• Journal of Genetic Medicine
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• 제16권2호
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• pp.85-89
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• 2019

Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive urea cycle disorder. HHH is caused by a deficiency of the mitochondrial ornithine transporter protein, which is encoded by the solute carrier family 25, member 15 (SLC25A15) gene. Recently, government supported Korean newborn screening has been expanded to include a tandem mass spectrometry (MS/MS) measurement of ornithine level. We report a case of a neonate with HHH syndrome showing a normal MS/MS measurement of ornithine level. A female newborn was admitted to neonatal intensive unit due to familial history of HHH syndrome. Her parents were consanguineous Parkistani couple. The subject's older sister was diagnosed with HHH syndrome at age of 30 months based on altered mental status and liver dysfunction. Even though the subject displayed normal ammonia and ornithine levels based on MS/MS analysis, a molecular test confirmed the diagnosis of HHH syndrome. At 1 month of age, amino acid analysis of blood and urine showed high levels of ornithine and homocitrulline. After 11 months of follow up, she showed normal growth and development, whereas affected sister showed progressive cognitive impairment despite no further hyperammonemia after protein restriction and standard therapy. Our report is in agreement with a previous Canadian study, which showed that neonatal samples from HHH syndrome patients demonstrate normal ornithine levels despite having known mutations. Considering the delayed rise of ornithine in affected patients, genetic testing, and repetitive metabolic testing is needed to prevent patient loss in high risk patients.

• Molecular & Cellular Toxicology
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• 제1권3호
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• pp.209-215
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• 2005

Recently, a large number of clinical experiments have shown that exposure of organic pollutants lead to various cancers through the abnormal cell growth. Environmental pollutants, such as 2, 3, 7, 8-Tetrachloro dibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons (PAHs), are carcinogen and are known to cause the cognitive disability and motor dysfunction in the developing of brain. The effects of these pollutants on neurodevelopmental disorder is well established, but the underlying mechanism(s) and similarity of gene expression profiles in human brain tumors with organic pollutants still remain unclear. In this study, we first examined the gene expression profiles in glioblastomas compared with meningioma that are kinds of primary human brain tumor by using human cDNA microarray. The results of cDNA microarray analysis revealed that 26 genes were upregulated (Z-ratio>2.0) and 14 genes were downregulated (Z-ratio<-2.0) in glioblastoma compared with meningioma. From the altered gene patterns, mitogen-activated protein kinase (MAPK) signaling related genes, such as MAP2K3, MAP3K11 and jun activated domain binding protein, and transcription factors, such as UTF2 and TF12, were upregulated in glioblastoma. Also, we tried to investigate the relation between important genes up- and down-regulated in giloblastoma and various organic pollutants. Therefore, the identification of changes in the patterns of gene expression may provide a better understanding of the molecular mechanisms involved in human primary brain tumors and of the relation between gene expression profiles and organic pollutants in brain tissue.

• 대한수의학회지
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• 제41권4호
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• pp.603-609
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• 2001

A transport stress is one of the main causes of economic losses and physiological dysfunction. The present study has been performed to suggest a method to decrease the adverse effects above mentioned from transport. The groups were prepared as follows; (1) Control group : 4 cattle transported for 5 hrs (274 km) without any treatment, (2) Treatment group : 4 cattle treated with electrolyte-mineral solution (I.V.) at 1 hr before the enrollment of transport under same experimental condition with Control group. The blood specimens were collected at 1 hr before transport, 2.3 hrs (135 km) and 5 hrs (274 km) after the enrollment of transport, and 1, 6 and 18 hrs after fulfillment of transport. The collected blood specimens were analyzed for cortisol and epinephrine. Core temperature and heart rate were measured with active biotelemetry in every 30 minutes from 0.5 hr before the start of transport to 18 hrs after the end of transport. In results, the level of cortisol considerably increased to the peak either in Control group ($5.3{\pm}1.3{\mu}g/d{\ell}$) and in Treatment group ($4.0{\pm}2.6{\mu}g/d{\ell}$) at 2.3 hrs in transport. The concentration of epinephrine of Treatment group had been higher than that of Control group from the start of transport to 18 hrs after the fulfillment of transport. Particularly there was the biggest gap between Control and Treatment groups, $424.0{\pm}194.1pg/m{\ell}$ and $209.1{\pm}65.1pg/m{\ell}$ respectively, at 6 hrs after the end of transport. The heart rates were considerably increased either in Control group ($81.5{\pm}18.5$ to $126.3{\pm}7.8beats/min$) and in Treatment group ($114.3{\pm}14.4$ to $140.8{\pm}22.4beats/min$) with the enrollment of transport. These results indicate that the concentration of cortisol and the heart rate were pertinent to cognitive parameters to evaluate physiological responses against stress such as transport. In addition, the intravenous administration of electrolyte-mineral solution could be suggested as the method to decrease the adverse effects from a transport stress.

