ABSTRACT Background: Hematologic neoplasms are associated with mutations in hematopoietic cells and chromosomal abnormalities. During aging, about 2–3% of the elderly have chromosomal abnormalities arising from clonal mosaicism, the immune system is impaired and the bone marrow loses its ability to replace blood cells. Objective: To describe the epidemiological and cytogenetic profile of hematological malignancies, highlighting the frequency of chromosomal alterations in these neoplasms associated with aging. Method: A retrospective cross-sectional study with analysis of karyotype exams results was performed in the Cytogenetic Laboratory of thee Blood Center of the Faculdade de Medicina de Marilia (FAMEMA) between 1998 and 2016. Blood samples from child and adult patients with different hematological malignancies treated in the Onco-hematology Outpatient Clinics of the local blood center and hospitals, and external clinics were tested. Results: Karyotype exam results of 746 patients with a mean age of 54.7 years (±23.1) were analyzed. The elderly had the highest frequency of hematological malignancies (50.9%), followed by adults (38.3%) and young people (10.7%); elderly women had the highest percentage (55.0%). Normal karyotypes (46,XX/46,XY) were more common (61.8%) compared to abnormal karyotypes, especially among the elderly (56.4%). Myeloproliferative neoplasms were an exception with 67.4% of abnormal karyotypes. Conclusion: There is a higher frequency of hematological malignancies among the elderly. It is possible to conclude that failures in genomic mechanisms and hematopoiesis with aging lead to the formation of cells with the chromosomal alterations found in hematological malignancies.

Abstract Background Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the human stomach and causes a variety of gastric diseases. This study evaluated the correlations between the -251 (T>A) (rs4073) polymorphism of interleukin-8 (IL-8), the etiology of gastric disease, and H. pylori infection in pediatric and adolescent patients. Methods DNA samples were obtained from 285 gastric biopsies from pediatric patients. H. pylori was detected by PCR, whereas PCR-RFLP was used to characterize the -251 (T>A) polymorphism of IL-8. Results The histological analysis revealed the presence of gastritis in 158 patients (55.44%). H. pylori was found in 71 samples (24.9%). The -251 (T>A) polymorphism revealed that 58 (29.47%) samples were TT, 143 (50.18%) samples were TA, and 84 (20.35%) samples were AA. Conclusions Our findings suggest that IL8-251 A allele may be an important risk factor for the development of gastric disease when associated with H. pylori infection.

Abstract Background Tumor necrosis factor plays a critical role in the pathogenesis of gastric diseases such as gastric cancer, and an abnormal inflammatory response has frequently been observed in dyspeptic patients. Helicobacter pylori infection can induce a gastric mucosal inflammatory response that may be influenced by -308 (G > A) polymorphisms and gene expression of theTNF-α gene. Methods One hundred and thirty-four gastric biopsy samples were collected from patients of both genders (61♂ and 73♀, mean age 40.3 ± 24.2 years) with gastric symptoms. The -308 (G > A) polymorphism of TNF-α was characterized using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The expression level was measured using real-time PCR, and relative quantification (RQ) was calculated using the comparative CT method (2-ΔΔCT). Results The analysis revealed an increase in TNF-α gene expression in patients with gastritis; on the other hand, no statistical differences were observed in patients with gastric cancer. In addition, no association was found among -308 polymorphism genotypes, virulence markers, or TNF-α gene expression. Conclusions Helicobacter pylori induces a large increase in TNF-α expression in patients with gastritis, regardless of tissue inflammation, but after the tissue becomes neoplastic, the presence of bacteria did not influence expression. These results suggest that the TNF-α pathway may play an important role in the progression from gastritis to gastric cancer

OBJETIVO:descrever a mortalidade de idosos por doenças cardiovasculares, respiratórias e neoplasias no município de Marília-SP, Brasil.MÉTODOS:estudo descritivo da mortalidade pelos grupos de três doenças segundo a Décima Revisão da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde (CID-10), nos períodos 1998-2000 e 2005-2007; utilizaram-se registros do Sistema de Informações sobre Mortalidade (Sim) e calcularam-se os coeficientes de mortalidade por idade e sexo.RESULTADOS:doenças do aparelho circulatório lideraram as causas de mortalidade dos idosos (39,25%); houve declínio da mortalidade por neoplasias em ambos os sexos e na faixa etária de 60-69 anos, câncer da próstata nos homens (-83,36%) e de mama nas mulheres (-70,96%); óbitos por doenças do aparelho respiratório aumentaram aos 80 e mais anos, em homens (+39,31%) e mulheres (+57,92%).CONCLUSÃO:a mortalidade dos idosos por doenças cardiovasculares e neoplasias apresentou declínio, enquanto aumentou por doenças respiratórias na faixa etária ≥80 anos.

