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Biomedical subjects

E Taioli

Publications and source records attributed to E Taioli.

At least 91 records · Page 5Linked to original sources

A case-control study on breast cancer and body mass. The American Health Foundation--Division of Epidemiology.

A hospital-based case-control study was carried out to examine the effect of body weight/fat and physical activity on risk of breast cancer on 617 newly diagnosed breast cancer cases and 531 controls matched to the cases by age (+/- 5 years), race, year of interview (+/- 1 year) and hospital of admission. Breast cancer was not found to be associated with height, while being overweight appeared to be protective in premenopausal women [odds ratio, OR = 0.4 (0.2-0.7) for cases who weighted > or = 72.7 kg versus controls]. Increased body mass index (BMI) was protective in premenopausal women [OR = 0.4 (0.2-0.6) in breast cancer cases with BMI > or = 27 versus controls], but not in postmenopausal women, for whom it was a risk factor [OR = 1.5 (1.0-2.3)]. Few women reported any strenuous physical activity from ages 15 to 22 years (22% of premenopausal, 13% of postmenopausal women), and no significant effect on breast cancer risk was observed.

Adult↗

Development of biomarkers of human exposure to carcinogens: the example of DNA-protein cross-links.

Biomarkers are considered to be more biologically informative than traditional methods and less prone to misclassification bias. However, new biomarkers are conceived in experimental laboratories and normally undergo extensive experimental in vitro and in vivo testing, usually without regard as to their potential use in humans. Whereas the epidemiologist had no role in the original development of the basic research idea leading to the initial formulation of a biomarker, the new biomarker or technical modification of an existing one are the product of observations in humans. The results of our field studies on DNA-protein cross-links (DPX) among chromate workers illustrates inherent difficulties in the process of development and validation of biomarkers.

Biomarkers↗

Kinetics of metallothionein gene induction by cadmium in human lymphocytes.

Induction of gene transcription is a complex process involving a diverse set of transcription factors and regulatory steps. We have taken a kinetic approach to analysis of metallothionein gene induction in human peripheral blood lymphocytes. By repeated measurements of MT mRNA after incubation of cells in vitro with CdCl2, we were able to determine individual-specific time related constants. The kinetics of induction for 3 individuals followed an S shaped curve and the data was fitted to a modified kinetic model of gene transcription. From this model, which assumes a cooperativity effect, transcriptional and RNA degradation rate constants could be calculated. The rate constant for transcription was doubled with the doubling of CdCl2 concentration, but the rate constant for RNA degradation was independent of Cd concentration.

Adult↗

Functional significance of different human CYP1A1 genotypes.

At least two different polymorphisms in the human CYP1A1 gene have been associated with an increased risk for tobacco-related lung cancer; however, the functional significance of these polymorphisms has not been determined. We measured CYP1A1 genotypes, gene expression levels and enzymatic activity levels in mitogen-stimulated lymphocytes to determine whether genetic polymorphisms in CYP1A1 alter transcriptional and/or post-transcriptional regulation of the gene. Genotypes were determined at two sites previously associated with lung cancer: a point mutation in exon 7 near the catalytic region of the enzyme and an Msp1 RFLP in the 3' non-coding region of the gene. Variant genotypes at the Msp1 site had no effect on CYP1A1 gene induction, however, variant genotypes at the exon 7 site were significantly associated with increased CYP1A1 gene inducibility. We also observed a significant interaction between the exon 7 polymorphism and smoking on mRNA levels. There was a 3-fold elevation in CYP1A1 enzymatic activity in exon 7 variant genotypes. When Msp1 and exon 7 genotypes were combined, there was an increased CYP1A1 inducibility and enzymatic activity in subjects with the exon 7 polymorphism, and in subjects with both polymorphisms.

Adult↗

Application of reliability models to studies of biomarker validation.

