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1.
Toxicol Lett ; 328: 1-6, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32315709

RESUMO

The genotoxicity of cationic lipopeptide nanoparticles (cLPNPs) was evaluated in vivo and in vitro comet assay and the in vivo chromosome aberrations test. In vitro comet assay, human blood cells were exposed to cLPNPs at the concentration of 2.5, 5, 10, 20, 40 and 100 µg/mL. Significant DNA damage was observed after 1 h exposure, but no effects were detected after 3 h. In vivo, cLPNPs were administered in single or five daily injection doses at 8, 20 and 40 mg/kg of body weight by subcutaneous injection to male mice. The cLPNPs caused DNA damage in the liver, lung and kidney, but not in the spleen. The kidney was more prone to genotoxic effects that persisted from 24 h to 14d after a single injection of cLPNPs. No statistically significant increase in the percentage of cells with chromosomal aberrations above the vehicle control was observed in mice bone marrow after a single or repeated injection of cLPNPs. In summary, cLPNPs shown to be genotoxic both in vivo and in vitro. The results suggest the importance of the use of highly sensitive methods, such as the comet assay, in order to determine the full genotoxic potential of nanoparticles.


Assuntos
Aberrações Cromossômicas/induzido quimicamente , Dano ao DNA , Lipopeptídeos/toxicidade , Nanopartículas/toxicidade , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Relação Dose-Resposta a Droga , Humanos , Injeções Subcutâneas , Rim/efeitos dos fármacos , Rim/patologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/patologia , Lipopeptídeos/química , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Nanopartículas/química
2.
Mutat Res ; 852: 503163, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32265037

RESUMO

Cardiac catheterization procedures are performed on about 20,000 children with congenital heart disease (CHD) annually in China. The procedure, which involves exposure to ionizing radiation, causes DNA damage and may lead to increased cancer risk. We have studied chromosomal aberrations (CA) in peripheral lymphocytes of CHD children. CA frequencies were assessed in an interventional group of 70 children who underwent cardiac catheterization and a control group of 51 children receiving open-heart surgery. Total CA and all chromosome-type aberrations were higher in the exposed children than in the control group. With respect to the type of septal defect, the translocation frequency was higher in patients with ventricular rather than atrial defects. Cardiac catheterization procedures increase CA frequencies and may also increase the risk of cancer.


Assuntos
Cateterismo Cardíaco/efeitos adversos , Aberrações Cromossômicas/efeitos da radiação , Cardiopatias Congênitas/cirurgia , Linfócitos/efeitos da radiação , Radiação Ionizante , Adolescente , Cateterismo Cardíaco/métodos , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Feminino , Cardiopatias Congênitas/patologia , Humanos , Linfócitos/imunologia , Masculino , Duração da Cirurgia , Cultura Primária de Células , Risco
3.
J Korean Med Sci ; 35(14): e82, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32281311

RESUMO

BACKGROUND: This study aimed to investigate the incidence and clinical significance of segmental chromosomal aberrations (SCAs) in Korean patients with neuroblastoma. METHODS: Patients diagnosed with neuroblastoma from 2012 to 2018 were included for retrospective review. Fluorescence in situ hybridization (FISH) was used to analyze four SCAs (MYCN amplification, 1p deletion, 11q deletion, and 17q gain). Clinical characteristics at diagnosis, early tumor response (reduction in primary tumor volume and neuron-specific enolase level after the first three cycles of chemotherapy), and survival rates were compared according to SCAs. RESULTS: Among 173 patients with FISH results, 92 (53.2%) had at least one of the four SCAs, while 25 (14.5%) had two co-aberrations, and eight (4.6%) had three co-aberrations. SCAs detected in our study were MYCN amplification (n = 17, 9.8%), 1p deletion (n = 26, 15.2%), 11q deletion (n = 44, 25.6%), and 17q gain (n = 46, 27.1%). Patients with MYCN amplification showed a better early response but a worse survival than those without (5-year overall survival: 46.2% ± 13.1% vs. 88.6% ± 3.4%). Furthermore, 1p deletion was associated with a better early response but a worse survival; however, it was not an independent factor for survival. We could not find any prognostic significance associated with 11q deletion or 17q gain. CONCLUSION: This is the first study investigating SCAs in Korean neuroblastoma patients. Prognostic significance of SCAs other than MYCN amplification was different from those reported in western countries. Further study with a larger cohort and longer follow-up is needed to confirm our findings.


