ASD by whole-exome sequencing. The roles of the TFB2M variation in the pathogenesis of ASD were investigated. Patient fibroblasts revealed increased transcription of mitochondrial genes and mitochondrial function in terms of ATP, membrane potential, oxygen consumption, and reactive oxygen species (ROS). Overexpression of the TFB2M variant in primary-cultured fibroblasts demonstrated significantly increased transcription of mitochondrial genes and mitochondrial function compared with overexpression of wild-type TFB2M. Molecular dynamics simulation of the TFB2M variant protein suggested an increase in the rigidity of the hinge region, which may cause alterations in loading and/or unloading of TFB2M on target DNA. Our results suggest that augmentation of mitochondrial gene expression and subsequent enhancement of mitochondrial function may be associated with the pathogenesis of ASD in Korean patients.
    Mesh-Begriff(e) Asian Continental Ancestry Group/genetics ; Autism Spectrum Disorder/genetics ; Base Sequence ; Cells, Cultured ; Child, Preschool ; DNA, Mitochondrial/genetics ; Female ; Fibroblasts/metabolism ; Gene Expression Regulation ; Genetic Predisposition to Disease ; Homozygote ; Humans ; Male ; Methyltransferases/chemistry ; Methyltransferases/genetics ; Mitochondria/metabolism ; Mitochondrial Proteins/chemistry ; Mitochondrial Proteins/genetics ; Models, Molecular ; Mutation/genetics ; Pedigree ; Transcription Factors/chemistry ; Transcription Factors/genetics
    Chemische Substanzen DNA, Mitochondrial ; Mitochondrial Proteins ; Transcription Factors ; Methyltransferases (EC 2.1.1.-) ; TFB2M protein, human (EC 2.1.1.-)
    Sprache Englisch
    Erscheinungsdatum 2018-11-07
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2018.10.194
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Weissella cibaria WIKIM28 ameliorates atopic dermatitis-like skin lesions by inducing tolerogenic dendritic cells and regulatory T cells in BALB/c mice.

    Lim, Seul Ki / Kwon, Min-Sung / Lee, Jieun / Oh, Young Joon / Jang, Ja-Young / Lee, Jong-Hee / Park, Hae Woong / Nam, Young-Do / Seo, Myung-Ji / Roh, Seong Woon / Choi, Hak-Jong

    Scientific reports

    2017  Band 7, Seite(n) 40040

    Abstract: ... E levels. Furthermore, the production of type 2 helper T (Th2) cytokines such as interleukin (IL)-4 ...

    Abstract The occurrence of atopic dermatitis (AD), a chronic inflammatory skin disease, has been increasing steadily in children and adults in recent decades. In this study, we evaluated the ability of the lactic acid bacterium Weissella cibaria WIKIM28 isolated from gatkimchi, a Korean fermented vegetable preparation made from mustard leaves, to suppress the development of AD induced by 2,4-dinitrochlorobenzene in a murine model. Oral administration of W. cibaria WIKIM28 reduced AD-like skin lesions, epidermal thickening, and serum immunoglobulin E levels. Furthermore, the production of type 2 helper T (Th2) cytokines such as interleukin (IL)-4, IL-5, and IL-13 decreased in peripheral lymph node cells. Moreover, the intake of W. cibaria WIKIM28 increased the proportion of CD4
    Mesh-Begriff(e) Administration, Oral ; Animals ; Bacterial Proteins/administration & dosage ; Bacterial Proteins/isolation & purification ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dermatitis, Atopic/chemically induced ; Dermatitis, Atopic/drug therapy ; Dermatitis, Atopic/pathology ; Disease Models, Animal ; Immune Tolerance ; Immunoglobulin E/blood ; Immunologic Factors/administration & dosage ; Immunologic Factors/isolation & purification ; Mice, Inbred BALB C ; Skin/pathology ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; Treatment Outcome ; Weissella/chemistry
    Chemische Substanzen Bacterial Proteins ; Immunologic Factors ; Immunoglobulin E (37341-29-0)
    Sprache Englisch
    Erscheinungsdatum 2017-01-09
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep40040
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Association between the CLOCK gene 3111 T > C polymorphism and an irregular menstrual cycle in Korean adolescents.

