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Biomedical subjects

E Conti

Publications and source records attributed to E Conti.

At least 19 recordsLinked to original sources

Selected micronutrients and oral and pharyngeal cancer.

The relation between selected micronutrients and oral and pharyngeal cancer risk was investigated using data from a case-control study conducted between January 1992 and November 1997 in Italy and Switzerland. Cases were 754 incident, histologically confirmed oral cancers (344 of the oral cavity and 410 of the pharynx) admitted to the major teaching and general hospitals in the study areas. Controls were 1,775 subjects with no history of cancer admitted to hospitals in the same catchment areas for acute, non-neoplastic diseases. Dietary habits were investigated using a validated food-frequency questionnaire. Odds ratios (ORs) were computed after allowance for age, sex, center, education, occupation, body mass index, smoking and drinking habits and non-alcohol energy intake. Micronutrients were analyzed both as continuous variables and in quintiles. In the former case, the unit was set to 1 SD of the distribution of controls. ORs for the continuous analysis were 0.95 for retinol, 0.61 for carotene, 0.91 for lycopene, 0.83 for vitamin D, 0.74 for vitamin E, 0.63 for vitamin C, 0.82 for thiamine, 0.87 for riboflavin, 0.59 for vitamin B6, 0.61 for folic acid, 0.62 for niacin, 0.91 for calcium, 0.88 for phosphorus, 0.65 for potassium, 0.82 for iron, 0.67 for non-alcohol iron and 0.89 for zinc; the 95% confidence interval excluded one for carotene, vitamin C and E, thiamine, vitamin B6, folic acid, niacin, potassium and iron. ORs were similar for the 2 sexes and in strata of age. When the combined intake of vitamins C and E and carotene was considered, the protective effect of each nutrient was more marked or restricted to subjects with low intake of the other 2. The association with vitamin C and carotene was independent of smoking and drinking habits, while that with vitamin E was less evident in those heavily exposed to alcohol or tobacco. In general, the more a micronutrient was correlated to total vegetable and fruit intake, the stronger was its protective effect against oral cancer.

Adult↗

Cessation of alcohol drinking and risk of cancer of the oral cavity and pharynx.

A strong, dose-dependent association exists between alcohol consumption and risk of cancer of the oral cavity and pharynx. The impact on risk of temporal aspects of drinking habits has been inadequately evaluated. Our case-control study included 754 individuals with incident cancer of the oral cavity and pharynx (median age 57) and 1,775 controls (median age 57) in the hospital for acute, non-neoplastic diseases who were interviewed in 2 Italian areas and in the Swiss Canton of Vaud between 1992 and 1997. The questionnaire included lifetime drinking and smoking habits. No influence of age at starting or duration of alcohol drinking was found. Risk increased substantially with the increase of weekly alcoholic drinks [Odds Ratios (OR) for >/= 91 drinks/week vs. never drinkers = 11.6]. Risk in former compared with current drinkers was 1.9-fold elevated. However, among individuals who had also stopped smoking, former drinkers showed lower ORs than current drinkers. The persistence of risk elevation several years after drinking cessation suggests that the role of alcohol is complex and it probably affects more than one stage of oral carcinogenesis. It remains to be clarified which impact prevention-driven drinking cessation may have on the excess of cancer of the oral cavity and pharynx due to elevated alcohol intake.

Adult↗

Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha.

BACKGROUND: Karyopherin alpha (importin alpha) is an adaptor molecule that recognizes proteins containing nuclear localization signals (NLSs). The prototypical NLS that is able to bind to karyopherin alpha is that of the SV40 T antigen, and consists of a short positively charged sequence motif. Distinct classes of NLSs (monopartite and bipartite) have been identified that are only partly conserved with respect to one another but are nevertheless recognized by the same receptor. RESULTS: We report the crystal structures of two peptide complexes of yeast karyopherin alpha (Kapalpha): one with a human c-myc NLS peptide, determined at 2.1 A resolution, and one with a Xenopus nucleoplasmin NLS peptide, determined at 2.4 A resolution. Analysis of these structures reveals the determinants of specificity for the binding of a relatively hydrophobic monopartite NLS and of a bipartite NLS peptide. The peptides bind Kapalpha in its extended surface groove, which presents a modular array of tandem binding pockets for amino acid residues. CONCLUSIONS: Monopartite and bipartite NLSs bind to a different number of amino acid binding pockets and make different interactions within them. The relatively hydrophobic monopartite c-myc NLS binds extensively at a few binding pockets in a similar manner to that of the SV40 T antigen NLS. In contrast, the bipartite nucleoplasmin NLS engages the whole array of pockets with individually more limited but overall more abundant interactions, which include the NLS two basic clusters and the backbone of its non-conserved linker region. Versatility in the specific recognition of NLSs relies on the modular.

