• Environmental Mutagens and Carcinogens
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• v.23 no.4
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• pp.131-134
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• 2003

There are significant differences in the extent of drug interactions between subjects. The influence of the genetic make up of drug metabolizing enzyme activities (CYP3A5, CYP2C19 and UDP-glucuronosyl transferase) on the pharmacokinetic drug interaction potential were studied in vivo. Nineteen healthy volunteers were grouped with regard to the $CYP3A5^{*}3$ allele, into homozygous wild-type (CYP3A5^{*}1/1^{*}1$, n=6), heterozygous $(CYP3A5^{*}1/^{*}3$, n=6), and homozygous variant-type $(CYP3A5^{*}3/^{*}3$, n=7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days), and also following rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. For omeprazole and moclobemide pharmacokinetic interaction study 16 healthy volunteers were recruited. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study n, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. In the UGT study pharmacokinetics and dynamics of 2 mg intravenous lorazepam were evaluated before and after rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. The subjective and objective pharmacodynamic tests were done before and 1, 2, 4, 6, 8, and 12 hrs after lorazepam administration. The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the $CYP3A5^{*}3/^{*}3$ group showed a greater decrease in systemic clearance than the $CYP3A5^{*}1/^{*}1$ group $(8.5\pm3.8$ L/h/70 kg vs. $13.5\pm2.7$ L/h/70 kg, P=0.027). The 1'-hydroxymidazolam to midazolam AUC ratio was also significantly lower in the $CYP3A5^{*}3/^{*}3$,/TEX> group $(0.58\pm0.35,$ vs. $1.09\pm0.37$ for the homozygous wild-type group, P=0.026). The inhibition of moclo-bemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor meta-bolizers, no remarkable changes in the pharmacokinetic parameters were observed. The area under the time-effect curves of visual analog scale(VAS), choice reaction time, and continuous line tracking test results of lorazepam was reduced by 20%, 7%, 23% respectively in induced state, and in spite of large interindividual variablity, significant statistical difference was shown in VAS(repeated measures ANOVA, p=0.0027).

• Tuberculosis and Respiratory Diseases
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• v.79 no.1
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• pp.14-21
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• 2016

Cough is one of the most common symptom of many respiratory diseases. The Korean Academy of Tuberculosis and Respiratory Diseases organized cough guideline committee and cough guideline was developed by this committee. The purpose of this guideline is to help clinicians to diagnose correctly and treat efficiently patients with cough. In this article, we have stated recommendation and summary of Korean cough guideline. We also provided algorithm for acute, subacute, and chronic cough. For chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered. If UACS is suspicious, first generation anti-histamine and nasal decongestant can be used empirically. In CVA, inhaled corticosteroid is recommended in order to improve cough. In GERD, proton pump inhibitor is recommended in order to improve cough. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, angiotensin converting enzyme inhibitor, habit, psychogenic cough, interstitial lung disease, environmental and occupational factor, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and idiopathic cough can be also considered as cause of chronic cough. Level of evidence for treatment is mostly low. Thus, in this guideline, many recommendations are based on expert opinion. Further study regarding treatment for cough is mandatory.

• Journal of Genetic Medicine
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• v.5 no.1
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• pp.26-33
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• 2008

Purpose : Phenylketonuria(PKU) is an inborn error of metabolism and a genetic disorder resulting from a deficiency of phenylalanine hydroxylase(PAH) and decreased activity of tetrahydrobiopterin(BH4).In this study the correlation between the DNA mutation and clinical manifestations was investigated and PAH DNA mutations were compared bewteen Asian and Caucasian populations. Methods : DNA was isolated from peripheral leukocytes. The PAH gene was amplified by Polymerase Chain Reaction(PCR) and the sequence was analyzed with Multiplex Ligation-dependent Probe Amplification(MLPA). Results : We characterized the PAH gene of 102 independent Korean patients with PKU. PAH nucleotide sequence analysis revealed 44 different mutations, including 10 novel mutations comprising 9 missense mutations(N207D, K95del, A447P, G344D, P69S, S391I, A202T, G103S, and I306L) and 1 novel splice-site variant mutation(IVS10-3C>G). R243Q was the most prevalent mutation in this study. A259T has not previously been reported in Asian populations, but we found that this mutation had a frequency of 10.1% in our study. Furthermore, the genotypes of $BH_4$ responsive patients were analyzed and were divided into two groups: $BH_4$ medication-only group and $BH_4$ medication with diet therapy group. In the $BH_4$ medication-only group and $BH_4$ medication with diet therapy group, R241C was the most common mutation. Conclusion : Novel mutations in the PAH gene of PKU patients are still being discovered. Additional information as to the frequency of mutations in the tetrahydrobiopterine responsive gene is also accumulating. We anticipate that knowledge of these PKU gene mutations will assist the diagnosis, genetic counseling, and therapeutic treatment of PKU patients in future.