• 한국산학기술학회논문지
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• 제16권1호
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• pp.462-470
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• 2015

본 연구는 사회경제적 차이가 아동의 뇌기능과 문제행동증후에 미치는 영향에 대해서 살펴보았다. 장애, 질병 또는 인지기능에 문제가 없는 저소득층(LIC) 아동 30명, 중산층(MC)아동 30명을 대상으로 2013년 1월부터 4월까지 뇌기능 분석과 K-CBCL을 이용한 아동문제행증후의 데이터를 측정 분석하였다. 연구 결과는 첫째, LIC아동은 MC아동보다 세타파(${\Theta}$), SMR파의 비율과 델타파(${\delta}$), 고베타파(${\beta}h$), 알파파(${\alpha}$):저베타(${\beta}l$)의 비율이 유의미하게 높게 나타났고, MC아동은 LIC아동보다 자기조절지수 주의지수 정서지수 항스트레스지수 브레인 지수의 값에서 더 유의미하게 높다는 것을 보여주었다. 둘째, 아동문제행동증후는신체증상, 우울/불안, 사회적 미성숙, 사고의 문제, 주의집중문제, 공격성, 내재화, 외현화, 총 문제행동, 정서불안정에 있어서 LIC아동이 MC아동에 비해서 더 유의미하게 높았고, MC아동은 사회성, 학업수행능력, 총 사회능력에서 LIC아동보다 유의미하게 높았다. 결론적으로, LIC아동과 MC아동의 사회경제적 차이가 상기 뇌기능과 문제행동증후에 영향을 미치는 것으로 밝혀졌다.

• 정신신체의학
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• 제17권1호
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• pp.30-36
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• 2009

연구목적 : 갑상선기능은 기분, 인지기능, 불안, 수면 등의 증상과 관련된다. 갑상선기능이상 시에 정신분열병 환자에서 음성증상, 기분, 신체증상에 어떤 차이가 있는지, 또 각각의 증상 변화와 어떻게 연관되는지를 연구하였다. 방법 : 정신분열병으로 입원했던 환자 65명을 입원 당시의 갑상선호르몬 수치에 따라 갑상선기능불안정 군과 갑상선기능정상 군으로 나누었다. 두 군의 입원 당시와 8주 후에 평가했던 음성증상평가척도(Scale for the Assessment of Negative Symptoms ; 이하 SANS), 양성증상평가척도(Scale for the for the Assessment of Positive Symptoms ; 이하 SAPS), 벡우울증척도(Beck Depression Inventory ; 이하 BDI), 신체감각증폭척도(Somatosensory Amplication Scale ; 이하 SSAS)의 변화를 비교하였다. 각 환자들은 항정신병약물 치료를 포함한 입원 치료를 받았으며, 갑상선기능이 불안정했던 경우 4주 후에 갑상선호르몬의 정상화를 확인하였다. 결과 : 8주 뒤에 갑상선기능정상 군과 갑상선기능불안정 군에서 SANS, BDI, SSAS 변화 차이가 의미 있게 나타났다. 갑상선기능정상 군에서 갑상선기능불안정 군에 비해 척도 점수가 크게 낮아졌는데, SANS는 23.3%(F=57.0, p<0.01), BDI는 19.6%(F=12.9, p<0.01), 신체감각증폭척도는 16.2%(F=17.1, p<0.01) 더 변화가 컸다. SANS, BDI, SSAS 세 지표 간에 유의한 상관관계는 없었다. 결론 : 정신분열병 환자들에게서 갑상선기능이 음성증상, 우울감, 신체증상에 관련된 예후에 표지가 될 수 있을 것이다.

