Showing papers by "Luisa Benussi published in 2008"

Low plasma progranulin levels predict progranulin mutations in frontotemporal lobar degeneration

Abstract: Background: Mutations in the progranulin gene ( PGRN ) were identified as the causal mechanism underlying frontotemporal lobar degeneration (FTLD). Most of these mutations are predicted to create null alleles leading to a 50% loss of progranulin transcript. Methods: Patients underwent clinical and neurologic examination at the Memory Clinic of the IRCCS S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy. We enrolled affected (n = 6) and unaffected at risk members (n = 73) of families carrying the FTLD associated progranulin Leu271LeufsX10 mutation; additionally, we included subjects affected by sporadic/familial FTLD (n = 65), controls (n = 75), and a family carrying the tau P301L mutation. The presence of mutations in PGRN and MAPT genes was investigated by direct sequencing of exonic and flanking intronic regions. Progranulin plasma and CSF levels were measured using ELISA. Results: We demonstrated that progranulin protein is strongly reduced (up to 3.93-fold) both in plasma and CSF of affected and unaffected subjects carrying mutations in progranulin gene (PGRN Leu271LeufsX10 and Q341X). We established a plasma progranulin protein cutoff level of 74.4 ng/mL that identifies, with specificity and sensitivity of 100%, mutation carriers among unaffected subjects. In FTLD, values ≤110.9 ng/mL give a specificity of 92.8% and a sensitivity of 100% for PGRN mutations. Conclusions: We propose the dosage of plasma progranulin as a useful tool for a quick and inexpensive large-scale screening of carriers of progranulin mutations and for monitoring future treatments that might boost the level of this protein. GLOSSARY: FTD = frontotemporal dementia; FTLD = frontotemporal lobar degeneration; PPA = primary nonfluent aphasia.

Decreased plasma levels of soluble receptor for advanced glycation end products in mild cognitive impairment

Abstract: Growing evidence advanced the idea that the soluble form of the receptor for advanced glycation end-products (sRAGE) might serve as a risk marker for several disorders including Alzheimer disease. We found a reduced level of circulating sRAGE in patients with mild cognitive impairment (MCI). The reduction of sRAGE in MCI, as well as the anticipation of the disease in patients with the lowest sRAGE levels (≤225 pg/ml), suggest a role of the RAGE axis in the pathogenesis of the disease.

The gas monitoring system for the Resistive Plate Chamber detector of the CMS experiment at LHC

Abstract: Due to its large volume (18 m3)the Resistive Plate Chamber (RPC) detector of the Compact Muon Solenoid (CMS) experiment at the LHC proton collider (CERN, Switzerland) will employ a gas re-circulation system. Since the mixture composition and quality are crucial issues for the detector operation, CMS-RPC will use an online gas analysis and monitoring system. An overview of both the CMS-RPC gas system and gas monitoring system is given and the project parameters are described.

Association of Blood Pressure and Genetic Background With White Matter Lesions in Patients With Mild Cognitive Impairment

Abstract: Background. White matter lesions (WMLs) may contribute to cognitive deficits in patients with mild cognitive impairment (MCI), but their pathogenesis is complex. Fluctuations of blood pressure (BP) over 24 hours and genetic predisposition to develop vascular damage have been implicated. Methods. In 63 MCI patients 65 years old or older, BP was measured both clinically and with ambulatory BP monitoring. Patients were classified in two groups: no/very mild (n = 34) and mild to severe (n = 29) WMLs, based on a visual scale on magnetic resonance (mean age 71.8 +/- 4.7 vs 74.6 +/- 5.1, and female gender 53% vs 66%, respectively). The volume of WMLs was measured by a semi-automatic method, separately for periventricular caps and rim, periventricular confluent, subcortical punctate, and subcortical confluent. Polymorphisms of cystatin C (CST3) and cholesterol 24-hydroxylase (CYP46) genes, putative risk factors for cerebrovascular disease, were determined. Results. The prevalence of cerebrovascular risk factors was similar in the two MCI groups of different WML severity, as well as clinic and ambulatory BP. In patients with mild to severe, but not in those with no/very mild WMLs, the volume of periventricular confluent WMLs increased with increasing daytime systolic BP (regression coefficient.47, 95% confidence interval [CI],.13 to.71 vs.02, 95% CI, -.32 to.36, p =.003 for the difference between slopes). The volume of other WML subtypes was not associated with ambulatory BP. Participants carrying both CST3*B and CYP46*T alleles were overrepresented in the MCI group with mild to severe WMLs (43% vs 17%, p.03). Conclusions. BP and gene putative risk factors for cerebrovascular disease are differentially associated with WMLs in two MCI groups of different WML severity. WMLs might develop for the convergence of innate with acquired factors.

Search for + ! pK + and D + ! K + K + Using Genetic Programming Event Selection

Abstract: Abstract We apply a genetic programming technique to search for the doubly Cabibbo suppressed decays Λ c + → p K + π − and D s + → K + K + π − . We normalize these decays to their Cabibbo favored partners and find BR ( Λ c + → p K + π − ) / BR ( Λ c + → p K − π + ) = ( 0.05 ± 0.26 ± 0.02 ) % and BR ( D s + → K + K + π − ) / BR ( D s + → K − K + π + ) = ( 0.52 ± 0.17 ± 0.11 ) % where the first errors are statistical and the second are systematic. Expressed as 90% confidence levels (CL), we find