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1.  Benzalkonium Chloride Induced Bronchoconstriction in Patients with Stable Bronchial Asthma 
Background
Although benzalkonium chloride (BAC)-induced bronchoconstriction occurs in patients with bronchial asthma, BAC-containing nebulizer solutions are still being used in daily practice in Korea. The aim of this study was to evaluate the effects of inhaled aqueous solutions containing BAC.
Methods
Thirty subjects with bronchial asthma and 10 normal controls inhaled up to three 600 µg nebulized doses of BAC using a jet nebulizer. FEV1 (forced expiratory volume at one second) was measured 15 minutes after each dose. Inhalations were repeated every 20 minutes until FEV1 decreased by 15% or more (defined as BAC-induced bronchoconstriction) or the 3 doses were administered.
Results
The percent fall in FEV1 in response to BAC inhalation was significantly higher in asthmatics than in normal subjects (p<0.05). BAC administration in subjects with asthma reached a plateau (maximal effect). BAC-induced bronchoconstriction was found in 6 asthmatics (20%), with two responders after the 2nd inhalation and after the 3rd inhalation. The percent fall in FEV1 in response to the 1st inhalation of BAC was significantly higher in asthmatics with higher bronchial hyperresponsiveness (BHR) than in those with lower BHR.
Conclusions
This study suggests that the available multi-dose nebulized solution is generally safe. However, significant bronchoconstriction can occur at a relatively low BAC dose in asthmatics with severe airway responsiveness.
doi:10.3904/kjim.2007.22.4.244
PMCID: PMC2687669  PMID: 18309682
Asthma; Benzalkonium chloride; Bronchoconstriction
2.  Anaphylaxis Caused by Benzalkonium in a Nebulizer Solution 
Journal of Korean Medical Science  2004;19(2):289-290.
Benzalkonium chloride (BAC) is commonly used as a bactericidal preservative in nebulizer solutions, and can cause paradoxical onchoconstriction following nebulizing therapy in some asthmatics. We describe a case of anaphylactic shock in a 23-yr-old asthmatic woman following an intradermal skin test with a salbutamol solution containing BAC. Since she complained of cough and dyspnea after inhalation therapy with a nebulizer solution, we conducted an intradermal skin test using the same solution, which contained BAC. About 10 min later, the patient reported dizziness, palpitations, and dyspnea. On examination, tachycardia, tachypnea, and hypotension were found. She was resuscitated with a subcutaneous injection of epinephrine and an infusion of saline. One month later, we conducted a bronchial provocation test with BAC, and she showed a positive response.
doi:10.3346/jkms.2004.19.2.289
PMCID: PMC2822313  PMID: 15082905
Anaphylaxis; Preservatives, Pharmaceutical; Skin Tests; Adrenergic beta-agonist
3.  Analysis of the Treatment of Two Types of Acute Urinary Retention 
Korean Journal of Urology  2012;53(12):843-847.
Purpose
This study analyzed the type of acute urinary retention (AUR) and evaluated the treatments used, including trial without catheter (TWOC).
Materials and Methods
This study was based on 299 patients who were treated for AUR from January 2007 to August 2009. The patients were classified into the spontaneous AUR group (group S) and the precipitated AUR group (group P), in which AUR was consecutive to triggering events. The treatment modalities including TWOC, the success rate of TWOC, age, prostate-specific antigen (PSA) levels, the volume of the prostate, and the drained volume at catheterization were analyzed in each group.
Results
Of 299 men with AUR, 160 (54%) had spontaneous AUR and 139 (46%) had precipitated AUR. Compared with group P, patients in group S were more likely to be treated by surgery, either immediately (16.9% vs. 3.6%, p<0.05) or after prolonged catheterization (42.2% vs. 29.1%, p<0.05). The success rate of TWOC was lower in men of older ages (≥70 years) and in those with enlarged prostates (≥50 ml), higher PSA levels (≥3 ng/ml), and a large drained volume at catheterization (≥1,000 ml).
Conclusions
In this group of AUR patients, there were slightly more patients with spontaneous AUR (54%) than with precipitated AUR (46%). The success rate of TWOC was more than 70% regardless of the type of AUR. Although TWOC is recommended primarily in the treatment of AUR, early surgical intervention should be considered if the patient has an enlarged prostate (≥50 ml) or a large drained volume at catheterization (≥1,000 ml).
doi:10.4111/kju.2012.53.12.843
PMCID: PMC3531637  PMID: 23301128
Prostatic hyperplasia; Urinary catheterization; Urinary retention
4.  Genetic populations of Bacillus anthracis isolates from Korea 
Journal of Veterinary Science  2012;13(4):385-393.
