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Pelayo Correa

Publications and source records attributed to Pelayo Correa.

At least 37 records · Page 2Linked to original sources
PubMed2004

Supraglottic and glottic carcinomas: epidemiologically distinct entities?

In the time period 1988-2000, a case-control study on laryngeal cancer was conducted in Montevideo, Uruguay. Four-hundred eighty-one (481) cases newly diagnosed and microscopically confirmed as squamous cell carcinomas were included. These cases were frequency matched with 481 nonneoplastic controls, admitted to the same hospitals as the cases. The purpose of our study was to compare odds ratios (ORs) by laryngeal subsite (supraglottis and glottis). ORs of supraglottic cancers displayed much higher risks than glottic carcinomas for most tobacco variables and for red wine intake. The differences between subsites were statistically significant, displaying heterogeneity between both subsites. Moreover, whereas black tobacco smokers displayed a significant increased risk of 1.7 (95% confidence interval [CI] 1.2-2.5) compared to smokers of blond (flue-cured) tobacco among supraglottic tumors, no effect of this type of tobacco was observed in glottic lesions. It could be suggested that concerning tobacco and alcohol effects, supraglottic and glottic squamous cell cancers are probably distinct epidemiologic entities.

Adult↗
PubMed2004

Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses.

T cells infiltrating tumors have a decreased expression of signal transduction proteins, a diminished ability to proliferate, and a decreased production of cytokines. The mechanisms causing these changes have remained unclear. We demonstrated recently that peritoneal macrophages stimulated with interleukin 4 + interleukin 13 produce arginase I, which decreases the expression of the T-cell receptor CD3zeta chain and impairs T-cell responses. Using a 3LL murine lung carcinoma model we tested whether arginase I was produced in the tumor microenvironment and could decrease CD3zeta expression and impair T-cell function. The results show that a subpopulation of mature tumor-associated myeloid cells express high levels of arginase I, whereas tumor cells and infiltrating lymphocytes do not. Arginase I expression in the tumor was seen on day 7 after tumor injection. Tumor-associated myeloid cells also expressed high levels of cationic amino acid transporter 2B, which allowed them to rapidly incorporate L-Arginine (L-Arg) and deplete extracellular L-Arg in vitro. L-Arg depletion by tumor-associated myeloid cells blocked the re-expression of CD3zeta in stimulated T cells and inhibited antigen-specific proliferation of OT-1 and OT-2 cells. The injection of the arginase inhibitor N-hydroxy-nor-L-Arg blocked growth of s.c. 3LL lung carcinoma in mice. High levels of arginase I were also found in tumor samples of patients with non-small cell carcinoma. Therefore, arginase I production by mature myeloid cells in the tumor microenvironment may be a central mechanism for tumor evasion and may represent a target for new therapies.

Amino Acid Sequence↗
PubMed2004

Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin.

Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.

ABO Blood-Group System↗
PubMed2004

13C-urea breath test for Helicobacter pylori in young children: cut-off point determination by finite mixture model.

The 13C-urea breath test (UBT) is currently regarded as one of the most important noninvasive diagnostic methods for detecting Helicobacter pylori (H. pylori) infection in adults and children. However, for infants and young children, the standard for UBT interpretation has not been validated, and its reliability has not been established for diagnosing H. pylori infection in this group. The primary outcome data from UBT consist of mixture data, which come from subjects whose H. pylori infection classifications are unconfirmed. In this paper, we propose the finite mixture distribution method to identify a reliable UBT cut-off value in a large baseline sample in which gastric biopsy is not available to confirm the H. pylori infection in younger children. Maximum likelihood estimators of the parameters in the mixture model were obtained using an expectation maximization (EM) algorithm. The standard deviation of the cut-off point was estimated by bootstrap methods. We applied the same analytical methods to the UBT results yielded from the follow up, as well as the overall UBT results in the longitudinal cohort data. The cut-off points from those UBT data sets are similar. The advantage of the finite mixture model is that it may be used to calculate sensitivity and specificity in the absence of other diagnostic tests.

