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Biomedical subjects

B Zweiman

Publications and source records attributed to B Zweiman.

At least 127 records · Page 7Linked to original sources

Quantitation by myeloperoxidase assay of neutrophil accumulation at the site of in vivo allergic reactions.

Skin window techniques to investigate neutrophil inflammatory reactions in human skin have been limited by cellular distortion and difficulties in quantitation. We have developed a quantitative approach based on the assessment of the myeloperoxidase (MPO) released from sonicated membrane filters to which exuding inflammative cells had adhered. Our studies have shown that (1) a standard curve can be derived for each subject from the linear relationship between amounts of MPO released and designated numbers of blood neutrophils which have been aspirated onto such filters; (2) the number of neutrophils adhering to filters appended to skin window sites can then be reliably estimated by comparing the amount of MPO released by sonication of such filters with the standard curve; and (3) neutrophil accumulation is greater at pollen-challenged than control sites in sensitive subjects.

Cell Count↗

Effect of treatment with Copolymer 1 (Cop-1) on the in vivo and in vitro manifestations of experimental allergic encephalomyelitis (EAE).

Injections of Copolymer 1 (Cop-1), a synthetic cathodic polymer, have been reported to prevent and treat successfully acute and recurrent EAE and has been employed in patients with multiple sclerosis (MS). It has been suggested that the therapeutic effect is due to cell-mediated immune (CMI) cross-reactivity between Cop-1 and myelin basic protein (MBP), the antigen that induces EAE. We found that Cop-1 treatment of guinea pigs (GP) sensitized with MBP in adjuvant (20 micrograms/animal): (a) lowers the incidence of clinical disease (8/20 vs 14/15); (b) decreases severity of disease in affected GP; (c) has little effect on pathologic lesions (mean pathology index +/- SEM: 1.2 +/- 0.2 vs 1.6 +/- 0.3; P greater than 0.1). Lymphocytes of MBP-sensitized GP treated with Cop-1 exhibited in vitro proliferative responses to MBP equivalent to lymphocytes of untreated EAE-GP (14,134 +/- 6,532 vs 11,821 +/- 3,874; mean cpm +/- SEM). GP sensitized to MBP or Cop-1 (100 micrograms/animal) showed reactivity to the sensitizing antigen but little in vitro reactivity to the other antigen. There was no correlation between the in vitro lymphocytes response to MBP and Cop-1 in individual GP. Treatment of MBP sensitized GP with calf-thymus histone (CTH) also resulted in a lower incidence of clinical EAE with less severe disease in affected GP. There was little effect on the pathologic index and no evidence of either inhibition of MBP-induced lymphocyte proliferative responses or cross-reactivity between MBP and CTH. Thus, treatment with Cop-1 or CTH inhibits clinical manifestations of acute EAE without suppressing inflammatory cell infiltrates or sensitization to MBP.

Animals↗

Antigen-induced local mediator release and cellular inflammatory responses in atopic subjects.

We report comparisons of histamine release and neutrophil exudation in skin-window sites of 27 pollen-sensitive subjects challenged with antigen or buffer. More histamine was released within 30 min into appended collection chambers in antigen sites vs control sites. There were also more neutrophils adhering to membrane filters applied for 1 hr to the blister bases in antigen-challenged sites vs buffer sites. Comparison of skin-test extinction dilution titer, histamine release, and neutrophil accumulation in antigen-challenged sites in individual subjects showed that (1) there was no correlation between degrees of local histamine and neutrophil accumulation, (2) the increase in histamine but not in neutrophils correlated inversely with the concentration of antigen required to elicit a minimum wheal, and (3) both histamine and neutrophil increases were induced by antigen in a dose-dependent manner.

Adult↗

Terbutaline modulation of human allergic skin reactions.

Terbutaline, a preferential beta 2-adrenergic agonist, has been shown to inhibit allergen-induced histamine release in vitro. In contrast, orally administered therapeutic doses of terbutaline do not inhibit antigen-induced wheal and flare reactions. We studied the effects of local terbutaline on antigen-induced whealing response, histamine release, cellular inflammatory response, and ultramicroscopic mast cell changes in antigen-challenged skin sites in ragweed-sensitive subjects. Results showed that ragweed challenge significantly induced increased histamine release in all subjects. In contrast, no such histamine release was observed at sites challenged with antigen in the presence of terbutaline. Thus locally applied terbutaline in nontoxic doses modulates mediator release in certain allergic reactions.