We present a model of biomarker validation developed in our laboratory, the results of the validation study, and the impact of the estimation of the variance components on the design of future molecular epidemiologic studies. Four different biomarkers of exposure are illustrated: DNA-protein cross-link (DNA-PC), DNA-amino acid cross link (DNA-AA), metallothionein gene expression (MT), and autoantibodies to oxidized DNA bases (DNAox). The general scheme for the validation experiments involves n subjects measured on k occasions, with j replicate samples analyzed on each occasion. Multiple subjects, occasions, and replicates provide information on intersubject, intrasubject, and analytical measurement variability, respectively. The analysis of variance showed a significant effect of batch variability for DNA-PC and MT gene expression, whereas DNAox showed a significant between-subject variability. Among the amino acids tested, cysteine and methionine showed a significant contribution of both batch and between-subject variability, threonine showed between-subject variability only, and tyrosine showed between-batch and between-subject variability. The total variance estimated through the experiment was used to calculate the minimum sample size required for a future epidemiologic study including the same biomarkers used for the reliability study. Such validation studies can detect the various components of variability of a biomarker and indicate needed improvements of the assay, along with possible use in field studies.

Amino Acids↗

Occupational exposures to Cd, Ni, and Cr modulate titers of antioxidized DNA base autoantibodies.

This study was undertaken to establish whether occupational exposures to derivatives of carcinogenic metals evoke inflammatory immune responses, as determined by the presence of elevated titers of antibodies (Ab) that recognize oxidized DNA bases. Sera obtained from the blood of steel welders (Delaware) and from workers of the Centra Ni-Cd Battery Factory (Poznań, Poland) were analyzed by the enzyme-linked immunosorbent assay. To determine specific and nonspecific binding, an oxidized thymidine [5-hydroxymethyl-2'-deoxyuridine (HMdU)] coupled to bovine serum albumin (HMdU-BSA) as well as mock-coupled BSA (M-BSA) were used as antigens for coating the wells of microtiter plates. Titers of anti-HMdU Ab were significantly elevated in the high Cd and Ni exposure groups (18.3 +/- 3.2 vs 10.8 +/- 2.1 A492/microliters; p < 0.05). The sera of the groups with low exposures to Cd and Ni also had enhanced titers of those Ab but those increases were not statistically significant. Interestingly, the Ab titers present in the sera of controls for Cd and Ni exposures appear to be constant regardless of the protein content. In contrast, both lightly and heavily exposed subjects exhibited Ab titers that increased with increasing protein content. When 12 randomly selected workers (4 from each of the control, lightly, and heavily exposed groups) were outfitted with personal monitors, anti-HMdU Ab titers of those workers showed a significant difference between the groups with light (< 100 micrograms/m3) and heavy (> 200 micrograms/m3) exposures to Cd (9.8 +/- 3.7 vs 22.1 +/- 3.7 A492/microliters; p < 0.01) and Ni (11.7 +/- 1.4 vs 31.0 +/- 1.8; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Antibody Reactions↗

Recognition of oxidized DNA bases by sera of patients with inflammatory diseases.

Chronic inflammatory conditions result from or contribute to many diseases. Prominent among them is systemic lupus erythematosus (SLE). Sera of SLE patients contain an array of various auto-antibodies (Ab), including antinuclear Ab of unknown etiologies. The most puzzling is formation of Ab directed against autologous DNA. Our hypothesis was that increased oxidant production causes oxidation of DNA bases, which provide antigenic determinants that elicit antioxidized DNA Ab. To test this hypothesis, we used oxidized DNA nucleoside (5-hydroxymethyl-2'-deoxyuridine [HMdU]) conjugated to bovine serum albumin (HMdU-BSA) as the antigen. The results of the enzyme-linked immunosorbent assay showed that these Abs are sensitively detectable in SLE sera and sera of various other inflammatory autoimmune diseases. The titers of anti-HMdU Ab were significantly higher (p < .01) than those present in the control sera. Anti-HMdU Ab were predominantly of the IgM isotype, with low levels of IgG and no IgA. Anti-HMdU Ab bound to the HMdU-BSA-coated wells in a concentration- and time-dependent manner. That binding was inhibited by HMdU-BSA and to a lesser extent by thymidine-BSA, a normal nucleoside conjugate. The specific binding appears to be inversely related to the age of the patients, but no significant differences were observed between the sexes of the same age.

Adult↗

A novel CYP1A1 gene polymorphism in African-Americans.

