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Biomedical subjects

J Hébert

Publications and source records attributed to J Hébert.

At least 55 records · Page 3Linked to original sources
PubMed1993

Chronic idiopathic urticaria: possible contribution of histamine-releasing factor to pathogenesis.

BACKGROUND: Histamine-releasing factor was recently shown to be clinically relevant in allergic rhinitis and asthma. HRF could also be involved in the pathogenicity of chronic idiopathic urticaria (CU). The purpose of this study was to investigate the role of HRF in the pathophysiology of CU. METHODS: Blisters were induced on lesional and nonlesional skin of 12 patients with CU and on normal skin of five control subjects. HRF activity and histamine content were measured in all samples recovered from each skin site. RESULTS: Significantly more HRF was found in blister fluids from lesional skin of patients with CU as compared with nonlesional skin and skin of control subjects. In addition, histamine content in blister fluids from affected skin of patients with CU was significantly higher in comparison with both nonlesional skin of patients with CU and skin of control subjects. HRF activity was also higher in blister fluids from nonlesional skin of patients with CU than that of control subjects, in spite of equivalent histamine content. CONCLUSION: These data suggest that the inflammatory reaction found in CU disease is associated with the cutaneous release of HRF.

Adult↗
PubMed1993

Lol p I-induced IL-4 and IFN-gamma production by peripheral blood mononuclear cells of atopic and nonatopic subjects during and out of the pollen season.

The reciprocal effects of IL-4 and IFN-gamma on IgE synthesis have been well established. It has also been shown that these two lymphokines are secreted by different subsets of CD4+ T cells (TH1 and TH2), and that TH2 helper T lymphocytes could be involved in the pathophysiology of allergic diseases. But little is known about the effects of an allergen on the profile of lymphokine synthesis by human peripheral blood mononuclear cells (PBMCs) of allergic and nonallergic subjects. We studied the production of IL-4 and IFN-gamma by PBMCs of atopic and nonatopic donors after in vitro stimulation by the group 1 allergen from Lolium perenne pollen (Lol p I), during and out of the grass pollen season. On natural exposure to pollen, Lol p I-induced IL-4 production was observed only with atopic donors (6 of 8), whereas the synthesis of IFN-gamma was observed for all nonatopic donors (7 of 7) and most allergic patients (5 of 7). At the time of the study, higher amounts of IFN-gamma were produced by PBMCs of nonatopic donors than by PBMCs of atopic patients. Out of the pollen season the production of IL-4 was not observed either by atopic (n = 11) or by nonatopic subjects (n = 5). On the other hand, IFN-gamma was produced by PBMCs of most subjects (atopic, 10 of 11; nonatopic, 5 of 5), but at the time of the study no difference was observed between the two groups. These results show that Lol p I induces different profiles of IL-4 and IFN-gamma production by PBMCs of atopic and nonatopic subjects. In atopic subjects this profile of lymphokine synthesis is influenced by the natural exposure to pollen, which is in keeping with the seasonal rise of IgE antibodies.

Adult↗
PubMed1993

Seasonal enhancement of IL-4 induced IgE synthesis by peripheral blood mononuclear cells of atopic patients.

The role of IL-4 on IgE synthesis has been well established. IL-4 has been shown to promote IgE production by B cells from atopic and non-atopic donors. In this study, the effects of natural exposure to pollens on IL-4-induced IgE synthesis by peripheral blood mononuclear cells of atopic and non-atopic donors were examined. The results confirm production of IgE in an IL-4 dose-dependent manner by PBMC cultures of these two groups. When cultures were performed out of the pollen season, following stimulation by IL-4, no significant differences was observed between the levels of IgE produced by PBMC of atopic and non-atopic donors. In contrast, upon natural exposure to pollens, significant higher levels of IgE were measured in the atopic group than in the non-atopic one. These results show that the pollen season influences the IL-4-induced IgE synthesis by PBMC of allergic patients and are in keeping with seasonal rise of specific IgE antibodies.

Dose-Response Relationship, Drug↗
PubMed1993

Production of Monoclonal Antibodies against the Major Capsid Protein of the Lactococcus Bacteriophage ul36 and Development of an Enzyme-Linked Immunosorbent Assay for Direct Phage Detection in Whey and Milk.

