• Journal of The Korean Society of Inherited Metabolic disease
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• v.21 no.1
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• pp.7-14
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• 2021

Purpose: Pseudohypoparathyroidism (PHP) is caused by genetic and epigenetic alteration in the GNAS locus, and characterized by the resistance to multiple hormones and the Albright's hereditary osteodystrophy (AHO) phenotype. This study investigated the phenotypic characteristics and molecular features of PHP. Methods: Eight patients who diagnosed as PHP were enrolled at Pusan National University Children's hospital and clinical features, biochemical and genetic findings were retrospectively reviewed. Results: Of a total of 8 patients, 5 were diagnosed with PHP1a, and 3 were diagnosed with PHP1b. Patients with PHP1a had three different mutations in the GNAS gene, and patients with PHPIb had imprinting defect in differentially methylated regions (DMRs) of the GNAS locus. Two novel GNAS variants were identified in patients with PHP1a, including c.313-2A>T and c.1094G>A. All patients with PHP1a displayed AHO features; short stature (80%), brachydactyly (80%), a round face (80%), obesity (40%), heterotopic ossification (60%), and intellectual disability (60%), whereas only one patient (33.3%) with PHP1b showed AHO feature such as a round face. When phenotypic features between PHP1a and PHP1b patients were compared, patients with PHP1b showed a tendency of higher current height standard deviation scores (SDS) compared to patients with PHP1a, (-3.2±2.1 vs.-1.1±0.8; P=0.06) Conclusions: This study summarizes the phenotypic and genetic features of the PHP patients. Although we found considerable clinical overlap between PHP1a and PHP1b, further long-term follow-up is needed to evaluate the growth and development of children with PHP, as well as the effects of end-organ resistances to endocrine hormones.

• Journal of Nutrition and Health
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• v.56 no.2
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• pp.155-167
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• 2023

Purpose: This study investigates the association between seafood consumption and frailty according to gender in the Korean elderly. Methods: Cross-sectional data from the Seventh (2016-2018) Korea National Health and Nutrition Examination Survey was procured for this study. Data from 3,675 subjects (1,643 men and 2,032 women) aged ≥ 65 years were analyzed. Levels of seafood intake were assessed by a one-day 24-hour dietary recall, and subjects were classified into three tertiles by gender according to frailty phenotype: robust, pre-frail, and frail. Multinomial logistic regression analysis was performed to clarify the association between seafood consumption and frailty for each gender. Results: The prevalence of frailty was determined as 13.4% for men and 29.7% for women. Participants with a higher seafood intake had higher intakes of grains, fruits, and vegetables, while the intake of meat was significantly lower. In both men and women, the group with higher seafood intake showed higher energy and micronutrient intakes. The frail prevalence and frailty score were significantly low in the highest tertiles of seafood consumption compared to the lowest tertile in men and women (p < 0.001). After adjusting for confounder, the highest tertile of seafood consumption showed a decreased risk of frailty compared to the lowest tertile only in women (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.32-0.78; p-trend = 0.008 vs. HR, 0.52; 95% CI, 0.32-0.83; p-trend = 0.008; respectively). Conclusion: Results of this study suggest that seafood consumption potentially decreases the risk of frailty in the elderly.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.3
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• pp.135-140
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• 2013

