Search PubMed⌕ Search

Biomedical subjects

B Zweiman

Publications and source records attributed to B Zweiman.

At least 145 records · Page 8Linked to original sources

Antigen-induced neutrophil chemotactic activity from sensitized lung.

We have used the model of ovalbumin-sensitized guinea pigs to define the source of antigen-derived, high-molecular-weight neutrophil chemotactic activity (NCA). Incubating sensitized lung fragments with specific antigen (ovalbumin) but not irrelevant antigen (bovine serum albumin) or buffer resulted in the release of high-molecular-weight NCA and histamine, suggesting a lung mast cell origin for NCA. High-molecular-weight NCA accounted for greater than 90% of the NCA observed after antigen-lung incubation. The importance of high-molecular-weight NCA in recruitment of neutrophilic leukocytes to the site of allergic inflammatory reactions is emphasized.

Animals↗

Plasma concentrations of histamine measured by radioenzymatic assay: effects of histaminase incubations.

To help resolve the current uncertainty as to whether assays for plasma histamine are measuring non-histamine compounds as well, we compared the effects of prior incubation with histaminase and buffer on measurements in (1) normal plasma, (2) buffer and normal plasma to which several amounts of exogenous histamine had been added, and (3) plasma obtained after inhalation-induced asthma or form the site of a local heat urticaria challenge. As measured by the radioenzymatic technique, low (1 to 4 ng/ml) levels of histamine-like material were present in normal plasma after incubation with either histaminase or buffer. In contrast, histaminase (but not buffer) incubation markedly reduced measured histamine in all other specimens. Exogenous histamine in buffer was reduced almost 100% by histaminase, whereas the degree of reduction in plasma specimens varied directly with the starting histamine level. Therefore it appears that low levels of histaminase-resistant material reacting in histamine assays is present in normal plasma. The use of histaminase incubation appears to be helpful in differentiating this from true histamine release in allergic reactions.

Amine Oxidase (Copper-Containing)↗

Antibodies to P2 and P1 myelin antigens in experimental allergic neuritis and allergic encephalomyelitis.

We confirmed earlier observations that experimental allergic neuritis (EAN) in Lewis rats induced by injection of bovine peripheral nerve myelin in complete Freund's adjuvant is not accompanied by development of experimental allergic encephalomyelitis. However, sera of these animals contained elevated titers of antibodies against central nervous system myelin basic protein (BP), likely induced by peripheral nerve P1 protein. Anti-BP antibodies were not seen in sera of rats with EAN induced by peripheral nerve P2 protein. Lack of encephalogenicity of bovine myelin in Lewis rats does not reflect simply lack of immune responses induced against BP.

Animals↗

Long-term growth in vitro of human cerebrospinal fluid T lymphocytes.

Investigations of central nervous system cellular immune reactivity in human disease, as reflected in the responses of cerebrospinal fluid lymphocytes, have been limited primarily due to the low numbers of cerebrospinal fluid lymphocytes available during routine diagnostic lumbar punctures in normal individuals and most patients with demyelinating diseases. We report the use of a T-cell growth factor generated by by phytochemagglutinin-stimulated, irradiated normal peripheral blood lymphocytes to maintain long-term proliferating cultures of human cerebrospinal fluid lymphocytes. Cerebrospinal fluid lymphocytes. Cerebrospinal fluid T-cell cultures were initiated from 10 to 14 cerebrospinal fluid samples with up to 5000-fold expansion of initial cell numbers. Few, if any, macrophage or surface immunoglobulin-bearing cells were present, while 80 to 90% of the cultured cells were T cells as demonstrated by rosette formation with sheep red blood cells. Mixed lymphocyte cultures with cultured cerebrospinal fluid T cells and irradiated, freshly isolated allogeneic peripheral blood lymphocytes yielded a positive response in four of the five cultures tested.

Cerebrospinal Fluid↗

Inhibitory effects of corticosteroids and histamine on human lymphocytes.

