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Biomedical subjects

C Pepe

Publications and source records attributed to C Pepe.

15 recordsLinked to original sources

Methyl group metabolism gene polymorphisms as modifier of breast cancer risk in Italian BRCA1/2 carriers.

BRCA1 and 2 are major cancer susceptibility genes but their penetrance is highly variable. The folate metabolism plays an important role in DNA methylation and its alterated metabolism is associated with cancer risk. The role of allele variants 677T and 1298C (MTHFR gene) and 2756G (MS gene) has been investigated as potentially modifying factors of BRCA gene penetrance, evaluated as age at first diagnosis of cancer, in 484 BRCA1/BRCA2 carriers and in 108 sporadic breast cancer cases as a control group. The genotype analysis has been performed by means of PCR/RFLP's. The analysis of association between a particular genotype and disease risk was performed using Cox Regression with time to breast or ovarian cancer onset as the end-point. The presence of 677T allele confers an increased risk of breast cancer in BRCA1 carriers (P = 0.007) and the presence of 1298C allele confers an increased risk of breast cancer in sporadic cases (P = 0.015).

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Proton affinity ladder for uridine and analogs: influence of the hydroxyl group on the sugar ring conformation.

A ladder of relative proton affinities (PA) for a series of modified uridines (e.g. araU, ddU, 5BrU, 5BrdU and 5IU) was established from competitive dissociations of proton-bound heterodimers using Cooks and co-workers' kinetic method. The studied heterodimers are constituted of a modified nucleoside and either an amino acid or a nucleoside with known PA value. These non-covalent heterodimers were prepared under electrospray conditions to be selected and dissociated into the ion-trap analyzer. These results allowed our PA ladder of uridine and deoxyuridine analogs substituted at the C-5 position in the uracil ring to be extended. From this scale, it was showed that the substitution of hydrogen atom at the C-2' position in the sugar ring by a hydroxyl group involves a decrease of about 7 kJ mol(-1). The experimental values for U, 5MeU, dU, 5MedU, ddU and araU are consistent with those obtained by DFT calculations (B3P86/6-31+G//B3LYP/6-31G(.)). Several neutral and protonated conformations of these compounds were considered, in particular the ring conformation of furanose and the orientation of the base with respect to the sugar ring. These calculated results showed the influence of sugar substituent on the conformation of the neutral form of theses nucleosides. However, the most stable protonated structure is the same for all the studied nucleosides except for araU, where the position of the anti 2'-OH group imposes a specific conformation.

Carbohydrates↗

Proton affinity of diastereoisomers of modified prolines using the kinetic method and density functional theory calculations: role of the cis/trans substituent on the endo/exo ring conformation.

The proton affinity (PA) of cis/trans-3-prolinoleucines and cis/trans-3-prolinoglutamic acids have been studied by the kinetic method and density functional theory (DFT) calculations. Several conformations of the neutral and the protonated modified prolines, in particular the endo and exo ring conformations, were analyzed with respect to their contribution to the PA values. When the substituent is an alkyl, both the diastereoisomers have the same PA value. However, the PA values for the diastereoisomers are different when the substituted chain contains functional groups (e.g. a carboxyl group). This variation in PA values could be attributed to the existence of intramolecular hydrogen bonds.

Algorithms↗

Ab initio calculations of proton affinities of glycine, proline, cysteine and phenylalanine: comparison with the experimental values obtained using an electrospray ionisation ion trap mass spectrometer.

The proton affinities of four characteristic amino acids, glycine, proline, cysteine and phenylalanine, have been calculated using three different types of wave function, HF, DFT and MP2. These wave functions were combined with several basis sets using the valence double- or triple-xi with polarisation functions, and included or not a diffuse d function on heavy atoms. Calculations were carried out using Gaussian 98 on a LINUX system (2 GHz, 2 GB of RAM). The calculated results have been compared with the experimental values obtained using Cooks' kinetic method, in particular on an electrospray ionisation ion trap mass spectrometer. An excellent agreement was found between the experimental values and the theoretical results obtained using the B3P86/6-31+G*//B3LYP/6-31G* level.

Amino Acids↗

A computational and experimental study of cation affinity (Na+) of nucleobases and modified nucleobases by electrospray ionization ion trap mass spectrometry.

Gas-phase Na+ affinities of modified or unmodified nucleobases were determined theoretically at the density functional theory level, with the B3P86 functional and the 6-31 + G* basis set, and experimentally using electrospray ionization ion trap mass spectrometry (ESI-ITMS) and the kinetic method. For the calculations, the sodium cation affinities (SCA) were obtained from energies of the most stable complexes of the free nucleobases. Experimentally and theoretically relative scales of cation affinities were determined using eight modified and unmodified nucleobases and a very good agreement was obtained.

Cations↗

Proton affinity of proline and modified prolines using the kinetic method: role of the conformation investigated by ab initio calculations.

The proton affinities of proline, cis-3-methylproline and cis-3-ethylproline have been measured by the kinetic method using an ion trap instrument; the values obtained are 936, 940.5, and 943 kJ mol(-1), respectively. The experimental values are consistent with those obtained by high-level ab initio calculations (B3LYP/6-31+G*//B3LYP/6-31G* and B3P86/6-31+G*//B3LYP/6-31G*). Several conformations of neutral and protonated proline were considered, in particular the endo and exo ring structure and the position of the carboxyl group. These results show the importance of the position of the hydrogen atom of the carboxyl group in determining the most stable protonated proline structure.

