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Biomedical subjects

E Conti

Publications and source records attributed to E Conti.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1998

Body size and colorectal-cancer risk.

Individuals whose energy intake exceeds expenditure are at increased risk of colorectal cancer. To determine whether body-size measurements at different ages were risk factors for cancer of the colon-rectum, we carried out a hospital-based case-control study in 6 Italian areas, 2 of which were in the South. Interviews were conducted with 1,217 subjects of both genders with incident histologically confirmed cancer of the colon, 726 with cancer of the rectum, and 4,136 controls hospitalized for acute, non-neoplastic, non-digestive conditions. The questionnaire included information on sociodemographic factors, and physical activity, a validated dietary history, height, weight at diagnosis and at 12, 30 and 50 years of age and waist-to-hip ratio (WHR). After allowance for education, physical activity, energy intake, family history of colorectal cancer and recent change in weight, the body-mass index (BMI) was significantly associated with colorectal-cancer-risk in men (odds ratio, OR, in highest vs. lowest quintile = 1.7; 95% confidence interval, CI, 1.3-2.3), but not in women (corresponding OR = 0.9; 95% CI, 0.7-1.2). Cases of both gender tended to have higher BMI than controls in adolescence, young adulthood and middle age. Height appeared unrelated to risk. In women, but not in men, WHR was positively associated with risk, independently of BMI (OR for > or = 0.90 vs. < or = 0.81 = 1.6; 95% CI; 1.2-2.1). Thus, excessive weight predicts colorectal-cancer risk in men, whereas abdominal obesity (i.e., a high WHR) represents a more reliable risk indicator in women.

Adult↗
PubMed1998

Crystallographic analysis of the recognition of a nuclear localization signal by the nuclear import factor karyopherin alpha.

Selective nuclear import is mediated by nuclear localization signals (NLSs) and cognate transport factors known as karyopherins or importins. Karyopherin alpha recognizes "classical" monopartite and bipartite NLSs. We report the crystal structure of a 50 kDa fragment of the 60 kDa yeast karyopherin alpha, in the absence and presence of a monopartite NLS peptide at 2.2 A and 2.8 A resolution, respectively. The structure shows a tandem array of ten armadillo repeats, organized in a right-handed superhelix of helices. Binding of the NLS peptide occurs at two sites within a helical surface groove that is lined by conserved residues. The structure reveals the determinants of NLS specificity and suggests a model for the recognition of bipartite NLSs.

Amino Acid Sequence↗
PubMed1998

Macronutrient intake and risk of colorectal cancer in Italy.

To provide further insight on the relationship between macronutrients and colorectal cancer, overall and by specific subsite(s), we carried out between 1992 and 1996 in 6 Italian areas a case-control study on 1,953 individuals of both sexes with incident colorectal cancer (age range 19-74) and 4,154 controls (age range 19-74) in hospital with acute, non-neoplastic diseases. A validated food-frequency questionnaire was used, including questions on 78 foods or recipes and on individual fat-intake pattern. The risk of cancer of the colon and rectum increased with total energy intake (odds ratio in highest vs. lowest quintile 1.43 and 1.50, respectively). The risk also rose significantly with an increase of starch intake, whereas it moderately decreased with an increase of protein intake. Monounsaturated fat intake appeared uninfluential, while saturated fat intake showed a modest direct association with rectal cancer. Polyunsaturated fat intake was inversely associated with colon cancer risk, particularly with the right colon.

Adult↗
PubMed1998

X-ray and spectrophotometric studies of the binding of proflavin to the S1 specificity pocket of human alpha-thrombin.

Proflavin can be used to study the interactions of inhibitors and substrates with thrombin by monitoring the changes in the visible absorption spectrum that occur on dye displacement. We have used microspectrophotometric methods to investigate the binding of proflavin to crystals of an alpha-thrombin-hirugen complex and have determined the structure by X-ray crystallography. The proflavin molecule binds in the S1 pocket of the enzyme with one of the amino groups hydrogen bonded to the carboxylate of Asp-189 while the protonated ring nitrogen is hydrogen bonded to the carbonyl of Gly-219. This result indicates that the proflavin displacement assay can be used to specifically monitor the binding of inhibitors to the S1 pocket.

Absorption↗
PubMed1998

Structure and expression of the human ubiquitin fusion-degradation gene (UFD1L).