Both corticosteroids and histamine inhibit mitogen-induced lymphocyte proliferation. Their mechanisms of inhibition were studied in lymphocytes exposed to methylprednisolone (MP) both in vivo and in vitro. Either in vivo MP treatment or in vitro histamine incubation depressed lymphocyte responsiveness to mitogen stimulation. The combination of both treatments depressed the proliferative responses to a further degree, representing a shift of baseline proliferation by in vivo MP treatment. For in vitro MP studies, normal lymphocytes cultured with varying concentrations of MP were significantly less stimulated by phytohemagglutinin (PHA) and concanavalin A (Con A). Addition of histamine (1 x 10(-3) M) as well as MP in vitro led to a further inhibition of proliferative responses of these cells in an additive pattern in cultures of all MP concentrations. Normal lymphocytes incubated in vitro with histamine, but not with MP, resulted in a rapid rise in intracellular cyclic adenosine monophosphate (cAMP). These findings suggest that corticosteroid and histamine act independently through different mechanisms.

Adrenal Cortex Hormones↗

Histamine suppression of in vivo eosinophil accumulation and histamine release in human allergic reactions.

Although it has been shown that histamine inhibits antigen-induced in vitro histamine release from basophils, it is unclear whether histamine inhibits in vivo mediator release in human allergic reactions. We report effects of exogenous histamine on histamine release and inflammatory cell responses in antigen-challenged skin sites in eight ragweed-sensitive individuals. Four heat-suction blisters in each subject were unroofed, and a collection chamber was appended to each blister base. Chamber A contained 1000 PNU/ml ragweed extract; chamber B contained buffered saline (control fluid); chamber C contained 1000 PNU/ml ragweed and 50 ng (5 x 10(-7) M) of histamine; and chamber D contained histamine alone (50 ng). Comparative analyses of chamber histamine levels in individual subjects showed that (1) histamine levels in chamber A were significantly greater than those in chamber B (p less than 0.01) and that histamine levels in chamber C were not significantly different than those in chamber D (p less than 0.5). Likewise, comparison of eosinophils attaching to membrane filters appended to the chamber bases for 2 hr showed that there were significantly more eosinophils in chamber A than in chamber B (p less than 0.01) and that there was no significant difference in eosinophil numbers on filters appended to chamber C vs chamber D. In three of four subjects studied, addition of exogenous histamine (50 ng/ml) to ragweed before intradermal injection inhibited the ultrastructural mast cell alterations seen within 10 min after injection of ragweed alone. In the one subject in which mast cell alterations were not prevented, exogenous histamine also did not inhibit antigen-induced histamine release or subsequent eosinophil accumulation in the skin chambers.

Eosinophils↗

Mediator release in local heat urticaria.

We described the sixteenth reported case of local heat urticaria, in a 59-yr-old woman with erythema and angioedema upon contact with hot water or outdoor heat exposure. Immersing her hand in 39 degrees to 40 degrees C heated water resulted in an erythematous, angioedematous response sharply demarcated by the line of immersion and was associated with immediate increases in histamine concentration (18 to 135 ng/ml) and high molecular weight neutrophil chemotactic activity (two to five times prechallenge levels) in venous blood draining the challenge site. We suggest that the local heat urticarial response in this woman was a form of physical urticaria associated with release of mast cell-derived mediators, akin to cold and cholinergic urticaria.

Angioedema↗

Spinal fluid basic protein immunoreactive material and spinal fluid lymphocyte reactivity to basic protein.

Levels of cerebrospinal fluid (CSF) basic protein (BP) immunoreactive material and CSF lymphocyte in vitro reactivity to BP were determined in patients with demyelinating and other inflammatory diseases of the nervous system. Elevated levels of BP and enhanced in vitro reactivity were observed, but there was no correlation between the magnitude of the in vitro response and the amount of BP-like material in CSF.

Demyelinating Diseases↗

Polyclonal B-cell activity in myasthenia gravis.