Objective: To evaluate correlations between serum anti-M${\ddot{u}}$llerian hormone (AMH) levels, phenotypes of polycystic ovary syndrome (PCOS), obesity, and metabolic parameters in patients with PCOS. Methods: A total of 175 patients with PCOS were diagnosed according to the Rotterdam Consensus were included. Exclusion criteria were age over 40, FSH>25 mIU/mL, and 17a-OHP>1.5 ng/mL. The Phenotypes of PCOS were divided into a severe form (oligo-anovulation, ANOV/hyperandrogenism/polycystic ovary morphology [PCOM]; n=59) and a mild form without HA (ANOV/PCOM, n=105). The serum AMH levels were classified into 3 groups (<5 vs. 5-10 vs. >10 ng/mL). Obesity was defined as body mass index (BMI) ${\geq}25kg/m^2$ (n=34). Results: The mean age was $25.9{\pm}5.7$ year and mean AMH level was $10.1{\pm}5.4$ ng/mL. The BMI ($kg/m^2$) was higher in group 1 ($24.2{\pm}6.3$) than in group 2 ($21.9{\pm}4.3$, p=0.046) or group 3 ($21.6{\pm}3.3$, p=0.019). There was no difference among the three groups in age, menstrual interval, antral follicle counts, androgens, or other metabolic parameters. The obesity group showed significantly lower AMH ($7.7{\pm}3.9$ ng/mL vs. $10.7{\pm}5.6$ ng/mL), p=0.004) and low-density lipoprotein levels ($93.1{\pm}21.2$ mg/dL vs. $107.5{\pm}39.3$ mg/dL, p=0.031), and showed higher total T ($0.74{\pm}0.59$ L vs. $0.47{\pm}0.36$ ng/mL, p=0.001), free T ($2.01{\pm}1.9$ vs. $1.04{\pm}0.8$ pg/mL, p=0.0001), and free androgen index ($6.2{\pm}7.9$ vs. $3.5{\pm}3.0$, p=0.003). After controlling for age factors and BMI, the serum AMH levles did not show any significant correlations with other hormonal or metabolic parmeters. Conclusion: For PCOS patients under the age 40, serum AMH is not negatively correlated with age. High serum AMH levels can not predict the phenotype of PCOS and metabolic disturbances in PCOS patients in the non-obese group. Further study might be needed to define the relation more clearly.

• Microbiology and Biotechnology Letters
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• v.35 no.3
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• pp.196-202
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• 2007

Mutations in the cystathionine ${\beta}$-synthase (CBS) gene cause homocystinuria, the most frequent inherited disorder in sulfur metabolism. CBS is the unique enzyme using both heme and pyridoxal 5-phosphate (PLP) for activity. Among the reported 140 mutations, one of the most common disease-causing alterations in human CBS is G307S mutation. To investigate the pathogenic mechanism of G307S by spectroscopic methods, we engineered the full length and the truncated G247S mutation of yeast CBS that is corresponding mutation to human G307S. Yeast CBS does not contain heme and thus gives a merit to study the spectroscopic properties. The UV-visible spectra of the purified full length and the truncated G247S yeast CBSs showed the total absence of PLP in the protein. The absence of PLP in G247S mutation was also confirmed by the PLP-cyanide adduct formation experiment, which was conducted by the incubation of the purified enzyme with KCN. The adducts were detected using a circular dichroism (CD) and a spectrofluorimeter. Radio isotope activity assay of full length and truncated G247S proteins also gave no activity. Our yeast G247S mutation data suggested that G307S might make the distortion of the active site so that cofactor PLP and substrate can not fit inside the active site. Our yeast CBS study addressed the reason why the G307S mutation in human CBS makes the enzyme inactive that consequently leads to severe clinical phenotype.

• Tuberculosis and Respiratory Diseases
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• v.48 no.1
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• pp.24-32
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• 2000

Purpose: Microsatellite instability(MSI) is frequently used as an indicator of microsatellite mutator phenotype(MMP) tumors. MSI has been observed in a percentage of non-small cell lung cancer(NSCLC). However, its role in tumorigenesis of NSCLC remains unknown. The frequency and pattern of MSI in NSCLC were evaluated and clinical parameters of MSI-positive tumors with those of MSS(microsatellite stable) tumors were compared. Materials and Methods: Twenty surgically resected NSCLCs were analyzed for 15 microsatellite markers located at chromosomes 3p and 9p. The peripheral blood lymphocytes of patients were used as the source of the normal DNA. Results: 1) Of 20 cases, 8(40%) demonstrated MSI. 2) Instability was observed more frequently in tri- and tetra-nucleotide repeats than in dinucleotide repeats. In all cases, instability appeared as a shift of individual allelic bands. 3) LDH was observed in 10(50%) of 20 tumors analyzed. 4) Of 20 cases, MSI-H tumor(showing MSI in the majority of markers) was absent. There were 5 MSI-L tumors(showing MSI in a greater than 10% of markers). 5) No significant difference was observed between MSI-L tumors and MSI-negative tumors in terms of clinicopathologic features such as pack-year history of smoking, histologic subtype, and(delete) stage of disease. There was also no significant difference in the incidence of LDH in relation to the status of MSI. Conclusion: These data strongly suggest that MSI plays different roles in lung and colon cancer. MMP pathway appears to be far less important in the tumorigenesis of NSCLC, caused mainly by cigarette smoke, with little familial tendency.

