Gangliosides and neurological diseases.
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Gangliosides↗
Biomedical subjects
P O Behan
Publications and source records attributed to P O Behan.
Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome.
OBJECTIVE: To study the dynamic function of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome. DESIGN: Prospective comparison of patients with postviral fatigue syndrome with two control groups. SETTING: Department of neurology, University of Glasgow, Southern General Hospital; department of psychiatry, St James's Hospital, Dublin. SUBJECTS: 15 patients with postviral fatigue syndrome, 13 age and sex matched healthy subjects, and 13 patients with primary depression. MAIN OUTCOME MEASURES: Serum prolactin concentrations before and one, two, and three hours after administration of buspirone. RESULTS: Because of the effects of sex hormones on prolactin secretion data for men and women were analysed separately. There was no significant difference in baseline prolactin concentrations between patients with postviral fatigue syndrome and healthy subjects or those with primary depression. However, the percentage difference between peak and baseline values was significantly higher in patients with postviral fatigue syndrome than the control groups (one way analysis of variance: women, p = 0.003; men, p = 0.004). CONCLUSIONS: The results suggest upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome but not in those with primary depression. The buspirone challenge test may therefore be useful in distinguishing these two conditions. Larger studies are required to explore the potential value of drugs acting on central 5-hydroxytryptamine receptors in the treatment of patients with the postviral fatigue syndrome.
Adult↗
Behavior, ectopias and immunity in BD/DB reciprocal crosses.
In a previous study, in which fertilized DBA ova were transferred into an autoimmune female, and NZB ova were transferred into a non-autoimmune female, we found that (1) the maternal environment affected the degree of autoimmunity, (2) the incidence of cortical ectopias was not affected by the maternal environment (3) DBA and NZB females had greater paw asymmetry if reared in an autoimmune uterus, and (4) avoidance learning scores were inversely related to degree of autoimmunity. In the present experiment, reciprocal crosses of DBA and BXSB mice were studied to confirm and extend the original findings. DB mice (DBA female x BXSB male) had greater immune activity than the BD animals, had poorer avoidance learning, but were better on black-white discrimination learning and the Lashley III maze. The BD mice had greater paw asymmetry. Only one of 38 animals had a cortical ectopia. The results lead to the following conclusions: (1) there is an inverse relationship between amount of immune activity and active avoidance learning; (2) some uterine factor in autoimmune mice causes females to have greater paw asymmetry; (3) cortical ectopias are under genetic control; and (4) the lesser immune activity of the BD mice suggests that they developed a suppressor system following early exposure to autoimmunity in the uterine/maternal environment.
Animals↗
A behavior profile of the MRL/Mp lpr/lpr mouse and its association with hydrocephalus.
Since the NZB and BXSB autoimmune mouse strains have cortical ectopias and associated behavioral changes, mice from the MRL/l (MRL/Mp lpr/lpr) autoimmune strain were given a series of behavioral tests followed by anatomical analyses of their brains and immune assays of plasma. No cortical ectopias were found, but this strain was discovered to have a high incidence of hydrocephalus: 46% had severe dilatation of the lateral and third ventricles, 30% had moderate dilatation, and 24% had minimal or no enlargement of the ventricles (total N = 57). Those mice in the severe hydrocephalus group were poorer in a nonspatial discrimination learning task, had less paw asymmetry, and were less active in a swimming task. No association was found between degree of hydrocephalus and any immune parameter.
Animals↗
Search for retrovirus in the chronic fatigue syndrome.
AIM: To examine peripheral blood and skeletal muscle from patients with chronic fatigue syndrome for exogenous retrovirus. METHODS: Blood samples from 30 patients and muscle biopsy specimens of 15 patients were examined for retroviral sequences by DNA extraction, polymerase chain reaction (PCR), and Southern blotting hybridisation. Sera were examined for human foamy virus by western immunoblotting and indirect immunofluorescence techniques. RESULTS: No differences between the patient and control populations was found for any of the PCR primer sets used (gag, pol, env, and tax regions of HTLV I/II). An endogenous gag band was observed in both the patient and control groups. All sera were negative for antibody to human foamy virus. CONCLUSION: The results indicate that there is no evidence of retroviral involvement in the chronic fatigue syndrome.