Bacillus (B.) anthracis is the pathogen that causes fatal anthrax. Strain-specific detection of this bacterium using molecular approaches has enhanced our knowledge of microbial population genetics. In the present study, we employed molecular approaches including multiple-locus variable-number tandem repeat analysis (MLVA) and canonical single-nucleotide polymorphism (canSNP) analysis to perform molecular typing of B. anthracis strains isolated in Korea. According to the MLVA, 17 B. anthracis isolates were classified into A3a, A3b, and B1 clusters. The canSNP analyses subdivided the B. anthracis isolates into two of the three previously recognized major lineages (A and B). B. anthracis isolates from Korea were found to belong to four canSNP sub-groups (B.Br.001/2, A.Br.005/006, A.Br.001/002, and A.Br.Ames). The A.Br.001/002 and A.Br.Ames sub-lineages are closely related genotypes frequently found in central Asia and most isolates were. On the other hand, B. anthracis CH isolates were analyzed that belonged to the B.Br.001/002 sub-group which found in southern Africa, Europe and California (USA). B.Br.001/002 genotype is new lineage of B. anthracis in Korea that was not found before. This discovery will be helpful for the creation of marker systems and might be the result of human activity through the development of agriculture and increased international trade in Korea.
doi:10.4142/jvs.2012.13.4.385
PMCID: PMC3539124  PMID: 23271180
Bacillus anthracis; canonical single-nucleotide polymorphism (canSNP); genotyping; multiple-locus variable-number tandem repeat analysis (MLVA)
5.  ABCC2 Haplotype is Associated With Antituberculosis Drug-Induced Maculopapular Eruption 
Genetic variants in ATP-binding cassette (ABC) transporter genes are associated with increased susceptibility to adverse drug reactions. We hypothesized that genetic variant ABC transporters (ABCB1 and ABCC2) may be candidate markers for predicting maculopapular eruption (MPE) induced by antituberculosis therapy. We compared the genotype distributions of single nucleotide polymorphisms and haplotypes in the ABCB1 and ABCC2 genes between 62 antituberculosis drug (ATD)-induced MPE cases and 159 ATD-tolerant controls using multivariate logistic regression analysis. There was no significant association between genetic polymorphisms in ABCB1 and ATD-induced MPE (P>0.05). Among seven selected SNPs of ABCC2, IVS3-49C>T in intron and I1324I were associated with ATD-induced MPE (P=0.029 and 0.036, respectively). In an analysis of the ABCC2 haplotypes (ht; -1549G>A_-24C>T_IVS3-49C>T_V417I), ht1[G-C-C-G] was significantly associated with ATD-induced MPE (P=0.032, OR=0.35, 95% CI: 0.16-0.95). No significant association between the other haplotypes and ATD-induced MPE was observed. An ABCC2 haplotype is associated with the presence of ATD-induced MPE in patients with tuberculosis and may be a genetic risk factor for the development of MPE induced by ATD.
doi:10.4168/aair.2012.4.6.362
PMCID: PMC3479231  PMID: 23115734
Adverse drug reaction; anti-tuberculosis drugs; ATP-binding cassette C2; eruption; polymorphism
6.  Depression, Anxiety, Stress Perception, and Coping Strategies in Korean Military Patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome 
Korean Journal of Urology  2012;53(9):643-648.
Purpose
The objective of this study was to examine the psychological features and coping strategies of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
Materials and Methods
The participants consisted of 55 military personnel suffering from CP/CPPS and 58 military personnel without CP/CPPS symptoms working at the Military Capital Hospital. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) was used to assess CP/CPPS symptoms. The Responses to Hospital Anxiety and Depression (HAD) scale, Social Readjustment Rating Scale, and Global Assessment of Recent Stress (GARS) scale were compared between the two groups. The Weisman Coping Strategy Scale was used to assess coping ability with CP/CPPS.
Results
The NIH-CPSI score of the CP/CPPS group was significantly higher than that of the control group for all domains including pain, urinary symptoms, quality of life, and summed score. The Anxiety and Depression domain of the HAD showed significant differences between the two groups. There were no significant differences in the Social Readjustment Rating Scale between the two groups, but the sum of the GARS score was higher in the CP/CPPS group than in the control group. These were correlated with the pain, quality of life, and sum domains of the NIH-CPSI. The Weisman Coping Strategy Scale showed that intellectualization, redefinition, and flexibility were higher in frequency in descending order, and that fatalism, externalization, and self-pity were lower in frequency.