We report the genomic organization, RNA and protein expression patterns of the gene encoding for the human homolog of the yeast ubiquitin fusion-degradation protein-1 (UFD1L). This enzyme is involved in a ubiquitin-dependent proteolytic pathway (UFD), firstly described in yeast. The human UFD1L gene is organized into 12 exons ranging in size from 33 to 161 bp. Sequence analysis of the 5'-flanking region of the gene revealed a high GC content, multiple CCAAT-binding motifs, CREB, CFT, and AP-2 sites. RNA transcripts were detected in all tissues and cell lines examined, including thymus, thymocytes, T- and B-cells, fibroblasts, chorionic villi, and amniocytes. In Western blot, the UFD1L antibody demonstrated the presence of multiple protein isoforms in all the tested tissues. Expression profile and promoter characteristics suggest UFD1L is a housekeeping gene with implications in the pathogenesis of DiGeorge/velo-cardio-facial syndrome, due to 22q11.2 deletions.

Adaptor Proteins, Vesicular Transport↗
PubMed1998

Structural basis for the inhibition of firefly luciferase by a general anesthetic.

The firefly luciferase enzyme from Photinus pyralis is probably the best-characterized model system for studying anesthetic-protein interactions. It binds a diverse range of general anesthetics over a large potency range, displays a sensitivity to anesthetics that is very similar to that found in animals, and has an anesthetic sensitivity that can be modulated by one of its substrates (ATP). In this paper we describe the properties of bromoform acting as a general anesthetic (in Rana temporaria tadpoles) and as an inhibitor of the firefly luciferase enzyme at high and low ATP concentrations. In addition, we describe the crystal structure of the low-ATP form of the luciferase enzyme in the presence of bromoform at 2.2-A resolution. These results provide a structural basis for understanding the anesthetic inhibition of the enzyme, as well as an explanation for the ATP modulation of its anesthetic sensitivity.

Adenosine Triphosphate↗
PubMed1998

The influence of reproductive and hormonal factors on the risk of colon and rectal cancer in women.

A case-control study was conducted between 1992 and 1996 in six Italian areas. It included 537 women with colon cancer, 291 women with rectal cancer and 2081 control women in hospital for acute conditions, unrelated to hormonal or gynaecological diseases. A higher age at menopause was associated with increased colon cancer risk (odds ratio (OR) for > or = 53 years compared with < 50 years = 1.39, 95% confidence interval (CI) 1.04-1.87). Among parous women, a significant trend of decreasing colon cancer risk with increasing number of births was seen for colon (OR for > or = 4 births compared with 1 birth = 0.62, 95% CI 0.42-0.90), but not for rectal cancer. Nulliparous women, however, were at lower risk than women with a single birth, and age at first birth was directly associated with risk. While oral contraceptive use showed no significant influence, ever users of hormone replacement therapy had a reduced risk of rectal cancer (OR = 0.56, 95% CI 0.31-1.01). Thus, the association of colorectal cancer with reproductive and menstrual factors is neither strong nor consistent.

Adult↗
PubMed1998

Family history of cancer and risk of colorectal cancer in Italy.

Subjects with a family history of colorectal cancer (CRC) are at increased risk of CRC, but quantification of the risk in different populations, the possible differences in risk according to localization of the cancer and the association of family history of other cancers with CRC risk are still open issues. We have therefore analysed data from a multicentric case-control study conducted in six Italian areas between 1992 and 1996 of 1225 incident cases of colon cancer, 728 cases of rectal cancer and 4154 controls admitted for acute conditions to the same network of hospitals as the cases. Unconditional logistic regression models including terms for gender, age, study centre, years of education and number of siblings were used to estimate the odds ratios (ORs) of CRC according to various aspects of history of CRC and other cancers in first-degree relatives. The OR for family history of CRC was 3.2 (95% confidence interval, CI, 2.5-4.1) for colon cancer and 2.2 (95% CI 1.6-3.1) for rectal cancer. Colon cancer was significantly associated with a family history of stomach (OR 1.4), bone (OR 2.1) and kidney (OR 2.3) cancers, while rectal cancer was significantly associated with a family history of lymphomas (OR 2.8). There was a 30% higher risk of colon and rectal cancer in subjects with a family history of any cancer, excluding intestine. The ORs for family history of CRC were 5.2 for colon and 6.3 for rectum when the proband's age was below 45 years. The ORs were similar when the affected relative was a parent or a sibling and in different strata of age of relative(s). For subjects with two or more first-degree relatives with CRC, the risk was 6.9 for the right colon, 5.8 for the transverse and descending colon, 3.8 for the sigma, 3.2 for the rectosigmoid junction and 1.9 for the rectum. This study confirms that a family history of CRC in first-degree relatives increases the risk of both colon and rectal cancer, the association being stronger at younger ages and for right colon.