A new Msp1 RFLP in the CYP1A1 gene has been found in genomic DNA from African-Americans. The polymorphism results from a single A-T to G-C transition in the 3' noncoding region approximately 300 bp upstream from the polyadenylation site. This mutation leads to cleavage of the normal 2.3 kb MspI restriction fragment into 1.3 and 1.0 kb fragments. The heterozygous mutation has been seen in 8 of 47 African-Americans, but was not detected in 191 Caucasians or 30 Asians. No linkage was observed with either of the two previously described polymorphisms in this gene.

Asia↗

Breast cancer--the optimal diet.

In summary, the evidence based upon global and metabolic epidemiology, and animal studies supported by biologic understanding of the various mechanisms in which dietary fat can affect promotion and progression of breast cancer supports the concept that dietary fat, in particular, certain types of fat, and dietary fiber affect the causation, promotion, and progression of breast cancer. The epidemiologic evidence of the link between breast cancer and dietary fat is still controversial due to methodological problems in designing a valid test. Also a number of studies dealt with the question of fat intake in pre-menopausal women, where admittedly the association is weak. What now needs to be done is to verify the effect of a low-fat diet in post-menopausal breast cancer patients. We suggest that a similar trial on pre-menopausal breast cancer patients in conjunction with ovarian ablation should be conducted. The question to be considered is what in terms of dose, type, and duration of fat and fiber will be required to obtain a measureable effect on the recurrence rate and survival of breast cancer patients.

Breast Neoplasms↗

Vitamin supplement use and risk for oral and esophageal cancer.

In a hospital-based case-control study, 290 oral cancer cases and 133 esophageal cancer cases were queried as to smoking status, alcohol consumption, and dietary exposures, including vitamin supplement history. Among oral cancer cases, vitamin E use appeared to exert a protective effect. Vitamins C and E had protective effects among esophageal cancer cases. When stratified by smoking status, the protective effect of vitamin C use in esophageal cancer was significant only among current smokers, as was vitamin B use. A reduced risk of oral cancer was correlated with multivitamin use and increasing vegetable consumption, as was vegetable/fruit consumption and vitamin C supplementation. Among esophageal cancer cases, increasing meat consumption and vitamin C use were associated with a significantly reduced cancer risk.

Adult↗

Prevalence and variability of orthostatic hypotension in the elderly. Results of the 'Italian study on blood pressure in the elderly (SPAA)'. The 'Gruppo di Studio Sulla Pressione Arteriosa nell'Anziano'.

The prevalence of orthostatic hypotension (OH) in an elderly outpatient population was assessed according to the most common criteria given in the literature. Short-term OH variability and relationships between OH and its known risk factors were also analysed. A sample of 3858 elderly outpatients aged 65 years or more was randomly recruited by 444 Italian general practitioners. The patients' blood pressure (BP) and heart rate were recorded in both lying and standing positions at two visits 7 days apart. Three definitions were used for the identification of OH: (1) a decrease in systolic BP greater than 20 mmHg (SOH); (2) a decrease in both systolic (greater than 20 mmHg) and diastolic (greater than 10 mmHg) BP (SDOH); (3) any decrease in systolic BP associated with symptoms (SyOH). Prevalence figures for SOH were 13.8% at the first and 12.6% at the second visit, and respectively 5.3 and 4.8% for SDOH, 14.1 and 11.8% for SyOH. All the criteria were met by less than 2% of subjects at each visit. The diagnosis of OH was confirmed at both visits in 36.3% of cases for SOH, in 25.7% for SDOH, and in 43.9% for SyOH. Each different OH definition identifies a population subgroup characterized by different sets of risk-factors. The presence and prevalence of OH is difficult to define because different people may be identified by the currently accepted criteria or by the same criterion over a short time.

Aged↗

Vitamin supplement use in a hospital-based population.

Vitamin supplement histories were taken from a sample of approximately 3,600 individuals (2,461 men and 1,181 women) from a hospital-based population. Multivitamin preparations were the most commonly used vitamin supplements (32% of men, 37% of women) followed by vitamins C (men 11%; women 16%) and E (men 17%; women 23%). The most common combination of supplements among the multi-users was vitamins C and E. Vitamin supplement use was positively associated with education in both sexes. Among women, there was a negative association between vitamin supplement consumption and Quetelet Index. No association was found between vitamin use and smoking status or alcohol use or amount of alcohol consumed.

