• Molecules and Cells
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• 제42권11호
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• pp.739-746
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• 2019

Significant knowledge about the pathophysiology of Alzheimer's disease (AD) has been gained in the last century; however, the understanding of its causes of onset remains limited. Late-onset AD is observed in about 95% of patients, and APOE4-encoding apolipoprotein E4 (ApoE4) is strongly associated with these cases. As an apolipoprotein, the function of ApoE in brain cholesterol transport has been extensively studied and widely appreciated. Development of new technologies such as human-induced pluripotent stem cells (hiPSCs) and CRISPR-Cas9 genome editing tools have enabled us to develop human brain model systems in vitro and readily manipulate genomic information. In the context of these advances, recent studies provide strong evidence that abnormal cholesterol metabolism by ApoE4 could be linked to AD-associated pathology. In this review, we discuss novel discoveries in brain cholesterol dysregulation by ApoE4. We further elaborate cell type-specific roles in cholesterol regulation of four major brain cell types, neurons, astrocytes, microglia, and oligodendrocytes, and how its dysregulation can be linked to AD pathology.

• 대한유전성대사질환학회지
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• 제22권1호
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• pp.1-8
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• 2022

Long-chain fatty acid oxidation disorders (LC-FAOD) are an autosomal recessive inherited rare disease group that result in an acute metabolic crisis and chronic energy deficiency owing to the deficiency in an enzyme that converts long-chain fatty acids into energy. LC-FAOD includes carnitine palmitoyltransferase type 1 (CPT1), carnitine-acylcarnitine translocase (CACT), carnitine palmitoyltransferase type 2 (CPT2), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), and trifunctional protein (TFP) deficiencies. Common symptoms of LC-FAOD are hypoketotic hypoglycemia, cardiomyopathy, and myopathy. Depending on symptom onset, the disease can be divided as neonatal period, late infancy and early childhood, adolescence, or adult onset, but symptoms can appear at any time. The neonatal screening test (NBS) can be used to identify the characteristic plasma acylcarnitine profiles for each disease and confirmed by deficient enzyme analysis or molecular testing. Before introduction of NBS, the mortality rate of LC-FAOD was very high. With NBS implementation as routine neonatal care, the mortality rate was dramatically decreased, but severe symptoms such as rhabdomyolysis recur frequently and affect the quality of life. Triheptanoin (Dojolvi^®), the first drug for pediatric and adult patients with molecularly confirmed LC-FAOD, has recently been approved by the US Food and Drug Administration in 2020. In this review, the diagnosis of LC-FAOD and treatment including triheptanoin are summarized.

• 한국발생생물학회지:발생과생식
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• 제4권1호
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• pp.109-114
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• 2000

본 연구는 사춘기전과 사춘기가 시작될 무렵의 흰쥐난소에서 에탄올이 steroidogenic acute regulatory protein(StAR)의 유전자 발현에 어떠한 영향을 미치는지 조사하고자 수행되었다. 생후 25일 째부터 매일 흰쥐에 에탄을 또는 생리식염수를 복강주사하고 생후 27일, 32일 째에 실험동물을 희생시켜 혈액과 난소를 적출하였다. 실험결과 에탄올은 혈중의 황체호르몬 함량을 유의하게 감소시켰으며, 자궁의 무게는 27일 째에는 에탄올처리군에서 유의하게 적었으나, 32일 째에는 차이를 나타내지 않았다. 사춘기의 시작을 나타내는 지표의 하나인 viginal opening은 에탄올처리군에서 현저히 지연되었으며, 난소에서의 StAr mRNA발현 또한 유의하게 감소됨을 알 수 있었다. 따라서 본 연구결과는 에탄올이 적어도 사춘기 난소의 기능 및 사춘기의 시작을 교란시킬 수 있으며, 이러한 영향의 일부는 난소내 StAR유전자 발현을 억제함으로써 나타난다고 사료된다.

• 대한한의학회지
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• 제28권4호
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• pp.8-12
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• 2007

Objectives : This study aimed to investigate the circadian variation in stroke types, ischemic stroke subtypes, and Sasang constitutions. Methods : 295 patients with acute stroke within 14 days onset were included, who were admitted to Kyunghee Oriental Medical Center from October 2005 to May 2007. The stroke onset time was subdivided into four groups of 6-hour intervals in a day. Stroke types, ischemic stroke subtypes, and Sasang constitutions in four groups were examined. Results : Most ischemic stroke occurred between 6:01-12:00 hours (30.2%). For ischemic stroke subtypes, the peak period of small-vessel occlusion was between 6:01-12:00 hours (33.2%), large-artery atherosclerosis was most common between 12:01-18:00 hours (39.5%), and cardiac embolism was most frequent between 18:01-24:00 hours (50%). In terms of Sasang constitution, Soyeumin and Taeyeumin were most common between 6:01-12:00 hours (36.4% versus 41.5%, respectively), but the peak time of Soyangin was between 12:01-18:00 hours (35.2%). Conclusion :Most ischemic stroke events occurred in the mid-to-late morning hours in the present study and there was a circadian variation of onset in ischemic stroke subtypes and Sasang constitution.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2007년도 Proceedings of The Convention of The Korean Society of Applied Pharmacology
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• pp.147-153
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• 2007

