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N Silver

Publications and source records attributed to N Silver.

8 recordsLinked to original sources
PubMed2005

Interaction between two quantitative trait loci affects fetal haemoglobin expression.

The biological mechanisms controlling complex quantitative traits are likely to be affected by interactions between genetic factors, sometimes referred to as epistasis. The identification of interacting loci through genetic analyse faces many challenges, and few examples of replicated findings of interaction exist for humans and model system organisms. The replication of an interaction, or the non-independence, of two quantitative trait loci (QTL) affecting the developmental switch from the expression of fetal to adult haemoglobin is reported here. Fetal haemoglobin expression in adults is a highly heritable, yet complex, phenotype. Using a sample of 874 dizygotic twin pairs of European descent, we found linkage to a QTL on chromosome 8 to be conditional on the twin pairs' genotypes at a polymorphism in the beta-globin complex; an interaction originally identified in a large Asian Indian kindred. The beta-globin polymorphism has been previously shown to be associated with fetal haemoglobin levels in adults. This study reports the first known replication of a genetic interaction between QTLs influencing a complex human trait.

Chromosomes, Human, Pair 8↗
PubMed2004

Chlamydophila pneumoniae infection of the central nervous system in patients with multiple sclerosis.

BACKGROUND: Chlamydophila pneumoniae has been postulated as an aetiological agent in the pathophysiology of multiple sclerosis. Previous studies show conflicting results. OBJECTIVE: To investigate patients with multiple sclerosis and other neurological diseases for evidence of past or present infection with C pneumoniae. METHODS: 19 patients with multiple sclerosis and 29 with other neurological diseases were studied. Evidence was sought for past or present infection with C pneumoniae using polymerase chain reaction (PCR) and cell culture of cerebrospinal fluid (CSF), and enzyme linked immunosorbent assay and microimmunofluorescence of serum. RESULTS: C pneumoniae was grown from the CSF of one patient with multiple sclerosis. PCR was negative in all cases. Anti-chlamydial antibodies were detected in the same proportion in each group. CONCLUSIONS: This study does not support the theory of an association between C pneumoniae and multiple sclerosis.

Adult↗
PubMed2003

Disability in multiple sclerosis is related to normal appearing brain tissue MTR histogram abnormalities.

BACKGROUND: Magnetization transfer ratio (MTR) histogram analysis provides a global measure of disease burden in multiple sclerosis (MS). MTR abnormalities in normal appearing brain tissue (NABT) provide quantitative information on the extent of tissue damage undetected by conventional T2-weighted (T2W) magnetic resonance imaging (MRI). AIMS: 1) To compare the MTR histograms from NABT across a broad spectrum of relapse onset MS patients, including relapsing-remitting (RR) MS (including newly diagnosed and benign subgroups) and secondary progressive (SP) MS. 2) To determine the relationship between clinical disability and NABT MTR histograms. METHODS: 2D spin echo magnetization transfer imaging was performed on 70 RRMS and 25 SPMS patients and compared with 63 controls. MTR histograms were acquired for NABT after extracting lesions and cerebrospinal fluid (CSF). T2W images were used to measure the brain parenchymal fraction (BPF) and T2 lesion load. RESULTS: MS patients had a disease duration ranging from 0.5 to 37 years and an Expanded Disability Status Scale (EDSS) score ranging from 0 to 8.5. There was a significant decrease in NABT mean MTR (+/- standard deviation) compared with controls (33.07 pu +/- 1.06 versus 34.26 pu +/- 0.47; P < 0.001) with an effect size of 2.56. The reduction in NABT mean MTR varied among patient groups from 4.9% for SPMS, 3% for all RRMS, 2.7% for early RRMS and 2.5% for benign MS, compared with controls. NABT mean MTR correlated significantly with T2 lesion load (r = -0.82) and BPF (r = 0.58). EDSS score correlated with NABT mean MTR (r = -0.43), BPF (r = -0.33) and with T2 lesion load (r = 0.59). Multivariate analysis using NABT MTR peak height, T2 lesion load and BPF combined only accounted for 38% of the variance in the EDSS (r = 0.62; P < 0.001). Disease duration accounted for an additional 14% of variance in the EDSS (r = 0.72; P < 0.001). CONCLUSIONS: There is evidence of diffuse abnormalities in NABT in addition to global brain atrophy in relapse onset MS patients, including those with recently diagnosed RRMS and benign MS. The abnormalities are greatest in patients with the more disabling SPMS. Atrophy, NABT and lesion abnormalities are all partly correlated; the processes marked by these MR measures all contribute to disability in MS, providing complementary information relevant to the complex pathological processes that occur in MS.