    Kim, Kye-Hyun / Kim, Yunsin / Ha, Juwon / Shin, Dong-Won / Shin, Young-Chul / Oh, Kang-Seob / Woo, Hee-Yeon / Lim, Se-Won

    Journal of psychosomatic obstetrics and gynaecology

    2015  Band 36, Heft 4, Seite(n) 148–154

    Abstract: ... whether an irregular menstrual cycle is associated with polymorphisms in the CLOCK (3111T > C) and/or PER3 ... 3111T > C and PER3 VNTR polymorphisms. A significant association was found between the CLOCK 3111T > C ... genotype and irregular menstrual cycles. Subjects with the 3111T > C genotype had a high risk ...

    Abstract The menstrual cycle is an example of a human infradian rhythm, but an altered sleep-wake cycle or a disrupted circadian rhythm can change the regularity of the menstrual cycle. In this study, we investigated whether an irregular menstrual cycle is associated with polymorphisms in the CLOCK (3111T > C) and/or PER3 (variable number tandem repeat, VNTR) genes, which are known to have an impact on the circadian rhythm. One hundred ninety-seven postmenarchal, adolescent girls from two girls' high schools in Seoul, Korea, were studied. All participants were requested to complete the Perceived Stress Scale (PSS), the State-Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI) to assess the emotional distress that might cause menstrual irregularity. Every participant donated a blood sample from which DNA was extracted and genotyped for the CLOCK 3111T > C and PER3 VNTR polymorphisms. A significant association was found between the CLOCK 3111T > C genotype and irregular menstrual cycles. Subjects with the 3111T > C genotype had a high risk of an irregular menstrual cycle compared with 3111T/T homozygous subjects (odds ratio [OR] = 2.88; 95% confidence interval [CI]: 1.26-6.55). When multivariate logistic regression analysis was performed to adjust for age, PSS, STAI, BDI and BMI, subjects with the 3111T > C polymorphism showed a significantly increased OR for irregular menstrual cycles (OR = 3.09; 95% CI: 1.32-7.21). There was no significant association between the PER3 VNTR polymorphism and the irregularity of the menstrual cycle (p > 0.05). The results of this study suggest that the CLOCK 3111T > C polymorphism could be an independent risk factor for irregular menstrual cycles, irrespective of psychological distress and endocrine or metabolic conditions, and could be used as a molecular marker for gynecological studies on this aspect.
    Mesh-Begriff(e) Adolescent ; Affective Symptoms/diagnosis ; Affective Symptoms/physiopathology ; CLOCK Proteins/genetics ; Female ; Humans ; Menstrual Cycle/genetics ; Menstrual Cycle/psychology ; Menstruation Disturbances/genetics ; Menstruation Disturbances/psychology ; Period Circadian Proteins/genetics ; Polymorphism, Single Nucleotide ; Republic of Korea
    Chemische Substanzen PER3 protein, human ; Period Circadian Proteins ; CLOCK Proteins (EC 2.3.1.48) ; CLOCK protein, human (EC 2.3.1.48)
    Sprache Englisch
    Erscheinungsdatum 2015
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 604816-x
    ISSN 1743-8942 ; 0167-482X
    ISSN (online) 1743-8942
    ISSN 0167-482X
    DOI 10.3109/0167482X.2015.1089229
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Immunosenescent CD8+ T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension.

    Youn, Jong-Chan / Yu, Hee Tae / Lim, Beom Jin / Koh, Myoung Ju / Lee, Jino / Chang, Dong-Yeop / Choi, Yoon Seok / Lee, Sang-Hak / Kang, Seok-Min / Jang, Yangsoo / Yoo, Ook Joon / Shin, Eui-Cheol / Park, Sungha

    Hypertension (Dallas, Tex. : 1979)

    2013  Band 62, Heft 1, Seite(n) 126–133

    Abstract: ... cytotoxic CD8(+) T cells. Circulating levels of C-X-C chemokine receptor type 3 chemokines were ... The pathogenic role of T cells in hypertension has been documented well in recent animal studies ... However, the existence of T-cell-driven inflammation in human hypertension has not been confirmed ...

