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Biomedical subjects

M Duddy

Publications and source records attributed to M Duddy.

6 recordsLinked to original sources
PubMed2006

B-cells in multiple sclerosis.

B-cells may be involved at many levels in the pathogenesis of MS, starting from the earliest stage of antigen capture, continuing through the processes of tissue damage and even extending through to remyelination and repair. Recent advances in our understanding of normal B-cell biology and abnormal regulation of their functions in relation to the pathology of MS are discussed in this review. Current treatments already target B-cell responses; consequently, this effect may be one explanation for the efficacy of these treatments in some types of MS. The results of specific anti-B-cell therapies are awaited. Even if success is limited, it is possible that targeting this important group of cells, whether as antigen-presenting cells, as regulators of immune responses or as antibody-secreting cells, will form at least part of more successful treatment strategies in the future.

Autoantibodies↗
PubMed2005

Cerebroventricular infusion of pentosan polysulphate in human variant Creutzfeldt-Jakob disease.

Variant Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform encephalopathy believed to be caused by the bovine spongiform encephalopathy agent, an abnormal isoform of the prion protein (PrP(sc)). At present there is no specific or effective treatment available for any form of CJD. Pentosan polysulphate (PPS), a large polyglycoside molecule with weak heparin-like activity, has been shown to prolong the incubation period of the intracerebral infection when administered to the cerebral ventricles in a rodent scrapie model. PPS also prevents the production of further PrP(sc) in cell culture models. These properties of PPS prompted its cerebroventricular administration in a young man with vCJD. Long-term continuous infusion of PPS at a dose of 11 microg/kg/day for 18 months did not cause drug-related side effects. Follow-up CT scans demonstrated progressive brain atrophy during PPS administration. Further basic and clinical research is needed in order to address the issue of efficacy of PPS in vCJD and in other prion diseases.

Adult↗
PubMed2003

CD83-positive dendritic cells are present in occasional perivascular cuffs in multiple sclerosis lesions.

Multiple sclerosis (MS) has a wide spectrum of clinical courses, characterized by multifocal central nervous system (CNS) damage, postulated to be mediated by CNS antigen-specific T cells. Dendritic cells (DC), the most potent antigen-presenting cell, play a pivotal role in the decision between T-cell activation or anergy. Monoclonal antibodies to CD1a (immature DC) and CD83 (mature DC) were used to screen lesions with evidence of recent demyelinating activity and chronic plaque and normal appearing white matter (NAWM) tissue sections from 12 MS cases by immunocytochemistry. No CD1a-positive cells were detected in the MS or control CNS tissue blocks investigated. CD83-positive cells were not detected in tissues from any of the control cases or in the majority of perivascular cuffs in the MS tissue sections. However; in eight of the MS tissue blocks with evidence of recent demyelination, and in one block each from chronic plaque and NAWM, small numbers of distinct CD83-positive cells were present within occasional perivascular cuffs. In one area only of MS NAWM were CD83-positive cells detected in the tissue parenchyma, in an area of intense immunological activity. DC in MS tissue may originate in the peripheral circulation as monocytes or immature DC and migrate to areas of plaque in response to signals received from CNS-produced chemokines.

Antigens, CD↗
PubMed2001

Immunological memory: contribution of memory B cells expressing costimulatory molecules in the resting state.

Traditionally, emphasis has been placed on the roles of Th cells in generating and amplifying both cellular and humoral memory responses. Little is known about the potential contributions of B cell subsets to immunological memory. Resting memory B cells have generally been regarded as poor APC, attributed in part to the relative paucity of costimulatory molecules identified on their surface. We describe a novel subpopulation of human memory B cells that express CD80 in their resting state, are poised to secrete particularly large amounts of class switched Igs, and can efficiently present Ag to and activate T cells. This functionally distinct B cell subset may represent an important mechanism by which quiescent human B cells can initiate and propagate rapid and vigorous immune memory responses. Finally, these studies extend recent observations in the murine system and highlight the phenotypic and functional diversity that exists within the human B cell memory compartment.

Antigen Presentation↗
PubMed2001

Worsening lipid profile is associated with progression of carotid artery stenosis.

BACKGROUND: To determine if uncontrolled hypercholesterolaemia predisposes to progression of carotid artery stenosis. METHODS: Fasting blood samples were collected from 76 patients referred for carotid duplex ultrasound for investigation of transient ischaemic attacks or recent stroke. Patients were grouped depending on the severity of the stenosis found. Patients on lipid lowering agents were excluded. The data were analysed using one way analysis of variance and the c2 test as appropriate. RESULTS: There were more men in the 70-99% group (15 vs 6, c2 = 10.6, p < 0.001, Table I). The total cholesterol was raised in all three groups. Patients with carotid stenosis of 70-99% had significantly elevated triglycerides (2.4 mmol vs 1.47 mmol and 1.37 mmol, p < 0.003), low HDL (1.14 mmol vs 1.45 mmol and 1.18 mmol, p < 0.003) and a higher cholesterol/HDL ratio (5.56 vs 4.29 and 4.71, p < 0.014) compared with the other two groups. There was no difference in lipoprotein(a) in the three groups. CONCLUSIONS: Increased triglycerides and low HDL cholesterol seen in the 70-99% group suggest that a worsening lipid profile is associated with progression of carotid artery stenosis.

Aged↗