Conclusions
The CP/CPPS patients had depression, anxiety, and higher perception of stress. In particular, these were closely related to the pain and quality of life of the patients.
doi:10.4111/kju.2012.53.9.643
PMCID: PMC3460008  PMID: 23061003
Anxiety; Depression; Prostatitis; Psychological adaptation; Psychological stress
7.  Genetic Variations in TXNRD1 as Potential Predictors of Drug-Induced Liver Injury 
Purpose
Drug-induced liver injury (DILI) is the most common adverse drug reaction; however, it is not easily predicted. We hypothesize that DILI has a common genetic basis. Based on the findings of previous animal studies on toxic hepatitis, we selected the thioredoxin reductase 1 gene (TXNRD1) as a candidate marker of DILI for this genetic association study.
Methods
Records from 118 patients with DILI were extracted from the database of the Adverse Drug Reaction Research Group in South Korea. Causative drugs included antituberculosis drugs (n=68, 57.6%), antibiotics (n=22, 18.6%), antiepileptic drugs (n=7, 5.9%), non-steroidal anti-inflammatory drugs (n=5, 4.2%), and others (n=16, 13.7%). Seven single nucleotide polymorphisms (SNPs) in TXNRD1 (rs10735393, rs4964287, rs4595619, rs10861201, rs11111997, rs4246270, and rs4246271) were scored in 118 DILI patients and in 120 drug-matched controls without liver injury.
Results
No differences were found between the frequencies of any of the 7 SNPs in the cases and controls; however, a significant association was found between a TTA haplotype composed of rs10735393, rs4964287, and rs4595619 and DILI using an allele model (odds ratio, 1.79; 95% confidence interval, 1.18-2.73; P=0.008; Bonferroni corrected P=0.024).
Conclusions
These results suggest that genetic variations in TXNRD1 favor the development of DILI, although a larger confirmative study is needed.
doi:10.4168/aair.2012.4.3.132
PMCID: PMC3328729  PMID: 22548205
Drug-induced liver injury; genetic association study; genetic polymorphism; single nucleotide polymorphisms; thioredoxin reductase 1
8.  Fatal Delayed Coronary Artery Perforation After Coronary Stent Implantation 
Korean Circulation Journal  2012;42(5):352-354.
Most type I and II perforations are predominately caused by hydrophilic and stiff wires, often presented in the delayed form, and do not require pericardial drainage or surgical interventions. However, we report a type III delayed coronary artery perforation at the site of stent implantation after intervention without any evidence of immediate perforations. To the best of our knowledge, this is the first case report of angiographic documentation and treatment of delayed coronary perforation at the site of stent, presented as a cardiac arrest.
doi:10.4070/kcj.2012.42.5.352
PMCID: PMC3369969  PMID: 22701137
Cardiac tamponade; Complications; Percutaneous transluminal coronary angioplasty; Drug-eluting stent
9.  Genome sequence of Desulfitobacterium hafniense DCB-2, a Gram-positive anaerobe capable of dehalogenation and metal reduction 
BMC Microbiology  2012;12:21.
Background
The genome of the Gram-positive, metal-reducing, dehalorespiring Desulfitobacterium hafniense DCB-2 was sequenced in order to gain insights into its metabolic capacities, adaptive physiology, and regulatory machineries, and to compare with that of Desulfitobacterium hafniense Y51, the phylogenetically closest strain among the species with a sequenced genome.
Results
The genome of Desulfitobacterium hafniense DCB-2 is composed of a 5,279,134-bp circular chromosome with 5,042 predicted genes. Genome content and parallel physiological studies support the cell's ability to fix N2 and CO2, form spores and biofilms, reduce metals, and use a variety of electron acceptors in respiration, including halogenated organic compounds. The genome contained seven reductive dehalogenase genes and four nitrogenase gene homologs but lacked the Nar respiratory nitrate reductase system. The D. hafniense DCB-2 genome contained genes for 43 RNA polymerase sigma factors including 27 sigma-24 subunits, 59 two-component signal transduction systems, and about 730 transporter proteins. In addition, it contained genes for 53 molybdopterin-binding oxidoreductases, 19 flavoprotein paralogs of the fumarate reductase, and many other FAD/FMN-binding oxidoreductases, proving the cell's versatility in both adaptive and reductive capacities. Together with the ability to form spores, the presence of the CO2-fixing Wood-Ljungdahl pathway and the genes associated with oxygen tolerance add flexibility to the cell's options for survival under stress.
