• Reproductive and Developmental Biology
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• v.35 no.2
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• pp.159-165
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• 2011

To explore the role of histone deactylase (HDAC) activation in an in vivo model of hypertrophy, we studied the effects of Trichostatin A (TSA). TSA subjected to thoracic aortic banding (TAB)-induced pressure stress in mice. In histological observations, TAB in treated mice showed a significant hypertrophic response, whereas the sham operation remained nearly normal structure with partially blunted hypertrophy. TSA treatment had no effect (measured as HW/BW) on sham-operated animals. TAB animals treated with vehicle manifested a robust ~50% hypertrophic response (p<0.05 vs sham). TAB mice treated with 2 mg/kg/day TSA manifested a blunted growth responses, which was significantly diminished (p<0.05) compared with vehicle-treated TAB mice. TAB mice treated with a lower dose of TSA (0.5 mg/kg/day) manifested a similar blunting of hypertrophic growth (~25% increase in heart mass). Furthermore, to determine activity duration of TSA in vitro, 1 nM TSA was added to H9c2 cells. Histone acetylation was initiated at 4 hr after treatment, and it was peak up to 18 hr, then followed by significantly reduced to 30 hr. We also analyzed the expression of p53 following TSA treatment, wherein p53 expression was elevated at 4 hr, and it was maintained to 24 hr after treatment. ERK was activated at 8 hr, and maintained till 30 hr after treatment suggesting an intracellular signaling interaction between TSA and p53 expression Taken together, it is suggested that HDAC activation is required for pressure-overload growth of the heart. Eventually, these data suggest that histone acetylation may be a novel target for therapeutic intervention in pressure-overloaded cardiac hypertrophy.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.42-48
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• 2012

Pompe disease is a rare lysosomal glycogen storage disorder caused by a total or partial deficiency of the acid ${\alpha}$-glucosidase (GAA) enzyme due to the GAA gene mutations. The classic infantile form of Pompe disease is a rapidly progressive multi-organ disease with hypotonia, generalized muscle weakness, and hypertrophic cardiomyopathy, usually leading to death in the first 2 years of life. Enzyme replacement therapy with recombinant human GAA has been shown to be effective and subsequently yielded promising results. Here, we present clinical and genetic characteristics of three Korean non-classic infantile Pompe patients, and the short term efficacy of enzyme replacement therapy. Considering that enzyme replacement therapy can change the natural course of infantile Pompe disease, early diagnosis and early initiation of treatment is critical to improving patient outcomes.

• Advances in pediatric surgery
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• v.20 no.2
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• pp.43-47
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• 2014

Purpose: Hypertrophic pyloric stenosis (HPS) is known to be one of the most common cause of surgery for infants and pyloromyotomy was considered to the standard treatment. There has been an ongoing debate about whether laparoscopic pyloromyotomy (LP) or open pyloromyotomy (OP) is the best option for treating HPS. The aim of this study is to evaluate safety and effectiveness of LP by comparing the clinical results of both surgical strategies performed by single surgeon. Methods: Between January 2000 and December 2013, 60 patients who underwent pyloromyotomy at Asan Medical Center performed by a surgeon were followed: open-supraumbilical incision (n=36) and LP (n=24). The parameters included sex, age and body weight at operation. Clinical outcomes included operation time, time to full feeding, postoperative hospital stay, and postoperative complications. Results: There were no significant differences in characteristics, postoperative hospital stay between the two groups. Time to full feeding was shorter in LP (OP 24.5 hours vs. LP 19.8 hours; p=0.063). In contrast, the mean operation time was longer in LP (OP 37.5 minutes vs. LP 43.5 minutes; p=0.072). Complications such as perforation of mucosal layer (OP 1 vs. LP 0) and wound problems (OP 2 vs. LP 0) were found to be not worse in laparoscopic group as compared with open group. Conclusion: There has no difference both laparoscopic and open-supraumbilical incision in terms of postoperative hospital stay, time to full feeds and frequency of complications.

• Applied Microscopy
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• v.2 no.1
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• pp.17-31
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• 1972

Light and electron microscopic studies were made to investigate the morphological changes in growing galls on the leaf of Lycium chinense MILL caused by Eriophyes kuko Kishda. The results are summarized as follows: 1. Light microscopy At the early stage of the invasion of E. kuko on the back side of the young leaf of L. chinense, the.epidermal cells become hypertrophic and develope a gall. As the gall grows, the cells of both palisade and spongy-layers become hypertrophic and these tissues are hard to be distinguished because of their irregular outgrowth. As the gall grows, the nuclei of the gall also become hypertrophic and larger than these of normal cells. 2. Electron microscopy Under electron microscopy the mitochondria, the golgi apparatus and the plastids of the advanced galls are degenerated and disintergrated and the cell walls become thicker than normal ones. The characteristic star bodies and the ring-form structures are found in the mature gall cells.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.21 no.1
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• pp.23-28
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• 1999

