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Biomedical subjects

B G Arnason

Publications and source records attributed to B G Arnason.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

Increased muscarinic cholinergic receptor density on CD4+ lymphocytes in progressive multiple sclerosis.

We measured the density and affinity of muscarinic cholinergic receptors (MR) in 29 chronic progressive and ten stable multiple sclerosis (MS) patients and 27 control subjects using [3H]N-methyl-scopolamine. The density of MR on CD4+ lymphocytes was significantly higher in chronic progressive MS (CPMS) than in controls (7.9 +/- 0.7 vs. 4.5 +/- 0.4 fmol/10(6) cells, p less than 0.001). Stable patients did not differ significantly from control subjects. Receptors of the M1 subtype were measured on CD4+ lymphocytes of nine patients and seven controls with the selective antagonist [3H]methylpirenzepine: M1/total receptor ratio was 64.1% in CPMS and 81.2% in controls, suggesting a selective increase of M2-type MR in CPMS. The findings may relate to parasympathetic denervation hypersensitivity of lymphocytes or to lymphocyte activation which is known to be associated with increased MR number.

Adult↗
PubMed1991

Increased lymphocyte beta-adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28- suppressor cell.

Beta-adrenergic receptor density on T cells from healthy humans is greatest on suppressor cells (CD8+, CD28-) and the effect of catecholamines, secreted by the sympathetic nervous system, predominates on this subset. The sympathetic skin response, a measure of sympathetic nervous system function, is absent in most patients with chronic progressive multiple sclerosis (MS). We measured beta-adrenergic receptor density on suppressor cells, cytotoxic cells, and monocytes from patients with chronic progressive MS and healthy control subjects. Control receptor density on suppressor cells was 2.8 +/- 0.3 fmol/10(6) cells versus a density of 5.1 +/- 0.7 fmol/10(6) cells for patients. Cytotoxic cell (CD8+, CD28+) receptor density was 1.4 +/- 0.4 fmol/10(6) cells in control subjects and 0.9 +/- 0.3 fmol/10(6) cells in the patients. Monocytes displayed beta-adrenergic receptor densities of 2.6 +/- 0.4 fmol/10(6) cells in normal individuals and 2.7 +/- 0.4 fmol/10(6) cells in the patient group. CD8 lymphocyte beta-adrenergic receptor densities in patients with relapsing-remitting and those with stable MS were not different from control values, yet were significantly less than the values for patients with chronic progressive MS. We find that mononuclear cells from healthy control subjects and patients with chronic progressive MS proliferate in response to 200 units/ml of recombinant human interleukin-2 (IL-2) similarly. However, IL-2 treatment increased beta-adrenergic receptor density on normal mononuclear cells, but failed to increase it on mononuclear cells from patients with chronic progressive MS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis.

Interleukin (IL) 1 beta, tumor necrosis factor alpha (TNF alpha), and IL-6 are cytokines which mediate cellular responses during immune activation and inflammation. In multiple sclerosis (MS) they might be responsible for T-cell activation (IL-1 beta), for demyelination (TNF alpha), and for immunoglobulin (Ig) synthesis (IL-6) within the central nervous system. We studied IL-1 beta, TNF alpha, and IL-6 levels in the cerebrospinal fluid (CSF) of 34 patients with MS, 43 patients with non-inflammatory neurological diseases (NIND), and 19 patients with inflammatory neurological diseases (IND). IL-6 was found in the CSF of 29% of MS, 7% of NIND, and 47% of IND patients. TNF alpha was detected in the CSF of 23% of MS, 7% of NIND, and 29% of IND. CSF IL-6 and TNF alpha levels were significantly higher in MS and IND than in NIND. IL-1 beta was rarely detected in the CSF of any group. At least one cytokine was detected in 52% of MS CSF, 11% of NIND CSF, and 64% of IND CSF. In MS patients, no relationship was observed between the incidence or the amount of intrathecal IgG synthesis or oligoclonal bands and the presence of any cytokine. We also evaluated cytokine levels in paired sera from 11 MS and 13 NIND patients. Low levels of IL-6 were detected in most sera from MS and NIND patients. TNF alpha was detected in only two MS sera, and IL-1 beta was undetectable in any sample. Our results indicate that increased CSF levels of the cytokines IL-6 and TNF alpha occur frequently in MS and IND, but there is no obvious relationship to intrathecal Ig synthesis.

Adult↗
PubMed1991

The function of the CD2 protein is abnormal in multiple sclerosis.