Central to developing new treatment strategies for late onset sporadic Parkinson's disease (PD) and early onset familial PD is resolving the enigma of the specific vulnerability exhibited by substantia nigra dopamine (DA) neurons despite multiple risk factors. Neuropathological evidence from both human and experimental models of PD firmly supports a significant role for oxidative stress (OS) and mitochondrial dysfunction in the death of nigral DA neurons. Largely unknown are the genes underlying selective susceptibility of nigral DA neuron to OS and mitochondrial dysfunction and how they effect nigral DA cell death. To overcome the paucity of nigral DA neurons as well as the dilution effect of non-DA cells in brain tissues, we have developed wild type DA cell line model, SN4741 and mutant DJ-1 (-/-) DA cells, appropriate for microarray analysis and differential mitochondrial proteomics. Mutations in the DJ-1 gene (PARK7), localized in cytoplasm and mitochondria, cause autosomal recessive early onset PD. Through microarray analysis using SN4741 cells followed by validation tests, we have identified a novel phylogenically conserved neuroprotective gene, Oxi-a, which is specifically expressed in DA neurons. The knockdown of the gene dramatically increased vulnerability to as. Importantly as down-regulated the expression level of the gene and recovery of its expression via transient transfection exerted significant neuroprotection against as insult. We also have identified altered expression of mitochondrial proteins and other familial PD genes in DJ-1 (-/-) mutant cells by differential mitochondrial proteomics. In DJ-1 (-/-) cells the knockdown of the other familial PD genes (Parkin and PINK1) dramatically increased susceptibility to as. Thus, further functional characterization of the Oxi-$\alpha$ gene family and the mitochondrial alteration in the DJ-1 (-/-) cell model will provide the rationale for the neuroprotective therapy against both sporadic and familial PD.

• Asian-Australasian Journal of Animal Sciences
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• 제13권10호
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• pp.1359-1366
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• 2000

An experiment was carried out to study plasma levels of hormones and metabolites of crossbred Holstein cattle during late pregnancy (28 days pre partum), early lactation (30 days post partum), mid-lactation (120 days post partum) and late lactation (210 days post partum). Two breed types of Holstein $Friesian{\times}Red$ Sindhi (50:50 = 50%HF) and Holstein $Friesian{\times}Red$ Sindhi (87.5:12.5 = 87.5%HF) were divided into four groups of four animals each. Two groups of each breed were fed with either rice straw treated with 5% urea or pangola hay (Digitaria decumbens) as the source of roughage throughout the experiments. There were a substantial increases in the mean levels of total triiodothyronine ($T_3$), insulin and glucagon at the onset of lactation, and maintained in a high levels during lactation advance for all groups of experiments. The mean levels of prolactin and thyroxine ($T_4$) were not significantly different among groups of animals, but the plasma cortisol concentration was slightly higher in both groups of 50%HF in comparison with those of 87.5%HF animals. The mean levels of plasma growth hormone (GH) of both groups of 87.5%HF animals feeding on either hay or urea treated rice straw markedly rose in the early period of lactation and markedly reduced in mid- and late lactation. These changes were accompanied with changes of milk yield. In contrast to 50%HF animals, plasma GH levels were considerably higher in the late pregnant period than in the early period of lactation and it remained constant as its value at the early lactation throughout the experimental period. The high levels of both plasma progesterone and estradiol concentration significantly declined after parturition and remained low through lactating period. The plasma glucose level in the 50%HF animals feeding on either hay or urea treated rice straw was higher than the 87.5%HF animals in all periods of experiments. Changes in plasma FFA levels of both types of crossbred animals were depended on the endocrine status during late pregnancy and lactation. The levels of plasma FFA of 50%HF animals were significantly higher (p<0.05) than those of 87.5%HF animals during late pregnancy. Both plasma ${\beta}$-hydroxybutyrate and lactate concentrations were not affected by feeding on either hay or urea treated rice straw during late pregnancy and lactation. These data demonstrate that there were no differences in the physiological performances in the same crossbred animals fed either hay or urea treated rice straw. The 87.5%HF animal has the genetic potential for a high milk yield and homeorhetic adaptation for mammary function differed from 50%HF animals during periods of lactation. Altering lactation persistency in 87.5%HF is regulated mainly by chronically acting growth hormones through the period of lactation.