Adult↗

Ecologic study of lung cancer risk factors in the U.S. and Japan, with special reference to smoking and diet.

Lung cancer mortality rates among United States and Japanese males were compared and related to smoking and dietary data. Mortality rates increased from 1950 to 1985 in both countries, but the absolute values are consistently lower in Japan (38.2 deaths/100,000 in 1985) than in the U.S. (72.2/100,000). The proportion of smokers is higher in Japan than in the U.S. since 1955. Japanese males start smoking considerably later than U.S. males, but smoke a higher quantity of cigarettes per day. Available information on inhalation practices and yield and type of cigarettes smoked showed no differences among the two countries large enough to account for the differences in mortality rates. Further data in this regard should be obtained. Dietary data show that fat consumption (as percentage of calories) is consistently higher in the U.S. than in Japan from 1950 (40% vs. 7.9%) through 1985 (43.5% vs. 24.5%). A linear relationship is observed between lung cancer mortality and fat intake. Our data support the hypothesis that dietary habits may modulate the carcinogenic effects of tobacco smoking.

Adult↗

Effects of long-term treatment with prazosin on left ventricular diastolic function in mild to moderate hypertension.

It is not well established if blood pressure control is associated with an improvement in diastolic function, whose impairment represents an early marker of cardiac involvement in systemic hypertension. The purpose of this study was to evaluate whether a prolonged treatment with an alpha 1-blocking agent can lead to a reversal of the abnormalities of left ventricular filling. Eleven never-treated patients with mild to moderate essential hypertension were examined before and after at least six months of treatment with prazosin. Cardiac function and left ventricular mass were measured by means of radionuclide ventriculography and echocardiography. Average blood pressure values significantly decreased during the treatment period: from 163.54 +/- 17.80 mm Hg to 146.81 +/- 13.14 mm Hg for systolic blood pressure and from 106.09 +/- 6.96 mm Hg to 92.90 +/- 8.93 mm Hg for diastolic blood pressure. All the indices of left ventricular mass showed a trend toward reduction, but the differences with respect to the baseline values did not reach statistical significance. Average value of ejection fraction was normal before treatment and did not change significantly after treatment. All indices of diastolic function were significantly lower than normal controls' values at the beginning of the study and tended to worsen at the end of the study. Our findings suggest that diastolic function is not consistently affected by the therapy with alpha 1-adrenoreceptor antagonists despite good blood pressure control.

Adult↗

Feasibility of a long-term low-sodium diet in mild hypertension.

The present study set out to assess the feasibility of long-term moderate dietary sodium restriction in patients with mild hypertension in general practice. After screening and a run-in phase of 6-8 weeks, a total of 77 previously undiagnosed mildly hypertensive patients were identified. Half of them were randomized to receive a few simple dietary instructions from their general practitioners in order to reduce salt usage; the others were randomized to receive no advice. The patients were followed up for 12 months with quarterly visits. A total of 56 patients (72.7%) completed the study, 26 on a low-sodium diet (LD) and 30 on their usual diet (UD). At each visit in the diet phase, patients provided 24h urine, which was analysed for volume and sodium concentration in order to assess their sodium intake. Blood pressure, heart the rate and body weight were recorded. The mean urinary sodium excretion for all diet phase visits overlapped in the two groups (177.0 +/- 32.9 vs. 169.3 +/- 49.4 mEq/24h respectively in the LD and UD groups). Nevertheless the mean systolic and diastolic blood pressures for all diet phase visits were significantly lower in the LD than in UD group (144.2 +/- 11.1/91.6 +/- 6.4 and 148.0 +/- 13.7/95.6 +/- 4.7 mmHg respectively, P less than 0.01). Our data suggest that it is not feasible at present to reduce sodium intake in mild hypertensives with simple and inexpensive dietary instructions, the only ones suitable for widespread application in general practice.

Adult↗