    Abstract The pathogenic role of T cells in hypertension has been documented well in recent animal studies. However, the existence of T-cell-driven inflammation in human hypertension has not been confirmed. Therefore, we undertook immunologic characterization of T cells from patients with hypertension and measured circulating levels of C-X-C chemokine receptor type 3 chemokines, which are well-known tissue-homing chemokines for T cells. We analyzed immunologic markers on T cells from patients with hypertension by multicolor flow cytometry. We then measured circulating levels of the C-X-C chemokine receptor type 3 chemokines, monokine induced by γ interferon (IFN), IFN γ-induced protein 10, and IFN-inducible T-cell α chemoattractant, in patients with hypertension and in age- and sex-matched control subjects by the cytometric bead array method. In addition, we examined histological features of IFN-inducible T-cell α chemoattractant expression from renal biopsy specimens of patients with hypertensive nephrosclerosis and control subjects. The total T-cell population from patients with hypertension showed an increased fraction of immunosenescent, proinflammatory, cytotoxic CD8(+) T cells. Circulating levels of C-X-C chemokine receptor type 3 chemokines were significantly higher in patients with hypertension than in control subjects. Furthermore, immunohistochemical staining revealed increased expression of the T-cell chemokine, IFN-inducible T-cell α chemoattractant, in the proximal and distal tubules of patients with hypertensive nephrosclerosis. Immunosenescent CD8(+) T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension, suggesting a role for T-cell-driven inflammation in hypertension. A more detailed characterization of CD8(+) T cells may offer new opportunities for the prevention and treatment of human hypertension.
    Mesh-Begriff(e) CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/pathology ; Chemotaxis, Leukocyte/immunology ; Female ; Flow Cytometry ; Humans ; Hypertension/immunology ; Hypertension/metabolism ; Hypertension/pathology ; Immunity, Cellular ; Immunohistochemistry ; Male ; Middle Aged ; Prospective Studies ; Receptors, CXCR3/biosynthesis
    Chemische Substanzen Receptors, CXCR3
    Sprache Englisch
    Erscheinungsdatum 2013-07
    Erscheinungsland United States
    Dokumenttyp Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.113.00689
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: Founder effects in two predominant intronic mutations of UNC13D, c.118-308C>T and c.754-1G>C underlie the unusual predominance of type 3 familial hemophagocytic lymphohistiocytosis (FHL3) in Korea.

    Seo, Ja Young / Song, Joon-Sup / Lee, Ki-O / Won, Hong-Hee / Kim, Jong-Won / Kim, Sun-Hee / Lee, Soo-Hyun / Yoo, Keon-Hee / Sung, Ki-Woong / Koo, Hong Hoe / Kang, Hyoung Jin / Shin, Hee Young / Ahn, Hyo-Seop / Han, Dong Kyun / Kook, Hoon / Hwang, Tai Ju / Lyu, Chuhl-Joo / Lee, Mi-Jung / Kim, Ji-Yoon /
    Park, Sung-Shik / Lim, Young-Tak / Kim, Bo-Eun / Koh, Kyung-Nam / Im, Ho Joon / Seo, Jong Jin / Kim, Hee-Jin

    Annals of hematology

    2013  Band 92, Heft 3, Seite(n) 357–364

    Abstract: ... sequencing of FHL2-4, targeted tests for c.118-308C>T and large intronic rearrangement mutations of UNC13D ... FHL3, 85 %) and three had PRF1 mutations (FHL2, 15 %). UNC13D:c.118-308C>T was detected in ten patients ... revealed significantly shared haplotypes in both c.118-308C>T and c.754-1G>C, indicating the presence ...

