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Biomedical subjects

B Lebel

Publications and source records attributed to B Lebel.

At least 19 recordsLinked to original sources

Differences in clinical and immunologic reactivity of patients allergic to grass pollens and to multiple-pollen species. II. Efficacy of a double-blind, placebo-controlled, specific immunotherapy with standardized extracts.

The IgE response of patients only allergic to grass pollens differs from response of patients allergic to multiple-pollen species. The IgE immunoblots to orchard-grass pollens confirmed that polysensitized patients had more proteins revealed than patients only allergic to grass pollens. To determine if both groups of patients present a different response toward specific immunotherapy (IT), a double-blind, placebo-controlled study was performed in 70 patients. Patients receiving the active treatment had a rush IT with either a standardized orchard grass-pollen extract or with a standardized mixed-pollen extract prepared, depending on the sensitivity of the patients. The maintenance dose was defined as that dose effective in grass-pollen IT in previous experiments. The same equipotent maintenance dose was administered for all pollen species. Symptom-medication scores during the pollen season and nasal challenge with orchard grass-pollen grains demonstrated that grass pollen-allergic patients had a significantly improved efficacy by comparison to placebo treatment, whereas polysensitized patients had a nonsignificant improvement. Serum grass-pollen IgG was significantly increased after IT in both treated groups. This study demonstrate that the response toward specific IT differs in patients only allergic to grass pollens by comparison to polysensitized patients.

Adolescent

Clinical and immunologic reactivity of patients allergic to grass pollens and to multiple pollen species. I. Clinical and immunologic characteristics.

The heterogeneity of pollen-allergic individuals is well-known but poorly characterized. Twenty-six patients were studied to characterize their immunologic and clinical patterns. Thirteen patients were allergic only to grass pollens, and 13 other patients were allergic to grass-pollen and other pollen species, including Cupressaceae, plane tree, olive, and Parietaria. The IgE response was assessed by the titration of serum total IgE and orchard grass-specific IgE, as well as by IgE immunoblots to orchard-grass pollens. Clinical reactivity was assessed by nasal challenge with orchard-grass pollens before the pollen season and nasal and bronchial symptom-medication scores between April 1 and June 15. Pollen counts were obtained during this period of survey. Polysensitized patients had significantly increased levels of serum total and specific IgE and a greater heterogeneity of IgE immunoblots, suggesting an enhanced qualitative and quantitative IgE immune response. Polysensitized patients had nasal and bronchial symptoms occurring earlier than grass pollen-allergic individuals, confirming the priming effect caused by other plans flowering with an earlier season for both nasal and bronchial mucosa. Alternatively, the early symptoms may be attributable to the tree pollens or might reflect the higher grass-pollen IgE level in the polysensitized group. Bronchial symptoms appeared a few weeks after nasal symptoms. Nasal challenges were similar in both groups, and the severity of nasal symptoms during the season was not significantly different in both groups, suggesting that the intensity of symptoms is not related to the sensitization nor to the IgE immune response of the subjects.

Adolescent

Antigenic challenge of immunized mice induces endogeneous production of IL-3 that increases histamine synthesis in hematopoietic organs.

Antigenic challenge of Nippostrongylus brasiliensis-infected mice induces a striking increase in histidine decarboxylase (HDC) activity in both spleen and bone marrow cells. This enhancement takes place within 1 h after injection, with a maximum at 4 h and a return to pretreatment values 20 h later. It is associated with the appearance of IL-3 in the sera of these mice. In addition, the intracellular histamine content in both hematopoietic organs is concomitantly increased. A similar injection of worm Ag into normal mice has no significant effect. Comparable enhancement of HDC activity and intracellular histamine content with almost identical kinetics is promoted by i.v. injection of rIL-3 into normal mice. Moreover, HDC levels in infected mice are increased to the same extent in response to either specific antigen or rIL-3 injection. Taken together these results support the conclusion that antigenic challenge of immunized mice induces endogeneous IL-3 which, in turn, promotes a rapid increase in histamine synthesis in hematopoietic organs.

Animals

Interleukin 3 induces histamine synthesis in the human hemopoietic system.

Recombinant human interleukin 3 (rhIL-3) induces an increase in histamine production by human bone marrow, fetal liver, and cord blood cells. This phenomenon, already significant after 3 days of incubation, is strikingly enhanced following either enrichment in immature cell subpopulations or CD8+ cell depletion. It results from an increase in histamine synthesis because of 1) the low level of histamine cell content before any incubation, 2) the parallel increase in both extra- and intracellular histamine levels in response to rhIL-3, and 3) the early IL-3-induced increase in L-histidine decarboxylase (HDC; EC 4.1.1.22) activity. Moreover, rhIL-3 has no similar activity on adult peripheral blood cells, suggesting that it might be specific to the hemopoietic system.

Adult

Correlation between symptoms and the threshold for release of mediators in nasal secretions during nasal challenge with grass-pollen grains.

