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J Oger

Publications and source records attributed to J Oger.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Enhanced adherence of endothelial cells to blood mononuclear cells in HAM/TSP].

We investigated the adhesion of blood mononuclear cells (MNC) isolated from patients with HTLV-1-associated myelopathy (HAM/TSP). MNC from HAM/TSP patients were significantly more adherent to activated endothelial monolayers than MNC from non-HAM/TSP (controls and HTLV-1 carriers) subjects. Blocking studies demonstrated that the adhesion molecules VLA-4 (CD49d), ICAM-1 (CD54), and L-selectin (CD62L) all contributed to increased binding. However, anti-ICAM-1 antibody was the most efficient in inhibiting binding HAM/TSP patients MNC to activated endothelial cells. Expression on MNC of molecules involved in adhesion was also studied by flow cytometry in HAM/TSP patients, HTLV-1 carriers, and healthy control subjects after two days culture without any mitogen. In HAM/TSP patients, L-selectin expression on CD4+ and CD8+ subsets was lower than in controls; interestingly, HAM/TSP patients had lower percentage of CD4+ subset expressing L-selectin than HTLV-1 carriers. The percentage of CD4+ and CD8+ cells expressing VLA-4 was found to be similar to controls in both HAM/TSP patients and HTLV-1 carriers. Following two days in culture without mitogen, the percentage of T cells expressing ICAM-1 increased in HAM/TSP and carriers, but not in controls. This study provides information regarding trans-endothelial migration of MNC across the blood brain barrier in HAM/TSP and suggests ICAM-1 and its counterpart molecule LAF-1 are involved in massive infiltration of lymphocytes observed in the spinal cord.

Adult↗
PubMed1996

A full genome search in multiple sclerosis.

The aetiology of multiple sclerosis (MS) is uncertain. There is strong circumstantial evidence to indicate it is an autoimmune complex trait. Risks for first degree relatives are increased some 20 fold over the general population. Twin studies have shown monozygotic concordance rates of 25-30% compared to 4% for dizygotic twins and siblings. Studies of adoptees and half sibs show that familial risk is determined by genes, but environmental factors strongly influence observed geographic differences. Studies of candidate genes have been largely unrewarding. We report a genome search using 257 microsatellite markers with average spacing of 15.2 cM in 100 sibling pairs (Table 1, data set 1 - DS1). A locus of lambda>3 was excluded from 88% of the genome. Five loci with maximum lod scores (MLS) of >1 were identified on chromosomes 2, 3, 5, 11 and X. Two additional data sets containing 44 (Table 1, DS2) and 78 sib pairs (Table 1, DS3) respectively, were used to further evaluate the HLA region on 6p21 and a locus on chromosome 5 with an MLS of 4.24. Markers within 6p21 gave MLS of 0.65 (non-significant, NS). However, D6S461, just outside the HLA region, showed significant evidence for linkage disequilibrium by the transmission disequilibrium test (TDT), in all three data sets (for DS1 chi2 = 10.8, adjusted P < 0.01)(DS2 and DS3 chi2 = 10.9, P < 0.0005), suggesting a modest susceptibility locus in this region. On chromosome 5p results from all three data sets (222 sib pairs) yielded a multipoint MLS of 1.6. The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility.

Chromosome Mapping↗
PubMed1996

Depression and multiple sclerosis.

The objective of the present study were (1) to ascertain the lifetime risk of a depression in a representative group of multiple sclerosis (MS) patients, (2) to assess the morbidity risks for depression among first-degree relatives of these MS patients, and (3) to compare these familial risks for first-degree relatives of MS patients with those for first-degree relatives of a primary depression population, i.e., depression but no MS. We psychiatrically evaluated 221 MS patients (index cases) using a structured clinical interview for the DSM-III-R and calculated the rate and lifetime risk of depression for these index cases using the product limit estimate of survival function. We obtained psychiatric histories for all first-degree relatives of index cases, and we calculated morbidity risks for depression for these relatives using the maximum likelihood approach and compared the risks using the likelihood ratio tests. Index cases had a 50.3% lifetime risk of depression. Morbidity risks for depression among first-degree relatives of index cases were decidedly lower when compared with morbidity risks among first-degree relatives of the reference population. Although there appears to be a very high rate of depression among MS patients, the data for their first-degree relatives do not support a clear genetic basis for this depression, or at least the same genetic basis that probably operates within families when depression occurs in the absence of MS.