Amino Acid Sequence↗

Production of polyunsaturated fatty acids by Pythium ultimum in solid-state cultivation.

The oleaginous fungus Pythium ultimum was cultivated on various solid substrates in order to achieve fungal oil enriched in the polyunsaturated fatty acids arachidonic acid and eicosapentaenoic acid. Cultivation parameters, such as incubation temperature and time, substrate composition, and moisture were optimized, so as to obtain as much as 3.5 mg eicosapentaenoic acid and 2.6 mg arachidonic acid/g of wet substrate consisting of 28.5% pearled barley, 5.75% spent malt grains, 5.75% linseed oil, and 60% nutrient solution.

Journal Article↗

Comparison of the effect of smoking and alcohol drinking between oral and pharyngeal cancer.

To compare the separate and combined effects of alcohol drinking and smoking between the 2 sites, we evaluated 274 men with oral cancer, 364 with pharyngeal cancer and 1,254 controls, frequency-matched for age and area of residence, from Italy and Switzerland. Extremely elevated risk increases for oral cancer (odds ratio, OR = 228) and pharyngeal cancer (OR = 100) were found for the highest joint level of drinking (>/=77 drinks/week) and smoking (>/=25 cigarettes/day). Ratios of ORs between oral cancer and pharyngeal cancer vs. controls, obtained by polytomous logistic regression, suggested that the risk increase for oral cancer was about 2-fold greater than that for pharyngeal cancer at each combined level of smoking and drinking, except at low levels of drinking in smokers. A clear departure from risk difference additivity was present for both oral and pharyngeal cancer in individuals heavily exposed to both factors versus non-smoking abstainers/light drinkers. Our findings thus help explain observations from descriptive epidemiology that, if smoking level in a population does not change substantially, but alcohol consumption increases, increase in oral cancer would be greater than at any other site in the upper aero-digestive tract, including cancer of the pharynx.

Adult↗

Risk factors for adenocarcinoma of the small intestine.

We have investigated the relation between alcohol, tobacco and dietary habits and risk of adenocarcinoma of the small intestine using data from 2 hospital-based case-control studies on intestinal cancers conducted in 6 Italian centres between 1985 and 1996. Cases were 23 patients below age 75 years with adenocarcinoma of the small intestine. Controls were 230 patients admitted to hospital for a wide spectrum of acute, non-neoplastic, non-digestive tract diseases, matched to cases on sex, age, study and centre. Odds ratios (ORs) were estimated using conditional logistic regression. Alcohol and tobacco consumption did not increase the risk of adenocarcinoma of the small intestine. The risk appeared to be directly related to intake of bread, pasta or rice (OR = 3.8), sugar (OR = 2.9) and red meat (OR = 4.6), and inversely to coffee (OR = 0.4), fish (OR = 0.3), vegetables (OR = 0.3) and fruit (OR = 0.6). Our results suggest that dietary correlates of adenocarcinoma of the small intestine are similar to those of colon cancer and at least of the same magnitude. While the present data are inconsistent with a major effect of tobacco or alcohol, a moderate association between these factors and small bowel cancer may have been obscured by the play of chance.

Adenocarcinoma↗

Isolation and characterization of a novel transcript embedded within HIRA, a gene deleted in DiGeorge syndrome.

We have isolated a few cDNAs from different human tissues, transcribed from the first intron of HIRA, a gene deleted in the DiGeorge syndrome. These cDNAs are produced by an intronic gene (22k48) which is transcribed by the HIRA opposite strand and is itself arranged in exons and subjected to alternative splicing. The longest continuum cDNA sequence we obtained is 3.6 kb long and contains 3 different exons and 2 introns. 22k48 cDNA is composed of several tandemly arranged repeated elements (Alu, LINEs, CAn) surrounding a unique sequence. In situ hybridization showed the presence of 22k48 RNA in the cytoplasm of CNS and PNS neurons. 22k48 RNA is able to bind cytoplasmic proteins in the range of 45 to 60 kDa. 22k48 is a new member of the small group of genes that are transcribed but not translated, and its haploinsufficiency could contribute to the pathogenesis of the DiGeorge syndrome.

Adult↗

Phylogenetic relationships of the silver saxifrages (Saxifraga, sect. Ligulatae haworth): implications for the evolution of substrate specificity, life histories, and biogeography.