Breath Tests↗
PubMed2004

Helicobacter pylori arginase inhibits T cell proliferation and reduces the expression of the TCR zeta-chain (CD3zeta).

Helicobacter pylori infects approximately half the human population. The outcomes of the infection range from gastritis to gastric cancer and appear to be associated with the immunity to H. pylori. Patients developing nonatrophic gastritis present a Th1 response without developing protective immunity, suggesting that this bacterium may have mechanisms to evade the immune response of the host. Several H. pylori proteins can impair macrophage and T cell function in vitro through mechanisms that are poorly understood. We tested the effect of H. pylori extracts and live H. pylori on Jurkat cells and freshly isolated human normal T lymphocytes to identify possible mechanisms by which the bacteria might impair T cell function. Jurkat cells or activated T lymphocytes cultured with an H. pylori sonicate had a reduced proliferation that was not caused by T cell apoptosis or impairment in the early T cell signaling events. Instead, both the H. pylori sonicate and live H. pylori induced a decreased expression of the CD3zeta-chain of the TCR. Coculture of live H. pylori with T cells demonstrated that the wild-type strain, but not the arginase mutant rocF(-), depleted L-arginine and caused a decrease in CD3zeta expression. Furthermore, arginase inhibitors reversed these events. These results suggest that H. pylori arginase is not only important for urea production, but may also impair T cell function during infection.

Apoptosis↗
PubMed2004

The future of gastric cancer prevention.

Despite advances in surgical treatment and chemotherapy, gastric cancer remains a major global health burden. The most recent estimates show that it is the fourth most common cancer and the second most common cause of cancer deaths worldwide. Various etiologic factors have been linked with the disease. It is widely accepted that Helicobacter pylori infection and high salt intake are positively associated with this neoplastic process. Controversial associations have been found with smoking or drinking habits. In contrast, there is convincing evidence that the adequate consumption of fresh fruits and vegetables reduces the risk of gastric cancer. Prevention intervention trials involving antioxidant supplements and anti- H. pylori treatment have shown beneficial effects in preventing the progression of pathologic changes in the gastric mucosa. On the other hand, recent advances related to differences in the genotypes of the bacteria and in human cytokine polymorphisms would allow the design and implementation of large-scale screening programs to identify subjects at the highest risk of gastric cancer. Curing the infection in such subjects and supplying adequate amounts of antioxidants should prevent a neoplastic outcome, and this intervention should be monitored by endoscopic surveillance.

Antioxidants↗
PubMed2004

Dietary patterns and risk of gastric cancer: a case-control study in Uruguay.

BACKGROUND: Gastric cancer is a frequent malignancy in the Uruguayan population. In northern counties, incidence rates reach high figures (age-standardized rates [ASR], 37.3 per 100,000 men and 18.3 per 100,000 women). Diet is a major determinant in gastric carcinogenesis. Because foods or food groups have the advantage over nutrients in being most directly related to dietary recommendations, we decided to conduct a case-control study on the relationships between food groups and risk of gastric cancer. For this purpose, we included 240 cases and 960 controls. METHODS: In the present study we employed three analytical approaches: (1) individual food group analysis, (2) factor analysis, and (3) analysis of empirical scores of risk. Individual analysis of food groups was performed by multiple unconditional logistic regression, with food groups being the explanatory variables. Nineteen food groups were created and categorized in tertiles according to the control distribution. Factor analysis aggregated intercorrelated foods in broader eating patterns. In this study we were able to identify three factors or patterns, arbitrarily labeled "starchy," "healthy," and "mixed." Finally, empirical scores of risk were created after examining the risk of each individual food and summing each significant item. This resulted in a risk enhancing score and a protective score. Both scores were categorized in tertiles according to the control distribution. RESULTS: The individual analysis of food groups showed increased risks of gastric cancer for rice, salted meat, stewed meat, white bread, potatoes, and tubers. On the other hand, raw vegetables, total fruits, legumes, and black tea were inversely associated with risk of gastric cancer. All three dietary patterns, generated by factor analysis, were significantly associated with gastric carcinoma risk. Whereas the starchy factor was directly associated with gastric cancer, the healthy and mixed patterns were strongly protective. Finally, the risk enhancing empirical score displayed an increased risk of gastric cancer (odds ratio [OR], 4.1, 95% confidence interval [CI], 2.6-6.6), whereas the protective score showed an important reduction in risk, of 0.38. CONCLUSION: This study displayed consistent results from three different approaches. Concerning different food groups, stewed and processed meat are rich in salt; rice, tubers, and winter squash are sources of starch; and vegetables and fruits are rich in ascorbic acid and carotenoids. All these substances have been strongly related to gastric carcinogenesis. Furthermore, this study suggests that diets rich in vegetables and fruits and with low amounts of salty and starchy foods are recommendable for the prevention of gastric cancer.