Biopsy↗

Cromolyn does not modulate human allergic skin reactions in vivo.

Cromolyn pretreatment frequently reduces antigen inhalation-induced bronchospasm possibly by inhibiting mast cell degranulation and mediator release. However, the local effects of cromolyn on type I hypersensitivity skin reactions are not well understood. We studied the effect of local cromolyn on antigen-induced skin reaction, histamine release, cellular inflammatory response, and ultramicroscopic changes of mast cells in 10 ragweed-sensitized subjects. Results showed that cromolyn 2% (nonirritant dose) does not modulate ragweed-induced skin whealing response, histamine release, and ultramicroscopic changes of mast cells. Thus, unlike the situation in the tracheobronchial tree, allergic skin reactions and associated events are not inhibited by local cromolyn application.

Adult↗

Effect of cimetidine on exogenous histamine inhibition of histamine release in vivo.

We previously reported that exogenous histamine inhibits in vivo histamine release and eosinophil accumulation in ragweed-challenged skin sites of sensitive human subjects. The mechanism(s) involved were unclear. In this study, we repeated similar approaches in four of the same subjects pretreated for 3 days with cimetidine, an H2 receptor antagonist. The pattern of exogenous histamine effects was now different in that local exogenous histamine (50 ng/ml) did not significantly alter ragweed-induced mast cell alteration, histamine release, or the degree of eosinophil accumulation in skin challenge sites. These findings suggest that the observed exogenous histamine inhibitory effects may be mediated through the H2 receptor.

Biopsy↗

Staphylococcal peptidoglycan: T-cell-dependent mitogen and relatively T-cell-independent polyclonal B-cell activator of human lymphocytes.

Staphylococcal cell wall products have been widely examined as probes for dissection of in vitro human immune responses. Mitogenic and polyclonal B-cell-activating properties have been attributed to intact cell walls or the protein A constituent thereof. We now report that staphylococcal peptidoglycan (PG), the major cell wall constituent, is not only a potent mitogen but also a polyclonal B-cell activator for human peripheral blood mononuclear cells (PBM). PG-induced proliferative responses of human PBM were comparable to that observed in pokeweed mitogen-stimulated cultures. As was true for pokeweed mitogen, PG-induced proliferation required the presence of T-cell help. Cultures of human PBM with PG also resulted in B-cell differentiation as reflected by an increase in numbers of immunoglobulin-secreting cells in stimulated cultures. In contrast to the proliferative response, PG-induced B-cell differentiation was relatively T-cell independent. This point became apparent when B-cell fractions were partially depleted of excessive numbers of monocytes before culture. Also, B-cell proliferation did not appear to be a major prerequisite for PG-induced B-cell differentiation responses. These data indicate that PG is a potent T-cell-dependent mitogen and relatively T-cell-independent polyclonal B-cell activator of human lymphocytes.

B-Lymphocytes↗

Analysis of B-cell activation of cerebrospinal fluid lymphocytes in multiple sclerosis.

We have developed a microculture system to study pokeweed mitogen (PWM)-induced B-cell differentiation responses of CSF lymphocytes from patients with multiple sclerosis (MS) and other neurologic diseases (OND). B-cell differentiation was assessed by (1) enumeration of immunoglobulin-secreting cells (IgSC) by a protein A reverse hemolytic plaque assay; and (2) quantitation of supernatant IgG by ELISA. Cultures of MS CSF cells and OND CSF cells responded to PWM with a similar frequency, with responses in CSF cell cultures exceeding responses in corresponding blood cell cultures in several instances in both groups of patients. Numbers of IgSC in unstimulated cultures of MS CSF cells exceeded numbers in cultures of autologous peripheral blood mononuclear cells (PBM). Results suggest that CSF cells may be a particularly reactive population compared with PBM.

B-Lymphocytes↗

Immune reactions to P2 protein in human inflammatory demyelinative neuropathies.

