• 대한기관식도과학회:학술대회논문집
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• 대한기관식도과학회 1982년도 제16차 학술대회연제순서 및 초록
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• pp.10.1-10
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• 1982

최근의 후두미세수술 (Laryngo-microsurgery)의 보편화와 이에 따른 음성외과학(phonosurgery)의 발달로 종전까지 성대결절이나 성대폴립등의 양성종양 절제나 반회신경 마비등예에서 진단된 성문간격 (glottic chink)을 $Teflon^{{\circledR}}$ injection등으로 치료해오던 후두경술(Laryngoscopy)하에서의 수술적 조작이 그 한계와 범위를 넘어서서 이제는 우리 나라에 있어서도 후두의 기능외과적인 측면에서 음성을 개선하려는 시도가 고조되고 있으며 특히 성대마비나 변성기발성장애 (Mutational dysphonia), 성대위축 (Vocal cord atrophy), 운동기능 항진성발성장애 (Hyperkinetic dysphonia), 성대구증(Sulcus vocalis)등을 위한 음성개선수술이 실시되고 있음은 우리나라의 음성외과학의 발전이라는 견지에서도 매우 기꺼운 일이다. 이러한 뜻에서 내시경술을 통해서 성대에 직접 수술적 조작을 가하지않고서도 성문외적으로 후두구조를 수술하여 성대의 위치와 물리적 성질을 변화시킴으로서 음성을 개선하려는 갑상연골성형술 (thyroplasty)이 성행되고 있음을 강조하고싶다. Isshiki(1974)는 이러한 thyroplasty 를 4종류로 분류하였으며 편측성 성대마비의 경우 I 형 thyroplasty (lateral compression of vocal cord) 와 IV형 thyroplasty (Lengthening of vocal cord) 가 효과적인 수술방법인데 이들 수술의 장점은 국소마취하에서 환자의 목소리를 들어가면서 lateral compression의 정도를 조정해서 시술할 수 있다는것과 갑상연골내측 연골막 밖에서 의 조작으로서 후두내 출혈이나 호흡곤란등의 위험성이 전혀 없다는 것이다. 본 교실에서는 1981 년 9월부터 1982년 3월까지 7개월간에 경험한 편측성 성대마비 7예에 대하여 국소마취하에서 thyroplasty를 시행하여 약간의 지견을 얻었기에 보고하는 바이다. 수술에 앞서서 모든 환자에게 미리 공기역학검사, 청각심리적검사, 스트로보스콥검사(stroboscopy) 및 음향분석(Sound spectrographic analysis) 을 실시하였으며 thyroplasty 시행 2 개월후에 상기한 검사를 다시 시행해서 수술전후의 음성을 비교관찰하여 다음과 같은 성적을 얻었다. 1) 공기역학검사상 최장발성지속시간 (Maximum phonation time)은 58 % 증가되었으며 이에따른 발성시호기유율 (Phonation quotient)과 평균호기유율(Mean flow rate)은 각각 58 %, 54 %로 감소되었다. 2) 청각심리적검사에서 애성의 정도가 호전되었으며 스트로보스콥검사에서도 발성시 성문간격의 개선을 보았다. 3) 음향분석도상에서 성대 진동의 주기성 (Periodicity)이 회복되었으며 특히 고주파역에서의 잡음분포가 감소되었다.

• Clinical and Experimental Pediatrics
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• 제45권10호
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• pp.1263-1272
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• 2002

