PubMed Health⌕ Search

Biomedical subjects

D A Compston

Publications and source records attributed to D A Compston.

At least 73 records · Page 4Linked to original sources
PubMed1994

Subacute sclerosing panencephalitis in Wales.

Twenty cases of subacute sclerosing panencephalitis (SSPE) occurring over an 18-year period in Wales are described and used as the basis for a comparison of measles infection, vaccination rates and the incidence of SSPE in England and Wales. Rates of measles infection were higher in Wales in all age groups, and fewer Welsh children were vaccinated, which maintained a high risk of SSPE per case of measles. Following vaccination, there was a more pronounced change in the age distribution of measles infection in Wales than in England, and it is proposed that one contribution to the high frequency of SSPE in the 1980s was the reservoir of measles in unvaccinated 2-4-year-olds, acting as a source of infection for children aged < 2 years, in whom the risk of SSPE following measles is known to be higher than in other groups.

Adolescent↗
PubMed1994

Acute encephalopathy: diagnosis and outcome in patients at a regional neurological unit.

Sixty-five patients with a diagnosis of acute encephalitis or encephalopathy were discharged from a regional neurological unit over a 17-year period. Investigation during the acute illness, or subsequent clinical and laboratory observations, yielded a definite or probable diagnosis in 34 of these patients, including herpes simplex encephalitis (8 cases), encephalitis due to other identified viruses (7 cases), vascular disease (7 cases) and multiple sclerosis (4 cases). In these 34 patients, mortality relating to the presenting illness was 50% and a further 29% had significant long-term neurological morbidity. In the other 31 patients, no cause for the encephalopathy was identified, despite extensive investigation. These patients had an alteration in conscious state, often with recurrent seizures (45%), focal neurological signs (52%), pyrexia (65%), abnormal electroencephalogram (85%) and cerebrospinal fluid lymphocytosis (80%). During follow-up (6 months to 15 years) none had recurrent encephalopathy, and 65% eventually made a complete recovery, although delayed by seizures in 6% and psychiatric illness in 13%. The mortality in this group relating to the acute illness was 6%. Overall, nearly half the patients with a discharge diagnosis of acute encephalitis or encephalopathy had a good prognosis for recovery, following a monophasic illness of undetermined cause.

Acute Disease↗
PubMed1993

Symptomatic Epstein-Barr virus infection and multiple sclerosis.

In a case-control study of 214 patients with multiple sclerosis, recall of infectious mononucleosis in subjects seropositive for Epstein-Barr viral capsid antigen was associated with a relative risk of 2.9 (95% CI 1.1 to 7.2). Those who reported having infectious mononucleosis before the age of 18 years had a relative risk of multiple sclerosis of 7.9 (95% CI 1.7 to 37.9). The pathogenesis of multiple sclerosis may involve an age-dependent host response to Epstein-Barr virus infection.

Antibodies, Viral↗
PubMed1993

Specific induction of intracellular calcium oscillations by complement membrane attack on oligodendroglia.

Oligodendroglia (ODG) are unique among glial cell types in their capacity to activate complement in the absence of antibody, causing insertion of the potentially damaging membrane attack complex (MAC) into the plasma membrane. Using microfluorimetry of indo-1 fluorescence we have detected a complex oscillatory [Ca2+]i response in ODG following exposure to sublethal dilutions of serum-derived complement. Oscillations were transitory and preceded complete and stable return to resting [Ca2+]i levels, whereas nonoscillating ODG underwent rapid lysis. Depletion of the terminal complement component C9 from serum removed the oscillatory stimulus, which could be restored by reconstitution with purified C9. Exposure to the C9-homologous peptide melittin produced [Ca2+]i oscillations similar in pattern to those induced by whole serum. However, this type of response could not be reproduced by Ca2+ ionophores or mechanical wounding, suggesting that oscillations cannot be provoked by Ca2+ influx alone and depend on the presence of the MAC or a pore-forming lesion. Oscillations were not prevented in the continuous presence of caffeine, demonstrating independence from caffeine-releasable intracellular stores. Inhibition of the endoplasmic reticular Ca(2+)-ATPase with thapsigargin produced an abrupt elevation in [Ca2+]i but did not alter the latency between exposure to serum and the initial complement-induced transient. However, the slope of this initial transient was considerably reduced and oscillations suppressed, demonstrating dependence of the oscillatory mechanism on functional endoplasmic reticular Ca2+ stores. The coincidence of ODG recovery with oscillating [Ca2+]i suggests that the complex calcium signal that follows MAC attack may stimulate repair or protective mechanisms.