The only major structural protein (35 kDa) of the lactococcal small isometric-headed bacteriophage ul36, a member of the P335 species, was isolated from a preparative sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Monoclonal antibodies (MAbs) were raised against the denatured 35-kDa protein. Six MAbs were selected and characterized. Western blots (immunoblots) showed that all MAbs recognized the 35 kDa but also a 45 kDa that is in lower concentration in the phage structure. Binding inhibition assays identified five families of MAbs that recognized nonoverlapping epitopes of the 35- and 45-kDa proteins. Immunoelectron microscopy showed that these two proteins are localized within the phage head, therefore indicating that the 35 kDa is a major capsid protein of ul36 and that the 45 kDa is a minor capsid protein. With two MAbs, a sandwich enzyme-linked immunosorbent assay (ELISA) was developed for direct detection of lactococcal phages in whey and milk samples. Whey and milk components, however, interfered with the conduct of the assay. Partial denaturation of milk samples by heat treatment in the presence of SDS and beta-mercaptoethanol removed the masking effect and increased the sensitivity of the assay by 100-fold. With the method used here, 10 PFU/ml were detected by the ELISA within 2 h without any steps to enrich or isolate bacteriophages.

Journal Article↗
PubMed1993

Biological activity of monoclonal anti-idiotypic antibody representing the internal image of the major allergenic component of Lolium perenne pollen.

Upon immunization with an anti-Lol p I (major allergenic component of Lolium perenne pollen) monoclonal antibody, we have previously produced anti-idiotypic monoclonal antibody (A7H2) displaying some internal image properties. The present study was designated to evaluate the capacity of this anti-idiotypic monoclonal antibody to mimic functionally the antigen by triggering histamine release from basophils of patients allergic to Lol p I. Anti-idiotypic monoclonal antibody, as the antigen, could induce histamine release in a dose-response fashion in all of the atopic patients (6/6). The inhibition of this histamine release by the addition of the idiotype (290A-167) confirmed the specificity of the reaction. Binding inhibition of human IgE to Lol p I demonstrated that the anti-idiotypic antibody recognized an idiotope expressed in the antigen-combining site of IgE molecules. Altogether, these data confirmed the internal properties of our anti-idiotypic antibody and it can mimic the original antigen in its capacity to trigger histamine release.

Adult↗
PubMed1992

Chronic idiopathic urticaria: profiles of skin mast cell histamine release during active disease and remission.

Chronic idiopathic urticaria (CIU) is characterized by the increased releasability of histamine by mast cells in normal-appearing skin. In active CIU, this abnormality is consistently present. To determine if this finding subsides when the disease goes into remission phase, we analyzed the histamine secretion in patients with CIU in remission (CIUR) compared with that of patients with CIU and in normal control (NC) subjects, with the skin-chamber technique. The profiles of histamine release in sites challenged with compound 48/80 were significantly different in the groups with CIU and CIUR. Furthermore, patients with CIUR did not differ from NC subjects in terms of histamine releasability under compound 48/80 stimulation (p greater than 0.1). These data suggest that the state of excessive skin mast cell sensitivity is a reversible and transient phenomenon in CIU disease.

Analysis of Variance↗
PubMed1992

Allergic rhinitis to ragweed pollen. I. Reassessment of the effects of immunotherapy on cellular and humoral responses.

This work presents a double-blind, placebo-controlled study of 27 patients with allergic rhinitis to ragweed who received preseasonal desensitization immunotherapy [IT] with alum-precipitated aqueous ragweed extracts. We reassessed the following parameters in relation to clinical responses: clinical scores, nasal reactivity to a provocative dose of ragweed causing a 75% fall in airflow rate (PD75), ragweed IgE and IgG, and ragweed-induced basophil histamine release (BHR). First, the nasal PD75 correlated with the severity of nasal symptoms (p less than 0.05). Second, we confirmed a significant symptomatic improvement in the IT-treated group either by clinical scores (p less than 0.05) or the prevention of the seasonal fall of the PD75 (p less than 0.005). Also, IT reduced the seasonal rise of IgE (p less than 0.02) and induced an increase in IgG (p less than 0.01) and a decrease in BHR (p less than 0.03). There was a significant correlation between IgE and BHR (r = 0.80; p less than 0.01). After selecting out the effects of IgE, the BHR was still higher in the placebo-treated group than in the IT-treated group (p less than 0.02), suggesting the involvement of other modulating factors. Symptomatic improvement after IT correlated only with the summation of both IgE and BHR (PD75; r = 0.64; p less than 0.005). This observation suggests that the severity of clinical symptoms is determined by several interacting factors and not by the antibody response alone.

