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Biomedical subjects

G Mazur

Publications and source records attributed to G Mazur.

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

Epitope mapping with peptides of Chi t I component III and immunomodulation of the Chi t immune response.

BACKGROUND: Hemoglobins of the Diptera family are known as aggressive inhalant allergens. METHODS: The whole sequence of the insect allergen Chi t I component III was studied for T-cell epitope activity in cell cultures of 15 sensitized patients with a panel of 17 overlapping synthetic peptides and 12 peptides obtained by tryptic cleavage. RESULTS: All but one of the peptides tested were found to be immunogenic. The nonstimulatory sequence 102-109 and two other tryptic peptides (69-90 and 110-135) were used in inhibition experiments. The Chi t I-induced proliferation was downregulated by all tested peptides when compared with stimulation with Chi t I alone. CONCLUSIONS: Because stimulation with phytohemagglutinin or tetanus toxoid was not influenced by the above-mentioned peptides, this mechanism seems to be specific for the antigen. Specific immunomodulation with nonstimulating peptides may offer new therapy approaches.

Adjuvants, Immunologic↗
PubMed1993

Detection of specific IgE in isocyanate and phthalic anhydride exposed workers: comparison of RAST RIA, Immuno CAP System FEIA, and Magic Lite SQ.

Sera from 94 workers occupationally exposed to isocyanate were tested by RAST RIA, Immuno CAP FEIA, and Magic Lite SQ (ML) against the allergens HDI, MDI, TDI, and phthalic anhydride. Twenty sera showed increased levels of diisocyanate-specific IgE antibodies, and five sera were phthalic anhydride positive. High total IgE titer was not correlated with positive specific IgE titer (r = 0.47), showing that nonspecific IgE binding was low. The results of ML and CAP correlated well (r = 0.91), but tended to be slightly higher than the results obtained with the RAST isotope test. CAP and RAST data also correlated significantly (r = 0.90), but the correlation between ML and RAST data was lower (r = 0.82). The results of the new in vitro tests, CAP and ML, showed good reproducibility (5% CV for CAP and 8% CV for ML). In summary, the CAP and ML methods were found to be appropriate for routine diagnosis of specific IgE antibodies against the allergens HDI, MDI, TDI, and phthalic anhydride.

Adult↗
PubMed1993

Activation of blood neutrophils in acute episodes of farmer's lung.

Farmer's lung often presents clinically as recurring acute episodes several hours after exposure to moldy hay. During these episodes the blood neutrophil count increases. Because activated neutrophils release toxic oxygen metabolites and proteinases, we hypothesized that the pulmonary reaction in farmer's lung may be induced by the secretory products of activated neutrophils. To evaluate this concept, we quantified the respiratory burst of separated blood neutrophils from patients with farmer's lung (n = 12) during standardized exposure tests with moldy hay. The respiratory burst of these cells was evaluated by measuring zymosan-stimulated and lucigenin-amplified chemiluminescence (CL). Asymptomatic farmers (n = 12) and normal volunteers with no prior exposure to moldy hay (n = 15) were used as control subjects. As expected, following exposure in the group of patients with farmer's lung, striking changes in VC, TLCO, and PaO2 were observed, whereas there were only minor changes in these parameters in both control groups. In all three groups a considerable increase in the blood leukocyte count was observed. The CL response of the blood neutrophils from patients with farmer's lung 6 h after exposure was significantly higher than before or 1 h after exposure (p < 0.05 for both comparisons), whereas there was no significant change in the CL response in either control group during the observation period. Our results indicate that antigen inhalation induces an increase in the number of circulating neutrophils in patients and controls, but in patients with an acute episode of farmer's lung the neutrophils are primed for an enhanced respiratory burst and may thereby damage the lung.

Acridines↗
PubMed1993

[Interleukin 2 (IL-2) and its receptor (IL-2R) in healthy individuals and with various disease states].

