Cytogenetic characterization and evaluation of c-MYC gene amplification in PG100, a new Brazilian gastric cancer cell line

Gastric cancer is the fourth most frequent type of cancer and the second cause of cancer mortality worldwide. The genetic alterations described so far for gastric carcinomas include amplifications and mutations of the c-ERBB2, KRAS, MET, TP53, and c-MYC genes. Chromosomal instability described for gastric cancer includes gains and losses of whole chromosomes or parts of them and these events might lead to oncogene overexpression, showing the need for a better understanding of the cytogenetic aspects of this neoplasia. Very few gastric carcinoma cell lines have been isolated. The establishment and characterization of the biological properties of gastric cancer cell lines is a powerful tool to gather information about the evolution of this malignancy, and also to test new therapeutic approaches. The present study characterized cytogenetically PG100, the first commercially available gastric cancer cell line derived from a Brazilian patient who had a gastric adenocarcinoma, using GTG banding and fluorescent in situ hybridization to determine MYC amplification. Twenty metaphases were karyotyped; 19 (95%) of them presented chromosome 8 trisomy, where the MYC gene is located, and 17 (85%) presented a deletion in the 17p region, where the TP53 is located. These are common findings for gastric carcinomas, validating PG100 as an experimental model for this neoplasia. Eighty-six percent of 200 cells analyzed by fluorescent in situ hybridization presented MYC overexpression. Less frequent findings, such as 5p deletions and trisomy 16, open new perspectives for the study of this tumor.

A implantação do plano de desenvolvimento da escola nas escolas públicas paulistas: análise crítico-propositiva

Este texto é fruto de um projeto de extensão que promove a reflexão entre professores da Universidade Estadual Paulista e diretores e supervisores da Delegacia de Ensino da Região de Marília/SP. O MEC vem defendendo a adoção do PDE nas escolas públicas que não atingiram as metas definidas pelo IDEB. Nosso objetivo é analisar as propostas do PDE, identificando suas origens, suas características e a concepção de gestão que o embasam. Do mesmo modo, confrontar com o PPP das escolas, analisando suas implicações e consequências para a gestão. A Metodologia adota as pesquisas: bibliográfica, documental (PDE e PPP) e a pesquisa ação com o grupo de estudos em que participam diretores e supervisores da rede estadual e docentes e discentes da UNESP. Como resultados, identificamos que a concepção de gestão, consubstanciada no PDE, caminha em sentido oposto ao da concepção do PPP, especialmente no que se refere à gestão democrática.

O ensino superior noturno no Brasil: história, crescimento e políticas públicas no início do século XXI

There are three distinct and complementary objectives The first objective is to present a short historical overview on the establishment of evening courses in Brazil (classes are held on weekdays, generally from 7:00 pm to 10:30 pm), including those in the higher education level, occurred on the middle of last century. The second objective is to demonstrate the growth of evening higher education, considering that in 1998, of the 2.1 million college enrollments, 55.3% were enrolled in evening courses; in 2010, twelve years later, of the 5.4 million students enrolled, there were 63.5% enrolled in evening courses. The third objective is to discuss current public policies to expand evening openings in public institutions which represent nowadays only 16.1% of the 3.4 million enrollments for evening classes. In the third objective it is included the discussion of programs for scholarships and tuition loans. The research results pointed to the importance of federal programs for scholarships and tuition loans for students from private institutions such as the 1,382,484 scholarships since 2004 (PROUNI Program) and the 847,000 tuition loans since 1999 (FIES Program). Important steps have been made by the Brazilian government. Considering that there are 3,987,424 enrollments in private institutions, the effectiveness of the programs for scholarships and tuition loans is still insufficient to meet the universal benefits for the student’s needs. Evening courses became the real instrument of social inclusion for many Brazilian youths and must be expanded quantitatively and qualitatively, with aggressive public policies, including also, scholarships and tuition loans.

Educação infantil e políticas públicas: algumas considerações a partir de um estudo de caso

O presente estudo tem como objetivos discutir a função da creche e da pré‐escola no contexto das políticas públicas para a educação infantil, bem como refletir sobre a formação necessária aos profissionais da educação infantil para alcançar uma melhor qualidade do atendimento. A pesquisa foi realizada por meio de um formato de investigação caracterizado como estudo de caso etnográfico. Essa forma de pesquisa nos permitiu conhecer, em maior profundidade, a cultura de uma instituição e as perspectivas dos profissionais que participavam de seu cotidiano. Nesse sentido, realizamos observações sistemáticas da rotina institucional, bem como, entrevistas não‐ estruturadas e semi‐estruturadas com as educadoras que atuavam na creche e na pré‐escola. O estudo evidenciou distinções quanto à escolaridade, à jornada de trabalho das educadoras que atuavam na creche e na pré‐escola, bem como nos objetivos educacionais estabelecidos para essas modalidades de atendimento a infância. As concepções das educadoras acerca dos objetivos da Educação Infantil retratam uma visão compensatória e preventiva.  