• Pediatric Infection and Vaccine
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• v.7 no.1
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• pp.83-93
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• 2000

Purpose : Urabe AM-9 strain was known to be associated with increased aseptic meningitis. The reason for high incidence of vaccine-associated meningitis was known that nucleotide(nt) substituted form G to A at position 1081 of the hemagglutinin-neuraminidase(HN) gene and therefore, glutamic acid changed to lysine at amino acid 335. We assessed by comparing nt sequence of the HN gene form Urabe AM-9 strain with wild strain and documented the correlation between nt substitution and vaccine-associated meningitis. Methods : Two lots of Urabe AM-9 vaccine distributed in Korea and mumps wild strains isolated from 1998 through 1999 were analysed. Analysis was made by nt sequencing following amplification of HN gene by RT-PCR. Results : Nucleotide substitution at position 343, 1476, 1570 was not found in both Urabe AM-9 vaccines and wild strains. But analysis of vaccine strains and wild strains isolated from patients revealed substitution from G to A at nt 1081 of the HN gene. Therefore, it encodes lysine instead of glutamic acid at amino acid 335. There was no mixture from of G and A at nt 1081. Nt at 1470 of one lot of Urabe AM-9 vaccines changed from C to A after Vero cell passage. Nt at 1727 of vaccines and wild strains was substituted A to G, so it encodes glycine instead of aspartic acid. Conclusion : Nucleotide analysis of HN gene revealed that nt 1081 of Urabe AM-9 vaccines and wild strains had wild type AAA($Lys^{335}$) instead of variant type GAA($Glu^{335}$). The results of this study suggest that there was a probability of vaccine-associated meningitis due to Urabe AM-9 in Korea before. But incidence of actual side effect was not evaluated because there was no reporting system in Korea.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.3
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• pp.85-91
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• 2017

Purpose: The aim of this study was to describe the clinical and biochemical features as well as the molecular analysis of a newly diagnosed illustrative case with ML II and to analyze the clinical features of 11 Korean patients with ML II/III. Method: Including a newly diagnosed patient, total 11 patients in 10 families were diagnosed as ML II (n=7) or ML III (n=4) were enrolled in the study. A diagnosis of ML II or III was made by demonstrating increased lysosomal enzyme activities in the plasma and sequence analysis of GNPTAB with characteristic clinical features. Result: A illustrative case of ML II patient was a 17 month-old boy showing characteristic facial appearance, multiple joint contractures with cardiac involvements. The enzyme assay showed increased lysosomal enzyme activities in the plasma. We identified compound heterozygous mutations in GNPTAB sequence analysis, including a frameshift (c.3428dupA [pAsn1143Lysfs*3]) and a nonsense variant c.673C>T (p.Gln225*). In total 11 patients with ML II/III, the patients with ML II showed severe growth retardation (height standard deviation score -3.2 [${\pm}1.5$]), compare to patients with ML III. Furthermore, patients with ML II patients had serious cardiac problem (n=4), hepatomegaly (n=3) and underwent tracheostomy (n=3) with further respiratory support due to respiratory distress. To improve osteoporosis and bone pain, all patients with ML III and four of 7 patients with ML II treated with intravenous pamidronate. Conclusion: Here we showed a newly diagnosed case of ML II and clinical features of 11 Korean patients with ML II or III. These data could be helpful for further diagnosis of mucolipidosis, a rare inherited metabolic disease, in Korea.

