Antibacterial activity and mechanism of action of analogues derived from the antimicrobial peptide mBjAMP1 isolated from Branchiostoma japonicum.

Objectives: The worldwide increase in antibiotic-resistant bacteria is a growing threat to public health. Antimicrobial peptides (AMPs) are potentially effective alternatives to conventional antibiotics. We therefore tested analogues of the AMP mBjAMP1 from Branchiostoma japonicum, which we produced by adding and/or replacing amino acids to increase antimicrobial activity against Gram-negative bacteria. Methods: We compared the antimicrobial activities of mBjAMP1 analogues against Gram-negative bacteria reference strains and 52 strains of Klebsiella pneumoniae isolated from patients. Antibiofilm activity and cytotoxicity were evaluated, and the mechanisms of action were then studied. Results: Analogue peptides exhibited greater antimicrobial and antibiofilm activities than mBjAMP1. In particular, the analogue IARR-Anal10 displayed not only the greatest antimicrobial and antibiofilm activities, but also no toxicity against human red blood cells or other mammalian cells. IARR-Anal10 had little or no effect on bacterial outer membrane permeability, membrane polarization or membrane integrity. Instead, it appears IARR-Anal10 binds bacterial DNA, as evidenced in DNA gel retardation assays. Thus, IARR-Anal10 likely kills bacteria through an intracellular mechanism. We also confirmed that IARR-Anal10 suppresses the virulence of K. pneumoniae to a degree similar to tigecycline, used to treat carbapenem-resistant Enterobacteriaceae infections. Notably, IARR-Anal10 did not induce development of resistance by K. pneumoniae, though both meropenem and tigecycline did so within a short time. Conclusions: These results suggest that IARR-Anal10 is a promising agent for treating infections caused by bacteria resistant to tigecycline and meropenem.

Synergistic effects and antibiofilm properties of chimeric peptides against multidrug-resistant Acinetobacter baumannii strains.

The increasing prevalence of drug-resistant pathogens highlights the need to identify novel antibiotics. Here we investigated the efficacies of four new antimicrobial peptides (AMPs) for potential drug development. The antibacterial activities, synergistic effects, and antibiofilm properties of the four chimeric AMPs were tested against Acinetobacter baumannii, an emerging Gram-negative, nosocomial, drug-resistant pathogen. Nineteen A. baumannii strains resistant to ampicillin, cefotaxime, ciprofloxacin, tobramycin, and erythromycin were isolated at a hospital from patients with cholelithiasis. All four peptides exhibited significant antibacterial effects (MIC=3.12 to 12.5 µM) against all 19 strains, whereas five commercial antibiotics showed little or no activity against the same pathogens. An exception was polymyxin, which was effective against all of the strains tested. Each of the peptides showed synergy against one or more strains when administered in combination with cefotaxime, ciprofloxacin, or erythromycin. The peptides also exhibited an ability to prevent biofilm formation, which was not seen with cefotaxime, ciprofloxacin, or erythromycin, though polymyxin also inhibited biofilm formation. Indeed, when administered in combination with ciprofloxacin, the AMP HPMA exerted a potent synergistic effect against A. baumannii biofilm formation. Collectively, our findings indicate that the AMPs tested have no cytotoxicity but possess potent antibacterial and antibiofilm activities and may act synergistically with commercial antibiotics.

Characterization of Rotavirus Infection in Hospitalized Children under 5 with Acute Gastroenteritis 5 Years after Introducing the Rotavirus Vaccines in South Korea.

