First Report of the Korean Lung Transplantation Registry.

BACKGROUND: The Korean Organ Transplantation Registry (KOTRY) began to register lung transplants in 2015. This is an initial report on the status of patients receiving lung transplants over the past 2 years. METHODS: We analyzed a total of 69 patients who received lung transplants in 2015 and 2016 and who registered with the KOTRY. RESULTS: The 69 patients were treated in 5 institutions. The average (SD) donor age was 39.2 (12.6) years; there were 40 male patients. The average (SD) recipient age was 55.7 (10.0) years, and the number of male recipients was 46. A total of 66 patients underwent bilateral lung transplantation, 3 underwent single-lung transplantation, and 1 underwent simultaneous heart-lung transplantation. The most frequent indication for lung transplantation was idiopathic pulmonary fibrosis (35 patients), followed by connective tissue disease-related interstitial lung disease (9) and acute respiratory failure (8). Prior to transplantation, 23 patients required ventilator care, and 12 required extracorporeal membrane oxygenation while on the waiting list. Episodes of acute rejection during follow-up were reported in 4, 2, 1, and 1 patients at 3, 6, 9, and 12 months, respectively. Infections requiring hospitalization were reported in 27, 10, 4, and 3 patients at 3, 6, 9, and 12 months, respectively. CONCLUSION: The establishment of KOTRY renders it possible to collect nationwide data on lung transplantation, improving research on the topic and clarifying clinical feasibility.

Implication of vitamin D-associated factors in patients with non-tuberculous mycobacterial lung disease.

BACKGROUND: Little information is available regarding vitamin D-associated factors in patients with non-tuberculous mycobacteria (NTM) lung disease. OBJECTIVE: To determine the association between vitamin D-related factors and susceptibility to NTM lung disease. DESIGN: The relative gene expression levels of cathelicidin (CAMP), defensin (DEFB4), vitamin D receptor (VDR) and 1-hydroxylase (CYP27B1), as well as the serum levels of 25-hydroxyvitamin D (25[OH]D), cathelicidin (LL-37), defensin (hBD-2) and vitamin D-binding protein (DBP) from 82 patients with NTM lung disease and 28 control subjects were analysed. RESULTS: Gene expression of CAMP and DEFB4 was significantly higher, and gene expression of VDR and CYP27B1 was significantly lower, in NTM patients than controls. Serum LL-37 and hBD-2 levels were not significantly different between NTM patients and controls; however, the serum DBP level was higher in NTM patients than controls. The serum vitamin D status of patients did not correlate with serum LL-37, hBD-2, or DBP concentration or gene expression of CAMP, DEFB4, VDR or CYP27B1. CONCLUSION: A higher level of gene expression for antimicrobial peptide is more likely to be associated with NTM lung disease than serum vitamin D status.

Genotyping of Mycobacterium intracellulare isolates and clinical characteristics of lung disease.

BACKGROUND: Variable number of tandem repeats (VNTR) loci were recently identified in Japanese isolates of Mycobacterium intracellulare. We hypothesised that some mycobacterial genotypes are more virulent than others, resulting in particular genotypes being associated with disease phenotype and progression. OBJECTIVE: To evaluate the VNTR loci of M. intracellulare in clinical isolates from Korean patients, and investigate the association between mycobacterial genotype and disease phenotype and progression. DESIGN: In total, 70 M. intracellulare clinical isolates were genotyped using 16 M. intracellulare VNTR loci. RESULTS: VNTR typing showed strong discriminatory power and genetic diversity for molecular epidemiological studies of M. intracellulare. In a phylogenetic tree, the M. intracellulare clinical isolates were divided into two clusters (A and B). Cluster A was observed more frequently (77%) than Cluster B; however, there was no association between the clinical characteristics, disease progression, drug susceptibility and clusters based on VNTR genotyping. CONCLUSIONS: VNTR typing could be used for epidemiological studies of M. intracellulare lung disease; however, no association was found between the specific VNTR genotypes of M. intracellulare and the clinical characteristics of Korean patients.

Clinical significance of mycobacterial genotyping in Mycobacterium avium lung disease in Korea.

SETTING: A recent study in Japan found that mycobacterial genotyping was associated with disease progression and susceptibility to certain drugs in Mycobacterium avium lung disease. However, it is not known whether this association is true in other populations. OBJECTIVE: To investigate the association between mycobacterial genotype, clinical characteristics and the progression of M. avium lung disease in Korean patients. DESIGN: A total of 102 M. avium clinical isolates were genotyped using M. avium tandem repeats-variable number of tandem repeats (MATR-VNTR). RESULTS: MATR-VNTR typing demonstrated a high discriminatory power and genetic diversity for molecular epidemiological studies of M. avium. In the phylogenetic tree, the M. avium clinical isolates were divided into three major clusters: A, B and C. Cluster A was observed most frequently (64/102, 63%), whereas cluster C was found in a minor proportion of the isolates (8/102, 8%). However, there was no association between the clinical characteristics, disease progression and drug susceptibility and the phylogenetic tree based on VNTR genotyping. CONCLUSIONS: MATR-VNTR genotyping may be useful for epidemiological studies of M. avium lung disease; however, no association was found between the specific VNTR genotypes of M. avium and the clinical characteristics of Korean patients.