Adult↗
PubMed1999

Spatial mapping of T2 and gadolinium-enhancing T1 lesion volumes in multiple sclerosis: evidence for distinct mechanisms of lesion genesis?

It is generally believed that most T2-weighted (T2) lesions in the central white matter of patients with multiple sclerosis begin with a variable period of T1-weighted (T1) gadolinium (Gd) enhancement and that T1 Gd-enhancing and T2 lesions represent stages of a single pathological process. Lesion probability maps can be used to test this hypothesis by providing a quantitative description of the spatial distribution of these two types of lesions across a patient population. The simplest prediction of this hypothesis would be that the spatial distributions of T1 Gd-enhancing and T2 lesions are identical. We generated T1 Gd-enhancing and T2 lesion probability maps from 19 patients with relapsing-remitting multiple sclerosis. There was a significantly higher probability (P = 0.001) for T2 lesions to be found in the central relative to the peripheral white matter (risk ratio 4.5), although the relative distribution of T1 Gd-enhancing lesions was not significantly different (P = 0.7) between central and peripheral white matter regions (risk ratio 0.6). Longitudinal data on the same population were used to demonstrate a similar distribution asymmetry between new T1 Gd-enhancing and new T2 lesions that developed over the course of 1 year. Alternative hypotheses to explain this observation were tested. We found no spatial difference in the likelihood of development of persistent T2 lesions following T1 Gd enhancement. The relative distribution of T1 Gd-enhancing lesions was shown to be independent of the dose of Gd contrast agent and the frequency of scanning. Our findings suggest that a proportion of the periventricular T2 lesion volume may arise from mechanisms other than those associated with early breakdown of the blood-brain barrier leading to T1 Gd enhancement.

Adult↗
PubMed1997

Single-dose gadolinium with magnetization transfer versus triple-dose gadolinium in the MR detection of multiple sclerosis lesions.

PURPOSE: To compare the efficacy of single-dose gadolinium with magnetization transfer contrast (MTC) with that of triple-dose gadolinium in detecting enhancing multiple sclerosis lesions. METHODS: Twenty-one patients with multiple sclerosis were examined with MR imaging first with 0.1 mmol/kg gadolinium (single dose) and then, after 24 to 72 hours, with 0.3 mmol/kg gadolinium (triple dose). T2-weighted fast spin-echo and T1-weighted spin-echo MR images with and without MTC were obtained before contrast administration followed by either T1-weighted spin-echo images with MTC (single dose) or conventional T1-weighted spin-echo images (triple dose), starting 5, 17, and 29 minutes after contrast administration. All images were evaluated in a blinded fashion and scored in random order by two readers. Outcome parameters included number of enhancing lesions, number of active MR examinations (those containing at least one enhancing lesion), contrast ratio (signal intensity of enhancing lesion divided by signal intensity of normal-appearing white matter), and size of enhancing lesions. RESULTS: Eighty-one percent more enhancing lesions and 49% more active MR examinations were detected when a triple dose of gadolinium was used as compared with a single dose. The level of agreement between readers as to the number of enhancing lesions was significantly higher for triple-dose than for single-dose gadolinium. With triple-dose gadolinium, contrast ratios and areas of enhancement increased by 10% and 33%, respectively. Delayed imaging increased the size of the lesion by 11% on single-dose MTC images and by 18% on triple-dose images. CONCLUSION: Triple-dose gadolinium is more effective (higher sensitivity and interobserver agreement) than single-dose gadolinium in combination with MTC in detecting enhancing multiple sclerosis lesions.

Adult↗