Assuntos
Aberrações Cromossômicas , Neuroblastoma/genética , Adolescente , Criança , Pré-Escolar , Cromossomos Humanos , Feminino , Amplificação de Genes , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Masculino , República da Coreia , Estudos Retrospectivos , Adulto Jovem
4.
Mutat Res ; 850-851: 503145, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247555

RESUMO

5-Fluorouracil (5-FU) is a widely used antineoplastic drug. In this work, a comprehensive study was performed to detect the extent of chromosomal damage and morphological sperm defects induced by 5-FU in male mice and the possible protective role of the iridoids-rich fraction of Pentas lanceolata leaves (IFPL). Six main groups were examined in micronucleus and chromosomal assays: I- control negative, II- control positive (i.p. treated with single dose of 75 mg/kg 5-FU), III- control plant (orally administrated IFPL, 300 mg/kg, 5 consecutive days), and IV-VI- treated with IFPL (100, 200 and 300 mg/kg, 5 consecutive days) plus 5-FU (i.p. treated at the last day). Samples were taken 24 h post treatment. The study of morphological sperm anomalies, single and repeated treatments were examined and samples were taken after 35 days from the 1st treatment. In bone marrow, 5-FU induced a significant increase in the micro-nucleated polychromatic erythrocytes, chromosome anomalies (CAs) and also cytotoxic effects. A significant percentage of CAs was recorded in spermatocytes after 5-FU treatment reached 22.80 ± 1.32 vs 4.20 ± 0.37 for control (mainly X-Y univalent, 90%). IFPL was recorded to be non-mutagenic in all tests examined. In addition, it alleviated the previous defects in a dose-dependent manner. A significant and dramatic increase in the percentage of morphological sperm defects was recorded after single and repeated treatments with 5-FU reached 13.24 ± 0.24, 30.42 ± 0.32 respectively vs 2.56 ± 0.14 for control. Amorphous head-sperm and sperm with coiled tail were the most pronounced types of abnormalities. Significant protection was detected with the highest tested dose of IFPL. In conclusion: 5-FU demonstrated to be a genotoxic agent. Its genotoxicity in germ cells is serious and may lead to reproductive toxicity, infertility or heritable defects. The results also demonstrated the biosafety of IFPL and its possible protective role in combined treatment with 5-FU.


Assuntos
Iridoides/farmacologia , Extratos Vegetais/farmacologia , Rubiaceae/química , Espermatozoides/efeitos dos fármacos , Animais , Aberrações Cromossômicas/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Iridoides/química , Masculino , Camundongos , Testes de Mutagenicidade , Extratos Vegetais/química , Espermatócitos/efeitos dos fármacos , Espermatócitos/patologia , Espermatozoides/patologia
5.
Mutat Res ; 850-851: 503152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247560

RESUMO

The aim of the present study was to assess the oxidative stress level and chromosomal damage induced by occupational exposure to low dose ionizing radiation (LDIR). Two hundred and eighteen hospital workers occupationally exposed to LDIR were included in this study, along with 118 healthy age- and gender-comparable controls. Occupational dosimetry records were collected over the last year and revealed that the accumulated annual dose for each hospital worker was below the permissible limit of the International Commission on Radiological Protection (ICRP). The individuals' oxidative and antioxidative status were determined by measuring the activities of copper zinc-superoxide dismutase (CuZn-SOD), glutathione peroxidase (GSH-Px), catalase (CAT) enzymes, and the levels of malondialdehyde (MDA) in erythrocytes. The effect of radiation on chromosomal integrity was measured by the frequency of micronuclei (MN) formation using the cytokinesis block technique. Our results showed that the activities of CuZn-SOD and CAT enzymes and MDA levels observed in the hospital workers were higher than those in the controls (p < 0.05). We did not find significant difference in GSH-Px enzyme activity between the two groups (p = 0.247). A higher frequency of MN was found in exposed groups than in the controls [3(1-5) ‰ versus 2(0.75-4) ‰; p<0.001]. The difference was significant for males (p = 0.012), but not females (p = 0.14). Multiple linear regression analysis showed differences in the oxidant activities and MN frequency between hospital workers and controls adjusted for age, gender, smoking status and drinking status. Correlation analysis indicated that the frequency of MN was positively associated with MDA levels (p < 0.05). Altogether, these results support the detrimental effects of chronic low dose radiation in humans, which involves the induction of oxidative stress and chromosomal damage.