Glucose metabolism in sporadic Creutzfeldt-Jakob disease: a statistical parametric mapping analysis of (18) F-FDG PET.

BACKGROUND AND PURPOSE: Reports describing functional neuroimaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), in sporadic Creutzfeldt-Jakob disease (sCJD) have consistently suggested that these tools are sensitive for the identification of areas of hypoperfusion or hypometabolism, even in the early stages of sCJD. However, there are few reports on the use of [18F]fluoro-2-deoxy-D-glucose (FDG) PET in sCJD, and most of them are single case reports. Only two small cohort studies based on visual inspection or a region of interest method have been published to date. Using a statistical parametric mapping (SPM) analysis of (18) F-FDG PET, we investigated whether there are brain regions preferentially affected in sCJD. METHODS: After controlling for age and gender, using SPM 2, we compared the glucose metabolism between (i) 11 patients with sCJD and 35 controls and (ii) the subset of five patients with the Heidenhain variant of sCJD and 35 controls. RESULTS: The patients with sCJD showed decreased glucose metabolism in bilateral parietal, frontal and occipital cortices. The Heidenhain variant of sCJD showed glucose hypometabolism mainly in bilateral occipital areas. CONCLUSIONS: Glucose hypometabolism in sCJD was detected in extensive cortical regions; however, it was not found in the basal ganglia or thalamus, which are frequently reported to be affected on diffusion-weighted images. The medial temporal area, which is possibly resistant to the prion deposits, was also less involved in sCJD.

Genetic polymorphism in exon 2 of cathepsin D is not associated with vascular dementia.

BACKGROUND: Cathepsin D, the most abundant lysosomal and endosomal aspartyl protease, shows beta and gamma secretase activity in vitro by cleaving the amyloid precursor protein (APP) into amyloid beta protein (Aß). Polymorphism at position 224, C224T, on exon 2 of cathepsin D gene (CTSD) has been associated with an increased risk for Alzheimer's disease (AD) by some investigators, but there have been contrary findings by others. However, an association between CTSD polymorphism and vascular dementia (VaD) has not been reported thus far. OBJECTIVE: To investigate whether a polymorphism at CTSD C224T is associated with VaD in the Korean population. METHODS: We compared the genotype and allele frequencies at this polymorphism site in clinically assessed 162 VaD patients with those in 197 healthy Koreans. RESULTS AND CONCLUSION: The major genotype frequency at CTSD C224T in normal controls was higher in the Asian population than in various European populations. Our study does not show a significant difference in genotype (P=0.3071) and allele (P=0.2291) frequencies of CTSD C224T between VaD and normal controls. This was the first genetic association study of CTSD in a VaD population.

Altered expression of type 1 inositol 1,4,5-trisphosphate receptor in the Ngsk Prnp deficient mice.

Doppel protein (Dpl) is a paralog of the cellular form of prion protein (PrP(C)). Its ectopic expression in the CNS elicits significant cerebellar Purkinje cell degeneration in some lines of PrP knockout mice. However, little is known about the Dpl-mediated neurodegenerative mechanism. To understand the molecular and intracellular pathways underlying Purkinje cell degeneration, here, we investigated the regulation of calcium-release channel protein, type 1 inositol 1,4,5-trisphosphate receptor (IP(3)R1) gene in Ngsk mice. These knockout mice express high levels of Dpl and eventually develop cerebellar degeneration. We observed that the expression level of IP(3)R1 gene is reduced in the cerebella of Ngsk mice as early as 3 months of age compared with age-matched controls along with the reduction in DNA binding activity of nuclear factor of activated-T cells (NFAT) which is transcription factor of IP(3)R1. Notably, expression of PrP restored the reduced DNA binding activity of NFATc4 by Dpl. Reduced expressions of brain-derived neurotrophic factor (BDNF) and ionotropic glutamate receptor subtype 2 or B (GluR2), which are regulated by NFATc4, were also restored by PrP expression. In light of these findings, we suggest a mechanism for Dpl-mediated Purkinje cell degeneration linked to reduced gene expression of proteins related to neuronal activity. Decrease in IP(3)R1 gene expression may lead to functional deficits and ultimately death of Purkinje cells in Ngsk mice.

PRNP 1368 polymorphism is not associated with sporadic Creutzfeldt-Jakob disease in the Korean population.

