Young Ah Lee's scientific contributionswhile working at Seoul National University Hospital and other institutions

Publications (80)

Publications citing this author (309)

    • One of the implications of stress involving the activation of many different brain regions and transmitter systems is that an endogenous stress state differs markedly from the condition of a brain that is otherwise 'at rest' but exposed to high GC levels. Indeed, several conditions that robustly elevate GC levels, such as physical exercise, mating, enriched environmental housing or intracranial self-stimulation, promote AHN (van Praag et al., 1999b, Takahashi et al., 2009, Galea et al., 2013, Kim et al., 2013, Yau et al., 2014a, Yau et al., 2014b, Opendak and Gould, 2015). This apparent paradox has been tested in experimental models employing, for example, repeated injections with exogenous GCs to imitate hypercortisolism.
    [Show abstract] [Hide abstract] ABSTRACT: Psychosocial stress, and within the neuroendocrine reaction to stress specifically the glucocorticoid hormones, are well-characterized inhibitors of neural stem/progenitor cell proliferation in the adult hippocampus, resulting in a marked reduction in the production of new neurons in this brain area relevant for learning and memory. However, the mechanisms by which stress, and particularly glucocorticoids, inhibit neural stem/progenitor cell proliferation remain unclear and under debate. Here we review the literature on the topic and discuss the evidence for direct and indirect effects of glucocorticoids on neural stem/progenitor cell proliferation and adult neurogenesis. Further, we discuss the hypothesis that glucocorticoid rhythmicity and oscillations originating from the activity of the hypothalamus-pituitary-adrenal axis, may be crucial for the regulation of neural stem/progenitor cells in the hippocampus, as well as the implications of this hypothesis for pathophysiological conditions in which glucocorticoid oscillations are affected.
    Full-text · Article · May 2016
    • case, however, was due to diencephalic syndrome, and all presentations were associated with radiation and tumour resection. Some suggest that the involvement of posterior hypothalamus associated with an intact pituitary gland can be the single reason to induce PP (Jolly, 1951). Some other studies have investigated more cases with longer follow-ups. Choi et al. (2013) studied 61 boys, and reported two cases of pilocytic astrocytoma. Jakubowska et al. (2011) followed 39 girls and 17 boys diagnosed with PP for 10 years, reporting 6 boys to reveal gonadotropin-dependent central puberty: 5 cases were idiopathic, and one had a brain tumour – astrocytoma. As it seems, the case presented is a rare phenomeno
    Full-text · Article · Aug 2015 · Parasitology
    • However, T. vaginalis possesses numerous mechanisms for evading host responses (reviewed in Figueroa-Angulo et al., 2012) including the ability to degrade human immunoglobulins and deposited C3b. T. vaginalis infection induces an influx of neutrophils into the genital tract, possibly by stimulating the production of high levels of IL-8 and leukotriene B4 (Nam et al., 2012), and mast cells are also implicated in the inflammation (Han et al., 2012). Suppression of T cell responses has been reported during active infection with T. vaginalis (Mason and Gwanzura, 1990).
    [Show abstract] [Hide abstract] ABSTRACT: Sexually transmitted infections (STIs) comprise more than 30 different bacterial, viral, protozoal, and yeast infections acquired during sexual intercourse and therefore directly afflicting the genital tracts or gaining systemic access across the genital mucosae. Effective vaccines have been developed against only two viral STIs (hepatitis B and human papillomavirus). For most STIs, the nature of the immune responses induced and the parameters of immunity against them are poorly understood. However, progress has been made in comprehending responses especially against Neisseria gonorrhoeae, Chlamydia trachomatis, Haemophilus ducreyi, and Candida albicans. An emerging aspect is that these well-adapted human pathogens exploit the unique characteristics of immunity in the reproductive tracts, eliciting responses favorable to their own survival and suppressing those that would be detrimental to them. Elucidation of the mechanisms whereby STI pathogens manipulate the host's immune responses will lead to novel approaches for therapy and vaccine development.