Blotting, Southern↗
Effects of the autoimmune uterine/maternal environment upon cortical ectopias, behavior and autoimmunity.
NZB and BXSB mice develop autoimmune disease and learn poorly on avoidance tasks. In addition, many of these mice have ectopic collections of neurons, which occur prenatally, in layer I of the cerebral neocortex. The purpose of these experiments was to evaluate the contribution of the uterine/maternal environment upon these variables by transferring fertilized ova to an autoimmune or a non-autoimmune maternal host. In Experiment 1 fertilized DBA ova were transferred into the uteri of BXSB maternal recipients. Later, these animals and conventionally reared DBAs were tested for paw preference, swimming rotation, water escape learning, and shuttlebox avoidance learning. Blood was taken for measurement of immune parameters, and their brains were examined for cortical ectopias. As compared to conventional DBAs, the ova transfer mice had greater amounts of anti-dsDNA autoantibodies, poorer avoidance learning, and poorer water escape learning; in addition, the females had greater paw asymmetry. There was only 1 ectopia in the 81 ova transfer animals, and none in the 78 control mice. In Experiment 2 fertilized NZB ova were transferred into the uteri of non-autoimmune hybrid females and the same procedures were followed as in Experiment 1. Ova transfer mice had lesser amounts of anti-dsDNA autoantibodies, better avoidance learning scores, and females had less paw asymmetry; in addition, within the ova transfer group males were clockwise swimmers whereas females swam counterclockwise. There were 4 ectopics out of 17 ova transfer mice (23.5%), which did not differ from the 40.5% of the control group. In both experiments the uterine environment did not affect the occurrence of ectopias.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome.
OBJECTIVE: To determine the presence of enteroviral sequences in muscle of patients with the postviral fatigue syndrome. DESIGN: Detection of sequences with the polymerase chain reaction in a well defined group of patients with the syndrome and controls over the same period. SETTING: Institute of Neurological Sciences, Glasgow. SUBJECTS: 60 consecutive patients admitted to the institute with the postviral fatigue syndrome who had undergone extensive investigation to exclude other conditions. 41 controls from the same catchment area without evidence of fatigue, all undergoing routine surgery. MAIN OUTCOME MEASURES: Routine investigations, serological screen for antibodies to a range of viruses, and presence of enteroviral RNA sequences in muscle biopsy specimens. RESULTS: 15 (25%) patients and 10 (24.4%) controls had important serological findings. 12 patients had neutralising antibody titres of greater than or equal to 256 to coxsackieviruses B1-5 (six positive for enteroviral RNA sequences, six negative); three were positive for Epstein-Barr virus specific IgM (two positive, one negative). Six controls had similar neutralising antibody titres to coxsackieviruses (all negative); one was positive for Epstein-Barr virus specific IgM (negative); and three had titres of complement fixing antibody greater than or equal to 256 to cytomegalovirus (all negative). Overall, significantly more patients than controls had enteroviral RNA sequences in muscle (32/60, 53% v 6/41, 15%; odds ratio 6.7, 95% confidence interval 2.4 to 18.2). This was not correlated with duration of disease, patient and age, or to raised titres of antibodies to coxsackieviruses B1-5. CONCLUSIONS: Persistent enteroviral infection of muscle may occur in some patients with postviral fatigue syndrome and may have an aetiological role.
Adolescent↗
Antibody to Coxsackie B virus in diagnosing postviral fatigue syndrome.
