PubMed Health⌕ Search

Biomedical subjects

A T Reder

Publications and source records attributed to A T Reder.

At least 19 recordsLinked to original sources
PubMed1992

Cytokines in the vitreous of patients with proliferative diabetic retinopathy.

Sixteen vitreous and paired serum samples from 13 patients with proliferative diabetic retinopathy, vitreous samples from seven cadaveric control subjects, and aqueous humor samples from 15 normal control subjects were assayed for the cytokines interleukin-1, tumor necrosis factor-alpha, interleukin-6, and interferon-gamma. Interleukin-6 was detected in 15 of 16 vitreous samples (94%) from diabetic patients, but it was not detected in any of the aqueous humor samples. Vitreous interleukin-6 levels positively correlated with ocular disease activity. Interleukin-1 was detected in seven of 16 vitreous samples (44%) and in four of ten aqueous humor samples (40%), whereas tumor necrosis factor-alpha and interferon-gamma were never detected in vitreous or aqueous fluid. Serum samples from diabetic patients and control subjects contained comparable low levels of interleukin-6. Interleukin-1, tumor necrosis factor-alpha, and interferon-gamma were not found in any of the sera. Because interleukin-6 can function as B-cell differentiation factor, this cytokine may have a role in immunoglobulin deposition in the ocular tissues and in the immunopathologic characteristics of proliferative retinopathy.

Adult↗
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↗
PubMed1992

Interferon-beta treatment does not elevate cortisol in multiple sclerosis.

Interferons (IFN) are used to treat cancer and multiple sclerosis (MS). High doses of IFN elevate serum cortisol, which may indirectly affect the course of either of these diseases. IFN-induced elevation of serum cortisol could speed recovery from exacerbations of MS. We find that IFN-beta at 9 or 45 MU every other day does not elevate serum or urine cortisol in MS. Clinical effects of IFN-beta in MS are likely to be direct, and not mediated indirectly through alteration of serum cortisol levels.

Adult↗
PubMed1992

Severe tetanus in immunized patients with high anti-tetanus titers.

Severe (grade III) tetanus occurred in three immunized patients who had high serum levels of anti-tetanus antibody. The disease was fatal in one patient. One patient had been hyperimmunized to produce commercial tetanus immune globulin. Two patients had received immunizations 1 year before presentation. Anti-tetanus antibody titers on admission were 25 IU/ml to 0.15 IU/ml by hemagglutination and ELISA assays; greater than 0.01 IU/ml is considered protective. Even though one patient had seemingly adequate anti-tetanus titers by in vitro measurement (0.20 IU), in vivo mouse protection bioassays showed a titer less than 0.01 IU/ml, implying that there may have been a hole in her immune repertoire to tetanus neurotoxin but not to toxoid. This is the first report of grade III tetanus with protective levels of antibody in the United States. The diagnosis of tetanus, nevertheless, should not be discarded solely on the basis of seemingly protective anti-tetanus titers.

Adult↗
PubMed1992

Regulation of production of adrenocorticotropin-like proteins in human mononuclear cells.

Cells of the immune system produce biologically active adrenocorticotropic hormone (ACTH). Many laboratories, however, have been unable to replicate experiments which demonstrate ACTH in immune cells. Sensitive immunohistochemical staining and digital scanning, confocal microscopy were used to study regulation of ACTH-like immunoreactivity (ACTH-IR) in human mononuclear cells. Cytoplasmic ACTH-IR was induced by corticotrophin releasing factor (CRF)/arginine vasopressin (AVP), and also by protein kinase C (PKC) activation and by the interferon (IFN-alpha beta inducer, Na-polyinosinic-polycytidylic acid (polyIC). Induction of cytoplasmic ACTH-IR was maximal within 6 hr of stimulation with CRF/AVP or phorbol myristate acetate (PMA). Recombinant human interleukin-1 beta (rhIL-1 beta) was also stimulatory, but rhIL-1 alpha had minimal effect. Regulation of ACTH-IR production in immune cells parallels the regulation of ACTH in the anterior pituitary, and ACTH-like material may affect immune responses.

Adrenocorticotropic Hormone↗
PubMed1992

MK-801 protects retinal neurons from hypoxia and the toxicity of glutamate and aspartate.

The protective effect of the anticonvulsant MK-801 and the antitussive dextromethorphan, which are both N-methyl-D-aspartate receptor antagonists, and kynurenic acid, a broad-spectrum excitotoxin antagonist, was tested in cultured rat retinal cells in an hypoxic environment. The protective effect of these antagonists also was tested in cultured retinal cells and in intact adult rat retinas exposed to the exogenous excitotoxins L-glutamic acid and N-methyl-D-aspartic acid. MK-801 and kynurenic acid protected retinal neurons from hypoxic damage and from the toxicity of exogenous L-glutamic acid and N-methyl-D-aspartic acid. Dextromethorphan, a less potent antagonist, did not protect the retinal neurons from hypoxic damage or the toxicity of exogenous L-glutamic acid, but did attenuate N-methyl-D-aspartate toxicity. These results provide evidence that the synaptic release of excitatory transmitters, most likely glutamate and aspartate, mediate the death of hypoxic retinal neurons. Compounds related to MK-801 may have possible therapeutic applications in the management of retinal ischemia.

Animals↗
PubMed1991

Internal capsule plaque and tonic spasms in multiple sclerosis.

