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Biomedical subjects

A Noronha

Publications and source records attributed to A Noronha.

12 recordsLinked to original sources

Contrasting effects of alpha, beta, and gamma interferons on nonspecific suppressor function in multiple sclerosis.

Interferons are biological molecules with antiviral, antiproliferative, and immunomodulatory actions. Interferon alpha (IFN-alpha) and -beta are potentially useful in the treatment of multiple sclerosis (MS). IFN-gamma, in contrast, increases the frequency of exacerbations of MS. In this study, we compared the effect of recombinant human IFN-alpha, -beta, and -gamma on suppressor function in patients with MS. Nonspecific suppressor cell function, measured in a concanavalin A suppressor assay, was significantly decreased in 16 patients with progressive MS (mean percent suppression +/- SEM, 14.4 +/- 5.5 in patients with MS, 33.5 +/- 4.8 in 16 normal subjects; p less than 0.001). Recombinant human IFN-beta augmented suppressor function in MS to 45.4 +/- 5.1% (p less than 0.001) and in control subjects to 56.8 +/- 3.8% (p less than 0.001). Similarly, recombinant human IFN-alpha improved suppression in MS to 43.0 +/- 5.6% (p less than 0.001) and in control subjects to 51.1 +/- 5.9% (p less than 0.001). In contrast, recombinant human IFN-gamma had no effect on suppressor function in patients with MS and in control subjects. This study shows that IFN-alpha and -beta augment deficient suppressor function in MS, whereas IFN-gamma has no effect on suppressor function in the progressive phase of the disease.

Adult

Preferential increase of IL-2R+ CD4+ T cells and CD45RB- CD4+ T cells in the central nervous system in experimental allergic encephalomyelitis.

We examined lymphocytes isolated from the spinal cord (SC), peripheral blood (PB) and lymph nodes (LN) draining the immunization site of Lewis rats with acute experimental allergic encephalomyelitis (EAE). Cells were analysed for T cell subset markers CD4 (mAb W3/25) and CD8 (mAb OX8), for IL-2R (mAb OX39), and for high molecular mass leukocyte common antigen (LCA, CD45RB) expression (mAb OX22). T cells expressing high (CD45RB+) or low (CD45RB-) molecular mass LCA are of different maturational stages and/or separate lineages. CD4+ T cells were more predominant in SC than in PB and LN; CD8+ T cells were scarce in SC but common in PB and LN. Activated CD4+ T cells (IL-2R+) were common in the SC and LN but infrequent in blood. CD4+ T cells that were CD45RB+ were scarce in the SC. In contrast, the majority of CD4+ T cells in the PB and LN were CD45RB+. The preferential accumulation of IL-2R+ CD4+ T cells and of CD45RB- CD4+ T cells in the central nervous system (CNS) indicates that a selective mechanism directs cell egress into CNS lesions in EAE.

Animals

Seasonal distribution of births in Alzheimer's disease.

We obtained season-of-birth data in 727 autopsy-confirmed cases of Alzheimer's Disease (AD) and compared these data with expected general population birth rates. There were no significant differences between quarterly birth rates in the AD group and expected quarterly birth rates. Edward's test for cyclical trends did not establish a peak period of birth in the AD sample. No significant differences between observed and expected quarterly birth rates were found when data were analyzed with regard to either family history of dementia or to gender. Edward's test for peak quarter was significant for AD females, however, with the peak period occurring early in the first quarter. These negative findings between observed and expected quarterly birth rates, based on the large number of autopsy-confirmed AD cases in this study, suggest that a season-of-birth effect in AD is highly unlikely.

Aged

Interferon beta augments suppressor cell function in multiple sclerosis.