목 적 : 레트증후군이란 1966년 Andreas Rett에 의해 처음 기술되었으며 생후 6개월에서 18개월 정도까지 비교적 정상 발달을 한 후 두위 발달의 감소와 함께 습득했던 인지 및 운동능력의 상실, 언어기능의 상실, 그리고 특징적인 손동작(상동행동)을 보이는 X 염색체 우성유전으로 생각되는 질환이다. 1999년 미국에서 그 결함 유전자인 MECP2 유전자가 Xq28에서 밝혀졌으나 우리 나라에서는 이 질환에 대한 전반적 이해가 부족하며 유전자 연구는 거의 전무한 상태이다. 이에 저자들은 우리 나라의 Rett 증후군 환아에서 MECP2 유전자의 결함이 어느 정도 나타나는지를 알고자 이 연구를 시행하였다. 방 법 : 2000년 2월부터 2001년 3월까지 본원을 방문한 Rett 증후군 환아 34례의 말초혈액을 EDTA (Ethylenediaminetetraacetic acid) 처리하여 5 cc 채취하여 냉동 보관한 후 해빙하여 DNA 표본을 추출했다. DNA의 추출은 E.Z.N.A blood DNA kit을 사용하였다. MECP2 유전자 네 종류의 axon은 PCR을 이용해 증폭하였고 primer sequence는 1999년 Amir 등에 의해 디자인 된 것(AF030876)을 사용하였다. ABI 377 DNA sequencer와 ABI PRISM dye cycle sequencing reaction kit을 사용하여 DNA sequencing을 시행하였고 우리 나라에서 최초로 발견된 유전자 변이에 대해서는 RFLP 분석을 통해 확인하였다. 결 과 : 1) MECP2 유전자의 변이를 보인 환아는 23례로 67.6%에서 관찰되었다. 2) 9종의 missense mutation과 3종의 nonsense mutation을 합해 총 12종의 유전자 변이가 관찰되었다. 3) 이들 돌연 변이 중 L100V, G161E, 그리고 T311M은 전세계적으로 우리 나라에서 처음 발견된 변이이다. 4) 23례의 유전자 변이는 대부분(78.3%) MBD와 TRD라는 기능영역에서 발견되었다. 5) 본 연구에서 T158M, R270X, 그리고 R306C가 자주 나타나는 유전자 변이였다. 결 론 : 우리 나라의 Rett 증후군 환아에서도 MECP2 유전자의 변이는 비교적 흔히 관찰되어 MECP2 유전자의 이상이 Rett 증후군을 유발하는 주 유전자 이상임을 확인하였고 Rett 증후군 환아의 확진을 위해 MECP2 유전자 검사가 필요할 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5599-5603
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• 2012

Background: The epidermal growth factor receptor (EGFR) is a potential therapeutic target for breast cancer treatment; however, its use does not lead to a marked clinical response. Studies of non-small cell lung cancer and colorectal cancer showed that mutations of genes in the PIK3CA/AKT and RAS/RAF/MEK pathways, two major signalling cascades downstream of EGFR, might predict resistance to EGFR-targeted agents. Therefore, we examined the frequencies of mutations in these key EGFR pathway genes in Chinese breast cancer patients. Methods: We used a high-throughput mass-spectrometric based cancer gene mutation profiling platform to detect 22 mutations of the PIK3CA, AKT1, BRAF, EGFR, HRAS, and KRAS genes in 120 Chinese women with breast cancer. Results: Thirteen mutations were detected in 12 (10%) of the samples, all of which were invasive ductal carcinomas (two stage I, six stage II, three stage III, and one stage IV). These included one mutation (0.83%) in the EGFR gene (rs121913445-rs121913432), three (2.50%) in the KRAS gene (rs121913530, rs112445441), and nine (7.50%) in the PIK3CA gene (rs121913273, rs104886003, and rs121913279). No mutations were found in the AKT1, BRAF, and HRAS genes. Six (27.27%) of the 22 genotyping assays called mutations in at least one sample and three (50%) of the six assays queried were found to be mutated more than once. Conclusions: Mutations in the EGFR pathway occurred in a small fraction of Chinese breast cancers. However, therapeutics targeting these potential predictive markers should be investigated in depth, especially in Oriental populations.

• 한국식물병리학회:학술대회논문집
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• 한국식물병리학회 2003년도 정기총회 및 추계학술발표회
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• pp.100.1-100
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• 2003

A dctA gene encoding a protein with identity to a C4-dicarboxylate/H+ was cloned from a beneficial biocontrol bacterium, P. chororaphis O6. Expression of the dctA was induced in minimal medium by several organic acids and was repressed by glucose. Highest expression was observed in early-log cells grown on fumarate and succinate with decline as cells approached late-log phase. The dctA transcript accumulated weakly when cells were grown on malate but strong expression was observed with benzoate. Expression of the dctA transcript was repressed in early-log cells upon addition of glucose to fumarate, but was detected as the cell culture aged. A dctA-deficient mutant of O6, constructed by marker exchange mutagenesis, did not grow on minimal medium containing succinate, benzoate, or fumarate, and growth on malate was delayed. The dctA mutant and wild type grew equally on glucose. The dctA mutant on cucumber roots in sterilized potting soil was colonized at levels comparable to those of the wild type, but induction level of disease resistance by the mutant against target leaf spot disease was decreased. These results may indicate that the dctA is essential for utilization of certain organic acids and its expression is controlled by the availability of sugars. In addition, the dctA is not essenitial for cucumber root colonization, but important for induction of disease resistance.

