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  • 1
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    Identification of Candidate Gene Variants in Korean MODY Families by Whole-Exome Sequencing
    S. Karger AG ; 2015
    In:  Hormone Research in Paediatrics Vol. 83, No. 4 ( 2015), p. 242-251
    Details
    In: Hormone Research in Paediatrics, S. Karger AG, Vol. 83, No. 4 ( 2015), p. 242-251
    Abstract: Aims: To date, 13 genes causing maturity-onset diabetes of the young (MODY) have been identified. However, there is a big discrepancy in the genetic locus between Asian and Caucasian patients with MODY. Thus, we conducted whole-exome sequencing in Korean MODY families to identify causative gene variants. Methods: Six MODY probands and their family members were included. Variants in the dbSNP135 and TIARA databases for Koreans and the variants with minor allele frequencies 〉 0.5% of the 1000 Genomes database were excluded. We selected only the functional variants (gain of stop codon, frameshifts and nonsynonymous single-nucleotide variants) and conducted a case-control comparison in the family members. The selected variants were scanned for the previously introduced gene set implicated in glucose metabolism. Results: Three variants c.620C 〉 T:p.Thr207Ile in PTPRD, c.559C 〉 G:p.Gln187Glu in SYT9, and c.1526T 〉 G:p.Val509Gly in WFS1 were respectively identified in 3 families. We could not find any disease-causative alleles of known MODY 1-13 genes. Based on the predictive program, Thr207Ile in PTPRD was considered pathogenic. Conclusions: Whole-exome sequencing is a valuable method for the genetic diagnosis of MODY. Further evaluation is necessary about the role of PTPRD, SYT9 and WFS1 in normal insulin release from pancreatic beta cells.
    Type of Medium: Online Resource
    ISSN: 1663-2818 , 1663-2826
    URL: Article
    DOI: 10.1159/000368657
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2015
    detail.hit.zdb_id: 2540224-9
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  • 2
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    Germ Cell Tumor Targeting Chemotherapy in Gastric Adenocarcinoma with an Endodermal Sinus Tumor Component: A Case Report
    S. Karger AG ; 2017
    In:  Chemotherapy Vol. 62, No. 1 ( 2017), p. 54-57
    Details
    In: Chemotherapy, S. Karger AG, Vol. 62, No. 1 ( 2017), p. 54-57
    Abstract: The most common sites for extragonadal germ cell tumors are the midline mediastinum, retroperitoneum and, much less frequently, the stomach. The stomach-originated primary germ cell tumor carries a poor prognosis, especially when metastasis occurs to the liver, with a mean survival time of 1 month. We describe the case of a 77-year-old male who presented with usual symptoms of gastric malignancy. Gastrectomy was performed. Histopathology of surgically resected tissue revealed a mixture of adenocarcinoma and endodermal sinus tumor components with α-fetoprotein production. After liver metastasis was identified, oxaliplatin and capecitabine were administered as palliative chemotherapy. The response was poor. For the second-line therapy, bleomycin, etoposide, and cisplatin (BEP) therapy was initiated. The overall response to these drugs was a partial response and the residual liver lesion was considered to be resectable. The patient died of pneumonia 11 months following the BEP session, representing an overall survival time of 22 months. Gastric adenocarcinoma with a germ cell tumor component is uncommon and an effective combination of chemotherapeutic agents is not yet clear. In this case, the patient received germ cell tumor-targeting chemotherapy and showed a durable response. Hence, germ cell-targeting cytotoxic agents have potential as the ‘front-line regimen'.
    Type of Medium: Online Resource
    ISSN: 0009-3157 , 1421-9794
    URL: Article
    DOI: 10.1159/000447117
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2017
    detail.hit.zdb_id: 1482111-4
    SSG: 15,3
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  • 3
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    Knockdown of PRKAR2B Results in the Failure of Oocyte Maturation
    S. Karger AG ; 2018
    In:  Cellular Physiology and Biochemistry Vol. 45, No. 5 ( 2018), p. 2009-2020
    Details
    In: Cellular Physiology and Biochemistry, S. Karger AG, Vol. 45, No. 5 ( 2018), p. 2009-2020
    Abstract: Background/Aims: Cyclic adenosine monophosphate (cAMP)-dependent type 2 regulatory subunit beta (Prkar2b) is a regulatory isoform of cAMP-dependent protein kinase (PKA), which is the primary target for cAMP actions. In oocytes, PKA and the pentose phosphate pathway (PPP) have important roles during the germinal vesicle (GV) stage arrest of development. Although the roles of the PKA signal pathway have been studied in the development of oocyte, there has been no report on the function of PRKAR2B, a key regulator of PKA. Methods: Using reverse transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR (qRT-PCR), immunohistochemistry, and immunofluorescence, we determined the relative expression of Prkar2b in various tissues, including ovarian follicles, during oocyte maturation. Prkar2b-interfering RNA (RNAi) microinjection was conducted to confirm the effect of Prkar2b knockdown, and immunofluorescence, qRT-PCR, and time-lapse video microscopy were used to analyze Prkar2b-deficient oocytes. Results: Prkar2b is strongly expressed in the ovarian tissues, particularly in the growing follicle. During oocyte maturation, the highest expression of Prkar2b was during metaphase I (MI), with a significant decrease at metaphase II (MII). RNAi-mediated Prkar2b suppression resulted in MI-stage arrest during oocyte development, and these oocytes exhibited abnormal spindle formation and chromosome aggregation. Expression of other members of the PKA family (except for Prkaca) were decreased, and the majority of the PPP factors were also reduced in Prkar2b-deficient oocytes. Conclusion: These results suggest that Prkar2b is closely involved in the maturation of oocytes by controlling spindle formation and PPP-mediated metabolism.
