• Title/Summary/Keyword: cytogenetic effect

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No benefit of hypomethylating agents compared to supportive care for higher risk myelodysplastic syndrome

  • Sohn, Sang Kyun;Moon, Joon Ho;Lee, In Hee;Ahn, Jae Sook;Kim, Hyeoung Joon;Chung, Joo Seop;Shin, Ho Jin;Park, Sung Woo;Lee, Won Sik;Lee, Sang Min;Kim, Hawk;Lee, Ho Sup;Kim, Yang Soo;Cho, Yoon Young;Bae, Sung Hwa;Lee, Ji Hyun;Kim, Sung Hyun;Song, Ik Chan;Kwon, Ji Hyun;Lee, Yoo Jin
    • The Korean journal of internal medicine
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    • v.33 no.6
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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.

Monosomal Karyotypes among 1147 Chinese Patients with Acute Myeloid Leukemia: Prevalence, Features and Prognostic Impact

  • Yang, Xiao-Fei;Sun, Ai-Ning;Yin, Jia;Cai, Cheng-Sen;Tian, Xiao-Peng;Qian, Jun;Chen, Su-Ning;Wu, De-Pei
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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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.

Increased Micronucleus Frequency in Peripheral Blood Lymphocytes Contributes to Cancer Risk in the Methyl Isocyanate-Affected Population of Bhopal

  • Senthilkumar, Chinnu Sugavanam;Akhter, Sameena;Malla, Tahir Mohiuddin;Sah, Nand Kishore;Ganesh, Narayanan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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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.

Effect of Mitogens, Supplement of β-mercaptoethanol and Fetal Bovine Serum Supplementation in Whole Blood Culture Medium for Bovine Chromosome Analysis

  • Takagi, M.;Tsuno, M.;Ohtani, M.;Acosta, T.J.;Miyamoto, A.;Miyazawa, K.;Sato, K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.15 no.5
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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.

Cytogenetic and Medical Examination Report of Accidental Exposure of Nuclear Power Plant Worker using Multiple Assays (원자력 발전소 피폭자 건강영향평가 사례보고)

  • Lee, Jung-Eun;Yang, Kwang-Hee;Jang, Yun-Kun;Jeong, Mee-Seon;Kim, Chong-Soon;Jin, Young-Woo
    • Journal of Radiation Protection and Research
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    • v.32 no.3
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    • pp.111-115
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    • 2007
  • A deuterium oxide leakage accident occurred on October 4, 1999, at nuclear power plant in Korea. The concentration of tritium in air increased and 22 workers were exposed by tritium at that time. It is well known that tritium causes internal exposure. Therefore, we examined complete blood cell count, physical and biological dosimetry fur 13 workers among whole 22 workers to check the health effect and to evaluate the dose estimation of tritium exposure. The leukocyte count test, one of general blood test, was normal. The estimated doses were 0 - 4.44 mSv by physical dosimetry and 0-37 mGy by biological dosimetry. This dose does not exceed radiation dose limit, and the clinical symptoms of the exposed workers were not shown. The consistency between clinical sign and estimated dose means that physical and biological dosimetry were very useful especially in accident evaluation.

The Study of X Chromosome Inactivation Mechanism in Klinefelter's Syndrome by cDNA Microarray Experiment

  • Jeong, Yu-Mi;Chung, In-Hyuk;Park, Jung Hoon;Lee, Sook-Hwan;Chung, Tae-Gyu;Kim, Yong Sung;Kim, Nam-Soon;Yoo, Hyang-Sook;Lee, Suman
    • Genomics & Informatics
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    • v.2 no.1
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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.

Multiple Exposures and Coexposures to Occupational Hazards Among Agricultural Workers: A Systematic Review of Observational Studies

  • Nguyen, Thi-Hai-Yen;Bertin, Melanie;Bodin, Julie;Fouquet, Natacha;Bonvallot, Nathalie;Roquelaure, Yves
    • Safety and Health at Work
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    • v.9 no.3
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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.

Selenium Effect on the Frequency of SCEs Induced by Heavy Metals in Human Lymphocytes (Selenium이 mercury, cadmium 및 chromium에 의한 자매염색분체교환(姉妹染色分體交換)의 빈도(頻度)에 미치는 영향(影響))

