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Biomedical subjects

J Mertin

Publications and source records attributed to J Mertin.

At least 19 recordsLinked to original sources

Overview of azathioprine treatment in multiple sclerosis.

The efficacy of azathioprine in the treatment of multiple sclerosis was assessed by meta-analysis of the results of all published blind, randomised, controlled trials. 793 patients were enrolled in 5 double-blind and 2 single-blind studies. After 1 year of treatment, the increase in Kurtzke disability status score was no different in treated and control groups, but at 2 years there was a small difference (-0.22; 95% confidence interval [CI] -0.43, 0.003) in favour of azathioprine treatment; this difference was sustained, but not increased, after 3 years. The probability of freedom from any relapse during 1, 2, and 3 years' treatment was significantly greater in the azathioprine-treated group (relative odds over 3 years 1.97; 95% Cl 1.27, 3.04), but it is debatable whether the slight clinical benefits of azathioprine outweigh its side-effects.

Azathioprine

[Rehabilitation in multiple sclerosis].

Rehabilitation is the only effective treatment in multiple sclerosis (MS), as long as the cause of this commonest neurological disease of younger adults is not known. No medical treatment constantly influences the course of the disease. Methods for restitution of functional impairments, for improvement of abilities and for adaptation of daily life according to constraints caused by disability and handicap are applied with the goal of enlarging personal free space. Inadequate prevention of complications is often the cause for apparent progressive deterioration of the disease. Efficient symptomatic therapies have helped to increase life expectancy and to improve quality of life of MS patients in recent years.

Humans

An influence of diet on transplantation immunity.

It was discovered by chance that mice raised under otherwise entirely conventional conditions of husbandry but fed upon autoclaved diet (diet A) had stronger cell-mediated immune reactions than those of mice raised under the same conditions but with an unmodified diet (diet B) : skin allografts were rejected more quickly, transplantation tolerance was more difficult to procure and fibrosarcomas induced by the injection of methylcholanthrene (MCA) arose more slowly and less often. Analysis showed that these findings could be explained at least in part by the discovery of Mertin & Hunt (1976, p. 928) that a partial deprivation of polyinsaturated fatty acids led to an intensification of cell-mediated immunity; on the other hand, experiments with dietary mixtures made it seem unlikely that this was the whole explanation and pointed towards some positive immunopotentiation by an ingredient of autoclaved diet. This, it was proposed, might be a compound of unknown composition resulting from the interaction of vitamin A with other dietary constituents. This interpretation was not supported by direct evidence but by confirming that retinol derivatives, especially retinyl acetate, could exercise an immunopotentiation of the kind and degree under investigation: retinyl acetate could counteract the immunosuppressive action of linoleic acid, though retinyl methyl ether was ineffective. Although retinyl derivatives may protect against MCA tumours by impeding its metabolic conversion to an oncogenic form, the effects of an autoclaved diet upon skin allograft survival, the induction of tolerance and the formation of tumours is probably mediated through an immunological mechanism.

Animals

Effects of the obese (ob/ob) genotype on spleen cell immune function.

Spleen cells from mice homozygous for the obese (ob) mutation killed DBA/2 mastocytoma target cells less well than spleen cells from lean littermates or unrelated age-and sex-matched controls of the same strain. Killing was impaired only when the attacker cells were primed in vivo, not following in vitro priming. Hence the effect of the ob/ob genotype is not to produce an irreversible functional change in the lymphocyte, but rather to produce an environment in which lymphocytes are less able to react to priming antigen. Not only were the spleen cells of in vivo primed obese mice less active than those of lean controls, but also their number per spleen was significantly decreased. Such a quantitive difference was no longer found in adrenalectomised animals, but the qualitative difference in spleen cell cytotoxic activity still occurred. This suggests that adrenocortical hyperfunction may affect immune function in obese mice, without necessarily being the only factor in the in vivo environment of obese mouse spleen cells capable of depressing cellular immune reactivity.

Adrenalectomy

The spleen is required for the suppression of experimental allergic encephalomyelitis by prostaglandin precursors.