    Type of Medium: Online Resource
    ISSN: 1015-8987 , 1421-9778
    URL: Article
    DOI: 10.1159/000487978
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2018
    detail.hit.zdb_id: 1482056-0
    SSG: 12
    SSG: 15,3
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  • 4
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    Health Insurance Status Is Related to Risk of Mortality and Hospitalization in Korean Maintenance Hemodialysis Patients: A Longitudinal Cohort Study
    S. Karger AG ; 2020
    In:  American Journal of Nephrology Vol. 51, No. 12 ( 2020), p. 975-981
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 51, No. 12 ( 2020), p. 975-981
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 There has been an increasing incidence of hemodialysis (HD) due to old age and comorbid condition such as diabetes. In general, socioeconomic status (SES) is known as one of the most important risk factors for patient mortality and morbidity. Whether low SES is associated with poorer outcome in HD patients is controversial. This study was performed to evaluate the association of health insurance status as a proxy indicator for SES upon mortality and hospitalization in maintenance HD patients. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We used HD-quality assessment data from the year of 2015 for collecting demographic and clinical data. The subjects were classified into Medical Aid (MA) recipients (low SES) and National Health Insurance (NHI) beneficiary (high SES). We analyzed mortality and hospitalization risk based on health insurance status using Cox proportional hazard model. A total of 35,454 adult HD patients ≥18 years old who received HD treatment more than twice weekly were included in the analysis. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The ratio between MA recipient and NHI beneficiary was 76.7 versus 23.3%. The MA recipient group demonstrated younger age and lower proportion of female, diabetes, hypertension, and cerebrovascular accidents compared to the NHI beneficiary group. After adjusting for age, gender, comorbidity, and laboratory parameters, the MA recipient group showed a significantly higher mortality risk compared to the NHI beneficiary group (hazard ratio 1.073 [1.009–1.14], 〈 i 〉 p 〈 /i 〉 = 0.025). The MA recipient group was also an independent risk factor for hospitalization after adjusting for age, gender, comorbidities, and laboratory parameters (hazard ratio 1.142 [1.108–1.178], 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Low SES as measured by health insurance status was associated with an increased risk of patient mortality and hospitalization in Korean maintenance HD patients.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000512855
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2020
    detail.hit.zdb_id: 1468523-1
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  • 5
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    Prestroke Antiplatelet Agents in First-Time Ischemic Stroke Are Related to Subtypes
    S. Karger AG ; 2016
    In:  European Neurology Vol. 75, No. 1-2 ( 2016), p. 89-95
    Details
    In: European Neurology, S. Karger AG, Vol. 75, No. 1-2 ( 2016), p. 89-95
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 It is not well known whether prestroke antiplatelet agents (PAs) are associated with the subtypes of ischemic stroke. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We screened patients in a hospital-based stroke registry. Patients who were admitted with a diagnosis of first-time ischemic stroke within 5 days of symptom onset were included. Ischemic stroke subtypes were classified in accordance with the Trial of ORG 10172 in Acute Stroke Treatment classification based on stroke mechanism: large-artery atherosclerosis (LA), cardioembolism (CE), small vessel occlusion (SVO), other determined (OC) or undetermined causes (UC). Multinomial logistic regression analyses were performed to evaluate the effect of PA on stroke subtypes before and after propensity score matching. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Among 3,025 patients, 748 (24.7%) were taking antiplatelet agents prior to stroke. After propensity score matching, 1,190 patients were ultimately included. The PA group was associated with strokes caused by SVO rather than LA in multinomial logistic regression of an unmatched dataset. However, multivariable analysis after propensity score matching demonstrated that PA use was associated with a higher probability of SVO and CE (OR 2.05, p 〈 0.001 and OR 1.62, p = 0.05, respectively) compared with LA. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 PAs were associated with specific index stroke subtypes.