We herein characterized rotavirus infection in hospitalized children under 5 years of age with gastroenteritis after introducing rotavirus vaccines in South Korea from 20 February 2012, to 31 March 2013. Enzyme-linked fluorescent immunoassay was performed to detect rotavirus antigens. G and P genotyping was performed using nested multiplex PCR. For the failed PCR samples, sequencing was conducted. We performed a test-negative case-control study to estimate vaccine effectiveness. Vaccine effectiveness was measured using a multivariate logistic regression model. Rotavirus was detected in 16 (13.2%) of the 121 patients, with a seasonal peak in April 2012. The dominant genotypes detected were G3P[8] (33.3%) and G4P[6] (26.7%), and vaccine effectiveness against rotavirus hospitalization was 84.9% [95% CI: 23.2−97.0] in the complete vaccinated group. A higher prevalence of rotavirus infection was observed among children with siblings than those without siblings (p < 0.001). Also, the presence of siblings was significantly associated with a history of nonvaccination (p < 0.001). In conclusion, the prevalence of rotavirus followed a decreasing trend, and there was no evidence of emergences of nonvaccine-type strains. Vaccine effectiveness against rotavirus hospitalization was 84.9%. Although children with siblings were more susceptible to rotavirus infection, they were less likely to receive vaccination against rotavirus.

Efficacy of a novel channel-cleaning ball brush for endoscope reprocessing: a randomized controlled trial.

BACKGROUND/AIMS: Endoscopic channels are difficult to clean and can cause infection transmission. We examined the effectiveness of a newly developed channel-cleaning ball brush (BB), which is sucked into the endoscopic channel and scrapes and cleans the lumen as it passes through. METHODS: The upper and lower gastrointestinal endoscopes used for patient examinations were randomly selected as the conventional brush (CB) or BB group. After manual cleaning, the presence or absence of carbohydrates, proteins, adenosine triphosphate, and hemoglobin was assessed. RESULTS: Fifty-six and 58 endoscopes were cleaned with the CB and BB, respectively. Carbohydrate and protein were detected in one (1.8%) and two endoscopes (3.4%) in the CB and BB groups, respectively (p=1.000). Hemoglobin was observed in one (1.8%) and three endoscopes (5.2%) in the CB and BB groups, respectively (p=0.636). The adenosine triphosphate levels were 10.6±15.9 and 12.5±14.3 relative light units in the CB and BB groups, respectively (p=0.496). Twenty-seven (48.2%) and 19 (32.8%) endoscopes were positive for microbial cultures in the CB and BB groups, respectively (p=0.136). CONCLUSION: The efficacy of BB was not significantly different from that of CB in the endoscopic channel-cleaning process.

Identification of 8-Digit HLA-A, -B, -C, and -DRB1 Allele and Haplotype Frequencies in Koreans Using the One Lambda AllType Next-Generation Sequencing Kit.

BACKGROUND: Recent studies have successfully implemented next-generation sequencing (NGS) in HLA typing. We performed HLA NGS in a Korean population to estimate HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies up to an 8-digit resolution, which might be useful for an extended application of HLA results. METHODS: A total of 128 samples collected from healthy unrelated Korean adults, previously subjected to Sanger sequencing for 6-digit HLA analysis, were used. NGS was performed for HLA-A, -B, -C, and -DRB1 using the AllType NGS kit (One Lambda, West Hills, CA, USA), Ion Torrent S5 platform (Thermo Fisher Scientific, Waltham, MA, USA), and Type Steam Visual NGS analysis software (One Lambda). RESULTS: Eight HLA alleles showed frequencies of ≥10% in the Korean population, namely, A*24:02:01:01 (19.5%), A*33:03:01 (15.6%), A*02:01:01:01 (14.5%), A*11:01:01:01 (13.3%), B*15:01:01:01 (10.2%), C*01:02:01 (19.9%), C*03:04:01:02 (11.3%), and DRB1*09:01:02 (10.2%). Nine previous 6-digit HLA alleles were further identified as two or more 8-digit HLA alleles. Of these, eight alleles (A*24:02:01, B*35:01:01, B*40:01:02, B*55:02:01, B*58:01:01, C*03:02:02, C*07:02:01, and DRB1*07:01:01) were identified as two 8-digit HLA alleles, and one allele (B*51:01:01) was identified as three 8-digit HLA alleles. The most frequent four-loci haplotype was HLA-A*33:03:01-B*44:03:01:01-C*14:03-DRB1*13:02:01. CONCLUSIONS: We identified 8-digit HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies in a healthy Korean population using NGS. These new data can be used as a representative Korean data for further disease-related HLA type analysis.