Dental anomalies in patients with down syndrome

The purpose of the present study was to evaluate the incidence of dental anomalies in Brazilian patients with Down syndrome. A sample with 49 panoramic x-rays of syndromic patients aged 3 to 33 years (22 male and 27 female) was used. The characteristics of dental anomalies were observed in the panoramic radiographs in both the primary and permanent dentition, according to the ICD (International Classification of Diseases). The corresponding tables and percentile analysis were elaborated. There was a high incidence of syndromic patients with different types of anomalies, such as taurodontism (50%), proven anodontia (20.2%), suspected anodontia (10.7%), conic teeth (8.3%) and impacted teeth (5.9%). In conclusion, patients with Down syndrome presented a high incidence of dental anomalies and, in most cases, the same individual presented more than one dental anomaly.

Análise das células tronco tumorais em neoplasias mamárias de cães

Mammary tumors are the most frequent cancers in dogs, representing about 50% of tumors, and have a higher incidence in females of middle aged and elderly. These tumors have been used as a model for breast cancer in women due to several common characteristics such as histological and immunohistochemical similarities. In the last decade, studies based on molecular profiles of breast cancer, made possible the identification of some neoplastic cells with characteristics of stem cells - cancer stem cells (CSC). One of the putative molecules of CSCs is CD44. Recent studies have established a crucial link between the epithelial-mesenchymal transition (EMT) and the acquisition of molecular and functional properties of stem cells. For that reason we analyzed the expression of proteins CD44, Cytokeratins AE1/AE3 and Vimentin, in dogs mammary tumors, to investigate the potencial for CSC markers, and its relation with the EMT using immunohistochemistry in paraffin embedded tissues making use of techniques such as Tissue MicroArrays (TMA). Immunostaining of cytokeratin had no significant difference between benign and malignant tumors (p ≥ 0,05), being more intense in malignant tumors. However vimentina showed higher staining intensity in benign tumors, but with no significant difference (p ≤ 0,05). The expression of CD44 was higher in malignant tumors that have greater proliferative and metastatic potencial, however its relation with EMT was not detected in the analyzed tumors. The techniques applied for the TMAs were efficient and can be used in routine and later researches.

Avaliação funcional pré e pós programa de exercício físico de pacientes em hemodialise

Model Study: An experimental study Introduction: Chronic Kidney Disease (CKD) refers to a syndromic diagnosis which leads to a progressive and irreversible loss of renal function. A hemodialysis patient may have limitations in functional capacity, pulmonary function and respiratory musclular strength impacting in quality of life. Objective: To evaluate the effects of an exercise program on pulmonary function, functional capacity, quality of life and pain in patients undergoing hemodialysis. Methodology: The study included 28 patients of both genders, women and men aged between 40 and 60 years undergoing dialysis at the Kidney Institute, Santa Casa de Misericordia in Presidente Prudente-SP. Primary outcomes included respiratory muscular strength measurements assessed by manovacuometry. The functional capacity was evaluated by a six minute walking test. A life quality questionnaire was applied to evaluate quality of life (SF36-KDQOL). Lung function was evaluated by spirometry. Pain was assessed by a visual analogue scale. The exercise program consisted of training 3 times a week for 40 minutes on hemodialysis during eight weeks. At the end of the program all patients were reassessed. Results: There was no significant difference in the values of FVC and FEV1 before and after the exercise program as well as the index Tiffenau. The value of post MIP was significantly higher than the value obtained in the pre program. For variable MEP no significant difference was found. Functional capacity evaluations showed that there were no significant differences (p> 0.05). The evaluation of quality of life, about the domains of specific areas of CKD showed statistical significance when comparing the list of symptoms and problems with overloading of renal disease and professional role. Indicators related to pain were significantly reduced after the program (P <0.05). Discussion: A chronic kidney patient faces complex situations of physical, social and financial aspects. Although no statistically significant results were found in all variables, the study corroborates to others found in the literature, which suggests that an exercise program can be positive for this population. Conclusion: Although lung capacity and functional capacity did not submit changes to the end of the study, reduced levels of pain, fatigue and dyspnea suggest improvement in functional performance after exercise programs.

