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Biomedical subjects

D W Sumner

Publications and source records attributed to D W Sumner.

9 recordsLinked to original sources

Comparison of in vitro demyelination and cytotoxicity of humoral factors in multiple sclerosis and other neurological diseases.

The distribution and nature of serum factors causing in vitro demyelination and glial lysis were investigated in multiple sclerosis (MS), other neurological diseases (OND), ill control and control groups. MS sera were unique in affecting only CNS myelin and glia whereas stroke and Guillain-Barré syndrome (GBS) sera brought changes to both CNS and PNS tissue. Through both visual scoring of myelin damage and the quantitative measurement of radiolabel release from cerebellar cultures, it was evident that the MS and OND groups have similar myelino- and cytotoxic effects. This may reflect MS and OND sera sharing similar humoral factors. 74% MS, 68% OND and 22% of control scores were above a score threshold designed to exclude culture handling trauma effects. When classified by their current disease state MS patients with severe and mild disease yielded higher in vitro scores than did those with moderate disease who comprised an older age group. No other clinical features of MS patients gave any association with in vitro serum effects. The rare demonstration of bound Fab IgG in cultures after MS serum tests indicates that immune mechanisms are unlikely to make a large contribution to serum-induced demyelination and cellular change in vitro.

Central Nervous System Diseases

New approach to study of in vitro toxicity of multiple sclerosis and other sera.

The in vitro effects of MS and control sera were quantified by the measurement of radiolabel released from myelinated cultures of rat cerebellum and compared with a visual assessment of myelin damage. Radiolabel release gave a sensitive index of serum effects in vitro which was free of the score assignment decisions that are associated with the visual assessment of myelin damage. Examination of the patterns of radiolabel release elicited by MS and control sera on cultures labelled with either L-[5-3H]tryptophan or galacto-D-[6-3H]cerebroside indicates that MS serum effects are not simply a stronger expression of the weak control serum effects.

Animals

Role of complement in demyelination in vitro by multiple sclerosis serum and other neurological disease sera.

Multiple sclerosis (MS) sera can demyelinate and cause selective cellular changes to organ cultures of rodent CNS which suggests possible immunoglobulin involvement. The complement dependence of this serum action was investigated using complement-inactivating agents and radiolabelled rat cerebellar cultures. After heat inactivation at 56 degrees C, the in vitro effects of MS, chronic relapsing experimental allergic encephalomyelitis (cr-EAE) and Guillain-Barré syndrome (GBS) sera were severely reduced or eliminated as measured by radiolabel release. On introducing a source of fresh complement, the cr-EAE and GBS serum effects were largely restored whereas MS serum effects remained suppressed. Inactivation of serum complement with mercaptoethanol and Zymosan was associated with marked reduction in serum myelinotoxicity; some restoration of in vitro effects was possible on adding fresh complement although this occurred to a greater extent with cr-EAE and GBS than with MS sera. Inactivation of the alternative complement pathway brought a limited reduction in MS serum activity in vitro which was not restored with fresh complement. It is concluded that complement is involved only to a limited extent in MS serum myelinotoxic effects and that MS serum effects in vitro are due to several components of which thermolabile substances make a significant contribution and are as yet uncharacterised.

Animals

In vitro toxicity of MS sera correlates with new clinical signs.

In vitro toxicity of sera from 10 MS patients was followed for up to 3 years. Myelinotoxicity and cytotoxicity measured as radiolabel release from rat cerebellar explants were almost continuously higher in than in controls while peaks of radiolabel release were associated with the emergence of new clinical signs in the MS patients.

Adult

Screening for malignant hyperpyrexia.

The methods used to screen patients for malignant hyperpyrexia at present are not sufficiently accurate. This paper reports more specific methods of detecting patients liable to develop malignant hyperpyrexia. A motor-point muscle biopsy is performed for histopathological examination and to detect muscle contracture in vitro after exposure to halothane and suxamethonium.

Acidosis