IL-2 is a cytokine that plays a central role in immune response. It stimulates cellular as well as humoral reactivity. The effect of IL-2 depends on the interaction with its receptor. Recent reports have documented that high affinity interleukin-2 receptors consist of two distinct IL-2 binding proteins, one being alpha chain (p55) and the other being IL-2 beta chain (p75). Expression of the alpha chain or the beta chain alone allows for low affinity or intermediate affinity IL-2 binding, respectively. Alpha receptor is present on activated cells, beta chain is present on resting cells. Decreased production of IL-2 and decreased expression of IL-2 receptor (IL-2R) after stimulation was found in primary and secondary immune deficiencies. Leukemic cells in adult T cell leukemia and hairy cell leukemia express markedly large numbers of IL-2 receptors. Since IL-2 receptors are present on malignant cells but not on normal resting cells, clinical trials have been initiated in which patients with adult T cell leukemia are treated with monoclonal antibody that binds to IL-2 receptor.

Antibodies, Monoclonal↗
PubMed1993

Tracheo- and bronchoesophageal fistulas in Hodgkin's disease.

Among 330 patients with Hodgkin's disease, in five development of fistula between the respiratory and alimentary tract was observed; tracheoesophageal in three and bronchoesophageal in two patients. Generalization of the disease was the cause of fistula in three patients; it appeared as a result of necrosis of the neoplastic infiltration during cytostatic treatment or radiotherapy. In the fourth patient the fistula was of iatrogenic origin (radiation induced damage), and in the fifth it was the result of secondary neoplasm (bronchial anaplastic cancer).

Adult↗
PubMed1992

[Exogenous allergic alveolitis: assessment of antigen-specific IgG antibodies using a new chemiluminescence method].

The demonstration of elevated levels of antigen-specific IgG antibodies is of importance for the diagnostic workup of patients with a suspected hypersensitivity pneumonitis. We established a solid phase immunoassay for the determination of these antibodies based on chemiluminescence (CLIA). The CLIA demonstrated a low level of unspecific binding. The reproducibility of the CLIA was evaluated by calculating the intra- and inter-variation; the variation coefficient was 4% (intra-variation) resp. 13% (inter-variation). Using the CLIA we quantified IgG antibodies against Aspergillus fumigatus (A.f.), Micropolyspora faeni (M.f.) and Thermoactinomyces vulgaris (T. v.) in the sera of patients with farmer's lung (FL, n = 10), healthy farmers (n = 13) and normal volunteers without prior hay contact (n = 12). For all 3 antigens the antibody levels of patients with FL were significantly higher than the titers of the other groups. As a comparison all sera were tested with an established solid phase radioimmunoassay (RIA). Using the RIA a statistically significant difference could only be demonstrated between the antibody levels of patients with FL and of normal volunteers without prior hay contact and was limited to the antigens A.f. and M.f. Comparing the results achieved with both assays on a point by point basis there was a good correlation for the antigens A.f. (r = 0.69; p less than 0.0001) and M.f. (r = 0.74; p less than 0.0001), whereas the correlation for T.v. was not satisfying (r = 0.42, p less than 0.02). In summary the CLIA is a promising new method for the determination of antigen specific IgG antibodies with the advantages of a radioimmunoassay without its potential hazards.

Alveolitis, Extrinsic Allergic↗
PubMed1991

Immunological cross-reactivity of hemoglobins in the Diptera family Chironomidae.

Polyclonal human IgE antibodies of patients sensitized to one species of the Diptera family Chironomidae as well as polyclonal rabbit anti-Chi t I hyperimmune serum recognize antigenic sites present in nearly all of the 33 species of this insect family. Evolutionary distantly related genera usually show weaker antibody binding. According to the pattern of reactivity of rabbit anti-Chi t I-component III, expression of the epitopes of this molecule varies considerably in the genera Chironomus and Glyptotendipes; it appears to be almost totally absent in all other species. Of five monoclonal antibodies raised against Chi t I-component III, two recognize an epitope which is expressed in nearly all closely related species. Three monoclonal antibodies recognize epitopes which are expressed in only a few species of the same genus. Our results demonstrate the presence of common as well as species-specific epitopes in chironomid hemoglobins which behave as potent inhalant allergens.

