• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.5-13
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• 2012

I-cell disease (mucolipidosis type II; MIM 252500) and pseudo-Hurler polydystrophy (mucolipidosis type III; MIM 252600) are disorders caused by abnormal lysosomal transport in cells. The presence of numerous inclusion bodies in the cytoplasm of fibroblasts, a lack of mucopolysacchariduria, increased lysosomal enzyme activity in serum, and decreased GlcNAc-phosphotransferase activity are hallmark. Here, we attempted to investigate phenotypical and biochemical characteristics of the knockoutmouse of GlcNAc-phosphotransferase ${\alpha}/{\beta}$ subunits; in addition, we also attempted to determine whether the lysosome enriched fraction derived from placenta can be beneficial to phenotype and biochemistry of the knockout mouse.We found that the knockout mouse failed to thrive and had low bone density, as is the case in human. In addition, skin fibroblasts from the animal had the same biochemical characteristics, including increased lysosomal enzyme activity in the culture media, in contrast to the relatively low enzyme activity within the cells. Intravenous injection of the lysosome rich fraction derived from placenta into the tail vein of the animal resulted in a gain of weight, while saline injected animals didn't.In conclusion, our study demonstrated the phenotypical and biochemical similarities of the knockout mouse to a mucolipidosis type II patient and showed the therapeutic potential of the lysosome enriched fraction. We admit that a larger scale animal study will be needed; however, the disease model and the therapeutic potential of the lysosome enriched fraction will highlight the hope for a novel treatment approach to mucopolipidosis type II, for which no therapeutic modality is available.

• Korean Journal of Microbiology
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• v.52 no.3
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• pp.286-297
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• 2016

Clostridium perfringens is both a ubiquitous environmental bacterium and a major cause of human gastrointestinal disease, and C. perfringens food poisoning ranks among the most common gastrointestinal diseases in developed countries. 120 isolates of C. perfringens were obtained from food-poisoning outbreaks in 2013~2014, Gyeonggi-do. Using PCR, all 120 isolates were identified as C. perfringens type A. Of the tested isolates, 49 isolates carried the cpe gene, 71 isolates carried the cpb2 gene. The outbreak cases of cpb2 and cpe /cpb2 genes were 7 and 7, whereas the outbreak cases of cpe-gene were 2. The epidemiological relationship between C. perfringens isolates has previously been investigated chiefly by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). The genetics relatedness of the isolates raged from 53.5-100% and 75 district PFGE type were observed. The PFGE results revealed a wide genetic diversity among the 64 cpb2 carrying isolates (except 7 isolates), while 46 cpe-carrying isolates (except 3 isolates) showed a high genetic similarity. The MLST analysis revealed that 14 cpe isolates (cpe-chromosomal isolates) belong to a distinct cluster that is significantly distant from all the other cpb2 isolates (cpe-plasmid carrying and cpe-negative isolates). The isolates carrying a cpb2 appear to be rarely related, and are more variable than chromosomal cpe isolates. The results suggest that the cpe-positive outbreak isolates showed close genetic relation, whereas the cpb2-positive isolates revealed a wide genetic diversity.

• Journal of Genetic Medicine
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• v.4 no.1
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• pp.64-71
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• 2007

Purpose : The purpose of this study was to evaluate the clinical utility of rapid detection of Down syndrome and Edward syndrome by Interphase Fluorescence in Situ Hybridization (FISH) analysis. Methods : Aretrospective study in 309 cases of amniotic fluid samples, analysed by interphase FISH with DNA probes specific to chromosome 18 and 21, was performed. All FISH results w ere compared with conventional cytogenetic karyotypings. Results : The results were considered as informative and they were obtained within 48 hrs. A case of Down syndrome and a case of Edward syndrome were diagnosed by FISH and confirmed by subsequent cytogenetic analysis. In 12 cases with normal FISH results, the cytogenetic analysis showed a case of partial trisomy 22, three cases of sex chromosomal aneuploidy, two cases of mosaicism, two cases of microdeletion, and four cases of structural rearrangement. Conclusion : FISH is a rapid and effective diagnostic method, which can be used as an adjunctive test to cytogenetic analysis, for prenatal identification of chromosome aneuploidies. For the more genome-wide screening with variety of probes, the technique of FISH is both expensive and labor-intensive.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.534-546
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• 1997