Adult↗
PubMed2004

Infrequency of microsatellite instability in complete and incomplete gastric intestinal metaplasia.

Chronic inflammation may be associated with microsatellite instability (MSI). To test the hypothesis that MSI frequently occurs in gastric intestinal metaplasia, we examined gastric biopsies from 58 subjects from an area of high risk for gastric cancer. These were selected to have 2 types of intestinal metaplasia: complete (31 subjects) and incomplete or mixed-type (27 subjects). None of the subjects had gastric cancer, but 95% had chronic inflammation with Helicobacter pylori. We used laser capture microdissection to retrieve metaplastic glands to compare with lymphocytes microdissected from the adjacent gastric mucosae in the same subjects. We performed microsatellite analysis using 6 microsatellite loci, including BAT26. None of the cases were found to have reproducible MSI, and only 1 case showed loss of heterozygosity at 1 marker, D3S1067. To test the sensitivity of our assay, we mixed templates to produce bands of different mobility and found that we could detect an aberrant microsatellite pattern if only 2% of the DNA showed that pattern. Our results indicate that MSI is a rare event in intestinal metaplasia in subjects who do not have gastric cancer.

Base Pair Mismatch↗
PubMed2004

Role and limitations of epidemiology in establishing a causal association.

Cancer risk assessment is one of the most visible and controversial endeavors of epidemiology. Epidemiologic approaches are among the most influential of all disciplines that inform policy decisions to reduce cancer risk. The adoption of epidemiologic reasoning to define causal criteria beyond the realm of mechanistic concepts of cause-effect relationships in disease etiology has placed greater reliance on controlled observations of cancer risk as a function of putative exposures in populations. The advent of molecular epidemiology further expanded the field to allow more accurate exposure assessment, improved understanding of intermediate endpoints, and enhanced risk prediction by incorporating the knowledge on genetic susceptibility. We examine herein the role and limitations of epidemiology as a discipline concerned with the identification of carcinogens in the physical, chemical, and biological environment. We reviewed two examples of the application of epidemiologic approaches to aid in the discovery of the causative factors of two very important malignant diseases worldwide, stomach and cervical cancers. Both examples serve as paradigms of successful cooperation between epidemiologists and laboratory scientists in the pursuit of the understanding of cancer etiology.

Carcinogens↗
PubMed2004

Phenotypic differences between esophageal and gastric intestinal metaplasia.

Intestinal metaplasia is a cancer precursor in the esophagus and the stomach. Marked differences exist between the carcinogenic processes in the two locations in terms of natural history and clinical significance. We investigated biopsies from 52 patients with Barrett's esophagus and from 50 patients with gastric intestinal metaplasia in an attempt to throw light on their pathogenic processes. Morphologic characteristics, presence of Helicobacter pylori (H. pylori), and markers of differentiation, inflammation, and proliferation were evaluated by histochemical and immunohistochemical techniques. The area covered by incomplete type of intestinal metaplasia and the proportion of sulfomucins were significantly higher in the esophagus than in the stomach. Immunoreactivity with MUC1, MUC2, MUC5AC, Das-1, cytokeratins 7 and 20, inducible nitric oxide synthase and cyclooxygenase-2 antibodies was also significantly greater in Barrett's esophagus than in gastric intestinal metaplasia. In gastric intestinal metaplasia, the presence of MUC1, MUC5AC, Das-1 and cytokeratin 7 was restricted to areas with the incomplete type of metaplasia. Cell proliferation (Ki-67) was significantly higher in Barrett's esophagus than in gastric intestinal metaplasia. H. pylori was absent in all of the patients with Barrett's esophagus, while it was present in 70% of the patients with gastric intestinal metaplasia. Our observations made clear that Barrett's esophagus shares some phenotypic characteristics with gastric intestinal metaplasia, leading us to suggest that both could arise in response to injuries with eventual carcinogenic potential. However, the progression to more advanced lesions could be modulated by the nature of the carcinogenic insult.