    Type of Medium: Online Resource
    ISSN: 0014-3022 , 1421-9913
    URL: Article
    DOI: 10.1159/000444295
    RVK:
    XA 10000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2016
    detail.hit.zdb_id: 1482237-4
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  • 6
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    Serum Human β-Defensin 2 Is Increased in Angioedema Accompanying Chronic Spontaneous Urticaria
    S. Karger AG ; 2021
    In:  International Archives of Allergy and Immunology Vol. 182, No. 11 ( 2021), p. 1066-1071
    Details
    In: International Archives of Allergy and Immunology, S. Karger AG, Vol. 182, No. 11 ( 2021), p. 1066-1071
    Abstract: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Chronic spontaneous urticaria (CSU) is a common cutaneous disease caused by mast-cell degranulation. Human β-defensin 2 (HBD2) is a well-known antimicrobial peptide that is also a pruritogen inducing vascular permeability via non-IgE-mediated mast-cell degranulation. 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 We investigated the associations between serum HBD2 levels and the clinical characteristics of CSU patients. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Serum samples from 124 CSU patients and 56 healthy controls were screened for the levels of HBD2 and translationally controlled tumor protein (TCTP)_ by using ELISA. The urticaria activity score over 7 days (UAS7) was used to measure disease activity in CSU patients. Accompanying angioedema was self-reported. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Serum HBD2 levels were higher in the CSU group than in healthy subjects (median [interquartile range], 84.1 [43.5, 142.5] vs. 59.5 [26.7, 121.5], 〈 i 〉 p 〈 /i 〉 = 0.034). In CSU patients, serum HBD2 level was negatively correlated with the peripheral basophil percentages (Spearman’s rho = −0.229, 〈 i 〉 p 〈 /i 〉 = 0.01) and vitamin D levels (−0.262, 〈 i 〉 p 〈 /i 〉 = 0.02), but positively correlated with TCTP levels (0.252, 〈 i 〉 p 〈 /i 〉 = 0.006). In CSU patients, HBD2 level was higher in those with than without angioedema (101.7 [50.9, 184.2] vs. 66.7 [37.9, 132.0] , 〈 i 〉 p 〈 /i 〉 = 0.019). It did not differ by aspirin hypersensitivity or atopy status, or autologous serum skin test positivity. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 A known mast-cell degranulator, HBD2 was elevated in the sera from CSU patients compared to healthy controls and may be involved in the pathogenesis of accompanying angioedema.
    Type of Medium: Online Resource
    ISSN: 1018-2438 , 1423-0097
    URL: Article
    DOI: 10.1159/000516952
    RVK:
    XA 49650
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1482722-0
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  • 7
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    Successful Treatment of Imatinib-Induced DRESS Syndrome Using Reslizumab without Cessation of Imatinib: A Case Report
    S. Karger AG ; 2021
    In:  Case Reports in Oncology Vol. 14, No. 3 ( 2021-10-22), p. 1548-1554
    Details
    In: Case Reports in Oncology, S. Karger AG, Vol. 14, No. 3 ( 2021-10-22), p. 1548-1554
    Abstract: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse drug reaction; reported cases are sometimes imatinib mesylate induced. The main treatment is the withdrawal of the causative drug, and most cases with imatinib-induced DRESS syndrome required withdrawal of imatinib. However, in such cases involving anticancer drugs, this may compromise cancer treatment. Herein, we report a patient with imatinib-induced DRESS syndrome that was successfully treated with reslizumab while continuing imatinib treatment. A 65-year-old female presented with facial edema and generalized skin rash after being given 400 mg imatinib 2 weeks ago for metastatic gastrointestinal stromal tumor. After stopping imatinib, the clinical symptoms improved. Imatinib desensitization was performed, and it was administered again. However, the clinical symptoms reappeared more severely 2 months after restart of imatinib, and the peripheral absolute eosinophil count increased to 1,690/μL. A diagnosis of imatinib-induced DRESS syndrome was made, based on the Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) criteria. Imatinib desensitization was repeated, but the clinical symptoms reappeared, and the peripheral eosinophilia persisted. We administered reslizumab, an interleukin-5 monoclonal antibody, without cessation of imatinib. The absolute eosinophil count decreased immediately, and the clinical symptoms improved gradually. After 2 weeks, the clinical symptoms reappeared mildly, but after administering reslizumab again, these disappeared completely. Reslizumab can be considered in the management of DRESS syndrome in cases wherein the causative medication needs to be continued.