Assuntos
Antioxidantes/metabolismo , Aberrações Cromossômicas/efeitos da radiação , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo/efeitos da radiação , Adulto , Antioxidantes/efeitos da radiação , Catalase/sangue , Feminino , Glutationa Peroxidase/sangue , Hospitais , Humanos , Masculino , Malondialdeído/sangue , Registros Médicos , Pessoa de Meia-Idade , Doses de Radiação , Radiação Ionizante , Radiometria , Superóxido Dismutase-1/sangue
6.
Medicine (Baltimore) ; 99(14): e19730, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243411

RESUMO

RATIONALE: Co-occurrence of cytogenetic and molecular abnormalities is frequently seen in patients with acute myeloid leukemia (AML). The clinical outcome and genetic abnormalities of AML may vary; therefore, genetic investigation must be complex, using several techniques, to have an appropriate characterization of the AML genome and its clinical impact. The available molecular markers can predict prognosis only partially. Acute promyelocytic leukemia subtype M3 (AML M3) is a subtype of AML characterized by the presence of promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) genes fusion. Targeted treatment with all-trans-retinoic acid (ATRA) and ATRA combined with arsenic trioxide significantly improved the survival of AML M3 patients. Unknown prognostic factors could contribute to the early death of these patients. PATIENT CONCERNS: We present the case of a young female (20 years old) patient, who presented at the emergency department 5 months after giving birth to her first child, complaining of asthenia, fatigue, general musculoskeletal pain, and fever (38°C), symptoms having been present for the previous 6 days. The patient denied any chronic diseases in her medical and family history. DIAGNOSIS: Laboratory analysis revealed severe pancytopenia. Cytogenetic and molecular analyzes revealed chromosomal abnormalities (trisomy 8), PML-RARA gene fusion, and fms-like tyrosine kinase 3 (FLT3) gene mutation. The immunophenotypic analysis was also suggestive for AML M3 according to the FAB classification. INTERVENTIONS: Specific treatment was initiated for AML M3 and for secondary conditions. Molecular and cytogenetic analyzes were performed to have a more detailed characterization of the patient's genome. OUTCOME: Seventy-two hours after admission, she developed psychomotor agitation, confusion, coma, and convulsion. Subsequent deterioration and early death were caused by intracerebral hemorrhage with multiple localization and diffuse cerebral edema. LESSONS: The presence of FLT3 internal tandem duplication (ITD) mutation may explain the rapid and progressive degradation of this AML M3 case and it may be used as a prognostic marker even when co-occuring with other markers such as PML-RARA gene fusion and trisomy 8. We consider that FLT3 ITD mutation analysis in young patients with AML should be performed as soon as possible. New strategies for patients' education, AML (or cancers in general) prevention, and treatment are needed.


Assuntos
Fusão Gênica/genética , Leucemia Mieloide Aguda/genética , Proteína da Leucemia Promielocítica/genética , Receptor alfa de Ácido Retinoico/genética , Trissomia/genética , Tirosina Quinase 3 Semelhante a fms/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 8/genética , Evolução Fatal , Feminino , Humanos , Mutação , Sequências de Repetição em Tandem , Adulto Jovem
7.
Cancer Treat Rev ; 86: 102013, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32278233

RESUMO

Retroperitoneal liposarcomas are rare tumours that carry a poorer prognosis than their extremity counterparts. Within their subtypes - well differentiated (WDL), dedifferentiated (DDL), myxoid (MLS) and pleomorphic (PLS) - they exhibit a diverse genomic landscape. With recent advances in next generation sequencing, the number of studies exploring this have greatly increased. The recent literature has deepened our understanding of the hallmark MDM2/CDK4 amplification in WDL/DDL and addressed concerns about toxicity and resistance when targeting this. The FUS-DDIT3 fusion gene remains the primary focus of interest in MLS with additional potential targets described. Whole genome sequencing has driven identification of novel genes and pathways implicated in WDL/DDL outside of the classic 12q13-15 amplicon. Due to their rarity; anatomical location and histologic subtype are infrequently mentioned when reporting the results of these studies. Reports can include non-adipogenic or extremity tumours, making it difficult to draw specific retroperitoneal conclusions. This narrative review aims to provide a summary of retroperitoneal liposarcoma genomics and the implications for therapeutic targeting.