Adult↗
PubMed1998

Meal frequency and coffee intake in colon cancer.

Several studies suggested that frequent eating may increase colon cancer risk. To further clarify this issue, a case-control study was carried out in six areas of Italy on 1,225 incident cases < 75 years of age with histologically confirmed colon cancer and 4,154 control subjects. The controls were hospitalized for acute, nonneoplastic conditions unrelated to long-term dietary modifications. After allowance for education, physical activity, intake of vegetables, and major energy sources, there was a trend of increasing risk with increasing eating frequency (odds ratio for > or = 4 vs. < or = 2 daily meals = 1.24). Coffee intake, which was inversely associated with cancer risk, exerted a modification effect, with an odds ratio of 1.89 for frequent eaters who drank fewer than two cups of coffee per day. Frequent eating increases, whereas high coffee intake decreases, the excretion of bile acids, which are suspected to be carcinogenic to the colon. Thus, it is conceivable that frequent coffee intake may counterbalance the effect of frequent eating.

Adult↗
PubMed1997

Intake of selected micronutrients and risk of colorectal cancer.

The relationship between various micronutrients and colorectal cancer risk was investigated using data from a case-control study conducted between January 1992 and June 1996 in Italy. Cases were 1,953 incident, histologically confirmed colorectal cancers (1,225 of the colon and 728 of the rectum), admitted to the major teaching and general hospitals in the study areas, and 4,154 controls with no history of cancer, admitted to hospitals in the same catchment areas for acute, non-neoplastic diseases unrelated to the digestive tract and requiring no long-term modifications of the diet. Dietary habits were investigated using a validated food-frequency questionnaire. Odds ratio (ORs) were computed after allowance for age, sex and other potential confounding factors, including physical activity, total energy and fibre intake. For most micronutrients, ORs were below unity with increasing quintile of intake. The most consistent protective effects were for carotene, riboflavin and vitamin C (Multivariate ORs from the continuous model, with unit set as the difference between the upper cut-point of the 4th quintile and that of the 1st one, were 0.65, 0.73 and 0.80, respectively). Inverse relationships were observed also for calcium and vitamin D (ORs of 0.85 and 0.93, respectively). When the combined effect of calcium and vitamin D and selected anti-oxidants was considered, the OR reached 0.46 in subjects reporting high calcium/vitamin D and high anti-oxidant intake compared to those reporting low intake of both groups of micronutrients. Most results were apparently stronger for colon cancer and among females. Our results provide further support for a protective effect of several micronutrients on colorectal cancer risk and some indications for a specific and stronger effect of selected anti-oxidants.

Adult↗
PubMed1997

Structural basis for the activation of phenylalanine in the non-ribosomal biosynthesis of gramicidin S.

The non-ribosomal synthesis of the cyclic peptide antibiotic gramicidin S is accomplished by two large multifunctional enzymes, the peptide synthetases 1 and 2. The enzyme complex contains five conserved subunits of approximately 60 kDa which carry out ATP-dependent activation of specific amino acids and share extensive regions of sequence similarity with adenylating enzymes such as firefly luciferases and acyl-CoA ligases. We have determined the crystal structure of the N-terminal adenylation subunit in a complex with AMP and L-phenylalanine to 1.9 A resolution. The 556 amino acid residue fragment is folded into two domains with the active site situated at their interface. Each domain of the enzyme has a similar topology to the corresponding domain of unliganded firefly luciferase, but a remarkable relative domain rotation of 94 degrees occurs. This conformation places the absolutely conserved Lys517 in a position to form electrostatic interactions with both ligands. The AMP is bound with the phosphate moiety interacting with Lys517 and the hydroxyl groups of the ribose forming hydrogen bonds with Asp413. The phenylalanine substrate binds in a hydrophobic pocket with the carboxylate group interacting with Lys517 and the alpha-amino group with Asp235. The structure reveals the role of the invariant residues within the superfamily of adenylate-forming enzymes and indicates a conserved mechanism of nucleotide binding and substrate activation.