Algorithms↗

[The evaluation by video capillaroscopy of the efficacy of a Ginkgo biloba extract with L-arginine and magnesium in the treatment of trophic lesions in patients with stage-IV chronic obliterating arteriopathy].

BACKGROUND AND AIMS: This study aimed to evaluate the influence of Ginkgo biloba extract with arginine and magnesium used for the treatment of trophic lesions in the lower limbs caused by both diabetic and non-diabetic microangiopathy. METHODS: A comparative study was carried out in 20 patients who were divided into two groups: 10 were treated with ASA plus Ginkgo biloba extract with arginine and magnesium and 10 with ASA plus conventional hemorheology. The observation time was extended to 6 months, taking into consideration patients with trophic lesions to the lower limbs suffering from diabetic and non-diabetic peripheral arterial occlusive disease. The evaluation was performed by clinical, ultrasonographic and perilesional video capillaroscopy monitoring. Ultrasonographic and video capillaroscopy instrumental methods were used because they provide a full picture of macro and microcirculatory conditions around lesions. RESULTS: The study showed the undoubted efficacy of Ginkgo biloba extract with magnesium and arginine in relation to the following points: reduced healing times for the trophic lesion compared to the control group, improved painful symptoms, increased perilesional neoangiogenesis. No significant differences were observed from a Doppler ultrasonographic point of view or with regard to the claudication free interval. CONCLUSIONS: Ginkgo biloba extract with arginine and magnesium can improve the dynamics of cutaneous trophism in lesions caused by diabetic and non-diabetic microangiopathy.

Aged↗

Anxiety sensitivity and drug choice in individuals seeking treatment for substance abuse.

Sixty-four men and 49 women who applied for admission to outpatient substance abuse programs provided information on their preferred chemical (e.g., alcohol) and information on their alcohol and other chemical use. They also completed a package of self-report questionnaires including the Anxiety Sensitivity Index (ASI). The results showed that men who scored high on the ASI were more likely than low ASI subjects to prefer depressants, especially alcohol. Subjects who scored low on the ASI were more likely to prefer marijuana. ASI score did not predict chemical preference among women. All female ASI groups (high, medium and low) showed a preference for alcohol. The implications of these findings are discussed.

Adult↗

Detection apparatus for multiple heterogeneous chemiluminescence immunoassay configurations.

We describe an apparatus for measuring signals emanated from two heterogeneous chemiluminescence immunoassay (CLIA) configurations: antibody-coated polystyrene beads, in reaction tray wells, and microparticles captured by a porous matrix. An optics and fluidics design which allows the use of a common detection head for these two different assay configurations is described. The detection head moves along three Cartesian coordinates to create a localized light-tight compartment around each individual disposable reaction vessel. Reproducibility of the light seal, trigger solution delivery, and mixing is achieved for acridinium-labeled CLIA. The coated polystyrene beads configuration is tested using beta HCG, CEA, and TSH assays. The microparticle-capture configuration is tested using beta HCG and HBsAg assays. The microparticle capture CLIA has shorter incubation times and the potential for ease of automation.

Data Interpretation, Statistical↗

Abbott prism: a multichannel heterogeneous chemiluminescence immunoassay analyzer.

We describe a multichannel heterogeneous immunoassay analyzer in which a sample is split between disposable reaction trays in a group of linear tracks. The system's pipettor uses noninvasive sensing of the sample volume and disposable pipet tips. Each assay track has (a) a conveyor belt for moving reaction trays to predetermined functional stations, (b) temperature-controlled tunnels, (c) noncontact transfer of the reaction mixture between incubation and detection wells, and (d) single-photon counting to detect a chemiluminescence (CL) signal from the captured immunochemical product. A novel disposable reaction tray, with separate reaction and detection wells and self-contained fluid removal, is used in conjunction with the transfer device on the track to produce a carryover-free system. The linear immunoassay track has nine predetermined positions for performing individual assay steps. Assay step sequence and timing is selected by changing the location of the assay modules between these predetermined positions. The assay methodology, a combination of microparticle capture and direct detection of a CL signal on a porous matrix, offers excellent sensitivity, specificity, and ease of automation. Immunoassay configurations have been tested for hepatitis B surface antigen and for antibodies to hepatitis B core antigen, hepatitis C virus, human immunodeficiency virus I and II, and human T-cell leukemia virus I and II.

Binding, Competitive↗

Reaction tray and noncontact transfer method for heterogeneous chemiluminescence immunoassays.

We describe a reaction tray for a heterogeneous chemiluminescence (CL) immunoassay having the following features: separate sample incubation and signal detection wells; a design that allows for noncontact transfer of the reaction mixture from incubation wells to detection wells; surface features to mate with a detector and create a light-tight seal for CL detection; and self-contained means for liquid removal. The reaction mixture is transferred by injecting a wash solution from a group of nozzles into the incubation well. Quantitative transfer of microparticles (transfer efficiencies greater than 95% and CV less than 5%) is achieved by injecting two 300-microL pulses of transfer solution at a rate of 2.1 m/s. The performance of the tray and method of transfer is tested by determining the precision of CL signal for a sample containing a concentration of anti-hepatitis B core antigen (anti-HBc) or hepatitis B surface antigen (HBsAg) close to the cutoff value for the assay.

Binding, Competitive↗