• 정신신체의학
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• 제4권1호
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• pp.21-36
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• 1996

본 연구는 월경전기 평가서(PAF)의 신뢰도와 타당도를 검증하고자 하였다. 서울시내 모 여고생 300명을 대상으로 PAF를 실시하여 검사 실시 상의 신뢰성이 의심되는 것을 제외한 250명 중에서 월경전기에 불편감을 느끼는가라는 질문에 예라고 응답한 230명의 자료에 대해 통계분석을 하였다. 피험자의 평균 연령은 $16.8{\pm}30.71$세, 초경연령은 $13.1{\pm}61.12$세였다. PAF 95문항의 평균과 반응빈도를 살펴본 결과 모든 문항에 골고루 응답되어 PMS의 다양성을 확인할 수 있었고 그 중에서도 한국 청소년의 주된 월경전기증상을 반영하는 것으로 보이는 21개 문항을 확인할 수 있었다. 검사의 내적 일치도는 ${\alpha}=.95$로 상당히 높아 문항의 동질성이 있음이 밝혀졌으며 검사-재검사 신뢰도는 r=.80으로 시간경과에 따른 검사의 안정성을 확인할 수 있었다. 요인분석 결과 충동성 및 불안정성 요인, 우울 요인, 철수 및 사회적 기능 손상 요인, 불안 및 인지기능 손상 요인, 신체생리적 변화 요인, 전반적 불편감 요인, 안녕감 증가 요인, 기타요인의 8개 요인구조가 확인되었다. 결론적으로 타당도 연구에서는 추출된 하위 요인구조 들이 월경전기 증상을 잘 반영하고 있으며 신뢰도 연구 결과도 만족스러운 수준을 보여 PAP가 월경전기 변화를 선별평가 하는데 유용하게 쓰일 수 있을 것으로 기대된다. 논의에서는 요인분석에 의한 분류체계를 Halbreich등(1982)의 주관적 평가기준에 의해 만들어진 형태학적 분류와 비교하여 보았고 마지막으로 본 연구의 제한점에 대해 논의해보았다.

• The Korean Journal of Pain
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• 제29권4호
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• pp.239-248
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• 2016

Background: The present study was undertaken to evaluate the incidence of chronic persistent post-surgical pain (CPPP) and the role of signal transduction genes in patients undergoing staging laparotomy for carcinoma ovary. Methods: The present observational study was undertaken following institutional ethical committee approval and informed consent from all the participants. A total 21 patients of ASA grade I to III with age 20-70 years, scheduled for elective staging laparotomy for carcinoma ovary were included. Patients were excluded if had other causes of pain, cognitive dysfunction or chronic neurological disorders. Statistical analysis of pool data was done using SPSS version-17. For various scales like GPE, PDQ, NPSI, the visual analogue scale (VAS), global perceived effect (GPE), the pain DETECT questionnaire (PDQ), and neuropathic pain symptoms inventory (NPSI), one factor repaeted measure ANOVA applied with simple contrast with baseline as on post-operative day 1 (considered as reference and compared with subsequent time-interval), and the P values were adjusted according to "Bonferroni adjustments". In patients with CPPP, the ${\Delta}ct$ values of mRNA expressions of genes at the end of postoperative day 90 were compared with the baseline control values by one factor repeated ANOVA. P value < 0.005 significant. Results: The present study demonstrates 38.1% (8 out of 21 patients) incidence of CPPP. The functional status and quality of life as were observed to be significantly diminished in all patients with chronic pain. An up-regulation in the mRNA expression of signal transduction and a positive correlation was noted between the mRNA expression of signal transduction genes and VAS score in all patients with CPPP at the end of postoperative day 90. Conclusions: The reported incidence of CPPP in patients with carcinoma ovary was 38.1%. An up-regulation and positive correlation between mRNA expression of signal transduction genes and VAS score depicts its potential role in the pathogenesis of CPPP.

• Journal of Nutrition and Health
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• 제40권1호
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• pp.14-23
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• 2007