OBJECTIVE: To study the association between coxsackie B virus infection and the postviral fatigue syndrome and to assess the immunological abnormalities associated with the syndrome. DESIGN: Case-control study of patients with the postviral fatigue syndrome referred by local general practitioners over one year. SETTING: General practitioner referrals in Dunbartonshire, Scotland. PATIENTS: 254 Patients referred with the postviral fatigue syndrome (exhaustion, myalgia, and other symptoms referable to postviral fatigue syndrome of fairly recent onset--that is, several months) and age and sex matched controls obtained from same general practitioner; 11 patients were rejected because of wrong diagnoses, resolution of symptoms, and refusal to participate, leaving 243 patients and matched controls. MAIN OUTCOME MEASURES: Detailed questionnaire (patients and controls) and clinical examination (patients) and blind analysis of blood sample at entry and after six months for determination of coxsackie B virus IgM and IgG antibodies and other variables (including lymphocyte protein synthesis, lymphocyte subsets, and immune complexes). RESULTS: Percentage positive rates for coxsackie B virus IgM at entry were 24.4% for patients and 22.6% for controls and for coxsackie B virus IgG 56.2% and 55.3% respectively; there were no significant differences between different categories of patients according to clinical likelihood of the syndrome nor any predictive value in a fourfold rise or fall in the coxsackie B virus IgG titre in patients between entry and review at six months. The rates of positive antibody test results in patients and controls showed a strong seasonal variation. Of the numerous immunological tests performed, only a few detected significant abnormalities; in particular the mean value for immune complex concentration was much higher in 35 patients and 35 controls compared with the normal range and mean value for total IgM was also raised in 227 patients and 35 controls compared with the normal range. CONCLUSIONS: Serological tests available for detecting coxsackie B virus antibodies do not help diagnose the postviral fatigue syndrome. Percentage positive rates of the antibodies in patients simply reflect the background in the population as probably do the raised concentrations of total IgM and immune complexes.
Adult↗
Mitochondrial abnormalities in the postviral fatigue syndrome.
We have examined the muscle biopsies of 50 patients who had postviral fatigue syndrome (PFS) for from 1 to 17 years. We found mild to severe atrophy of type II fibres in 39 biopsies, with a mild to moderate excess of lipid. On ultrastructural examination, 35 of these specimens showed branching and fusion of mitochondrial cristae. Mitochondrial degeneration was obvious in 40 of the biopsies with swelling, vacuolation, myelin figures and secondary lysosomes. These abnormalities were in obvious contrast to control biopsies, where even mild changes were rarely detected. The findings described here provide the first evidence that PFS may be due to a mitochondrial disorder precipitated by a virus infection.
Adolescent↗
Clinical spectrum of postviral fatigue syndrome.
Many different neurological and psychiatric syndromes follow viral infections, but their clinical pictures and pathogeneses are poorly understood. The syndromes include acute disseminated encephalomyelitis (post-infectious encephalomyelitis), the Guillain-Barre syndrome (post-infectious neuritis) and Reye's syndrome. Recently, attention has been focused on another common postviral neurological syndrome, i.e. the postviral fatigue syndrome (PVFS)--termed myalgic encephalomyelitis (ME) and a host of other designations. PVFS occurs both sporadically and in epidemics, with cases being reported from all over Europe, the United States, Australasia and South Africa. It is difficult to make the diagnosis and this has meant, in the past, that it is not until an epidemic has occurred that random cases which presented in the preceding years are realised to represent the same condition. With renewed interest in the syndrome and greater attention from physicians, however, diagnosis of sporadic cases is now becoming more common.
Antigens, Viral↗
Changes in natural killer cell phenotype in patients with post-viral fatigue syndrome.
We analysed peripheral blood CD56+ natural killer (NK) cell subsets in 23 carefully characterized patients with post-viral fatigue syndrome (PFS), compared with 19 healthy controls, using fluorochrome-conjugated, specific monoclonal antibodies and the FACScan. We found significantly increased percentages of CD56+, and especially CD56bright+ NK cells in PFS patients. We also found significantly increased percentages of CD56+ high affinity interleukin-2 (IL-2) receptor (CD25)+ and CD56+ transferrin receptor (CD71+) subsets of cells, most of which also stained brightly for CD56. Also, we found an increased percentage of CD56+ CD3+ cells, many of which stained brightly for CD56, although there was no increase in the percentage of CD56- CD3+ T cells in these patients. These observations, in conjunction with very low percentage of CD56- CD25+ cells, suggest that there is a preferential involvement of this minor subset of CD56+ CD3+ T cells in PFS. Finally, a decreased percentage of CD56+ Fc gamma receptor (CD16)+ NK cells was identified, which suggests a reduced capacity of antibody-dependent cellular cytotoxicity in PFS patients. Subsets of CD56+ NK cells co-expressing CD2, CD4 or CD8 did not show any significant difference between PFS patients and healthy controls. These phenotypic changes provide laboratory evidence of immunological abnormalities in this syndrome, and, we suggest, may be consistent with persistent viral infection.
