RESUMO
BACKGROUND: Lake Malawi cichlids represent one of a growing number of vertebrate models used to uncover the genetic and developmental basis of trait diversity. Rapid evolutionary radiation has resulted in species that share similar genomes but differ markedly in phenotypes including brains and behavior, nuptial coloration and the craniofacial skeleton. Research has begun to identify the genes, as well as the molecular and developmental pathways that underlie trait divergence. RESULTS: We assemble a compendium of gene expression for Lake Malawi cichlids, across pharyngula (the phylotypic stage) and larval stages of development, encompassing hundreds of gene transcripts. We chart patterns of expression in Bone morphogenetic protein (BMP), Fibroblast growth factor (FGF), Hedgehog (Hh), Notch and Wingless (Wnt) signaling pathways, as well as genes involved in neurogenesis, calcium and endocrine signaling, stem cell biology, and numerous homeobox (Hox) factors-in three planes using whole-mount in situ hybridization. Because of low sequence divergence across the Malawi cichlid assemblage, the probes we employ are broadly applicable in hundreds of species. We tabulate gene expression across general tissue domains, and highlight examples of unexpected expression patterns. CONCLUSIONS: On the heels of recently published genomes, this compendium of developmental gene expression in Lake Malawi cichlids provides a valuable resource for those interested in the relationship between evolution and development.
Assuntos
Ciclídeos/genética , Proteínas de Peixes/genética , Regulação da Expressão Gênica no Desenvolvimento , Genes Controladores do Desenvolvimento/genética , Animais , Ciclídeos/crescimento & desenvolvimento , Evolução Molecular , Modelos Animais , FenótipoRESUMO
BACKGROUND: Periprosthetic infection is commonly caused by Staphylococcus aureus and, if resistant to methicillin (MRSA), is associated with increase in severity and costs to patient and healthcare systems. MRSA colonizes 1-5% of the population, therefore using a screening and decolonisation protocol the risk of periprosthetic infection could be reduced. The objective of our study is to report the results of a preoperative MRSA screening and management protocol utilised at our hospital. METHODS: All patients undergoing a total joint arthroplasty at our hospital were preoperatively screened for MRSA colonization with swab samples of five different locations. Exposure to risk factors were investigated in colonised patients and they were treated for 5 days prior surgery with nasal mupirocin, chlorhexidine sponges and oral tablets. RESULTS: During the 48 months of the study, MRSA colonisation was identified in 22 (1.01%) of 2188 patients operated. The culture was positive only in the nasal swab in 55 patients. In five patients the nasal culture was negative, but they had another positive swab culture (three in the groin and two perianal). None of the patients reported a history of recent antibiotic treatment or hospitalization. CONCLUSION: At our institution, the prevalence of MRSA colonisation is 1.01% in patients undergoing hip and knee arthroplasty. Interestingly, our screening protocol included samples from five different anatomic locations, and it is important to highlight that we found patients with negative nares culture and positive cultures in other locations. Therefore, the number of carriers may be underdiagnosed if only nasal samples are obtained. LEVEL OF EVIDENCE: IV.
RESUMO
In most conventional radiation therapy treatments, special attention is payed for neutron contamination when working with energy beams above 8 MeV and generally it is only considered for shielding requirements, not for dose study in patients or employees. The present work is focused on studying the unwanted generated photoneutrons in a Medical Linear Accelerator (LinAc) Varian TrueBeam using a 6 MeV radiation treatment beam. To that, Monte Carlo (MC) simulation code MCNP6.1.1 was used. This version of the code allows the use of unstructured mesh geometries as a novelty, offering more reliable results and higher speed computation. The particularity of the studied LinAc is the presence of a beryllium filter at the treatment head. Since Beryllium causes photonuclear reactions (γ, n) at energies much lower than other LinAc composing materials, this work aims to analyze if this type of units, when using low energy treatment beams (6 MeV), produce neutron pollution and to ensure that this unwanted radiation can be considered negligible.
