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Biomedical subjects

G J Gleich

Publications and source records attributed to G J Gleich.

At least 325 records · Page 18Linked to original sources
PubMed1984

Induction of nasal late-phase reactions by insufflation of ragweed-pollen extract.

We studied changes in NAC in 17 ragweed-sensitive individuals after intranasal ragweed-challenge testing. All patients experienced immediate symptoms of sneezing, rhinorrhea, and nasal congestion that were associated with marked decreases in NAC (mean = 68%). In 10 trials patients also experienced late (greater than 0 hr) symptoms of nasal congestion with or without rhinorrhea; the mean late NAC decrease in this group was 42%. In contrast, no late symptoms were noted in nine trials, and the mean NAC decreased 5% in this group (p less than 0.003). Attempts to passively transfer immediate or late nasal sensitivity to one individual by spraying the nasal cavity with IgE antibody-containing serum, by packing the nose with cotton pledgets soaked in serum, by injecting serum directly into the inferior turbinate, and by transfusion with IgE-containing serum were not successful. We conclude that symptomatic late-phase reactions occur in the nose after intranasal challenge in about 50% of patients and that these symptomatic reactions can be confirmed objectively by rhinomanometry.

Adult↗
PubMed1984

Epithelial damage in nasal polyps.

Bronchial epithelial damage occurs regularly in bronchial asthma, but it is not known whether such damage occurs in the mucosa of nasal polyps. We obtained nasal polyp tissues from thirty patients and we examined these tissues for evidence of epithelial damage. Immediately after resection, polyp tissue was fixed in Karnovsky's fixative, embedded in methacrylate and stained with Giemsa pH 6 X 5. Normal nasal tissue from eight patients undergoing nasal septal reconstruction was similarly processed. As a disease control, we examined tissue from eight patients with nasal polyps associated with cystic fibrosis. Tissues were viewed by microscopy and epithelial damage was expressed as the percent of surface involved. Twenty-eight of the thirty patients with idiopathic nasal polyps (93%) showed complete loss of nasal mucosa in varying degrees (range 3-81% of surface; mean, 29%). All patients showed evidence of some epithelial damage, either complete loss or marked desquamation (range 9-99% of surface; mean 54%). In contrast, six of eight biopsies from patients undergoing septal reconstruction and five of eight nasal polyps from patients with cystic fibrosis showed little or no evidence of epithelial damage. The results indicate that nasal polyps regularly show evidence of epithelial damage similar to that seen in bronchial asthma, and this abnormality may partly explain the rhinorrhea which is prominently associated with nasal polyps.

Adult↗
PubMed1984

Charcot-Leyden crystal protein and eosinophil granule major basic protein in sputum of patients with respiratory diseases.

Sputum eosinophilia is characteristic of bronchial asthma, and sputum specimens from patients with asthma contain eosinophil-derived substances including Charcot-Leyden crystals (CLC) and the eosinophil granule major basic protein (MBP). Prior observations have indicated that an elevated sputum level of MBP is associated with asthma. To determine whether CLC protein was also elevated in asthma, we measured by specific radioimmunoassays the quantities of MBP and CLC protein in sputum specimens from 106 consecutive patients with various respiratory diseases and in sputum specimens from 10 patients hospitalized for asthma. The CLC protein was detected in all sputum samples, and the levels in the 116 samples averaged 3.5 micrograms/ml (range, 0.01 to 25 micrograms/ml). The CLC protein was significantly elevated in sputum specimens from patients with acute asthma and from patients with certain other respiratory diseases when associated with bronchopulmonary infection. In contrast, MBP levels in the 116 samples averaged 0.32 micrograms/ml (range, 0.01 to 8.8 micrograms/ml) and were significantly elevated only in patients with asymptomatic or acute asthma. Sputum MBP was not elevated in patients with bronchopulmonary infections unless acute asthma was also present. Thus, an elevated sputum MBP level was specifically associated with asthma, whereas an elevated CLC protein level was associated with both asthma and with bronchopulmonary infection in certain patient groups.

Asthma↗
PubMed1984

Stimulation of basophil and rat mast cell histamine release by eosinophil granule-derived cationic proteins.

Major basic protein (MBP), an arginine-rich basic polypeptide that constitutes the crystalloid core of the large specific eosinophil granule, has previously been shown to stimulate noncytolytic histamine release from human basophils and rat mast cells by an IgE-independent mechanism. Two additional basic polypeptides present in eosinophil granules, eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), were examined for similar activity in the present study. Acid-solubilized eosinophil granules were fractionated by chromatography on a Sephadex G-50 column. Incubation of basophil-containing human mononuclear cells with the individual column fractions demonstrated that histamine release occurred only with the fractions that contained MBP. The selectivity of the basophil response for MBP was confirmed by using equimolar concentrations of purified MBP, ECP, and EDN. In contrast, both MBP and ECP, but not EDN, stimulated histamine release from purified rat peritoneal mast cells. Reduction and alkylation of the MBP molecule diminished the response of human basophils to MBP but enhanced the potency of the molecule with rat mast cells. The distinct potency of MBP as a stimulus for histamine secretion from human basophils suggests that eosinophil release of MBP may be a specific event in the augmentation of immediate hypersensitivity reactions and other disorders characterized by eosinophilia.