Using a protein A-reverse hemolytic plaque assay, we found that some patients with myasthenia gravis have increased numbers of circulating immunoglobulin secreting cells (IgSC). This pattern was not related to drug therapy, age, sex, duration of symptoms, thymectomy, or serum levels of AChR antibody, although elevated IgSC values tended to occur in patients with active symptoms. The responses of peripheral blood mononuclear cells to pokeweed mitogen were normal. These data suggest increased in vivo polyclonal B-cell activation in some myasthenic patients, although in vitro polyclonal B-cell activation is normal.

Acetylcholine↗

Heterogeneity of polyclonal B-cell activity in systemic lupus erythematosus.

We have examined the abnormal in vitro polyclonal B-cell activity observed in patients with systemic lupus erythematosus (SLE) using a staphylococcal protein A reverse hemolytic plaque assay. We have found the mean level of circulating immunoglobulin secreting cells (IgSC) in 30 SLE patients to be significantly elevated compared to that of normal subjects, although half of the SLE patients fell within the normal range. Cultures of SLE peripheral blood mononuclear cells (MC) stimulated with optimal or suboptimal doses of pokeweek mitogen (PWM) showed depressed IgSC responses as a group, compared to cultures of normal MC (p less than 0.005), although a fraction of patients had normal responses. In 11 of 30 SLE patients, IgSC were less numerous in stimulated than in unstimulated cultures, whereas all normal subjects showed augmented IgSC response in stimulated cultures (p less than 0.005). Impaired in vitro response was not due to (1) altered PWM induced activation, (2) aberrant kinetic response or (3) decreased survival in culture of SLE MC. Of note, altered IgSC responses did not appear to reflect antecedent in vivo B-cell activation. Numbers of circulating IgSC and PWM-induced IgSC were not correlated with clinical and serological indices of disease activity or status of corticosteroid therapy. These data indicate considerable heterogeneity with respect to polyclonal B-cell activity in SLE, and provide further insight into the relationships of in vivo and in vitro B-cell activation in patients with this disease.

Antibody-Producing Cells↗

In vivo release of eosinophil chemoattractant activity in human allergic skin reactions.

A search was made for in vivo release of factor(s) that may be responsible for prominent eosinophil accumulations in human allergic skin reactions. Using a specially designed skin chamber appended to the base of unroofed skin blisters, we have found at ragweed-challenged sites in sensitive subjects the release of significantly greater histamine (15 +/- 3 ng/ml) than at control sites (3 +/- 0.5 ng/ml). Eosinophil accumulation after 2 hr was also significantly greater on membrane filters appended to ragweed-challenged sites than control sites (55 +/- 15 vs 4 +/- 0.5). Intradermal injection of ultrafiltrates of the chamber fluids from antigen-challenged sites, but not of fluids from control sites, induced prominent eosinophil accumulation (mean = 25/mm2) when injected intradermally in autologous uninvolved skin. Neither ultrafiltered antigen solution nor histamine (employed in concentrations similar to those released in the chambers) evoked such in vivo responses when injected intradermally in the same subjects (mean = less than 1/mm2). The eosinophil responses to injected ultrafiltered chamber fluid from antigen-challenged sites peaked at 30 min, whereas even greater eosinophil responses to unaltered antigen started after 60 min. These findings suggest that in vivo release of a low m.w. factor or factors other than histamine is very likely responsible for at least part of the in vivo eosinophil accumulation in human allergic reaction sites. Additional findings suggest that a significant portion of the time lag between intradermal antigen and dermal eosinophil accumulation is encompassed by local mediator release.

Asthma↗

Comparison of plasma histamine and cyclic nucleotides after antigen and methacholine inhalation in man.