Conclusions
D. hafniense DCB-2's genome contains genes consistent with its abilities for dehalogenation, metal reduction, N2 and CO2 fixation, anaerobic respiration, oxygen tolerance, spore formation, and biofilm formation which make this organism a potential candidate for bioremediation at contaminated sites.
doi:10.1186/1471-2180-12-21
PMCID: PMC3306737  PMID: 22316246
10.  Effect of Ultra-marathon (308 km) Race on Bone Metabolism and Cartilage Damage Biomarkers 
Objective
To evaluate the potential effects of a 308-km ultra-marathon on bone and cartilage biomarkers.
Method
Venous blood samples were collected at pre-race, 100 km, 200 km, and 308 km checkpoints. The following markers of cartilage damage and bone metabolism were studied: osteocalcin (OC), osteoprotegerin (OPG), and calcium, phosphorous, and cartilage oligomeric matrix protein (COMP).
Results
Blood samples were taken from 20 male runners at four different checkpoints. Serum COMP was increased by 194.1% (130.7% at 100 km and 160.4% at 200 km). Serum OPG was significantly increased by 158.57% at 100 km and 114.1% at 200 km compared to the pre-race measures. OC was transiently suppressed at 200 km. Serum calcium and phosphorous concentrations decreased compared to the pre-race measures.
Conclusion
This study showed that the 308-km ultra-marathon induced several changes, including transient uncoupling of bone metabolism, increased bone resorption, suppressed bone formation, and bone turnover and had a major impact on cartilage structure.
doi:10.5535/arm.2012.36.1.80
PMCID: PMC3309329  PMID: 22506239
Ultra-marathon; Osteoprotegerin; COMP; Osteocalcin
11.  260 Association Between Genetic Polymorphisms of ABCC2 Transporter and the Susceptibility to Maculopapular Eruption Induced by Antituberculosis Drugs 
Background
ATP-binding cassette (ABC) transporter proteins play an important role in drug disposition. Polymorphisms of ABC transporter genes (ABCC2 and ABCB1) may be risk markers for maculopapular eruption (MPE) induced by unusual accumulation of antituberculosis drugs (ATD) itself or metabolites.
Methods
We compared genotype distributions of single nucleotide polymorphisms and haplotypes in ABCC2 and ABCB1 genes between 62 ATD-induced MPE cases and 159 ATD-tolerant controls using multivariate logistic regression analysis.
Results
Among the 7 selected SNPs of ABCC2, -1549G>A in promoter and IVS3-49C>T in intron were associated with ATD-induced MPE (P = 0.032 and P = 0.029, respectively). ABCC2 haplotype1 [G-C-C-G] was significantly associated with ATD-induced MPE (P = 0.032, OR = 0.35, 95% CI, 0.29-0.95). However, there was no significant association between other genetic polymorphisms in ABCB1 and ATD-induced MPE.
Conclusions
These results suggest that genetic variations of ABCC2 are a potential risk factor for ATD-induced MPE.
doi:10.1097/01.WOX.0000412017.99479.f7
PMCID: PMC3512837
12.  The reno-protective effect of a phosphoinositide 3-kinase inhibitor wortmannin on streptozotocin-induced proteinuric renal disease rats 
Diabetic nephropathy (DN) is a progressive kidney disease that is caused by injury to kidney glomeruli. Podocytes are glomerular epithelial cells and play critical roles in the glomerular filtration barrier. Recent studies have shown the importance of regulating the podocyte actin cytoskeleton in early DN. The phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, simultaneously regulates Rac1 and Cdc42, which destabilize the podocyte actin cytoskeleton during early DN. In this study, in order to evaluate the reno-protective effects of wortmannin in early DN by regulating Rac1 and Cdc42, streptozotocin (STZ)-induced proteinuric renal disease (SPRD) rats were treated with wortmannin. The albuminuria value of the SPRD group was 3.55 ± 0.56 mg/day, whereas wortmannin group was 1.77 ± 0.48 mg/day. Also, the albumin to creatinine ratio (ACR) value of the SPRD group was 53.08 ± 10.82 mg/g, whereas wortmannin group was 20.27 ± 6.41 mg/g. Changes in the expression level of nephrin, podocin and Rac1/Cdc42, which is related to actin cytoskeleton in podocytes, by wortmannin administration were confirmed by Western blotting. The expression levels of nephrin (79.66 ± 0.02), podocin (87.81 ± 0.03) and Rac1/Cdc42 (86.12 ± 0.02) in the wortmannin group were higher than the expression levels of nephrin (55.32 ± 0.03), podocin (53.40 ± 0.06) and Rac1/Cdc42 (54.05 ± 0.04) in the SPRD group. In addition, expression and localization of nephrin, podocin and desmin were confirmed by immunofluorescence. In summary, we found for the first time that wortmannin has a reno-protective effect on SPRD rats during the early DN. The beneficial effects of wortmannin in SPRD rats indicate that this compound could be used to delay the progression of the disease during the early DN stage.