ALP (alkaline phosphatase) is a membrane-bound metalloenzyme that is expressed in osteoblasts, hepatocytes, lung, kidney, endothelial cells, leukocytes and other cells. Normal soft tissue and skin show little tissue nonspecific ALP (TN-AP), However, scar tissue contains high levels of TN-AP activity, and in fact, TN-AP is expressed intensely in regenerating connective tissue after the wounding. The purpose of this study was to evaluate the change of ALP expression in hypertrophic scar model in rabbits and the effect of triamcinonolone on ALP expression. Adult male New Zealand white rabbits, weighing about 2.5 kg, were used. After full-thickeness wounding over the ventral surface of each ear, either saline (control ear) or triamcinolone (contralateral ear) was injected on day 16. Rabbits were sacrificed on day 3, 7, 15, 17, 19, 23, and the specimens were retrieved en bloc. Histologic and immunohistochemical examinations of tissue samples were done. The results obtained were as follows: On day 3, ALP reaction was observed on fibroblasts and inflammatory cells in wound margin. On day 7, ALP reaction was more intense than day p in capillaries, inflammtory cells, and fibroblasts behind newly formed epithelium. On day 15, ALP reaction was lessened in both groups and appeared mainly in subepidermal capillary network, Since day 17, ALP reaction was lessened in both groups and weaker in triamcinolone-injected group than in saline-injected group. These results suggest that ALP reaction isn't increased in triamcinolone-injected scar and triamcinolone reduces scar not by increasing TN-AP expression but other mechanism.

• Molecules and Cells
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• v.44 no.7
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• pp.500-516
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• 2021

Cardiac hypertrophic signaling cascades resulting in heart failure diseases are mediated by protein phosphorylation. Recent developments in mass spectrometry-based phosphoproteomics have led to the identification of thousands of differentially phosphorylated proteins and their phosphorylation sites. However, functional studies of these differentially phosphorylated proteins have not been conducted in a large-scale or high-throughput manner due to a lack of methods capable of revealing the functional relevance of each phosphorylation site. In this study, an integrated approach combining quantitative phosphoproteomics and cell-based functional screening using phosphorylation competition peptides was developed. A pathological cardiac hypertrophy model, junctate-1 transgenic mice and control mice, were analyzed using label-free quantitative phosphoproteomics to identify differentially phosphorylated proteins and sites. A cell-based functional assay system measuring hypertrophic cell growth of neonatal rat ventricle cardiomyocytes (NRVMs) following phenylephrine treatment was applied, and changes in phosphorylation of individual differentially phosphorylated sites were induced by incorporation of phosphorylation competition peptides conjugated with cell-penetrating peptides. Cell-based functional screening against 18 selected phosphorylation sites identified three phosphorylation sites (Ser-98, Ser-179 of Ldb3, and Ser-1146 of palladin) displaying near-complete inhibition of cardiac hypertrophic growth of NRVMs. Changes in phosphorylation levels of Ser-98 and Ser-179 in Ldb3 were further confirmed in NRVMs and other pathological/physiological hypertrophy models, including transverse aortic constriction and swimming models, using site-specific phospho-antibodies. Our integrated approach can be used to identify functionally important phosphorylation sites among differentially phosphorylated sites, and unlike conventional approaches, it is easily applicable for large-scale and/or high-throughput analyses.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.3
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• pp.265-272
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• 2021

Purpose: Hypertrophic pyloric stenosis (HPS) is the most common cause of gastric obstruction in newborns. Extra-mucosal pyloromyotomy can be performed through a small laparotomy or laparoscopy. The aim of this study was to compare the two surgical techniques. We also analyzed the incidence of HPS in infants in the last 10 years in relation to the demographic trend of our province. Methods: We analyzed all the cases of HPS treated at our Unit between January 2010 and December 2019. The data were obtained from operating systems. Data about the demographic trends, in particular, the number of births and the population residing in the province of Verona from 2010 to 2019, were also retrieved. Results: During the study period, 60 patients were treated for HPS and met the inclusion criteria. Of these, 56 males and 4 females with an average age of 38±14 days at surgery were included. No differences were found in terms of the duration of surgery, post-operative complications, duration of hospitalization, and weight at the time of surgery. The only statistically significant data was the chlorine level in cases with and without post-operative vomiting (97±3.5 vs. 102±3.3 mmol/L, p<0.05). There was a lower incidence of HPS from 2014 to 2019; however, there was no significant evidence regarding the correlation between this and the reduced birth rate recorded in the province of Verona during the same period. Conclusion: Although laparoscopic pyloromyotomy is a highly complex procedure, it is a feasible alternative to the classic open technique.

