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Biomedical subjects

G J Gleich

Publications and source records attributed to G J Gleich.

At least 343 records · Page 19Linked to original sources
PubMed1983

Distinctive cationic proteins of the human eosinophil granule: major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin.

The human eosinophil granule contains a number of cationic proteins that have been identified and purified to homogeneity, including the major basic protein (MBP), the eosinophil cationic protein (ECP), and the eosinophil-derived neurotoxin (EDN). Because of confusion in the literature regarding the distinctiveness of MBP and ECP, we investigated the immunochemical and physicochemical properties of these purified proteins by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels (SDS-PAGE), by specific double antibody radioimmunoassays (RIA) for MBP and ECP, and by fractionation of acid-solubilized eosinophil granules on Sephadex G-50 columns. Analysis of a mixture of the three purified proteins by SDS-PAGE showed that they migrated as three distinct bands with differing m.w. Comparison by specific RIA for MBP and ECP did not demonstrate any appreciable immunochemical cross-reactivities among the three proteins. Sephadex G-50 column fractions of acid-solubilized eosinophil granules were analyzed by RIA and by SDS-PAGE analysis of individual column fractions. MBP, ECP, and EDN eluted at different volumes from Sephadex G-50 columns as determined by RIA and SDS-PAGE. Soluble extracts of eosinophil granules from patients with the hypereosinophilic syndrome contained between six and 64 times more MBP than ECP on a weight basis. These observations demonstrate that MBP, ECP, and EDN are distinctive cationic proteins of the human eosinophil granule and that eosinophil granules from patients with eosinophilia contain considerably greater quantities of MBP than ECP.

Binding, Competitive↗
PubMed1982

Identification by immunofluorescence of eosinophil granule major basic protein in lung tissues of patients with bronchial asthma.

To clarify the role of the eosinophil in asthma, tests were done to find out whether eosinophil granule major basic protein (MBP) is present at sites of epithelial damage in cases of asthma; this protein is toxic to respiratory epithelium and its levels are raised in the sputa of patients with asthma. The test used was an indirect immunofluorescence test, and the specimens tested were formalin-fixed, paraffin-embedded lung tissue obtained post mortem from patients with asthma and from control patients who had died of other diseases. The antiserum used was specific for MBP because it stained only eosinophils in the peripheral blood and because its activity was removed by absorption with MBP. Both controls and asthmatic patients had MBP in the cells, but patients dying of status asthmaticus also had extracellular MBP in mucus plugs, on damaged epithelial surfaces, and in necrotic areas below the basement membrane. Patients who had died of other diseases associated with severe asthma also had extracellular MBP in mucus plugs and on damaged epithelial surfaces. The results suggest that MBP in the eosinophil granule is released into respiratory tissue of patients with severe asthma and that it is associated with tissue damage.

Adult↗
PubMed1982

Formation of Charcot-Leyden crystals by human basophils.

Charcot-Leyden crystals (CLC) are currently believed to be unique to the eosinophil and a hallmark of active eosinophilic inflammation or proliferation. The distinctiveness of the CLC to the eosinophil was questioned in 1965 by Archer and Blackwood (9), but their demonstration of CLC formation in basophils was ignored and later dismissed (1) as being the result of eosinophil contamination of basophil-enriched cell suspensions. We reexamined this question and showed that basophils obtained from the peripheral blood of normal individuals form CLC and that basophils contain a protein that is immunochemically indistinguishable from eosinophil CLC protein. These conclusions are based upon the findings that (a) crystal formation in basophils was demonstrated by specific histochemical staining of crystal-containing cells in highly enriched basophil suspensions prepared by fluorescence-activated cell sorter (FACS) purification of surface IgE-positive cells, (b) that enrichment for surface IgE-positive cells (primarily basophils) by the FACS also enriched for cells staining positively by immunofluorescence for eosinophil CLC protein, and (c) that CLC protein was measured by radioimmunoassay in cell extracts prepared from purified basophil suspensions containing 97-99% basophils and absolutely no contaminating eosinophils. These basophil extracts contained a protein immunochemically indistinguishable from eosinophil CLC protein. Based upon these findings, the CLC or the protein comprising the crystal (lysophospholipase) can no longer be considered as distinctive to the eosinophil. We must now consider the possibility that the presence of CLC in tissues, sputum, or stool may also represent basophil involvement in disease processes.

Animals↗
PubMed1982

Recurrent incapacitating mucosal ulcerations. A prodrome of the hypereosinophilic syndrome.

The hypereosinophilic syndrome is a multisystem disease characterized by infiltration of eosinophils in bone marrow, heart, and other organs. Cutaneous involvement occurs, but usually it appears late in the disease and is of less importance than the cardiac and other organ involvement. We describe two patients with the hypereosinophilic syndrome (HES) in whom the initial manifestations of the disease were recurrent, severe mucosal ulcers involving the mouth and genitalia. In both patients, the mucosal involvement antedated the cardiac manifestations of the disease, and in both, the disease was refractory to treatment.

Adult↗
PubMed1982

Penicillin allergy: clinical experience with a battery of skin-test reagents.