Adolescent↗
PubMed1995

Interferon-beta downregulates interferon-gamma-induced class II MHC molecule expression and morphological changes in primary cultures of human brain microvessel endothelial cells.

Regulation of class II MHC (Ia) antigen expression by interferons beta and gamma was studied in an in vitro model of the blood-brain barrier. Primary cultures of human brain microvessel endothelial cells were incubated with IFN-beta, gamma or a combination of the two cytokines and surface expression of class II MHC molecules was investigated with the immunogold silver staining technique and enzyme-linked immunosorbent assay. Treatment of monolayers with IFN-beta (100-6000 U/ml) failed to induce Class II MHC molecules. Co-incubation with IFN-gamma (100 U/ml), with or without pretreatment with IFN-beta, significantly inhibited the IFN-gamma-induced de novo expression in a concentration-dependent manner. Downregulation was less significant when incubation with both cytokines was preceded by 2-day treatment with IFN-gamma and was not observed in cultures incubated for an additional 4 days with IFN-gamma. Endothelial cells treated with IFN-gamma exhibited prominent morphological changes and frequent overlapping. These changes were not observed in the presence of either IFN-beta or both cytokines in the media. IFN-beta alone, or in combination with IFN-gamma, significantly inhibited the growth of endothelial cells, while only slight inhibition was observed with IFN-gamma. The results of these studies suggest that IFN-beta may function in modulating IFN-gamma-mediated immune responses in the human central nervous system at the level of the blood-brain barrier and this negative regulatory mechanism may be, at least in part, responsible for the recently reported beneficial effect of IFN-beta in relapsing-remitting multiple sclerosis.

Cells, Cultured↗
PubMed1995

Human T-lymphotropic virus type 1 in coastal natives of British Columbia: phylogenetic affinities and possible origins.

Human T-lymphotropic virus type 1 (HTLV-1) infection has been discovered recently in people of Amerindian descent living in coastal areas of British Columbia, Canada. DNA sequencing combined with phylogenetic analysis and restriction fragment length polymorphism (RFLP) typing of HTLV-1 strains recovered from these British Columbia Indians (BCI) was conducted. Sequence-based phylogenetic trees distributed the BCI isolates among the Japanese subcluster (subcluster B) and the geographically widely distributed subcluster (subcluster A) of the large HTLV-1 cosmopolitan cluster. Long terminal repeat (LTR) RFLP typing revealed three distinct, equally frequent LTR cleavage patterns, two of which were of previously recognized Japanese and widely dispersed cosmopolitan types. A third, new cleavage pattern was detected which may have arisen by recombination between two other HTLV-1 genotypes. Our results suggest multiple origins for HTLV-1 in BCI, which are equally consistent with (i) a cluster of recent sporadic infections, (ii) ancient endemic vertical transmission through Amerindian lineages, or (iii) both.

Base Sequence↗
PubMed1995

Ventilatory muscle strength and endurance in myasthenia gravis.

Patients with generalized myasthenia gravis (MG) often have associated ventilatory muscle involvement. It is not known whether patients with isolated ocular muscle involvement have identifiable involvement of their ventilatory muscles. Most studies have assessed muscle involvement by measuring muscle strength; however, we hypothesized that measures of ventilatory muscle endurance may be more sensitive tests of ventilatory muscle involvement in myasthenia gravis. We studied 17 patients with myasthenia gravis (four with ocular involvement alone and 13 with varying degrees of generalized myasthenia gravis). Spirometry, ventilatory muscle strength (maximum inspiratory and expiratory pressures (MIP and MEP)) and endurance (2 min incremental threshold loading test) were measured before and 20 min after i.m. neostigmine. We compared the results with those of 10 normal controls. We found no difference between patients with isolated ocular involvement and controls. Ocular myasthenia gravis patients did not improve after neostigmine. The patients with generalized myasthenia gravis had reduced baseline ventilatory muscle strength (MIP 67 cmH2O (70% of predicted), MEP 86 cmH2O (50% of pred) and endurance (mean maximal load achieved = 246 g, mean pressure at highest load (P) = 19.4 cmH2O) compared with controls. After neostigmine, there was a significant increase in MIP in patients with generalized myasthenia gravis and a trend towards an increased MEP. As a group, the patients with generalized myasthenia gravis did not demonstrate a change in their ventilatory muscle endurance after neostigmine; however, there was considerable interpatient variability in response. We conclude that patients with isolated ocular MG have normal ventilatory muscle strength when tested conventionally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Demyelination and ethnicity: experience at the University of British Columbia Multiple Sclerosis Clinic with special reference to HTLV-I-associated myelopathy in British Columbian natives.