• 한국동물학회지
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• 제39권3호
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• pp.231-238
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• 1996

여러 종류의 폐암과 췌장암 세포주를 배양하여 DNA를 분리하였다. 분리한 DNA는 PCR(Polymerase Chain Reaction)로 증폭하여 염기 서열화를 시행하여 K-ras와 p53 유전자들의 돌연변이 종류. 빈도 및 가능한 관계에 대하여 조사하였다. 연구한 암세포주 중 약 81%가 종양 유전자 K-ras와 암 억제 유전자 p53 중 적어도 하나의 돌연변이를 가지고 있었으며 두 유전자 각각에 대해서는 암 세포주 중 약 54.5%에서 돌연변이가 나타났다. 발견된 돌연변이의 종류는 1개의 세포주에 발견된 넌센스 돌연변이 이외에는 모두 미스센스 돌연변이가 일어났으며 2개의 세포주에서 일어난 염기 삽입이외에는 모두 염기 치환이 일어났다. 현재까지 p53 코돈 중 ras와 동시에 돌연변이가 일어난다고 보고된 코돈 이외에도 p53 코돈 164-165과 248이 K-ras와 동시에 돌연변이가 발생하였고, p53 유전자의 돌연변이의 위치에 관계없이 K-ras 유전자에서는 exon 1. 코돈 12개에서 돌연변이가 발생하였다.

• 분석과학
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• 제10권5호
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• pp.378-385
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• 1997

본 실험은 human glutathione S-transferase P1-1의 tyrosine 7 잔기에 대한 변이체를 작성하고, 기질특이성과 저해제의 효과를 조사하여, 이 잔기의 기능을 분석한 것이다. 1,2-dichloro-4-nitrobenzene과 1,2-epoxy-3-(p-nitrophenoxy)propane에 대한 GSH 포합반응에 대한 활성은 야생형에 비해 변이체 Y7F에서는 3~5%로 크게 저하하였으며, 효소에 결합한 GSH의 thiol기의 pKa는 2.4 pK 높았다. 저해제 hematin에 대한 $I^{50}$값은 야생형과 변이체 Y7F에서 비슷하게 나타났으며, 저해제 benastatin A와 S-(2,4-dinitrophenyl) glutathione에 대한 $I^{50}$값들은 다소 감소하였다. 이러한 결과들로부터 tyrosine 7 잔기는 기질의 결합에 관여하기보다 GSH-chloronitrobenzene 유도체와 GSH-epoxide 포함반응에 대한 촉매활성에 중요하다고 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10299-10306
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• 2015

The esophageal squamous cell carcinoma (ESCC) is thought to develop through a multi-stage process. Epigenetic gene silencing constitutes an alternative or complementary mechanism to mutational events in tumorigenesis. Posttranscriptional regulation of human leukocyte antigen class I (HLA-I) and antigen processing machinery (APM) proteins expression may be associated with novel epigenetic modifications in cancer development. In the present study, we determined the expression levels of HLA-I antigen and APM components by immunohistochemistry. Then by a bisulfite-sequencing PCR (BSP) approach, we identified target CpG islands methylated at the gene promoter region of APM family genes in a ESCC cell line (ECa109), and further quantitative analysis of CpG site specific methylation of these genes in cases of Kazakh primary ESCCs with corresponding non-cancerous esophageal tissues using the Sequenom MassARRAY platform. Here we showed that the development of ESCCs was accompanied by partial or total loss of protein expression of HLA-B, TAP2, LMP7, tapasin and ERp57. The results demonstrated that although no statistical significance was found of global target CpG fragment methylation level sof HLA-B, TAP2, tapasin and ERp57 genes between ESCC and corresponding non-cancerous esophageal tissues, there was significant differences in the methylation level of several single sites between the two groups. Of thesse only the global methylation level of LMP7 gene target fragments was statistically higher ($0.0517{\pm}0.0357$) in Kazakh esophageal cancer than in neighboring normal tissues ($0.0380{\pm}0.0214$, p<0.05). Our results suggest that multiple CpG sites, but not methylation of every site leads to down regulation or deletion of gene expression. Only some of them result in genetic transcription, and silencing of HLA-B, ERp57, and LMP7 expression through hypermethylation of the promoters or other mechanisms may contribute to mechanisms of tumor escape from immune surveillance in Kazakh esophageal carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1053-1055
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• 2016