From 1971 through August 1978, 778 patients underwent penicillin skin testing. Each patient gave a history of previous penicillin allergy. The skin-test reagents consisted of (1) fresh solutions of commercially prepared penicillin G (PEN G), ampicillin (AMP), and methicillin (METH); (2) polylysine conjugates of the major antigenic determinants of each of the three drugs: and (3) alkaline hydrolysates of each drug. A total of 108 (14%) patients showed positive reactions to one or more of the reagents. Certain patients showed reactivity to many reagents, whereas others reacted selectively to only one or two reagents. Addition of reagents of AMP and METH resulted in a greater number of positive reactors than when reagents of PEN G alone were used. Of the group whose skin tests were negative, 290 (43%) were later treated with penicillin, twelve of these (4.1%) had allergic reactions. Eight of the group of whose skin tests were positive were subsequently treated, and four of these (50%) had allergic reactions again. A group 151 patients whose skin tests were negative and 27 patients whose skin tests were positive were treated with a cephalosporin. Only two patients had allergic reactions to the drug: both had had negative skin tests to penicillin. We conclude that the risk of subsequent allergic reactivity to penicillin is much lower if the skin tests are negative than if positive, that testing with semisynthetic penicillins increases the number of skin-test reactors, and that the incidence of allergic reactions is low in patients treated with cephalosporin.

Ampicillin↗
PubMed1982

Ra3 skin test response and HLA-A2, antigen E, and IgE: evidence of interactions between antigen E and HLA.

A positive association of Ra3 skin test responses with HLA-A2 has previously been reported to be evident in individuals with low IgE levels and to a greater extent in these individuals than those with high IgE levels. We give evidence based on an analysis of data from 133 individuals that Ra3 response is positively correlated with HLA-A2 among individuals with low Antigen E response and negatively associated with HLA-A2 among individuals with high Antigen E response. Furthermore, we have evidence that any observed interaction between Ra3, IgE, and HLA-A2 can be explained by the correlation between IgE and Antigen E response, and that it is Antigen E response which interacts in the relationship between HLA-A2 and Ra3 skin test response.

Alleles↗
PubMed1982

Serum IgD in subjects with and without chronic obstructive pulmonary disease: a previous finding restudied.

A previous study of matched pairs of subjects with and without COPD showed higher geometric mean values of serum IgD among the affected subjects. In an attempt to replicate this finding in another sample a cooperative study was undertaken to measure IgD in subjects from an epidemiologic study of airway obstructive disease from a different geographic region. The relationship between serum IgD (Ine scale) and % FEV1, was identical in the 2 samples. The lack of statistical significance when analyzing the Arizona sample in a matched pair fashion is attributed to an underrepresentation of subjects with very low % FEV1, and smaller sample size.

Adult↗
PubMed1982

Inhibition of antibody-dependent eosinophil-mediated cytotoxicity by heparin.

Killing of bloodstream forms of Trypanosoma cruzi, the unicellular parasite that causes Chagas' disease in humans, by human eosinophils in the presence of specific antibody to the parasite was inhibited by the polyanion heparin in a dose-dependent manner. The concentration of heparin required to completely abolish eosinophil-effected killing of the flagellate increased as the eosinophil to parasite ratio increased. These results suggest that antibody-dependent eosinophil-mediated cytotoxicity is mediated by basic constituents of the eosinophil granule.

Antibody Specificity↗
PubMed1982

Membrane marker characterization of the eosinophil colony-forming cell.

We investigated the membrane markers of the eosinophil colony-forming cell (EO-CFC). Eosinophil colonies were identified by their ability to show densely packed cell growth and by staining for cyanide-resistant peroxidase activity. Bone marrow cells were characterized prior to soft agar culture by one of two methods: (1) standard erythrocyte (E) and erythrocyte-antibody-complement (EAC) rosetting, or (2) by the human T- and B-cell surface markers, Leu 1 and HLA-DR, using the fluorescence-activated cell sorter. Eosinophil colonies developed mainly from the nonrosetting, null cell population. EO-CFC lacked the human T-cell marker Leu 1, but demonstrated the human B-cell marker, HLA-DR. EO-CFC were also present in peripheral blood and possessed similar properties to those in the bone marrow. The results indicate that EO-CFC are derived from the null lymphocyte cell population and possess HLA-DR markers.

Antibodies, Monoclonal↗
PubMed1982

Ablation of immunity to Amblyomma americanum by anti-basophil serum: cooperation between basophils and eosinophils in expression of immunity to ectoparasites (ticks) in guinea pigs.