Polymorphism C1420T of Serine hydroxymethyltransferase gene on maternal risk for Down syndrome

Recent researches have investigated the factors that determine the maternal risk for Down syndrome (DS) in young woman. In this context, some studies have demonstrated the association between polymorphisms in genes involved on folate metabolism and the maternal risk for DS. These polymorphisms may result in abnormal folate metabolism and methyl deficiency, which is associated with aberrant chromosome segregation leading to trisomy 21. In this study, we analyzed the influence of the polymorphism C1420T in Serine hydroxymethyltransferase (SHMT) gene on maternal risk for DS and on metabolites concentrations of the folate pathway (serum folate and plasma homocysteine and methylmalonic acid). The study group was composed by 105 mothers with DS children (case group) and 185 mothers who had no children with DS (control group). The genotype distribution did not show significant statistical difference between case and control mothers (P = 0.24) however a protective effect between genotypes CC (P = 0.0002) and CT (P < 0.0001) and maternal risk for DS was observed. Furthermore, the SHMT C1420T polymorphism (rs1979277) does not affect the concentration of metabolites of folate pathway in our DS mothers. In conclusion, our data showed a protective role for the genotypes SHMT CC and CT on maternal risk for DS. The concentrations of metabolites of folate pathway did not differ significantly between the genotypes SHMT.

MSX2 copy number increase and craniosynostosis: copy number variation detected by array comparative genomic hybridization

Fleury Group

Análise dos resultados maternos e fetais dos procedimentos invasivos genéticos fetais: um estudo exploratório em Hospital Universitário

OBJETIVO: Caracterizar as indicações das gestantes que procuraram o serviço de Medicina Fetal do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo para realização de procedimentos invasivos diagnósticos e avaliar os resultados dos cariótipos fetais e de suas gestações. MÉTODOS: Estudo observacional retrospectivo das gestantes que realizaram biópsia de vilo corial (BVC), amniocentese e cordocentese no período de fevereiro de 2005 a dezembro de 2009. Não foram incluídos outros procedimentos diagnósticos ou procedimentos terapêuticos. O resultado da gestação foi obtido através de consulta de prontuário eletrônico e/ou físico e/ou contato telefônico. RESULTADOS: Foram realizados 713 procedimentos (113 BVC, 340 amniocenteses e 260 cordocenteses). A principal indicação para a realização dos procedimentos invasivos foi a presença de alterações estruturais nos fetos, seguido por valores aumentados da translucência nucal e pela idade materna avançada. O cariótipo fetal esteve alterado em 186 casos (26,1%). A trissomia do cromossomo 18 foi a aneuploidia mais comum, seguida pela trissomia do 21, a monossomia do X e a trissomia do cromossomo 13. Ocorreram 4,9% de abortamento, 25,7% de natimortos e 13% de neomortos. Oito gestantes optaram pela interrupção judicial, e 99% das gestantes cujos fetos não apresentavam malformação e que apresentavam cariótipo fetal normal tiveram nativivos.

Second-trimester soft markers: relation to first-trimester nuchal translucency in unaffected pregnancies

Objective Genetic sonography following first-trimester combined screening appears to increase substantially detection rates for Down syndrome but it relies on the unproved assumption of independence between these tests. In this study we aimed to investigate the relationship between first-trimester nuchal translucency (NT) and a series of second-trimester soft markers and structural defects in unaffected pregnancies. Methods NT measurement in the first trimester was followed by second-trimester scan (18 to 23 + 6 weeks) including examination for three categorical markers (intracardiac echogenic foci, hyperechogenic bowel and structural defects) and measurement of nasal bone length, nuchal-fold thickness, femur length, humerus length, renal pelvis diameter and prenasal thickness. All continuous variables were expressed in multiples of the median (MoM) for gestation and correlation coefficients between log-transformed NT and second-trimester variables were calculated. In addition, frequencies of soft markers and structural defects in cases with increased NT were compared to those with normal NT, using MoM cut-offs. Results In a dataset of 1970 cases, NT was significantly correlated (P < 0.05) with all second-trimester continuous variables, the correlation being strongest for nuchal-fold thickness (r = 0.10). There was a higher frequency of cases with second-trimester nuchal-fold thickness above the 97.5th centile (10.7 vs. 2.2%) and hyperechogenic bowel (2.4 vs. 0.1%) in cases with increased NT. Conclusions Straightforward reassessment of risk using likelihood ratios derived from the second-trimester genetic sonogram might lead to inaccurate estimates. Multivariate models using continuous second-trimester variables might be preferable in sequential screening strategies. Copyright. 2012 ISUOG. Published by John Wiley & Sons, Ltd.