Background: Polycythemia rubra vera (PV), being a primary polycythemia, is caused by neoplastic proliferation of erythroid, megakaryocytic and granulocytic lineages which result in panmyelosis. PV patients have a somatic acquired mutation in the Janus kinase (JAK2) pathway, rendering cell proliferation independent of the normal regulatory mechanisms that regulate erythropoiesis. The rational of this study was to determine the prevalence of the JAK-2 V617F mutation in Pakistani patients with PV. Materials and Methods: In this cross sectional study, 26 patients with PV were enrolled from January 2010 to December 2014. Patients were diagnosed based on WHO criteria for PV. All were screened for G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by an allele specific PCR. Results: The mean age was $53.4{\pm}9.31years$ (range 36-72) and the male to female ratio was 2:1. The frequency of JAK2 V617F positivity in our PV patients was found to be 92.3%. Overall 30.7% of patients were asymptomatic and remaining 69.3% presented with symptomatic disease. The mean hemoglobin was $18.1{\pm}1.9g/dl$ with the mean hematocrit of $55.6{\pm}8.3%$. The mean total leukocyte count was $12.8{\pm}7.1{\times}10^9/l$ and the platelet count was $511{\pm}341.9{\times}10^9/l$. A positive correlation of JAK2 V617F mutation was established with high TLC count (P=0.01). No correlation of JAK2 V617F could be established with age or gender (P>0.05). Conclusions: The JAK2 V617F mutation frequency in our PV patients was similar to those reported internationally. Screening for the mutation in all suspected PV cases could be beneficial in differentiating patients with reactive and clonal erythrocytosis.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1321-1324
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• 2012

Background: DNA polymerase beta ($pol{\beta}$) is a key enzyme in the base excision repair pathway. It is 39kDa protein, with two subunits, one large subunit of 31 kDa having catalytic activity between exon V to exon XIV, and an 8 kDa smaller subunit having single strand DNA binding activity. Exons V to VII have double strand DNA binding activity, whereas exons VIII to XI account for the nucleotidyl transferase activity and exons XII to XIV the dNTP selection activity. Aim: To examine the association between $pol{\beta}$ polymorphisms and the risk of ovarian cancer, the present case control study was performed using 152 cancer samples and non-metastatic normal samples from the same patients. In this study, mutational analysis of $pol{\beta}$ genomic DNA was undertaken using primers from exons IX to XIV - the portion having catalytic activity. Results: We detected alteration in DNA polymerase beta by SSCP. Two specific heterozygous point mutations of $pol{\beta}$ were identified in Exon 9:486, A->C (polymorphism 1; 11.18%) and in Exon 11:676, A->C (polymorphism 2; 9.86%). The correlation study involving polymorphism 1 and 4 types of tissue showed a significant correlation between mucinous type with a Pearson correlation value of 4.03 (p=0.04). The association among polymorphism 2 with serous type and stage IV together have shown Pearson ${\chi}^2$ value of 3.28 with likelihood ratio of 4.4 (p=0.07) with OR =2.08 (0.3-14.55). This indicates that there is a tendency of correlation among polymorphism 2, serous type and stage IV, indicating a risk factor for ovarian cancer. Conclusion: Hence, the results indicate that there is a tendency for $pol{\beta}$ polymorphisms being a risk factor for ovarian carcinogenesis in India.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6803-6806
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• 2013

Background: Interferon regulatory factor 6 (IRF6) is a transcription factor with distinct and conserved DNA and protein binding domains. Mutations within the protein binding domain have been significantly observed in subjects with orofacial cleft relative to healthy controls. In addition, recent studies have identified loss of expression of IRF6 due to promoter hypermethylation in cutaneous squamous cell carcinomas. Since mutational events occurring within the conserved domains are likely to affect the function of a protein, we investigated whether regions within the IRF6 gene that encodes for the conserved protein binding domain carried mutations in oral squamous cell carcinoma (OSCC). Materials and Methods: Total chromosomal DNA extracted from 32 post surgical OSCC tissue samples were amplified using intronic primers flanking the exon 7 of IRF6 gene, which encodes for the major region of protein binding domain. The PCR amplicons from all the samples were subsequently resolved in a 1.2% agarose gel, purified and subjected to direct sequencing to screen for mutations. Results: Sequencing analysis resulted in the identification of a mutation within exon 7 of IRF6 that occurred in heterozygous condition in 9% (3/32) of OSCC samples. The wild type codon TTC at position 252 coding for phenylalanine was found to be mutated to TAC that coded for tyrosine (F252Y). Conclusions: The present study identified for the first time a novel mutation within the conserved protein binding domain of IRF6 gene in tissue samples of subjects with OSCC.