doi:10.3858/emm.2012.44.1.004
PMCID: PMC3277897  PMID: 22056625
albuminuria; diabetic nephropathies; nephrin; podocin; podocytes; wortmannin
13.  Drosophila TRPA1 channel is required to avoid the naturally occurring insect repellent citronellal 
Current biology : CB  2010;20(18):1672-1678.
Summary
Plants produce naturally occurring insect repellents, such as citronellal, which is the main component of citronellal oil and is among the most widely-used-naturally-occurring insect repellents. However, the molecular pathways through which insects sense botanical repellents are unknown. Here, we showed that Drosophila used two pathways for direct avoidance of citronellal. The olfactory co-receptor, Or83b, which is required for the response to the synthetic repellent DEET, contributed to citronellal repulsion, and was essential for citronellal-evoked action potentials. Mutations affecting the Ca2+-permeable cation channel, TRPA1 resulted in a comparable defect in avoiding citronellal vapor. The TRPA1-dependent aversion to citronellal relied on a G protein/phospholipase C (PLC) signaling cascade, rather than direct detection of citronellal by TRPA1. Loss of TRPA1, Gq or PLC caused an increase in the frequency of citronellal-evoked action potentials in olfactory receptor neurons. Absence of the Ca2+-activated K+ channel, Slowpoke, resulted in a similar impairment in citronellal avoidance, and an increase in the frequency of action potentials. These results suggest that TRPA1 is required for activation of a BK channel to modulate citronellal-evoked action potentials, and for aversion to citronellal. In contrast to Drosophila TRPA1, Anopheles gambiae TRPA1 was directly and potently activated by citronellal, thereby raising the possibility that mosquito TRPA1 may be a target for developing improved repellents to reduce insect-borne diseases such as malaria.
doi:10.1016/j.cub.2010.08.016
PMCID: PMC2946437  PMID: 20797863
14.  Avoiding DEET through insect gustatory receptors 
Neuron  2010;67(4):555-561.
Summary
DEET is the most widely used insect repellent worldwide. In Drosophila olfactory receptor neurons (ORNs), DEET is detected through a mechanism that employs the olfactory receptor, OR83b. However, it is controversial as to whether ORNs respond directly to DEET or whether DEET blocks the response to attractive odors. Here, we showed that DEET suppressed feeding behavior in Drosophila and this effect was mediated by gustatory receptor neurons (GRNs). DEET was potent in suppressing feeding as <0.1% DEET elicited aversive behavior. Inhibition of feeding by DEET required multiple gustatory receptors (GRs), which were expressed in inhibitory GRNs. DEET stimulated action potentials in GRNs that respond to aversive compounds, and this response was lost in Gr32a, Gr33a and Gr66a mutants. Since 0.02% DEET elicited action potentials, we conclude that DEET directly activates of GRNs. We suggest that the effectiveness of DEET in pest control owes to its dual action in inducing avoidance simultaneously via GRNs and ORNs.
doi:10.1016/j.neuron.2010.07.006
PMCID: PMC2929391  PMID: 20797533
15.  anti-Diastereo- and Enantioselective Carbonyl (Hydroxymethyl)allylation from the Alcohol or Aldehyde Oxidation Level: Allyl Carbonates as Allylmetal Surrogates 
Enantioselective transfer hydrogenation of carbonate 1a in the presence of aromatic, allylic or aliphatic alcohols 2a–2i employing a cyclometallated iridium C,O-benzoate derived from allyl acetate, 4-cyano-3-nitrobenzoic acid and (S)-SEGPHOS delivers products of (hydroxymethyl)allylation 4a–4i in good isolated yields (60–74%), good anti-diastereoselectivities (5:1–10:1 dr) and exceptional levels of enantiocontrol (93–99% ee). Under identical reaction conditions, but in the presence of isopropanol, aldehydes 3a–3i are converted to an equivalent set of adducts 4a–4i in good isolated yields (58–74%), good anti-diastereoselectivities (4:1–14:1 dr) and exceptional levels of enantiocontrol (95–99% ee). Thus, identical sets of adducts 4a–4i are produced with equal facility from the alcohol or aldehyde oxidation level. These studies represent the first general method for enantioselective carbonyl (hydroxymethyl)allylation, a process that has no highly stereoselective counterpart in conventional allylmetal chemistry.
