Autoimmune diseases of the neuroimmune system and mental disease.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to O Abramsky.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Subacute sclerosing panencephalitis developed during pregnancy in a 27-year-old woman and immediately after delivery in an 18-year-old woman. In both, disease took an acute and fulminant course culminating in a vegetative state within several weeks. It is suggested that the relative older age of disease presentation and the unusually rapid neurologic deterioration were partially due to immunologic and hormonal alterations of pregnancy.
In five patients with peripheral neuropathy due to vitamin B12 deficiency, electrodiagnostic studies demonstrated severe reduction in sensory nerve conduction velocities compatible with a demyelinating disorder affecting sensory nerve fibres. It is suggested that in some patients lack of vitamin B12 may cause primary sensory demyelinating neuropathy.
The causes and clinical features of chronic progressive myelopathy (CPM) were evaluated in a retrospective study of 107 patients. A special emphasis was put on those in whom no underlying cause for the myelopathy could be determined. Of 76 such, 39 (51%) had oligoclonal immunoglobulins (Ig) in the CSF and were therefore considered as possible MS, while the remainder, without oligoclonal Ig, were designated "myelopathy of unknown origin" (MUO). Our "possible MS" group was similar clinically to reported series of proven spinal MS, and it seems therefore, that the presence of oligoclonal Ig permits the recognition of a group of patients with myelopathy who might be at a greater risk for MS. Patients with MUO differed from possible MS patients in several clinical characteristics, but most significantly in disease course and levels of functional disability which were more benign in the former. Myelopathy in possible MS patients was also of a primary pyramidal and asymmetrical nature. It is therefore suggested that the segregation of patients with CPM of undetermined origin into 2 separate groups based on the presence or absence of oligoclonal Ig might be of prognostic significance.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To investigate which parts of the acetylcholine receptor are involved in the initiation and development of myasthenia gravis (MG), peptides representing different sequences of the human acetylcholine receptor alpha-subunit were synthesized. These peptides were tested for their ability to stimulate T cells of myasthenic patients and healthy control patients in proliferation assays and to bind to sera antibodies. Three of eight peptides discriminated significantly between the two groups in the proliferation assay, as well as in their ability to bind to serum antibodies. HLA-DR3 and DR5 were associated with proliferative responses to specific AChR peptides in the group of myasthenics. Acetylcholine receptor epitopes that might play a specific role in myasthenia gravis thus were demonstrated.
Explore the source record for details and available documents.
The significant regional variation in brain superoxide dismutase (SOD) activity was similar in mice from both warm and cool cohorts. Mice in the cool cohort generally had higher SOD activity, which varied significantly with body temperature in striatum and in preoptic area of the hypothalamus. Changes in SOD activity following heating were revealed only when warm and cool cohorts were analysed separately. SOD activity decreased significantly in striatum, hypothalamus, and hippocampus of the cool cohort only. The decline was to levels consistent with those of the warm cohort. Body temperature of cool mice increased more than that of warm mice following each increment of heating so resultant body temperatures became similar. The role of SOD as part of a differential defense against heat stress in warm and cool mice is presented.
Using [3H]-dopamine (DA) as the ligand of choice, we have shown that rat lymphocytes possess DA binding sites. The binding of [3H]-DA was specific, saturable, and of high affinity. The specific binding in membranes obtained from Con A-activated lymphoblasts was greater than the binding in respective unactivated lymphoid cells, and displaced by lower concentrations of unlabeled ligand. [3H]-DA was displaced specifically by DA, norepinephrine, and apormorphine. The binding sites were insensitive to neuroleptic drugs such as sulpiride, bromocryptine, and haloperidol. On the basis of these findings, we have suggested that lymphocytes possess a receptor site for catecholamines and the receptor for DA might be a D-3 receptor type.
Myelin basic protein (MBP) was serially measured in 177 CSF samples of 33 patients with leptomeningeal metastases and in 34 cancer controls. The mean level in cancer controls (free of neural involvement) was 5.7 +/- 0.33 ng/ml (normal less than 5 ng/ml) with abnormal elevation of MBP detected in 17%. The activity of the leptomeningeal disease was classified as either acute-progressive, stable or in remission on the basis of clinical and CSF cytological findings. CSF MBP levels were analysed in each stage. Abnormal elevation of MBP was detected in 74% of the 68 samples obtained in the acute-progressive stage (mean +/- SEM: 18.25 +/- 1.4 ng/ml, P less than 0.0001), in 24% of the 79 samples in the stable phase (mean: 7.99 +/- 0.8 ng/ml, NS) and in 20% of the 30 samples in remission (mean 5.7 +/- 0.3 ng/ml, NS). Similar changes in levels of CSF MBP were also observed in longitudinal studies of patients responding to treatment or relapsing to the acute stage. Eight patients developed treatment induced necrotizing leukoencephalopathy with typical CT-scan findings; elevated levels of CSF MBP were detected in 7 of them (mean: 21 +/- 3 ng/ml) when measured within 2 weeks of diagnosis but not when measured 2 months earlier. Our study suggests that in leptomeningeal metastases, CSF MBP levels are indicators of the disease activity, particularly if longitudinal determinations are used.
