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Biomedical subjects

B M Stadler

Publications and source records attributed to B M Stadler.

At least 73 records · Page 4Linked to original sources
PubMed1991

[Relationship between T-subsets and clinical aspects of HIV-associated diseases].

HIV predominantly infects the CD4+ T cells, which during the progression of the disease are eliminated, causing an immune deficiency which renders the patients more susceptible to infections. To evaluate the relevance of the CD4+ T cell elimination and thus the clinical usefulness of CD4/CD8 subset determinations in HIV infected persons, we investigated whether analyses of 667 subset determinations of 365 patients correlated with clinical stages of HIV-infection (CDC classification). Progress of HIV related disease was accompanied by a fall in CD4+ cells and an increase in CD8+ cells, leading to a drastically reduced CD4/CD8 ratio. This change of T-cell subset values correlated well with the clinical classification (CDC). It was, however, only statistically significant if percent values were used, but not if absolute CD4 cell counts, calculated from the peripheral lymphocyte count, were considered. While patients in CDC stage IVC2 (mainly Candida stomatitis) did not differ from stages IIB, IIIB, IVA, we found statistically lower CD4 values if the patients had stage IVA plus IVC2. Stage IVC1 (mainly Pneumocystis carinii pneumonia [PcP, n = 20]) had even lower CD4 values, as PcP appeared almost exclusively in patients with CD4 counts below 20% or 200/microliter. The lowest CD4 counts were observed in patients with Kaposi sarcoma (n = 11) with CD4 cells less than 10% and significant elevated values of CD8 cells (greater than 50%). While the total lymphocyte count correlated with the absolute counts of CD4 and CD8 cells, it was impossible to estimate the T-subset distribution from the absolute lymphocyte count. Our investigations show that a decreased number of circulating CD4 cells correlates well with an increased tendency to develop infections, and thus support the relevance of CD4 cell measurements for the optimal care of asymptomatic HIV infected persons in particular. They also show that the percent values correlate better with clinical stage than the absolute CD4 cell count.

CD4-Positive T-Lymphocytes↗
PubMed1991

IgE hidden in immune complexes with anti-IgE autoantibodies in children with asthma.

Serum levels of IgE, anti-IgE autoantibodies (Abs), and IgE/IgG anti-IgE immune complexes (ICs) were measured in 110 children with asthma and 90 healthy control children. Significantly enhanced levels of IgE/anti-IgE IC were detected in children with asthma. However, only a weak correlation was found between anti-IgE auto-Ab serum levels and the degree of lung function abnormalities in children with asthma. However, children with asthma with low serum IgE levels had elevated IC serum levels of IgE/anti-IgE auto-Abs, suggesting that IgE might be hidden within these ICs and is therefore not measurable in vitro. The significant elevation of IgE/anti-IgE IC serum levels raises the question whether IgE within ICs is neutralized or might still be involved in immunologic mechanisms responsible for clinical symptoms of bronchial asthma.

Adolescent↗
PubMed1991

IgG anti-IgE autoantibodies in immunoregulation.

Human sera contain anti-IgE autoantibodies with diverse biological functions in vitro. Opposite functions can be shown for triggering of IgE-mediated histamine release from human basophils in terms of anaphylactogenic or nonanaphylactogenic autoantibodies. Furthermore, autoantibodies are either capable of removing IgE from the surface of CD23-positive cells of binding more IgE to such cells. A similar dichotomy seems also to exist for the effect of autoantibodies on human IgE mRNA synthesis as well as IL-4-induced proliferation of human mononuclear cells. Thus, anti-IgE autoantibodies may represent a key factor in the manifestation and the development of allergic disease.

Antibodies, Anti-Idiotypic↗
PubMed1991

Are allergen-specific IgG mainly IgG anti-IgE autoantibodies?

A large proportion of specific IgE occurred in immune complexes with anti-IgE autoantibodies in sera from nonhyposensitized allergic patients. These autoantibodies were misinterpreted as 'specific IgG' in different immunoassays such as dot immunoassays and the radioallergosorbent test (RAST), leading to overestimation of specific IgG. Purified immune complexes contained even more IgG than IgE antibodies. Heating of the complexes liberated specific IgE, producing an upwards RAST class shift. Thus anti-IgE autoantibodies are hiding the specific IgE, which is thereby underestimated. It is not known whether the hiding anti-IgE autoantibodies are also effectively neutralizing circulating or cell-bound IgE and might represent the actual blocking antibody.