Assuntos
Lipossarcoma/genética , Neoplasias Retroperitoneais/genética , Animais , Antineoplásicos Alquilantes/uso terapêutico , Aberrações Cromossômicas , Genômica/métodos , Humanos , Lipossarcoma/tratamento farmacológico , Lipossarcoma/metabolismo , Proteínas de Fusão Oncogênica/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/metabolismo , Trabectedina/uso terapêutico
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(2): 470-475, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32319381

RESUMO

OBJECTIVE: To explore the value of CpG-oligonucleotide(CpG-ODN) immunostimulatory method in chromosome culture of chronic lymphocytic leukemia (CLL) cells and to compare the differences between related studies at home and abroad, so as to improve the success rate of CLL karyotype culture and the detection rate of abnormal karyo-types. METHODS: Bone marrow samples from 82 CLL patients were collected and cultured with phytohemagglutinin (PHA), CpG-oligonucleotide plus interleukin-2 (CpG-ODN DSP30+IL-2) for 72 hours. Chromosomes were prepared and analyzed by conventional cytogenetics (CC). Meanwhile, D13S25, Rb1, ATM, p53 and CSP12 probes were used for interphase fluorescence in situ hybridization (iFISH) test. The differences of chromosome culture and iFISH test results between two cell stimulants were compared. RESULTS: The success rate of karyotype culture in PHA and CpG-ODN DSP30+IL-2 immunostimuli (analyzable mitotic t >20) was 90.2% (74 cases), 68.3% (56 cases) respectively, and the detection rate of abnormal karyotype was 13.5% (10 cases) and 46.4% (26 cases), respectively. The success rate of karyotype culture in PHA group was significantly higher than that in CpG-ODN DSP30+IL-2 group (P=0.01). The detection rate of abnormal karyotypes in CpG-ODN DSP30+IL-2 group was significantly higher than that in PHA group, and the difference was statistically significant (P=0.003). The detection rate of abnormal karyotypes in iFISH group was 74.4% (61 cases), which was significantly higher than that in CpG-ODN DSP30+IL-2 group (P=0.000). iFISH detection could verify the abnormalities detected by CC analysis. CONCLUSION: Application of CpG-ODN DSP30+IL-2 immunostimulation method in culture of CLL cells can enhance the detection rate of abnormal karyotypes, especially the detection of various translocations suggesting poor prognosis.


Assuntos
Leucemia Linfocítica Crônica de Células B , Aberrações Cromossômicas , Humanos , Imunização , Hibridização in Situ Fluorescente , Oligodesoxirribonucleotídeos
9.
Asian Pac J Cancer Prev ; 21(3): 639-645, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32212788

RESUMO

OBJECTIVE: Chromosome detection is important in the diagnosis and prognosis of Myelodysplastic syndrome (MDS) patients. About 50% of MDS patients have chromosomal abnormalities. Moreover, chromosome 5 and 7 are common genetic abnormalities in MDS patients and use to identify prognosis risk group and the proper treatment in MDS patients. The objective of this study was to evaluate chromosomal abnormalities and clinical features of MDS patients in upper northern Thailand. METHODS: Fifty bone marrow (BM) specimens were examined by conventional cytogenetic (CC) technique and fluorescence in situ hybridization (FISH) technique for detected chromosome 5 and 7 abnormalities. The clinical features were comparison between MDS patients with chromosomal abnormalities and those with normal karyotype. RESULTS: Chromosomal abnormalities were detected in 8/50 MDS patients by CC and 17/50 cases by FISH technique. When the CC and FISH techniques were combined, chromosomal abnormalities increased to 21/50 cases.  Abnormalities of isolated chromosome 5 were found in 13 cases and were associated with lower level of percentage blast of BM (p = 0.003) and higher level of hemoglobin (p = 0.019). Moreover, abnormalities of chromosome 7 were found in 3 cases, 1 case of isolated del(7q) and 2 cases of -7 and del(7q) with complex abnormalities. These three cases were associated with higher level of percentage blast of BM (p = 0.010). CONCLUSION: This study showed the frequency and pattern of chromosomal abnormalities of MDS patients in upper northern Thailand were different from other populations. MDS with isolated chromosome 5 abnormalities had clinical characteristics corresponding with patients in good prognosis risk group. However, MDS patients with chromosome 7 and complex abnormalities showed higher percentage blast of BM which high risk to progression to acute myeloid leukemia (AML). Combined CC and FISH techniques detect chromosomal abnormalities with greater frequency than when either technique is used alone.
.