Suppressor cell function has been previously reported to be decreased in patients with progressive multiple sclerosis (MS). The abnormality could not be corrected in vitro and was present even after patients were treated with immunosuppressive agents. We now report that interferon beta augments suppressor cell function in vitro in progressive MS. Nonspecific suppressor cell function as measured in a concanavalin A (Con A) suppressor assay was reduced in 24 MS patients (mean percent suppression, 19.6 +/- 2.2) when compared to 19 normal subjects (mean percent suppression, 35.0 +/- 3.3). The data are highly significant (p less than 0.001). When recombinant human interferon beta (10(3) units/ml) was added to lymphocyte cultures with Con A, suppressor activity improved significantly. The mean percent suppression improved from 19.6 +/- 2.2 to 37.8 +/- 2.6 in MS (p less than 0.001) and from 35.0 +/- 3.3 to 46.2 +/- 3.5 (p less than 0.025) in control subjects. This study shows that recombinant interferon beta improves suppressor function in humans, an effect that is particularly significant in progressive MS.

Adult

Tau fraction of transferrin is present in human aqueous humor and is not unique to cerebrospinal fluid.

In view of the many similarities between the aqueous humor and the cerebrospinal fluid (CSF), we investigated whether the tau fraction of transferrin, which is believed to be specific for CSF, is also present in aqueous humor. Samples of aqueous humor and CSF from clinically normal individuals were analyzed by SDS-PAGE and isoelectric focusing (IEF), and probed with anti-transferrin antiserum and the lectin Limax flavus agglutinin. Specific bands which corresponded to transferrin and its tau fraction were detected in both fluids. After isolation of these bands by affinity chromatography with anti-transferrin antiserum, we detected a single, diffuse fraction at an apparent molecular weight of 80 kDa in both aqueous humor and CSF. Peptide mapping revealed no detectable difference in this fraction between the two fluids. The detection of the tau fraction in human aqueous humor indicates that this molecule cannot be considered a specific cerebrogenic marker as had been thought previously. In view of the known growth-promoting properties of transferrin, its isolation from both ocular and cranial fluids attains special significance.

Aged

Pericarotid cluster headache.

Cluster headache is generally not associated with recognised disease, and the pathogenesis remains unclear. The onset of typical cluster headaches is reported in a patient with nasopharyngeal carcinoma. The tumor encircled the internal carotid artery but did not extend intracranially. It thus appears possible that cluster headaches may be triggered by processes involving the carotid artery.

Carcinoma, Squamous Cell

Effect of dorsal hippocampal lesion compared to dorsal hippocampal blockade by atropine on reference memory in vision deprived rats.

In order to study the primacy of the hippocampus in place learning function 24 male adult albino rats were hippocampally-lesioned in dorsal hippocampus involving fornical damage (group I); sham operated for comparison with group I (group II); cannulated for instillation of atropine sulphate in the same loci as group I (group III); and cannulated for instillation of saline which served as control for group III (group IV). All the animals were enucleated and their reference memory (long-term memory) was tested, using open 4-arm radial maze. There was loss of reference memory in groups I and III. However, hippocampally-lesioned animals, showed recovery of reference memory deficit within a short period of 10 days or so. Whereas atropinized animals showed persistent reference memory deficit as long as the instillation effect continued. The mechanism involved in the recovery of reference memory in hippocampally-lesioned animals and persistent deficit of reference memory in atropinized animals has been postulated to explain the primacy of hippocampus in the place learning function under normal conditions.

Animals

Activated suppressor cell function in multiple sclerosis--clinical correlations.

Activated suppressor cell function mediated by either freshly isolated peripheral blood mononuclear cells (MNCs), freshly isolated CD8+ lymphocytes or by CD8+ cell lines, has previously been found to be reduced compared to controls in multiple sclerosis (MS) patients with progressive disease (MS-P). In this study, we found that suppressor activity mediated by CD8+ cell lines, derived from MS patients with stable disease (MS-S) patients and maintained in culture for 14 days, was significantly greater (45 +/- 6%) compared to that mediated by MS-P patients' CD8+ cells (11 +/- 4%, P less than 0.005). The MS-S suppressor values were, however, suggestively reduced compared to controls (60 +/- 6%, P less than 0.05). MNC-mediated suppressor values for the MS-S group (61 +/- 5%) did not differ from the control group (67 +/- 6%). Values for the MS-P group (7 +/- 6%) were significantly reduced compared to MS-S and control groups. Cytotoxic activity mediated by CD8+ cell lines showing defective suppressor function did not differ from control values. The cell lines in MS and control did not differ with respect to their rate of proliferation in the presence of IL-2 and OKT3. Suppressor function in this assay was ablated if exogenous IL-2 was removed from the culture media. These data suggest that defective activated suppressor function is characteristic of the progressive form of MS, although a suppressor defect is also partially expressed in stable MS patients when CD8+ cell lines are studied.