The silver saxifrages (Saxifraga sect. Ligulatae Haworth; Saxifragaceae) exhibit remarkable variation of substrate specialization, with strictly calcicole to calcifuge species, as well as life histories which range from semelparity to iteroparity. They occur almost exclusively in the European mountain ranges and display high levels of endemism. Sequences from chloroplast and nuclear ribosomal DNA were obtained to resolve phylogenetic relationships among the silver saxifrages and related taxa and to gain insight into the evolution of substrate specificity, life history, and biogeography. The resulting phylogenies suggested that (1) Saxifraga sect. Ligulatae, as traditionally defined, does not constitute a monophyletic group; (2) lime-secreting hydathodes in calcifuge species apparently represent a secondary nonaptation; (3) semelparity evolved independently two or three times in the silver saxifrages and allied sections, possibly in response to climatic changes that occured during the Pleistocene; and (4) narrow endemics, for example S. cochlearis, likely evolved from the fragmentation of the widespread S. paniculata into refugial populations that became isolated during the glacial maxima of the Pleistocene.

Biological Evolution↗

Succinoglycan production by solid-state fermentation with Agrobacterium tumefaciens.

Succinoglycan was produced by cultivating Agrobacterium tumefaciens on various solid substrates, including agar medium, spent malt grains, ivory nut shavings, and grated carrots, impregnated with a nutrient+ solution. Fermentations were performed on a laboratory scale, both under static conditions and with agitation, using bottles and a prototype horizontal bioreactor. Several fermentation parameters were examined and optimized, including carbon and nitrogen composition, water content and layer thickness of the substrate. The yields and rheological properties of the polymers obtained under different fermentation conditions were compared. The highest succinoglycan yield was achieved in static cultivation, reaching 42 g/l of impregnating solution, corresponding to 30 g/kg of wet substrate. The polymer production in the horizontal bioreactor was faster, but the final yield was lower (29 g/l of impregnating solution).

Agrobacterium tumefaciens↗

Pictures in cell biology. Structures of nuclear-transport components.

The past three years have seen the solution of several nuclear transport component structures and recently of the structure of a regulator bound to part of a nuclear pore complex (NPC) protein. These structures have provided a wealth of valuable information about the proteins involved and suggested strategies for further investigation of their properties. We do not have space here to go into detail about this information, so instead we are illustrating the structures and providing primary references enabling interested readers to find further information. On this page, we are concentrating on the GTPase Ran and proteins that modulate its activity, and on the facing page are the other transport factors, some of which also interact directly with Ran. Notably absent at the moment are the nuclear pore complex component s, apart from one domain of RanBP2. Only when theses are characterized fully will we really be able to understand how transport substrates move across the nuclear envelope.

Animals↗

Energy intake and dietary pattern in cancer of the oral cavity and pharynx.

OBJECTIVE: To explore the role of energy and macronutrients in cancers of the oral cavity and pharynx. METHODS: Case-control study: 754 individuals with first incident cancer of the oral cavity and pharynx and 1775 controls in hospital for acute, non-neoplastic diseases were interviewed in two Italian areas and in the Swiss Canton of Vaud between 1992 and 1997. RESULTS: Cases reported higher total energy intake, due to higher intake of alcohol energy. Non-alcohol energy intake was lower in cases than controls. The composition of diet also differed: proteins (OR for an addition of 100 kcal/day = 0.8) and monounsaturated fatty acids (OR = 0.8) were inversely associated, while saturated fatty acids (OR = 1.4) were directly associated with oral cancer risk. Vegetable intake, which was positively correlated with oil intake, was lower in cases than controls, but accounted only partly for the observed difference in fat intake pattern. CONCLUSIONS: Alcohol energy may not be used efficiently after some threshold. Protein deficiency may enhance cancer risk in heavy drinkers. An opposite influence of different types of fat is emerging for cancer of the oral cavity and pharynx as well as other sites of the upper aero-digestive tract.

Adult↗

Physical activity and risk of cancers of the colon and rectum: an Italian case-control study.

We investigated the relationships between risk of colon and rectal cancers and physical activity in both sexes at different ages by a case-control study conducted between 1991 and 1996 in six Italian centres. Cases were 1225 patients (688 men, 537 women) below the age of 75 with colon cancer and the controls included 4154 patients (2073 men, 2081 women) admitted to hospital for acute, non-neoplastic conditions. We also analysed 722 cases of rectal cancer. Compared with the lowest level of occupational physical activity at 30-39 years old the odds ratios (OR) for the highest level were 0.64 (95% confidence interval, CI 0.44-0.93) in men and 0.49 (95% CI 0.33-0.72) in women. The inverse association in both sexes was similar at 15-19 and 50-59 years old. No association was found in either sex for leisure-time physical activity. For both sexes the inverse relationship between occupational physical activity at 30-39 years old and colon cancer risk was not significantly heterogeneous across strata of selected covariates, and for ascending, transverse, descending and sigmoid colon. Rectal cancer risk was not associated with any measure of physical activity (OR = 1.32 for men and 0.88 for women for the highest level of occupational physical activity at 30-39 years old compared with the lowest). This study confirms that occupational physical activity is protective against colon, but not against rectal cancer.