doi:10.1021/ja100949e
PMCID: PMC2848290  PMID: 20225853
16.  A Case of Eosinophilic Esophagitis With Food Hypersensitivity 
Eosinophilic esophagitis (EoE) is a disorder characterized by isolated eosinophilic infiltration of the esophagus with esophageal symptoms. Although some patients with EoE are related to food hypersensitivity, it is hard to identify causative foods. This report describes a case of EoE with dysphagia. A 28-year-old man presented with dysphagia and substernal discomfort for 15 days. He had taken a protein complex for 2 months. Endoscopy showed several linear furrows and multiple mucosal nodularities on the lower and mid esophagus, and the biopsies of esophagus revealed marked eosinophil infiltration in the mucosa. The skin testing for the protein complex was positive. The patient was successfully treated with withholding treatment.
doi:10.5056/jnm.2010.16.3.315
PMCID: PMC2912125  PMID: 20680171
Eosinophils; Esophagitis; Food hypersensitivity; Withholding treatment
17.  Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells 
BMC Immunology  2010;11:33.
Background
Resistin, a member of adipokine family, is known to be involved in the modulation of immune responses including inflammatory activity. Interestingly, resistin is secreted by adipocytes in mice and rats whereas it is secreted by leukocytes in humans. However, the mechanism behind the effect of resistin on the expansion of regulatory T cells (Tregs) remains poorly understood. Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs.
Results
Both protein and mRNA expression of FoxP3, a representative marker of Tregs, increased in a dose-dependent manner when peripheral blood mononuclear cells were treated with resistin. At the same time, resistin had no direct effect on the induction of FoxP3 in CD4+ T cells, suggesting an indirect role through other cells type(s). Since DCs are an important player in the differentiation of T cells, we focused on the role of DCs in the modulation of Tregs by resistin. Resistin suppressed the expression of interferon regulatory factor (IRF)-1 and its target cytokines, IL-6, IL-23p19 and IL-12p40, in DCs. Furthermore, FoxP3 expression is increased in CD4+ T cells when co-cultured with DCs and concomitantly treated with resistin.
Conclusion
Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.
doi:10.1186/1471-2172-11-33
PMCID: PMC2914082  PMID: 20591185
18.  Mouse Homologue of the Schizophrenia Susceptibility Gene ZNF804A as a Target of Hoxc8 
Using a ChIP-cloning technique, we identified a Zinc finger protein 804a (Zfp804a) as one of the putative Hoxc8 downstream target genes. We confirmed binding of Hoxc8 to an intronic region of Zfp804a by ChIP-PCR in F9 cells as well as in mouse embryos. Hoxc8 upregulated Zfp804a mRNA levels and augmented minimal promoter activity in vitro. In E11.5 mouse embryos, Zfp804a and Hoxc8 were coexpressed. Recent genome-wide studies identified Zfp804a (or ZNF804A in humans) as a plausible marker for schizophrenia, leading us to hypothesize that this embryogenic regulatory control might also exert influence in development of complex traits such as psychosis.
doi:10.1155/2010/231708
PMCID: PMC2876248  PMID: 20508826
19.  A Case of Rhabdomyolysis Associated with Use of a Pneumatic Tourniquet during Arthroscopic Knee Surgery 
The common causes of rhabdomyolysis include trauma, hypoxia, drugs, toxins, infections and hyperthermia. Operative insults, including direct trauma and ischemia, have the potential to cause the development of rhabdomyolysis. Pneumatic tourniquets used during arthroscopic knee surgery to prevent blood loss have led to many complications such as nerve paralysis and vascular injuries. Rhabdomyolysis can also be caused by prolonged pneumatic tourniquet application without a midapplication release, and also from an increased application pressure, but the actual incidence of this is low. In order to prevent rhabdomyolysis, the clinicians must be aware of such risks and follow strict guidelines for the application time, the midapplication release and also the inflation pressure. Vigorous hydration and postoperative patient surveillance are helpful to prevent rhabdomyolysis. We have recently experienced a case of rhabdomyolysis after the arthroscopic knee surgery, and the rhabdomyolysis could have been associated with the use of a pneumatic tourniquet.
doi:10.3904/kjim.2010.25.1.105
PMCID: PMC2829407  PMID: 20195412
Rhabdomyolysis; Tourniquets; Kidney failure, acute
20.  Repression of TNF-α-induced IL-8 expression by the glucocorticoid receptor-β involves inhibition of histone H4 acetylation 
Experimental & Molecular Medicine  2009;41(5):297-306.