• Journal of Pharmacopuncture
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• v.25 no.3
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• pp.258-267
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• 2022

Objectives: Hypertrophic scars (HSs) are caused by abnormal wound healing. To date, no standard treatment has been made available for HSs. Scrophularia striata has been reported to accelerate wound healing and has the potential to prevent HS formation. In this study, we investigated the anti-scarring effects of S. striata extract (SSE) in a rabbit ear model of scarring. Methods: In this study, New Zealand white rabbit (weight: 2.3-2.5 kg) were used. In the prevention phase of the study, three test groups received 5%, 10%, and 15% ointments of SSE in the Eucerin base, the fourth group received Eucerin, and the fifth group received no treatment. The samples were obtained on day 35 after wounding. In the treatment phase of the study, the test groups received an intralesional injection of SSE (5%, 10%, and 15%), the fourth group received an intralesional injection of triamcinolone, the fifth group received a solvent (injection vehicle), and the sixth group received no treatment. To evaluate the anti-scarring effects of SSE, the scar elevation index (SEI), epidermis thickness index (ETI), collagen deposition, and MMP2 and MMP9 gene expression were evaluated. Results: A significant reduction in SEI, ETI, and collagen deposition was noted in animals treated with SSE compared with the control groups. In addition, topical SSE stimulated MMP2 and MMP9 gene expression. Conclusion: The findings of this study demonstrate the potential for SSE in the prevention and treatment of HS. SSE could be prepared as an appropriate formulation to treat wounds and prevent abnormal scarring.

• Korean Circulation Journal
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• v.53 no.9
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• pp.606-618
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• 2023

Background and Objectives: The prognostic or safety implication of renin-angiotensin-aldosterone system inhibitors (RASi) in hypertrophic cardiomyopathy (HCM) are not well established, mainly due to concerns regarding left ventricular outflow tract (LVOT) obstruction aggravation. We investigated the implications of RASi in a sizable number of HCM patients. Methods: We enrolled 2,104 consecutive patients diagnosed with HCM in 2 tertiary university hospitals and followed up for five years. RASi use was defined as the administration of RASi after diagnostic confirmation of HCM. The primary and secondary outcomes were all-cause mortality and hospitalization for heart failure (HHF). Results: RASi were prescribed to 762 patients (36.2%). During a median follow-up of 48.1 months, 112 patients (5.3%) died, and 94 patients (4.5%) experienced HHF. Patients using RASi had less favorable baseline characteristics than those not using RASi, such as older age, more frequent history of comorbidities, and lower ejection fraction. Nonetheless, there was no difference in clinical outcomes between patients with and without RASi use (log-rank p=0.368 for all-cause mortality and log-rank p=0.443 for HHF). In multivariable analysis, patients taking RASi showed a comparable risk of all-cause mortality (hazard ratio [HR], 0.70, 95% confidence interval [CI], 0.43-1.14, p=0.150) and HHF (HR, 1.03, 95% CI, 0.63-1.70, p=0.900). In the subgroup analysis, there was no significant interaction of RASi use between subgroups stratified by LVOT obstruction, left ventricular (LV) ejection fraction, or maximal LV wall thickness. Conclusions: RASi use was not associated with worse clinical outcomes. It might be safely administered in patients with HCM if clinically indicated.

• Journal of Cardiovascular Imaging
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• v.31 no.1
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• pp.41-48
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• 2023

BACKGROUND: The function of left atrium (LA) is difficult to assess because of its ventricle-dependent, dynamic movement. The aim of this study was to assess LA function using velocity vector imaging (VVI) and compare LA function in patients with hypertrophic cardiomyopathy (HCMP) and left ventricular hypertrophy (LVH) with normal controls. METHODS: Fourteen patients with HCMP (72% male, mean age of 52.6 ± 9.8), 15 hypertensive patients with LVH (88% male, mean age of 54.0 ± 15.3), and 10 age-matched controls (83% male, mean age of 50.0 ± 4.6) were prospectively studied. Echocardiographic images of the LA were analyzed with VVI, and strain rate (SR) was compared among the 3 groups. RESULTS: The e' velocity (7.7 ± 1.1; 5.1 ± 0.8; 4.5 ± 1.3 cm/sec, p = 0.013), E/e' (6.8 ± 1.6; 12.4 ± 3.3; 14.7 ± 4.2, p = 0.035), and late diastolic SR at mid LA (-1.65 ± 0.51; -0.97 ± 0.55; -0.82 ± 0.32, p = 0.002) were significantly different among the groups (normal; LVH; HCMP, respectively). The e' velocity, E/e', and late diastolic SR at mid LA were significantly different between normal and LVH (p = 0.001; 0.022; 0.018), whereas LA size was similar between normal and LVH (p = 0.592). The mean late diastolic peak SR of mid LA was significantly correlated with indices of diastolic function (E/e', e', and LA size). CONCLUSIONS: The SR is a useful tool for detailed evaluation of LA function, especially early dysfunction of LA in groups with normal LA size.