Multiple sclerosis: what can and cannot be done.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to E J Field.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In the present paper are discussed the diagnostic problems in M.S., there has been difficulty in certain diagnostic on the first modest signs in a proportion perhaps as high as 20% and the absence of a specific and reliable laboratory test has long been felt. This study describes two specific laboratory tests in M.S. The MEM-LAD test (macrophage electrophoretic mobility linoleic acid depression) and the E-UFA test (erythrocyte-unsaturated fatty acid). It may be noted that whilst the E-UFA and MEM-LAD test will diagnose (or esclude) M.S. the former is simpler, but is limited to M.S., the latter on the other hand once mastered is applicable in the whole range of clinical immunology were lymphocyte sensitisation is to be measured.
Certain morphological similarities between scrapie--a naturally occurring disease of sheep, long looked upon as a paradigm of 'slow infections'--and the ageing process in normal animals led to a study of the development of new antigens both in scrapie-affected animals and in normal mice and humans. It was found that with advancing age new antigen(s) identical with, or similar to, those occurring in scrapie (where the time co-ordinate of aging in the brain seems foreshortened) make their appearance both in mice and humans, and lead to special sensitization of lymphocytes in normal guinea pigs injected with old tissues so that the difference in the lymphocyte response to scrapie or normal test antigen (SND) is exaggerated. It may be that the 'new antigen(s)' depend upon molecular rearrangement of membrane structure perhaps induced by an external agent (not necessarily a virus). Thymectomy in the new-born mouse or rat produces in many cases 'runting' which appears in many ways to be a caricature of ageing. The SND is greatly increased at a very early age by the process of thymectomy and there is evidence that it may be held up by implantation of neonatal thymus tissue into the deprived animals. During the first years of life there appears to be the same difference in the constitution of erythrocyte membranes which moves towards the adult type towards puberty. This may be part of a general phenomenon of significance in the physiopathology of childhood. Finally the analogy between the changes occurring the kuru-scrapie-CJD complex and old age, and the somewhat new antigenic materials emerging in them must not be taken to imply that any virus is per se concerned with the ageing process. No 'virus of old age' is known. It seems to the writer that it is much more likely that ageing (and the diseases mentioned) are associated with membrane steric rearrangement (which can be transmitted--but not necessarily by a classical virus). In the writer's opinion it is a reasonable hypothesis to entertain that as the cell 'ages' and becomes a less favourable habitat for viruses (normally built into its DNA and/or RNA) they emerge, may take on recognizable forms, and indeed may attempt to seek younger and better homes. No doubt we all carry a load of such inapparent 'viruses' which (like our fellow humans) are likely to abandon us in old age. It is a commonplace that we have an embarras de richesse of viruses and it may be some of these which have been 'isolated' from old tissues.
The absolute electrophoretic mobility of erythrocytes from MS patients is reduced in the presence of 0.08 mg/ml of linoleic or arachidonic acid, whilst that of normal or other neurological disease patients is increased in the presence of these acids. When an MS patient ingests gamma-linolenate (in capsule form equivalent to 413.4 mg of gamma-linolenic acid and 2.664 g of linoleic acid per day) the reaction of MS erythrocytes begins to change. After 3 or 4 months the reaction becomes normal with arachidonic acid (i.e. mobility is speeded up) and 2 months or so later this occurs also with linoleic acid. Very prolonged administration of gamma-linolenate leads to a markedly increased sensitivity to the effect of prostaglandins (PGE2) on RBC mobility. The observations are interpreted to mean the induction of a biochemical-biophysical change in the membranes, and the significance of this in the aetiology and treatment of multiple sclerosis is discussed.
A test of measurement of the electrophoretic mobility of macrophages (EMM) is used for detection of the product secreted by the sensitized lymphocytes after the contact with the antigen. Thus, by reduction of the macrophage mobility it is possible to assess the sensitization level of the lymphocyte population under study. This offers a possibility of using this test for the diagnosis of some infectious diseases, for provisional diagnosis of malignant growth, and also of destructive affections of the nervous system. The EMM test finds wide application in the determination of compatibility of donor's and the recipient's tissues before the transplantation, and also to assess the efficacy of immunodepressive therapy.