Serial determinations of plasma histamine and cyclic nucleotides (adenosine monophosphate [AMP] and guanosine monophosphate [GMP]) were performed after inhalation of antigen and methacholine in four groups of subjects. In the first group, consisting of six antigen-sensitive subjects exhibiting bronchospasm after inhalation of ragweed or grass antigen, plasma histamine was elevated within 2 min and persisted for 30 min after inhalation of antigen. Peak histamine levels were between 18 to 80 ng/ml. In the second group, consisting of four nonatopic subjects, neither bronchospasm nor histamine was observed, despite inhalation of the same or 10-fold increased concentrations of antigen. In the third group, consisting of six subjects (three atopic and three nonatopic) exhibiting bronchospasm after inhalation of 2.5 to 10 mg of methacholine, sustained increases of histamine began at 1 min and persisted for 60 min after inhalation of methacholine. In the fourth group, seven subjects (two atopic, five nonatopic) without demonstrable bronchospasm despite inhalation of 2.5- to 10-fold increased doses of methacholine, no histamine was detected in the plasma at any time after inhalation of methacholine. Serial measurements of cyclic nucleotides showed no consistent changes in serum levels of cyclic AMP or cyclic GMP following inhalation challenge. We conclude that serum levels of histamine but not cyclic nucleotides change during bronchospasm induced by either antigen or methacholine.

Adult↗

Effects of theophylline, terbutaline, and prednisone on antigen-induced bronchospasm and mediator release.

Eleven subjects demonstrating clinical, skin, and inhalation sensitivity to grass or ragweed pollen underwnet serial inhalation challenges, with and without orally administered theophylline, terbutaline, and prednisone. Comparisons of antigen sensitivity and mediator release were made during these challenges. All three drugs significantly reduced antigen sensitivity (PD20 inhalation units increasing from 670 to greater than or equal to 3,280). Peak plasma histamine levels after antigen challenge decreased from 11.4 ng/ml to less than or equal to 3.4 ng/ml during all drug administrations. Similarly, the percent increase in serum neutrophil chemotactic activity (NCA) also decreased, from 96% to less than or equal to 36% during drug administrations. However, even at antigen doses resulting in bronchospasm during drug administration the systemic appearance of NCA and histamine were reduced. We conclude that prednisone, theophylline, and terbutaline significantly reduce antigen-induced bronchospasm and mediator release. The occurrence of bronchospasm despite the inhibition of histamine and NCA suggests either that the local concentration of these mediators are critical or that other mediators produce the bronchospasm observed.

Adult↗

Patterns of mast cell alterations and in vivo mediator release in human allergic skin reactions.

Patterns of in vivo histamine release in skin sites challenged with ragweed antigen were compared in five human subjects sensitive to this antigen and four nonallergic individuals, using a newly developed skin-chamber technique. These findings were compared with inflammatory cell responses in the reaction sites and patterns of ultramicroscopic mast cell alterations in biopsy specimens of skin tests in the same subjects. Definite mast cell alterations occurred within 15 sec and appeared maximal within 5 to 10 min after antigen injection. Histamine levels in appended chambers increased after a lag of 10 to 30 min and were elevated for at least 60 min after antigen challenge. Eosinophils accumulated only in antigen-induced reaction sites. However, there was no precise quantitative correlation among the degree of change in these three measurements. These appear to be promising approaches to further in vivo studies of human allergic reactions.

Antigens↗

In vivo and in vitro effects of methylprednisolone on human lymphocyte proliferation.

Lymphocytes obtained from normal volunteers 4 hr after intravenous methylprednisolone (1 mg/kg of body weight) were significantly less stimulated in vitro by several concentrations of phytohemagglutinin and concanavalin A. This effect was not due to diurnal variations. Significant decreases in the levels of circulating T lymphocytes (p < 0.001) at this time suggested cellular redistribution as a factor in decreased mitogen responsiveness. However, incubation of plasma, obtained 1 hr after methylprednisolone injection, with normal autologous lymphocytes suppressed the in vitro responses as well, indicating an additional direct corticosteroid effect on the lymphocytes.

Adult↗