OBJECTIVE:to describe elderly mortality from cardiovascular and respiratory diseases and neoplasms in Marilia (SP).METHODS:this is a descriptive study of mortality from three diseases as defined by the 10th International Classification of Diseases, between 1998-2000 and 2005-2007. Mortality Information System records were used. Mortality rates by age and sex were calculated.RESULTS:circulatory diseases were the main causes of death among the elderly (39.25%). Neoplasm decline was noticed in both sexes and in those aged 60-69, particularly prostate cancer in men (-83.86%) and breast cancer (-70.96%) in this age group. Deaths from respiratory diseases increased in patients aged 80 and older: 39.31% in men and 57.92% in women.CONCLUSION:mortality from circulatory diseases and neoplasms among the elderly showed a decline, with increased mortality from respiratory system problems in patients 80 years of age and older.

OBJETIVO: descrever a mortalidade de idosos por doenças cardiovasculares, respiratórias e neoplasias no município de Marília-SP, Brasil. MÉTODOS: estudo descritivo da mortalidade pelos grupos de três doenças segundo a Décima Revisão da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde (CID-10), nos períodos 1998-2000 e 2005-2007; utilizaram-se registros do Sistema de Informações sobre Mortalidade (Sim) e calcularam-se os coeficientes de mortalidade por idade e sexo. RESULTADOS: doenças do aparelho circulatório lideraram as causas de mortalidade dos idosos (39,25%); houve declínio da mortalidade por neoplasias em ambos os sexos e na faixa etária de 60-69 anos, câncer da próstata nos homens (-83,36%) e de mama nas mulheres (-70,96%); óbitos por doenças do aparelho respiratório aumentaram aos 80 e mais anos, em homens (+39,31%) e mulheres (+57,92%). CONCLUSÃO: a mortalidade dos idosos por doenças cardiovasculares e neoplasias apresentou declínio, enquanto aumentou por doenças respiratórias na faixa etária ≥80 anos.

OBJECTIVE: to describe elderly mortality from cardiovascular and respiratory diseases and neoplasms in Marilia (SP). METHODS: this is a descriptive study of mortality from three diseases as defined by the 10th International Classification of Diseases, between 1998-2000 and 2005-2007. Mortality Information System records were used. Mortality rates by age and sex were calculated. RESULTS: circulatory diseases were the main causes of death among the elderly (39.25%). Neoplasm decline was noticed in both sexes and in those aged 60-69, particularly prostate cancer in men (-83.86%) and breast cancer (-70.96%) in this age group. Deaths from respiratory diseases increased in patients aged 80 and older: 39.31% in men and 57.92% in women. CONCLUSION: mortality from circulatory diseases and neoplasms among the elderly showed a decline, with increased mortality from respiratory system problems in patients 80 years of age and older.

Background:Only a few Helicobacter pylori-infected individuals develop severe gastric diseases and virulence factors of H. pyloriappear to be involved in such clinical outcomes. Duodenal ulcer promoting gene A (dupA) is a novel virulence factor ofHelicobacter pylori that is associated with duodenal ulcer development and reduced risk for gastric carcinoma in some populations. The aims of the present study were to determine the presence ofdupA gene and evaluate the association amongdupA and other virulence factors includingcagA and vacA in Brazilian patients. Gastric biopsies were obtained from 205 dyspeptic patients (100 children and 105 adults). DNA was extracted and analyzed for the presence of H. pylori and its virulence factors using the polymerase chain reaction method.Results:Patients with gastritis tested positive for H. pylori more frequently. The dupA gene was detected in 41.5% of them (85/205); cagA gene was found in 98 isolates (47.8%) andvacA genotype s1/m1 in 50.2%, s1/m2 in 8.3%, s2/m2 in 36.6%, s2/m1 in 0.5% and s1/s2/m1/m2 in 4.4%. We also verified a significant association between cagA and dupA genes [p = 0.0003, relative risk (RR) 1.73 and confidence interval [CI] = 1.3-2.3]. The genotypes s1/m1 were also associated with dupA gene (p = 0.0001, RR: 1.72 and CI: 1.3-2.2). The same associations were found when analyzing pediatric and adult groups of patients individually.Conclusion:Ours results suggest that dupA is highly frequent in Brazilian patients and is associated with cagA gene andvacA s1/m1 genotype, and it may be considered an important virulence factor in the development of gastric diseases in adults or children.

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.

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 < 0.001). No association of AD with either the IL-1α or the IL-8 polymorphism was observed, nor was any interactive effect between both polymorphisms. These results confirm previous studies in other populations, in which polymorphisms IL-8 -251T > A and IL-1α-889C > T were not found to be risk factors for AD.