A combined familial study of multiple sclerosis (MS) in England and in the Rostock area of the GDR using the macrophage electrophoretic mobility (MEM)-LAD test embracing 132 relatives has revealed a closely similar pattern of distribution of "anomalous" LAD (Linoleic Acid Depression) values in relatives (77% type of reaction) to that originally reported in the British study. The anomaly in predominantly associated with females--all mothers of MS patients being affected, whilst daughters and sisters are also represented. In addition unusual full MS type of reaction (90% reduction) has been found in some children related to patients. There is clearly a genetic element in the development of MS probably mainfested in the inborn mishandling of unsaturated fatty acids suggested by Thompson; no recognizable pattern of inheritance is noticeable even within the combined material. There is evidence that the metabolic anomaly alone does not inevitably lead to MS, and the full abnormality may be present at an early age. A survey about the examinations and a selection of characteristic family trees of MS are given, illustrating the manner in which the 77% type anomaly is distributed with occasional omission of a generation.
Explore the source record for details and available documents.
Erythrocytes from patients with Multiple Sclerosis (MS) show a highly significant reduction in their absolute electrophoretic mobility in the presence of linoleic and arachidonic acids (LA; AA). Patients with other (destructive) neurological disease (OND) and normal subjects show an increased absolute mobility of their erythrocytes in the presence of LA and AA. About 40 per cent of blood relatives of MS patients show an intermediate type of reaction - being slowed by LA and speeded up by AA. Administration of LA (or gamma linolenate) to an MS patient for some months leads to change in the mobilities from the MS to normal type, the AA result altering first. The effect of LA and AA on the absolute mobility of RBC may thus be used as a simple laboratory test involving a long established technique and eliminating the animal and other needs of the macrophage electrophoretic mobility (MEM) test. The implications of these findings for our understanding and handling of MS are briefly discussed.
In this study the macrophage electrophoretic mobility (MEM) test was modified by using tanned sheep erythrocytes in place of guinea pig peritoneal macrophages as the indicator cells of lymphocyte sensitization to antigens. This modification is named the tanned sheep erythrocyte electrophoretic mobility (TEEM) test, and a comparison of the kinetics of the two systems allowed the following conclusions to be made: 1) Treatment of freshly drawn sheep red blood cells with a concentration of 1/40,000 tannic acid produced optimum results in the TEEM test. 2) Lymphocyte-antigen and lymphocyte-number response curves show similarity in the two test systems. 3) A plateau response with slowing factor is achieved at a lower dilution in the TEEM test than in the MEM test. 4) Whilst similarity in the first stage reaction was found in the two systems, in the second stage of the test (at 37 degrees C) tanned sheep red cells gave a plateau response after 45 min instead of the 60 min found in the MEM test. 5) The two slowing factors showed similar gel filtration patterns with molecular weights between 13,000 and 15,000 daltons, and had equivalent activity in both test systems. 6) The disadvantages of the guinea pig macrophage as an indicator cell are discussed. 7) The TEEM test seems simpler to perform than the MEM test and may be widely applicable in clinical immunology for the estimation of lymphocyte sensitization.
A double-blind controlled trial has been undertaken to assess the value of a preparation containing polyunsaturated fatty acids (PUFA) in human cadaveric renal transplantation. Eighty-nine patients were studied and followed for 6 months after transplantation. Forty-four took the PUFA preparation and 45 the placebo (oleic acid). Other immunosuppression was standardised. Functional graft survival was significantly better in the PUFA group than in those taking the placebo during the first 3 to 4 months post-transplant. At 6 months, however, although the difference between the groups persisted, it was no longer statistically significant. Complications were equally distributed between the groups.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.