• 한국환경농학회:학술대회논문집
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• 2009.07a
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• pp.273-282
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• 2009

The transmissible spongiform encephalopathies (TSEs) disease group are fatal neurodegenerative disorders affecting a wide range of hosts. The group includes kuru and Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats and Bovine spongiform encephalopathy (BSE) in cattle. The exact nature of the infectious agent involved in the transmission of these diseases remains controversial. However, a central event in their pathogenesis is the accumulation in infected tissues of an abnormal form of a host-encoded protein, the prion protein (PrP). Whereas the normal cellular protein is fully sensitive to protease ($PrP^{sen}$), the disease-associated prion protein ($PrP^d$) is only partly degraded ($PrP^{res}$), its amino-terminal end being removed. BSE was first reported in the mid-80s in the UK. Ten years later, a new form of human prion disease, variant CJD (vCJD) developed in the wake of the BSE epidemic, and there is now strong scientific evidence that vCJD was initiated by the exposure of humans to BSE-infected tissues, thus indicating a zoonotic disease. However, the ban on the feeding of animal-derived proteins to ruminants, and the apparent lack of vertical transmission of BSE, have led to a decline in the incidence of the disease within cattle herd and therefore, an assumed decreased risk for human contacting vCJD. The origin of the original case(s) of BSE still remains an enigma even though three hypotheses have been raised. Hypotheses are i) sheep- or goat-derived scrapie-infected tissues included in meat and bone meal fed to cattle, ii) a previously undetected sporadic or genetic bovine TSE contaminating cattle feed or iii) originating from a human TSE through animal feed contaminated with human remains. A host cellular membrane protein ($PrP^C$), which is abundant in central nervous system tissue, appear to be conformationally altered in the diseased host into a prion protein ($PrP^{Sc}$). This $PrP^{Sc}$ is detergent insoluble and partially protease-resistant ($PrP^{res}$). The term $PrP^{res}$ is normally used to describe the protein detected after protease treatment, in techniques such as Western immunoblotting, and enzyme-linked immunosorbant assay using fresh/frozen tissue. Immunohistochemistry may performed with formalin-fixed tissues. Also, clinical signs of the BSE are one of the major diagnostic indicators. Recently, atypical forms (known as H- and L-type) of BSE have appeared in several European countries, Japan, Canada and the United States. An unusual case was also reported in a miniature zebu. The atypical BSE fall into two groups based on the relative molecular mass (Mm) of the unglycosylated $PrP^{res}$ band relative to that of classical BSE, one of the higher Mm (H-type) and the other lower (L-type). Both types have been detected worldwide as rare cases in older animals, at a low prevalence consistent with the possibility of sporadic forms of prion diseases in cattle. This raises the unwelcome possibility that vCJD could increase in the human population. Now, active surveillance program against BSE is going on in Korea. In regional veterinary service lab, ELISA is applied to screen the BSE in slaughter and confirmatory tests by Western immunoblotting and immunohistochemisty are carried out if there are positive or suspect in the screening test. Also, the ruminant feed ban is rigorously enforced. Removal of specified risk materials such as brain and spinal cord from cattle is mandatory process at slaughter to prevent the infected material from entering the human food chain.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.3
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• pp.284-295
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• 2020

In December 2019, the first coronavirus disease- 2019 (COVID-19) patient was reported in Wuhan, Hubei Province, China. Since then, the number of patients who suffered severe acute respiratory syndrome caused by the novel Coronavirus (SARS-CoV-2 or 2019-nCoV) has increased dramatically in Korea. This new variant virus induces pulmonary diseases, including cough, sore throat, rhinorrhea, dyspnea, and pneumonia. Because SARS-CoV-2 is an RNA virus, real-time reverse-transcriptase PCR has been used widely to diagnose COVID-19. As the Korea Centers for Disease Prevention and Control (KCDC) and Ministry of Food & Drug Safety (MFDS) approved emergency use authorization, clinical specimens collected from COVID-19 patients and even healthy people have been clinically diagnosed by laboratory medicine. Based on a literature search, this paper reviews the epidemiology, symptoms, molecular diagnostics approved by KCDC, a current diagnosis of COVID-19 in the laboratories, the difference between molecular and serological diagnosis, and guidelines for clinical specimens. In addition, the Korean guidelines of biosafety for clinical laboratory scientists are evaluated to prevent healthcare-associated infection. The author's experience and lessons as clinical laboratory scientists will provide valuable insights to protect the domestic and international health community in this COVID-19 pandemic around the world.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.389-396
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• 1994

