Human population studies with the exfoliated buccal micronucleus assay: statistical and epidemiological issues.

Objectives: Micronucleus (MN) assay in buccal exfoliated cells is a minimally invasive method for monitoring genetic damage in human populations. Statistical and epidemiological issues related to the design and analysis of studies based on this biomarker are addressed.

Methods: A systematic review of recent literature on the buccal MN assay has been carried out to provide a state-of-the-art evaluation of how critical topics such as control for confounding, sample size and statistical power, number of cells scored, endpoint selection, and statistical modelling, are considered.

State of the art survey of the buccal micronucleus assay--a first stage in the HUMN(XL) project initiative.

The study of DNA damage in exfoliated buccal cells is a minimally invasive method for monitoring populations for exposure to genotoxic agents. The presence of micronuclei (MN) and other nuclear anomalies within these cells has been shown to be associated with genetic defects in genome maintenance, accelerated ageing, genotoxic damage and some degenerative diseases. To identify important information gaps regarding these biomarkers, a new initiative was launched within the framework of the HUman MicroNucleus (HUMN) collaborative programme, the HUMN(XL) project ('XL' designating eXfoLiated cell).

A novel Bim-BH3-derived Bcl-XL inhibitor: biochemical characterization, in vitro, in vivo and ex-vivo anti-leukemic activity.

BH3-only members of the Bcl-2 family exert a fundamental role in apoptosis induction. This work focuses on the development of a novel peptidic molecule based on the BH3 domain of Bim. The antiapoptotic molecule Bcl-X(L), involved in cancer development/progression and tumour resistance to cytotoxic drugs, is a target for Bim.

Internalization via Antennapedia protein transduction domain of an scFv antibody toward c-Myc protein.

We constructed a single-chain variable fragment miniantibody (G11-scFv) directed toward the transactivation domain of c-Myc, which is fused with the internalization domain Int of Antennapedia at its carboxyl terminus (a cargo-carrier construct). In ELISA experiments, an EC(50) for binding saturation was achieved at concentrations of G11-scFv-Int(-) of approximately 10(-8) M. Internalization of a fluoresceinated Fl-G11-scFv-Int(+) construct was observed in intact human cultured cells with confocal microscopy.

Normalization of low-density microarray using external spike-in controls: analysis of macrophage cell lines expression profile.

Background: The normalization of DNA microarrays allows comparison among samples by adjusting for individual hybridization intensities. The approaches most commonly used are global normalization methods that are based on the expression of all genes on the slide and on the modulation of a small proportion of genes. Alternative approaches must be developed for microarrays where the proportion of modulated genes and their distribution are unknown and they may be biased towards up- or down-modulated trends.

Inhibition of a protein-protein interaction between INI1 and c-Myc by small peptidomimetic molecules inspired by Helix-1 of c-Myc: identification of a new target of potential antineoplastic interest.

c-Myc is a transcription modulator proto-oncogene. When overexpressed, it becomes an important contributor to the multi-hit process of malignant transformation. In two earlier papers in this journal (see refs.

Sequence specific peptidomimetic molecules inhibitors of a protein-protein interaction at the helix 1 level of c-Myc.

Our work is focused in the broad area of strategies and efforts to inhibit protein-protein interactions. The possible strategies in this field are definitely much more varied than in the case of ATP-pocket inhibitors. In our previous work (10), we reported that a retro-inverso (RI) form of Helix1 (H1) of c-Myc, linked to an RI-internalization sequence arising from the third alpha-helix of Antennapedia (Int) was endowed with an antiproliferative and proapoptotic activity toward the cancer cell lines MCF-7 and HCT-116.

Chlorination by-products (CBPs) in drinking water and adverse pregnancy outcomes in Italy.

Chlorination by-products (CBPs) in drinking water have been associated with an increased risk of adverse pregnancy outcomes, including small for gestational age at term (term-SGA) and preterm delivery. Epidemiological evidence is weakened by a generally inaccurate exposure assessment, often at an ecological level. A case control study with incident cases was performed in nine Italian towns between October 1999 and September 2000.

Influence of age, sex, and growth variables on phalangeal quantitative ultrasound measures: a study in healthy children and adolescents.

Skeletal status by phalangeal quantitative osteosonography (DBM Sonic BP-IGEA) was examined in 1227 healthy children (641 boys and 586 girls) aged 3-16 years. Aims of the study were to evaluate some physical parameters pertaining to the ultrasound transmission crossing the phalanx in a school-age population and to relate these values to age, sex, and growth variables. A correlation was found between AD-SoS (amplitude-dependent speed of sound) and BTT (bone transmission time) and, age, height, weight, and pubertal stage, respectively.

Synthesis of photoactivable inhibitors of osteoclast vacuolar ATPase.

Amides of (2Z,4E)-5-[(5,6-dichloroindol-2-yl)]-2-methoxy-N-[3-[4-[3-(carboxymethoxy)phenyl)] piperazin-1-yl]propyl]-2,4-pentadienamide (1) and of 5-(5,6-dichloro-2-indolyl)-2-methoxy-2,4-pentadienoic acid (2) are strong inhibitors of the vacuolar ATPase located on the plasma membrane of osteoclasts. In order to understand which V-ATPase subunit is involved in the interaction with these novel inhibitors, analogues containing a photoactivable group and an iodine atom were designed. A series of alcohols or amines containing the photoactivable trifluoroaziridinophenyl or benzophenone moiety and an iodine atom were linked to the above acids via an ester or amide group.

[Laparoscopic versus mini-cholecystectomy: analysis of hospital costs and social costs in a prospective randomized study].

The aim of the study was to calculate the hospital and social costs in relation to efficacy of clinical outcome, hospital stay and time off work in two groups of patients randomly treated with laparoscopic or mini-cholecystectomy. One hundred and eighty-one patients with simple, symptomatic gallstone disease were included in the study; of these, 9 cases were excluded because of conversion to conventional cholecystectomy. Eighty-six cases underwent laparoscopic cholecystectomy and 86 mini-cholecystectomy.

162 HIV-1 infected pregnant women and vertical transmission. Results of a prospective study.

Background: Aim of this paper is to describe the changes over a 16-year period of the characteristics and management of HIV infected pregnant women.

Methods: Prospective study: analysis of data obtained from 162 women and 176 infants. Factors evaluated included: maternal socio-demographic level, immunological and virological parameters, antiretroviral therapy, mode of delivery, pregnancy outcome and babies follow-up.

Screening and treatment for cervical intraepithelial neoplasia (CIN) in HIV-infected women.

Background: To determine: 1) whether the pathology correlates with the degree of immunosuppression, 2) whether there is a relation between pathology and antiretroviral therapies, 3) whether Papanicolau (Pap) smears correlate with colposcopic and histologic findings, 4) whether there is rapid genital disease progression after standard gynaecologic care.

Methods: Retrospective study. Immunologic, gynaecologic and virologic data were extracted either from patients charts or from laboratory testing.

Novel 7-oxyiminomethyl derivatives of camptothecin with potent in vitro and in vivo antitumor activity.

In an attempt to synthesize potential anticancer agents acting by inhibition of topoisomerase I (Topo I) a new series of oxyiminomethyl derivatives in position 7 of camptothecin (CPT) was prepared. The synthesis relied on the condensation of 20S-CPT-7-aldehyde or 20S-CPT-7-ketones with alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl O-substituted hydroxylamines. The compounds were tested for their cytotoxic activity in vitro against H460 non-small lung carcinoma cell line, the activity being for 24 out of 37 compounds in the 0.