Increased expression of a number of proinflammatory genes, including IL-8, is associated with inflammatory conditions such as asthma. Glucocorticoid receptor (GR)β, one of the GR isoforms, has been suggested to be upregulated in asthma associated with glucocorticoid insensitivity and to work as a dominant negative inhibitor of wild type GRα. However, recent data suggest that GRβ is not a dominant negative inhibitor of GRα in the transrepressive process and has its own functional role. We investigated the functional role of GRβ expression in the suppressive effect of glucocorticoids on tumor necrosis factor (TNF)-α-induced IL-8 release in an airway epithelial cell line. GRβ expression was induced by treatment of epithelial cells with either dexamethasone or TNF-α. GRβ was able to inhibit glucocorticoid-induced transcriptional activation mediated by binding to glucocorticoid response elements (GREs). The suppressive effect of dexamethasone on TNF-α-induced IL-8 transcription was not affected by GRβ overexpression, rather GRβ had its own weak suppressive activity on TNF-α-induced IL-8 expression. Overall histone deacetylase activity and histone acetyltransferase activity were not changed by GRβ overexpression, but TNF-α-induced histone H4 acetylation at the IL-8 promoter was decreased with GRβ overexpression. This study suggests that GRβ overexpression does not affect glucocorticoid-induced suppression of IL-8 expression in airway epithelial cells and GRβ induces its own histone deacetylase activity around IL-8 promoter site.
doi:10.3858/emm.2009.41.5.033
PMCID: PMC2701978  PMID: 19307749
asthma; glucocorticoids; histone acetyltransferases; histone deacetylases; interleukin-8; receptors, glucocorticoid; tumor necrosis factor-α
21.  Epidemiology of Hemorrhagic Fever with Renal Syndrome in Endemic Area of the Republic of Korea, 1995-1998 
Journal of Korean Medical Science  2006;21(4):614-620.
We conducted an epidemiologic study to understand temporal and spatial patterns of hemorrhagic fever with renal syndrome (HFRS) in the Republic of Korea (ROK). We estimated the incidence among civilians in endemic areas through the active surveillance system during the major epidemic periods, from September to December, between 1996 and 1998. We also estimated the prevalence among Korean military personnel from 1995 to 1998. In addition, we assessed seroprevalence, subclinical infection rate, and vaccination rates in both civilians and military personnel. The incidence in civilians ranged from 2.1 to 6.6 per 100,000 person-months. The annual prevalence in the military personnel was 40-64 per 100,000 military populations, and remained generally constant throughout the study period with seasonal variation. This is the prospective epidemiologic data set on HFRS in the ROK since the inactivated Hantaan virus vaccine was licensed for use in the late 1990s. These results will be invaluable in establishing a national immunization program against HFRS.
doi:10.3346/jkms.2006.21.4.614
PMCID: PMC2729880  PMID: 16891802
Hemorrhagic Fever with Renal Syndrome; Hantaan virus; Epidemiology; Incidence; Prevalence; Korea
22.  Association Between Sensitization to Outdoor Spider Mites and Clinical Manifestations of Asthma and Rhinitis in the General Population of Adults 
Journal of Korean Medical Science  2006;21(2):247-252.
It has been demonstrated that spider mites such as the two-spotted spider mite (Tetranychus urticae) are important allergens for fruit farmers. A total of 2,467 adults (795 metropolitan urban, 788 non-metropolitan urban, and 884 rural subjects) were enrolled. They responded to the questionnaire, and underwent methacholine bronchial provocation tests as well as skin prick tests to locally common aeroallergens including the two-spotted spider mite. The prevalences of asthma and rhinitis as reported on the questionnaire were 7.8% and 16.4% of adults aged 20-35, 9.4% and 24.7% of those 36-50, and 17.7% and 21.7% of those older than 50, respectively. Among the older group, the two-spotted spider mite was the most common sensitizing allergen, although it was second of that of house dust mites among the other two age groups. Sensitization to the two-spotted spider mite was significantly associated with the prevalence of asthma and rhinitis among the younger age group, and associated with the prevalence of rhinitis among the older age group. The two-spotted spider mite might be a common sensitizing allergen in the general population of adults, and sensitization to this mite may play a role in the manifestation of asthma and rhinitis symptoms during adulthood.