• Journal of Chest Surgery
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• 제49권6호
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• pp.478-480
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• 2016

Spontaneous perforation of the esophagus after forceful vomiting is known as Boerhaave syndrome, a rare and life-threatening condition associated with a high rate of mortality. The management of Boerhaave syndrome is challenging, especially when diagnosed late. Herein, we report the successful management of late-diagnosed Boerhaave syndrome with T-tube drainage in a 55-year-old man. The patient was transferred to our institution 8 days after the onset of symptoms, successfully managed by placing a T-tube, and was discharged on postoperative day 46 without complications.

• Clinical and Experimental Pediatrics
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• 제59권11호
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• pp.440-445
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• 2016

Purpose: This study aimed to identify prognostic factors of neurological outcomes, including developmental delay, cerebral palsy and epilepsy in late-preterm and term infants with perinatal asphyxia. Methods: All late-preterm and term infants with perinatal asphyxia or hypoxic-ischemic insults who admitted the neonatal intensive care unit of Inje University Sanggye Paik Hospital between 2006 and 2014 and were followed up for at least 2 years were included in this retrospective study. Abnormal neurological outcomes were defined as cerebral palsy, developmental delay and epilepsy. Results: Of the 114 infants with perinatal asphyxia, 31 were lost to follow-up. Of the remaining 83 infants, 10 died, 56 had normal outcomes, and 17 had abnormal outcomes: 14 epilepsy (82.4%), 13 cerebral palsy (76.5%), 16 developmental delay (94.1%). Abnormal outcomes were significantly more frequent in infants with later onset seizure, clinical seizure, poor electroencephalography (EEG) background activity, lower Apgar score at 1 and 5 minutes and abnormal brain imaging (P<0.05). Infants with and without epilepsy showed significant differences in EEG background activity, clinical and electrographic seizures on EEG, Apgar score at 5 minutes and brain imaging findings. Conclusion: We should apply with long-term video EEG or amplitude integrated EEG in order to detect and management subtle clinical or electrographic seizures in neonates with perinatal asphyxia. Also, long-term, prospective studies with large number of patients are needed to evaluate more exact prognostic factors in neonates with perinatal asphyxia.

• Tuberculosis and Respiratory Diseases
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• 제66권2호
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• pp.122-126
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• 2009

조혈모세포이식 후 1년 이내에 발생하는 폐 합병증의 진단 및 분류는 확립되어 있으나, 수 년 이상 장기간 생존자에게서 발생하는 폐 합병증에 대해서는 잘 알려져 있지 않다. 저자들은 8년 전 동종 조혈모세포이식을 시행받고, 호흡곤란을 주소로 내원한 18세 여자 환자에서, 폐조직 생검을 통해 비분류성 간질성 폐렴을 진단하였으나, 스테로이드 치료에도 불구하고 급격한 악화를 보여 호흡부전으로 사망한 1예를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

• 사회복지연구
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• 제39호
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• pp.5-28
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• 2008

본 연구의 목적은 한국청소년패널조사(KYPS) 자료를 활용하여 청소년기 흡연의 상이한 발달궤적 변화에 영향 미치는 예측요인들을 분석하는 것이다. 준모수적 집단중심모형(Semi-parametric group-based modeling)을 통해 청소년기 흡연에는 점증형 흡연집단(escalator), 실험형 흡연집단(experimenter), 후발형 흡연집단(late onsetter), 비흡연집단(non initiator) 등 4가지 발달궤적이 존재하는 것으로 밝혀졌다. 비행, 음주 등 다른 영역의 발달궤적과 달리 흡연에는 중단형 집단이 없는 것으로 나타났다. 또한 다항 로지스틱 회귀분석을 통해 사회발달모형(social development model) 내의 위험요인과 보호요인을 중심으로 흡연집단들을 구분하는 요인을 살펴본 결과, 모든 발달영역의 위험요인과 보호요인 대부분이 13세 시기에 흡연하지 않았던 청소년 중 계속해서 비흡연하는 집단과 이후 흡연을 늦게 시작한 집단을 구분하는 것으로 나타났다. 반면 13세에 이미 흡연하고 있었던 청소년 중 계속해서 흡연을 증가시키는 집단과 점차 흡연을 감소시키는 집단을 구분하는 요인은 자아존중감, 학업성취 등 소수로 나타났다. 흡연집단을 구분하는 위험요인과 보호요인들은 발달적으로 적절하고 효과적인 예방프로그램의 구성요소를 발견할 수 있도록 도와준다. 본 연구의 결과를 통해 13세에 흡연하고 있지 않은 집단은 물론 이미 흡연을 시작한 집단까지도 원조할 수 있는 중학교 시기 금연프로그램을 개발할 수 있는 단초를 마련하였다.