Association between small intestinal bacterial overgrowth and peripheral bacterial DNA in cirrhotic patients.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is regarded as the major risk factor of bacterial translocation. Few studies have investigated the direct relation between SIBO and translocation in cirrhotic patients. The purpose of this study is to examine the correlation between SIBO and bacterial DNA in the peripheral blood of patients with cirrhosis. AIMS: The purpose of this study is to examine the correlation between SIBO and bacterial DNA in the peripheral blood of patients with cirrhosis. METHODS: Fifty-three cirrhosis cases and 42 controls underwent a lactulose breath test (LBT) every 15 min for 180 min. To detect and identify the presence of bacterial DNA fragments in peripheral blood, multiplex polymerase chain reaction (PCR) was performed. RESULTS: The positive rate of LBT was significantly different between the two groups: 60.4% in the patient group and 28.6% in the controls. The SIBO positive rate was 81.3% in the cirrhosis patients with ascites, which was significantly higher than 51.4% in the cirrhosis patients with no ascites (P = 0.03). Eight of the nine patients (88.9%) who had a history of one or more hepatic encephalopathy was SIBO-positive, which was higher than the patients who had had no hepatic encephalopathy. In the cirrhosis group, 32 patients (60.4%) were SIBO-positive, and ten of them (31.3%) were bacterial DNA-positive. Only one case (4.8%) was bacterial DNA-positive in the absence of SIBO-positive. In a multivariate analysis, only the existence of SIBO was the independent risk factor for bacterial DNA (P = 0.026). CONCLUSIONS: SIBO in cirrhosis patients was observed at a very high frequency, and SIBO showed a high correlation with bacterial translocation, suggesting that SIBO could be a major risk factor of bacterial translocation, especially in ascitic patients.

Aquaporin-2 urinary excretion in cirrhosis: relationship to vasopressin and nitric oxide.

The aquaporin (AQP) water channel plays an important role in the regulation of water. AQP2 is expressed in the collection duct of the kidney, serving as the final channel that helps to regulate water excretion in the kidneys and affecting the regulation of water and hyponatremia in cirrhotic patients. So far, research on aquaporin expression in cirrhosis has had various results. The purpose of this study is to investigate the factors that affect the regulation of expression of AQP in patients with cirrhosis. The study comprised 81 cirrhosis patients and 18 control subjects. In each group, 24-h urine was collected and nitric oxide and vasopressin levels were measured in the blood. The amount of urinary AQP was measured by Western blot. In this study, the positivity rate and amount of expression of AQP was higher in the cirrhotic group than that of the control group. AQP expression in urine was also compared between the groups with use of diuretics and the groups with no use of diuretics. A 57.4% positivity was observed with the former, whereas a 51.5% was seen in the latter. No significance was found between the groups (P = 0.581). Expression of AQP in compensated cirrhotic patients is significantly higher than decompensated cirrhotic patients and is especially higher in cirrhotic patients with ascites than with no ascites. There is no relationship between the concentration of vasopressin and expression of AQP. Concentration of serum NOx is higher in cirrhotic patients than the control group and there is a positive association between the concentration of serum nitric oxide and AQP in urine. In conclusion, expression of AQP is increased in cirrhotic patients and is significantly higher in patients with ascites. There is a positive association between the expression of AQP and concentration of serum nitric oxide.

Changing molecular epidemiology of group B streptococcus in Korea.

The prevalence of group B streptococcus (GBS) among pregnant women and disease burdens in neonates and adults are increasing in Korea. Colonizing isolates, collected by screening pregnant women (n=196), and clinical isolates collected from clinical patients throughout Korea (n=234), were serotyped and screened for antibiotic resistance. Serotype III (29.8%) and V (27.7%) predominated, followed by Ia (17.0%). Antibiotic resistance was higher among clinical than colonizing isolates for erythromycin (35.1% and 26.9%; P=0.10) and for clindamycin (49.4% and 42.1%; P=0.17). erm(B) occurred in 91.9% of erythromycin resistant isolates, and 84.0% of isolates resistant to clindamycin. Only five isolates (4.2%) resistant to erythromycin were susceptible to clindamycin; by contrast, and unique to Korea, 34% of isolates resistant to clindamycin were erythromycin susceptible. Among these 60 erythromycin-susceptible & clindamycin-resistant isolates, 88% was serotype III, and lnu(B) was found in 89% of strains. Four fifths of the serotype V isolates were resistant to both erythromycin and clindamycin. Further characterization of the genetic assembly of these resistance conferring genes, erm(B) and lnu(B), will be useful to establish the clonal lineages of multiple resistance genes carrying strains.

