Cytogenetic effect of 5-azacytidine in patients with hematological malignancies

BACKGROUND: Recently, the importance of cytogenetics has grown in the diagnosis, prognosis and treatment of leukemias and myelodysplastic syndromes. 5-azacytidine is a drug that has well-known cytogenetical effects and is approved in the treatment of myelodysplastic syndromes. To date, no studies have been performed to evaluate the impact of 5-azacytidine on the chromosomes of patients with hematological neoplasias. This study aimed to investigate the effects of 5-azacytidine on chromosomes of patients with different hematological malignancies using G-band analyses to identify possible cytogenetical alterations. METHODS: The peripheral blood of 18 patients with hematological malignancies and 18 controls was collected in heparinized tubes. 5-azacytidine was added, at a final concentration of 10-5M, to cultures 7 hours prior to harvest. RESULTS: Uncoiled centromeric/pericentromeric heterochromatin of chromosomes-1, 9 and 16 occurred more frequently in the patients than in controls. This higher frequency of uncoiled heterochromatin was statistically significant (p-value = 0.004) for chromosome-9. Conversely, we observed that the fragile site at 19q13 was more frequent in controls (p-value = 0.0468). CONCLUSIONS: The results of this study suggest that satellite sequences, located in the heterochromatin of chromosome-9, are hypomethylated in hematological malignancies. This hypomethylation may contribute to the disease, activating transposable elements and/or promoting genomic instability, enabling the loss of heterozygosity of important tumor suppressor genes. An investigation of the 19q13 region may help to understand whether or not the predominant occurrence of the fragile site at 19q13 in controls is due to hypermethylation of this region.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Faculdade de Medicina de Marília Hemocentro Genetics LaboratoryUniversidade Federal de São Paulo (UNIFESP) Department de MorphologyFaculdade de Medicina de Marília Hematology DepartmentUniversidade do Sagrado CoraçãoUNIFESP, Department de MorphologySciEL

cagA positive Helicobacter pylori in Brazilian children related to chronic gastritis

Helicobacter pylori is a spiral-shaped Gram-negative bacterium. It colonizes the gastric mucosa of humans and persists for decades if not treated. Helicobacter pylori infection affects more than half of the world's population and invariably results in chronic gastritis. The cagA gene is present in about 60 to 70% of H. pylori strains; it encodes a high-molecular-weight protein (120 to 140 kDa) and several investigators have noted a correlation between strains that possess cagA and the severity of gastric mucosal inflammation. We examined the relation between cagA status in H. pylori strains and chronic gastritis with inflammatory processes in children from Marília, São Paulo, Brazil. One-hundred-twenty-one children were analyzed histopathologically and by polymerase chain reaction (PCR) to detect H. pylori and cagA. We then looked for an association between cagA presence and inflammatory infiltration. Using histology and PCR, we found 47% H. pylori positive infection; 29 children were diagnosed with chronic gastritis, while 28 showed normal mucosa by histopathological analysis. CagA presence was genotyped in both groups, and an inflammatory infiltrate was studied in all infected children with chronic gastritis. We found cagA strains in 20 of 29 (69%) children with chronic gastritis and 18 of 28 (64%) with normal mucosa, demonstrating a strong relationship between the strains and the inflammatory process. We found a positive association between an inflammatory process associated with H. pylori of cagA+ strains and chronic gastritis development.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)School of Medicine of Marília Department of Genetic and Molecular Biology HemocentroUNIFESP-EPM Department of GeneticFAMEMA Department of PathologyUNIFESP, EPM, Department of GeneticSciEL

HISTÓRICO E REESTRUTURAÇÃO DAS LINHAS DE PESQUISA DO PROGRAMA DE PÓS-GRADUAÇÃO EM SAÚDE E ENVELHECIMENTO

Esta revisão narrativa apresenta estudos desenvolvidos no curso de mestrado acadêmico do Programa de Pós-graduação em Saúde e Envelhecimento, da Faculdade de Medicina de Marília (Famema), o qual foi aprovado pela CAPES em 2011, com início em 2012. Atualmente, possui duas linhas de pesquisa: (1) Educação e cuidado à saúde no ciclo da vida, (2) Aspectos biológicos e clínicos do binômio saúde-doença no processo de envelhecimento. Integra a Rede dos Programas de Pós-Graduação Interdisciplinares em Envelhecimento (REPRINTE) desde a sua implementação. Importante ressaltar que o Programa de Pós-graduação em Saúde e Envelhecimento não está voltado exclusivamente à formação acadêmico-científica em Geriatria ou Gerontologia, mas também ao “cuidado à saúde e ao enfrentamento de doenças ao longo do processo do envelhecimento", ou seja, do nascimento até a morte. Nos primeiros oito anos de funcionamento do Programa (2012 a 2020), três linhas de pesquisa estavam vigentes, tendo sido configuradas desde o envio da Apresentação de Propostas de Cursos Novos (APCN) à CAPES. Com o transcorrer do curso e as experiências adquiridas, ficou evidente a necessidade de uma profunda reestruturação das linhas e dos projetos de pesquisa cadastrados no programa. Assim, esta narrativa descreve o histórico e o processo de reestruturação das linhas de pesquisa do programa e a revisão dos projetos a elas vinculados

Detection of Helicobacter pylori in gastric biopsies, saliva and dental plaques of dyspeptic patients from Marília, São Paulo, Brazil: presence of vacA and cagA genes