Nasal challenges with pollen grains represent one of the techniques of provocation. However, the clinical criteria of positivity are not clearly established. Nasal challenges with increasing numbers of orchard-grass pollen grains were performed in 60 patients allergic to grass pollens and 20 normal subjects. Before any challenge, the nose was washed three times with saline and then lactose, and 50, 150, 450, 1350, and 4050 orchard-grass pollen grains were insufflated into the nostrils until a symptom score of 5 was reached. This score was mainly based on major symptoms of allergic rhinitis, for example, rhinorrhea, nasal obstruction, sneezes, and to a lesser extent, on minor symptoms, such as pruritus, conjunctivitis, and pharyngitis. Nasal secretions were obtained after each challenge by lavage. Histamine was titrated by a radioimmunoassay with a monoclonal antibody against acylated histamine. Prostaglandin D2 (PGD2) was assayed with an enzyme immunoassay with a polyclonal antibody against PGD2 methoxamine. None of the normal subjects had a symptom score greater than 2; 55/60 patients had a positive challenge. The release of PGD2 was significantly (p less than 0.001, Kruskal-Wallis test) correlated with a symptom score of 5; 74.5% of patients had a significant release of PGD2 in nasal secretions. In contrast, although 58.2% of patients had a release of histamine in nasal secretions when the challenge was positive, the correlation with symptom scores was not significant. PGD2 in nasal secretions increased 3.7-fold after a positive nasal challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Antiallergic activity of H1-receptor antagonists assessed by nasal challenge.

Most oral drugs used for the treatment of allergic rhinitis are classified as H1-receptor antagonists, and although they represent major sales throughout the world, their mechanism of action is still poorly known. In an attempt to understand better the in vivo therapeutic effects of these drugs, a double-blind, crossover study was carried out. The study compared the effects of terfenadine and loratadine, nonsedative H1-receptor antagonists, on the immediate allergic response of the upper airways to challenge with orchard-grass pollens in 14 highly allergic subjects. Increasing numbers of pollen grains were insufflated into the nostrils, and the response of the subjects was assessed by examining symptoms and measuring the release of histamine and prostaglandin D2 in nasal secretions. Each drug was administered for a week before challenge. This study demonstrated the clinical efficacy of both drugs by comparison to that of a control day, since symptoms were observed for a significantly (p = 0.014) greater number of pollen grains. Only one patient had a significant release of histamine when they were treated with loratadine versus 10 during control day (p less than 0.0023) and six when they were treated with terfenadine (p less than 0.01). Prostaglandin D2 release occurred with a higher allergen dose when patients were treated with both drugs. This study indicates that some H1 antagonists also possess antiallergic activities.

Adult

Spontaneous and non-specific release of histamine and PGD2 by bronchoalveolar lavage cells from asthmatic and normal subjects: effect of nedocromil sodium.

Mast cells have been implicated in the pathogenesis of allergic asthma but their role in non-allergic asthma remains to be elucidated. The spontaneous and non-specific release of histamine by suboptimal doses of calcium ionophore A23187 was studied in bronchoalveolar lavage cells obtained from nine asthmatic and seven healthy individuals. Bronchoalveolar lavage was performed with saline, and total cells were incubated without any secretagogue (spontaneous histamine release) or after addition of 1.25, 2.5 and 5 microM of A23187 for 30 min (net maximal release). Histamine was titrated by using a very sensitive radioimmunoassay using a monoclonal antibody against acylated histamine. The spontaneous release was similar in asthmatic (20.6 +/- 8.2%) and healthy individuals (17.4 +/- 8.4%). The net maximal release of histamine was significantly greater in asthmatic patients (28.1 +/- 17.4%) than in normal subjects (10.3 +/- 8.9%). The release of histamine was significantly correlated to the release of PGD2 measured by enzyme immunoassay using a polyclonal antibody against methoxamine-PGD2 (Spearman rank test: 0.78, P less than 0.01). In eight subjects, the release of histamine by A23187 was studied in the presence of nedocromil sodium and it was observed that this drug significantly (P less than 0.05) decreased the net maximal release of histamine. This study shows that mast cells from asthmatic individuals have a greater releasability than those of normal subjects.

Adult

Nasal challenge with pollen grains, skin-prick tests and specific IgE in patients with grass pollen allergy.

Nasal challenges with pollen grains are as close as possible to natural pollen exposure, but they are not well documented in grass pollen allergy. Forty-four grass pollen allergic patients and ten non-allergic volunteers were tested by means of nasal challenge, quantitative skin-prick tests with a standardized orchard grass pollen extract and serum-specific IgE. Nasal challenges were performed with lactose and increasing concentrations of orchard grass pollen grains (15-3645 grains, three-fold increase). The test was considered to be positive when a symptom score over 5 was obtained, since this score had been previously correlated with the release of PGD2 in nasal secretions. All control subjects and 3/44 patients had a negative challenge. The number of orchard pollen grains required to elicit a positive challenge was 332 +/- 440 (range: 15-1215 grains) and the distribution was Gaussian. This number is higher than expected according to pollen calendars performed during the season, but owing to the priming effect of the nasal mucosa by allergens it is compatible to natural exposure. The correlation between nasal provocation tests and skin-prick test end-points was significant (P less than 0.005, Spearman rank test). Conversely there was no correlation between nasal challenge or skin-prick test end-point and serum-specific IgE.