BACKGROUND: Human prion protein gene (PRNP) is considered a critical and fundamental gene in determining the incidence of human prion diseases. Codons 129 and 219 play an important role in the susceptibility to sporadic Creutzfeldt-Jakob disease (CJD). An association between sporadic CJD and the polymorphism (PRNP 1368) in an upstream of PRNP exon 1 has been reported in the British and German populations, but study in the Dutch population has failed to confirm an association. PURPOSE: To investigate whether the PRNP 1368 polymorphism is associated with sporadic CJD in the Korean population. METHODS: We compared the genotype and allele frequencies of PRNP 1368 polymorphism in 171 sporadic CJD patients with those in 212 healthy Koreans. RESULT AND CONCLUSION: A significant difference of genotype and allele frequencies at PRNP 1368 was found between the normal Korean population and various European populations. In contrast to the results in the British and German populations, our study does not show a significant difference in genotype (P = 0.2763) and allele (P = 0.3750) frequencies of PRNP 1368 between sporadic CJD and normal controls.

Polymorphisms at codons 129 and 219 of the prion protein gene (PRNP) are not associated with sporadic Alzheimer's disease in the Korean population.

Polymorphisms of prion protein gene (PRNP) at codons 129 and 219 play an important role in the susceptibility to Creutzfeldt-Jakob disease (CJD). Alzheimer's disease (AD) and prion diseases, such as CJD, are both characterized by the accumulation of abnormally folded proteins in the brain. An association between sporadic AD and the PRNP polymorphism at codon 129 has been reported in several studies, but other studies have failed to confirm an association. To investigate whether PRNP polymorphisms are associated with an increased risk for developing sporadic AD in the Korean population, we compared the genotype, allele, and haplotype frequencies of PRNP polymorphisms in 271 sporadic AD patients with those in 236 healthy Koreans. Our study does not show a significant difference in PRNP genotype, allele, and haplotype frequency at codons 129 and 219 between sporadic AD and normal controls. Analyses stratifying by age at disease onset, and gender also failed to reveal any association between these polymorphisms and sporadic AD. These results indicate that these PRNP polymorphisms have no direct influence on the susceptibility to sporadic AD in the Korean population.

JC polyomavirus reactivation is not associated with herpes zoster.

Herpes zoster (HZ) is a neurocutaneous disease caused by Varicella-zoster virus (VZV) as a consequence of declined cell-mediated immunity, immune suppression and immunodeficiency. As reactivation of JC polyomavirus (JCPyV) might be linked with immunodeficiency or immunosuppressive therapy, the relationship between HZ and JCPyV reactivation was investigated. The incidence of JCPyV in urine samples from 102 patients with HZ and 100 healthy individuals from South Korea was determined by PCR. The incidence values for HZ patients and control individuals did not differ significantly (24.5% vs. 20.0%, respectively, P = 0.5391). When different age groups were monitored, the positivity values of 21.1%, 20.0%, and 30% were found for 20-39, 40-59 and over 60 year-old patients, respectively. In order to determine the genotype of JCPyV isolates, their VP1-large T antigen (VT)-intergenic region was PCR amplified, sequenced and analyzed. Three distinct types, namely 1, 2A and 7B were found in 8%, 24%, and 68% of were found among 25 isolates from HZ patients. Using phylogenetic analysis, the type 1 isolates were assigned to the 1C subtype. These results indicate that HZ does not play an important role in JCPyV reactivation and is not associated with JCPyV.

Synthesis of tetrakis(multifluoro-4-pyridyl)porphin derivatives as acetylcholinesterase inhibitors.

New tetrakis(multifluoro-4-pyridyl)porphin derivatives (2-4) and water soluble porphyrin (5) were synthesized to investigate their interactions with acetylcholinesterase from electric eel. These compounds have been found to be the potent reversible inhibitors of the enzyme with Ki values of microM range. In addition, porphyrin (5) showed broad spectrum of anticancer activities.

Molecular analysis of prion protein gene (PRNP) in Korean patients with Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD), a relatively uncommon human dementia, is caused by an unconventional slow infectious agent. Several cases of CJD, clinically or histopathologically diagnosed, have been reported in Korea. In order to confirm the diagnosis of CJD and also differential diagnosis of sporadic and familial types of CJD in Korea, we studied two patients who had symptoms of CJD. The histopathological and immunohistochemical studies showed spongiform neurodegeneration and expression of abnormal isoform of prion protein (PrPSc) in astrocytes. Thus, these two patients were diagnosed CJD. To investigate whether these patients were sporadic or familial type of CJD, the molecular analyses of the prion protein gene (PRNP) were done by restriction fragment length polymorphism (RFLP) and DNA sequencing. In the cases of a healthy Korean and two CJD patients, no point mutation was detected in the known hot spots (178, 180, 200, 210, and 232) and they exhibited wild type PRNP sequences. We concluded that both patients have a sporadic type of CJD, but not familial type.