Animals↗
PubMed1991

Stimulation of human peripheral blood lymphocytes with chironomid hemoglobin allergen (Chi t I).

Hemoglobins (Chi t I) of the dipteron species Chironomus thummi thummi are known to cause severe allergic diseases in humans. We tested the allergen-specific stimulation of human peripheral blood lymphocytes (PBL) by Chi t I and its nine main components. Further, we applied fragments of the well-analyzed component III, obtained by cleavage with trypsin as well as arginine protease. In this way, we screened the molecule in order to identify T-cell epitopes. The whole component was found to be immunogenic and to have regions demonstrating varying PBL stimulation. In addition, interindividual patterns of reactivity, probably due to genetic restriction, were found. A T-cell epitope could be shown to be within the site 98-111, as predicted by application of Rothbard's algorithms.

Allergens↗
PubMed1991

[Uptake and distribution of epidermal growth factor in certain organs of the dog].

Epidermal growth factor (EGF) besides salivary glands and saliva has been lately detected in kidney and urine. The liver was previously considered as the most important place of this peptide's metabolism. A little was known about other places of EGF degradation. In our studies which were performed on anesthetized dogs EGF was administered by intravenous infusion to compare the different places of its degradation. Plasma EGF level was measured in blood samples taken from femoral artery and from cervical, femoral, renal, portal and hepatic vein. Basal plasma EGF level was 8 +/- 2 pg/ml. During exogenous infusion of hEGF in dose of 0.25 and 1.0 micrograms/kg/h arterial plasma levels were increased to 622 +/- 128 pg/ml and 1441 +/- 294 pg/ml respectively. After blood passage by the brain, lower leg, small bowel and liver percent of decrease in plasma EGF level was about 30-40%. In comparison to arterial value, the renal venous plasma level was decreased significantly by about 95%. Amount of EGF detected in urine during i.v. infusion decreased approximately by 30%. Mean half life of EGF was 2.32 +/- 0.5 min. Our study strongly suggests that EGF detected in urine is mostly cleared out by kidneys.

Animals↗
PubMed1990

Allergen-directed expression of Fc receptors for IgE (CD23) on human T lymphocytes is modulated by interleukin 4 and interferon-gamma.

T lymphocytes bearing Fc receptors (FcR) for immunoglobulins are known to have immunoglobulin class-specific regulatory functions. Here we report that expression on T cells of the low-affinity FcR for IgE (Fc epsilon RII/CD23) is preferentially induced by stimulation with antigens that cause an IgE response. T cells from eight patients allergic to the hemoglobin of Chironomus thummi thummi mosquito larvae (CHIT I) were analyzed for reactivity with the anti-FcERII/CD23 monoclonal antibody (mAb) M-L25 under various conditions. No Fc epsilon RII/CD23+ T cells were observed among freshly isolated, resting peripheral blood mononuclear cells (PBMC). Stimulation of PBMC with CHIT I, however, induced a marked although transient Fc epsilon RII/CD23 expression on a large portion of the allergen-activated T lymphocytes. It reached a maximum of 37.2 +/- 4.6% Fc epsilon RII/CD23+ T cell blasts on day 5 of culture. The selectivity of this expression became evident when compared to non-allergenic control antigens: after stimulation of PBMC with tetanus toxoid or purified protein derivative from tuberculin a maximum of 4.6% +/- 1.4% and 4.2% +/- 1.1% T cell blasts was found to express Fc epsilon RII/CD23, respectively. Activation by an anti-CD3 mAb was insufficient to induce Fc epsilon RII/CD23 on T cells. The allergen-stimulated Fc epsilon RII/CD23+ T cells exclusively belonged to the CD4+CD29+ helper inducer T cell subset. Using a cDNA probe coding for the B cell Fc epsilon RII/CD23, Northern blot analysis revealed a 1.7-kb Fc epsilon RII/CD23 mRNA in extracts of highly purified allergen-stimulated T cells. It was of the same size as Fc epsilon RII/CD23 mRNA of the lymphoblastoid B cell line WI-L2. Of several cytokines tested [interleukin (IL) 1 to IL 6, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha] only IL 4 and IFN-gamma significantly modified allergen-induced Fc epsilon RII/CD23 expression on T cells. The latter was enhanced nearly twofold in the presence of IL 4, and was almost completely abrogated by IFN-gamma. IL 4, however, could not increase the number of Fc epsilon RII/CD23+ T lymphocytes either alone or in combination with an anti-CD3 mAb. Taken together, the selective induction of Fc epsilon RII/CD23 on T cells by allergen and its inclusion in the regulatory network of cytokines point to an important role of Fc epsilon RII/CD23+ T lymphocytes in the human IgE response.