Background : The p53 and retinoblastoma(Rb) tumor suppressor genes are associated with the pathogenesis of several types of human cancer. Substantial proportion of the primary lung cancers or cell lines have been reported to have the p53 and/or the Rb gene mutations. But, so far there is no report on the analysis of the Rb gene polymorphism as one of the genetic susceptibility marker. This study was undertaken to establish the gene frequencies of the polymorphic genotypes of the p53 and Rb genes in Koreans to evaluate the possible involvement of these genotypes as a risk factor of lung cancer. Methods : In this study 145 controls without previous and present tumor history and 128 lung cancer patients were subjected to analysis. The two intragenic polymorphisms of the p53 gene(exon 4/ AccII, intron 6/MspI) and one intron 17/XbaI polymorphism of the Rb gene were analysed by the method of polymersae chain reaction- restriction fragment length polymorphisms(PCR-RFLPs). The genotype of the intron 3/16 bp repeat polymorphism of p53 was determined by PCR and direct gel electrophoresis. Results : There were no significant differences in the genotype distributions of the p53 gene between lung cancer patients and controls. But heterozygotes(Arg/Pro) of the exon 4/AccII polymorphisms were slightly over-represented than controls, especially in the Kreyberg type I cancer, which was known to be associated with smoking. The intron 3/16 bp duplication and the intron 6/MspI polymorphisms were in complete linkage disequilibrium. About 95% of the individuals were homozygotes of the common alleles both in the 16 duplication and MspI polymorphisms, and no differences were deteced in the genotype distributions between lung cancer patients and controls. Overall genotype distributions of the Rb gene polymorphisms between lung cancer patients and controls were not significantly different However, the genotype distributions in the Kreyberg type I cancer were significantly different from those of controls(p = 0.0297) or adenocarcinomas(p = 0.0008). It was noticeable that 73.4% of the patients with adenocarcinomas were heterozygotes(r1/r2) whereas 39.2% of the Kreyberg type I cancer were heterozygous at this polymorphisms. In the lung cancer patients, significant differences were also noted between the high dose smokers and low dose smokers including non-smokers(p = 0.0258). The relative risk to Kreyberg type I cancer was significantly reduced in the individuals with the genotype of r1/r2(odds ratio = 0.46, 95% C.I. = 0.25-0.86, p = 0.0124). The combined genotype distribution of the exon 4 AccII of the p53 and the intron 17 Rb gene polymorphisms in Kreyberg type I cancers were significantly different from dose of controls or adenocarcinomas. The highest odds ratio were observed in the individuals with the genotypes of Arg/Pro and r2/r2(odds ratio = 1.97,95% C.I. = 0.84-4.59) and lowest one was in the patients with Arg/Arg, r1/r2 genotype(odds ratio = 0.54, 95% C.I. = 0.25-1.14). Conclusion : The p53 and the Rb gene polymorphisms modulate the risk of smoking induced lung cancer development in Koeans. However, the exact mechanism of risk modulation by these polymorphism remains to be determined. For more discrete clarification of associations between specific genotypes and lung cancer risk, the evaluations of these polymorphisms in other ethnics and more number of patients will be needed.

• Journal of Gastric Cancer
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• v.5 no.1
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• pp.10-15
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• 2005

Purpose: Recently the role of vitamins, folate in particular, has been emphasized in the maintenance of health. Folate deficiency is known to give rise to developmental delay, immature vascular disease, neural tube defect, acute leukemia, atherosclerotic vascular disease, delivery defects, breast cancer, and particularly gastrointestinal neoplasia. Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in folate metaboism, and influences DNA synthesis and DNA methylation. Generally, folate deficiency is associated with gastrointestinal neoplasms. The amino-acid- changing and enzyme-activity-reducing nucleotide polymorphism (766C$\rightarrow$T/ Ala222Val) has been described in the MTHFR polymorphism and leads to low enzyme activity that may reduce the capacity of DNA methylation and possibly uracil mis-incorporation into DNA. These processes may be critical in the oncogenic transformation of human cells, especially in colorectal carcinomas. We investigated the relationship between the MTHFR polymorphism in gastric cancer and the tumor site, the smoking history, and the alcoholic history. Materials and Methods: Ninety-six (96) individuals with gastric cancer and 287 healthy persons were analyzed. Blood sampling was performed, PCR-RFLP was analyzed, and MTHFR polymorphism genotypes of C/C, C/T, and T/T were obtained and analyzed statistically for their correlation. Results: In the gastric cancer group there were 69 ($72\%$) males and 27 ($28\%$) females. There were also 58 cases ($60\%$) involving the gastric lower body, 20 cases ($21\%$) the gastric mid-body, and 18 cases ($19\%$) the gastric upper body. In the control group there were 169 ($59\%$) males and 118 ($41\%$) females. Among the gastric cancer, 56 ($61\%$) smoking patients, 40 ($39\%$) non-smoking patients, 45($47\%$) alcoholic patients, 51 ($53\%$) non-alcoholic patients. In the gastric cancer group, MTHER polymorphisms were C/C in 18 ($19\%$) cases, C/T in 59 ($61\%$) cases, T/T in 19 ($20\%$) cases. In the control group polymorphisms were C/C 116 ($40\%$) cases, C/T 103 ($36\%$) cases, and T/T 68 ($24\%$) cases (P=0.045). In cases of lower gastric body cancer, polymorphisms were C/C in 16 ($24\%$) C/C in 16 ($24\%$) cases and C/T or T/T in 42 ($72\%$) cases. In cases of upper and mid-body cancer, polymorphisms were C/C in 2 ($5\%$) cases and C/T or T/T 36 ($95\%$) cases (P=0.006). In the non-smoking patient group, polymorphisms were C/C in 5 (12%) cases and C/T or T/T in 35 ($88\%$) cases. In the smoking patient group, C/C in 13 ($23\%$) cases and C/T or T/T in 43 ($77\%$) cases (P=0.189). In the non-alcoholic patient group, polymorphisms were C/C in 6 ($12\%$) cases and C/T or T/T in 45 ($88\%$) cases. In the alcoholic patient group, polymorphisms were C/C in 12 ($26\%$) cases and C/T or T/T in 33 ($74\%$) cases (P=0.063) Conclusion: MTHFR polymorphisms are associated with gastric cancer and tumor site, but not with smoking and alcohol drinking.