Adult

Defective suppressor cell function mediated by T8+ cell lines from patients with progressive multiple sclerosis.

Activated suppressor cell function, induced with either concanavalin A or OKT3 and mediated by either unfractionated mononuclear cells or "panning" enriched T8+ cells, freshly isolated from peripheral blood, is reduced in patients with progressive multiple sclerosis (MS) as compared with control donors. In this study, we generated T8+ cell lines from the peripheral blood of these same patients and controls. Suppressor activity, mediated by T8+ cells exposed to OKT3 on days 1, 7, and 14 of culture and then treated with mitomycin C on day 16, was significantly reduced in the MS group (mean percent suppression 13% +/- 5) as compared with the control group (68% +/- 6, n = 8, p less than 0.001). No differences were noted in [3H]thymidine uptake by the OKT3-stimulated T8+ cell lines of MS and control groups. Mean percent suppression mediated by T4+ cell lines did not differ between MS and control groups (15% +/- 4, n = 3, vs 22% +/- 2, n = 4). These current data suggest that the previously observed defect in T8+ cell-mediated activated suppressor cell function in MS is a persistent one, favoring the postulate that the defect reflects intrinsic alterations in this cell population rather than a transient effect of serum factors on T8+ cell function.

Antigens, Differentiation, T-Lymphocyte

Pure motor hemiplegia, medullary pyramid lesion, and olivary hypertrophy.

The case is presented of a 60 years old man who developed sudden right hemiplegia without other accompanying neurological signs and later a spastic hemiparesis. Neuropathological studies indicated an ischaemic lesion of the left medullary pyramid which was accompanied by hypertrophy of the left inferior olivary nucleus. An additional lesion, demyelination of the right gracile tract, is poorly explained. This case represents the second reported instance of pure motor hemiplegia due to a circumscribed lesion in the medullary pyramid and possibly an unique instance of olivary hypertrophy without obvious damage to the central tegmental tract, ipsilateral superior cerebellar peduncle, or contralateral dentate nucleus. The olivary hypertrophy is thought to have arisen from local damage to the termination of the central tegmental fibres at the left inferior olivary nucleus. The question of the development of spasticity in a pure pyramidal tract lesion is discussed.

Hemiplegia

Four-arm radial open maze (FAROM) as a tool for assessing the effect of atropine in spatial memory of the rats.

Place learning behaviour for working (short term) memory and reference (long term) memory is studied with the Four-arm radial open maze (FAROM) in 18 rats divided equally in three groups. In group I, 0.5 mg of atropine was injected intra-peritoneally 30 minutes before the trial. In group II, saline and in group III Glycopyrrolate were injected instead. Twenty three hours hungry animals were tested on each day in the maze to search for food kept in one of the eight cul-de-sacs of maze. The latency i.e. the time to reach the goal cul-de-sacs, as well as the error score i.e. the number of entries in the non-goal cul-de-sacs were counted during six consecutive trials, per day. Each trial duration was 5 minutes or the time taken by the animal to search the goal compartment whichever was less. The inter-trials period was 10 min and the work was carried out for a period of 3 weeks. The results show that atropine does block effectively both the memory faculties i.e. working and reference memory and that level of memory deficit induced by atropine is related to the rate of drug uptake by the central cholinergic receptors.

Animals