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M Ferraroni

Publications and source records attributed to M Ferraroni.

At least 19 recordsLinked to original sources
PubMed2006

Preliminary crystallographic analysis of salicylate 1,2-dioxygenase from Pseudaminobacter salicylatoxidans.

Salicylate 1,2-dioxygenase, a new ring-fission dioxygenase from the naphthalenesulfonate-degrading strain Pseudaminobacter salicylatoxidans which oxidizes salicylate to 2-oxohepta-3,5-dienedioic acid by a novel ring-fission mechanism, has been crystallized. Diffraction-quality crystals of salicylate 1,2-dioxygenase were obtained using the sitting-drop vapour-diffusion method at 277 K from a solution containing 10%(w/v) ethanol, 6%(w/v) PEG 400, 0.1 M sodium acetate pH 4.6. Crystals belong to the primitive tetragonal space group P4(3)2(1)2 or P4(1)2(1)2, with unit-cell parameters a = 133.3, c = 191.51 A. A complete data set at 100 K extending to a maximum resolution of 2.9 A was collected at a wavelength of 0.8423 A. Molecular replacement using the coordinates of known extradiol dioxygenases structures as a model has so far failed to provide a solution for salicylate 1,2-dioxygenase. Attempts are currently being made to solve the structure of the enzyme by MAD experiments using the anomalous signal of the catalytic Fe(II) ions. The salicylate 1,2-dioxygenase structural model will assist in the elucidation of the catalytic mechanism of this ring-fission dioxygenase from P. salicylatoxidans, which differs markedly from the known gentisate 1,2-dioxygenases or 1-hydroxy-2-naphthoate dioxygenases because of its unique ability to oxidatively cleave salicylate, gentisate and 1-hydroxy-2-naphthoate with high catalytic efficiency.

Bacteria, Aerobic↗
PubMed2005

Resveratrol and breast cancer risk.

Resveratrol is a non-flavonoid polyphenol that has attracted attention as a potential anticancer agent in vitro and in vivo, but scanty epidemiological data are available. We have therefore analysed the relation between dietary intake of resveratrol and breast cancer risk using data from a case-control study conducted between 1993 and 2003 in the Swiss Canton of Vaud on 369 cases and 602 controls. Compared with the lowest tertile of total resveratrol intake, the multivariate odds ratios (OR) were 0.50 for the intermediate and 0.39 for the highest tertile, and the trend in risk was significant. A significant inverse association was observed for resveratrol from grapes (OR = 0.64 and 0.55), but not for wine. The inverse relation between resveratrol and breast cancer risk was not explained by several potential confounding factors, including detailed allowance for alcohol intake, nor attributable to a non-specific favourable effect of fruit on breast cancer risk.

Adult↗
PubMed2004

Reproducibility and validity of coffee and tea consumption in Italy.

OBJECTIVE: The reproducibility and validity of coffee, decaffeinated coffee and tea intake has not been adequately studied, particularly in Italy, where coffee drinking is peculiar in terms of type and amount of coffee consumed. DESIGN: We compared coffee and tea consumption, measured by two interviewer-administered food frequency questionnaires (FFQ), with average intake derived from two 7-day dietary (DD) records (the reference method) on 395 volunteers. The Pearson correlation coefficients (r) were used to assess both reproducibility and validity of information on coffee intake. RESULTS: A satisfactory level of reproducibility and validity of the pattern consumption was observed for coffee, decaffeinated coffee and tea. The reproducibility for both sex combined showed r of 0.74-0.78 for coffee, 0.57-0.65 for decaffeinated coffee and 0.61-0.67 for tea. The validity was about 0.70 for coffee, around 0.58 for decaffeinated coffee and 0.56-0.60 for tea intake. CONCLUSIONS: The FFQ is a satisfactorily reliable and valid instrument for collecting information on coffee, decaffeinated coffee and tea intake.

Adult↗
PubMed2001

Low-risk diet for colorectal cancer in Italy.

An innovative approach was used to define a low-risk diet for colorectal cancer from a multicentric case-control study of 1953 incident cases and 4154 hospital controls from Italy. A logistic regression model was fitted on the reported intake of five macronutrients, and the estimated coefficients were used to compute a diet-related logistic risk score (LRS). The mean of LRS within risk decile ranged from 0.89 to 1.86. Total energy intake and absolute consumption of each macronutrient increased with increasing LRS. In relative terms, however, starch intake showed an almost threefold increase across subsequent score levels, while a decline was observed for unsaturated fat, sugar and protein. Saturated fat consumption remained fairly stable in relative terms. When food groups were considered, bread and cereals dishes, cakes and desserts and refined sugar were positively associated, while the consumption of vegetables, fruit, fish, poultry and olive oils was inversely associated with LRS.

Adult↗
PubMed2000

Structural basis of hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase.

