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Biomedical subjects

B Zweiman

Publications and source records attributed to B Zweiman.

At least 91 records · Page 5Linked to original sources
PubMed1987

Neutrophil activation in human inflammatory skin reactions.

To determine the functional activity of neutrophils emigrating to the sites of ongoing human allergic inflammatory reactions, we assessed the intensity of their intracellular oxidative metabolism by measuring the intracellular oxidation by H2O2 of the dye, 2',7'-dichlorofluorescein diacetate (DCFH-DA), to fluorescent 2',7'-dichlorofluorescein. The intensity of intracellular fluorescence was measured by flow cytometry. In 13 atopic subjects, two denuded skin blister bases were challenged for 5 hours with pollen antigen and two blister bases with buffer. Both the level of histamine and mean number of cells recovered at antigen sites were greater than at buffer sites. Oxidation of DCFH-DA by neutrophils recovered from both antigen and buffer sites was significantly greater than that of autologous peripheral blood neutrophils (PBNs), reflecting an increase in the spontaneous generation H2O2 of cells recovered from the sites of inflammation. DCFH-DA oxidation by cells recovered from sites of antigen incubation was significantly greater than cells from buffer site incubations. Neutrophils from both antigen and buffer sites could be stimulated further in vitro by phorbol myristate acetate to the same level of H2O2 generation as phorbol myristate acetate-stimulated PBNs. In five subjects studied, the noncellular component of chamber fluids collected at 1 and 5 hours stimulated PBNs to increase their oxidative metabolism by 42% to 62%; however, this increased level of intracellular H2O2 was still much less than the spontaneous H2O2 generation observed in cells recovered from sites of allergic inflammation. The increased oxidative metabolism of neutrophils in human allergic and inflammatory skin reactions has important pathophysiologic implications for the role of these cells in inflammatory responses.

Adult↗
PubMed1987

Release of tryptase together with histamine during the immediate cutaneous response to allergen.

Better in vivo techniques are needed for objective assessment of mast cell-dependent events. Tryptase, a neutral protease selectively concentrated in human mast cells, appears along with histamine in skin chamber fluid overlying sites of allergen challenge in sensitive human subjects. Maximal amounts of histamine were found 0 minutes to 30 minutes after challenge; maximal amounts of tryptase were found 30 minutes to 60 minutes after challenge. The later appearance of tryptase most likely reflects its slower diffusion through tissue after release of tryptase from cutaneous mast cells as a macromolecular complex with proteoglycan. The mean weight ratio of tryptase (134,000 molecular weight tetramer) to histamine (111 molecular weight) in chamber fluid after allergen challenge during a 1-hour time course was 4:1. Total amounts of tryptase and histamine recovered in the 0.3 ml chamber fluid samples after a 1-hour challenge averaged 95 ng and 26 ng, respectively. Tryptase levels in skin chamber fluid are an accurate indicator of mast cell activation.

Adolescent↗
PubMed1987

In vivo effects of corticosteroids on human allergic responses. I. Effects of systemic administrations of steroids.

In order to better understand the effects of corticosteroids in allergic disease, the relative degrees of allergen-induced cutaneous histamine release and granulocyte accumulation were evaluated in atopic volunteers following intravenous placebo or methylprednisolone administration. In nine subjects, a single intravenous dose of methylprednisolone (1 mg/kg) did not inhibit histamine release but did significantly reduce granulocyte accumulation at both allergen and buffer-challenged sites during five and one-half to six and one-half hours following steroid injection. These findings suggest that the corticosteroid-induced anti-inflammatory effects at allergic reaction sites do not include inhibition of local mediator release. Furthermore, the steroid-induced inhibition of inflammatory cell accumulation is not specific for the allergic reaction.

Administration, Oral↗
PubMed1987

Eosinophilic fasciitis with atypical features.

Eosinophilic fasciitis has been reported to be a syndrome distinct from progressive systemic sclerosis, due to the absence of Raynaud's phenomenon, visceral disease, and autoantibodies as well as steroid responsiveness and an abnormal histopathologic appearance that primarily involves the lower subcutis and fascia. More recent studies, however, have noted considerable overlap in the clinical, pathologic, and laboratory features of these two entities. We report a case that further blurs the distinction between eosinophilic fasciitis and progressive systemic sclerosis.

Aged↗
PubMed1986

Antibodies to acetylcholine receptor and tetanus toxoid: in vitro synthesis by thymic lymphocytes.

