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Biomedical subjects

R Montesano

Publications and source records attributed to R Montesano.

304 records · Page 17Linked to original sources
PubMedDate not supplied

Aflatoxin exposure, malaria and hepatitis B infection in rural Gambian children.

Aflatoxin-albumin adduct levels were measured in serum samples obtained from a group of Gambian children. The relationships between exposure to aflatoxin and the prevalence of malaria, between exposure and humoral and cellular responses in vitro to defined malaria antigens and, amongst children with evidence of exposure to hepatitis B infection, between aflatoxin and carriage of the hepatitis B surface antigen (HBsAg), were assessed. Aflatoxin-albumin adduct was found in nearly all serum samples collected during a survey performed at the end of the dry season and levels of adduct were generally high (up to 720 pg aflatoxin-lysine equivalent/mg albumin). Higher levels of aflatoxin-albumin adduct were detected in Wollof children than in children of other ethnic groups and marked variation in mean adduct levels between villages was observed. Aflatoxin-albumin adduct levels were higher in children who were HbsAg positive and in children with Plasmodium falciparum parasitaemia than in controls. However, levels of adduct had no consistent effect on either malaria-specific antibody responses, lymphoproliferative responses in vitro, or morbidity from malaria during the subsequent rainy season. Much lower levels of aflatoxin-albumin adduct were detected in repeat samples obtained at the end of the rainy season. There was poor correlation between dry and rainy season levels of adduct in individual children. We have shown that Gambian children are exposed to high levels of aflatoxin. The seasonal variation of aflatoxin-albumin adduct and marked fluctuation of adduct with time in individual children need to be considered in the future planning of epidemiological studies using this marker of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxins↗
PubMedDate not supplied

Evidence for polarization of plasma membrane domains in pancreatic endocrine cells.

Polarization of plasma membrane domains is an essential feature of secretory epithelial cells from exocrine glands. The surface of exocrine cells (a typical example is the acinar cell of the pancreas) is separated into an apical domain, where secretion occurs by exocytosis, and a basolateral domain, which senses variations of the internal milieu and is enriched with receptors for various hormones and secretagogues. It is unknown whether secretion is polarized in endocrine cells (except for thyroid follicular cells, which are organized into cavitary structures). To determine whether distinct plasma membrane domains exist in endocrine cells, we infected monolayer cultures of pancreatic endocrine cells with enveloped RNA viruses known to bud selectively from either the apical or basolateral domain in polarized epithelial cells. This asymmetrical budding is thought to reflect the polarized nature of the infected cells, as in non-polarized cells such as fibroblasts, the same viruses bud nonselectively from the entire cell surface. We show here that influenza virus and vesicular stomatitis virus (VSV) emerge asymmetrically from cultured pancreatic islet cells; this represents the first evidence for polarization of plasma membrane domains in pancreatic endocrine cells.

Animals↗
PubMedDate not supplied

Alkylation of DNA and carcinogenicity of N-nitroso compounds.

The possible mode of action of two classes of highly organ- and species-specific carcinogenic N-nitroso compounds, namely the N-nitrosamines and N-nitrosamides, is outlined in this review. Chemical or enzymatic conversion of these agents into active alkylating species is a prerequisite for their biological activity. Although these species are capable of reacting with all cellular macromolecules, there is good evidence that their ability to attack DNA is related to their carcinogenicity. This paper reviews the reasons and experimental support for the hypothesis that it is specifically alkylation of DNA at the O6 position of guanine that initiates malignant transformation, an important factor being the presence of an enzyme system capable of eliminating O6-alkylguanine from DNA. No such repair reaction appears to exist for this or other alkylation products when they are present in RNA. The activity of this system is enhanced by chronic administration of alkylating agents, and the role that this may play in carcinogenesis is discussed.

Alkylation↗
PubMedDate not supplied

Molecular dosimetry of aflatoxin-N7-guanine in human urine obtained in The Gambia, West Africa.

Hepatocellular carcinoma is one of the major human cancers, causing at least 250,000 deaths each year. Two of the major risk factors for this disease are aflatoxin exposure and hepatitis B virus. This study was undertaken to explore the relationship between dietary exposure to aflatoxins and the excretion of the major aflatoxin-DNA adduct and other metabolites into the urine of chronically exposed people who were either hepatitis B virus surface antigen-positive or -negative. The diets of 20 individuals, 10 males and 10 females, with ages ranging from 15 to 56 years, were monitored for 1 week, and aflatoxin intake levels were determined for each day. Starting on the fourth day, total 24-h urines were consecutively obtained for 4 days. The subjects were generally paired for hepatitis B virus status. Preparative monoclonal antibody affinity chromatography/high-performance liquid chromatography and competitive enzyme-linked immunosorbent assays were carried out on each of the urine samples, and the relationship between aflatoxin intake values and the excretion of (a) total aflatoxin metabolites and (b) aflatoxin-N7-guanine (AFB-N7-guanine) was determined. The average intake of total aflatoxins was 12.0 micrograms for the entire study group during the 1-week collection period. However, there was considerable day-to-day variation in exposures, from a low of zero to a high of 29.6 micrograms total aflatoxins/day. Initial efforts to characterize total aflatoxin metabolites in the urine samples were made by competitive enzyme-linked immunosorbent assay. The correlation coefficient for the analysis was 0.65, with P < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Dietary intake of aflatoxins and the level of albumin-bound aflatoxin in peripheral blood in The Gambia, West Africa.