• Journal of Life Science
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• v.27 no.9
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• pp.975-985
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• 2017

To investigate the beneficial effects of an agar gel mask (AGM) on UV-induced photoaging, SKH-1 hairless mice were treated with a topical application of AGM and an AGM dipped in essence (AGMdE). The mice were divided into an no radiation group, UV + AGM, UV + AGMdE, and UV + vehicle (PBS) treatment groups. Alterations in skin wrinkles, skin phenotype, histological structures, oxidative status, and toxicity were then evaluated during 4 weeks of exposure. The topical application of AGM and AGMdE inhibited wrinkle formation, suppressed the erythema index, prevented transepidermal water loss, and enhanced skin hydration. In addition, epidermal thickness recovered to a similar level as that in the no irradiation group in the UV + AGM and UV + AGMdE treatment groups compared with the UV + vehicle (distilled water) group. Furthermore, the expression levels of matrix metalloproteinase-1 (MMP-1) and tyrosinase were reduced in the UV + AGM and UV + AGMdE treatment groups, although the highest level varied. Moreover, superoxide dismutase (SOD) activity was significantly lower in the UV + AGM and UV + AGMdE treatment groups as compared with the UV + vehicle group. No significant alterations induced by most toxic compounds were measured in serum biochemical markers and liver and kidney histological features of the UV + AGM and UV + AGMdE treatment groups. These results suggest that AGM may protect against skin aging by regulating skin morphology, histopathological structures, and oxidative conditions.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.3
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• pp.99-106
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• 2018

Mucolipidosis type III (pseudo-Hurler polydystrophy) is a mucolipids degrading disorder caused by a mutation in the GNPTAB gene and is inherited by autosomal recessive. It is diagnosed by examining highly concentrated mucolipids in blood and the diagnosis can be confirmed by genetic testing. Mucolipidosis type III is a rare and progressive metabolic disorder. Its initial signs and symptoms usually occur around 3 years of age. Clinical manifestations of the disease include slow growth, joint stiffness, arthralgia, skeletal abnormalities, heart valve abnormalities, recurrent respiratory infection, distinctive facial features, and mild intellectual disability. Here, we are presenting two siblings of mucolipidosis type III, a 4-year-old female and a 2 years and 7 months old male with features of delayed growth and coarse face. The diagnosis was confirmed by [c.2715+1G>A(p.Glu906Leufs*4), c.2544del(p.Glu849Lysfs*22)] mutation in targeted gene panel sequencing. In this case, c.2544del is a heterozygote newly identified mutation in mucolipidosis type III and was not found in the control group including the genome aggregation database. And it is interpreted as a pathogenic variant considering the association with phenotype. Here, we report a Korean mucolipidosis type III patients with novel mutations in GNPTAB gene who have been treated since early childhood. Owing to recent development of molecular genetic techniques, it was possible to make early diagnosis and treatment with pamidronate was initiated appropriately in case 1. In addition to these supportive therapies, efforts must be made to develop fundamental treatment for patients with early diagnosis of mucolipidosis.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.2
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• pp.62-67
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• 2018

Hunter syndrome, also known as mucopolysaccharidosis Type II (MPS II), is one of the lysosomal storage diseases caused by a lack of the enzyme iduronate 2-sulfatase (I2S). Lack of the I2S enzyme activity leads to accumulation of the glycosaminoglycans (GAG), causing dysfunction of multiple organs and systems. MPS II is an X-linked recessive disease due to mutation of IDS gene located on long arm of the X chromosome (Xq28). To date, more than 350 mutations of IDS gene have been identified in Hunter syndrome. Phenotypes of MPS II are classified as either severe or attenuated depending on the degree of cognitive impairment. Because the phenotype of MPS II is related to the type of mutation, identifying mutations is useful in predicting prognosis. We recently had a case of MPS II diagnosed by exome sequencing in a 7 month old boy with infantile spasm uncontrolled by AED. He was diagnosed with hearing loss at 2 months of age, and he took vigabatrin and prednisolone to control infantile spasms diagnosed at 3 months of age. At 6 months of age, whole exome sequencing was performed to evaluate the infantile spasm and hearing loss in this patient, and the mutation c.851C>T (p.Pro284Leu) inherited from hemizygous mother was revealed. The results of urine Cetylpyridinium Chloride (CPC) precipitation test, which were negative until 8 months of age, were positive from 9 months of age. We report a case of MPS II diagnosed by exome sequencing and treated through enzyme replacement therapy from 9 months after birth.

• Molecules and Cells
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• v.45 no.12
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• pp.896-910
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• 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.