A complex chromosomal rearrangement involving chromosomes 2, 5, and X in autism spectrum disorder

Here, we describe a female patient with autism spectrum disorder and dysmorphic features that harbors a complex genetic alteration, involving a de novo balanced translocation t(2;X)(q11;q24), a 5q11 segmental trisomy and a maternally inherited isodisomy on chromosome 5. All the possibly damaging genetic effects of such alterations are discussed. In light of recent findings on ASD genetic causes, the hypothesis that all these alterations might be acting in orchestration and contributing to the phenotype is also considered. (C) 2012 Wiley Periodicals, Inc.

Genetic polymorphisms modulate the folate metabolism of Brazilian individuals with Down syndrome

Individuals with Down syndrome (DS) carry three copies of the Cystathionine beta-synthase (C beta S) gene. The increase in the dosage of this gene results in an altered profile of metabolites involved in the folate pathway, including reduced homocysteine (Hcy), methionine, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM). Furthermore, previous studies in individuals with DS have shown that genetic variants in genes involved in the folate pathway influence the concentrations of this metabolism's products. The purpose of this study is to investigate whether polymorphisms in genes involved in folate metabolism affect the plasma concentrations of Hcy and methylmalonic acid (MMA) along with the concentration of serum folate in individuals with DS. Twelve genetic polymorphisms were investigated in 90 individuals with DS (median age 1.29 years, range 0.07-30.35 years; 49 male and 41 female). Genotyping for the polymorphisms was performed either by polymerase chain reaction (PCR) based techniques or by direct sequencing. Plasma concentrations of Hcy and MMA were measured by liquid chromatography-tandem mass spectrometry as previously described, and serum folate was quantified using a competitive immunoassay. Our results indicate that the MTHFR C677T, MTR A2756G, TC2 C776G and BHMT G742A polymorphisms along with MMA concentration are predictors of Hcy concentration. They also show that age and Hcy concentration are predictors of MMA concentration. These findings could help to understand how genetic variation impacts folate metabolism and what metabolic consequences these variants have in individuals with trisomy 21.

Mutational analyses of the signals involved in the subcellular location of DSCR1

Abstract Background Down syndrome is the most frequent genetic disorder in humans. Rare cases involving partial trisomy of chromosome 21 allowed a small chromosomal region common to all carriers, called Down Syndrome Critical Region (DSCR), to be determined. The DSCR1 gene was identified in this region and is expressed preferentially in the brain, heart and skeletal muscle. Recent studies have shown that DSCR1 belongs to a family of proteins that binds and inhibits calcineurin, a serine-threonine phosphatase. The work reported on herein consisted of a study of the subcellular location of DSCR1 and DSCR1-mutated forms by fusion with a green fluorescent protein, using various cell lines, including human. Results The protein's location was preferentially nuclear, independently of the isoform, cell line and insertion in the GFP's N- or C-terminal. A segment in the C-terminal, which is important in the location of the protein, was identified by deletion. On the other hand, site-directed mutational analyses have indicated the involvement of some serine and threonine residues in this event. Conclusion In this paper, we discuss the identification of amino acids which can be important for subcellular location of DSCR1. The involvement of residues that are prone to phosphorylation suggests that the location and function of DSCR1 may be regulated by kinases and/or phosphatases.

Avaliação da qualidade de vida após sinusectomia endoscópica para rinossinusite crônica

A rinossinusite crônica é uma doença de etiologia não definida que impacta significativamente a qualidade de vida dos pacientes. A sinusectomia endoscópica foi demonstrada como um tratamento eficaz em melhorar a qualidade de vida dos pacientes em outros países; contudo, não existem estudos nacionais. OBJETIVO: Avaliar a associação cirurgia endoscópica nasossinusal com a qualidade de vida doença-específica dos pacientes com rinossinusite crônica com e sem polipose nasossinusal pelo SNOT-20. Desenho: Estudo prospectivo. PACIENTES E MÉTODOS: Pacientes submetidos à sinusectomia endoscópica após ausência de melhora ao tratamento medicamentoso foram avaliados pelo questionário SNOT-20p antes e 12 meses após a cirurgia. Avaliou-se a melhora na pontuação total e nos cinco itens considerados mais importantes por cada paciente. Avaliamos também a presença de correlação entre a pontuação pré-operatória e a melhora pós-operatória e se havia diferença entre a melhora segundo sexo. RESULTADOS: Incluímos 43 pacientes com idade de 44 (19), md (IIQ); e 60,5% (26/43) do sexo masculino. Os pacientes apresentaram melhora estatisticamente significativa no SNOT-20 e SNOT-20 (5+), e correlação entre a pontuação pré-operatória e a melhora da pontuação (p<0.001). Não houve diferença entre melhora da pontuação na qualidade de vida segundo o sexo. CONCLUSÃO: A sinusectomia endoscópica em pacientes com rinossinusite crônica apresenta associação com melhora da QV doença-específica estatisticamente significativa.