Allergens↗
PubMed1990

Human IgE mRNA expression by peripheral blood lymphocytes stimulated with interleukin 4 and pokeweed mitogen.

Expression of human IgE mRNA by peripheral blood lymphocytes (PBL) and an IgE-producing myeloma cell line, U-266, was examined by Northern blot hybridization and compared with IgE levels in culture supernatants. A 2.35-kb IgE mRNA was detected in unstimulated atopic PBL and U-266 cells but not in normal PBL, and its levels correlated with IgE protein levels in the supernatant. Upon stimulation with interleukin 4, a new 1.75-kb transcript was revealed in both atopic and normal PBL but not in U-266 cells. Its expression did not correlate with IgE levels in the supernatant. Pokeweed mitogen also induced the expression of the 1.75-kb transcript without concomitant induction of IgE synthesis by normal PBL and even suppressed the spontaneous expression of the 2.35-kb transcript and IgE protein synthesis by atopic PBL. Interferon-gamma, which suppressed both the 2.35-kb transcript and IgE protein production, had no inhibitory effect on the 1.75-kb transcript. Expression of the 1.75-kb transcript was already high after 2 days of stimulation and peaked around day 4. The length of the transcript is smaller than that of mRNA coding for secreted human IgG and IgA and contains all four C epsilon exon sequences, suggesting it might be a truncated transcript without v region and might be a human counterpart of the murine germ-line C epsilon transcript.

Blotting, Northern↗
PubMed1990

A long-term follow-up study of hyposensitization with immunoblotting.

The formation of specific IgE, IgG1, and IgG4 antibodies was investigated by immunoblotting during hyposensitization with timothy grass-pollen extract and 6 years later, Until the end of immunotherapy, specific IgG antibody levels increased. Also simultaneously, the number of allergenic components detected by IgG increased. However, this IgG response was similar in responding and nonresponding patients; thus, it did not correlate with the clinical outcome of the therapy. More allergenic compounds were also detected by IgE on immunoblots, but again without correlation to success of therapy. Six years after immunotherapy, the therapeutic effect was still present, although by now the observed immunoglobulin-binding patterns were similar to patterns observed in the same patients' sera collected before the initiation of hyposensitization. Thus, changes of antibody-binding patterns in immunoblot do not relate to the success or failure of immunotherapy.

Allergens↗
PubMed1990

[The clinical significance of anti-IgE antibodies in the treatment of allergic rhinopathy].

A simple assay, based on monoclonal antibodies, was used to measure "free" anti-IgE antibodies or anti-IgE antibodies in immune complexes of IgE and anti-IgE. No significant correlation was found between serum IgE levels and the concentration of anti-IgE antibodies. Furthermore, patients who were successfully treated by hyposensitization therapy showed only unmeasurable or extremely low anti-IgE antibody levels in their serum. However, patients who were unsuccessfully treated by hyposensitization had elevated anti-IgE serum titers. Thus, determination of anti-IgE antibodies might become a tool for predicting the success of hyposensitization therapy.

Adolescent↗
PubMed1990

Natural anti-IgE auto-antibodies interfere with diagnostic IgE determination.

A simple method is described which enables measurement of anti-IgE antibodies in free form as well as in immune complexes of IgE and anti-IgE. Anti-IgE antibodies were purified from serum of one selected blood donor with highly elevated levels of such autoantibodies. These purified anti-IgE auto-antibodies inhibited the measurement of myeloma IgE. Purification also revealed that 98% of the subject's serum IgE was masked by anti-IgE auto-antibodies. Our data suggest that IgE determinations in sera containing anti-IgE antibodies might be underestimated.

Adolescent↗
PubMed1990

Enhancement of basophil histamine release by a human basophil-like cell promoting activity.

