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Biomedical subjects

E Conti

Publications and source records attributed to E Conti.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Estimation and projections of colorectal cancer trends in Italy.

BACKGROUND: Occurrence of and prognosis for tumours of the colon and rectum are thought to be changing rapidly due to simultaneous changes in risk factor prevalence, early diagnosis and treatment. In this paper time trends of morbidity, survival and mortality for colorectal cancer during the period 1970-1990 are estimated and analysed. METHODS: Mortality trends were obtained from official death certificates. Relative survival rates were computed from population-based cancer registries. Incidence and prevalence rates were estimated from mortality and survival data. RESULTS: Incidence rates were increasing during the period considered, with a lower rate of increase for the youngest birth cohorts. Relative survival rates of both colon and rectum cancers were higher for women, and for younger age groups, and were positively associated with period of diagnosis. No significant survival difference among the cancer registries used was found. A total of about 155,000 prevalent cases, 40% of which had been diagnosed > or = 7 years before, were estimated in the Italian population for the year 1990. Mortality rates were slightly increasing for men and stable for women. Projections of colorectal cancer trends to the year 2000 indicate major expected rises in both incidence and prevalence. CONCLUSION: Colorectal cancer represents a problem of growing impact for health services in Italy. This conclusion can probably be extended to many developed countries.

Adult↗

Mechanisms of adenosine-induced epicardial coronary artery dilatation.

BACKGROUND: In order to ascertain whether human adenosine-induced dilatation of epicardial arteries is direct or flow-mediated, we compared the effects of intracoronary adenosine infusion on epicardial coronary arteries with those produced by dipiridamole, a selective arteriolar vasodilator. METHODS AND RESULTS: In 24 patients with angiographically normal coronary arteries, coronary blood flow velocity was measured by a Doppler wire during intracoronary infusion of adenosine or dipyridamole, which is known to increase intramyocardial adenosine concentration. Coronary angiograms were obtained at baseline and immediately after the end of each infusion period; coronary diameters 5 mm distal to the wire tip were measured by computer-assisted quantitative coronary angiography. Peak coronary blood flow velocities during adenosine or dipyridamole infusions were similar (52.0 +/- 15.5 and 47.9 +/- 24.2 cm.s-1, P = ns). Coronary diameters immediately after adenosine and dipyridamole infusions were similar and both higher than that at baseline (2.80 +/- 0.63 and 2.86 +/- 0.64 vs 2.44 +/- 0.69 mm, P < 0.05). The absolute and percentage increases of coronary artery diameters in response to adenosine were highly correlated to coronary blood flow velocity (R = 0.622, intercept -0.10 +/- 0.14, P = 0.002 and R = 0.617, intercept -15.2 +/- 9.9, P = 0.001, respectively); similar correlations were found in response to dipyridamole (R = 0.708, intercept -0.44 +/- 0.19, P < 0.001 and R = 0.649, intercept -13.5 +/- 8.7, P < 0.001, respectively). Finally the absolute and percentage changes of coronary artery diameters caused by adenosine were highly correlated to those caused by dipyridamole (R = 0.840 P < 0.001 and R = 0.836, P < 0.001 respectively). CONCLUSIONS: A significant correlation exists between epicardial coronary vasodilation and coronary blood flow velocity during intracoronary adenosine infusion, thus suggesting that epicardial coronary vasodilation induced by adenosine is predominantly flow-mediated rather than direct. This conclusion is supported by the observation that similar findings were obtained using dipyridamole, which can only dilate epicardial coronary arteries indirectly, through the increase in coronary blood flow velocity caused by the inhibition of intramyocardial adenosine re-uptake.

Adenosine↗

[Cystadenocarcinoma of the pancreas. Case report and review of the literature].

Pancreatic cystadenocarcinoma is a quite rare neoplasm. Due to the low incidence and recent nosographic arrangement, the natural evolution and the clinical development of this type of neoplasm are not well known. The Authors report their experience and a review of the Literature trying to establish the criteria for the classification, diagnosis and therapy of pancreatic cystadenocarcinoma.

Aged↗

Body size indices and breast cancer risk before and after menopause.