Adolescent↗
Association of amyotrophic lateral sclerosis, Hoigne's syndrome and residence in Guam.
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Adult↗
Unsuccessful treatment of subacute sclerosing panencephalitis treated with transfusion of peripheral blood lymphocytes from an identical twin.
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Adult↗
A case of progressive encephalomyelitis with rigidity and positive antiglutamic acid decarboxylase antibodies [corrected].
A 50 year old woman developed progressive encephalomyelitis with rigidity over a three year period. Her CSF contained oligoclonal bands and both her serum and CSF contained antibodies directed against GABA-ergic synapses (antiglutamic acid decarboxylase [corrected] antibodies). These antibodies have recently been described in cases of stiff man syndrome. Both disorders may be part of a clinical spectrum that has an underlying autoimmune basis.
Autoantibodies↗
The muscle findings in the neuroleptic malignant syndrome associated with lysergic acid diethylamide.
A detailed pathological description of the muscle findings in a case of the neuroleptic malignant syndrome (NMS) following ingestion of lysergic acid diethylamide (LSD) is given, including the first ultrastructural analysis. Focal necrosis, oedema, and hypercontraction of fibres with glycogen and lipid depletion, were identified, all of which had resolved completely a year later. The findings are compared with those in malignant hyperthermia. It is suggested that the results support the view that in NMS, the muscle rigidity is due to central mechanisms and, in both this disorder and malignant hyperthermia, it is responsible for the hyperpyrexia and its life-threatening complications.
Adult↗
Bilateral internuclear ophthalmoplegia as a false localizing sign.
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Adult↗
Brain abnormalities in immune defective mice.
Mouse strains with or without immune disorders were examined in order to further assess the incidence of brain anomalies in immune-disordered strains. The brain was examined in Nissl-stained serial sections under a light microscope for the presence of abnormalities, with specific attention to ectopic collections of neurons in layer I of the neocortex, as reported in the autoimmune New Zealand Black (NZB) and BXSB strains. The present study was designed to survey additional strains with immune disorders (Snell dwarf, C57BL/6J-nu/nu, BALB/cByJ-nu/nu, and SJL) and 7 control strains without immune disorders. In addition, we attempted to replicate past findings in the highly affected BXSB strain and the MRL/1 strain, which develops autoimmune disease, but has a low incidence of brain abnormalities. The largest number of brain abnormalities (20-40%) were seen in the C57BL/6J-nu/nu, Snell dwarf and BXSB strains. The anomalies in the C57BL/6J-nu/nu and BXSB mice consisted of ectopic neurons in layer I of the neocortex, whereas the Snell dwarf mice had either neuron-free areas in the cortex, or rippling of cortical layers II-IV, and one case had agenesis of the corpus callosum. Between 4% and 8% of the mice from the SJL, MRL/1, and MRL +/+ strains had either neuron-free areas in the cortex or ectopic neurons in layer I. The BALB/cByJ-nu/nu and control strains did not have any cortical abnormalities. Future studies will be designed to determine whether immune-based alterations to the developing brain are responsible for the brain anomalies present in immune-disordered strains.
Animals↗
Assay of complement activation in mouse serum by ELISA.
We describe a simple, sensitive and reproducible ELISA assay for complement activation in mouse serum, based on measurement of the opsonization of purified, heat-aggregated mouse gamma-globulin bound to the solid phase. This assay measures mainly classical pathway activation, and we used it to show significant differences in complement activation in sera from mice of various autoimmune, immunodeficient and immunologically normal strains. This assay has the advantage over existing methods of requiring minimal volumes of serum, and of avoiding problems of species incompatibility.
Animals↗