Impact of inherited polymorphisms in glutathione S-transferase M1, microsomal epoxide hydrolase, cytochrome P450 enzymes on DNA, and blood protein adducts of benzo(a)pyrene-diolepoxide

The benzo(a)pyrene (BaP) metabolite benzo(a)pyrenediolepoxide (BPDE) is strongly implicated as a causative agent of lung cancer. To assess the risk of exposure to BaP, we made a combined analysis of levels of BPDE adducts to hemoglobin (Hb), serum albumin (SA), and lymphocyte DNA in 44 patients with incident lung cancer, as a prototype of a population mainly exposed to tobacco-derived BaP. We also investigated whether genetic polymorphisms of cytochrome P450IA1 (CYPIA1), microsomal epoxide hydrolase (mEH), and glutathione S-transferase M1 (GSTM1), which are involved in BaP metabolism, can be determinants of adduct formation. BPDE-Hb, BPDE-SA, and BPDE-DNA adducts were quantified as BaP tetrols released from hydrolysis of macromolecules and measured by high-resolution gas chromatography-negative ion chemical ionization-mass spectrometry to achieve high specificity and sensitivity. Individuals with detectable Hb adducts were positive for SA adducts but not vice versa, suggesting that BPDE-Hb adducts are less informative indicators of BaP exposure. Using PCR methods on DNA, we characterized GSTM1 deletion, CYPIA1 MspI and exon 7 valine variants, and mEH polymorphisms at amino acid positions 113 (EH3) and 139 (EH4). Levels of BPDE adducts were no different among CYPIA1, mEH, and GSTM1 genotypes. However, individuals with measurable BPDE-SA adducts were CYPIA1 variant carriers more frequently (P = 0.03). There was a slightly higher percentage of DNA detectable adducts in subjects with CYPIA1 exon 7 valine polymorphism. When subjects were classified by both polymorphisms on the mEH gene, those with two slow alleles (EH3 homozygous mutated) and no fast alleles (EH4 homozygous wild type) had a lower frequency of BPDE-SA adducts and no DNA adducts (P = 0.06). These results are based on a small number of observations thus far, but this exploratory study suggests that CYPIA1 and mEH variants might have an impact on BPDE exposure markers such as BPDE-SA adducts. Chemical specificity in adduct measurements is important to identify the biomarkers that reflect BaP exposure more accurately.     

Lymphangiosarcoma of the pubic region: a rare complication arising in congenital non-hereditary lymphedema

Lymphangiosarcoma is a rare, aggressive, vascular neoplasm arising in chronic congenital or acquired lymphedema. Although it is most frequently associated with post-mastectomy lymphedema (Stewart-Treves's syndrome), lymphangiosarcoma can exceptionally arise in congenital hereditary lymphedema (Milroy's syndrome and Meige's syndrome) and non-hereditary lymphedema (congenital, praecox or forme tarde lymphedemas). We report a case of lymphangiosarcoma of the pubic region, supported by immunohistochemical studies, in a 42-year-old woman affected by congenital, non-hereditary lymphedema of the left genital region and homolateral lower limb. In addition, molecular analysis demonstrated the absence of Kaposi's sarcoma-associated Herpes virus (KSHV) DNA sequences in tumour lesions. To our knowledge, this is the first case of lymphangiosarcoma associated with congenital non-hereditary lymphedema confined to the pubic region. The literature concerning the cases of lymphangiosarcoma arising in congenital hereditary and non-hereditary lymphedema is reviewed. Moreover, we emphasized the importance of regular clinical controls in all patients affected by chronic lymphedema. In fact, although the prognosis of this neoplasm is very poor, a prompt diagnosis and a rapid, ablative surgery associated with radiation therapy can increase the possibility of survival of these patients.     

A two-level fanout system for the CDF silicon vertex tracker

The Fanout system is part of the Silicon Vertex Tracker (SVT), a new trigger processor designed to reconstruct charged particle trajectories at level 2 (L2) of the CDF trigger, with a latency of 10 μs and an event rate up to 100 kHz. The core of SVT is organized as 12 identical slices, which process in parallel the data from the 12 independent azimuthal wedges of the Silicon Vertex Detector (SVXII). Each SVT slice links the digitized pulse heights found within one SVXII wedge to the tracks reconstructed by the level I (L1) fast track finder (XFT) in the corresponding 30° angular region of the Central Outer Tracker (COT). Since the XFT tracks are transmitted to SVT as a single data stream, their distribution to the proper SVT slices requires dedicated fanout logic. The fanout system has been implemented as a multiboard project running on a common 20 MHz clock. Track fanout is performed in two steps by one Fanout A and two Fanout B boards. The architecture, design, and implementation of this system are described     

Traceability of the 10-kΩ standard at IEN

The traditional scaling method used at the Istituto Elettrotecnico Nazionale (IEN) for the calibration of the 10-kΩ standard is compared with more straightforward techniques: one based on the linearity of a DVM and the other on a commercial current comparator bridge. For the three methods, the measurement results and the uncertainty budgets are reported. The agreement is better than 1×10^-7     

FDTD analysis of crosstalk in multilayer printed circuits

A theoretical analysis has been developed to study the crosstalk in crossed bundles of parallel lines. The model is based on the theory of the coupled transmission lines and the resulting system of differential equations has been solved by means of the finite difference, time-domain (FDTD) method. The frequency response of the network has been achieved by the discrete fourier transform (DFT) algorithm; measurements, performed with a vectorial network analyser, show a good agreement with numerical simulation.