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Biomedical subjects

P Mocarelli

Publications and source records attributed to P Mocarelli.

67 records · Page 4Linked to original sources
PubMedDate not supplied

Renal cell carcinoma and normal kidney protein expression.

Renal cell carcinoma (RCC), a human kidney cancer from the proximal tubular epithelium, accounts for about 3% of adult malignancies. Molecular and cytogenetic analysis have highlighted deletions, translocations, or loss of heterozygosity in the 3p21-p26, a putative RCC locus, as well as in 6q, 8p, 9pq, and 14pq. Studies on phenotypic expression of human kidney tissue and on post-translational modifications in RCC have not yet provided a marker for early renal cell carcinoma diagnosis. Current diagnostic methods do not help to detect the tumor before advanced stages. We therefore used two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to study normal and tumor kidney tissues in ten patients suffering from RCC. A human kidney protein map in the SWISS-2DPAGE database accessible through the ExPASy WWW Molecular Biology Server was established. Of 2789 separated polypeptides, 43 were identified by gel comparison, amino acid analysis, N-terminal sequencing, and/or immunodetection. The comparison between normal and tumor kidney tissues showed four polypeptides to be absent in RCC. One of them was identified as ubiquinol cytochrome c reductase (UQCR), whose locus has elsewhere been tentatively assigned to chromosome 19p12 or chromosome 22. A second polypeptide was identified as mitochondrial NADH-ubiquinone oxido-reductase complex I whose locus is located on chromosome 18p11.2 and chromosome 19q13.3. These result suggest that the lack of UQCR and of mitochondrial NADH-ubiquinone oxidoreductase complex I expression in RCC may be caused by unknown deletions, or by changes in gene transcription or translation. It might indicate that mitochondrial disfunction plays a major role in RCC genesis or evolution.

Amino Acid Sequence↗
PubMedDate not supplied

Stratified analysis of multivariate clinical data: application of a Mantel-Haenszel approach.

Laboratory determinations on children aged 6 to 10 years obtained over a 5-year period are analysed by a method described in detail for differentiating between children from exposed and control areas of Seveso, Italy. In the analysis, stratification is employed to distinguish the separate days of laboratory measurement. The analyses permit the study of differences based on all variables simultaneously as well as on each variable separately. Results are obtained for each individual year and for longer intervals of 2 successive years, 3 successive years, 4 successive years, and all 5 years. The results and some statistical aspects of the analysis are discussed.

Analysis of Variance↗
PubMedDate not supplied

Seveso Women's Health Study: does zone of residence predict individual TCDD exposure?

The compound, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is produced as an unwanted by-product of various chemical reactions and combustion processes, including the manufacture of chlorinated phenols and derivatives. In animals, TCDD exposure is associated with toxic, carcinogenic, developmental, and reproductive effects. In 1976, a chemical plant explosion in Seveso, Italy, exposed the residents in the surrounding community to the highest exposure to TCDD known in humans. Materials from an aerosol cloud of sodium hydroxide, sodium trichlorophenate and TCDD were deposited over an 18.1 km2 area. As evidence of the significant level of TCDD exposure, numerous animals died and 193 cases of chloracne were reported among residents of the area. Initially, the contaminated area was divided into three major exposure Zones (A, B, R) based on the concentration of TCDD in surface soils. To date, the majority of epidemiologic studies conducted in Seveso have used Zone of residence as a proxy measure of exposure. The purpose of the present study is to validate the use of Zone of residence in Seveso as a proxy measure of exposure against individual serum TCDD measurement, and to determine whether questionnaire information can improve the accuracy of the exposure classification. Using data collected from the Seveso Women's Health Study (SWHS), the first comprehensive epidemiologic study of the reproductive health of women in Seveso, we determined that Zone of residence is a good predictor of individual serum TCDD level, explaining 24% of the variance. Using questionnaire information could have improved prediction of individual exposure levels in Seveso, increasing the percent of the variation in serum TCDD levels explained to 42%.

Adolescent↗
PubMedDate not supplied

Seveso Women's Health Study: a study of the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on reproductive health.

