• The Korean journal of internal medicine
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• 제33권6호
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• pp.1194-1202
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• 2018

Background/Aims: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. Methods: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. Results: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were $53.1%{\pm}10.7%$ for allo-HCT with HMA, $75%{\pm}21.7%$ for allo-HCT without HMA, $17.3%{\pm}3.6%$ for HMA, and $20.8%{\pm}6.9%$ for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ${\geq}65years$ (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. Conclusions: For the H/VH risk group, very poor cytogenetic risk, age ${\geq}65years$, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5421-5426
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• 2012

A monosomal karyotype (MK), defined as ${\geq}2$ autosomal monosomies or a single monosomy in the presence of additional structural abnormalities, was recently identified as an independent prognostic factor conveying an extremely poor prognosis in patients with acute myeloid leukemia (AML). In the present study, after excluding patients with t(15;17), t(8;21), inv(16) and normal karyotypes, 324 AML patients with cytogenetic abnormalities were the main subject of analysis. The incidences of MK were 13% in patients aged 15 to 60 years and 18% in those between 15 and 88 years old. MK was much more prevalent among elderly patients (p < 0.001) and was significantly associated with the presence of -7, -5, del(5q), abn12p, abn17p, -18 or 18q-, -20 or 20q- and CK (for all p < 0.001 except for abn12p p=0.009), and +8 or +8q was less frequent in MK+ AML(p=0.007). No correlation was noted between monosomal karyotype and FAB subtype (p > 0.05); MK remained significantly associated with worse overall survival among patients with complex karyotype (p=0.032); A single autosomal monosomy contributed an additional negative effect in OS of patients with structural cytogenetic abnormalities (P=0.008). This report presents the prevalence, feature and prognostic impact of MK among a large series of Chinese AML patients from a single center for the first time.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4409-4419
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• 2015

The Bhopal gas tragedy involving methyl isocyanate (MIC) is one of the most horrific industrial accidents in recent decades. We investigated the genotoxic effects of MIC in long-term survivors and their offspring born after the 1984 occurrence. There are a few cytogenetic reports showing genetic damage in the MIC-exposed survivors, but there is no information about the associated cancer risk. The same is true about offspring. For the first time, we here assessed the micronucleus (MN) frequency using cytokinesis-blocked micronucleus (CBMN) assay to predict cancer risk in the MIC-affected population of Bhopal. A total of 92 healthy volunteers (46 MIC-affected and 46 controls) from Bhopal and various regions of India were studied taking gender and age into consideration. Binucleated lymphocytes with micronuclei (BNMN), total number of micronuclei in lymphocytes (MNL), and nuclear division index (NDI) frequencies and their relationship to age, gender and several lifestyle variabilities (smoking, alcohol consumption and tobacco-chewing) were investigated. Our observations showed relatively higher BNMN and MNL (P<0.05) in the MIC-affected than in the controls. Exposed females (EF) exhibited significantly higher BNMN and MNL (P<0.01) than their unexposed counterparts. Similarly, female offspring of the exposed (FOE) also suffered higher BNMN and MNL (P<0.05) than in controls. A significant reduction in NDI (P<0.05) was found only in EF. The affected group of non-smokers and non-alcoholics featured a higher frequency of BNMN and MNL than the control group of non-smokers and non-alcoholics (P<0.01). Similarly, the affected group of tobacco chewers showed significantly higher BNMN and MNL (P<0.001) than the non-chewers. Amongst the affected, smoking and alcohol consumption were not associated with statistically significant differences in BNMN, MNL and NDI. Nevertheless, tobacco-chewing had a preponderant effect with respect to MNL. A reasonable correlation between MNL and lifestyle habits (smoking, alcohol consumption and tobacco-chewing) was observed only in the controls. Our results suggest that EF and FOE are more susceptible to cancer development, as compared to EM and MOE. The genotoxic outcome detected in FOE reflects their parental exposure to MIC. Briefly, the observed cytogenetic damage to the MIC-affected could contribute to cancer risk, especially in the EF and FOE.

• Asian-Australasian Journal of Animal Sciences
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• 제15권5호
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• pp.615-621
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• 2002

We investigated the effects of the mitogen supplements of 3 types, pokeweed mitogen (PWM), phytohemagglutinin (PHA) and concanavalin A (ConA), to a whole blood culture system on the number of metaphase spreads obtained in perinatal bovine chromosome analysis. In addition, the supplementation of ${\beta}$-mercaptoethanol (${\beta}$-ME) and FBS was examined in such system. Significant differences (p<0.05) were seen in the number of metaphase spreads with PHA stimulation compared to both PWM and ConA stimulation. When examined the effects of ${\beta}$-ME supplementation, the number of metaphase spreads was significantly (p<0.05) increased at $30{\mu}M$ ${\beta}$-ME compared to control. When evaluated FBS supplementation during PWM stimulation, no significant effect of the supplementation was found. Finally, the effects of the cortisol concentration (10-20, 20-30 and >30 ng/ml) of the blood samples were examined. There was no significant effect of cortisol concentration (p>0.05) among these 3 cortisol concentration groups. The mean percentages of normal metaphase plates (2n=60) from each calf 1) with ${\beta}$-ME, 2) without ${\beta}$-ME and 3) with FBS stimulated with PWM were not significantly different (p>0.05). In conclusion, these findings may be useful in cytogenetic screening programs for not only perinatal calves but also for mature cattle.