The significance of immune reactions against peripheral nervous system antigens in the human inflammatory polyneuropathies is still uncertain. Using a very sensitive assay, we found greatly increased levels of anti-P2 antibodies in sera of animals with experimental allergic neuritis (EAN) but no increases in humans with acute Guillain-Barré syndrome (GBS), chronic relapsing polyneuritis (CRIP), axonal neuropathy, or normals. P2 protein and CNS basic protein did not induce any increased proliferation in lymphocytes of GBS or CRIP patients. We conclude that P2 and BP appear unlikely to be targets for humoral or cellular immune reactivity in GBS or CRIP.

Adolescent↗

In vitro synthesis of antibodies to acetylcholine receptor by peripheral blood mononuclear cells of patients with myasthenia gravis.

We studied the in vitro synthesis of antibodies to acetylcholine receptor (anti-AChR) by peripheral blood mononuclear cells (PBM) of patients with myasthenia gravis (MG) and normal subjects (NS). PBM from three of eight patients with generalized MG (MG-G) synthesized anti-AChR in vitro in the absence of pokeweed mitogen (PWM), and seven of eight did so in the presence of PWM. In individual subjects with MG-G, the levels of anti-AChR secreted in vitro by PBM correlated with serum anti-AChR antibody levels (r = 0.77) but not with the amount of IgG secreted in vitro (r = 0.44). No anti-AChR secretion was seen in culture of PBM from a patient with ocular MG, a patient with thymoma without MG, or six NS.

Adult↗

Thymic lymphocyte subpopulations in myasthenia gravis.

We compared the percentages of thymic mononuclear cells (TMC) that bind monoclonal antibodies to T-cell subpopulations in patients with myasthenia gravis (MG) and non-MG patients undergoing cardiac surgery (CS). There were no significant differences in percentages of OKT3+, OKT4+, OKT6+, or OKT8+ cells or the OKT4:OKT8 ratio. There was an increase in the percentage of Ia+ (immune response gene-associated antigen) TMC in MG compared with CS but no significant differences in B cells or phagocytic cells. The Ia+ cells could be abnormal B cells, activated T cells, or thymic dendritic cells.

Adult↗

Monoclonal antibody analysis of blood T-cell subsets in myasthenia gravis.

Analysis of peripheral blood T -cell subsets and B-cells in patients with myasthenia gravis was performed using monoclonal antibodies and antibody against surface immunoglobulins (SIg) in an immunofluorescent technique. We found a modest but significant decrease in percentages of OKT3- and OKT8-positive cells (thought to represent total T-cells and T-suppressor/cytotoxic cells, respectively) in myasthenics as a group. The percentage of OKT3-positive cells was significantly decrease in patients with late-onset disease (greater than 35 years old), while the percentage of OKT8-positive cells was significantly reduced in those with early-onset myasthenia (greater than 35 years old). Both thymectomized and nonthymectomized patients exhibited a decreased percentage of OKT3-positive cells. No significant difference was found between the percentages of SIg-positive cells in myasthenics and controls. Our results suggest that only modest imbalances of circulating immunoregulatory lymphocytes occur in myasthenia gravis; however, it is conceivable that the small differences observed in this study may reflect pathogenetically important reductions in a functionally distinct lymphocyte subpopulation.

Adolescent↗

Oligoclonal IgG in the cerebrospinal fluid of guinea pigs with acute experimental allergic encephalomyelitis.

The cerebrospinal fluid (CSF) of guniea pigs with experimental allergic encephalomyelitis was examined for the presence of oligoclonal IgG using polyacrylamide gel electrophoresis. Oligoclonal IgG (greater than or equal to 2 bands) was seen in the CSF obtained from 3/4 animals with experimental allergic encephalomyelitis induced by myelin basic protein and 2/3 with spinal cord-induced disease. It was not seen in CSF of 3 non-sensitized, 4 adjuvant-sensitized and 7 liver-sensitized guinea pigs. Scanning of stained gels confirmed the oligoclonal pattern. The bands were found in the region of gels which bound [125I]Staphylococcal Protein A. The data demonstrate that a non-infectious inflammatory reaction within the central nervous system can result in an oligoclonal IgG pattern in the CSF.

Animals↗