Adult↗

Food groups, oils and butter, and cancer of the oral cavity and pharynx.

To elucidate the role of dietary habits, a study was carried out in 1992-1997 in the province of Pordenone in Northeastern Italy, and those of Rome and Latina in central Italy. Cases were 512 men and 86 women with cancer of the oral cavity and pharynx (lip, salivary glands and nasopharynx excluded) and controls were 1008 men and 483 women who had been admitted to local hospitals for a broad range of acute non-neoplastic conditions. The validated dietary section of the questionnaire included 78 foods or recipes and ten questions on fat intake patterns. After allowance for education, smoking, alcohol and total energy intake, significant trends of increasing risk with increasing intake emerged for soups, eggs, processed meats, cakes and desserts, and butter. Risk was approximately halved in the highest compared to the lowest intake quintile for coffee and tea, white bread, poultry, fish, raw and cooked vegetables, citrus fruit, and olive oil. The inverse association with oils, especially olive oil, was only slightly attenuated by allowance for vegetable intake. Thus, frequent consumption of vegetables, citrus fruit, fish and vegetable oils were the major features of a low-risk diet for cancer of the oral cavity and pharynx.

Adult↗

Atypical deletions suggest five 22q11.2 critical regions related to the DiGeorge/velo-cardio-facial syndrome.

Deletions of chromosome 22q11.2 have been associated with distinct phenotypes including DiGeorge syndrome (DGS) and velo-cardio-facial (VCFS) syndrome. These diseases result from a failure to form derivatives of the third and fourth branchial arches during development. DGS/VCFS deletions usually encompass about 3 Mb of genomic DNA in more than 90% of patients. However, deletion mapping studies have failed to demonstrate the existence of a single small region of overlap (SRO) and ruled out any obvious correlation between site or size of deletion and severity of clinical phenotype. We describe three patients carrying 'atypical' deletions presenting the DGS/VCFS phenotype. A comparative analysis of deletions in our patients and those previously published has suggested the existence of five distinct critical regions within the 22q11.2 locus. This observation argues that DGS/VCFS results from haploinsufficiency secondary to a complex and as yet unexplained molecular mechanism, probably involving chromatin effects in mediating gene expression throughout the entire region.

Child, Preschool↗

Education, socioeconomic status and risk of cancer of the colon and rectum.

BACKGROUND: Socioeconomic correlates of cancer of the large bowel differ in various countries and calendar periods and may differ for the colon and rectum. Thus, the relationship between education and social class and risk of cancers of the colon and rectum was considered. METHODS: Combination of two hospital-based case-control studies conducted in six Italian centres between 1985 and 1996. Cases were 3533 patients aged < 79, with histologically confirmed cancer of the colon (n = 2180) or rectum (n = 1353), and controls were 7062 patients admitted to hospital for a wide spectrum of acute, non-neoplastic, non-digestive tract diseases. RESULTS: Compared to individuals with < 7 years of education the multivariate odds ratios (OR) of colon cancer for those with > or = 16 years were 2.45 (95% confidence interval [CI]: 1.87-3.23) in men and 1.29 (95% CI: 0.88-1.90) in women, with significant trends in risk. No significant association emerged between education and risk of rectal cancer, with OR of 1.18 (95% CI: 0.83-1.70) and 1.01 (95% CI: 0.61-1.67) respectively for men and women in the highest educational category compared to the lowest. Social class was also related to colon cancer risk: the OR were 2.30 (95% CI: 1.82-2.90) in men and 1.33 (95% CI: 1.03-1.73) in women in the highest versus the lowest social class. No association was found between social class and rectal cancer risk, with OR of 1.18 for either men or women in the highest as compared to the lowest social class. No significant heterogeneity was found for the association between education and colon cancer risk in either sex across strata of age at diagnosis, coffee, alcohol and vegetable intake, family history of the disease, and in anatomical subsites within the colon. CONCLUSION: This study, based on a uniquely large dataset, indicates that there are different social class correlates for colon and rectal cancer. Consequently the two sites should not be combined in studies considering lifestyle factors in the aetiology of these neoplasms.

Adult↗