  • Koh, Dai-Ha;Ki, No-Suk
    • Journal of Preventive Medicine and Public Health
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    • v.23 no.1 s.29
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    • pp.1-10
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    • 1990
  • The protective effect of sodium selenite($Na_2SeO_3$) against the cytogenetic toxicity of heavy metals was investigated on human whole-blood cultures in relation to induction of sister chromatid exchange (SCE) in secondary metaphase chromosome. Methylmercury chloride($CH_3HgCl$), cadmium chloride($CdCl_2$), potassium dichromate($K_2Cr_2O_7$), and sodium selenite caused to the typically dose-dependent increase in sister chromatid exchanges (SCEs) by the concentrations ranging from $0.3{\mu}M\;to\;10{mu}M$. However, the inductions of sister chromatid exchanges by methylmercury chloride or cadmium chloride were inhibited by the simultaneous addition of sodium selenite $1.2{mu}M$. The frequencies of SCE were decreased to the level of control in the molar ratios as 2:1, 1:1, 1:2, and 1:4 of selenium selenite vs. methylmercury chloride, and as 1:1 and 1:2 of selenium selenite vs. cadmium chloride, while the frequencies of SCE induced by potassium dichromate were not changed by the addition of sodium selenite in culture condition. Mitotic indices were decreased in the higher concentrations of chemicals and not significantly changed by the simultaneous addition of sodium selenite to the culture condition containing each chemicals.

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Improved Early Survival in Backcrosses of Male Mud Loach (Misgurnus mizolepis)$\times$Cyprinid Loach (M. anguillicaudatus) Hybrids to Femal Cyprinid Loach (미꾸리, Misgurnus anguillicaudatus의 생존율 향상을 위한 역교배체 생산)

  • 박인석;김봉석;임재현;박효민;남윤권;정창화;김동수
    • Journal of Aquaculture
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    • v.10 no.3
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    • pp.363-371
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    • 1997
  • Backcross hybridization between female cyprinid loach(Misgurnus anguillicaudatus) any male mud loach (M. mizolepis)$\times$cyjprinid loach hybrid were made, and its effect on early survival, cytogenetic traits, and gonad development were examined. Mean fertilization rate and hatching success of backcross hybrids were similar to those found in the maternal species, the cyprinid loach. However, the backcross hybrids revealed significantly improved early survival up to yolk sac absorption (86.0%) compared to cyprinid loach (0%) under low culture temperature ($15^{\circ}C$). the erythrocytic size and DNA content of backcross hybrids were nearly intermediate to those of the parents. Karyological analysis of backcross hybrids displayed two kinds of modal chromosome number of 2n=48 or 2n=49. Growth of backcross hybrids over 6 months after hatching was proven to be intermediate between their parental species. Although backcross hybrids had intermediate values between those of thier parents in most morphometric traits, overall external morphology of backcross hybrids was morer simlar to cyprinid loach than mud loach$\times$cyprinid loach hybrid. Histological examination of gonads at 2 and 4 months of age revealed that no female was obseved in backcross hybrid groups, suggesting the possibility of production of monosex male population.

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Pericentric Inversion of the X Chromosome in a Male with Azoospermia and in the Family of a Pregnant Female Carrier (무정자증을 보이는 남성과 정상 생식력을 가진 여성의 가계에서 관찰된 X 염색체의 Pericentric Inversion)

  • Lee, Bom-Yi;Ryu, Hyun-Mee;Lee, Moon-Hee;Park, Ju-Yeon;Kim, Jin-Woo;Lee, Joong-Shik;Kim, Hye-Ok;Kim, Min-Hyung;Park, So-Yeon
    • Journal of Genetic Medicine
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    • v.5 no.2
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    • pp.139-144
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    • 2008
  • We report on two cases of pericentric inversion of X chromosome. The cases were found in a 40-year-old man with azoospermia and in a family of a 38-year-old pregnant woman. The first case with 46,Y,inv(X)(p22.1q27) had concentrations of LH, prolactin, estradiol, and testosterone that were within normal ranges; however, FSH levels were elevated. Testis biopsy revealed maturation arrest at the primary and secondary spermatocytes without spermatozoa. There were no microdeletions in the 6 loci of chromosome Y. For the second case, the cytogenetic study of thepregnant woman referring for advanced maternal age and a family history of inversion X chromosome was 46,X,inv(X)(p22.11q27.2). The karyotype of her fetus was 46,X,inv(X)(p22.1q27). Among other family members, the karyotypes of an older sister in pregnancy and her fetus were 46,X,inv(X)(p22.11q27.2), and 46,Y,?inv(X), respectively. The proband's father was 46,Y,inv(X)(p22.11q27.2). All carriers in the family discussed above were fertile and phenotypically normal. In addition, the ratio of inactivation of inv(X) by RBG-banding was discordant between the two sisters, with the older sister having only 4.1% of cells carrying inactivated inv(X) while the proband had a 69.5% incidence of late replicating inv(X). Therefore, we suggest that the cause of azoospermia in the first case might be related to inversion X chromosome with positional effect. Also, the family of the second case showing normal phenotype of the balanced inv(X) might be not affected any positional effect of genes.

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