doi:10.3346/jkms.2006.21.2.247
PMCID: PMC2733999  PMID: 16614509
Tetranychidae; Spider Mites; Asthma; Rhinitis
23.  Helicobacter pylori eradication has no effect on metabolic and inflammatory parameters. 
BACKGROUND: An increased risk in coronary heart disease associated with Helicobacter pylori (H. pylon) appears to be partially mediated by modifications of the atherogenic lipoprotein and inflammatory parameters. We conducted a controlled trial aimed at evaluating the changes of metabolic and inflammatory parameters after H. pylon eradication. METHODS: We included in the study 169 patients with H. pylori infection and conducted a retrospective longitudinal survey of 87 subjects (76 men, 11 women) who received treatment for H. pylon eradication and 82 control subjects (63 men, 19 women) who did not receive treatment. We compared pre- and posteradication (one year after) the metabolic and inflammatory parameters, such as blood sugar, lipid profiles, insulin resistance, white blood cell count and C-reactive protein. RESULTS: No significant changes from the baseline in metabolic and inflammatory parameters within each group were observed. Changes in the serum levels of metabolic and inflammatory parameters were similar between the two groups. CONCLUSIONS: Metabolic and inflammatory parameters, including blood sugar, lipid profiles, insulin resistance, white blood cell count and C-reactive protein, were not changed after H. pylori eradication treatment. H. pylori eradication has no effect on metabolic and inflammatory parameters.
Images
PMCID: PMC2568737  PMID: 15868771
24.  Two cases of anaphylaxis after laminaria insertion. 
Journal of Korean Medical Science  2003;18(6):886-888.
Anaphylaxis following laminaria insertion rarely occurs but may be a life-threatening condition. Laminaria tents, prepared from natural sea kelp, are commonly used prior to elective termination of pregnancy to achieve cervical dilatation. We report herein two cases of anaphylaxis caused by IgE-mediated hypersensitivity to laminaria. Two women, each of whom had undergone at least one previous abortion where a laminaria had been utilized, developed anaphylactic reaction following laminaria insertion. The reaction included urticaria, nausea, breathing difficulty, and hypotension. The patients subsequently underwent skin testing and measurement of serum specific IgE level to laminaria extract, and were shown to elicit positive responses to laminaria. The implication and impact of laminaria allergy on gynecologic procedures are significant and this allergy should be included in the list of differential diagnoses for hypersensitive reaction in gynecologic procedures.
PMCID: PMC3055140  PMID: 14676449
25.  Terminal Restriction Fragment Length Polymorphism Data Analysis for Quantitative Comparison of Microbial Communities 
Terminal restriction fragment length polymorphism (T-RFLP) is a culture-independent method of obtaining a genetic fingerprint of the composition of a microbial community. Comparisons of the utility of different methods of (i) including peaks, (ii) computing the difference (or distance) between profiles, and (iii) performing statistical analysis were made by using replicated profiles of eubacterial communities. These samples included soil collected from three regions of the United States, soil fractions derived from three agronomic field treatments, soil samples taken from within one meter of each other in an alfalfa field, and replicate laboratory bioreactors. Cluster analysis by Ward's method and by the unweighted-pair group method using arithmetic averages (UPGMA) were compared. Ward's method was more effective at differentiating major groups within sets of profiles; UPGMA had a slightly reduced error rate in clustering of replicate profiles and was more sensitive to outliers. Most replicate profiles were clustered together when relative peak height or Hellinger-transformed peak height was used, in contrast to raw peak height. Redundancy analysis was more effective than cluster analysis at detecting differences between similar samples. Redundancy analysis using Hellinger distance was more sensitive than that using Euclidean distance between relative peak height profiles. Analysis of Jaccard distance between profiles, which considers only the presence or absence of a terminal restriction fragment, was the most sensitive in redundancy analysis, and was equally sensitive in cluster analysis, if all profiles had cumulative peak heights greater than 10,000 fluorescence units. It is concluded that T-RFLP is a sensitive method of differentiating between microbial communities when the optimal statistical method is used for the situation at hand. It is recommended that hypothesis testing be performed by redundancy analysis of Hellinger-transformed data and that exploratory data analysis be performed by cluster analysis using Ward's method to find natural groups or by UPGMA to identify potential outliers. Analyses can also be based on Jaccard distance if all profiles have cumulative peak heights greater than 10,000 fluorescence units.
doi:10.1128/AEM.69.2.926-932.2003
PMCID: PMC143601  PMID: 12571013

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