Assuntos
Aberrações Cromossômicas , Síndromes Mielodisplásicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 5 , Cromossomos Humanos Par 7 , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Pessoa de Meia-Idade , Tailândia
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 389-391, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219819

RESUMO

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the analysis of 824 samples from miscarriage or stillbirth. METHODS: Copy number variations (CNVs) in the abortic chorionic villi or stillbirth tissues were detected by CMA. RESULTS: All specimens were successfully analyzed, among which 381 (46.2%) were diagnosed with chromosomal abnormalities, which included 312 (81.9%) numerical abnormalities, 66 (17.3%) structural abnormalities and 3 (0.8%) uniparental disomies. Among numerical chromosomal abnormalities, aneuploidies was most common (92.0%), with trisomy 16 and 45,X accounting for 41 (13.1%) and 63 (20.2%) of the cases, respectively. Among the 66 structural chromosomal aberrations, there were 26 (39.4%) CNVs duplications, 20 (30.3%) CNVs deletions, and 20 (30.3%) CNVs duplication and deletions. 33 CNVs were predicted as have a high chance to lead to a disease. CONCLUSION: CMA is a reliable, robust, and high-resolution method for the analysis of miscarriage or stillbirth samples. Numerical aberrations, in particular chromosomal aneuploides, are the main cause for spontaneous abortions and stillbirths.


Assuntos
Aborto Espontâneo/genética , Aberrações Cromossômicas , Transtornos Cromossômicos , Análise em Microsséries , Natimorto/genética , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Variações do Número de Cópias de DNA , Feminino , Humanos , Gravidez
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 392-396, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219820

RESUMO

OBJECTIVE: To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) for prenatal diagnosis. METHODS: G-banding karyotyping and CMA were simultaneously performed on 546 women who were subjected to amniocentesis during middle pregnancy. RESULTS: In total 82 cases were detected with chromosomal abnormalities. The two methods were consistent in 43 cases, which included 14 trisomy 21, 6 trisomy 18, 1 trisomy 13, 14 sex chromosomal aneuploidies, 4 chromosomal deletions, 3 chromosomal duplications and 1 sex chromosomal mosaicism. Fifteen fetuses with chromosomal abnormalities detected by CMA were missed by karyotyping analysis, which included 9 microdeletions and 6 microduplications. Sixteen fetuses with chromosomal abnormalities detected by karyotyping analysis were missed by CMA, which included 15 chromosomal translocations and 1 sex chromosomal mosaicism. In 7 cases, the results of karyotyping analysis and CMA were inconsistent. One supernumerary marker chromosome detected by karyotyping analysis was verified by CMA as 9p13.1p21.1 duplication. CONCLUSION: Combined chromosomal karyotyping and CMA can significantly improve the detection rate for chromosomal abnormalities, which has a great value for prenatal diagnosis.


Assuntos
Transtornos Cromossômicos , Cariotipagem , Análise em Microsséries , Diagnóstico Pré-Natal , Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Feminino , Humanos , Gravidez
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 405-409, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219823

RESUMO

OBJECTIVE: To carry out genetic testing for 3 fetuses with abnormal prenatal screening. METHODS: Fetal ultrasound, karyotype analysis, single nucleotide polymorphism (SNP) array and fluorescence in situ hybridization were performed. RESULTS: Abnormalities of chromosome 22 were found with all 3 fetuses. Fetus 1 harbored a 7.1 Mb deletion in 22q13.2q13.33 region, which involved 54 OMIM genes including SHANK3 and FBLN1. Fetus 2 had a mosaicism karyotype, with 12% of cells harboring a 6.6 Mb deletion in 22q13.31q13.33, covering 48 OMIM genes such as SHANK3 and PPARA, and 5% of cells harboring a 26.1 Mb duplication in 22q11.1q13.2 involving 285 OMIM genes. Fetus 3 carried a tandem duplication of 1.7 Mb in 22q11.1q11.21, which involved 10 OMIM genes including CECR1, CECR2 and ATP6V1E1. No abnormality was found in the three couples by chromosomal karyotyping and SNP array analysis. CONCLUSION: The severity of diseases caused by chromosome 22 abnormalities not only depends on the range of the deletion or duplication, but is also closely related to chromosome structure, gene dose and genetic environment. Combined ultrasonography and various genetic testing techniques in prenatal diagnosis can greatly increase the detection rate of genetic diseases with substantial phenotypic variation.