Allergens↗
PubMed1990

Histamine release from human basophils by the insect allergen Chi t I.

Hemoglobins of the Diptera species Chironomus thummi thummi (Chi t I) are potent inhalant allergens. Chi t I-specific histamine release was measured by a new radioimmunoassay in whole human blood taken from 20 sensitized patients, 11 exposed nonsensitized probands, and 11 nonexposed controls. The sensitized patients, who all had positive skin tests and radioallergosorbent test results with Chi t I, showed a significantly higher histamine release than the two other groups. However, within the patient group, the percentage of released histamine did not correlate with the intensity of the skin test response or the concentration of Chi t I-specific IgE antibodies. Our results demonstrate that this method is a sensitive and specific in vitro test for evaluation of IgE-mediated sensitization.

Adult↗
PubMed1988

A common epitope on major allergens from non-biting midges (Chironomidae).

A synthetic peptide corresponding to sequence 91-101 of the Chironomus thummi thummi haemoglobins (Chi t I) components III and IV was used to investigate binding and cross-reactivity with polyclonal human IgE and rabbit IgG antibodies and murine IgG1 subclass monoclonal antibodies (MABs). The synthetic peptide reacted with antibodies from all three mammals. The specificity of the reaction, especially that with IgE antibodies was shown by dose dependent inhibition with native Chi t I component III. Epitope(s) reacting with these antibodies were also found in haemoglobins from 14 of the 15 chironomid species analyzed. The synthetic peptide III/IV 91-101 enabled the identification of an important antigenic/allergenic determinant of the broadly distributed insect family Chironomidae. The antigenic potency of this synthetic peptide as shown by testing with human IgE, rabbit IgG and mouse MABs, and the widespread occurrence of the epitope in an identical or homologous sequence and/or superficial location, qualifies the peptide for therapeutic applications in medicine.

Allergens↗
PubMed1987

Epitope mapping of major insect allergens (chironomid hemoglobins) with monoclonal antibodies.

Monoclonal antibodies (m ABs) were raised against the physically and chemically well-defined insect allergen, component CTT III from Chironomus thummi thummi (CTT) hemoglobin. With these m ABs, we observed epitopes present in as many different hemoglobin (Hb) molecules from the widespread insect family Chironomidae as possible. These Hbs were identified as important allergens in previous studies. Twenty m ABs from seven different clones were tested for specificity against the CTT Hbs III, IIIa, IV, and I to X, as well as against Hbs from 14 other chironomid species; m ABs 1 to 3 were found to be specific for an epitope that was expressed on the CTT III component as well as in Hbs from three other species. m ABs 5 to 7 and 15 recognized an epitope expressed in CTT III, CTT IIIa, CTT IV, and in Hbs from 13 other species. m ABs 8 to 14 and 16 to 20 demonstrated heteroclitic behavior, that is, they bound CTT IIIa better than the immunogen CTT III. Reactivity of m AB 6 with a clinically relevant epitope was demonstrated by up to 15% inhibition of antibody binding by human IgE from sensitized patients. Our results demonstrate that clinically relevant allergenic epitopes can be localized on different molecules with m ABs. This could be important in the development of immunotherapy protocols with highly purified or fragmented allergens.

Allergens↗
PubMed1986

Structure, antigenic determinants of some clinically important insect allergens: chironomid hemoglobins.