Animals↗
PubMed1992

The role of calcium in rat oligodendrocyte injury and repair.

The role of intracellular calcium in oligodendrocyte injury is investigated using cultured rat oligodendrocytes. Calcium ionophores A23187 and ionomycin mimic both complement and perforin attack, causing oligodendrocyte lysis at concentrations which do not lyse other glia. Membrane vesiculation, the mechanism by which oligodendrocytes resist and recover from complement and perforin attack, is also induced by A23187. Oligodendrocytes are more susceptible to complement attack in the presence of a calmodulin inhibitor (W7), which also inhibits vesiculation. These results imply that calmodulin is involved in membrane repair from complement attack, and indicate that changes in intracellular calcium play an important yet paradoxical role in the oligodendrocyte response to injury, dictating both susceptibility and cellular recovery.

Animals↗
PubMed1992

Mechanisms of oligodendrocyte interaction with normal human serum--defining the role of complement.

The interaction of human serum with oligodendroglia was investigated in vitro using purified cultured neonatal rat oligodendrocytes. Previous evidence for antibody independent classical pathway complement activation was confirmed; the results also showed a deficit in the protection of rat oligodendrocytes from complement attack suggesting a deficiency in the expression of terminal regulatory proteins of the complement cascade. Thus, rat oligodendrocytes are selectively sensitive to normal serum due both to complement activation and impaired protection from terminal complement attack.

Animals↗
PubMed1992

Occurrence of a multiple sclerosis-like illness in women who have a Leber's hereditary optic neuropathy mitochondrial DNA mutation.

Eight women are described who presented with bilateral, usually sequential, optic neuropathy, six of whom later developed a neurological syndrome indistinguishable from multiple sclerosis (MS). Magnetic resonance imaging, performed in five of the patients with an MS-like illness and in the two others with optic neuropathy alone, showed widespread white matter lesions as seen in MS. All of these women had matrilineal relatives with Leber's hereditary optic neuropathy, although this was not always apparent at presentation, and the most common mitochondrial DNA mutation associated with this disorder was detected in each of the women and their affected relatives. On the basis of observations made in these patients, the clinical features of Leber's hereditary optic neuropathy in males, and evidence for mitochondrially encoded peptides involved in the immune response in rodents, we propose that optic nerve damage in this disease could be immunologically mediated and that mitochondrial genes may contribute to susceptibility to MS.

Adult↗
PubMed1992

Multiple sclerosis in the Cambridge health district of east Anglia.

A survey of multiple sclerosis (MS) in the Cambridge Health District has identified 374 cases in a population of 288,410, giving a prevalence of 130 per 100,000. A total of 322 cases (86%) had either clinically definite or probable multiple sclerosis on 1 July 1990 (112 per 100,000) and 52 cases (14%) had suspected multiple sclerosis (18 per 100,000.) The incidence during 1989-91 was 5.94 per 100,000 per year. The prevalence figure is higher than in recent surveys from other southern parts of the United Kingdom, but correction for the age and sex characteristics of the at risk population eliminates these differences. The overall prevalence of multiple sclerosis is probably between 108 and 120 per 100,000 in the southern United Kingdom.

Adolescent↗
PubMed1992

EDMUS, a European database for multiple sclerosis.