The relationship between various body size indices and breast cancer risk before and after menopause was elucidated by means of a case-control study conducted between June 1991 and April 1994 in 6 Italian centers on 2,569 patients aged below 75 with histologically confirmed breast cancer, and on 2,588 controls admitted to the hospital for a wide spectrum of acute, non-neoplastic, non-hormone-related diseases. Weight and, more consistently, body mass index (BMI, kg/m2) at diagnosis were inversely related to pre-menopausal breast cancer risk and directly to post-menopausal risk. An 8-unit increase in BMI resulted in an odds ratio of 0.8 for pre-menopausal and of 1.2 (significant) for post-menopausal women. Risk seemed to increase gradually after menopause in the 7th (OR for an 8-unit BMI increase, 1.3) and 8th decades (OR, 1.6) of life. Conversely, height, waist-to-hip ratio, bra cup size and weight (or BMI) in adolescence and in young adulthood did not exert a significant or consistent influence on breast cancer risk. The apparent relationship with BMI at middle age and weight gain between age 30 years and diagnosis was eliminated by allowance for BMI at diagnosis. The age-related pattern of the association between BMI and breast cancer risk after menopause may reflect a duration-risk relationship, and resembles the effect of post-menopausal estrogen use, which seems greater among older women.

Adult↗

Intake of macronutrients and risk of breast cancer.

BACKGROUND: The association between risk of breast cancer and dietary fat and intakes of other energy sources remains controversial. The Italian population offers special opportunities to assess the influence of high intakes of unsaturated fat and starch and, because the population has low awareness of diet and cancer issues, there is less scope for recall bias. We have assessed the relations of various macronutrient intakes with risk of breast cancer. METHODS: In this case-control study, 2569 women with incident breast cancer (median age 55 years) and 2588 control women (median age 56 years) in hospital with acute, non-neoplastic diseases, were interviewed in six different areas of Italy between 1991 and 1994. A validated food-frequency questionnaire was used. It included questions on 78 foods and recipes grouped into six sections, as well as specific questions on individual fat intake pattern. FINDINGS: The risk of breast cancer decreased with increasing total fat intake (trend p 0.01) whereas the risk increased with increasing intake of available carbohydrates (trend p = 0.002). The odds ratios for women in the highest compared with the lowest quintile of energy-adjusted intake were 0.81 for total fat and 1.30 for available carbohydrates. Starch was the chief contributor to the positive association with available carbohydrates. High intakes of polyunsaturated and unsaturated fatty acids (i.e., polyunsaturated fatty acids plus oleic acid) were associated with a decreased risk of breast cancer (odds ratios for highest vs lowest quintile 0.70 and 0.74, respectively). Conversely, the intakes of saturated fatty acids, protein, and fibre were not significantly associated with breast-cancer risk. INTERPRETATION: This case-controls study shows that unsaturated fatty acids protect against breast cancer, possibly because intake of these nutrients is closely correlated with a high intake of raw vegetables. The findings also suggest a possible risk in southern European populations, of reliance on a diet largely based on starch.

Adult↗

Crystal structure of firefly luciferase throws light on a superfamily of adenylate-forming enzymes.

BACKGROUND: Firefly luciferase is a 62 kDa protein that catalyzes the production of light. In the presence of MgATP and molecular oxygen, the enzyme oxidizes its substrate, firefly luciferin, emitting yellow-green light. The reaction proceeds through activation of the substrate to form an adenylate intermediate. Firefly luciferase shows extensive sequence homology with a number of enzymes that utilize ATP in adenylation reactions. RESULTS: We have determined the crystal structure of firefly luciferase at 2.0 A resolution. The protein is folded into two compact domains. The large N-terminal domain consists of a beta-barrel and two beta-sheets. The sheets are flanked by alpha-helices to form an alphabetaalphabetaalpha five-layered structure. The C-terminal portion of the molecule forms a distinct domain, which is separated from the N-terminal domain by a wide cleft. CONCLUSIONS: Firefly luciferase is the first member of a superfamily of homologous enzymes, which includes acyl-coenzyme A ligases and peptide synthetases, to have its structure characterized. The residues conserved within the superfamily are located on the surfaces of the two domains on either side of the cleft, but are too far apart to interact simultaneously with the substrates. This suggests that the two domains will close in the course of the reaction. Firefly luciferase has a novel structural framework for catalyzing adenylate-forming reactions.

Adenosine↗

Intake of selected micronutrients and the risk of breast cancer.

To investigate the relation between selected micronutrients and breast cancer risk, we conducted a case-control study of breast cancer between June 1991 and April 1994 in 6 Italian areas. The study included 2569 women admitted to the major teaching and general hospitals of the study areas with histologically confirmed incident breast cancer and 2588 control women with no history of cancer, who were admitted to hospitals in the same catchment areas for acute, non-neoplastic, nongynecological conditions unrelated to hormonal or digestive tract diseases or to long-term modifications of the diet. Dietary habits, including alcoholic beverage consumption, were investigated using a validated food frequency questionnaire, including 78 foods or food groups, several types of alcoholic beverages, some "fat intake pattern" questions and some open sections for foods consumed frequently by the subject and not reported in the questionnaire. To control for potential confounding factors, several multiple logistic regression models were used. When major correlates, energy intake and the mutual confounding effect of the various micronutrients were taken into account, beta-carotene, vitamin E and calcium showed a significant inverse association with breast cancer risk. The estimated odds ratios of the 5th quintile compared to the lowest one were 0.84 for beta-carotene, 0.75 for vitamin E and 0.81 for calcium. No significant association emerged for retinol, vitamin C, thiamin, riboflavin, iron and potassium. Our results suggest that a diet rich in several micronutrients, particularly beta-carotene, vitamin E and calcium, may be protective against breast cancer.