9G TestTM Cancer/Lung: A Desirable Companion to LDCT for Lung Cancer Screening.

A complimentary biomarker test that can be used in combination with LDCT for lung cancer screening is highly desirable to improve the diagnostic capacity of LDCT and reduce the false-positive rates. Most importantly, the stage I lung cancer detection rate can be dramatically increased by the simultaneous use of a biomarker test with LDCT. The present study was conducted to evaluate 9G testTM Cancer/Lung's sensitivity and specificity in detecting Stage 0~IV lung cancer. The obtained results indicate that the 9G testTM Cancer/Lung can detect lung cancer with overall sensitivity and specificity of 75.0% (69.1~80.3) and 97.3% (95.0~98.8), respectively. The detection of stage I, stage II, stage III, and stage IV cancers with sensitivities of 77.5%, 78.1%, 67.4%, and 33.3%, respectively, at the specificity of 97.3% have never been reported before. The receiver operating characteristic curve analysis allowed us to determine the population-weighted AUC of 0.93 (95% CI, 0.91-0.95). These results indicate that the 9G testTM Cancer/Lung can be used in conjunction with LDCT to screen lung cancer. Furthermore, obtained results indicate that the use of 9G testTM Cancer/Lung with LDCT for lung cancer screening can increase stage I cancer detection, which is crucial to improve the currently low 5-year survival rates.

Clinical Characteristics of Campylobacter Enterocolitis in Korean Adults: A Retrospective Study at a Single Center.

Background/Aims: Although the diarrheal disease caused by Campylobacter bacteria has been continuously increasing in Korea, there has been limited study on the clinical aspects of Campylobacter enteritis in adults in Korea. The purpose of this study was to analyze the clinical features and characteristics of adult patients with Campylobacter enteritis. Methods: This retrospective study included patients diagnosed with Campylobacter enterocolitis at Nowon Eulji University Hopsital between January 2016 and December 2017. Campylobacter enterocolitis was diagnosed through polymerase chain reaction of stools from patients with acute diarrhea. Results: Among 630 hospitalized patients with acute diarrhea, Campylobacter enterocolitis was diagnosed in 88 patients (14.0%). The mean age was 37.9±19.1 years. Campylobacter enterocolitis was most prevalent in the summer (52 patients, 59.1%). Patients exhibited more than 10 times of diarrhea in 36 (40.9%), high fever above 39°C in 19 (21.59%), and abdominal pain above 5 points on the numeric rating scale in 23 (26.14%) cases. In abdominal CT scan, pancolitis was found in 58 patients (65.9%). Small intestine was involved in 37 patients (42.4%). Mean CRP was 10.14 mg/dL (range 0.72-32.27 mg/dL). The duration of diarrhea after antibiotics treatment was 2.34±1.51 days in the ciprofloxacin treatment group and 2.26±1.71 days in the 3rd cephalosporin treatment group. Conclusions: Campylobacter enterocolitis was common during summer. Commonly healthy young adults were hospitalized due to severe symptoms of Campylobacter enterocolitis. Whole colon and small bowel were frequently involved. Most patients were treated with antibiotics, and the efficacy of 3rd cephalosporin treatment was not inferior to that of ciprofloxacin treatment.

Analysis of Syndecan-2 Methylation in Bowel Lavage Fluid for the Detection of Colorectal Neoplasm.