EDMUS is a minimal descriptive record developed for research purposes to document clinical and laboratory data in patients with multiple sclerosis (MS). It has been designed by a committee of the European Concerted Action for MS, organised under the auspices of the Commission of the European Communities. The software is user-friendly and fast, with a minimal set of obligatory data. Priority has been given to analytical data and the system is capable of automatically generating data, such as diagnosis classification, using appropriate algorithms. This procedure saves time, ensures a uniform approach to individual cases and allows automatic updating of the classification whenever additional information becomes available. It is also compatible with future developments and requirements since new algorithms can be entered in the programme when necessary. This system is flexible and may be adapted to the users needs. It is run on Apple and IBM-PC personal microcomputers. Great care has been taken to preserve confidentiality of the data. It is anticipated that this "common" language will enable the collection of appropriate cases for specific purposes, including population-based studies of MS and will be particularly useful in projects where the collaboration of several centres is needed to recruit a critical number of patients.

Database Management Systems↗
PubMed1992

Oligodendrocytes lack glycolipid anchored proteins which protect them against complement lysis. Restoration of resistance to lysis by incorporation of CD59.

Rat oligodendrocytes, which activate the classical pathway of complement in the absence of antibody, are highly sensitive in a reactive lysis assay using human C5b6 and EDTA serum. Oligodendrocytes may be relatively deficient in glycolipid-linked complement regulatory protein(s), since digestion with phosphatidylinositol-specific phospholipase C (PI-PLC) failed to increase their sensitivity to serum, whereas complement-insensitive astrocytes, when treated with PI-PLC, became strikingly sensitive. To test the hypothesis that oligodendrocytes lack terminal complement regulatory molecule(s), human erythrocyte CD59, a recently described complement regulatory protein, was purified to homogeneity. The biological activity of the preparation was confirmed by reincorporating the protein into guinea-pig erythrocytes through its glycolipid anchor, which resulted in dose-dependent protection against human C5b6 and EDTA serum. Incorporation of 10(5) molecules of human CD59 into rat oligodendrocytes resulted in good protection against homologous human complement (76%), and significant protection against rat complement homologous to the cell (36%). Protection could be reversed using an antibody to CD59.

Animals↗
PubMed1992

Interactions between oligodendrocytes and microglia. A major role for complement and tumour necrosis factor in oligodendrocyte adherence and killing.

Interactions between rat microglia and oligodendrocytes were examined in vitro in order to characterize the stages of adherence, phagocytosis and cytotoxicity against oligodendrocytes by microglia. Under resting conditions, microglia showed minimal contact with oligodendrocytes and exhibited surface staining of myelin basic protein and myelin debris only; they were not cytotoxic for oligodendrocytes and did not produce tumour necrosis factor (TNF). On activation with either gamma-interferon or lipopolysaccharide and interferon, these cells increased surface binding for myelin basic protein, showed greater contact with living oligodendrocytes and produced TNF in both secreted and cell surface bound forms. Secreted TNF was capable of killing oligodendrocytes but the cell surface bound form did this more efficiently. In the presence of complement, activated microglia showed significant phagocytosis of myelin basic protein which was not obvious in the unactivated cells. These results suggest that activated microglia in the presence of complement are sufficient to kill and phagocytose the oligodendrocyte-myelin complex in vitro.

Animals↗
PubMed1992

The morbidity of multiple sclerosis.

Although the clinical course of multiple sclerosis is benign in up to one-third of patients, it is important to recognize the high rate of morbidity in others. Most individuals pass through a remitting phase but in a significant proportion the clinical manifestations subsequently recur, persist or slowly progress, and disability accumulates with time. Here we describe the frequency and spectrum of morbidity in a population based cohort of patients with multiple sclerosis. These statistics will guide those providing health care resources and planning services for patients with multiple sclerosis.

Adolescent↗
PubMed1991

Type III collagen mutations cause fragile cerebral arteries.