In this paper we report a study of the effects of splenectomy on the immunosuppressive action of essential fatty acids (EFA) which is thought to be mediated through prostaglandins (PG) produced in the spleen. Experimental allergic encephalomyelitis (EAE) was induced in normal, splenectomized and sham splenectomized Lewis rats. EFA were administered orally, the animals in the control groups being treated with liquid paraffin. Treatment with EFA significantly suppressed clinical disease in those animals in which EAE was induced by the inoculation of central nervous system material of guinea-pigs or by passive transfer by Con A-stimulated spleen cells. Splenectomy abrogated the suppressive effect of EFA. This observation, together with previous results showing the abrogation of EFA immunosuppression by an inhibitor of the biosynthesis of PG from EFA, led us to postulate a close relationship between EFA, PG and a splenic factor suppressing immunopathological mechanisms in EAE.

Animals

[EEG changes following spirolactone treatment (author's transl)].

EEG studies were done on patients with CNS disease who were treated with d-aldosterone and spirolactone. The baseline EEGs of these patients were found to be slightly abnormal. During infusion of the spirolactone derivative potassium canrenoate a transient deterioration of preexisting EEG disturbances was observed; in addition, bursts of increased muscle activity and transient relative bradycardia were seen. These findings indicate that potassium canrenoate or its lipophilic metabolite canrenone may affect the nervous system directly, possibly via a disturbance in the electrolyte balance. These results are compatible with recent findings in animal studies.

Aldosterone

Reduction by linoleic acid of the severity of experimental allergic encephalomyelitis in the guinea pig.

This paper reports the effects of supplementation of the diet with linoleic acid on the severity of experimental allergic encephalomyelitis (EAE) in guinea pigs. Clinical signs of disease (e.g. paresis, paraplegia, urinary incontinence), weight loss, frequency of perivascular lesions in the central nervous system and ability of isolated lymph node cells to respond to myelin basic protein in vitro were all reduced by linoleic acid supplementation. Linoleic acid was effective when fed at a dose of 0.5 ml/day from 7 to 21 days after sensitization of the animals with basic protein, i.e., before and during the time in which clinical signs normally appeared. The same daily dose fed from 7 days before to 7 days after sensitization, i.e., ceasing about 7 days before the normal time of appearance of clinical signs, produced no significant effect. Feeding linoleic acid to normal guinea pigs significantly altered the fatty acid composition of their serum and lymph nodes, but not of their brain. Of several possible explantations for the protective effect of lineolic acid in EAE, we considered action by this essential fatty acid on the immune system most likely.

Animals

Suppression by essential fatty acids of experimental allergic encephalomyelitis is abolished by indomethacin.

Experimental allergic encephalomyelitis in Lewis rats was suppressed by treatment with essential fatty acids (EFA) given perorally. This treatment effect could be abolished by administration of a drug (Indomethacin) known to inhibit biosynthesis of certain prostaglandins from EFA. This observation suggests that the suppressive effect of EFA on cell-mediated immune reactions is brought about by EFA-derived prostaglandins.

Animals

Importance of the spleen for the immuno-inhibitory aciton of linoleic acid in mice.

Certain immuno-inhibitory effects of a polyunsaturated fatty acid, linoleic acid (C18:2), no longer occur after splenectomy of young adult CBA mice. This observation suggest that the spleen is a major intermediary in the action of C18:2 on the lymphoreticular system. Pathways of this action remain to be elucidated. Possibilities include C18:2-stimulated suppressor cell generation in the spleen, or excess biosynthesis of immuno-inhibitory prostaglandins by splenic macrophages.

Animals

Micromethods for induction and assay of mouse mixed lymphocyte reactions and cytotoxicity.

A new method in which induction of mixed lymphocyte responses and cytotoxicity can be performed under identical conditions is described. This enables the investigation of the relationship between MLR and cytotoxicity. A micro method for the 51Cr release assay for cytotoxicity is described using both mitogen-induced blasts and tumors as target cells. Under the conditions used data obtained is suitable for linear regression analysis, enabling quantitative comparisons to be made.

Animals

Hyperphenylalaninaemia and experimental allergic encephalomyelitis.

Previous suggestions to the effect that a reduced proportion of long chain and unsaturated fatty acids in the CNS as induced by experimental hyperphenylalaninaemia in young rats may alter the biochemical reactivity and stability of the myelin have been examined using experimental allergic encephalomyelitis (EAE). Lewis rats treated chronically with phenylalanine during development showed a higher susceptibility to EAE and a more severe course of the disease than their medium-treated litter mates. The possible implications of this observation for EAE as an experimental model of multiple sclerosis (MS) is discussed briefly in the light of the decreased levels of unsaturated fatty acids found in the CNS of MS patients.

Animals