Adult↗
PubMed1992

Allergic rhinitis to ragweed pollen. II. Modulation of histamine-releasing factor production by specific immunotherapy.

A number of cytokines, including histamine-releasing factors (HRFs), have a role to play in IgE-mediated asthma. However, the influence of HRF in allergic rhinitis without asthma remains to be revealed. This article presents a double-blind, placebo-controlled study on the role of HRF in ragweed-allergic rhinitis and its modulation by natural pollen exposure and specific immunotherapy (IT). Twenty-seven patients allergic to ragweed were randomly assigned to receive either preseasonal alum-precipitated aqueous extracts of ragweed or placebo. Before the onset of therapy and during the ragweed-pollen season, subjects were evaluated for each of the following: clinical scores, ragweed IgE and IgG antibody levels, and spontaneous and allergen-driven HRF production. Thirteen nonatopic volunteers were also studied in the same protocol. First, before the initiation of therapy, more HRF was produced by both unstimulated and ragweed-stimulated mononuclear cells (MNCs) of atopic subjects as compared to MNCs of nonatopic subjects. Second, MNCs of the placebo-treated group produced significantly more spontaneous and ragweed-specific HRF during the pollen season compared to the preseasonal values. Finally, specific IT not only improved the clinical manifestation of allergy but also prevented the seasonal rise of spontaneous and ragweed-driven HRF production, along with a well-known change in other immunologic parameters associated with successful IT.

Adult↗
PubMed1992

Increase in T3 levels during hypocorticism in patients with chronic secondary adrenocortical insufficiency.

The clinical and biochemical manifestations of secondary adrenocortical insufficiency are not well defined in the medical literature. This study was designed to determine the clinical and laboratory features suggesting the diagnosis of adrenal insufficiency in 15 chronic ACTH deficiency patients during low and normal cortisol states. Except for fatigue and weakness, the characteristic clinical manifestations of primary adrenal insufficiency occurred rarely. ACTH deficiency did not significantly modify blood glucose, serum calcium, sodium, potassium and differential white blood cell count. However, serum T4 was lower (65 +/- 19 vs 95 +/- 21 nmol/l, p less than 0.001) during cortisol deficiency, while T3 was higher (2.4 +/- 0.67 vs 2.0 +/- 0.60 nmol/l, p less than 0.001). Furthermore, rT3 decreased significantly during hypocorticism (0.27 +/- 0.07 vs 0.18 +/- 0.07 nmol/l, p less than 0.001). The T4/T3 ratio was significantly lower than the normal in 15 out of the 17 episodes of ACTH deficiency (29 +/- 12.5 vs 57 +/- 9.4, p less than 0.0001). We conclude that the increase in T3 and decrease in T4 levels are associated with chronic secondary adrenocortical insufficiency. This laboratory feature could be due, at least in part, to the increased peripheral conversion of T4 to T3 during cortisol deficiency.

Adrenal Cortex Diseases↗
PubMed1991

Reversible hypertriiodothyroninaemia due to adrenal insufficiency.

It is well known that an excess of glucocorticoids affects thyroid tests. The effect of adrenal deficiency on thyroid hormones is less well defined. We here describe the case of a 33-year-old woman with Cushing's disease who was cured by trans-sphenoidal surgery. During the postoperative period, a secondary adrenal insufficiency developed. The thyroid blood tests then revealed elevated L-triiodothyronine (T3) levels and a decrease in reverse T3. These findings suggest that secondary adrenal deficiency may be associated with high T3 levels, which may be due to an increase in the peripheral conversion of thyroxine (T4) to T3.

Adrenal Insufficiency↗
PubMed1990

Generation of anti-idiotypic and anti-anti-idiotypic monoclonal antibodies in the same fusion. Support of Jerne's Network Theory.