    Abstract Familial hemophagocytic lymphohistiocytosis (familial HLH or FHL) is a potentially fatal autosomal recessive disorder. Our previous study demonstrated that UNC13D mutations (FHL3) account for ~90 % of FHL in Korea with recurrent splicing mutation c.754-1G>C (IVS9-1G>C). Notably, half of the FHL3 patients had a monoallelic mutation of UNC13D. Deep intronic mutations in UNC13D were recently reported in patients of European descent. In this study, we performed targeted mutation analyses for deep intronic mutations and investigated on the founder effect in FHL3 in Korean patients. The study patients were 72 children with HLH including those with FHL3 previously reported to have a monoallelic UNC13D mutation. All patients were recruited from the Korean Registry of Hemophagocytic Lymphohistiocytosis. In addition to conventional sequencing of FHL2-4, targeted tests for c.118-308C>T and large intronic rearrangement mutations of UNC13D were performed. Haplotype analysis was performed for founder effects using polymorphic markers in the FHL3 locus. FHL mutations were detected in 20 patients (28 %). Seventeen patients had UNC13D mutations (FHL3, 85 %) and three had PRF1 mutations (FHL2, 15 %). UNC13D:c.118-308C>T was detected in ten patients, accounting for 38 % of all mutant alleles of UNC13D, followed by c.754-1G>C (26 %). Haplotype analyses revealed significantly shared haplotypes in both c.118-308C>T and c.754-1G>C, indicating the presence of founder effects. The deep intronic mutation UNC13D:c.118-308C>T accounts for the majority of previously missing mutations and is the most frequent mutation in FHL3 in Korea. Founder effects of two recurrent intronic mutations of UNC13D explain the unusual predominance of FHL3 in Korea.
    Mesh-Begriff(e) Adolescent ; Child ; Child, Preschool ; Female ; Founder Effect ; Haplotypes/genetics ; Humans ; Infant ; Introns/genetics ; Lymphohistiocytosis, Hemophagocytic/diagnosis ; Lymphohistiocytosis, Hemophagocytic/epidemiology ; Lymphohistiocytosis, Hemophagocytic/genetics ; Male ; Membrane Proteins/genetics ; Mutation/genetics ; Republic of Korea/epidemiology
    Chemische Substanzen Membrane Proteins ; UNC13D protein, human
    Sprache Englisch
    Erscheinungsdatum 2013-03
    Erscheinungsland Germany
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1064950-5
    ISSN 1432-0584 ; 0939-5555 ; 0945-8077
    ISSN (online) 1432-0584
    ISSN 0939-5555 ; 0945-8077
    DOI 10.1007/s00277-012-1628-6
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel: Association of C(-106)T polymorphism in aldose reductase gene with diabetic retinopathy in Chinese patients with type 2 diabetes mellitus.

    Deng, Yu / Yang, Xiu-fen / Gu, Hong / Lim, Apiradee / Ulziibat, Munkhtulga / Snellingen, Torkel / Xu, Jun / Ma, Kai / Liu, Ning-pu

    Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih

    2014  Band 29, Heft 1, Seite(n) 1–6

    Abstract: Objective: To identify the possible association between C(-106)T polymorphism of the aldose ... the grading of 7-field fundus color photographs of both eyes. Genotypes of the C(-106)T polymorphism (rs759853 ... 267/268), with one case of failure in the DR group. The frequencies of the T allele in the C(-106)T ...

    Abstract Objective: To identify the possible association between C(-106)T polymorphism of the aldose reductase (ALR) gene and diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM).
    Methods: From November 2009 to September 2010, patients with T2DM were recruited and assigned to DR group or diabetic without retinopathy (DWR) group according to the duration of diabetes and the grading of 7-field fundus color photographs of both eyes. Genotypes of the C(-106)T polymorphism (rs759853) in ALR gene were analyzed using the MassARRAY genotyping system and an association study was performed.
    Results: A total of 268 T2DM patients (129 in the DR group and 139 in the DWR group) were included in this study. No statistically significant differences were observed between the 2 groups in the age of diabetes onset (P=0.10) and gender (P=0.78). The success rate of genotyping for the study subjects was 99.6% (267/268), with one case of failure in the DR group. The frequencies of the T allele in the C(-106)T polymorphism were 16.0% (41/256) in the DR group and 19.4% (54/278) in the DWR group (P=0.36). There was no significant difference in the C(-106)T genotypes between the 2 groups (P=0.40). Compared with the wild-type genotype, odds ratio (OR) for the risk of DR was 0.7 (95% CI, 0.38-1.3) for the heterozygous CT genotype and 0.76 (95% CI, 0.18-3.25) for the homozygous TT genotype. The risk of DR was positively associated with microalbuminuria (OR=4.61; 95% CI, 2.34-9.05) and insulin therapy (OR=3.43; 95% CI, 1.94-6.09).
    Conclusions: Microalbuminuria and insulin therapy are associated with the risk of DR in Chinese patients with T2DM. C(-106)T polymorphism of the ALR gene may not be significantly associated with DR in Chinese patients with T2DM.
    Mesh-Begriff(e) Albuminuria/epidemiology ; Albuminuria/urine ; Aldehyde Reductase/genetics ; Asian Continental Ancestry Group ; China ; Cohort Studies ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/ethnology ; Diabetes Mellitus, Type 2/genetics ; Diabetic Retinopathy/drug therapy ; Diabetic Retinopathy/ethnology ; Diabetic Retinopathy/etiology ; Diabetic Retinopathy/genetics ; Female ; Gene Frequency ; Humans ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/adverse effects ; Hypoglycemic Agents/therapeutic use ; Insulin/administration & dosage ; Insulin/adverse effects ; Insulin/therapeutic use ; Logistic Models ; Male ; Multivariate Analysis ; Polymorphism, Single Nucleotide ; Risk
    Chemische Substanzen Hypoglycemic Agents ; Insulin ; Aldehyde Reductase (EC 1.1.1.21)
    Sprache Englisch
    Erscheinungsdatum 2014-04-01
    Erscheinungsland China
    Dokumenttyp Clinical Trial ; Journal Article
    ZDB-ID 1083365-1
    ISSN 1001-9294
    ISSN 1001-9294
    DOI 10.1016/s1001-9294(14)60016-x
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Vitamin C enters mouse T cells as dehydroascorbic acid in vitro and does not recapitulate in vivo vitamin C effects.