Background/Aims: Syndecan-2 (SDC2) methylation was previously reported as a sensitive serologic biomarker for the early detection of colorectal cancer (CRC). The purpose of this study was to investigate whether SDC2 methylation is detectable in precancerous lesions and to determine the feasibility of using SDC2 methylation for the detection of CRC and precancerous lesions in bowel lavage fluid (BLF). Methods: A total of 190 BLF samples were collected from the rectum at the beginning of colonoscopy from patients with colorectal neoplasm and healthy normal individuals. Fourteen polypectomy specimens were obtained during colonoscopy. A bisulfite pyrosequencing assay and quantitative methylation-specific polymerase chain reaction were conducted to measure SDC2 methylation in tissues and BLF DNA. Results: SDC2 methylation was positive in 100% of villous adenoma (VA) and high-grade dysplasia, and hyperplastic polyp samples; 88.9% of tubular adenoma samples; and 0% of normal mucosa samples. In the BLF DNA test for SDC2 methylation, the sensitivity for detecting CRC and VA was 80.0% and 64.7%, respectively, at a specificity of 88.9%. The BLF of patients with multiple tubular adenomas, single tubular adenoma and hyperplastic polyps showed 62.8%, 26.7% and 28.6% rates of methylation-positive SDC2, respectively. Conclusions: Our results demonstrated that SDC2 methylation was a frequent event in precancerous lesions and showed high potential in BLF for detecting patients with colorectal neoplasm.

Vitamin D Status and Its Association with the SCORAD Score and Serum LL-37 Level in Korean Adults and Children with Atopic Dermatitis.

BACKGROUND: Vitamin D insufficiency could be associated with the prevalence of atopic dermatitis (AD). OBJECTIVE: To examine vitamin D status and the relations between serum 25-hydroxyvitamin D levels, SCORAD score, serum LL-37 level, and body mass index (BMI) in Korean AD patients, and to explore whether these associations differ between adults and children. METHODS: Serum 25-hydroxyvitamin D levels, serum LL-37, and clinical features were analyzed in a total of 72 Korean patients with AD (39 adults and 33 children) and 140 healthy control subjects (70 adults and 70 children). RESULTS: Serum 25-hydroxyvitamin D levels were significantly reduced in children with AD (15.06±4.64 ng/ml) compared with normal children in the control group (16.25±6.60 ng/ml) (p=0.036). Significant inverse correlations were found between BMI and 25-hydroxyvitamin D level (r=-0.315, p=0.007) and between the SCORAD score and serum LL-37 level (r=-0.3, p=0.011) in the total AD patients. CONCLUSION: The results showed that serum vitamin D levels were lower in children with AD than in healthy children; however, the same relation was not observed between adults with AD and healthy adults. Serum 25-hydroxyvitamin D concentration was not significantly correlated with AD severity or serum LL-37 levels in our study population.

Natural polymorphisms of protease in protease inhibitor-naive HIV-1 infected patients in Korea: a novel L63M in subtype B.

To establish a baseline for monitoring resistance mutation to protease inhibitors (PI), we determined protease(PR) sequences in peripheral blood mononuclear cells obtained from 43 PI-naive Korean HIV-1 infected patients. Interestingly, phylogenetic analysis revealed that 41 of the sequences belonged to subtype B, one belonged to subtype A, and one was unique, not clustering with any subtype. Thirty-one (76%) of the 41 sub-type B sequences formed a subclade within subtype B, a so-called "Korean B cluster." Polymorphisms were observed at 34 (34.3%) of the PR codons. One patient (2.3%) harbored a primary resistance-conferring mutation, L90M along with L63P and A71V, and all 43 strains showed some secondary associated with drug resistance. The percentage of patients with 7, 5, 4, 3, 2, and 1, resistance mutations were 2%, 2%, 14%, 23%,37%, and 9%, respectively. A novel polymorphism in subtype B, L63M was detected in two patients. Another patient showed a gross deletion (257 bp) after codon 91. The average genetic distance of the 41 subtype B sequences to the HXB2 sequence was 3.0% (range, 1.0-5.1%). Six hemophiliacs were infected with a domestic strain of HIV-1 subtype B, while the other two hemophiliacs were infected with nondomestic subtype B and had lived outside Korea. Although this is the first report on the molecular nature of PR in Korea, there is also a need to establish baselines for nonsubtype B HIV-1.