Aged↗
PubMed2004

Determinants of Helicobacter pylori seroprevalence in Mexican adolescents.

BACKGROUND: Helicobacter pylori infection is one of the most common human infections and is considered to play an etiologic role in several gastroduodenal diseases. In this study we determined the H. pylori seroprevalence among adolescents in Morelos, Mexico, and explored the association between seroprevalence and socioeconomic, dietary and lifestyle variables. MATERIALS AND METHODS: A cross-sectional study was conducted in 5861 Mexican subjects aged 11-21 years. H. pylori infection was determined by an enzyme-linked immunosorbent assay previously validated in Mexico. A self-administered questionnaire was used to collect information on sociodemographic factors, housing, living conditions and food consumption. Multivariate logistic regression methods were used to obtain odds ratios and 95% confidence intervals. RESULTS: The overall H. pylori seroprevalence was 47.6%; 40.6% in preadolescents (11-14 years), 48.6% in adolescents (15-17 years), and 59.8% in young adults (18-24 years). A positive association was found between age and H. pylori seroprevalence. Inverse associations were found for availability of drinking water, sewerage, and home appliances at the time of the subject's birth, a proxy variable of socioeconomic status. Intake of milk products and total fats was positively associated with infection. CONCLUSIONS: This large seroprevalence study showed that H. pylori infection is frequent among adolescents in Mexico. An early acquisition of infection is indirectly suggested. Some variables denoting low socioeconomic status were inversely associated with H. pylori seroprevalence. Associations with intake of milk products and total fats suggest new hypotheses in this field of research.

Adolescent↗
PubMed2004

Age at acquisition of Helicobacter pylori infection: comparison of two areas with contrasting risk of gastric cancer.

BACKGROUND: Helicobacter pylori infection is usually acquired during childhood and is a known risk factor for the development of gastric malignancies in adulthood. It has been reported that early age at first infection may determine a neoplastic outcome in adults. The purpose of this study was to determine the prevalence of Helicobacter pylori infection in children residing in areas with high (Pasto) and low risk (Tumaco) of gastric cancer in Colombia to evaluate whether differences in the age of acquisition of H. pylori infection were present in the two populations. MATERIALS AND METHODS: The study sample was based on a census taken in 1999. Using the (13)C-urea breath test, we compared the prevalence of H. pylori infection among children aged 1-6 years. RESULTS: Among 345 children in Pasto, 206 (59.7%) were H. pylori-positive, compared with 188 (58.6%) among 321 children in Tumaco. The two populations share a common pattern of very early age at infection and marked increase in prevalence during the first 4 years of life. No differences in any one year were observed when comparing the two groups. CONCLUSIONS: The prevalence of infection was similarly high and increased with age in both populations. In these populations the age of acquisition of H. pylori after 1 year of age does not appear to be a primary factor responsible for the differences in the rates of gastric cancer incidence in adults. Previous findings in adults showed lower prevalence of the most virulent genotypes in Tumaco compared to Pasto, and bacterial virulence may play a key role in determining cancer outcome.

Age of Onset↗
PubMed2004

The biological model of gastric carcinogenesis.