Aflatoxin is implicated as a risk factor for hepatocellular carcinoma in areas of the world with a high incidence of this tumor. The present study was designed to validate the use of aflatoxin-albumin adducts in peripheral blood as a measure of individual exposure to this carcinogen. Dietary intake of aflatoxin was measured at the individual level in 20 residents of Keneba, West Kiang, The Gambia, over a 7-day period and correlated with the level of aflatoxin bound to peripheral blood albumin at the beginning and end of the study. Complementary enzyme-linked immunosorbent assay and high-performance liquid chromatography-fluorescence techniques were used to assay the aflatoxin adducts. All subjects were exposed to aflatoxin originating from several food types, with an average daily intake of 1.4 micrograms/day. A significant correlation (r = 0.55; P = < 0.05) was observed between the dietary intake and the level of albumin-bound aflatoxin at the end of the study. In addition, a good agreement was obtained with the two analytical techniques. A comparison of matched chronic hepatitis B surface antigen carriers with noncarriers did not reveal any difference in adduct formation for a given dietary intake of aflatoxin. These studies demonstrate the validity of aflatoxin-albumin adducts as a marker of human exposure to this carcinogen.

Adolescent↗
PubMedDate not supplied

Aflatoxin, liver enzymes, and hepatitis B virus infection in Gambian children.

The relative contribution of, and possible mechanism of interaction between, aflatoxin and hepatitis B virus (HBV) in the development of primary hepatocellular carcinoma can be better investigated now that markers of individual exposure to both factors are available. In this study, blood samples were collected over a 1-month period from 117 children aged 3 to 4 years, resident in Kuntair or Kerr Cherno in the Upper Niumi District of The Gambia. Samples were analyzed for aflatoxin-albumin (AF-alb) adducts, markers of HBV infection, liver enzymes [serum alanine aminotransferase (ALT)] as markers of liver damage, and glutathione S-transferase M1 genotype. All but two children showed detectable serum AF-alb with levels ranging from 2.2 to 250.4 pg aflatoxin B1-lysine equivalent/mg albumin. There was a significant positive correlation between AF-alb and ALT (r = 0.4; P < 0.001). HBV carriers showed moderately higher levels of AF-alb than noncarriers but the difference was not statistically significant and the association between AF-alb and ALT was unchanged when the HBV carriers were excluded from the analysis, suggesting that factors other than HBV infection contributed to the association. The null glutathione S-transferase M1 genotype was infrequent (17.7%) in this population and was not associated with any difference in AF-alb adduct levels compared to glutathione S-transferase M1-positive individuals. However, the percentage of individuals with the null genotype varied significantly between ethnic groups with 32.1% in Fula, 8.8% in Mandinka, and 13.3% in Wollof.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxins↗
PubMedDate not supplied

[Hepatocellular carcinoma: a preventable cancer].

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and a public health concern in many developing countries. The main risk factor is the chronic carriage state of the hepatitis B virus which is found in about 20% of the adult population in many African and Asian countries. Other important risk factors are HCV infection, aflatoxin exposure and alcohol consumption. The Gambia Hepatitis Intervention Study was launched in 1986 with the aim of evaluating the efficacy of the hepatitis B vaccination, given in early infancy, in preventing HBV infection, its chronic carriage status, and later, HCC. For this purpose, a randomised vaccine trial was designed and carried out. Over a period of four years a total of 124.577 children were recruited, one half received the usual EPI vaccines (BCG, DTP, OPV, measles, yellow fever) and the other half the hepatitis B vaccine in addition to the EPI ones. Hepatitis B vaccination has been successfully integrated into the "Expanded Programme of Immunization" in The Gambia, since every new born baby can receive this vaccination in addition to the EPI vaccine. The first mid point evaluation showed that in four-year-old children, hepatitis B vaccine efficacy was 84% in preventing infection and 94% in preventing chronic carriage status of HBV. Other mid point evaluations are still ongoing. A nationwide Cancer Registry was set up to detect HCC cases in the cohort under study. Follow-up through the Cancer Registry is planned for the next 30 years.

Adult↗