Animals↗
PubMed1984

Deposition of eosinophil granule major basic protein onto microfilariae of Onchocerca volvulus in the skin of patients treated with diethylcarbamazine.

We investigated the association between eosinophil degranulation, as evidenced by the deposition of granule major basic protein (MBP), and the killing of microfilariae of Onchocerca volvulus in vivo following treatment with diethylcarbamazine (DEC). Utilizing an immunofluorescence procedure for the cellular and extracellular localization of eosinophil MBP in formalin-fixed, paraffin-embedded tissues, we studied skin biopsies from onchocerciasis patients before and during treatment with topically or orally administered DEC. Before DEC, there was little or no inflammatory response in either dermis or epidermis and microfilariae were essentially intact. Immunofluorescent staining for MBP revealed some filamentous fluorescence associated with dermal collagen fibers, very few eosinophils, and no fluorescence in association with intact microfilariae. In contrast, during treatment with DEC, immunofluorescent staining for MBP revealed extensive eosinophil infiltrates in both dermis and epidermis with numerous intraepidermal eosinophil abscesses containing degenerating microfilariae. An intense extracellular immunofluorescence for MBP surrounded degenerating microfilariae in the dermis and epidermis in both the presence and absence of eosinophil infiltrates as early as 4.5 hours after starting therapy. Many intact nondegenerating microfilariae were also present, but they did not show immunofluorescent staining for MBP nor a surrounding inflammatory infiltrate. The results show that immediately following administration of DEC, eosinophils localize and degranulate around microfilariae in the skin and release granule MBP onto or in close proximity to the parasite's surface. Because of the striking association between eosinophil localization, degranulation, and deposition of MBP onto microfilarial surfaces, and the degeneration of microfilariae in the skin, these observations support the hypothesis that the eosinophil, through helminthotoxic granule proteins such as MBP, damages the microfilariae of O. volvulus.

Adult↗
PubMed1984

Episodic angioedema associated with eosinophilia.

Four patients with recurrent attacks of angioedema, urticaria, and fever were seen. During attacks, body weights increased up to 18% and leukocyte counts reached 108,000/microliters (88% eosinophils). Glucocorticoid therapy caused defervescence, diuresis, and decreased total leukocyte and eosinophil counts. The two children received prednisone intermittently; the adults did not require treatment or their conditions were controlled by alternate-day prednisone administration. No patient had evidence of cardiac involvement (follow-up, 2-17 years). The disease does not threaten the function of vital organs. One patient remained in spontaneous remission for 20 years before symptoms recurred. Although it might be classified as a variant of the hypereosinophilic syndrome, we believe that this syndrome is a separate entity because of its distinctive characteristics and its benign course.

Adolescent↗
PubMed1984

Evidence for secretion of human eosinophil granule major basic protein and Charcot-Leyden crystal protein during eosinophil maturation.

Prior electron microscopic studies have suggested that immature eosinophils degranulate during normal maturation in human bone marrow. This hypothesis was tested by measuring levels of eosinophil granule major basic protein (MBP) and Charcot-Leyden crystal (CLC) protein in bone marrow sinusoidal blood. MBP and CLC protein levels were elevated initially in bone marrow sinusoidal blood from normal volunteers when compared with peripheral blood, and levels of both proteins decreased during serial sampling; CLC protein levels remained significantly elevated, while MBP levels declined to equal those of peripheral blood. To investigate whether MBP and CLC protein were secreted during eosinophil maturation, bone marrow cells were cultured in soft agar; MBP and CLC protein levels were measured in culture supernatants by RIA. There was a significant positive correlation between eosinophil colony growth and levels of each protein. Electron micrographs of cells in soft agar colonies provided ultrastructural evidence for secretion of granule products by immature eosinophils. These results support prior observations that eosinophil promyelocytes degranulate during maturation.

Adult↗
PubMed1983

Elevated serum levels in human pregnancy of a molecule immunochemically similar to eosinophil granule major basic protein.