Streptococcus pneumoniae hyaluronate lyase (spnHL) is a pathogenic bacterial spreading factor and cleaves hyaluronan, an important constituent of the extra- cellular matrix of connective tissues, through an enzymatic beta-elimination process, different from the hyaluronan degradation by hydrolases in animals. The mechanism of hyaluronan binding and degradation was proposed based on the 1.56 A resolution crystal structure, substrate modeling and mutagenesis studies on spnHL. Five mutants, R243V, N349A, H399A, Y408F and N580G, were constructed and their activities confirmed our mechanism hypothesis. The important roles of Tyr408, Asn349 and His399 in enzyme catalysis were proposed, explained and confirmed by mutant studies. The remaining weak enzymatic activity of the H399A mutant, the role of the free carboxylate group on the glucuronate residue, the enzymatic behavior on chondroitin and chondroitin sulfate, and the small activity increase in the N580G mutant were explained based on this mechanism. A possible function of the C-terminal beta-sheet domain is to modulate enzyme activity through binding to calcium ions.

Amino Acid Sequence↗
PubMed1999

The crystal structure of the monomeric human SOD mutant F50E/G51E/E133Q at atomic resolution. The enzyme mechanism revisited.

The crystal structure of the engineered monomeric human Cu,ZnSOD triple mutant F50E/G51E/E133Q (Q133M2SOD) is reported at atomic resolution (1.02 A). This derivative has about 20 % of the wild-type activity. Crystals of Q133M2SOD have been obtained in the presence of CdCl2. The metal binding site is disordered, with both cadmium and copper ions simultaneously binding to the copper site. The cadmium (II) ions occupy about 45 % of the copper sites by binding the four histidine residues which ligate copper in the native enzyme, and two further water molecules to complete octahedral coordination. The copper ion is tri-coordinate, and the fourth histidine (His63) is detached from copper and bridges cadmium and zinc. X-ray absorption spectroscopy performed on the crystals suggests that the copper ion has undergone partial photoreduction upon exposure to the synchrotron light. The structure is also disordered in the disulfide bridge region of loop IV that is located at the subunit/subunit interface in the native SOD dimer. As a consequence, the catalytically relevant Arg143 residue is disordered. The present structure has been compared to other X-ray structures on various isoenzymes and to the solution structure of the same monomeric form. The structural results suggest that the low activity of monomeric SOD is due to the disorder in the conformation of the side-chain of Arg143 as well as of loop IV. It is proposed that the subunit-subunit interactions in the multimeric forms of the enzyme are needed to stabilize the correct geometry of the cavity and the optimal orientation of the charged residues in the active channel. Furthermore, the different coordination of cadmium and copper ions, contemporaneously present in the same site, are taken as models for the oxidized and reduced copper species, respectively. These properties of the structure have allowed us to revisit the enzymatic mechanism.

Binding Sites↗
PubMed1998

Alcohol consumption and risk of breast cancer: a multicentre Italian case-control study.

The relationship between alcohol consumption and breast cancer risk was investigated using data from a co-operative case-control study conducted in Italy between 1991 and 1994 on 2569 incident, histologically confirmed breast cancer cases and 2588 controls in hospital for acute, non-neoplastic, non-hormone related conditions. Overall, 915 (38%) cases and 1048 (43%) controls were abstainers. Compared with them, the odds ratio (OR), adjusted only for age, was 1.31 (95% confidence interval (CI) 1.13-1.53) for drinkers and became 1.39 (95% CI 1.(1)21-1.60) after correction for measurement error. The multivariate OR was 1.21 for drinkers of < or = 5.87 g/day and 1.23, 1.19, 1.21, 1.41 for drinkers of 5.88-13.40, 13.41-24.55, 24.56-27.60, > 27.60 g/day, respectively. The trend in risk was significant (chi 2 = 12.28, P < 0.0005). The association was apparently stronger in premenopausal women (OR = 1.80 for > 27.60 g/day). Considering the different types of alcoholic beverages (wine, beer, digestives, grappa and other spirits), a significant direct trend in breast cancer risk was seen for wine with an OR of 1.27 (95% CI 1.06-1.53) for the category > 26.34 g/day. The ORs were also above unity for beer, grappa, digestives and spirits drinkers. No appreciable interaction was observed between alcohol drinking and body mass index, smoking, or any other covariate considered. Thus, the present data, based on a validated alcohol consumption questionnaire and on a population characterised by a relatively high alcohol consumption in women, confirmed that alcohol drinking is moderately related to breast cancer risk. If causal, this association could explain 12% (95% CI, 5-19%) of breast cancers in Italy, thus representing one of the major avoidable risk factor for breast cancer.

Adult↗
PubMed1998

Alcohol intake and risk of cancers of the colon and rectum.

