Dr. Cesare Saltini
University of Modena
71, Via del Pozzo
Modena, Italy 41100
Phone: 059-379-198
Fax: 059-370-913
Email: tisio@mednw1.unimo.it
Projects are approved by an IRB located at: Azienda Ospedaliera Policlinico di Modena.
The approving IRB does not operate under a Multiple Project Assurance (MPA) recognized by DOE or by the Department of Health and Human Services (HHS).
Number of Human Subjects Projects reported: 1
Project Identifier: MDNA-93-DEFG0293ER61714
Project Title:
Structural and Functional Basis of Genetic Susceptibility to Chronic Beryllium Disease
Principle Investigator:
Dr. Cesare Saltini
Project started in: 1993
Project Funding Information:
Project received funding in Fiscal Year 1995.
Project used human subjects in Fiscal Year 1995.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: October 20, 1995
IRB Approval Number: RPC#5281
Number of Human Subjects in the Last Reporting Period for this Project: 50
(Reporting periods vary.)
Type of Human Subjects Involvement:
The objective of the research is the characterization of the structural and functional basis of chronic beryllium disease (CBD) and the evaluation of the potential use of genetic markers for the diagnosis of CBD risk.
The methodologies used will primarily involve, 1) cell isolation and deoxyribonucleic acid (DNA) extraction from peripheral blood samples to create a cell and a DNA bank from CBD patients and healthy beryllium-exposed individuals, 2) in vitro experiments of beryllium presentation to T-cells derived from CBD patients to evaluate the role of the human leukocyte antigen (HLA) class II molecules and particularly of the HLA-DP Glu69 polymorphism, 3) DNA molecular typing for the identification of the CBD-associated HLA-DP Glu69 polymorphism.
Human subjects involved in this study will not be exposed to any chemical or radioactive substances or ionizing radiation. Human subjects involved in this study will be asked to undergo venipuncture for in vitro beryllium-stimulated lymphocyte proliferation testing (Be-LPT) and DNA studies. Subjects with abnormal Be-LPT will undergo bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) for diagnostic purposes. Those who are diagnosed as CBD cases will undergo a second bronchoscopy with BAL. Peripheral blood mononuclear cells (PBMCs) will be isolated from whole blood and used in in vitro experiments of antigen presentation and generation of beryllium-specific T-cell lines and clones. Genomic DNA will be isolated from whole blood and used in polymerase chain reaction (PCR) amplification with primers specific for HLA-DP exon 2 and analysis of the PCR product by hybridization with specific oligonucleotide probes and direct PCR sequencing. Study data (genetic testing data and the Be-LTT data from CBD patients and beryllium-exposed controls transmitted to the P.I.) are stored in secured files and locked in cabinets in a locked room in the Principal Investigator's laboratory in Modena. Dr. Wiedemann at the Cleveland Clinic Foundation (Cleveland, OH) will be responsible for safeguarding clinical data.
Risks of participation in the first part of the study will be limited to minor pain and bruising from blood drawing. Risks of bronchoscopy with BAL and TBB are rare (fewer than 5% of all procedures) and consist of soreness of nose, transient fever, mild bleeding, and bronchospasm. Pneumonias are very uncommon (fewer than 1%) and death occurs in fewer than 0.001 percent of all bronchoscopies.