Adult↗

The role of reproductive and menstrual factors in cancer of the breast before and after menopause.

The aim of the study was to elucidate the role of reproductive and menstrual factors in the aetiology of breast cancer, overall and by menopausal status. A cooperative case-control study was conducted between 1991 and 1994 in six different Italian areas (including three from the centre and the south). The study included 2569 histologically confirmed incident cases of breast cancer (median age 55 years, range 23-78 years) and 2588 control women (median age 56 years, range 20-79 years) admitted to the same hospitals for a variety of acute conditions unrelated to the hypotheses in study. A trend of increasing risk with increasing age at menopause (odds ratio (OR) for age at menopause > or = 53 versus < 45 years = 1.8; 95% confidence interval (CI) = 1.4-2.2). High parity reduced cancer risk (OR for > or = 4 versus 1 birth = 0.7; 95% CI = 0.5-0.9). Overall, nulliparous women showed a 20% lower risk than uniparous ones (OR = 0.8; 95% CI = 0.7-1.0). Late age at first birth (or pregnancy) had an independent adverse effect (OR for first birth at > or = 32 versus < 20 years = 1.7; 95% CI = 1.3-2.1) both before and after menopause. An approximately 2-fold elevation of breast cancer risk was evident up to 10 years after the last birth. No trend in risk was evident for induced abortions (OR = 1.2 for 1 and 1.1 for > or = 2 induced abortions versus 0). Other examined menstrual and reproductive characteristics did not seem important. Multiparity, early age at first birth and early age at menopause were therefore the most important determinants of breast cancer risk. The effects of the timing of births was significantly heterogeneous in pre- and postmenopausal women because of the transient adverse effect of such events, evident only in premenopausal women.

Adult↗

Socioeconomic status, migration and the risk of breast cancer in Italy.

BACKGROUND: High socioeconomic status and migration to a higher risk area have been linked to increased breast cancer risk. To evaluate the occurrence of breast cancer in women of different social class and residential history, we conducted a multicentre case-control study in Italy. METHODS: A total of 2569 cases of incident breast cancer were ascertained in northern, central and southern Italy. The controls were 2588 women admitted for a wide spectrum of acute conditions to the same hospitals where cases had been hospitalized. The effect of socioeconomic variables was evaluated with multiple logistic regression after stratification and adjustment for age, origin, centre, and selected reproductive and dietary factors. RESULTS: Compared to housewives, managers and professionals had a 1.7-fold increased risk, whereas the relative risk was 0.7 and 0.6 respectively in helpers and manual workers. The risk of breast cancer also increased with increasing social level of the husbands's occupation and subjects's number of years of schooling. Women who originated in central and southern Italy, and migrated to northern Italy after age 24, but not those who migrated at a younger age, had a relative risk of 0.6 and 0.7 respectively, compared to lifelong residents in northern Italy. CONCLUSIONS: Our findings show that correlates of sociocultural level and place of origin exert an influence on breast cancer risk which is not accounted for completely by known risk factors (i.e. reproductive and menstrual characteristics and recent dietary habits). Such influence may thus occur early in life.

Breast Neoplasms↗

Physical activity and breast cancer risk.

Data from a multicentric case-control study on breast cancer conducted in Italy were used to analyze the relationship of occupational and leisure-time physical activity with breast cancer risk. Cases were 2569 histologically confirmed incident breast cancer cases, and controls were 2588 patients admitted to the same network of hospitals of cases for acute, nonneoplastic, nonhormone related diseases. After allowance for major identified potential confounding factors (including an estimate of total calorie intake), the odds ratios (ORs) were 0.70, 0.71, 0.64, and 0.54 in subsequent levels of physical activity at work at ages 30-39, compared to the lowest level. The association was similar for occupational physical activity at ages 15-19 and still apparent at ages 50-59, with risk estimates of 0.86, 0.85, 0.85, and 0.62. The ORs for the highest versus the lowest category of leisure-time physical activity were also below unity (ORs for the highest level of leisure-time physical activity at ages 15-19, 0.95; at ages 30-39, 0.76; and at ages 50-59, 0.66). The protection of physical activity was apparently stronger below age 60 at diagnosis and was consistent across the strata of selected covariates, although the protection was somewhat greater for more educated women.

Adolescent↗