Since its creation in 1980, the Multiple Sclerosis Clinic at the University of British Columbia has actively followed over 2,500 patients from the Canadian province of British Columbia (BC) who have clinically definite multiple sclerosis (MS). These patients include 2,496 European Caucasians from a BC population of 3,858,505 (prevalence 64.7/100,000) in contrast with 92 patients of other ethnic origin (prevalence 14.6/100,000). Prevalence was higher in South Asians (15.7 from a population of 114,355) than in East Asians (6.25 from 287,845). Among individuals with native ancestry, MS was not rare when there was also European ancestry (46 cases from a population of 94,615), but MS was not encountered in pure-blooded natives (0 cases from 74,420 individuals). In contrast, among 5 patients with HTLV-I-associated myelopathy (HAM), 4 (from a population of 74,420) were of single native ancestry and only 1 (from a population of 94,615) was of multiple ancestry, including native ancestry. HAM was not found among Caucasians. This preliminary account clearly establishes that HAM is linked to native ancestry and that MS is linked to Caucasian ancestry.

British Columbia↗
PubMed1992

Sleep disturbance, depression, and lesion site in patients with multiple sclerosis.

We examined the prevalence of sleep problems in a sample of patients with mild but clinically definite multiple sclerosis (n = 143) and sought to determine whether there was a relationship between the presence of sleep complaints and the level of depression. As magnetic resonance imaging scans were available for a subsample of the patients with multiple sclerosis (n = 117), we also wanted to determine whether there was a relationship between the site of the lesion and the presence of sleep difficulties. The prevalence of sleep difficulties was three times higher in the patients with multiple sclerosis than the control group (25.2% vs 8.2%). Moreover, the presence of sleep complaints was associated with higher levels of depression. Three lesion sites that subserve supplemental motor areas were significantly related to the presence of sleep complaints. These findings suggest that, for some patients with MS, sleep disturbance and accompanying increases in depression may be a function of the lesion site resulting in nocturnal spasms.

Adult↗
PubMed1992

Ventricular size, cognitive function and depression in patients with multiple sclerosis.

The purpose of this study was to explore further the hypothesis that changes in cognitive function may occur in the mild stages of multiple sclerosis (MS) by determining whether ventricular enlargement was related to cognitive function. Ten measures of ventricular size were made in a sample of 123 MS patients with mild disability and 60 well-matched healthy controls. In addition, sixteen tests of cognitive function and the Beck Depression Inventory were administered. For the MS group, there were significant correlations between the ventricular measures and cognitive performance but not for the normal controls. Scores on the Beck Depression Inventory were not correlated with either cognitive performance or ventricular enlargement. These findings suggest that for the MS group cognitive impairment was related to the disease process but not to the level of depression.

Adult↗
PubMed1992

Treatment of acquired autoimmune myasthenia gravis: a topic review.

We propose a new approach to staging the disease based on clinical and immunological response to treatment. We oppose clinical remission to immunological remission and define total clinical remission as the goal of therapy. We describe the use, side effects and indications of established therapies. Acetylcholine esterase inhibitors are only a symptomatic treatment as is plasma exchange. Usefulness and limits of thymectomy, corticosteroids and immunosuppressants are described here. Their goal is to reduce the auto-immune process. Long-term hazards from these medications are described and methods to reduce their potential risks are suggested. We suggest the number of patients having life threatening complications while undergoing aggressive immunosuppression can be reduced by a systematic approach to follow-up. In the second part of this review article, adapting management to specific situations is emphasized in refractory disease, respiratory failure, neonatal and juvenile forms of the disease. The special situation of seronegative myasthenia is discussed.

Autoimmune Diseases↗
PubMed1991

Empirical support for psychological profiles observed in multiple sclerosis.