Helicobacter pylori, a gram-negative bacterium, possesses two important virulence factors: the vacuolating toxin (vacA), and the cytotoxin-associated gene product (cagA). The aim of the present study was to evaluate the presence of H. pylori in the stomach and oral cavity of humans and compare the cagA and vacA genotypes of H. pylori found in different samples (stomach, saliva and dental plaque) from the same patient. Gastric biopsies, saliva and dental plaques were obtained from 62 dyspeptic adults. DNA was extracted and evaluated for the presence of H. pylori and the alleles cagA and vacA. Persons with gastritis had a higher frequency of H. pylori -positive samples in the stomach while positive samples from gastric biopsies were significantly correlated with those from the oral cavity. There was a high H. pylori frequency in patients while the cagA gene was associated with vacA s1 alleles in gastric biopsies. Our results suggest a reservoir of the species in the oral cavity and that, in one patient, more than one H. pylori strain may exist in the saliva, dental plaque and stomach. We found a relationship between gastric infection and the bacterium in the oral cavity, with the cytotoxin genotype varying between saliva and dental plaque.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Sacred Heart University Postgraduate Program in Oral BiologyMarília Medical School Blood Center Department of GeneticsMarília Medical School Department of Anatomic PathologyMarília Medical School Department of Digestive System SurgeryFederal University of São Paulo Department of MorphologyUNIFESP, Department of MorphologySciEL

Gene polymorphism of interleukin 1 and 8 in chronic gastritis patients infected with Helicobacter pylori

Background: Epidemiological investigations have indicated that Helicobacter pylori induces inflammation in the gastric mucosa regulated by several interleukins. The genes IL1B and IL8 are suggested as key factors in determining the risk of gastritis. The aim of this paper was to evaluate the association of gene polymorphism of interleukin-1 and interleukin-8 with chronic gastrits in H. pylori infected patients. A total of 60 patients underwent endoscopic procedure. Biopsy samples were collected for urease test, histopathological and molecular exams. The DNA of theses samples was extracted for detection of H. pylori and analysis of the genes mentioned above. Patients with gastritis had a higher frequency of H. pylori-positive samples. Result: H. pylori was detected in 30/60 patients (50%) by PCR. As for polymorphism of interleukin 8 (-251) gene we observed a statistical difference when analyzed TA (p = 0.039) and TT (p = 0.047) genotypes. In the IL1B31 there was a statistical difference in TT (p = 0.01) genotype and in theIL1B-511 there wasn’t any statistical difference. Conclusion: Our results suggest a strong correlation between the presence of chronic gastritis and infection byH. pylori and that IL1B-31TT and IL8-251TT genotypes appear to act as protective factors againstH. pylori infection while IL8-251TA genotype may comprise a risk factor for infection with this bacterium.Marília Medical School FAMEMA Blood Center Department of GeneticsSacred Heart UniversityMarília Medical School Department of Digestive System SurgeryFederal University of São Paulo Department of MorphologyMarília Medical School Department of Radiotherapy and OncologyFAMEMA Hemocentro Laboratório de GenéticaUNIFESP, Department of MorphologySciEL

Interleukin-8-251T > A, Interleukin-1α-889C > T and Apolipoprotein E polymorphisms in Alzheimer's disease.

An inflammatory process has been involved in numerous neurodegenerative disorders such as Parkinson's disease, stroke and Alzheimer's disease (AD). In AD, the inflammatory response is mainly located in the vicinity of amyloid plaques. Cytokines, such as interleukin-8 (IL-8) and interleukin-1α (IL-1α), have been clearly involved in this inflammatory process. Polymorphisms of several interleukin genes have been correlated to the risk of developing AD. The present study investigated the association of AD with polymorphisms IL-8 -251T > A (rs4073) and IL-1α-889C > T (rs1800587) and the interactive effect of both, adjusted by the Apolipoprotein E genotype. 199 blood samples from patients with AD, 146 healthy elderly controls and 95 healthy young controls were obtained. DNA samples were isolated from blood cells, and the PCR-RFLP method was used for genotyping. The genotype distributions of polymorphisms IL-8, IL-1α and APOE were as expected under Hardy-Weinberg equilibrium. The allele frequencies did not differ significantly among the three groups tested. As expected, the APOE4 allele was strongly associated with AD (p A and IL-1α-889C > T were not found to be risk factors for AD

Association of interleukin 1 beta polymorphisms and haplotypes with Alzheimer's disease

Our study aimed to associate IL-1 beta and IL-1RN polyrnorphisms with AD disease in comparison with elderly control group from São Paulo - Brazil. We genotyped 199 Alzheimer's disease (AD) patients, 165 elderly control and 122 young control samples, concerning VNTR (IL-1RN) and -511C>T and -31T>C (IL-1 beta) polymorphisms. Our findings revealed that -511C/-31T/2-repetitions VNTR haplotype had a protective effect for AD when compared to EC (p=0.005), whereas -511C/-31C/1-repetition VNTR haplotype was associated as a risk factor for AD (p=0.021). Taken together, we may suggest that there is a relevant role of IL-1 genes cluster in AD pathogenesis in this Brazilian population. (c) 2012 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade do Sagrado Coracao de BauruConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Faculdade de Medicina de Marilia (FAMEMA)USC, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Dept Morfol, Disciplina Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Disciplina Neurol Ambulatorio Neurol Comportament, São Paulo, BrazilFac Med Marilia FAMEMA, Hemoctr, Disciplina Genet, São Paulo, BrazilFac Med Sao Jose do Rio Preto, Nucleo Pesquisa Bioquim & Biol Mol, São Paulo, BrazilUniv Marilia UNIMAR, Fac Med, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Dept Morfol, Disciplina Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Disciplina Neurol Ambulatorio Neurol Comportament, São Paulo, BrazilFAPESP: 06/07240-3FAPESP: 09/15857-9FAPESP: 04/15273-3Web of Scienc