Although reproductive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure have been reported in numerous investigations of animals, studies of this association in humans are limited. In 1976, an explosion in Seveso, Italy exposed the surrounding population to among the highest levels of TCDD recorded in humans. The relatively pure exposure to TCDD and the ability to quantify individual level TCDD exposure from sera collected in 1976 for the Seveso cohort affords a unique opportunity to evaluate the potential dose-response relationship between TCDD exposure and a spectrum of reproductive endpoints. The Seveso Women's Health Study (SWHS) is the first comprehensive study of the reproductive health of a human population exposed to TCDD. The primary objectives of the study are to investigate the relationship of TCDD and the following endpoints: (1) endometriosis; (2) menstrual cycle characteristics; (3) age at menarche; (4) birth outcomes of pregnancies conceived after 1976; (5) time to conception and clinical infertility; and (6) age at menopause. Included in the SWHS cohort are women who were 0-40 yr old in 1976, who have adequate stored sera collected between 1976 and 1980, and who resided in Zones A or B at the time of the accident. All women were interviewed extensively about their reproductive and pregnancy history and had a blood draw. For an eligible subset of women, a pelvic exam and transvaginal ultrasound were conducted and a menstrual diary was completed. More than 95% of the women were located 20 yr after the accident and roughly 80% of the cohort agreed to participate. Data collection was completed in July 1998, serum TCDD analysis of samples for analysis of endometriosis as a nested case-control study was completed in October 1998, and statistical analysis of these data should be completed in early 1999. Serum samples are now being analyzed in order to relate TCDD levels with the remaining reproductive outcomes.

Adult↗
PubMedDate not supplied

Surface antigen on Ehrlich ascites tumor cells.

Ehrlich Ascites Tumor (EAT) may be regarded as an extreme example of a reduced expression of normal histocompatibility antigens which is also reflected in its ability to grow in almost any mouse strain. In this report we discuss some evidence about a specific antigenicity detected on the cell surface of EAT strain maintained by serial transfer in C57BL/6 mice. The antiserum against EAT antigen was prepared by immunizing rabbits with an extract obtained by KCl treatment of EAT cells and then tested for cytotoxicity on EAT cells. The specificity, confirmed by using the indirect immunofluorescence test and the inhibition of cytotoxicity by EAT antigen, was also discussed.

Animals↗
PubMedDate not supplied

Serum dioxin levels in Seveso, Italy, population in 1976.

On July 10, 1976, an explosion at a chemical plant near Seveso, Italy, released a mixture of chemicals, including 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,4,5-trichlorophenol. As a result, several thousand people in the Seveso area may have been exposed to those chemicals. At that time, human exposure assessment was based primarily on soil levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Medical examinations of this potentially exposed population and control subjects were begun in 1976 and in some cases continued until 1985. In 1988, we began assessing human exposure in this population by measuring 2,3,7,8-tetrachlorodibenzo-p-dioxin in small volumes of serum specimens remaining from the medical examinations. As expected, we found that the median serum dioxin levels were highest among people who lived closest to the explosion and were progressively lower among groups living farther away. These measurements have allowed us to assess exposure more accurately among individuals in this population and to relate exposure to various health effects. We found that some individuals in the exposed population had among the highest serum dioxin levels ever reported, yet chloracne was the only unequivocal effect found; cancer risks are still being investigated. We also found that other individuals with as high or higher serum dioxin levels did not develop chloracne. We also found that the serum half-life of dioxin in this population was 7-8 years, which agrees with other findings although we do report some differences in the serum half-life of TCDD for women and children. We also observed an increase in the percentage of female newborns to parents who resided in Zone A at the time of the explosion, and we also report on the 1976 serum dioxin levels in people who later developed cancer.

Accidents↗
PubMedDate not supplied

[Seveso: biological monitoring of dioxin pollution. An example of environmental medicine. Multicentric and interdisciplinary applied research].

In 1976 the population of an area including Seveso (about 30,000) affected by the fallout of a toxic cloud containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) started a health monitoring plan which lasted until 1985. Smaller groups were monitored until 1997. The large number of people and the different toxic effects on organs have gathered different discipline experts including informatic. This work has permitted the not easy observation both of minor and bigger effects during two decades.

Environmental Medicine↗