• Journal of Radiation Protection and Research
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• 제32권3호
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• pp.111-115
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• 2007

원자력 발전소의 중수누출에 따른 삼중수소 농도증가에 의한 방사선 내부피폭과 이에 대한건강영향평가를 실시하였다. 전체 22명 가운데 13명에 대하여 검사를 실시하였으며, 이들의 내부피폭량은 $0{\sim}4.44\;mSv$ 였다. 일반혈액검사 중 백혈구수치의 변화를 이용하여 평가한 결과에서 결정적 영향에 대한 특이사항은 나타나지 않았으며, 생물학적 선량평가 방법을 이용한 체내피폭량은 $0{\sim}37\;mGy$로 확인되었다. 결론적으로 방사선 피폭은 허용한도를 초과하지 않았으며, 결정적 영향인 임상적 증상이 보이지 않았다. 이와 같이 의학적 징후와 선량평가 추정치와의 일치성은 사고시 특히 물리적 생물학적 선량평가가 유용함을 보여 준다.

• Genomics & Informatics
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• 제2권1호
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• pp.30-35
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• 2004

To investigate the XIST gene expression and its effect in a Klinefelter's patient, we used Klinefelter's syndrome (XXY) patient with azoospermia and also used a normal male (XY) and a normal female (XX) as the control, We were performed cytogenetic analysis, Y chromosomal microdeletion assay (Yq), semi-quantitative RT-PCR, and the Northern blot for Klinefelter's syndrome (KS) patient, a female and a male control, We extracted total RNA from the KS patient, and from the normal cells of the female and male control subjects using the RNA prep kit (Qiagen), cDNA microarray contained 218 human X chromosome-specific genes was fabricated. Each total RNA was reverse transcribed to the first strand cDNA and was labeled with Cy-3 and Cy-5 fluorescein, The microarray was scanned by ScanArray 4000XL system. XIST transcripts were detected from the Klinefelters patient and the female by RT-PCR and Northern blot analysis, but not from the normal male, In the cDNA microarray experiment, we found 24 genes and 14 genes are highly expressed in KS more than the normal male and females, respectively. We concluded that highly expressed genes in KS may be a resulted of the abnormal X inactivation mechanism.

• Safety and Health at Work
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• 제9권3호
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• pp.239-248
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• 2018

Background: Workers may be exposed to various types of occupational hazards at the same time, potentially increasing the risk of adverse health outcomes. The aim of this review was to analyze the effects of multiple occupational exposures and coexposures to chemical, biomechanical, and physical hazards on adverse health outcomes among agricultural workers. Methods: Articles published in English between 1990 and 2015 were identified using five popular databases and two complementary sources. The quality of the included publications was assessed using the methodology developed by the Effective Public Health Practice Project assessment tool for quantitative studies. Results: Fifteen articles were included in the review. Multiple chemical exposures were significantly associated with an increased risk of respiratory diseases, cancer, and DNA and cytogenetic damage. Multiple physical exposures seemed to increase the risk of hearing loss, whereas coexposures to physical and biomechanical hazards were associated with an increased risk of musculoskeletal disorders among agricultural workers. Conclusion: Few studies have explored the impact of multiple occupational exposures on the health of agricultural workers. A very limited number of studies have investigated the effect of coexposures among biomechanical, physical, and chemical hazards on occupational health, which indicates a need for further research in this area.

• Journal of Preventive Medicine and Public Health
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• 제23권1호
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• pp.1-10
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• 1990

셀레늄이 수은, 카드뮴 및 크롬의 세포독성에 미치는 영향을 파악하고자 이들 중금속을 $0.3{mu}M$에서 $10{mu}M$까지 6개 농도로 각각 희석하여 $1.2{mu}M$의 셀레늄과 함께 혈액 배양에 첨가하고, 48시간 경과후 fluorescence-plus-Giemsa 염색에 의해 2차분열 중기의 염색체에서 자매염색분체교환(SCE)현상을 관찰하여, 셀레늄을 첨가하지 않았을 때의 결과와 비교하였다. 셀레늄을 다른 중금속들의 경우와 동일한 농도로 단독 첨가한 경우 SCE빈도는 $5.9{\pm}2.64$회에서 $12.3{\pm}3.99$회의 범위로 변하였고, 수은은 $6.5{\pm}2.70$회에서 $15.7{\pm}2.75$회, 카드뮴은 $6.7{\pm}2.65$회에서 $11.2{\pm}4.13$회, 크롬은 $7.0{\pm}2.58$회에서 $14.9{\pm}6.43$회의 범위로 농도증가에 비례하여 SCE빈도가 상승하였으며, 이때 세포분열지수는 공히 농도증가에 반비례하여 고농도군에서는 현저히 낮았다. 중금속들과 $1.2{mu}M$의 셀레늄을 동시에 첨가시킨 조건에서는 수은의 경우, 셀레늄과 수은의 몰(mol)농도비가 1:1, 1:2, 1:4의 조건에서, 카드뮴의 경우 1:2 및 1:4의 조건에서 SCE빈도의 현저한 감소를 나타냈으나 크롬의 경우는 셀레늄의 첨가와 무관하였으며, 세포분열지수는 전반적으로 셀레늄의 첨가에 별다른 영향을 받지 않았다.