Helicobacter pylori is an important human pathogen that causes chronic gastritis and is associated with the development of peptic ulcer disease and gastric malignancies. The oral cavity has been implicated as a potential H. pylori reservoir and may therefore be involved in the reinfection of the stomach, which can sometimes occur following treatment of an H. pylori infection. The objectives of this paper were (i) to determine the presence of H. pylori in the oral cavity and (ii) to examine the relationship between oral H. pylori and subsequent gastritis. Gastric biopsies, saliva samples and dental plaques were obtained from 78 dyspeptic adults. DNA was extracted and evaluated for the presence of H. pylori using polymerase chain reaction and Southern blotting methods. Persons with gastritis were frequently positive for H. pylori in their stomachs (p < 0.0001) and there was a statistically significant correlation between the presence of H. pylori in gastric biopsies and the oral cavity (p < 0.0001). Our results suggest a relationship between gastric infection and the presence of this bacterium in the oral cavity. Despite this, H. pylori were present in the oral cavity with variable distribution between saliva and dental plaques, suggesting the existence of a reservoir for the species and a potential association with gastric reinfection.

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.

A colonização do Helicobacter pylori está associada com gastrite crônica, úlcera péptica, metaplasia intestinal, adenocarcinoma e linfoma gástrico. O objetivo desse estudo foi comparar os resultados do diagnóstico histológico usado de rotina na detecção do H. pylori com o diagnóstico molecular. Foram utilizadas amostras de 80 lesões gástricas (gastrite crônica, gastrite atrófica, úlcera gástrica e metaplasia intestinal), 18 amostras de adenocarcinoma gástrico e 10 amostras de mucosa gástrica normal H. pylori negativas (controle). Todas as amostras foram avaliadas histologicamente (coloração com hematoxilina-eosina e Giemsa) e pela PCR com a amplificação dos genes antígeno espécie-específico (H3H4) e urease A (H5H6) do H. pylori e pelo gene humano CYP1A1, como controle da qualidade do DNA. Nas amostras de lesão benigna e adenocarcinoma gástrico, a infecção foi detectada em 43% (42/98) e 71% (70/98), respectivamente, para os diagnósticos histológico e molecular (p = 0,0001). O teste de PCR detectou o H. pylori em 27,5% (22/80) das lesões gástricas benignas e em 50% (9/18) dos adenocarcinomas gástricos, com diagnóstico histológico negativo para essa bactéria. Cerca de 2,5% das amostras, exclusivamente de lesões benignas, com diagnóstico histológico positivo apresentaram resultado molecular negativo, para ambos os primers. Diferenças estatisticamente significantes foram encontradas entre os métodos histológico e molecular, em metaplasia intestinal (p = 0,0461) e adenocarcinoma gástrico (p = 0,0011), devido à subdetecção do H. pylori pelo método histológico, e provavelmente pela baixa densidade da bactéria conseqüente à atrofia severa da mucosa gástrica, nesses dois tipos de lesões. Nossos achados demonstram que o método de PCR é mais eficaz para diagnosticar a infecção por H. pylori, principalmente, em metaplasia intestinal e adenocarcinoma gástrico.

Helicobacter pylori colonization is associated with chronic gastritis, peptic ulcers, intestinal metaplasia, adenocarcinoma and lymphoma of the stomach. The objective of this study was to compare the results of the routinely used histology with molecular diagnosis for the detection of H. pylori. Eighty samples from gastric lesions (chronic gastritis, atrophic gastritis, gastric ulcer, and intestinal metaplasia), 18 gastric adenocarcinoma and 10 normal mucosa H. pylori-negative (control) samples were obtained. All samples were examined histologically (hematoxylin-eosin and Giemsa staining), and PCR amplifications of the species-specific antigen gene (H3H4) and urease A gene segment (H5H6) of H. pylori were made, using the human gene CYP1A1 for DNA quality control. In the benign lesion and adenocarcinoma the infection was detected in 43% (42/98) and 71% (70/98) by histological and molecular diagnosis (p = 0.0001), respectively. The PCR test detected H. pylori in 27.5% (22/80) of the benign gastric lesions and in 50% (9/18) of the gastric adenocarcinoma cases, the histological diagnosis being negative for this bacterium. About 2.5% of the samples, exclusively from benign lesions and with a positive histological diagnosis, showed negative molecular results for both primers. Statistically significant differences were found between the histological and the molecular method in intestinal metaplasia (p = 0.0461) and gastric adenocarcinoma (p = 0.0011), due to underdetection of H. pylori by the histological method, which is probably due to the low density of the bacterium as a consequence of the severe atrophy of the gastric mucosa. Our findings suggest that PCR is the more efficient method for the assessment of H. pylori infection, especially in metaplasia and gastric adenocarcinoma.