We have shown that serum levels of a molecule immunochemically similar to eosinophil granule major basic protein (MBP) are elevated in pregnant women throughout gestation. MBP levels increase during gestation and plateau at approximately 7,500 ng/ml by the 20th wk (greater than 10-fold above normal). Levels return to normal after delivery, with a T1/2 of 13.7 d. The MBP in pregnancy serum is remarkably similar to the eosinophil granule MBP in that: (a) pregnancy MBP fully inhibits the binding of radiolabeled MBP standard in a double antibody radioimmunoassay; (b) this inhibition reaction is specific for human MBP because pregnancy serum produces no inhibition of the binding of radiolabeled guinea pig MBP in the guinea pig MBP radioimmunoassay; (c) in a two-site immunoradiometric assay for MBP, slopes of dose-response curves for pregnancy serum, purified MBP, and serum from a patient with hypereosinophilic syndrome are identical, and maximal binding is comparable; (d) reduction and alkylation of pregnancy sera increases measured MBP 100-fold, as previously shown for eosinophil granule MBP in serum; and (e) the MBP in pregnancy serum demonstrates the same pattern of heat lability as has been previously reported for MBP. Four observations have raised the possibility that the eosinophil is not the source of the MBP in pregnancy serum: (a) no correlation between serum MBP level and peripheral blood eosinophil count exists in pregnant women, in contrast to previous studies of patients with eosinophilia; (b) levels of three other eosinophil-associated proteins are normal or low in pregnancy sera, whereas the serum levels of these proteins are elevated in patients with eosinophilia; (c) the slopes of dose-response curves for pregnancy sera and MBP standards differ in the double antibody radioimmunoassay; and (d) the molecule in pregnancy serum elutes from Sephadex G-50 columns at the void volume, while eosinophil granule MBP and the MBP in serum of patients with eosinophilia elute at a volume consistent with the previously established molecular weight of 9,300. These findings suggest that the MBP in pregnancy serum is derived from a source other than the eosinophil.

Animals↗
PubMed1983

Localization of eosinophil granule major basic protein in human basophils.

In experiments using an immunofluorescent method to localize human eosinophil granule major basic protein (MBP) in cells and tissues, a small number of cells stained for MBP that subsequently could not be identified as eosinophils. Because the Charcot-Leyden crystal protein, another eosinophil protein, was recently identified in basophils, we tested whether MBP might also be a constituent of blood basophils. Highly purified, eosinophil-free basophil suspensions were prepared using the fluorescence-activated cell sorter (FACS) to sort basophil-containing mononuclear cell preparations stained with fluorescein-conjugated sheep IgG anti-human IgE antibody. Using these FACS-purified basophils, we found that: (a) enrichment for surface IgE-positive cells (greater than 95% basophils) by FACS also enriched for cells staining for MBP by immunofluorescence; (b) MBP appeared to be localized in the histamine-, heparin-containing granules; (c) significant quantities of MBP were measurable by radioimmunoassay (RIA) in freeze-thaw detergent extracts of purified basophils; and (d) RIA dose-response curves for extracts of purified eosinophils and basophils had identical slopes. The MBP content of basophils from normal individuals averaged 140 ng/10(6) cells, whereas purified eosinophils from normal donors and patients with the hyper-eosinophilic syndrome averaged 4,979 and 824 ng/10(6) cells, respectively. MBP was also detected by immunofluorescence and RIA in cells obtained from a patient with basophil leukemia, although the MBP content for basophil leukemia cells was lower than that for normal basophils. We conclude that basophils contain a protein that is immunochemically indistinguishable from eosinophil granule MBP.

Basophils↗
PubMed1983

Activation of basophil and mast cell histamine release by eosinophil granule major basic protein.

Major basic protein (MBP) is a primary constituent of eosinophil granules. In this report, we demonstrate that MBP from human eosinophil granules initiates a nonlytic histamine release from human leukocytes. A direct effect of MBP on basophils was confirmed using purified human basophils. The kinetics of release were similar to those reported for poly-L-arginine, although MBP was less potent than poly-L-arginine of similar molecular weight. Reduction and alkylation of MBP diminished both the potency and efficacy of the molecule. Native MBP also stimulated histamine secretion from purified rat peritoneal mast cells in a manner characteristic of other polycations. These results emphasize the bidirectional nature of the basophil/mast cell-eosinophil regulatory axis.

Animals↗
PubMed1983

Comparison of ultrasensitive methods for the measurement of IgE.

Because the study of human IgE synthesis and regulation requires exquisitely sensitive and rapidly performed methods for assay of in vitro IgE production, we compared 4 methods for radiometric immunoassay (RIA) of human IgE: double antibody RIA (DARIA), ultrasensitive enzymatic RIA (USERIA), sensitive paper radioimmunosorbent test (SPRIST) and microtiter solid-phase RIA (MSPRIA). IgE protein was measured in serum samples and cord bloods. The USERIA and the MSPRIA consistently detected levels of IgE as low as 27-35 pg/ml. The DARIA and SPRIST were less sensitive. Comparison of the USERIA and the MSPRIA favored the latter because: (1) it is a more rapidly performed assay, (2) it involves fewer manipulations, and (3) it has less variability. We conclude that the MSPRIA for IgE is superior to the other methods both as a research tool for measuring minute quantities of IgE protein (as in tissue culture supernatants) and for measuring IgE in serum samples where concentrations fall below 1 ng/ml (0.42 IU/ml; 1 IU = 2.4 ng).