In active multiple sclerosis (MS), T cell adhesion to sheep red blood cells (SRBC) is deficient. The CD2 protein mediates adhesion to SRBC. Since ligands that bind CD2 can activate T cells, we studied adhesion and activation through CD2 in leukocytes from MS patients. Mononuclear cells (MNC) from patients with MS formed markedly fewer avid T cells (TA; T cells binding greater than or equal to 10 SRBC) than MNC from controls. CD2 antigen expression as measured by FACS analysis on T cells and on T cell subsets was equivalent in MS and controls and rose to a comparable extent in both groups after cell activation; yet activated MS MNC continued to form fewer TA than control cells. Avid rosette formation may be reduced by prostaglandins (PG) secreted by monocytes. Exposure to PG in vitro decreased TA% only in controls, suggesting refractoriness to exogenous PG in MS, perhaps because endogenous PG had already acted. The finding that indomethacin increased TA in MS cells favors this formulation. MNC were activated through CD2 using mAb 9-1 paired with mAb 9.6. Proliferation was significantly diminished in MNC from MS patients compared to MNC from normal controls. Thus, even though T cell membrane expression of CD2 appeared normal in MS, adhesion to SRBC and activation through the CD2 protein were defective.

Alprostadil↗
PubMed1990

Sympathetic skin responses are decreased and lymphocyte beta-adrenergic receptors are increased in progressive multiple sclerosis.

Immune abnormalities, including deficient CD8 lymphocyte-mediated suppression, have been implicated in the progression of multiple sclerosis (MS). The peripheral sympathetic branch of the autonomic nervous system innervates the lymphoid organs and affects immune function. Animals with an ablated sympathetic nervous system develop more severe experimental allergic encephalomyelitis than control animals and exhibit an increased density of beta-adrenergic receptors on their lymphocytes. Experimental allergic encephalomyelitis shares many features with MS. Accordingly, we investigated the psychogalvanic skin reflex in patients with rapidly progressive MS and found that 13 patients (57%) lacked this sympathetic-mediated response. The density of beta-adrenergic receptors on lymphocyte subsets was increased in progressive MS, most notably on the CD8 suppressor/cytotoxic subset. B lymphocytes had the greatest number of receptors with 12.1 +/- 1.8 fmol/10(6) cells in control subjects and 18.7 +/- 2.6 fmol/10(6) cells in patients with MS. CD8 lymphocytes possessed an intermediate number of receptors with 3.4 +/- 0.4 fmol/10(6) cells in control subjects and 9.1 +/- 1.6 fmol/10(6) cells in patients with MS. CD4 lymphocytes demonstrated the fewest receptors with 1.2 +/- 0.1 fmol/10(6) cells in control subjects and 1.8 +/- 0.4 fmol/10(6) cells in patients with MS. No differences in the affinity or function (cyclic adenosine monophosphate levels in response to 10(-5) M (-)isoproterenol) of the adrenergic receptor were found when patients with progressive MS and control subjects were compared. Autonomic abnormalities in progressive MS and the increased beta-adrenergic receptor density found on CD8 lymphocytes may be related.

Adult↗
PubMed1990

Sympathetic nervous system and PC12 pheochromocytoma-derived factors suppress stimulation of lymphocytes.

We have reported previously that ablation of the sympathetic nervous system augments immune responses in mice and rats. In the present study we show that a factor present in the sympathetic cervical ganglia of newborn rats suppresses Con A-induced stimulation of splenic T lymphocytes significantly whether added prior to, throughout, or following exposure to Con A. We also show that rat PC 12 pheochromocytoma cells secrete a factor which has the same inhibitory effect on T cell proliferation as the sympathetic ganglia-derived factor.

Animals↗
PubMed1989

Comparison of sympathetic skin response with quantitative sudomotor axon reflex test in diabetic neuropathy.

The sympathetic skin response (SSR), the quantitative sudomotor axon reflex test (Q-SART), and cardiac beat-to-beat variability with respiration as measured by the expiratory/inspiratory ratio (E/I ratio) were studied in 39 patients with diabetic neuropathy of whom 33 also had one or more symptoms of autonomic involvement. In the lower extremities 87% of the patients with an absent SSR had an abnormal Q-SART (P less than 0.001), and 81% of patients with the SSR present had a normal Q-SART (P less than 0.02). The E/I ratio was abnormal in all but one of 23 patients with an absent SSR in the foot, and a normal E/I ratio was present only in those patients (n = 7) with the SSR present in hand and foot, and in an eighth patient who had SSR absent in the foot and present in the hand. A similar correlation was found between the E/I ratio and the Q-SART in the foot, although 4 of 25 patients with an abnormal foot Q-SART had a normal E/I ratio. We conclude that the concordance of results of the SSR and Q-SART supports the combined use of these tests to uncover early distal sympathetic failure in diabetic neuropathy.

Adult↗
PubMed1989

The beta-adrenergic agonist isoproterenol suppresses experimental allergic encephalomyelitis in Lewis rats.

Treatment with the beta-adrenergic agonist isoproterenol suppresses clinical and histological experimental allergic encephalomyelitis in Lewis rats. The effect of isoproterenol treatment is greater when the drug is given from the time of immunization through the acute phase of the illness or from 8 to 14 days post-immunization than when given for the first 7 days after immunization.