A patient developed hemilateral tonic spasms associated with a relapse of multiple sclerosis. An area of demyelination in the right internal capsule was observed on a magnetic resonance imaging scan. This lesion was not detectable on a second magnetic resonance imaging scan 10 months after the spasms had ceased. Paroxysmal symptoms in multiple sclerosis may represent transient phenomena related to inflammation in acute plaques.

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↗
PubMed1991

Interferon-gamma and tumour necrosis factor induce expression of major histocompatibility complex antigen on rat retinal astrocytes.

Cultured rat retinal astrocytes were tested by indirect immunofluorescence staining for their ability to express class I and II major histocompatibility complex (MHC) antigens under basal culture conditions and after three days of stimulation with two recombinant cytokines, rat interferon-gamma (IFN-gamma) and human tumour necrosis factor alpha (TNF alpha). Under basal culture conditions low levels of class I antigens were detected on a small percentage of cells, but there was no visible class II. IFN-gamma and TNF alpha stimulation enhanced class I expression. TNF alpha had no effect on class II expression, whereas IFN-gamma induced the expression of class II in a dose dependent manner. These findings suggest that retinal astrocytes might play a part in immunological events occurring in the retina.

Animals↗
PubMed1991

Soluble CD8 levels in the CSF and serum of patients with multiple sclerosis.

CD8 is a membrane glycoprotein of 34 kd on cytotoxic/suppressor T lymphocytes and is an endogenous ligand for MHC class I proteins on target cells. CD8 is released in a soluble form upon T-lymphocyte activation. In multiple sclerosis (MS), T lymphocytes exhibit decreased membrane expression of the CD8 molecule and defective suppressor function. We measured soluble CD8 (sCD8) levels in the CSF of patients with MS, other inflammatory neurologic diseases (INDs), and noninflammatory neurologic diseases (NINDs). sCD8 levels in the CSF of MS and IND patients were elevated compared with NIND patients. Patients with acute infections of the CNS showed the highest absolute values of sCD8, but the amount of sCD8 per CSF white blood cell was greatest in MS and NIND patients. We found no difference in serum sCD8 levels among the groups. In MS, the combination of increased CSF sCD8 levels and sCD8 per cell may reflect CD8 T-lymphocyte activation within the brain or immunodysregulation confined to the CNS.

Antigens, CD↗
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↗
PubMed1988

Comparison of in vivo and in vitro glucocorticoid sensitivity in depression: relationship to the dexamethasone suppression test.

The effect of in vivo (1 mg) and in vitro (10(-7)-10(-10) M) dexamethasone administration on mitogen-induced lymphocyte proliferation was examined in drug-free depressed patients, nondepressed psychiatric patients, as well as normal controls, and was related to the results of a standard overnight Dexamethasone Suppression Test (DST). The effect of oral dexamethasone administration was also examined for its effect on lymphocyte cytosolic glucocorticoid receptor content. Oral dexamethasone administration significantly decreased both phytohemagglutinin (PHA) and concanavalin A (Con-A) induced lymphocyte proliferation, as well as glucocorticoid receptor number in suppressors, whereas dexamethasone failed to decrease these responses in nonsuppressors. Nonsuppressors had significantly lower serum dexamethasone levels compared to suppressors at both 8:00 AM and 4:00 PM. However, when differences in serum dexamethasone levels were covaried out, there were still significant differences between suppressors and nonsuppressors on the dexamethasone-induced mitogen changes, but the changes in glucocorticoid receptor content were no longer significant. In vitro incubation of lymphocytes with dexamethasone produced a dose-related decrease in mitogenesis, which was not different between the depressed and nondepressed groups. However, at physiologically relevant concentrations of dexamethasone (10(-9)-10(-10) M), nonsuppressors as compared to suppressors were more resistant to the immunosuppressive effects of in vitro dexamethasone on the Con-A response. The inhibitory effect of in vitro dexamethasone on Con-A-stimulated lymphocytes was positively correlated with basal 4:00 PM cortisol values. In conclusion, in vitro techniques are useful probes to assess glucocorticoid sensitivity in depression. The present results also further support the hypothesis that glucocorticoid insensitivity is associated with DST nonsuppression.

Adult↗
PubMed1987

Susceptibility of astrocytes to class I MHC antigen-specific cytotoxicity.

Cell-mediated immune mechanisms contribute to tissue injury within the central nervous system (CNS) in a number of experimental diseases, including experimental allergic encephalomyelitis and some viral infections, and may mediate lesion formation in multiple sclerosis. We investigated the conditions under which murine astrocytes can become susceptible targets of cytotoxic T cells. We demonstrate that mouse astrocytes in vitro can be susceptible targets of class I major histocompatibility complex (MHC)-specific cytotoxicity mediated by L3 cytotoxic T lymphocytes (CTL). Expression of appropriate class I MHC antigen on the astrocytes is a requirement, because only cells bearing the H-2d phenotype are susceptible to lysis by L3 cells. BALB/c-H-2dm2 astrocytes lacking the specific determinant recognized by L3 cells are not susceptible to lysis. Astrocyte lysis can, however, occur under culture conditions in which MHC antigen expression is immunocytochemically low or undetectable. Cytolysis can be inhibited by pretreatment of the effector L3 cells with either anti-Lyt-2 monoclonal antibody (mAb) or anti-clonotypic mAb and by preincubation of the glial target cells with an appropriate anti-H-2 antibody (anti-H-2Ld). mAb to lymphocyte function-associated antigen does not inhibit cytotoxicity of the L3 clone against glial cells. Knowledge regarding the role of CTL within the CNS, including the surface molecules involved in glial cell lysis, could further the development of immunotherapies designed to effect immune reactivity within the CNS.

Animals↗