Assuntos
Berílio , Aceleradores de Partículas , Método de Monte Carlo , FótonsRESUMO
Radiation Therapy Planning Systems (RTPS) currently used in hospitals contain algorithms based on deterministic simplifications that do not properly consider electrons lateral transport in the areas where there are changes of density, and as a result, erroneous dose predictions could be produced. According to this, the present work proposes the use of Monte Carlo method in brachytherapy planning systems, which could affect positively on the radiotherapy treatment planning, since it provides results that are more accurate and takes into account the in homogeneities density variations. This paper presents a Monte Carlo (MC) simulation of a brachytherapy prostate treatment with I-125 seeds, using the latest version of MCNP, v.6.1.1. To that, a 3D model of the anatomy of a real anonymized patient is created from the segmentation of Computed Tomography (CT) images. Treatment over this 3D model is simulated and the dose given to each organ is obtained. These doses are compared with those calculated by deterministic planning system used in hospital demonstrating the effectiveness of MC method in the planning of brachytherapy treatments, because of not only the results precision but also regarding the affordable computing times.
Assuntos
Braquiterapia , Algoritmos , Humanos , Radioisótopos do Iodo , Masculino , Método de Monte Carlo , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
The purpose of this work is to develop an automatic methodology to obtain the dose received by a patient, (classified by organs), after being subjected to ionizing radiation because of CT images acquisition. The methodology starts from CT images, these images are automatically segmented and voxelized taking into account the CT numbers in order to obtain a 3D model used in Monte Carlo Simulations to calculate the dose inside the patient.Monte Carlo codes used in this work are MCNP.6.1.1, (whose results will be taken as a reference values) and MC-GPU, which appears to be a good candidate to be implemented in the methodology since his GPU parallelization offers a high speed calculation. Results show good agreement between simulated values obtained by MC-GPU and MCNP6.1.1.
Assuntos
Tomografia Computadorizada por Raios X , Humanos , Método de Monte Carlo , Imagens de FantasmasRESUMO
Glioblastoma is the most common primary tumor of the central nervous system, but the underlying genetic changes that give rise to these tumors are still poorly understood. We report a primary glioblastoma with an unusual age of presentation. The patient was a 22-year-old man with a survival of 16 months. Morphological findings showed an increase of cellularity with positive GFAP and EGFR expression, increase of proliferate index, vascular hyperplasia with glomeruloid structures and necrosis. Molecular analysis showed EGFR amplification. No mutations of the TP53 or amplification of MDM2 and CDK4 were detected. Neither homozygous deletion of the 9p21 locus genes nor aberrant methylation were found. The cytogenetic study showed a clonal karyotype. The metaphases presented, among other anomalies, a small ring chromosome and double-minutes chromosomes. Using FISH and CGH techniques, it was found that the ring chromosome was a partial trisomy of chromosome 7, and the region implicated corresponded to 7p13-q21. Partial trisomies in glioblastoma could play an important role in defining those regions where genes implicated in this tumor process may be found. We studied the possible correlation of these findings with the tumoral phenotype.
Assuntos
Neoplasias Encefálicas/genética , Cromossomos Humanos Par 7 , Genes erbB-1/genética , Glioblastoma/genética , Cromossomos em Anel , Adulto , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/ultraestrutura , Cromossomos Humanos Par 7/ultraestrutura , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/metabolismo , Amplificação de Genes , Proteína Glial Fibrilar Ácida/metabolismo , Glioblastoma/cirurgia , Glioblastoma/ultraestrutura , Humanos , Imuno-Histoquímica , Cariotipagem , Masculino , Trissomia/patologiaRESUMO
This work presents a Monte Carlo simulation using the last version of MCNP, v. 6.1.1, of a Varian CLinAc emitting a 15MeV photon beam. The main objective of the work is to estimate the photoneutron production and activated products inside the medical linear accelerator head. To that, the Varian LinAc head was modelled in detail using the manufacturer information, and the model was generated with a CAD software and exported as a mesh to be included in the particle transport simulation. The model includes the transport of photoneutrons generated by primary photons and the (n, γ) reactions which can result in activation products. The validation of this study was done using experimental measures. Activation products have been identified by in situ gamma spectroscopy placed at the jaws exit of the LinAc shortly after termination of a high energy photon beam irradiation. Comparison between experimental and simulation results shows good agreement.