Upon immunization of mice with a mAb (290A-167) directed against an epitope of Lol p I (the major allergenic determinant of Lolium perenne), both anti-idiotypic (aId) mAb (Ab2) and anti-aId mAb (Ab3) were produced. The Ab2 displayed the following internal image properties of Lol p I: it can be affinity-purified on an immobilized Id column; its binding to the anti-Lol p I mAb (290A-167) is inhibited by Lol p I; it inhibits in a dose-response fashion the binding of the specific Id to Ag. It is recognized by anti-Lol p I antisera from different species such as mouse, human, and goat. The Ab3 which binds to Lol p I was also produced from the same fusion. This binding was inhibited significantly by aId mAb (Ab2), anti-Lol p I mAb (290A-167) and Lol p I. These data indicate that the two mAb with specificity for Lol p I (290A-167 and Ab3) share similar reactivity to the Ag and that aId mAb is the internal image of the epitope recognized by the Id. We showed also that the capacity of rabbit aId Ab directed against the 290A-167 Id to inhibit the binding of Ab1 and Ab3 to Ag was almost abolished by passage over a Ab3-coated Sepharose column. This would suggest that not only are the two mAb with reactivity to Lol p I (Ab1 and Ab3) directed against identical epitopes, but that they in fact shared identical idiotopes as well. The production of identical mAb upon immunization with either the Ag or the aId mAb supports that the conceptual framework proposed by Jerne finds its biologic application in the course of an immune response.

Animals↗
PubMed1990

Effects of H1-antihistamine drug regimen on histamine release by nonlesional skin mast cells of patients with chronic urticaria.

Profiles of compound 48/80-induced histamine release (HR) from mast cells of uninvolved skin from patients with chronic urticaria (CU) and from a normal control (NC) group were compared, and the effects of anti-H1 medications were assessed versus placebo. Then, patients with CU (15) and NC subjects (10) were randomly assigned to take either hydroxyzine (100 mg/day), terfenadine (120 mg/day), or placebo for 28 days. The effects of such treatment on the clinical response and on the profile of compound 48/80-induced HR during a 4-hour period were analyzed. Treatment with hydroxyzine in patients with CU improved the clinical symptoms and modified the profile of HR; more histamine was recovered at 1 hour (p less than 0.05) and 2 hours (p less than 0.05), as compared with baseline. Terfenadine and placebo had no effect on the clinical response or on the profiles of HR. In the NC group, the amounts of histamine recovered at 1 hour after challenge with compound 48/80 were lower than amounts of the pretherapy values (p less than 0.01). It could be concluded that (1) the profile of HR in patients with CU is reproducible during a period of 28 days, (2) only hydroxyzine modifies both the clinical response and the profile of HR, and (3) anti-H1 compounds decrease the HR in the NC group.

Adult↗
PubMed1990

Detection of auto-anti-idiotypic antibodies to Lol p I (rye I) IgE antibodies in human sera by the use of murine idiotypes: levels in atopic and non-atopic subjects and effects of immunotherapy.

Anti-idiotypic antibodies (anti-Id Abs) are involved in the regulation of a number of immune responses including the IgE antibody production. In atopic patients, the increased synthesis of IgE antibodies could be related to a defective production of regulatory anti-Id Abs. In the present study, we first developed a sensitive assay for measuring the levels of anti-Id Abs directed against antibodies specific for Lol p I, the major allergenic determinant of Lolium perenne (rye grass). In this assay, we used previously described murine monoclonal anti-Lol p I antibodies that were shown to share epitopic specificities with human anti-Lol p I IgE and IgG antibodies, thus short-cutting the need for purification of F(ab')2 fragments of human IgG Abs and insuring optimal specificity and sensitivity. Levels of anti-Id Abs against two anti-Lol p I monoclonal antibodies (290A-167, 348A-6) were higher in normal volunteers than in untreated atopic patients. Specific immunotherapy increased the levels of anti-Id Abs to those of normal volunteers. These observations suggest a role for the Id-anti-Id network in the regulation of IgE antibody production.

Allergens↗
PubMed1990

Mapping of Bet v I epitopes by using murine monoclonal antibodies.