Premature vascular aneurysms and fragility of cerebral arteries are commonly associated with type III collagen mutations and physical signs suggesting a generalized abnormality of connective tissue. Sometimes these traits are clearly genetically transmitted. Here we present seven examples of early cerebrovascular aneurysms or fragility including five examples of carotid cavernous sinus aneurysms. With one exception in which we suspect the mutation is too small to be detected, all of them had easily visible abnormalities of their type III collagen proteins. Further work in progress will eventually allow the characterization of their mutations at gene sequence level and will be followed by the ability to prevent transmission of the mutant genes in these families.

Adult↗
PubMed1991

Imaging Ca2+ changes in individual oligodendrocytes attacked by T-cell perforin.

Cytosolic-free calcium changes in cultured rat oligodendrocytes attacked with murine T-cell perforin were measured using digital image processing of fura-2-loaded cells. Permeability to the membrane impermeant dye, propidium iodide, and the ability to retain fura-2 were also assessed. Oligodendrocyte response to perforin attack was heterogeneous, ranging from small, transient increases in cytosolic calcium to rapid cell death. Changes in cytosolic calcium occurred in all cells and about half of the cells also became permeable to propidium iodide. Only a minority of these cells proceeded to lysis, as evidenced by loss of fura-2. The cytosolic-free calcium rises visualized here in single cells could initiate non-lethal effects, thereby disturbing oligodendrocyte function and synthesis and maintenance of myelin.

Animals↗
PubMed1991

Oligodendrocyte-macrophage interactions in vitro triggered by specific antibodies.

The final pathway of myelin destruction in immune-mediated demyelination is phagocytosis by macrophages. As part of a systematic study of mechanisms of myelin-oligodendrocyte injury, we have used an in vitro approach to investigate interactions between rat oligodendrocytes and macrophages in order to identify the conditions under which macrophages adhere to and damage oligodendrocytes. No adherence was seen when macrophages alone were co-cultured with homologous oligodendrocytes. However, macrophage attachment to oligodendrocytes was triggered not only by antibody to the major cell-surface component galactocerebroside, but also by antibody to the quantitatively minor antigen, myelin-oligodendrocyte glycoprotein; immunocytochemical observations suggested that phagocytosis of myelin antigen also occurred. No such changes were seen in the presence of an irrelevant (anti-progesterone) antibody, or in the presence of activated complement. These results emphasize that a variety of antibodies, including those to minor myelin-oligodendrocyte antigens, may play a significant role in the development of demyelinated lesions.

Animals↗
PubMed1990

Complement mediated serum cytotoxicity against oligodendrocytes: a comparison with other cells of the oligodendrocyte-type 2 astrocyte lineage.

Rat oligodendrocytes are known to be susceptible to complement attack when exposed to homologous serum as a consequence of anti-myelin antibody independent classical pathway complement activation and attack. We have now compared this susceptibility with that of other cells of the oligodendrocyte-type 2 astrocyte (O-2A) lineage, and show that while type 2 astrocytes are not sensitive, O-2A progenitors are only relatively resistant to serum cytotoxicity, higher concentrations of complement resulting in cell damage. The implications of these findings for the pathogenesis of demyelinating disease are discussed.

Animals↗
PubMed1990

Demographic characteristics of multiple sclerosis in south east Wales.

The non-uniform distribution of multiple sclerosis in the United Kingdom has been attributed to genetic, exogenous and selective factors. Within the county of South Glamorgan the disease is most prevalent amongst middle-aged married or divorced caucasian women, born in England rather than Wales, occupying flats located in affluent communities with superior amenities where rates of owner occupation are high. The disease is least prevalent amongst young single Welsh-born or non-caucasian males living in rented accommodation located in less affluent communities with a higher population density. These observations may, in part, be related to superior ascertainment of the former group, but some, as yet unidentified, characteristic of the environment may also be relevant.

Adolescent↗