Assuntos
Transtornos Cromossômicos/diagnóstico , Cromossomos Humanos Par 22/genética , Testes Genéticos , Cariotipagem , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal , Aberrações Cromossômicas , Deleção Cromossômica , Transtornos Cromossômicos/genética , Feminino , Feto , Humanos , Hibridização in Situ Fluorescente , Gravidez , Fatores de Transcrição
13.
Am J Hum Genet ; 106(4): 525-534, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32220293

RESUMO

Despite next-generation sequencing, which now allows for the accurate detection of segmental aneuploidies from in vitro fertilization embryo biopsies, the origin and characteristics of these aneuploidies are still relatively unknown. Using a multifocal biopsy approach (four trophectoderms [TEs] and one inner cell mass [ICM] analyzed per blastocyst; n = 390), we determine the origin of the aneuploidy and the diagnostic predictive value of segmental aneuploidy detection in TE biopsies toward the ICM's chromosomal constitution. Contrary to the prevalent meiotic origin of whole-chromosome aneuploidies, we show that sub-chromosomal abnormalities in human blastocysts arise from mitotic errors in around 70% of cases. As a consequence, the positive-predictive value toward ICM configuration was significantly lower for segmental as compared to whole-chromosome aneuploidies (70.8% versus 97.18%, respectively). In order to enhance the clinical utility of reporting segmental findings in clinical TE biopsies, we have developed and clinically verified a risk stratification model based on a second TE biopsy confirmation and segmental length; this model can significantly improve the prediction of aneuploidy risk in the ICM in over 86% of clinical cases enrolled. In conclusion, we provide evidence of the predominant mitotic origin of segmental aneuploidies in preimplantation embryos and develop a risk stratification model that can help post-test genetic counseling and that facilitates the decision-making process on clinical utilization of these embryos.


Assuntos
Blastocisto/fisiologia , Embrião de Mamíferos/fisiologia , Desenvolvimento Embrionário/genética , Aneuploidia , Aberrações Cromossômicas , Cromossomos/genética , Hibridização Genômica Comparativa/métodos , Feminino , Fertilização In Vitro/métodos , Humanos , Incidência , Gravidez , Diagnóstico Pré-Implantação/métodos
15.
Zhonghua Xue Ye Xue Za Zhi ; 41(2): 143-148, 2020 Feb 14.
Artigo em Chinês | MEDLINE | ID: mdl-32135632

RESUMO

Objective: To study the value of unmethylated cytosine guanine dinucleotide oligodeoxynucleotide (DSP30) and IL-2 in the conventional cytogenetic (CA) detection of the chromosomal aberrations in chronic lymphocytic leukemia (CLL) . Methods: Bone marrow or peripheral blood cells of CLL patients were cultured with DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Fluorescence in situ hybridization (FISH) was performed in 85 patients. CA results were compared with data obtained by FISH. Results: Among 89 CLL patients, the success rate of chromosome analysis was 94.38% (84/89) . Clonal aberrations were detected in 51 patients (51/84, 60.71%) . Of them, 27 (27/51, 52.94%) were complex karyotype. Among 85 CLL patients tested by FISH, chromosomal abnormalities were detected in 74 (74/85, 87.06%) patients, of which 2 (2/74) patients were complex karyotypes, accounting for 2.70%. Of the 85 CLL patients examined by FISH, 50 had abnormal karyotype analysis, 30 had normal karyotype, 5 failed to have chromosome analysis. Among them, 25 cases showed clonal aberrations by FISH assay but normal by CA, and 4 cases were normal by FISH but displayed aberrations in chromosome analysis, and totally 78 (91.76%) cases with abnormality detected by the combination of the two methods. The frequency of 13q- abnormality detected by FISH was significantly higher than that by CA analysis (69.41%vs 16.67%, P<0.001) , while the frequency of 11q-,+12 and 17p- detected by two methods showed no significant difference (P>0.05) . The detection rate of complex abnormalities in conventional karyotype analysis was higher than that in FISH (50.98%vs 2.70%) . In addition, 11 low-risk and 9 intermediate-risk patients according to FISH results showed complex karyotype by cytogenetics, and were classified into high-risk cytogenetic subgroup. Conclusion: DSP30 and IL-2 are effective in improving the detection rate of CA in CLL patients (60.71%) and CA is more effective to detect complex karyotype. However, FISH had a higher overall abnormality detection rate (87.06%) than CA, especially for 13q-. The combination of CA and FISH not only enhanced the detection rate of clonal aberrations to 91.76%, but also provided more precise prognosis stratification for CLL patients, thus to provide more information for clinical implication.