    Article · Dec 2015 · Parasitology
    • Activation of host cell PTP occurred through a calcium-dependent calpain protease responsible for PTP1B cleavage that led, at last, to cell death (Teixeira and Mann, 2002). Reinforcing these data, activation of host cell calpain by E. histolytica was also observed by others (Kim et al., 2007; Jang et al., 2011) and was shown to modulate the degradation of STAT proteins (STAT3 and STAT5) and NF-κB (p65) in Caco-2 cells (Kim et al., 2014). Furthermore, pretreatment of Caco-2 cells with calpeptin (a calpain inhibitor) or calpain silencing partially reduced Entamoeba-induced DNA fragmentation (Kim et al., 2014).
    [Show abstract] [Hide abstract] ABSTRACT: Giardia lamblia, Cryptosporidium spp. and Entamoeba histolytica are important pathogenic intestinal parasites and are amongst the leading cause worldwide of diarrheal illness in humans. Diseases caused by these organisms, Giardiasis, Cryptosporidiosis and Amoebiasis, respectively, are characterized by self-limited diarrhea but can evolve to long-term complications. The cellular and molecular mechanisms underlying the pathogenesis of diarrhea associated with these tree pathogens are being unraveled, with knowledge of both the strategies explored by the parasites to establish infection and the methods evolved by hosts to avoid it. Special attention is being given to molecules participating in parasite-host interaction and in the mechanisms implicated in the diseases pathophysiologic processes. This review focuses on cell mechanisms that are modulated during infection, including gene transcription, cytoskeleton rearrangements, signal transduction pathways and cell death.
    Full-text · Article · Mar 2016
    • In girls, reaching a body mass of 48 kg determines the timing of first menses (Frisch and Revelle, 1970; Freedman et al., 2003; Gluckman and Hanson, 2006; Ahmed et al., 2009). Obese girls reach this mass faster, resulting in earlier onset of puberty (Freedman et al., 2003; Gluckman and Hanson, 2006; Ahmed et al., 2009) possibly due to higher levels of insulin signaling (Codner and Cassorla, 2009; Lee et al., 2011; and stained with phalloidin. After photographing, these areas were quantified using the ImageJ.
    [Show abstract] [Hide abstract] ABSTRACT: Despite their fundamental importance for body size regulation, the mechanisms that stop growth are poorly understood. In Drosophila melanogaster, growth ceases in response to a peak of the molting hormone ecdysone that coincides with a nutrition-dependent checkpoint, critical weight. Previous studies indicate that insulin/insulin-like growth factor signaling (IIS)/Target of Rapamycin (TOR) signaling in the prothoracic glands (PGs) regulates ecdysone biosynthesis and critical weight. Here we elucidate a mechanism through which this occurs. We show that Forkhead Box class O (FoxO), a negative regulator of IIS/TOR, directly interacts with Ultraspiracle (Usp), part of the ecdysone receptor. While overexpressing FoxO in the PGs delays ecdysone biosynthesis and critical weight, disrupting FoxO-Usp binding reduces these delays. Further, feeding ecdysone to larvae eliminates the effects of critical weight. Thus, nutrition controls ecdysone biosynthesis partially via FoxO-Usp prior to critical weight, ensuring that growth only stops once larvae have achieved a target nutritional status.
    Full-text · Article · Nov 2014
    • Incidence of type 1 diabetes increases continuously worldwide [1][2][3]of progression to end-stage renal disease (ESRD) and one of the major predictors of premature death [4, 5] the association between rapid GFR decline and renal hyperfiltration is not well described in Type 1 diabetes. We hypothesized that renal hyperfiltration (estimated glomerular filtration rate, eGFR \u2265 120 mL/min/1.73
    Full-text · Article · Mar 2017
    • Even a congenital onset of GH excess has been suggested by linear growth acceleration occurring within the first month of life in children with documented gigantism11). There are a few cases of pituitary gigantism have been reported in Korean children and adolescents12,13). Our patients were 14 years of age at the time of diagnosis and presented with extremely tall stature.
    [Show abstract] [Hide abstract] ABSTRACT: Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings.
    Full-text · Article · Jun 2014
    • This result suggests that MAPK-dependent CD63 expression plays a key role in the exocytotic degranulation of HMC-1 cells induced by TvSP. Previous studies have demonstrated that T. vaginalis-secreted lipid mediator LTB4 induces IL-8 production in mast cells via BLT-dependent activation of NF-kB and CREB [3]. Further, NOX2-derived ROS regulates surface trafficking of BLT1 during exocytotic degranulation in human eosinophils stimulated with LTB4 [16].