The biological model of gastric carcinogenesis can be described as a series of sequential phases. The first consists of a chronic active inflammatory response to Helicobacter pylori infection. Infiltration of the gastric mucosa by mucosa-associated lymphoid tissue and polymorphonuclear neutrophils, as well as damage to the epithelial cells, characterize this phase. The second phase is dominated by alterations of the epithelial cell cycle, especially increased rates of apoptosis and cell proliferation. These changes may be responsible for the multifocal atrophy that characterizes the type of gastritis associated with an increased risk of cancer. The third, more advanced phase of the model displays nuclear and architectural abnormalities, which may represent progressive mutational events as expected in classical molecular models of carcinogenesis. The importance of a comprehensive view of the biological model is stressed.

Cell Differentiation↗
PubMed2003

Detection and typing of Helicobacter pylori cagA/vacA genes by radioactive, one-step polymerase chain reaction in stool samples from children.

The detection and molecular typing of Helicobacter pylori virulence genes in human stool specimens by polymerase chain reaction (PCR) require an adequate amount of bacterial DNA and an appropriately adjusted PCR protocol. DNA was isolated from stool samples of 39 H. pylori-infected and nine uninfected Colombian children using the QIAamp Kit following the manufacturer's instructions but with modifications. DNA templates were amplified for the vacA s and m regions and for the cagA gene by PCR using radioactively labeled (32P) primers. The modifications in the standard Qiagen protocol of stool DNA extraction increased the final concentration of eluted total stool DNA 4.7 times (117 +/- 17 versus 22 +/- 3 ng/microl; P < 0.0001). Nevertheless, its amplification by regular PCR programs (30-40 cycles) did not generate visible signals because of the very low ratio of H. pylori DNA to other DNA. PCR for 80 cycles successfully amplified vacA in 36/39 samples (sensitivity, 92.3%) and cagA fragments in 21/39 (53.8%) fecal DNA samples. Both s and m vacA regions were amplified in 33/36 (91.7%) DNA samples. The s1m1 genotype was the most commonly isolated variant, accounting for 17/36 or 47.2% of positive samples. The s2m2 genotype was ascertained to be frequent also (14/36 or 38.9%). Almost all (94.1%) s1m1 genotypes were cagA positive. The majority of s2m2 genotypes (78.6%) were not associated with the cagA gene. Neither cagA nor vacA fragments were amplified from DNA isolates of H. pylori-uninfected children nor from DNA isolated from six gastrointestinal bacterial strains (specificity, 100%). The data suggest that the proposed modified technique of DNA extraction and PCR assay of stool samples may be an effective and reliable noninvasive tool for the detection and typing of H. pylori cagA/vacA virulence genes in infected individuals.

Antigens, Bacterial↗
PubMed2003

A positive assay for identification of cagA negative strains of Helicobacter pylori.

A new PCR protocol was developed for the positive identification of cagA negative Helicobacter pylori strains. Amplification of a portion of the genome across the insertion point of the cag pathogenicity island (the ES-"empty site") generated a 106-bp fragment, which produces a positive signal for cagA negative strains. Combined with the results of the cagA assay, the signals for ES allowed the complete characterization of the patients' cagA status. DNA sequencing analysis confirmed the identity of the ES fragment. The new protocol and cagA assay were applied to 22 DNA preparations isolated from stools from H. pylori infected adult patients and to 21 DNA preparations isolated from stools from H. pylori infected children. The same analysis was also performed on nine colonies of H. pylori derived from gastric biopsies of nine of the adult patients. The total number of cagA positive cases from adult patients was 14 or 63.6% (11 mono- and 3 mixed) and of the cagA negative cases (or ES positive) was 9 or 40.9% (6 mono- and 3 mixed). Of the 21 stool DNA samples from children, 6 (28.6%) were cagA positive, 12 (57.1%) were cagA negative and 3 (14.3%) were positive for cagA and for the ES simultaneously. The proportions of mixed cagA positive and cagA negative H. pylori infections were almost equal in adults and children (13.6% and 14.3%, respectively). No reaction products of the proper fragment sizes for cagA or the empty site (ES) were obtained from any of the stool DNA samples of 10 H. pylori uninfected subjects (100% specificity). This noninvasive assay discriminates consistently cagA negative cases from cagA positive strains and from amplification failures. It can be a useful tool for clinical and epidemiological studies of H. pylori infection.

Adult↗