Humans↗
PubMed1983

Allergen-controlled study of intranasal immunotherapy for ragweed hay fever.

Previous studies of intranasal immunotherapy have not included control groups treated with an irrelevant allergen. In the present double-blind study, we tested the effectiveness of intranasal immunotherapy in 20 patients sensitive to both short ragweed (SRW) and orchard grass (OG). Patients sprayed increasing concentrations of either SRW (n = 11) or OG (n = 9) extract intranasally six times per day for 8 wk before the SRW pollination season. The effects of this treatment were determined by analysis of symptom score diaries and clinical examinations during the SRW pollination season. SRW-treated patients received cumulative AgE doses from 3 to 59 micrograms (mean 21); this mean dose was approximately sevenfold less than that used in a previous study from our laboratory. All patients reported immediate hay fever symptoms after use of the nasal spray. Five patients (four SRW- and one OG-treated) reported episodes of mild epistaxis during treatment; no other unexpected side effects were noted. During the treatment period, more SRW-treated patients showed signs of nasal obstruction and edematous nasal mucosa than OG-treated control patients (p less than 0.03). During the SRW pollination season, the SRW-treated patients reported lower mean weekly symptom scores than the OG-treated control patients, but the difference was not statistically significant. Supplemental antihistamine use was significantly higher (p less than 0.016) in the OG-treated control patients during the SRW pollination period. Subjective assessment of treatment efficacy by patients was similar in both treatment groups. We conclude that intranasal immunotherapy was of only marginal benefit in this study.

Administration, Intranasal↗
PubMed1983

Localization of eosinophil granule major basic protein in chronic urticaria.

The role of the eosinophil in the pathogenesis of cutaneous diseases is not known. The eosinophil granule major basic protein (MBP), constituting the core and accounting for greater than 50% of the eosinophil granule, is toxic to helminths and mammalian cells. To determine whether eosinophil degranulation occurs in lesions of chronic urticaria, we performed an indirect immunofluorescence assay on sections of formalin-fixed, paraffin-embedded tissue, utilizing affinity chromatography-purified antibody to MBP. Twelve of 28 biopsies showed evidence of degranulation as judged by the deposition of MBP outside the eosinophil. The positive staining was of 3 types: (1) small blood vessel walls (5 patients), (2) dispersion of granular material (9 patients), and (3) focal or diffuse immunofluorescence of connective tissue fibers (11 patients). These results suggest a possible role for the cytotoxic molecule MBP in the evolution of lesions of chronic urticaria.

Adolescent↗
PubMed1983

Immunofluorescence identification of eosinophil granule major basic protein in the flame figures of Wells' syndrome.

An indirect immunofluorescence assay using formalin-fixed paraffin-embedded skin was performed on six biopsies from four patients with eosinophilic cellulitis (Wells' syndrome) to determine the extracellular localization of eosinophil granule major basic protein (MBP). Serial sections from each biopsy were treated with either affinity chromatography-purified antihuman-MBP or staphylococcal protein A purified rabbit IgG (control material). There was striking extracellular fluorescence localized to flame figures, and intracellular staining of eosinophils in all sections treated with anti-MBP as compared with controls. The pattern of MBP extracellular staining corresponded to the configuration of each flame figure (as verified by counterstain of the same section with haematoxylin and eosin). These findings show that MBP can be used as a marker for determining eosinophil degranulation and, because MBP is localized to flame figures, they suggest that MBP may play a pathogenic role in Wells' syndrome.

Adult↗
PubMed1983

Effects of trichinellosis on levels of eosinophils, eosinophil major basic protein, creatine kinase and basophils in the guinea pig.

The effects of multiple infections with Trichinella spiralis on the levels of eosinophil major basic protein (MBP), creatine kinase (CK), and leucocytes were studied in the guinea pig. Plasma MBP levels increased after each of four successive infections with T. spiralis. The times of peak elevations in MBP levels and eosinophilia correlated significantly, and both peaks occurred earlier with increased infection dose. CK levels were elevated most dramatically in the primary infection. A direct correlation between peak CK values and larval dose was observed, and the peak occurred earlier with larger larval doses. A dose-dependent basophilia was observed in the primary infection and, like the eosinophil response, basophilia occurred earlier and was markedly enhanced after the second infection. The elevations in MBP levels and eosinophil counts persisted into the third and fourth infections; the basophil response persisted only through the third infection.

Animals↗