    [Show abstract] [Hide abstract] ABSTRACT: Trichomonas vaginalis is a flagellated protozoan parasite that causes vaginitis and cervicitis in women and asymptomatic urethritis and prostatitis in men. Mast cells have been reported to be predominant in vaginal smears and vaginal walls of patients infected with T. vaginalis. Mitogen-activated protein kinase (MAPK), activated by various stimuli, have been shown to regulate the transcriptional activity of various cytokine genes in mast cells. In this study, we investigated whether MAPK is involved in ROS generation and exocytotic degranulation in HMC-1 cells induced by T. vaginalis-derived secretory products (TvSP). We found that TvSP induces the activation of MAPK and NADPH oxidase in HMC-1 cells. Stimulation with TvSP induced phosphorylation of MAPK and p47phox in HMC-1 cells. Stimulation with TvSP also induced up-regulation of CD63, a marker for exocytosis, along the surfaces of human mast cells. Pretreatment with MAPK inhibitors strongly inhibited TvSP-induced ROS generation and exocytotic degranulation. Finally, our results suggest that TvSP induces intracellular ROS generation and exocytotic degranulation in HMC-1 via MAPK signaling.
    Full-text · Article · Oct 2015
    • And cardiovascular disease is based on atherosclerosis (AS), the hallmark of cardiovascular diseases, which is the leading cause of mortality all over the world. Many studies reported that patients with diabetes have 2 to 10 times increased risk of developing atherosclerotic disease (Atabek, Akyürek, Eklioglu, & Alp, 2014; Lee et al., 2011; Pozza, Netz, Schwarz, & Bechtold, 2010; Tantawy, Adly, El Maaty, & Amin, 2009). Carotid intima–media thickness (CIMT) level is the symbol of early atherosclerosis, it has been shown to be the marker of preclinical atherosclerosis (Gimenez et al., 2010), and measurement of the CIMT is independently associated with an increased cardiovascular disease (Atabek, Pirgon, Kurtoglu, & Imamoglu, 2006 ).
    [Show abstract] [Hide abstract] ABSTRACT: To derive a more precise estimation of carotid intima-media thickness (CIMT) levels in patients with type 1 diabetes mellitus (T1DM) by meta-analysis. PubMed and Embase databases were searched to identify all available studies comparing CIMT levels between T1DM group and control group. Meta-analysis was performed to compare the difference of overall mean CIMT levels between the two groups. Publication bias was evaluated by funnel plot, Begg' test and Egger' test. Meta-regression analysis was conducted to investigate the influential factors on CIMT difference. The meta-analysis was conducted by STATA 12.0 software. A total of 1840 articles were obtained after searching databases; 47 studies were finally included in the meta-analysis. Significant heterogeneity was observed among these studies (Q=768.75, P<0.001, I(2)=94.0%). Compared with the control group, the T1DM group had significantly higher CIMT levels (standardized mean difference: 1.01, 95% CI: 0.75-1.28; P<0.001). A likely source of heterogeneity was Newcastle-Ottawa Scale (NOS) scores and sample size ratio of patents and controls. The funnel plot did not show a skewed or asymmetrical shape, and the result of Begg' test and Egger' test was P=0.178 and P=0.145 respectively. Accordingly, it could be assumed that publication bias was not present. T1DM patients have significantly increased CIMT levels compared to control subjects. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Apr 2015
    • This was originally highlighted in 1985 by a meta-analysis of 215 intracranial germ cell tumors [6], where over a third of germinoma patients had been symptomatic for greater than 6 months before diagnosis. Evidence from our work and that of comparable studies suggests little improvement has been made in reducing this symptom interval over the past 30 years [14, 18, 20, 22, 40, 41] . The insidious, non-specific symptomatology of neurohypophyseal lesions undoubtedly underpins this issue, including the gradual modification of fluid balance to counteract impaired osmoregulation in cases of DI.