Adenosine Monophosphate↗
PubMed1997

Food groups and risk of colorectal cancer in Italy.

The proportion of colorectal cancer attributed to dietary habits is high, but several inconsistencies remain, especially with respect to the influence of some food groups. To further elucidate the role of dietary habits, 1,225 subjects with cancer of the colon, 728 with cancer of the rectum and 4,154 controls, hospitalized with acute non-neoplastic diseases, were interviewed between 1992 and 1996 in 6 different Italian areas. The validated food-frequency questionnaire included 79 questions on food items and recipes, categorised into 16 food groups. After allowance for non-dietary confounding factors and total energy intake, significant trends of increasing risk of colorectal cancer with increasing intake emerged for bread and cereal dishes (odds ratio [OR] in highest vs. lowest quintile = 1.7), potatoes (OR = 1.2), cakes and desserts (OR = 1.1), and refined sugar (OR = 1.4). Intakes of fish (OR = 0.7), raw and cooked vegetables (OR = 0.6 for both) and fruit other than citrus fruit (OR = 0.7) showed a negative association with risk. Consumption of eggs and meat (white, red or processed meats) seemed uninfluential. Most findings were similar for colon and rectum, but some negative associations (i.e., coffee and tea, and fish) appeared stronger for colon cancer. Our findings lead us to reconsider the role of starchy foods and refined sugar in light of recent knowledge on the digestive physiology of carbohydrates and the insulin/colon cancer hypothesis. The beneficial role of most vegetables is confirmed, with more than 20% reduction in risk of colorectal cancer from the addition of one daily serving.

Adult↗
PubMed1997

Illness behavior, affective disturbance and intestinal transit time in idiopathic constipation.

Patients with constipation differ not only from healthy subjects but can also be categorized into two groups: slow transit constipation (STC) and normal transit constipation (NTC) using measures of total intestinal transit time (TITT). We investigated the role of illness behavior and affective state in 45 NTC and 29 STC patients as compared with 20 healthy subjects. All subjects completed the Illness Behavior Questionnaire (IBQ), the Symptom Questionnaire (SQ), and the CES-D to assess illness behavior, psychological distress, and depression. The constipated patients reported more psychological distress than healthy subjects. Within the constipated group, the NTC subjects had significantly higher scores on the IBQ dimensions of hypochondriasis and disease affirmation. Our results suggest that even among constipated patients psychological distress is prominent and that measures of illness behavior help to discriminate among different pathophysiological groups.

Adult↗
PubMed1997

The apolipoprotein E epsilon4 allele causes a faster decline of cognitive performances in Down's syndrome subjects.

The apolipoprotein E gene (APOE), located on human chromosome 19, has three common alleles (epsilon2, epsilon3, epsilon4) which encode for the three main isoforms indicated as E2, E3 and E4 respectively. Several findings indicate epsilon4 allele as an important risk factor in both sporadic and familial late-onset Alzheimer's disease (AD). Pathological changes similar to AD are seen in almost all patients with Down's syndrome (DS) aged over 35 (senile plaques, neurofibrillary tangles and neuronal loss); a proportion of these may subsequently develop dementia. Aim of this study is to evaluate the possible pathological role of epsilon4 allele as risk factor for developing AD in a DS population. ApoE epsilon4 allele frequency is not significantly different in DS cases and controls. We found a statistically significant inverse correlation between full scale IQ values and age of patients in the subgroup of DS subjects selected for the presence of at least one epsilon4 allele, while no correlation was observed in DS subjects with other ApoE genotypes. A longitudinal analysis of cognitive performances (available in 38 patients) showed a faster rate of decline in intellectual ability in those subjects carrying at least one epsilon4 allele. Our data support the hypothesis that ApoE epsilon4 allele has a contributory role in accelerating the mental deterioration of AD-type in DS patients.

Adolescent↗
PubMed1997

Aspirin and colorectal cancer.

The relationship between aspirin use and colorectal cancer risk was examined by a case-control study in Italy. Regular aspirin use was reported by only 47 (3.5%) cases and 77 (4.1%) control subjects, giving a multivariate odds ratio (OR) of 0.7 (95% CI 0.5-1.0) after allowance for education, physical exercise and selected dietary factors.

Adult↗