Though increasing attention is being paid to psychological aspects of multiple sclerosis, much research continues to examine patients as differing in quantity rather than quality of psychological abnormality or response. Cluster analysis was used to identify distinctive psychological profiles in a large sample of patients with multiple sclerosis. It employed three measures, carefully chosen to capture the main responses historically observed in multiple sclerosis. These measures were (1) the patient's physical disability-impairment, assessed by a neurologist; (2) physical disability-impairment as perceived and reported by the patient; and (3) self-reported psychological well-being (or distress) independent of physical signs and symptoms. The optimal solution from the cluster analysis separated the 99 patients into 10 clusters, which were collapsed into four profiles, consistent with the labels "depression," "denial," "exaggerated somatic," and "severity-related." These data give strong empirical support to the existence of discrete and distinctive coping styles in multiple sclerosis.

Adult↗
PubMed1991

Neuropsychological performance in patients with mild multiple sclerosis.

Although changes in cognitive function in patients with multiple sclerosis (MS) have been reported, these changes have been traditionally associated with the later stages of the disease. In the current study, a comprehensive neuropsychological battery was administered to MS patients (N = 86) in whom the disease progression was relatively mild and in remission and a demographically well-matched control group (N = 46). Besides the expected differences in tests of motor function, the two groups also differed on a number of cognitive tests with no motor demands. The two cognitive functions that appear impaired were learning and memory. Given that similar deficits have been found in MS patients with more severe symptoms, it is argued that changes in cognitive function can occur in the mild stages of the disease.

Adult↗
PubMed1990

Interaction of rubella virus with human immune cells. I. Permissiveness of lymphocyte subpopulations.

The ability of rubella virus to infect and replicate in various lymphocyte subpopulations was examined. Purified populations of B-cells, CD4+ T-cells and CD8+ T-cells were found to support high levels of viral replication. In addition, when mixed PBMC were infected in vitro, viral antigen was shown to be expressed on the surfaces of CD4+ and CD8+ T-cells by flow cytometry indicating that RV does not have a selective tropism for a specific type of lymphoreticular cell.

Antibodies, Monoclonal↗
PubMed1989

Serial magnetic resonance scanning in multiple sclerosis: a second prospective study in relapsing patients.

A prospective study of serial magnetic resonance (MR) scans of the brain was carried out every 2 weeks for 4 to 6 months in 9 patients with mild, clinically definite, relapsing/remitting multiple sclerosis (MS). Six of the 9 patients developed a total of 12 asymptomatic new lesions in various parts of the brain. In none of the patients were the changes on MR scan accompanied by relevant new neurological symptoms or signs. New MR lesions had a characteristic temporal profile, reaching a maximum size in approximately 4 weeks before gradually shrinking, usually leaving a small residual abnormality indistinguishable from chronic MS lesions. The frequent occurrence of new asymptomatic lesions indicates that MS may be a more active process even in mildly affected asymptomatic patients than has been previously realized. The results emphasize the potential importance of using MR scanning to measure disease activity in laboratory studies of MS and in the assessment of treatment, particularly in asymptomatic patients in the early stages. We suggest that the expanding and contracting new lesions are the basic or primary lesion in MS, that the characteristic demyelinated plaque is represented by the small residual area that these lesions shrink down to, and that the typical collection of scattered white matter lesions in chronic MS may represent the accumulated residua of dozens or more of these active lesions occurring over many years.

Adult↗
PubMed1989

Search for nicotinic acetylcholine receptors on human leukocytes: absence of alpha-bungarotoxin binding in studies of healthy individuals and myasthenia gravis patients.

To investigate whether nicotinic acetylcholine receptors might be present on blood mononuclear cells we studied the binding [125I]alpha-bungarotoxin to mononuclear cells from three normal controls and seven myasthenia gravis patients. The medulloblastoma cell line, TE671, which expresses a functional nicotinic acetylcholine receptor having pharmacological properties similar to that of skeletal muscle receptor, was used as a positive control for alpha-bungarotoxin binding. None of the mononuclear cell samples studied exhibited specific binding of alpha-bungarotoxin.

Bungarotoxins↗
PubMed1989

Chronic progressive multiple sclerosis: changes in phenotype and function of T helper subsets.

We have measured pokeweed mitogen-induced IgG secretion by peripheral blood mononuclear cells obtained from two different groups of progressive multiple sclerosis (MS) patients. MS patients with chronic progressive active disease (CPMS-A) have higher IgG secretion than stable (burnt-out) patients (CPMS-S). We have also measured suppressor cell function and phenotyped the T helper cells of some CPMS-A patients. This group differed from CPMS-S and from controls: they had high IgG secretion, low suppression and their T helper phenotypes showed a high ratio of T helper/inducers over T suppressor/inducers.

Chronic Disease↗