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Nêutrons , Aceleradores de Partículas , Radioisótopos de Cobre/química , Raios gama , Método de Monte Carlo , Fótons , Tungstênio/químicaRESUMO
Previous studies have shown that allelic losses in a locus mapping to the chromosomal region 4p14-16 are indicative of poor prognosis in colorectal cancer. To further characterize the region involved and to confirm earlier observations, we have analyzed losses of heterozygosity (LOH) in nine microsatellite markers spanning this region in a prospective series of 181 colorectal carcinomas. The extent and the nature of the allelic imbalance were also ascertained by comparative genomic hybridization analysis of selected cases. The minimum common deleted region was confined to marker D4S2397 (LOH in 35% of the informative cases). Surrounding markers displayed LOH in 13-25% of informative cases and (other than the D4S2397 marker itself) showed a higher rate of allelic imbalances in association with mutations in the p53 tumor suppressor gene. Tumors with lymph node invasion also displayed increased rates of LOH in most markers. Regarding patient outcome, LOH solely at the D4S2397 locus was indicative of a shorter disease-free survival (P = 0.027). In consequence, two patterns of allelic loss are defined within the 4p14-16 region: (a) gross losses associated with tumor progression and probably attributable to the genomic instability related to the inactivation of the p53 tumor suppressor gene; and (b) specific losses limited to the D4S2397 locus (within an estimated fragment of 2 Mb) and associated with increased tumor aggressiveness. The presence of one or more putative tumor suppressor genes in this region is postulated.
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Cromossomos Humanos Par 4 , Neoplasias Colorretais/genética , Perda de Heterozigosidade , Repetições de Microssatélites , Alelos , Mapeamento Cromossômico , Códon , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Seguimentos , Genes p53 , Genes ras , Marcadores Genéticos , Humanos , Metástase Linfática , Valor Preditivo dos Testes , Prognóstico , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
A Theratron 780 (MDS Nordion) 60Co radiotherapy unit has been simulated with the Monte Carlo code MCNP. The unit has been realistically modelled: the cylindrical source capsule and its housing, the rectangular collimator system, both the primary and secondary jaws and the air gaps between the components. Different collimator openings, ranging from 5 x 5 cm2 to 20 x 20 cm2 (narrow and broad beams) at a source-surface distance equal to 80 cm have been used during the study. In the present work, we have calculated spectra as a function of field size. A study of the variation of the electron contamination of the 60Co beam has also been performed.
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Algoritmos , Radioisótopos de Cobalto/análise , Modelos Estatísticos , Proteção Radiológica/métodos , Radiometria/métodos , Radioterapia/instrumentação , Simulação por Computador , Análise de Falha de Equipamento , Método de Monte Carlo , Dosagem RadioterapêuticaRESUMO
Induced radioactivity and photoneutron contamination inside a radiation therapy bunker of a medical linear accelerator (Linac) is investigated in this work. The Linac studied is an Elekta Precise electron accelerator which maximum treatment photon energy is 15 MeV. This energy exceeds the photonuclear reaction threshold (around 7 MeV for high atomic number metals). The Monte Carlo code MCNP6 has been used for quantifying the neutron contamination inside the treatment room for different gantry rotation configuration. Walls activation processes have also been simulated. The approach described in this paper is useful to prevent the overexposure of patients and medical staff.
Assuntos
Nêutrons , Aceleradores de Partículas , Relação Dose-Resposta à Radiação , Humanos , Modelos Teóricos , Método de Monte CarloRESUMO
The frequency and types of chromosome aberrations induced by ionizing radiation in cancer patients were evaluated in 24 cases studied just before and immediately after radiotherapy. The incidence of aberrant metaphases prior to treatment was 9.98% and increased significantly after treatment to 32.8%. The frequency of chromosome aberrations before radiotherapy was, with the exception of the cases of breast cancer and seminoma, significantly higher than that in our laboratory controls. A comparison of chromosome abnormalities observed before and after treatment indicated that dicentric translocations, rings, and reciprocal translocations increased by a factor of 23, 13, and 11, respectively, after radiotherapy. Ionizing radiation produces more asymmetrical than symmetrical chromosome aberrations and more two-break than one-break anomalies.