Mechanisms by which the central nervous system may be influenced during the course of an immune response probably exist but remain obscure. In an attempt to determine any neurophysiological changes during such responses, we have employed a conscious animal model bearing chronically implanted recording electrodes in the preoptic area/anterior hypothalamus (PO/AH) and hypothalamic paraventricular nucleus (PVN). Rats were sensitized to sheep red blood cells (SRBC) injected intraperitoneally. Basal PO/AH multiunit activity (MUA) increased significantly to a maximum 5 days after SRBC injection and correlated with the initial appearance of anti-SRBC serum antibodies. Significant decreases in PO/AH MUA were recorded on Days 3 and 8 following the sensitization. PVN MUA decreased significantly for the first 3 days following immunization and then returned to a basal rate before increasing on Day 6. On the ninth and tenth days following the SRBC injection, both PO/AH and PVN MUA levels had returned to those recorded before immunization. A further group of animals was examined for PO/AH MUA changes during induction of a secondary response to SRBC. Firing rates increased significantly between Days 4 and 9 following the injection, the maximum increase being on Day 6. The profile of this response was different from that recorded during the first response, with no decreases recorded. The results are discussed in terms of neuroimmunomodulatory mechanisms such as those influencing neuroendocrine secretory function.
Using [3H]DA as the ligand of choice, we have shown that rat thymocytes possess dopamine binding sites. The binding of [3H]DA was specific, saturable and of high affinity. [3H]DA binding was rapid and reversible; [3H]DA was totally displaced by low concentrations of dopamine, norepinephrine, and apomorphine. The binding sites were insensitive to neuroleptic drugs such as sulpiride, bromocriptine, and haloperidol. On the basis of these findings, we have suggested that thymocytes possess a D-3 receptor type.
In order to examine possible neurophysiological changes during an immune response, we have recorded neural activity in a conscious animal bearing chronic recording electrodes in the preoptic area/anterior hypothalamus (PO/AH) and hypothalamic paraventricular nucleus (PVN). Male rats were sensitized with sheep red blood cells (SRBC) injected intraperitoneally. Basal PO/AH multiunit activity (MUA) was recorded as 14.7 +/- 2.1 Hz prior to sensitization and was seen to increase significantly to a maximum of 33.1 +/- 6.0 Hz (p less than 0.005) five days after SRBC injection. This increase correlated with the initial appearance of anti-SRBC serum antibodies at a mean antibody titer of 1:32. Also recorded were decreases in PO/AH MUA on days 3 and 8 after the sensitization (8.2 +/- 2.4 Hz, p less than 0.005); 7.1 +/- 3.3 Hz, p less than 0.005, respectively). Basal PVN MUA was recorded as 14.7 +/- 2.4 Hz. It decreased significantly for the first three days after immunization, and then returned to a basal rate before increasing to 25.9 +/- 8.4 Hz (p less than 0.005) on day 6. On the ninth and tenth days after SRBC injection PO/AH and PVN MUA levels returned to those recorded before immunization.
The development of experimental autoimmune encephalomyelitis (EAE) was prevented in rats immunized with encephalitogenic antigen two weeks, but not twelve weeks, after stereotaxic electrolytic destruction of the anterior hypothalamus. Serum antibody level to the antigen myelin basic protein was decreased, and in vitro lymphocyte transformation response to a mitogen was increased. On the other hand, incidence and intensity of chronic experimental autoimmune myasthenia gravis (EAMG) induced by acetylcholine receptor immunization were higher in rats with anterior hypothalamic lesion. In addition, expression of EAE in rats was inhibited when dopamine and norepinephrine in brain were depleted due to intraventricular injection of 6-hydroxydopamine or subcutaneous injection of reserpine. The study indicates hypothalamic modulatory effects on autoimmune response as well as possible involvement of neurotransmitters in this kind of neuroimmunomodulation.
Based on the successful use of a basement membrane-like extracellular matrix (ECM) as a physiological substrate for the growth of adult rat oligodendrocytes, we have applied the system to oligodendroglia of human origin. ECM is excreted and deposited on a culture dish by endothelia cells. Glial cells isolated from fresh human brains by a Percoll density gradient were maintained on ECM for several weeks in vitro. Cells identified as oligodendrocytes by anti-galactocerebroside (GalC) could be transferred and replated on ECM-coated plates. In one case, GalC-positive cells isolated from a biopsy of an 8-year old girl were able to incorporate [3H]thymidine as revealed by autoradiography. ECM can be used successfully for the growth and in vitro maintenance of human oligodendrocytes.
Ampicillin trihydrate aggravated the symptoms of two myasthenic patients. One patient had severe temporary weakness after an ampicillin sodium challenge. Ampicillin increased the preexisting electrical decrement in three rabbits with experimental autoimmune myasthenia gravis while the drug had no deleterious effects in less affected or normal animals. Myasthenic patients receiving ampicillin should be closely monitored for possible acute exacerbations.