• 한국양식학회지
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• 제10권3호
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• pp.363-371
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• 1997

미꾸리 암컷과 미꾸라지 (Misgurnus mizolepis))$\times$미꾸리(M. anguillicaudatus) 잡종 수컷을 교배시켜 역교배체를 생산하였다. 역교배체의 수정율과 부화율은 친어 수컷으로 사용된 미꾸리와 유사하였다. 더욱이 역교배체는 난황흡수기에 저온에 저항성을 보여 전 실험군이 폐사한 미꾸리군에 비하여 단 14%의 낮은 초기 사망률을 나타내어 뚜렷한 생존율 증가가 관찰되었다. 역교배체의 적혈구 크기와 DNA 함량은 친어 암, 수의 중간을 나타내었고 역교배체는 2n=48 혹은 2n=49인 2가지 종류의 2배체 염색체수를 나타내었다. 부화후부터 6개월 동안 동일 조건에서 성장률을 조사한 결과, 역교배체는 친어 암, 수의 중간 성장을 보여 어류양식시 새로운 양식대상 어종으로의 가능성을 시사하였다. 역교배체는 거의 미꾸리와 체색 및 형태에서 유사하였으나 형질계측결과 친어 암수의 중간을 나타내는 형질 및 몇 개의 새로운 획득형질이 관찰되었다. 역교배체는 부화후 2개월 및 부화후 4개월에서 각기 성비를 조직학적으로 조사한 결과 암컷을 전혀 발견할 수 없어 전 수컷 단성집단 생산의 가능성을 보였다.

• Journal of Genetic Medicine
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• 제5권2호
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• pp.139-144
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• 2008

무정자증을 보이는 40세 남성과 3대에 걸쳐 정상 생식력과 표현형을 보이는 38세 산모의 가계에서 동원체를 포함한 X 염색체의 역위를 경험한 바, 이를 문헌고찰과 함께 보고하고자 한다. 첫 번째 증례의 남성 환자는 정상범위의 LH, prolactin, estradiol, testosterone 혈중농도를 보였으나 FSH는 20 mIU/mL을 보여 정상수치보다 높았다. 조직학적 소견으로는 정소 내 제 1, 제 2 정모세포의 발달이 정지되어 있었지만 Y 염색체의 sY84, sY129, sY134, sY254, sY255, SRY 부위에 대한 미세결실은 없었다. 그 외 특이할 만한 임상적 소견은 보이지 않았다. 환자의 말초혈액으로부터 세포유전학적 검사로 GTL-분염법 판독을 한 결과, 46,Y,inv(X)(p22.1q27)로 나타났다. 두 번째 증례의 산모와 그 태아는 각각 46,X,inv(X)(p22.11q27.2), 46,X,inv(X)(p22.1q27)의 핵형이 관찰되었다. 이 산모의 가계는 본 연구실에서 친언니의 산전진단 시 언니, 언니의 태아, 환자의 아버지가 각각 46,X,inv(X)(p22.11q27.2), 46,Y,?inv(X), 46,Y,inv(X)(p22.11q27.2)의 형태로 inv(X)가 관찰된 기록이 있었고 대상자 모두 inv(X)로 인한 특징적인 임상적 증상은 보이지 않았다. 또한 RBG-분염법을 통해 관찰한 X 염색체의 비활성화는 언니의 inv(X) 비활성화 비율이 4.1%, 환자는 69.5%로 혈액세포 내에서의 X 염색체의 비활성화 비율은 서로 다르게 관찰되었다. 따라서 이 가계의 inv(X)는 특정 유전자의 손상이 없는 균형적 역위이며, X염색체의 역위현상으로 인한 비정상 표현형이나 생식기능의 결함은 관찰되지 않았다. 그러나 증례 1의 남성의 경우 세포유전학적으로 동일한 위치에 절단점을 가졌으나 생식세포의 발달과정의 결함이 관찰되었으며, 절단점 주변에 위치한 중요한 유전인자들의 손상 가능성이 제기되었다.