We have systematically screened the genome for evidence of linkage disequilibrium (LD) with multiple sclerosis (MS) by typing 6000 microsatellite markers in case–control and family based (AFBAC) ...cohorts from the Italian population. DNA pooling was used to reduce the genotyping effort involved. Four DNA pools were considered: cases (224 Italian MS patients), controls (231 healthy Italians), index (185 index cases from trio families) and parents (the 370 parents of the patient included in the Index pool), respectively.
After refining analysis of the most promising 14 markers to emerge from this screening process, only marker D2S367 retained evidence for association.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To better understand the presumed immune system dysregulation of chronic dysimmune neuropathy (CDN) patients, we designed a study to evaluate the levels of pro‐ and anti‐inflammatory cytokines in the ...most common forms of CDN: chronic inflammatory demyelinating polyneuropathy (CIDP), and anti‐myelin‐associated glycoprotein (MAG)‐related polyneuropathy (MAGnp). Sixteen patients fulfilled diagnostic criteria for CIDP, 14 were diagnosed with MAGnp, and 36 were classified as exhibiting “chronic idiopathic polyneuropathy” (CIP). Cytokine production in mitogen‐stimulated peripheral blood mononuclear cells (PBMCs) was analyzed by flow cytometry. CIDP and MAGnp patients were compared with CIP patients, those with monoclonal gammopathy without polyneuropathy (MGUS), and healthy controls (HC). We observed an increase in pro‐inflammatory cytokines in the CIDP group, whereas interleukin‐10 (IL‐10) was augmented in the MAGnp patients. These distinctive immune alterations may represent a biological tool in differential diagnosis and future therapeutic approaches. Muscle Nerve 42: 864–870, 2010
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Oxidative stress, linked to Abeta-lipid interactions, plays a pathogenetic role in Alzheimer's disease. We investigated modifications of lipid peroxidation products in plasma of 52 AD patients, 42 ...healthy controls and 16 patients with amyotrophic lateral sclerosis, a neurodegenerative disease where oxidative stress also plays a pathogenetic role. Final lipid peroxidation products were measured in plasma by thiobarbituric acid reactive substances (TBARS) assay before and after ex vivo oxidative stress catalysed by copper. There were no significant changes at basal conditions, but after copper-induced oxidation TBARS levels were higher in AD patients (19.0 microM +/- 2.2) versus both controls (5.2 microM +/- 0.8, p<0.001) and ALS patients (7.6 microM +/- 2.1, p<0.01). Stimulated TBARS levels were significantly higher in mild and moderate AD (p<0.0001) with respect to controls, but not in severe AD patients, with a significant inverse correlation between disease severity and lipid peroxidation (p<0.005, r2=0.21). Treatment of a subgroup (13) of mild and moderate AD patients with vitamin C and E for three months decreased plasma lipoperoxidation susceptibility by 60%. Thus, oxidative stress, expressed as ex vivo susceptibility to lipid peroxidation, appears to be an early phenomenon, probably related to AD pathogenetic mechanisms.
Classic Kaposi's sarcoma (CKS) is a multifocal vascular mesenchymal tumour of unknown origin. Human herpesvirus 8 (HHV8) is
now considered to be strongly involved, as a necessary co-factor, though ...insufficient for development of the disease. Additional
identified risk factors include environmental factors, personal habits and genetic susceptibility, with different loci suspected
of being risk factors for CKS. Since various human leukocyte antigen (HLA) patterns have been suggested as potential host-related
co-factors, the distribution of these alleles was studied in 41 CKS patients, 285 geographically-matched healthy controls
(HC) and 17 HHV8-positive controls. Molecular typing of HLA was performed using the polymerase chain reaction sequence-specific
primer method (SSP-PCR). Frequency distribution was evaluated by the Chi-squared test with Yates' correction. Odds ratios
(OR) and respective 95% confidence limits (CI) were calculated. A significantly higher frequency of HLA-DRB1*13 was observed
among the CKS patients (20.7%) compared to the HC (9.8%) (p<0.01; OR: 2.32; 95%CI: 1.21-4.41). Overall, these results indicated
that HLA-DRB1*13 may play a role in the development of CKS, while HLA-DQB1*0604 allele involvement occurs in linkage disequilibrium
with HLA-DRB1*13. To our knowledge, this is the first study documenting an HLA-DRB1 and -DQB1 loci association with CKS development
in the mainland Italian population.
HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic myelopathy, usually with adult-onset. Very few cases of childhood-onset have been described, most presenting with ...progressive paraparesis and sphincteric disturbances as in the adult form. Here we report a young male with childhood-onset of HAM/TSP and progressive cognitive and behavioral disturbances. A serological screening revealed HTLV-I infection, confirmed by Western Immunoblotting analysis. Molecular characterization of amplified HTLV-I proviral DNA has been performed both in the patient and his mother by LTR sequence analysis, and HLA genotype inheritance was evaluated. Our case indicates the possibility that cognitive dysfunctions may be one manifestation of HTLV-I infection in childhood.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Following the development of progressive multifocal leukoencephalopathy (PML) in two multiple sclerosis (MS) patients treated with natalizumab and interferon-β (IFNβ), a possible correlation between ...JC virus (JCV), the etiological agent of PML, and MS has received heightened interest. In particular, attention has focused on assessing whether IFNβ treatment could affect the replication of JCV and thus its frequency in the peripheral blood of MS patients and whether the presence of JCV DNA in peripheral blood could be a predictive marker of the risk of developing PML. In order to answer to these questions, peripheral blood samples were collected from 59 INFβ-treated, 39 untreated relapsing-remitting MS patients, and 98 healthy controls (HCs) and JCV DNA levels were determined and quantified by means of a real-time polymerase chain reaction (Q-PCR) assay. Overall, no differences were found in the presence or viral load of JCV DNA of MS patients and the HCs, but JCV DNA was significantly less frequent in the peripheral blood of IFNβ-treated patients (13.6%) compared to the untreated MS patients (46.1%) and the healthy controls (28.6%). These results suggest that the presence of JCV in the blood of MS patients cannot be considered as a marker or a risk factor for PML development. In addition, they indicate that treatment with INFβ can lead to the reduction of presence of the JCV genome in the peripheral blood of MS patients and, thus, that this drug probably does not increase the risk of PML in MS patients treated with IFNβ.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract A dynamic equilibrium between proliferation and programmed cell death (PCD) of auto-reactive T lymphocytes plays a pivotal role in the prevention of autoimmune diseases. We analyzed T ...lymphocytes myelin basic protein (MBP)-specific PCD and proliferation in demyelinating diseases. Results showed that MBP-specific PCD was significantly decreased in CD4+ and CD8+ T lymphocytes of progressive multifocal leukoencephalopathy (PML), not determined leukoencephalopathy (NDLE), and acute MS (AMS) patients compared to patients with stable MS (SMS) and healthy controls. MBP-specific proliferation/PCD rates were high in CD4+ T lymphocytes of PML, NDLE, and AMS patients, and in CD8+ T cells of PML and AMS individuals alone. Alterations of the balance between MBP-specific proliferation and PCD are present in demyelinating diseases and could play a major role in the pathogenesis of these diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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