Assuntos
Leucemia Linfocítica Crônica de Células B , Aberrações Cromossômicas , Citogenética , Humanos , Hibridização in Situ Fluorescente , Interleucina-2
16.
PLoS Genet ; 16(3): e1008615, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32130223

RESUMO

The relative linear order of most genes on bacterial chromosomes is not conserved over evolutionary timescales. One explanation is that selection is weak, allowing recombination to randomize gene order by genetic drift. However, most chromosomal rearrangements are deleterious to fitness. In contrast, we propose the hypothesis that rearrangements in gene order are more likely the result of selection during niche adaptation (SNAP). Partial chromosomal duplications occur very frequently by recombination between direct repeat sequences. Duplicated regions may contain tens to hundreds of genes and segregate quickly unless maintained by selection. Bacteria exposed to non-lethal selections (for example, a requirement to grow on a poor nutrient) can adapt by maintaining a duplication that includes a gene that improves relative fitness. Further improvements in fitness result from the loss or inactivation of non-selected genes within each copy of the duplication. When genes that are essential in single copy are lost from different copies of the duplication, segregation is prevented even if the original selection is lifted. Functional gene loss continues until a new genetic equilibrium is reached. The outcome is a rearranged gene order. Mathematical modelling shows that this process of positive selection to adapt to a new niche can rapidly drive rearrangements in gene order to fixation. Signature features (duplication formation and divergence) of the SNAP model were identified in natural isolates from multiple species showing that the initial two steps in the SNAP process can occur with a remarkably high frequency. Further bioinformatic and experimental analyses are required to test if and to which extend the SNAP process acts on bacterial genomes.


Assuntos
Aclimatação/genética , Cromossomos Bacterianos/genética , Duplicação Gênica/genética , Rearranjo Gênico/genética , Seleção Genética/genética , Aberrações Cromossômicas , Evolução Molecular , Frequência do Gene/genética , Ordem dos Genes/genética , Genoma Bacteriano/genética , Modelos Teóricos , Filogenia
17.
Chemosphere ; 249: 126193, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32086064

RESUMO

Propanil can produce methemoglobinemia, hemolytic anemia, hepatotoxicity, metabolic disorder and nephrotoxicity. It also has a genotoxic effect, although it is not listed as a carcinogen and it continues to be applied excessively throughout the world. Consequently, in this study the cytogenotoxic effect of propanil was evaluated, using apical root cells of Allium cepa and Lens culinaris. In which, L. culinaris seeds and A. cepa bulbs were subjected to 6 treatments with propanil (2, 4, 6, 8, 10 and 12 mg L-1) and to distilled water as control treatment. Subsequently, the root growth was measured every 24 h for 3 days. Next, the mitotic index and cellular anomalies were determined. Whereby, decreased root development was observed in all treatments. Likewise, greater inhibition of mitosis was evidenced in L. culinaris compared to A. cepa. In addition, chromosomal abnormalities, such as nucleus absence, sticky chromosomes in metaphase and binucleated cells, were present in most of the treatments. Thus, the presence of micronuclei and the results of L. culinaris, indicate the high cytogenotoxicity of propanil and the feasibility of this species as bioindicator.


Assuntos
Herbicidas/toxicidade , Lens (Planta)/efeitos dos fármacos , Cebolas/efeitos dos fármacos , Propanil/toxicidade , Allium , Núcleo Celular , Aberrações Cromossômicas , Dano ao DNA , Biomarcadores Ambientais , Mitose , Índice Mitótico , Raízes de Plantas/efeitos dos fármacos , Testes de Toxicidade
18.
Pediatrics ; 145(3)2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32098788

RESUMO

OBJECTIVES: In this study, we benchmark outcomes and identify factors associated with tracheostomy placement in infants of very low birth weight (VLBW). METHODS: Data were prospectively collected on infants of VLBW (401-1500 g or gestational age of 22-29 weeks) born between 2006 and 2016 and admitted to 796 North American centers. Length of stay (LOS), mortality, associated surgical procedures, and comorbidities were assessed, and infants who received tracheostomy were compared with those who did not. Multivariable logistic regressions were performed to identify risk factors for tracheostomy placement and for mortality in those receiving tracheostomy. RESULTS: Of 458 624 infants of VLBW studied, 3442 (0.75%) received tracheostomy. Infants with tracheostomy had a median (interquartile range) LOS of 226 (168-304) days and a mortality rate of 18.8%, compared with 58 (39-86) days and 8.3% for infants without tracheostomy. Independent risk factors associated with tracheostomy placement included male sex, birth weight <1001 g, African American non-Hispanic maternal race, chronic lung disease (CLD), intraventricular hemorrhage, patent ductus arteriosus ligation, and congenital neurologic, cardiac, and chromosomal anomalies. Among infants who received tracheostomy, male sex, birth weight <751 g, CLD, and congenital anomalies were independent predictors of mortality. CONCLUSIONS: Infants of VLBW receiving tracheostomy had twice the risk of mortality and nearly 4 times the initial LOS of those without tracheostomy. CLD and congenital anomalies were the strongest predictors of tracheostomy placement and mortality. These benchmark data on tracheostomy in infants of VLBW should guide discussions with patient families and inform future studies and interventions.