The relationship between alcohol drinking (mainly wine) and risk of colon and rectal cancer was considered in a case-control study conducted between 1991 and 1996 in six Italian centers. Cases were 1,225 patients < 75 years of age with histologically confirmed cancer of the colon and 728 patients with cancer of the rectum; controls were 4,154 patients admitted to hospital for a wide spectrum of acute, nonneoplastic diseases. Compared with never drinkers, the odds ratios (OR) for current drinkers in the higher quintile of total alcohol intake (> 51.82 g ethanol/day) were 1.01 for colon cancer and 0.90 for rectal cancer, and those for ex-drinkers were 1.20 and 1.07, respectively. The OR for wine drinkers in the highest quartile of intake were 1.07 for colon cancer and 0.97 for rectal cancer. No association was found with duration of the habit, time since starting, or age at starting. Among ex-drinkers, no association appeared with time since stopping. No significant heterogeneity was found across strata of age at diagnosis, sex, education, smoking status, physical activity, family history of colorectal cancer, beta-carotene, vitamin C, coffee, total fiber and folate intake, and number of meals per day. No significant association appeared for various intestinal subsites.

Adult↗
PubMed1998

Alcohol, methylxanthine-containing beverages, and colorectal cancer in Córdoba, Argentina.

The relationship between social class indicators, body mass index (BMI), selected life-style habits (alcohol, coffee, maté and tea drinking) and colorectal cancer was investigated in a case-control study conducted between 1993 and 1997 in Córdoba, Argentina, a relatively high mortality area of colorectal cancer. Cases were 190 patients below age 80 years with incident, histologically confirmed colorectal adenocarcinomas, and controls were 393 patients admitted to hospital for a wide spectrum of acute, non-neoplastic disorders. Higher social class, based on occupation of the head of the household, was significantly associated with colorectal cancer risk: the odds ratios (OR) and 95% confidence intervals (95% CI) were 1.9 (1.2-2.9) for intermediate and 2.0 (1.2-3.4) for the highest as compared to the lowest social class individuals. When compared with subjects whose BMI was < 25 kg/m2, the OR was 1.1 (0.7-1.6) for those with BMI 25 to 29 kg/m2, and 1.3 (0.7-2.3) for those > or = 30. In comparison with alcohol abstainers, the OR was 2.8 (1.6-5.1) for drinkers, and there was a significant trend in risk with dose. The association was observed with wine (the most common alcoholic beverage in Argentina), as well as for beer and spirits. The consumption of coffee, maté and tea was not significantly related to colorectal cancer, but the ORs were below unity (0.9 (0.7-1.3) for coffee, 0.9 (0.6-1.2) for maté and 0.8 (0.6-1.2) for tea drinkers). The relationship between social class, alcohol drinking and colorectal cancer were consistent across strata of sex and age. This study confirms that colorectal cancer has positive social class correlates. The association with alcohol drinking is apparently stronger than previously reported, and may be due to the role of chance and/or peculiar correlates of alcohol drinking in this Argentinean population.

Adult↗
PubMed1997

Fibers and breast cancer risk.

Data from a multicenter case-control study on breast cancer conducted in Italy were used to analyze the relationship between various types of fibers and breast cancer risk. Cases were 2,569 women with histologically confirmed, incident breast cancer; controls were 2,588 women admitted to the same network of hospitals for acute, nonneoplastic, non-hormone-related diseases. Cases and controls were interviewed between 1991 and 1994 using a validated food frequency questionnaire. The data were modeled through multiple logistic regression, controlling for demographic and reproductive breast cancer risk factors. The continuous odds ratios for the difference between the upper cut point of the fourth and the first quintile of intake were 0.90 [95% confidence interval = 0.82-0.98, p (for trend) < 0.05] for cellulose and 0.94 (95% confidence interval = 0.86-1.02) for soluble fibers. The protection tended to be stronger in premenopausal women. No material association was found for noncellulose polysaccharides and lignin. This study, based on a large data set from various Italian regions, suggests that fiber intake may confer some protection against breast cancer, particularly for cellulose and also for soluble fibers, i.e., those of vegetable origin. This possible protection has been related to an influence of fibers on levels and availability of estrogens and other steroid hormones in breast carcinogenesis.

Adult↗
PubMed1997

Macronutrients, energy intake, and breast cancer risk: implications from different models.

We used data from a case-control study, conducted in Italy on 2,569 incident cases of breast cancer and 2,588 controls, to fit various energy adjustment models in the estimate of the effect of selected nutrients and alcohol on breast cancer risk. When we fit the standard multivariate and residual models, including total energy intake and the different macronutrients one at a time, the odds ratios (OR) related to 100 kcal per day were 0.90 for protein, 0.96 for saturated fat, 0.88 for unsaturated fat, 0.95 for sugar, 1.07 for starch, and 1.06 for alcohol. When we included all of the different sources of calorie intake in a single model with energy sources partitioned, the OR of adding 100 kcal per day was 0.91 for protein, 1.22 for saturated fat, 0.89 for unsaturated fat, 0.98 for sugar, 1.08 for starch, and 1.07 for alcohol. The estimates from the residual models that included various macronutrients separately were similar to those of the extended energy partition model.