Determination of the molecular structure and properties of allergens that elicit severe immediate-type hypersensitivity diseases in humans and a knowledge of the structure of their antibody-binding sites should provide new insight into the pathogenetic mechanisms of allergic diseases. Monomeric and homodimeric hemoglobins (CTT I to X) have been identified as potent allergenic components of Chironomidae, a family of Diptera. Immunologic investigations of peptides of three of these hemoglobins (CTT IV, CTT VI, and CTT VIII) showed that human antibodies of the E and G classes recognize at least two different sites within each molecule. Individual hemoglobin peptides were aligned with homologous regions of chironomid hemoglobin CTT III, whose tertiary structure has been determined by x-ray analysis at a resolution of 1.4 angstroms. The antigenic site CTT IV(91 to 101) showed the following characteristics: (i) seven polar or hydroxylated amino acids, from a total of eleven, occupying predominantly superficial regions; (ii) the property of linkage to other molecules by hydrogen bonds or solvent clusters; and (iii) high thermal mobility factors. In contrast, peptide CTT IV(102 to 108), which does not bind human antibodies, contained no polar amino acids and had low thermal mobility factors. These results support the idea that the antigenicity of clinically relevant proteins is related to regions with a predominance of polar amino acids and with low energy barriers between different conformations, which allow high flexibility, including site-specific adaptation in antibody binding.

Allergens↗
PubMed1986

Determination of toluene diisocyanate in air by HPLC and band-tape monitors.

An improved HPLC method was developed for determining the atmospheric concentration of toluene diisocyanate (TDI). 1-(2-pyridyl)-piperazine in toluene was used as reagent absorber solution together with reversed phase chromatography and a simple efficient buffer system (0.1% trifluoroacetic acid--acetonitrile, 85:15%) in an isocratic elution mode. The values for atmospheric TDI concentration obtained with two continuous band-tape monitors were checked using the values from HPLC as reference. Under identical experimental conditions the two instruments (both model 7005) gave readings varying by more than 100%. At low humidity the band-tape values were considerably lower than the HPLC values. At an absolute humidity of 11.7 g H2O/m3 (58% relative humidity) the value from instrument 1, but not instrument 2, agreed with those from HPLC. The values obtained with band-tape devices in the continuous monitoring of TDI concentration in places of work, or epidemiological studies, should be assessed with caution. HPLC offers a useful reference method for monitoring the accuracy of such devices.

Air↗
PubMed1986

[Intrinsic oxygen affinity of hemoglobins: the hemoglobin of bisons (Bison bonasus,Bovidae)].

The hemoglobin from a European Bison (Bison bonasus) was analysed and the complete primary structures of the alpha I-, alpha II-and beta-chains have been determined. The alpha I- and alpha II-chains differ only at position alpha 19 (Asp----Gly). The beta-chains are homogeneous. The sequences are compared with the globin chains of Bison bison and bovine and the polymorphism of the alpha-chains is discussed. On the basis of the primary structure it may be concluded that the hemoglobin of Bison bonasus belongs to the group of hemoglobins with intrinsically low oxygen affinity.

Amino Acid Sequence↗
PubMed1984

Oxygen binding properties of hemoglobin from the white rhinoceros (beta 2-GLU) and the tapir.

The beta-chain of rhinoceros hemoglobin contains glutamic acid at position beta 2, and important site for the binding of organic phosphates. We have investigated the oxygen binding properties of this hemoglobin and its interaction with ATP, 2,3-diphosphoglycerate, CO2 and chloride. The results show that the presence of GLU at position beta 2 nearly abolishes the effect of organic phosphates and CO2, whereas the oxygen-linked binding of chloride is not affected. Thus rhinoceros hemoglobin has only protons and chloride anions as major allosteric effectors for the control of its oxygen affinity. From the results obtained with hemoglobin solutions it can be calculated that the blood oxygen affinity of the rhinoceros must be rather high with a P50 of about 20 torr at pH 7.4 and 37 degrees C, which conforms with observations obtained for other large mammals.

Animals↗