Basophils infiltrate the skin and other tissues as part of T lymphocyte and/or antibody-mediated immune responses to certain protein antigens, viruses, tumors, and parasites. Although basophils may comprise a significant fraction of leukocytes in these reactions, their precise role has been poorly understood. Guinea pigs expressing acquired immunity to the tick Amblyomma americanum develop basophil- and eosinophil-rich cutaneous inflammatory responses at tick feeding sites, and tick rejection is associated with extensive local basophil degranulation. We report that a specific anti-basophil serum (ABS) eliminate basophils at tick feeding sites and abolished immunity to A. americanum. ABS does not react with eosinophils and did not reduce blood or bone marrow eosinophils; however, ABS-treated animals had diminished eosinophils at tick feeding sites, perhaps because these sites were deficient in basophil-derived eosinophil-chemotactic factors. AES treatment markedly reduced feeding site eosinophils, did not affect basophil levels, and partially impaired tick resistance. Taken together, our experiments suggest cooperation between basophils and eosinophils in the expression of immunity to ticks in guinea pigs.

Animals↗
PubMed1982

IgG subclasses in monoclonal gammopathy of undetermined significance.

One hundred seventy-five patients with a serum monoclonal IgG who had been followed up for more than 5 years without the development of multiple myeloma, amyloidosis, or other serious diseases were designated as having MGUS. The monoclonal IgG of 83% of patients was classified as IgG1; that of 9%, IgG2; that of 6%, IgG3; and that of 2%, IgG4. The median values for hemoglobin, leukocytes, platelets, calcium, creatinine, size of the M spike, and plasma cell content in the bone marrow were not significantly different in the four subclass groups. The IgA level was reduced in 8% and the IgM in 20% of the total group. The uninvolved IgG subclass levels were reduced in 81% of the IgG1 patients and in all the IgG2, IgG3, and IgG4 patients. The patients with MGUS wer compared to 229 patients with multiple myeloma. The monoclonal IgG of the myeloma patients was classified as IgG1 (73%), IgG2 (14%), IgG3 (8%), and IgG4 (6%). The median hemoglobin values were higher in IgG3 and IgG4 groups. Renal insufficiency and size of the M protein spike were similar in the four subclass groups. Either IgA or IgM was reduced in 75% of the patients. The uninvolved IgG subclasses were reduced in 96.5% of all patients. The 5-year actuarial survival was 30% for the IgG1 group and 33% for the IgG2 group. Twenty patients with MGUS subsequently developed multiple myeloma. Analysis of the results from these patients did not show a difference from the other MGUS patients. The results suggest that the IgG subclass in MGUS does not affect either the features of the disease or the tendency for later development of multiple myeloma.

Adult↗
PubMed1981

Recovery of eosinophils from the peritoneal cavity of the guinea pig.

We studied the effects of various conditions on the recovery of eosinophils from the peritoneal cavity of guinea pigs repeatedly lavaged with saline. We compared the effects of ether and halothane on eosinophil production in guinea pigs either lavaged with saline alone or receiving an injection of polymyxin B before saline lavage. With both anesthetics polymyxin B caused a rapid and consistent increase in eosinophil production, although neutrophils were present. With halothane anesthesia, saline lavage alone yielded mean eosinophil values near those found in the polymyxin group. In contrast, saline lavage alone with ether anesthesia yielded a significantly lower mean eosinophil value than in the polymyxin groups with either anesthetic and the saline lavage alone with halothane anesthesia (P less than 0.05). Additional studies showed that females guinea pigs produced greater numbers of peritoneal eosinophils than male guinea pigs and that peritoneal eosinophilia was maintained for up to 20 weeks by weekly peritoneal lavage with saline alone. Castration of male guinea pigs did not result in eosinophil production comparable to female guinea pigs. Infection with Trichinella spiralis did not enhance peritoneal eosinophilia commensurate with that seen in the peripheral blood. These results indicate that saline lavage alone is a sufficient stimulus for eosinophil production in guinea pigs anesthetized with halothane, that greater numbers of eosinophils are produced in females than males and, finally, that eosinophil production continues at high levels for more than 20 weeks.

Animals↗
PubMed1981

Immunotherapy with short ragweed fraction A:D-glutamic acid:D-lysine polymer in ragweed hay fever.

We report the first human trial of immunotherapy employing the nonimmunogenic carrier, D-glutamic acid:D-lysine linked to short ragweed (SRW) fraction A (fraction A:D-GL). Twelve SRW-sensitive patients with no immunotherapy during the previous 19 yr received a 2-mo (7/79 to 9/79) course of fraction A:D-GL (average dose 49.5 mg, range 21 to 78 mg). We compared their symptom scores and serologic changes with two control groups of SRW-sensitive patients. Patients receiving fraction A:D-GL demonstrated at least a tenfold decrease in skin-test sensitivity to SRW and had statistically lower mean seasonal symptom scores (p less than 0.02) than untreated controls. Mean seasonal symptom scored did not differ statistically from those of control patients on year 4 of immunotherapy. In contrast to the expected suppression of IgE, we found that fraction A:D-GL stimulated both IgE and IgG responses to SRW and SRW-antigen E. These increases in IgE and IgG antibodies were significantly greater than in the control groups and appeared to be due largely to injection of fraction A:D-GL. Though fraction A:D-GL was generally well tolerated, we noted mild generalized urticaria in three patients, and large local reactions in five others. The difference between our results and the earlier results in mice may reside in the particular characteristics of this preparation of fraction A:D-GL.

Adult↗