Adolescent

Histamine-producing cell stimulating factor (HCSF) and interleukin 3 (IL 3): evidence for two distinct molecular entities.

Because homogeneously purified interleukin 3 (IL 3) can induce an increase in histamine synthesis by normal bone marrow cells like histamine-producing cell stimulating Factor (HCSF), it has been suggested that HCSF and IL 3 might be identical. In this paper, we provide evidence that HCSF activity can be obtained without IL 3 activity (determined by the proliferation of an IL 3-dependent cell line). This distinction between HCSF and IL 3 has been achieved in three different ways: a) biochemical separation of HCSF from IL 3 in crude secondary MLC supernatants with description of different physicochemical characteristics of the two molecules; b) demonstration of an HCSF activity devoid of IL 3 activity in P388D1 conditioned medium, with the same characteristics as HCSF produced during secondary MLC but different from WEHI-3-derived HCSF activity resulting from IL 3; c) demonstration of a lack of inhibition of HCSF-induced histamine synthesis by anti-IL 3 immunoglobulins that clearly diminish IL 3-induced histamine production. These results demonstrate that two distinct factors (IL 3 and HCSF) promote histamine synthesis, but that IL 3 has more general effects on hemopoietic cells, whereas HCSF seems to be restricted to histamine-producing cells.

Animals

[Is the histamine-producing cell stimulating factor (HCSF) identical to interleukin 3 (IL-3)?].

Since homogeneously purified Interleukin 3 can induce an increase in histamine synthesis by normal bone marrow cells (HCSF activity), it has been suggested that HCSF and IL3 could be identical. In this paper, we show evidence that HCSF activity can be obtained without any IL3 activity (determined by the proliferation of an IL3-dependent cell line). This distinction has been achieved in two different ways: (a) the physico-chemical separation of HCSF and IL3 from crude secondary MLC supernatants and (b) the spontaneous production by the P388D1 cell line of a factor possessing all the characteristics of HCSF without any IL3 activity. In addition, preliminary results show that anti-IL3 antibodies do not inhibit the increase in histamine synthesis induced by HCSF while it strongly diminishes that induced by IL3.

Animals

[Blood histamine and response of spleen cells to phytohemagglutinins during moderate magnesium deficiency in the rat].

Blood histamine and spleen cell stimulation index by PHA were determined in either magnesium deficient or control Rats. Between the 10th and 17th days of diet (hyperemia and dermatosis period), histaminemia was significantly higher in deficient animals (485 ng/ml) than in control ones (112 ng/ml), but at the 32nd day it came back to normal values. The mean spleen cell stimulation index by PHA was depressed in deficient animals mainly between the 10th and 17th day of the deficiency; 33% of control mean value. A negative correlation is found between histamine level and stimulation index.

Animals

[Sensitization to penicillin following cutaneous side-effects of ampicillin].

Sensitization to penicillin was determined in vitro in twenty subjects, 30 days after cutaneous side-effects due to ampicillin. The study inclued the detection of anti-penicillin IgE, IgM, a lymphoblastic transformation test and a leucocyte migration test. No difference could be demonstrated between the sensitization 30 days after an ampicillin reaction and the sensitization 30 days after a penicillin reaction.

Adult

Lymphocyte transformation, leucocyte migration, specific IgE, IgG and IgM before, during, and after penicillin treatment without adverse reaction. A follow-up study.

This in vitro follow-up study of the penicillin-induced immune response by a well-tolerated regimen was conducted with an association of four tests: lymphocyte transformation test; leucocyte migration test; passive anaphylaxis on monkey lung tissue; and passive hemagglutination. It showed (1) that previously sensitized subjects (including IgE) tolerated the treatment by pencillin. (2) That the treatment induced either a transient positive conversion of previously negative tests or a negative conversion of previously positive tests. These in vitro findings are in accordance with previously established concepts based upon cutaneous tests and must be taken into consideration when interpretating in vitro diagnosis of penicillin allergy.

Adolescent

The penicillin antigens: presentation in the leucocyte migration test (a study with penicillin and penicilloylated proteins).

The response of the leucocyte migration test (LMT) to benzyl penicillin (BP) was compared with the response of LMT to benzyl penicilloylated human gamma globulins (BPO HGG) and to benzyl penicilloylated human serum albumin (BPO HSA). Patients with and without hypersensitivity to penicillins were investigated. No statistical differences were found between the response to BP and to BPO HGG or BPO HSA; this finding supports the fact that the BPO groups generated by BP are mainly implicated in the triggering of the LMT when BP is used as antigen. A strongly penicilloylated HSA appeared to be the most effective mode of the antigen presentation for the detection of BPO-specific cellular immunity in patients with and without clinical symptoms of hypersensitivity to the penicillins.

Adult