A basophil-like cell promoting activity (BaPA) is a lymphokine which has the ability to proliferate metachromatically staining cells in human bone marrow. We studied the effect of BaPA on histamine release from human peripheral basophils. BaPA did not directly induce histamine release from basophils. However BaPA ranging from 0.001 to 0.5 U/ml enhanced histamine release from basophils stimulated with anti-IgE, calcium ionophore A23187 or FMLP in a dose-dependent manner. On the basis of recent observations that in addition to their capacity for proliferating progenitor cells, colony-stimulating factors are capable of regulating functions of end-stage cells of the same lineage, this finding that BaPA is able to modulate a basophil function raises the possibility that BaPA also regulates progenitors of basophils.

Basophil Degranulation Test↗
PubMed1990

Influence of IgE fragments on IgE determination.

IgE fragments were detected by polyclonal and monoclonal anti-IgE antibodies using Western blot techniques and immunoassays. Other antibodies detected only intact IgE molecules. In the presence of IgE fragments, higher IgE levels were estimated, depending on the epitope specificity of the antibodies used in the IgE determination assays. IgE fragments have been found together with intact IgE in isolated material from different human sera and also from culture supernatant of an IgE-producing cell line. Our data demonstrate that IgE fragments may be assessed and represent a potential pitfall in diagnostic IgE determinations.

Antibodies, Anti-Idiotypic↗
PubMed1990

[New perspectives in the modulation of allergic inflammation].

Current studies on IgE-dependent allergic reactions focus on the regulation of IgE synthesis by cellular IgE receptors or by their fragments, so-called IgE-binding factors. Recent studies suggest that lymphokines, such as interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), may be more relevant in the modulation of IgE synthesis. Under this aspect studies should concentrate on the role of anti-isotypical anti-IgE antibodies which can be found frequently in IgE-mediated responses. Further studies have given new insights in the variation of releasability and lymphokine-mediated conditioning of effector cells, depending on the type of allergic reaction. Pretreatment of neutrophils with granulocyte macrophage- colony stimulating factor (GM-CSF), or basophils with interleukin-3 (IL-3) renders these cells capable of producing or releasing inflammatory mediators, such as histamine, leukotrienes or platelet activating-factor (PAF). The fact that the interaction of purified lymphokines, such as IL-3 or IL-8 with basophils causes the release of mediators, indicates a possible mechanism for the induction of immediate and delayed allergic reactions. New insights in these mechanisms may offer new immunopharmacological aspects in the treatment of allergic reactions. IgE-mediated allergic reactions can be divided into two distinct phases. During the period of sensitization allergen exposure causes the production of class E immunoglobulins (IgE) in genetically predisposed persons. Repeated allergen exposure in sensitized persons leads to bridging of IgE molecules with basophils or mast cell membranes which finally causes the production and the release of inflammation mediators, such as histamine, leukotrienes and PAF.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Cytokine mRNA levels in antigen-stimulated peripheral blood mononuclear cells.

Levels of cytokine mRNA coding for granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), interleukin (IL) 2, IL 1 beta, IL 4 or IL 6 have been measured by Northern blot analysis after antigen stimulation. As source for RNA we used peripheral blood mononuclear cells (PBMC) from donors which showed a proliferative response after tetanus toxoid or Candida albicans stimulation. For comparison PBMC were also stimulated with lectins and anti-CD3 antibody. With some variations among donors, antigens clearly induced measurable levels of IFN-gamma, GM-CSF and IL 2 mRNA. Increased levels for IL 6 were also detected after antigen stimulation. In contrast to polyclonal T cell stimuli, antigens showed delayed kinetics of mRNA steady-state levels and resembled in this respect more closely the stimulation with pokeweed mitogen. Thus, cytokine mRNA levels may be assessed in unfractionated PBMC after antigen stimulation. The two tested antigens also clearly show a cytokine pattern distinct from that induced in polyclonal stimulations such as anti-CD3.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Regulatory effect of recombinant interleukin (IL)3 and IL4 on cytokine gene expression of bone marrow and peripheral blood mononuclear cells.