A case of cholesterosis bulbi with secondary glaucoma treated by vitrectomy and intravitreal bevacizumab.

We report on a case of cholesterosis bulbi concurrent with secondary glaucoma. A 36-year-old man, with a history of long-standing retinal detachment in his right eye after the irrigation and aspiration of a congenital cataract, presented with a clinical picture of elevated intraocular pressure and ocular pain. Upon slit-lamp examination, we found a ciliary injection and a pseudohypopyon of polychromatic crystals. Gonioscopic examination revealed a large amount of crystals deposited on the trabecular meshwork and mild rubeosis iridis, but the neovascularization of the angle could not be clearly confirmed due to the presence of so many crystals. Pars plana vitrectomy was performed to remove clusters of crystals and bevacizumab was injected intravitreally to treat iris neovascularization. Aqueous aspirate was examined by light microscopy and the typical highly refringent cholesterol crystals were identified. Intraocular pressure returned to a normal level after the bevacizumab injection, although severe cholesterosis was still evident in the anterior chamber. To our knowledge, this would be the first Korean case of cholesterosis bulbi combined with chronic retinal detachment and presumed neovascular glaucoma, which was treated by pars plana vitrectomy and intravitreal bevacizumab injection.

[The prevalence of Yersinia infection in adult patients with acute right lower quadrant pain].

BACKGROUND/AIMS: Clinical manifestations of intestinal yersiniosis include enterocolitis, mesenteric adenitis, and terminal ileitis presenting with fever, right lower quadrant pain, and leukocytosis. According to a previous Korean study in 1997, Yersinia was revealed in two among 15 adult patients with mesenteric adenitis (13%). However, recent reports on the prevalence of Yersinia infection in adult patients are few. The aim of this study was to investigate the prevalence of Yersinia infection in adult patients with acute right lower quadrant pain. METHODS: Adult patients (>18 years) who visited Eulji medical center, due to acute right lower quadrant pain were enrolled prospectively from December 2007 to July 2009. Abdominal CT, stool culture, serologic test for Yersinia, and Widal test were performed. RESULTS: Among 115 patients, 5 patients were excluded due to positive Widal test or salmonella culture. In 110 patients, abdominal CT showed right colitis in 20 (18.2%), terminal ileitis in 16 (14.5%), mesenteric adenitis in 13 (11.8%), acute appendicitis in 10 (9.1%), acute diverticulitis in 7 (6.4%), non specific mucosal edema in 36 (32.7%) and no specific lesion in 8 (7.3%). Two (1.8%) of the 110 patients had antibodies to Yersinia. One patient showed acute enteritis and the other patient was diagnosed with acute appendicitis and underwent appendectomy. No Yersinia species were grown on stool or tissue culture. CONCLUSIONS: Nowadays, among adult Korean patients presenting with acute right lower quadrant pain, there have been few incidences of Yersinia infection.

[Comparison of the efficacies of silver-containing dressing materials for treating a full-thickness rodent wound infected by methicillin-resistant Staphylococcus aureus].

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) may cause infections during wound dressing. We aimed to compare the antibacterial activities and wound-healing effects of commercially available silver-coated or silver-impregnated wound dressings on MRSA-infected wounds. METHODS: Full-thickness skin defects were made on the back of rats (N=108) and were infected with MRSA. The rats were divided into the following 6 groups according to the dressing used for the wounds: nanocrystalline silver (Acticoat), silver carboxymethylcellulose (Aquacel-Ag), silver sulfadiazine (Medifoam silver), nanocrystalline silver (PolyMem silver), silver sulfadiazine (Ilvadon), and 10% povidone iodide (Betadine). We analyzed the wound sizes, histological findings, and bacterial colony counts for the groups. We also inoculated the silver materials on Mueller-Hinton agar plates containing MRSA and compared the inhibition zones in the agar plates. RESULTS: The order of the rate of wound-size decrease was Acticoat>Aquacel-Ag>PolyMem silver>Medifoam silver>Ilvadon>Betadine. The histological findings revealed that the Acticoat showed more reepithelialization and granulation tissue formation and less inflammatory cell infiltration than the other materials. The order of the time required for wound healing was Acticoat>Aquacel -Ag>PolyMem silver>Ilvadon>Medifoam silver>Betadine. The bacterial colony counts reduced in all the groups, except in the Medifoam silver group. The order of the size of the inhibition zone was Acticoat>Aquacel-Ag>Ilvadon>PolyMem silver>Betadine>Medifoam silver. CONCLUSIONS: Silver-coated or silver-impregnated wound dressings can be used for treating MRSAinfected wounds. Considering its superior efficacy in comparison to the efficacies of other silver-coated or silver-impregnated wound dressings, Acticoat should be preferentially used for the treatment of MRSA-infected skin wounds.