Elevated plasma homocysteine (Hcy) is a risk factor for cognitive dysfunction and Alzheimer disease, although the mechanism is still unknown. Both folate and betaine, a choline metabolite, play essential roles in the remethylation of Hcy to methionine. Choline deficiency may be associated with low folate status and high plasma Hcy. Alterations in DNA methylation also have established critical roles for methylation in development of the nervous system. This study was undertaken to assess the effect of choline and folate deficiency on Hcy metabolism and genomic DNA methylation status of the liver and brain. Groups of adult male Sprague Dawley rats were fed on a control, choline-deficient (CD), folate-deficient (FD) or choline/folate-deficient (CFD) diets for 8 weeks. FD resulted in a significantly lower hepatic folate (23%) (p<0.001) and brain folate (69%) (p<0.05) compared to the control group. However, plasma and brain folate remained unaltered by CD and hepatic folate reduced to 85% of the control by CD (p<0.05). Plasma Hcy was significantly increased by FD $(18.34{\pm}1.62{\mu}M)$ and CFD $(19.35{\pm}3.62{\mu}M)$ compared to the control $(6.29{\pm}0.60{\mu}M)$ (p<0.001), but remained unaltered by CD. FD depressed S-adenosylmethionine (SAM) by 59% (p<0.001) and elevated S-adenosylhomocysteine (SAM) by 47% in liver compared to the control group (p<0.001). In contrast, brain SAM levels remained unaltered in CD, FD and CFD rats. Genomic DNA methylation status was reduced by FD in liver (p<0.05) Genomic DNA hypomethylation was also observed in brain by CD, FD and CFD although it was not significantly different from the control group. Genomic DNA methylation status was correlated with folate stores in liver (r=-0.397, p<0.05) and brain (r = -0.390, p<0.05), respectively. In conclusion, our data demonsoated that genomic DNA methylation and SAM level were reduced by folate deficiency in liver, but not in brain, and correlated with folate concentration in the tissue. The fact that folate deficiency had differential effects on SAM, SAH and genomic DNA methylation in liver and brain suggests that the Hcy metabolism and DNA methylation are regulated in tissue-specific ways.

• 대한소아치과학회지
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• 제47권1호
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• pp.93-98
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• 2020

Lesch-Nyhan 증후군은 hypoxanthine-guanine phosphoribosyl transferase 결핍으로 인해 발생한 purine 대사 장애의 열성 유전 질환이다. 이 증후군은 신경 장애, 행동 장애 및 과요산혈증(hyperuricemia) 등의 증상이 나타난다. 특징적으로 자해 습관은 2 - 3세경 시작되는데, 구강 주위 조직이나 손, 발을 물어 뜯는 양상이 나타난다. 이 증례는 2세 7개월의 Lesch-Nyhan 증후군 환아의 자해습관을 반 고정식 립 범퍼를 이용하여 차단한 증례를 보고하는 바이다. 반 고정식 립 범퍼는 전통적인 인상채득 방식을 필요로 하지 않고 내원 당일 치료해 줄 수 있는 장점이 있으며, 보호자에 의해 탈, 부착이 가능하여 환아의 구강위생 관리에 용이하였다. 장치 장착 2 개월 후, 치아 주위 조직이 회복되고 연속성이 유지되는 양호한 결과를 보였다. 장치 장착 11개월 후, 양호한 회복양상이 유지되었으며 추가적인 외상이나 자해행동의 악화는 관찰되지 않았다. 따라서, semi-fixed lip bumper는 Lesch-Nyhan syndrome 환아의 자해습관을 차단하기 위한 interim appliance로 사용하는데 유용할 것으로 사료된다.

• 동의신경정신과학회지
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• 제23권2호
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• pp.99-120
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• 2012

Objectives : The oriental medicine Jangwonhwan, a boiled extract of 12 medicinal herbs/mushrooms, has been prescribed to patients with cognitive dysfunction, as originally described in the Korean medical text, DonguiBogam(amnesia chapter). Recently, a modified formula of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushrooms, was shown to reduce the ${\beta}$-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model for Alzheimer's disease. The toxicity of LMK02-Jangwonhwan was investigated in SD rats, by a daily oral administration for 13 weeks and NOAEL(No observed adverse effect dose), a definite toxic dose and target organ, as well. Methods : Quality control of the tablet form of LMK02-Jangwonhwan was established by estimating the indicative components, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelicagigas Nakai. The toxicity of LMK02-Jangwonhwan was investigated in 6 week old, specific pathogen free (SPF), Sprageu-Dawley rats by oral administration. Each test group consisted of 10 male and 10 female rats. The groups received doses of 500, 1,000 or 2,000 mg/kg/day of test substance for 13 weeks. The clinical signs, death rate, body weight, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemistry, organ weight and pathological changes were examined and compared with those of the control group. Results : The 13-week repeated oral treatment doses didn't result in any specific symptoms or death. There were no significant changes in the rat's weight and food consumption. Further, ophthalmic examination, urinalysis, hematological, serum biochemistry test and organ weight revealed no significant differences. Conclusions : The no-observed-adverse-effect level(NOAEL) of LMK02 for male and female Sprague-Dawley rats was determined as 2,000mg/kg/day and the target organ wasn't confirmed. Because no significant adverse effects were observed, the target organ could not be determined.