    [Show abstract] [Hide abstract] ABSTRACT: The pituitary bright spot is acknowledged to indicate functional integrity of the posterior pituitary gland, whilst its absence supports a diagnosis of central diabetes insipidus (DI). This feature was evaluated, together with the incidence and clinical characteristics of DI in children with suprasellar/neurohypophyseal germinomas. We performed a review of all suprasellar (SS) or bifocal (BF) germinoma pediatric patients treated in Toronto since 2000. Demographics, symptomatology, treatment outcome and imaging were evaluated. Nineteen patients fulfilled inclusion criteria (10 SS, 9 BF; median age 12.5 years (6.2-16.8 years)). All remained alive at 6.4 years median follow-up (1.2-13.7 years) after receiving chemotherapy and radiotherapy (13 focal/ventricular, four whole brain, two neuraxis), with only one progression. All had symptoms of DI at presentation with a symptom interval above one year in eight cases (42 %). Desmopressin was commenced and maintained in 16 patients (84 %). The pituitary bright spot was lost in most diagnostic interpretable cases, but was appreciated in three patients (18 %) who had normal serum sodium values compared to 'absent' cases (p = 0.013). For two such cases, spots remained visible until last follow-up (range 0.4-3.3 years), with one still receiving desmopressin. No case of bright spot recovery was observed following therapy. Protracted symptom intervals for germinoma-induced central DI may reflect poor clinical awareness. Explanations for persistence of the pituitary bright spot in symptomatic patients remain elusive. Desmopressin seldom reverses the clinical features of germinoma-induced DI to allow discontinuation, nor does treatment cause bright spot recovery.
    Full-text · Article · Sep 2014
    • Some studies suggested that PN components, such as amino acid, cause cholestasis. In 2006, Choi et al. [6] reported that the frequency of PNAC in VLBWIs could be decreased by adjusting the composition of amino acid mixtures in PN. Also, ω-6 fatty acids, phytosterols in soybean oil, and trace elements such as copper and manganese, acting as toxicants, can lead to cholestasis [7,8].
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: Parenteral nutrition (PN)-associated cholestasis (PNAC) is one of the most common complications in very low birth weight infants (VLBWIs). The aim of this study is to evaluate the risk factors of PNAC in VBLWIs. Methods: We retrospectively reviewed the medical records of 322 VLBWIs admitted to the neonatal intensive care unit of our hospital from July 1, 2009 to December 31, 2013. We excluded 72 dead infants; 6 infants were transferred to another hospital, and 57 infants were transferred to our hospital at 2 weeks after birth. The infants were divided into the cholestasis and the non-cholestasis groups. PNAC was defined as a direct bilirubin level of ≥2.0 mg/dL in infants administered with PN for ≥2 weeks. Results: A total of 187 VLBWI were enrolled in this study; of these, 46 infants developed PNAC. Multivariate logistic regression analysis showed that the risk factors of PNAC in VLBWI were longer duration of antimicrobial use (odds ratio [OR] 4.49, 95% confidence interval [95% CI] 4.42-4.58), longer duration of PN (OR 2.68, 95% CI 2.41-3.00), long-term lack of enteral nutrition (OR 2.89, 95% CI 2.43-3.37), occurrence of necrotizing enterocolitis (OR 2.40, 95% CI 2.16-2.83), and gastrointestinal operation (OR 2.19, 95% CI 2.03-2.58). Conclusion: The results of this study suggest that shorter PN, aggressive enteral nutrition, and appropriate antimicrobial use are important strategies in preventing PNAC.
    Full-text · Article · Mar 2016
    • We were able to show that satisfaction with health care is highest in conditions with a homogenous profile and available standard, evidence based guidelines such as type 1 diabetes, juvenile arthritis and cystic fibrosis (majority of participants in the pulmonary group) and easy access to clinics for outpatient adolescents. In childhood onset type 1 diabetes, care is typically transitioned around age 16 in a fairly standardized manner both in pediatric and in adult services [30]. Access to specialized care, medication and patient education programs is easier compared to other conditions.