Assuntos
Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Traqueostomia , Afro-Americanos , Aberrações Cromossômicas , Anormalidades Congênitas/epidemiologia , Permeabilidade do Canal Arterial/cirurgia , Feminino , Mortalidade Hospitalar , Humanos , Recém-Nascido , Hemorragias Intracranianas/epidemiologia , Tempo de Internação/estatística & dados numéricos , Pneumopatias/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais
19.
Cytogenet Genome Res ; 160(1): 22-28, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32018267

RESUMO

We report on a novel variant of the dicentric chromosome 17;20 (dic (17;20)(p11.2;q11.2) in a patient with de novo myelodysplastic syndrome (MDS). Based on FISH and array-CGH, the variant turns out to be an insertion of chromosome 17 (17p11.2-telomere 17) into chromosome 20 with breakpoints at 20q11.22 and 20q13.33. Based on conventional chromosome analysis and G-banding patterns, the region 17p11.2-17q25 was directly inserted between 20q11.22 and 20q13.33. The breakpoint junctions occurred within KCNJ12 (17p11.2), UQCC1 (20q11.2), and CDH4 (20q13.3), leading to 5' deletions of all the genes and positioning the 3' of UQCC1 next to KCNJ12 at 17p11.2 and CDH4 next to an unknown gene at 17q25-20q13.3. In addition, the centromere of chromosome 17 was not active, transforming the primary constriction to a flat band. Therefore, the novel insertion variant is a pseudo dicentric derivative chromosome with one functional centromere: 45,XX,der(17;20)del(20)(q11.22q13.33)ins(20;17)(q11.2;p11.2q25). A review of the literature of all dic(17;20) cases is presented. For the first time, we report an array-CGH characterization of such rare variant that revealed to be an insertion.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 20/genética , Hibridização Genômica Comparativa , Síndromes Mielodisplásicas/genética , Linhagem da Célula , Centrômero/ultraestrutura , Bandeamento Cromossômico , Deleção Cromossômica , Feminino , Rearranjo Gênico , Humanos , Cariotipagem , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Canais de Potássio Corretores do Fluxo de Internalização/genética , Translocação Genética
20.
Medicine (Baltimore) ; 99(5): e19014, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000445

RESUMO

To investigate the association between pathogenic copy number variants (p-CNVs) and abnormal karyotypes detected by chromosomal microarray analysis (CMA) and echogenic intracardiac focus (EIF).This was a retrospective study of fetuses with EIF with CMA data at the Prenatal Diagnosis Center of the West China Second University Hospital of Sichuan University between September 2014 and May 2017. Fetuses were assigned to the isolated EIF and non-isolated EIF groups according to the presence of other ultrasound abnormalities.Among 244 pregnant women, there were 143 cases of isolated EIF and 101 of non-isolated EIF. CMA revealed chromosome abnormality (n = 9 (3.7%): trisomy 21, n = 4; sexual trisomy, n = 2; and p-CNV, n = 3), variants of unknown significance (VOUS, n = 19), and benign CNV (b-CNV, n = 216). Among the fetuses with isolated EIF, 5 had chromosomal abnormalities (3.5%). Among the fetuses with non-isolated EIF, four had chromosomal abnormalities (4.0%). All fetuses with trisomy 21 were in the non-isolated group. The frequency of labor induction was 66.7% (6/9) among the fetuses with chromosome abnormality and 21.1% (4/19) among those with VOUS. Among those with chromosomal abnormalities, one (11.1%) had congenital heart disease.In pregnant women without high-risk factors for chromosomal abnormalities, ultrasound abnormalities, including EIF, could be an indication for CMA. Ultrasound abnormalities (including EIF) and chromosome abnormality could indicate a high risk of CHD. The presence of EIF and at least another ultrasound abnormality could indicate a high risk of trisomy 21.


Assuntos
Aberrações Cromossômicas , Cardiopatias Congênitas/genética , Análise em Microsséries , Diagnóstico Pré-Natal , Adolescente , Adulto , Feminino , Aconselhamento Genético , Humanos , Gravidez , Estudos Retrospectivos , Fatores de Risco , Ultrassonografia Pré-Natal
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