Assuntos
Aberrações Cromossômicas , Neoplasias/radioterapia , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Disgerminoma/genética , Disgerminoma/radioterapia , Feminino , Doença de Hodgkin/genética , Doença de Hodgkin/radioterapia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias Testiculares/genética , Neoplasias Testiculares/radioterapia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/radioterapiaRESUMO
This report describes the fourth case of heritable 18p monosomy, which was ascertained by prenatal diagnosis. Cytogenetic analysis of amniotic fluid cells by G-banding showed an apparently distal 18p chromosome deletion and a derivative X chromosome resulting from a translocation between the X and Y chromosomes. Analysis of peripheral blood lymphocytes from the parents by G-banding revealed the same chromosome 18 deletion in the mother, who did not have the X/Y translocation. Comparative genomic hybridization (CGH) studies confirmed the loss of chromosome region 18p11.3-pter previously detected, and eliminated the presence of unbalanced reorganizations of other chromosome regions. No subtle translocation was detected by fluorescence in situ hybridization (FISH) studies using whole chromosome specific painting probes. This is a new report of a heritable 18p monosomy. Although in our case the mother had several minor congenital malformations, the loss of 18p11.3 band was not associated with any obvious phenotypic alteration in the fetus.
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Deleção Cromossômica , Cromossomos Humanos Par 18/genética , Adulto , Amniocentese , Feminino , Humanos , Cariotipagem , Hibridização de Ácido Nucleico , Gravidez , Translocação Genética , Cromossomo X , Cromossomo YRESUMO
We have investigated the preferential bending of some chromosome sites in blood cultures from normal and chromosomally abnormal subjects. A total of 2,262 centromeric and 2,718 non-centromeric bends were recorded, and 69 non-centromeric sites were found not to bend at random. 15q11-13 bending was found to be the most frequent non-random autosomal bend. Bends on chromosomes may be remnants of a folded chromosome state in the nucleus, and may facilitate the preferential involvement of some chromosomal bands in structural reorganizations such as the isoacentric fragments, or contribute to the high frequency of interstitial deletions and isodicentric inversion duplications involving the 15q11-13 region.
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Cromossomos Humanos/fisiologia , Células Sanguíneas/citologia , Células Cultivadas , Centrômero/genética , Centrômero/fisiologia , Bandeamento Cromossômico , Cromossomos Humanos/genética , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 15/fisiologia , Feminino , Humanos , Masculino , Metáfase , Mitose , Modelos BiológicosRESUMO
Centromere-specific DNA probes for chromosomes 4, 7 and 18 were used to simultaneously analyze chromosome loss, non-disjunction, breaks within the labeled region, and nucleoplasmic bridges induced by gamma rays in binucleated human lymphocytes. The doses used were 0, 1, 2 and 4 Gy, and approximately 1000 cells were scored per dose. Micronucleus frequency increased in a linear-quadratic fashion. For chromosome loss, significant increases were observed at 2 and 4 Gy, whereas for non-disjunction significant increases were observed at 1 Gy; thus non-disjunction allowed us to detect the effects of radiation at a lower dose than chromosome loss. The use of centromere-specific probes allowed discrimination between the clastogenic and aneugenic effects of ionizing radiation. The analysis of chromosome loss, not taking fragmented signals into account, ensures the detection of an aneugenic effect, which was not possible using pancentromeric probes. The frequency of chromosome breakage within the labeled regions was higher in nuclei than in micronuclei, suggesting an increase in the engulfment of chromosomal material by nuclei as a consequence of the presence of cytochalasin B in the cultures. Chromatin filaments connecting main nuclei, the so-called nucleoplasmic bridges, were observed in irradiated samples, and are a manifestation of rearranged chromosomes producing anaphase bridges.
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Centrômero , Linfócitos/efeitos da radiação , Não Disjunção Genética , Relação Dose-Resposta à Radiação , Raios gama , Humanos , Hibridização in Situ Fluorescente , Linfócitos/ultraestrutura , Testes para MicronúcleosRESUMO
In a study of chromosome fragility carried out under folate and thymidine deficiency conditions, we observed a seven- to ninefold increase of the incidence of premature centromere divisions (PCDs) affecting all chromosomes. This early separation of centromeres is clearly a culture effect and distinct from PCD and centromere splitting (CS), which imply a defect in the centromere of one or more chromosomes.