    [Show abstract] [Hide abstract] ABSTRACT: Background: The transition of health care of youth (age 15-25) with chronic conditions requires the assessment of adolescents' access, use and needs as well as satisfaction with the health services they use. The aim of this study was to test the adolescent adaptation of the parent version "Child Health Care Questionnaire - Satisfaction, Utilization and Needs" (CHC-SUN) concerning its psychometric performance and appropriateness for adolescents and young adults. Methods: The Youth Health Care Measure (YHC-SUN) was designed to allow self-report of youth and it was pilot-tested in a small sample using cognitive debriefing. A cross-sectional survey in a sample of youth with chronic conditions in the transition period was carried out. Results: One hundred eighty-two ambulatory care patients with three conditions participated in the survey. The subscales of the section on satisfaction with care showed excellent internal consistencies, uni-dimensionality and fit to the model of the parent version. There was no impact of gender and education on satisfaction with care. Associations with age, diagnosis, experiences with care and health literacy affecting the satisfaction with care indicate discriminatory and content validity. Conclusions: Potential applications of the new instrument are evaluations of health care services for adolescents and young adults using self-reports and evaluations of transition programs and interventions such as patient education.
    Full-text · Article · May 2016
    • Parhamifar et al.[33]established that stimulation of epithelial cells with LTD 4 at a concentration of 40 nM resulted in internalization of CYSLTR1 and, to a lesser extent, CYSLTR2 from the plasma membrane to the nuclear membrane. After stimulation with 20 nM LTB 4 trafficking of intracellular BLT1R to the cell surface in human eosinophils was observed[34]. In this study, we estimated, for the first time, the effect of LTs on their own receptor expression in mast cells.
    [Show abstract] [Hide abstract] ABSTRACT: The effects of LTs are mediated by GPCRs: cysLTs interact with CYSLTR1, CYSLTR2, or GPR17, and LTB4 acts via BLT1R or BLT2R. Data relating to the presence of these receptors in mature tissue mast cells are not entirely known. By confocal microscopy with image analyses and flow cytometry, we established that native rat mast cells isolated from peritoneal cavity constitutively express all studied receptors. Moreover, we clearly documented that LTs by themselves can influence their own receptor expression. Low concentrations of LTs induce translocation of LT receptors from cell interior to plasma membrane, which can lead to increased mast cell responsiveness to LT stimulation. High concentrations of LTs cause internalization and, in consequence, reduction in the number of receptors on the cell surface, and it may result in desensitization of mast cells to subsequent LT stimulation. These observations may imply a physiological feedback mechanism regulating mast cell sensitivity to LT activation within tissues.
    Full-text · Article · Apr 2017
    • Other than, it has been demonstrated that 4-HNE is able to modulate activation of NF-κB, for example, 4-HNE may induce cell death by activating NF-κB pathways (Yin et al. 2015). It is known that during the ALA, active NF-κB upregulate the IL-8 synthesis, which is a crucial mediator in inflammation and tissue injury (Lee et al. 2014 ). In addition , it is known that 4-HNE stimulates the activation of Nrf2 signalling pathway (Chen and Niki, 2006).
    [Show abstract] [Hide abstract] ABSTRACT: Entamoeba histolytica is the causative agent of amoebic liver abscess (ALA), which course with an uncontrolled inflammation and nitro-oxidative stresses, although it is well known that amoeba has an effective defence mechanisms against this toxic environment, the underlying molecular factors responsible for progression of tissue damage remain largely unknown. The purpose of the present study was to determine during the acute stage of ALA in hamsters, the involvement of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor-kappa B (NF-κB), which are activated in response to oxidative stress. From 12 h post-infection the ALA was visible, haematoxylin-eosin and Masson's trichrome stains were consistent with these observations, and alanine aminotransferase, alkaline phosphatase and γ-glutamyl transpeptidase serum activities were increased too. At 48 h after infection, liver glycogen content was significantly reduced. Western blot analyses showed that 4-Hydroxy-2-nonenal peaked at 12 h, while glycogen synthase kinase-3β, cleaved caspase-3, pNF-κB, interleukin-1β and tumour necrosis factor-α were overexpressed from 12 to 48 h post-infection. Otherwise, Nrf2 and superoxide dismutase-1, decreased at 48 h and catalase declined at 36 and 48 h. Furthermore, heme oxygenase-1 was increased at 12 and 24 h and decreased to normal levels at 36 and 48 h. These findings suggest for the first time that the host antioxidant system of Nrf2 is influenced during ALA.
    Article · Nov 2016