Thymic lymphocytes (TL) of patients with myasthenia gravis (MG) have been reported to synthesize antibodies to acetylcholine receptors (anti-AChR). Incubation of TL with pokeweed mitogen (PWM), a polyclonal T cell- and monocyte-dependent activator of B cell differentiation, was reported to inhibit TL in vitro synthesis of anti-AChR. We studied the TL of 16 patients with MG without thymoma. TL of 10 of 16 patients synthesized anti-AChR in vitro without stimulation. In the presence of PWM, the amount of anti-AChR synthesized by the TL of these 10 patients increased in five, decreased in three, and was unaffected in two. There was a correlation between serum anti-AChR titer and PWM-stimulated synthesis (r = 0.87), but not with unstimulated synthesis (r = 0.33) of anti-AChR by TL. There was no correlation between the amount of synthesized anti-AChR and the amount of secreted IgG or with the percentage of B cells (surface Ig+) in the TL suspensions. TL of three age-matched cardiac surgery controls failed to synthesize detectable anti-AChR, although two of three synthesized IgG. Four patients with MG were booster immunized with tetanus toxoid (TT) 3 to 4 wk prior to thymectomy. TL of three synthesized anti-TT in vitro, whereas TL of three nonboosted MG patients failed to synthesize anti-TT. Thus, we have shown that TL of some patients with MG are capable of anti-AChR synthesis, with evidence of heterogeneity of the in vitro response, and the B cell repertoire in the thymus may, in part, reflect recent systemic immune events of the host.

Adult↗
PubMed1986

Suppressor T cells in myasthenia gravis and antibodies to acetylcholine receptor.

We cultured blood mononuclear cells of patients with myasthenia gravis both with and without removal of T8 suppressor cells. The levels of synthesized antibodies to acetylcholine receptor and IgG as well as the frequency of immunoglobulin-secreting cells were all higher in pokeweed mitogen-stimulated cultures depleted of T8+ cells. Thus, autologous suppressor cells within the T8+ population exert some regulatory control over antiacetylcholine receptor-producing cells in patients with myasthenia gravis.

Adult↗
PubMed1986

Effect of thymectomy on blood T-cell subsets in myasthenia gravis.

We studied peripheral blood mononuclear T-cell subsets in 23 patients with myasthenia gravis who had undergone thymectomy at least one year before study. An increase in the T4+/T8+ (helper-inducer/suppressor-cytotoxic cell) ratio was seen, similar to that previously reported in nonthymectomized patients with myasthenia gravis. Six patients were studied before and after thymectomy and no consistent alteration in the pattern of T-cell subsets was detected. We were not able to demonstrate a quantitative effect of thymectomy on peripheral blood mononuclear T-cell subsets in patients with myasthenia gravis.

Adult↗
PubMed1986

Humoral immune responses within the human central nervous system following systemic immunization.

We investigated sequential humoral immune responses in the CSF and blood of 6 stable multiple sclerosis (MS) patients without decreases in the blood-brain barrier. Anti-tetanus toxoid antibodies (anti-TT Ab) increased to a similar relative degree within the CSF and blood starting within 2 weeks after subcutaneous booster injection of TT. In 3 of 4 subjects, CSF lymphocytes obtained at 2 weeks secreted anti-TT Ab to the same degree as autologous blood lymphocytes when cultured with pokeweed mitogen. These findings suggest a prompt antibody response within the CSF to systemically administered antigen, not due to diffusion from the serum, with active trafficking of TT-sensitized lymphocytes into the central nervous system.

Adult↗
PubMed1986

B cell activation in multiple sclerosis.

A microtechnique was established for the study of the limited numbers of cells available in CSF. The method allowed for the determination of the number of immunoglobulin-secreting cells (IgSC) as well as the quantitation of immunoglobulin or specific antibody secreted into the culture medium. Dose-response curves and kinetic profiles for the IgSC responses induced by pokeweed mitogen (PWM), a polyclonal B cell activator, were similar for CSF cells (CSFC) and peripheral blood mononuclear cells (PBMC). When equal numbers of unstimulated CSFC and PBMC from patients with multiple sclerosis (MS) were cultured, both the number of IgSC and the amount of secreted IgG were significantly greater in CSFC cultures. The addition of PWM resulted in the differentiation of B cells among both CSFC and PBMC, as shown by an increase of both the number of IgSC and the amount of secreted IgG. Results with cultures of unstimulated cell suspensions from MS patients suggested that CSF cells from these patients may be activated in vivo. The addition of mitomycin-C treated autologous peripheral blood mononuclear cells (PBMCM) to cultures of small numbers of CSFC or PBMC resulted in an augmentation of the number of IgSC in both, whether or not they were stimulated with PWM, and also in an increased secretion of IgG into the culture supernatants. This culture system should prove useful in functional studies when limited numbers of cells are available.

B-Lymphocytes↗
PubMed1985

Transfer of experimental allergic neuritis with P2-reactive T-cell lines.

Experimental allergic neuritis (EAN) was induced in normal Lewis rats by systemic passive transfer of T-cell lines responding to P2 protein. These cells had predominantly helper phenotype and could induce EAN within 7 days following adoptive transfer. There was no anti-P2 antibody response in the recipients of the P2-reactive cells recovered from donors with high anti-P2 antibody levels. This study provides direct evidence that T cells are important for the induction of EAN. Furthermore, there was no evidence of a pathogenic role for anti-P2 antibody in passive EAN.

Animals↗