Assuntos
Centrômero/ultraestrutura , Fragilidade Cromossômica , Metotrexato/farmacologia , Células Cultivadas , Centrômero/efeitos dos fármacos , Bandeamento Cromossômico , Sítios Frágeis do Cromossomo , Humanos , Cariotipagem , Valores de Referência , Timidina/metabolismoRESUMO
The chromosomal aberration rate and the expression of fragile sites induced by aphidicolin were evaluated in metaphase chromosomes obtained from peripheral blood lymphocytes of two untreated patients with multiple primary cancers. Spontaneous aberrations of chromosome number and structure and chromosome fragility were compared with controls with the use of the same methods. Chromosomal aberration rates and expression frequencies of fragile sites were significantly higher in the patients than in normal control subjects. In the patients, all but one structural chromosome aberration involved at least one fragile site. Our results suggest that fragile sites may be unstable regions of the human genome, which might play an important role in the genetic instability associated with cancer predisposition.
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Fragilidade Cromossômica , Neoplasias Gastrointestinais/genética , Linfócitos/patologia , Segunda Neoplasia Primária/genética , Neoplasias Urológicas/genética , Idoso , Carcinoma de Células de Transição/sangue , Carcinoma de Células de Transição/genética , Aberrações Cromossômicas , Sítios Frágeis do Cromossomo , Neoplasias Gastrointestinais/sangue , Humanos , Neoplasias Renais/genética , Linfócitos/fisiologia , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/sangue , Neoplasias do Colo Sigmoide/sangue , Neoplasias do Colo Sigmoide/genética , Neoplasias Gástricas/sangue , Neoplasias Gástricas/genética , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/genética , Neoplasias Urológicas/sangueRESUMO
We describe two cases of transitional cell carcinoma of the bladder associated with trisomy 7. In one of them, trisomy 7 was the only chromosome abnormality observed. In the second case, trisomy 7 was found in 25 (80.6%) of the metaphases; in two of them this was the only anomaly, while in three metaphases trisomy 8 was also present, and in other two trisomy 10 was also observed. Our results suggest that trisomy 7 could be a primary change in TCC, and a review of the literature indicates that when it is present as the sole karyotypic abnormality is may be associated with a non-invasive behavior of the tumor.
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Carcinoma de Células de Transição/genética , Cromossomos Humanos Par 7 , Trissomia , Neoplasias da Bexiga Urinária/genética , Idoso , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 8 , Feminino , Humanos , Cariotipagem , MasculinoRESUMO
We describe a simple method for isolation of high-molecular-weight DNA from cells fixed in Carnoy's solution for cytogenetic studies. DNA samples were extracted from NIH3T3 cells, and no apparent degradation was noticed. This method should be useful for molecular analysis of cells fixed for cytogenetic studies.
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Ácido Acético , DNA/isolamento & purificação , Células 3T3 , Acetatos , Animais , Clorofórmio , Desoxirribonuclease BamHI , Eletroforese em Gel de Ágar , Etanol , Etídio , Fixadores , CamundongosRESUMO
Monosomy for chromosome 9, as well as loss of heterozygosity for markers on this chromosome, has been detected in a high percentage of transitional cell carcinomas (TCC) of the bladder. We report a case of a TCC of the bladder with an interstitial del(9)(q11q21.2) that could be indicative of the presence of a putative tumor-suppressor gene related to bladder tumor progression. To elucidate the role of chromosome 9 in bladder tumors, it would be interesting to study a possible loss of heterozygosity in this chromosome region.
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Carcinoma de Células de Transição/genética , Deleção Cromossômica , Cromossomos Humanos Par 9 , Neoplasias da Bexiga Urinária/genética , Aberrações Cromossômicas , Genes Supressores de Tumor , Humanos , Cariotipagem , Masculino , Pessoa de Meia-IdadeRESUMO
The long-term cytogenetic effect of radio- or chemotherapy or both on male germ cells was evaluated by study of the chromosomal abnormalities in spermatozoa of four men treated for cancer 5-18 years earlier. The cytogenetic analysis of 422 sperm metaphases showed no differences in the aneuploidy rate. The incidence of structural chromosome aberrations was 14.0%, however, which is much higher than in controls. Thus, the high incidence of structurally aberrant spermatozoa observed in our long-term study indicates that antitumoral treatments affect stem-cell spermatogonia and that aberrant cells can survive germinal selection and produce abnormal spermatozoa.