The different determinants of birch pollen extracts, as shown by SDS-PAGE analysis, range from 10 to 94 kDa. These determinants were then electrotransferred on nitrocellulose strips and allowed to react with human IgE Ab from sensitive patients in order to identify the allergenic determinants. Several minor (43, 35, 28 and 21 kDa) and the major (17 kDa) allergenic determinants were identified. Murine monoclonal antibodies (mAb) were then produced against the major allergenic determinant (Bet v I) and their specificity confirmed by immunoblot. One of them, mAb 3F10, was used to affinity-purify the Bet v I. The purity of this material was confirmed by SDS-PAGE analysis and its reactivity on immunoblot against human IgE ensured its biological activity. These mAb were then gathered on four families based on their pattern of reactivity with Bet v I. Indeed four different epitopes on the molecule were identified. Binding inhibition studies using two of them (mAb 5F9 and 8F12) suggested that the epitopes of Bet v I recognized by these mAb are not overlapping. On another hand, the binding of 8H7 and 3F10 was partially inhibited by 5F9 and the binding of 3F10, by 8F12. These data suggest that those two latter epitopes are somewhat overlapping. Finally, the mAb 5F9 could inhibit the binding of human IgE on the affinity-purified Bet v I up to 40% and then shares a common idiotope with human specific IgE Ab of allergic patients.

Allergens↗
PubMed1989

Mapping of Lol p I allergenic epitopes by using murine monoclonal antibodies.

Murine monoclonal antibodies (MAbs) against three non-overlapping epitopes of Lol p I allergen were previously produced and subsequently used for purification of the allergen. In the present study, these MAbs were further characterized, and the biological activity of the purified allergen assessed. The three MAbs were of the IgG isotype and carried a kappa light chain. Their affinity constants were in the range of 7.4-15.1 x 10(-9) mol/l. Purified Lol p I kept its biological activity, as shown by its ability to induce histamine release by basophils of Lol p I-sensitive patients. The profiles of histamine release induced by either Lol p I or crude Lolium perenne extracts were comparable. This observation suggests that human IgE bound to basophils are polyspecific which has been confirmed by immunoblot and inhibition assay. Our data indicated also that Lol p I possesses a major allergenic epitope recognized by all human serum IgE tested. This epitope seems to be partially shared by those recognized by the three MAbs. Finally, preincubation of Lol p I with either one of the Mabs did not affect significantly the basophil-histamine release induced by the purified allergen. This suggests that Lol p I possesses allergenic sites other than the one shared by MAbs and IgE Abs.

Allergens↗
PubMed1989

Mapping of cat albumin using monoclonal antibodies: identification of determinants common to cat and dog.

Cat and dog albumins from commercial extracts were used to produce monoclonal antibodies (MoAb). Anti-cat albumin MoAb recognized both cat and dog albumin equally, as did anti-dog albumin MoAb; this confirms cross-reactivity between cat and dog. The MoAb were separated into two groups according to their epitopic specificity; they recognized two overlapping epitopes of cat albumin. Furthermore, by competitive inhibition of radio-allergosorbent test (RAST), it was shown that one MoAb group inhibited significantly the binding of human IgE antibodies (from a pool of 13 patients allergic to both cats and dogs) to insolubilized cat or dog extracts. These observations suggest that murine anti-cat or anti-dog MoAb and human IgE antibodies recognize identical or closely related determinants on cat and dog albumin.

Albumins↗
PubMed1988

Study of the epitope structure of purified Dac G I and Lol p I, the major allergens of Dactylis glomerata and Lolium perenne pollens, using monoclonal antibodies.

The use of mAb allowed us to further analyze the cross-reactivity between purified Dac g I and Lol p I, the major allergens of Dactylis glomerata (cocksfoot) and Lolium perenne (Rye grass), respectively. It was first shown, using IEF, followed by immunoprinting, that serum IgE antibodies from most grass-sensitive patients recognize both Dac g I and Lol p I. Second, three different anti-Lol p I mAb, 290A-167, 348A-6, and 539A-6, and one anti-Dac g I mAb, P3B2 were all shown to react with Dac g I and Lol p I, indicating that the two molecules share common epitopes. Epitope specificity of the mAb was determined by competitive binding inhibition of a given labeled mAb to solid phase fixed Dac g I or Lol p I by the mAb. The results indicated that the four mAb are directed against four different and non-overlapping epitopes present on both allergens. Using double-binding RIA, our data strongly suggest that the common epitopes are not repetitive on both molecules. In addition to their similar physicochemical characteristics, such as isolectric points and m.w., Dac g I and Lol p I share four identical epitopes. Binding inhibition of human IgE to Lol p I and Dac g I by the mAb was also assessed. The results indicated that each mAb was able to inhibit such reactions to variable degree but no additive inhibition was observed when two mAb of different specificities were used in combination, suggesting that the human IgE binding site is partially shared by each epitope recognized by the four mAb.

Allergens↗