Adult↗
PubMed1997

Gastric cancer risk factors in subjects with family history.

Until now, it has been unclear whether there are differences in various risk factor profiles for familial gastric cancer, i.e., gastric cancer among subjects with a family history of the disease. A total of 722 gastric cancer patients and 2024 controls were admitted between 1985 and 1992 to a network of hospitals in the Greater Milan area. Of these, 88 cases and 103 controls who reported a family history of gastric cancer in first degree relatives were considered in the present analysis. There was no relationship between gastric cancer risk and tobacco smoking or alcohol drinking. Shorter duration of electrical refrigerator use was related to a nonsignificant increased risk and a high daily meal frequency was associated with an increased gastric cancer risk. Significant direct trends of risk were observed for pasta (odds ratio, OR = 4.20 for the highest versus the lowest tertile), bread (OR, 2.86), red meat (OR, 3.38), and preserved meat (OR, 1.90). Inverse associations were observed for increasing consumption of selected vegetables and fruits, chiefly peppers (OR = 0.31), total fruits (OR, 0.47), and citrus fruits (OR, 0.38). With reference to selected micronutrients, a significant inverse trend in risk with increasing consumption for beta-carotene (OR, 0.27) and ascorbic acid (OR, 0.20) was observed. These results suggest that dietary risk factors for subjects with a family history of gastric cancer in first-degree relatives are not appreciably different from well-established risk factors of the disease in the general population.

Case-Control Studies↗
PubMed1996

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↗
PubMed1996

Attributable risks for colorectal cancer in northern Italy.

Using data from a case-control study conducted between 1985 and 1992 in northern Italy on 828 cases of colon cancer, 498 cases of rectal cancer and 2,024 controls in hospital for acute, non-neoplastic, non-digestive tract disorders, we estimated the percent population attributable risk (PAR) for colorectal cancer in relation to beta-carotene, vitamin C (as markers of a diet rich in fruit and vegetables), red meat and seasoning fat intake, daily meal frequency and family history of the disease. On the basis of multivariate odds ratios, adjusted for total calorie intake, a low intake of beta-carotene accounted for 39% of all the cases and a low intake of vitamin C for 14%. These two micronutrients together explained 43% of all colorectal cancer cases in this population. A high frequency of intake of red meat consumption explained 17% of all cases, and a high score of seasoning fats 4%. A higher daily meal frequency was responsible for 13% of the cases, and these 5 dietary factors together explained 63% of colorectal cancer cases in this population. Family history of colorectal cancer accounted for 4% of all cases. These estimates were similar for colon and rectal cancers separately, in males and females, and in younger and elderly subjects, except for seasoning fats and family history, whose PARs were apparently greater for colon cancer and at younger age. Thus, even though available dietary data were limited in several aspects, and the PAR estimates were based on somewhat arbitrary assumptions regarding the exposure distribution, about two-thirds of all colorectal cancers in this population could be explained in terms of a few risk factors or risk indicators considered. This would correspond to the avoidance of a large proportion of the over 18,000 deaths from colorectal cancer registered per year in the whole of Italy.

Adult↗
PubMed1996

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↗
PubMed1996

Software for attributable risk and confidence interval estimation in case-control studies.

The increasing interest in obtaining model-based estimates of attributable risk (AR) and corresponding confidence intervals, in particular when more than one risk factor and/or several confounding factors are jointly considered, led us to develop a program based on the procedure described by Benichou and Gail for case-control data. This program is structured as an SAS-macro. It is suited to analysis of the relationship between risk factors and disease in case-control studies with simple random sampling of controls, in terms of relative risks and ARs, by means of unconditional logistic regression analysis. The variance of the AR is obtained by the delta method and is based on three components, namely, (i) the variance-covariance matrix of the vector of the estimated probabilities of belonging to joint levels of the exposure and confounding factors conditional on being a case, (ii) the variance-covariance matrix of the odds ratio parameter estimates from the logistic model, and (iii) the covariances between these probability and parameter estimates. Only a limited number of commands is requested from the user (i.e., the name of the work file and the names of the variables considered). The estimated relative risks for all the factors included in the model, the attributable risk for the exposure factor under consideration, and the corresponding 95% confidence intervals are given as outputs by the macro. Computational problems, if any, may arise for large numbers of covariates because of the resulting large size of vectors and matrices. The macro was tested for reliability and consistency on published data sets of case-control studies.

Age Factors↗