Background : The two most important purposes of fiberoptic bronchoscopy in lung cancer patients are obtaining tissue diagnosis and staging. The direct sign of lung cancer on FOB includes visible tumor, with smooth or nodular surface, with or without necrosis and infiltration. Variant cell types of lung cancer have their characteristic biological behaviors respectively. For example, squamous cell carcinoma grows slowly, invades locally and has easy necrosis resulting in cavitation, whereas adenocarcinoma shows early metastasis, small cell carcinoma shows rapid growth and higher early metastasis rate. Based on this, it could be hypothesized that each cell type may have characteristic bronchoscopic finding. Method : To answer this question, we reviewed 106 cases which were diagnosed as primary lung cancer and had bronchoscopically visible specific cancerous lesions. Results : The results were as follows. 1) Squamous cell carcinoma accounted for 66 cases(62.2%), adenocarcinoma 15 cases(14.2%), large cell carcinoma 3 cases(2.8%). 2) The endobronchial tumor lesion was arbitrarily classified into 5 types according to gross characteristics. Type A, multilobulating mass with necrosis, accounted for 24.5%, type B, multilobulating mass without necrosis, 25.5%, type C, round beefy mass, 9.4%, type D, infiltration with mucosal irregularity, 6.6%, and type E, infiltration without mucosal irregularity, 34%. 3) The analysis of correlation between endobronchial tumor pattern and specific cell type revealed that squamous cell carcinoma had relation with the morphologic type B and small cell carcinoma had relation with the morphologic type E, but adenocarcinoma had no preponderance in morphologic type. The gross appearance had influence on the diagnostic yields of biopsies and the diagnostic yields of lobulating mass types(type A, B) were higher than those of other types. Conclusion : From the above observations, it could be concluded that squamous cell carcinoma and small cell carcinoma have relations with specific types of bronchoscopic morphology, but not the case in adenocarcinoma.

• The Journal of the Korean bone and joint tumor society
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• v.11 no.1
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• pp.25-31
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• 2005

Purpose: This study was designed to know the usefulness of the MRI to distinguish lipoma and well differentiated liposarcoma (WDL). Materials and methods: 47 lipomatous tumors with MRI were reviewed among the 107 lipomatous tumors operated in our department. MRI examinations and their corresponding pathology reports were compared to determine sensitivity, specificity, diagnostic ability, positive predictable value and negative predictable value. Statistical analysis was performed to know the relationship between malignancy of the tumor (WDL) with the age and gender of the patients, and location, depth, size and the enhancement of tumors in MRI. Results: Among 28 lipoma in MRI examinations, 26 were proved as lipoma in pathology, and only 6 were WDL from 19 suspicious lesions in MRI, and others were proved as lipoma variants mostly. The varieties of lipoma variants were fibrolipoma, angiolipoma, spindle cell lipoma, lipoblastoma and angiomyolipoma. The sensitivity, specificity, diagnostic ability, positive predictable value and negative predictable value of MRI were 100%, 68 %, 72%, 31% and 100% in WDL, and 90%, 89%, 89%, 93% and 84% in lipoma. Among the variants to distinguish WDL and lipoma, the size of tumor and enhancement in MRI were significant statistically (p<0.05). Conclusion: MRI was highly sensitive in detection of WDL and highly specific in detection of simple lipoma. The size of tumor and enhancement in MRI were significant variants to distinguish WDL and lipoma. When MRI finding is non-specific, it is more likely to represent one of lipoma variants.

• Journal of Korean Society of Forest Science
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• v.58 no.1
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• pp.1-7
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• 1982

Megagametophyte and embryo tissue of Pinus densiflora were subjected to study the inheritance of glutamate-oxalate transaminase(GOT) and leucine aminopeptidase(LAP), and linkage relationship among isozyme loci coding both enzymes by starch gel zone-electrophoresis. Four zones of activity were observed for GOT. No variation was found in the fastest migrating zone (GOT-A). Electrophoretic phenotypes of the other two zones (GOT-B and GOT-C) showed 1:1 segregation ration, suggesting that each zone is controlled by a single locus. Foru and three alleles were identified at both loci respectively. The isozyme pattern of the fourth zone(GOT-D), migrated cathodally, coincided precisely with that of GOT-C. Whether the two zones are controlled by the same locus or by two tightly linked loci remained unknown. In all three variant GOT zones, heterozygoes embryos produced triple band patterns, indicating that GOT isozyme in Pinus densiflora is a dimer. Two zones of activity stained for LAP were found. The segregation of the two zones (LAP-A and LAP-B) suggested that tow loci control each of both isozymes. Two and three alleles were identified at both loci. GOT-B and LAP-B were found to be tightly linked, showing an average recombination frequency of 12.5 percent. Slight deviation from independent assortment was observed between GOT-B and GOT-C, with recombination frequency of 41 percent.