Polymorphisms of microsomal triglyceride transfer protein gene and phosphatidylethanolamine N-methyltransferase gene in alcoholic and nonalcoholic fatty liver disease in Koreans.

BACKGROUND: The pathogenesis of fatty liver is likely to depend on a complex interaction of environmental and genetic factors. We investigated a large-scale analysis of the association between microsomal triglyceride transfer protein (MTTP) and phosphatidylethanolamine N-methyltransferase (PEMT) polymorphism in alcoholic and nonalcoholic fatty liver disease. METHODS: Five hundred and eighty-eight patients who visited the health promotion center were enrolled. To elucidate the possible role of genetic variation affecting triglyceride metabolism in fatty liver disease, the MTTP-I128T and PEMT-V175M polymorphisms were studied. RESULTS: The I/I genotype and I allele frequency of MTTP polymorphism with alcoholic fatty liver was significantly higher than that of the normal control group (P=0.026 vs. 0.005). Genotype and allele frequency of PEMT, however, did not show a significant difference between control and fatty liver. I/I genotype of MTTP gene frequency in the drinkers with fatty livers was 85.4%, which was significantly higher than that in the drinkers without fatty liver, which was 68.4% (P=0.013). With regard to biochemical indicators, the alanine aminotransferase value of the I/I group was significantly higher than that of the I/T and T/T groups (P=0.04). Asparate aminotransferase, gamma-glutamyl transpeptidase, triglyceride, apolipoprotein B, and glucose concentration tended to be lower in the I/T and T/T groups than in the I/I group, but no statistically significant difference was found. CONCLUSION: In this study, MTTP-I128T polymorphism is associated with central obesity, elevated liver enzymes, and alcoholic fatty liver disease.

[A case of a Korean adult affected by type B Niemann-Pick disease: secondary sea-blue histiocytosis and molecular characterization].

Niemann-Pick disease (NPD) is an inherited metabolic disorder caused by a deficiency of the enzyme acid sphingomyelinase coded by SMPD1 gene. In contrast with type A NPD, a severe neurodegenerative disease of infancy, type B NPD patients have little or no neurodegeneration, and frequently survive into adulthood. Although over 100 mutations have been found within the SMPD1 gene causing NPD, there was only one report about SMPD1 mutation status of a Korean NPD patient. We report a case of a 32-yr-old female, who presented with thrombocytopenia without any neurologic involvement. Hepatosplenomegaly was detected by both physical examination and imaging studies, and a thoracic radiograph examination showed a pattern of interstitial lung disease. Biochemical tests revealed increased liver enzymes, cholesterol, triglyceride, and LDL-cholesterol, and decreased HDL-cholesterol. Sea-blue or foamy vacuolated histiocytes occurred in bone marrow and liver. Sequencing analysis of SMPD1 using genomic DNA from peripheral leukocytes identified a compound heterozygote of two mutations at exon 2: p.E246K and p.A357V. The former is a known mutation in an Italian patient, and the latter has not been reported yet. She has received oral rosuvastatin to treat hyperlipidemia at a dose of 10 mg per day for 4 months. This is the second report in which the mutation of SMPD1 gene was detected in a Korean NPD patient. The active genetic analysis of SMPD1 gene in patients with typical findings of type B NPD would enable us to facilitate diagnosis as well as to accumulate data on molecular characteristics of Korean NPD patients.