    Type of Medium: Online Resource
    ISSN: 1662-6575
    URL: Article
    DOI: 10.1159/000519471
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 2458961-5
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  • 8
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    RASD1 Knockdown Results in Failure of Oocyte Maturation
    S. Karger AG ; 2016
    In:  Cellular Physiology and Biochemistry Vol. 40, No. 6 ( 2016), p. 1289-1302
    Details
    In: Cellular Physiology and Biochemistry, S. Karger AG, Vol. 40, No. 6 ( 2016), p. 1289-1302
    Abstract: Background: Ras dexamethasone-induced protein (RASD1) is a member of Ras superfamily of small GTPases. RASD1 regulates various signaling pathways involved in iron homeostasis, growth hormone secretion, and circadian rhythm. However, RASD1 function in oocyte remains unknown. Methods: Using immunohistochemistry, immunofluorescence, and quantitative real-time RT-PCR, RASD1 expression in mouse ovary and RASD1 role in oocyte maturation-related gene expression, spindle formation, and chromosome alignment were analyzed. RNAi microinjection and time-lapse video microscopy were used to examine the effect of Rasd1 knockdown on oocyte maturation. Results: RASD1 was highly detected in oocytes transitioning from primordial to secondary follicles. Rasd1 was highly expressed in germinal vesicle (GV), during GV breakdown, and in metaphase I (MI) stage as oocytes mature, and its expression was significantly downregulated in MII stage. With knockdown of Rasd1, maturation in GV oocytes was arrested at MI stage, showing disrupted meiotic spindling and chromosomal misalignment. In addition, Obox4 and Arp2/3, engaged in MI-MII transition and cytokinesis, respectively, were misregulated in GV oocytes by Rasd1 knockdown. Conclusion: These findings suggest that RASD1 is a novel factor in MI-MII oocyte transition and may be involved in regulating the progression of cytokinesis and spindle formation, controlling related signaling pathways during oocyte maturation.
    Type of Medium: Online Resource
    ISSN: 1015-8987 , 1421-9778
    URL: Article
    DOI: 10.1159/000453182
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2016
    detail.hit.zdb_id: 1482056-0
    SSG: 12
    SSG: 15,3
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  • 9
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    Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma
    S. Karger AG ; 2023
    In:  Oncology Vol. 101, No. 2 ( 2023), p. 96-104
    Details
    In: Oncology, S. Karger AG, Vol. 101, No. 2 ( 2023), p. 96-104
    Abstract: 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The associations of 279 SNPs with chemotherapy response and overall survival (OS) were analyzed in 314 lung adenocarcinoma patients who underwent PEM chemotherapy. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Among the SNPs investigated, 18 were significantly associated with response to chemotherapy, while 28 with OS. Of these SNPs, rs549794A & #x3e;G in an enhancer which is expected to regulate the expression of 〈 i 〉 ribosomal protein S3 〈 /i 〉 ( 〈 i 〉 RPS3 〈 /i 〉 ) gene was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ratio = 0.59, 95% CI = 0.36–0.97, 〈 i 〉 p 〈 /i 〉 = 0.04; adjusted hazard ratio = 1.44, 95% CI = 1.09–1.91, 〈 i 〉 p 〈 /i 〉 = 0.01, respectively). Previous studies suggested that RPS3, a multi-functional protein with various extraribosomal activities, may play a role in chemotherapy resistance. Therefore, it is postulated that rs549794-induced change in the expression level of RPS3 may affect the response to PEM chemotherapy and consequently the survival outcomes in lung adenocarcinoma patients. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 This study suggests that genetic variants in the histone modification regions may be useful for the prediction of clinical outcomes of PEM chemotherapy in advanced lung adenocarcinoma.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000527492
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2023
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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  • 10
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    Genetic Polymorphisms in Activating Transcription Factor 3 Binding Site and the Prognosis of Early-Stage Non-Small Cell Lung Cancer
    S. Karger AG ; 2021
    In:  Oncology Vol. 99, No. 5 ( 2021), p. 336-344
    Details
    In: Oncology, S. Karger AG, Vol. 99, No. 5 ( 2021), p. 336-344
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Among those SNPs, 〈 i 〉 HAX1 〈 /i 〉 rs11265425T & #x3e;G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00–1.69, 〈 i 〉 p 〈 /i 〉 = 0.05), and 〈 i 〉 ME3 〈 /i 〉 rs10400291C & #x3e;A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46–0.95, 〈 i 〉 p 〈 /i 〉 = 0.03). Regarding 〈 i 〉 HAX1 〈 /i 〉 rs11265425T & #x3e;G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding 〈 i 〉 ME3 〈 /i 〉 rs10400291C & #x3e;A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher 〈 i 〉 HAX1 〈 /i 〉 promoter activity than T allele. 〈 i 〉 HAX1 〈 /i 〉 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, 〈 i 〉 ME3 〈 /i 〉 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, 〈 i 〉 HAX1 〈 /i 〉 rs11265425T & #x3e;G and 〈 i 〉 ME3 〈 /i 〉 rs10400291C & #x3e;A are associated with the clinical outcomes of patients in surgically resected NSCLC.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000514131
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
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