    Maeng, Hyung Gun / Lim, Hyunja / Jeong, Young-Joo / Woo, Ami / Kang, Jae Seung / Lee, Wang Jae / Hwang, Young-Il

    Immunobiology

    2009  Band 214, Heft 4, Seite(n) 311–320

    Abstract: ... including immune response. In fact, in vivo administration of vitamin C modulates T cell proliferation and ... cytokine secretion. In this study, we analyzed the mechanism by which mouse T cells take up vitamin C, and ... whether this uptake directly affected T cell functions. T cells internalized more vitamin C when they were activated ...

    Abstract Vitamin C is an essential micronutrient, which has been implicated in various biological processes, including immune response. In fact, in vivo administration of vitamin C modulates T cell proliferation and cytokine secretion. In this study, we analyzed the mechanism by which mouse T cells take up vitamin C, and whether this uptake directly affected T cell functions. T cells internalized more vitamin C when they were activated, due to enhanced glucose transporter (GLUT)-1 and GLUT-3 expression that persisted up to 48 h after activation. Blocking oxidation of ascorbic acid (the reduced form of vitamin C) in the culture medium with 1,4-dithio-threitol (DTT) almost completely inhibited the enhanced vitamin C uptake. The presence of vitamin C at low concentrations during in vitro T cell activation did not affect proliferation or cytokine secretion (IFN-gamma, TNF-alpha, or IL-4) in response to PMA/ionomycin. In contrast, high concentrations (0.25-0.5 mM) of vitamin C lowered cell viability, reduced thymidine uptake, and decreased cytokine secretion. In conclusion, activated T cells upregulated GLUT-1 and -3 to increase vitamin C uptake. They took up vitamin C mostly in its oxidized form, rarely in its reduced form. Application of vitamin C to T cells in vitro did not recapitulate previously reported in vivo responses to vitamin C, suggesting that in vivo, vitamin C modulates T cells indirectly through other components of the microenvironment.
    Mesh-Begriff(e) Animals ; Ascorbic Acid/chemistry ; Ascorbic Acid/immunology ; Ascorbic Acid/metabolism ; Biological Transport/drug effects ; Cell Proliferation/drug effects ; Cell Survival/immunology ; Cytokines/antagonists & inhibitors ; Cytokines/secretion ; Dehydroascorbic Acid/chemistry ; Dehydroascorbic Acid/immunology ; Dehydroascorbic Acid/metabolism ; Dithiothreitol/pharmacology ; Glucose Transporter Type 1/genetics ; Glucose Transporter Type 1/immunology ; Glucose Transporter Type 1/metabolism ; Glucose Transporter Type 3/genetics ; Glucose Transporter Type 3/immunology ; Glucose Transporter Type 3/metabolism ; Immunomagnetic Separation ; Ionomycin/pharmacology ; Lymphocyte Activation/drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Oxidation-Reduction/drug effects ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Tetradecanoylphorbol Acetate/pharmacology ; Thymidine/metabolism
    Chemische Substanzen Cytokines ; Glucose Transporter Type 1 ; Glucose Transporter Type 3 ; Slc2a1 protein, mouse ; Slc2a3 protein, mouse ; Ionomycin (56092-81-0) ; Tetradecanoylphorbol Acetate (NI40JAQ945) ; Ascorbic Acid (PQ6CK8PD0R) ; Dithiothreitol (T8ID5YZU6Y) ; Thymidine (VC2W18DGKR) ; Dehydroascorbic Acid (Y2Z3ZTP9UM)
    Sprache Englisch
    Erscheinungsdatum 2009
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 563292-4
    ISSN 1878-3279 ; 0171-2985
    ISSN (online) 1878-3279
    ISSN 0171-2985
    DOI 10.1016/j.imbio.2008.09.003
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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