Adrenergic beta-Agonists↗
PubMed1989

PC12 pheochromocytoma and sympathetic nervous system derived trophic factors augment growth of neuroblastoma.

A trophic factor secreted by PC12 rat pheochromocytoma augments growth of C1300 neuroblastoma clonal lines S20, N18 and C46, but does not affect growth of the NIE 115 line. A trophic factor present in newborn sympathetic ganglia has the same biological effect on neuroblastoma cell lines. PC12 cells and sympathetic ganglia are both of neural crest origin; possibly both secrete the same trophic factor.

Adrenal Gland Neoplasms↗
PubMed1989

Expression and modulation of K+ currents in oligodendrocytes: possible role in myelinogenesis.

We have used whole-cell and single-channel recording techniques to investigate the electrophysiological properties of cultured ovine oligodendrocytes (OLGs). Our studies have led to the following conclusions. (1) Cultured mature OLGs express a variety of voltage-dependent K+ conductances including an outward current that consists of a transient component and a steady-state component, as well as an inwardly rectifying K+ current. (2) These conductances are expressed sequentially as a function of development in culture. The inwardly rectifying K+ current appears later than the outward current. (3) Although process extension may influence the expression of the ion channels, the majority of the K+ channels are located in the soma of OLGs, probably concentrated in the basal plasma membrane. (4) Finally, the activation of K+ channels in OLGs can be inhibited by two distinct second messengers, cAMP acting through protein kinase A and diacylglycerol acting through protein kinase C, the effects of which perhaps converge at the level of a common phosphorylated enzyme or regulatory protein. Both cAMP and diacylglycerol have been implicated as factors important in controlling the induction of a myelinogenic metabolism associated with OLG substratum attachment. Thus, membrane ion channels may provide an important intermediate step linking cellular substratum attachment to the eventual induction of myelinogenesis.

Animals↗
PubMed1989

Increased N-myc mRNA expression associated with dibutyryl cyclic AMP induced neuroblastoma differentiation.

The N-myc cellular oncogene is frequently amplified and expressed at a high level in neuroectodermal tumor cells such as neuroblastoma and retinoblastoma. We examined N-myc expression in NCB-20 hybrid (N18TG2 neuroblastoma x embryonic Chinese Hamster brain) cells. After five days of culture, cells treated with 1 mM db cAMP show extensive neurite outgrowth and secrete acetylcholinesterase into the media at a level three times higher than untreated control. In situ hybridizations, dot blots, and Northern analyses reveal four- to eight-fold higher levels of N-myc mRNA in the treated, differentiated cells than in the untreated, undifferentiated controls. Our results show that the highly differentiated state is not incompatible with a high level of N-myc mRNA.

Acetylcholinesterase↗
PubMed1988

Forskolin and phorbol esters decrease the same K+ conductance in cultured oligodendrocytes.

Cultured ovine oligodendrocytes (OLGs) express a number of voltage-dependent potassium currents after they attach to a substratum and as they begin to develop processes. At 24-48 hours following plating, an outward potassium current can be identified that represents a composite response of a rapidly inactivating component and a steady-state or noninactivating component. After 4-7 days in culture, OLGs also develop an inward rectifier current. We studied the effects of forskolin and phorbol 12-myristate 13-acetate (PMA) on OLG outward currents. These compounds are known to alter the myelinogenic metabolism of OLGs. PMA, an activator of protein kinase C (PK-C), has been shown to enhance myelin basic protein phosphorylation while forskolin acting on adenylate cyclase, and thereby increasing cAMP, inhibits it. Both forskolin and PMA increase the phosphorylation of 2'3'-cyclic nucleotide phosphodiesterase, an OLG/myelin protein. We found that forskolin decreased the steady-state outward current at 120 mV by 10% at 100 nM, and by 72% at 25 microM from a holding potential of -80 mV. The time course of inactivation of the peak currents was decreased, affecting both the fast and slow time constants. There was no significant change in the steady-state parameters of current activation and inactivation. The effect of forskolin was attenuated when the adenylate cyclase inhibitor adenosine (2 mM) was present in the intracellular/pipette filling solution. The results of PMA experiments were similar to those obtained with forskolin. Whereas the amplitude of the currents in the presence of PMA was reduced by 28% at 1.5 nM and 60% and 600 nM, the decay phase of the peak currents was less affected. The PMA effect could still be seen when the intracellular Ca2+ was reduced to less than or equal to 10 nM with 5 mM BAPTA, but was inhibited when the cells were pre-exposed to 50 microM psychosine, a PK-C inhibitor. It is postulated that the potassium currents in OLG can be physiologically modulated by two distinct second-messenger systems, perhaps converging at the level of a common phosphorylated enzyme or regulatory protein.

Animals↗