This study shows that both recombinant human interleukin (rhIL)3 and rhIL4 induced proliferation in bone marrow (BM) cells of myelogenous leukemia patients in a manner similar to that reported using normal BM cells. However, we additionally found that these cytokines also influenced expression of other cytokines. Namely, using a reproducible dot blot hybridization technique we observed on the one hand that BM cells were capable of constitutively expressing low levels of cytokine mRNA coding for IL3, IL4, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte (G)-CSF and IL 1 beta, and on the other hand that in normal peripheral blood mononuclear cells rhIL4 inhibited mRNA expression coding for GM-CSF, G-CSF, IL3 and IL 1 beta, while IL4 mRNA and 28S rRNA was not affected. In contrast, rhIL3 marginally enhanced mRNA coding for IL3, GM-CSF, G-CSF and IL 1 beta and counteracted the inhibitory effect of IL4. In long-term cultures rhIL3 and rhIL4 had no significant effect on spontaneous cytokine gene expression of myelogenous leukemia-derived peripheral blood or BM cells, but made these cells more sensitive for subsequent stimulation with different polyclonal stimuli. Thus, IL3 and IL4 already modulate cytokine gene expression during the initiation of cell culture and differentiate BM cells into populations of cells which are capable of responding with an enhanced cytokine gene expression after polyclonal stimulation.

Biological Factors↗
PubMed1989

Factors influencing proliferation and histamine content of cultured human bone marrow cells.

Various human lymphokines such as semipurified human interleukin 3 (IL 3), recombinant human IL 3, granulocyte colony stimulating factor (G-CSF), and recombinant human interleukin 4 (IL 4) stimulated growth of human bone marrow cells, but from all these factors tested, only IL 3 by itself was able to cause an increase in histamine content. Fibroblast monolayers as well as factors in their supernatants also increased proliferation and histamine content of bone marrow cells. Concentrated supernatants (Mr greater than 10,000) also inhibited cell proliferation and induced histamine content. The same fraction concentrated on a Mr cut-off greater than 50,000 enhanced cell growth and the total histamine content per culture. Thus, fibroblast supernatants contained both growth promoting and inhibitory factors. However, using the rat basophilic leukemia (RBL) cell line as a test system for such fibroblast-derived differentiation factors, we showed that if cell proliferation was inhibited, histamine content was also enhanced. Furthermore, certain drugs known to inhibit cell division, such as sodium butyrate or hydroxyurea, were also found to cause an increase in histamine content of RBL cells. Thus, our data demonstrate that basophil/mast cell differentiation, in terms of augmentation of cellular histamine levels, may be achieved by exposure to certain growth-inducing cytokines, factors inhibiting proliferation or pharmacological agents which inhibit cell proliferation.

Bone Marrow↗
PubMed1989

Effect of anti-IgE antibodies on IgE binding to CD23.

Human sera contain anti-IgE autoantibodies. Using a human B lymphoblastoid cell line (Wil-2WT cells) and monoclonal murine anti-IgE antibodies (BSW17 and Le27) we investigated a possible role of such anti-IgE antibodies. A 100-fold excess of monoclonal anti-IgE antibodies inhibited binding of 125I labeled IgE to Fc epsilon RII on Wil-2WT cells. Further, both monoclonal anti-IgE antibodies dissociated surface bound IgE from Fc epsilon RII on Wil-2WT cells. However, BSW17 which does not trigger histamine release from human leucocytes, was much more effective in dissociating Fc epsilon RII bound IgE than Le27 which triggers histamine release. These results may suggest that naturally occurring IgG anti-IgE antibodies are able to inhibit binding of IgE to its receptor.

Antibodies, Anti-Idiotypic↗
PubMed1989

Potential role of anti-IgE antibodies in vivo.

Murine monoclonal antibodies which recognize similar epitopes as the naturally occurring human IgG anti-IgE antibodies were used to study their role in interfering with the effector functions of IgE. Two types of antibodies were found which were either anaphylactogenic or did not release histamine from human basophils. However, both types of antibodies were capable of inhibiting binding of IgE to Fc epsilon RII. Furthermore, the nonanaphylactic antibody was capable of removing IgE from Fc epsilon RII+ cells, but no antibodies were found which removed IgE from Fc epsilon RI+ cells. Thus, anti-IgE antibodies may interfere with the pathophysiological role of IgE.

Antibodies, Anti-Idiotypic↗
PubMed1989

New perspectives in the modulation of allergic inflammation.

Studies on the regulation of IgE synthesis by IgE cellular receptors or fragments thereof, the so-called IgE-binding factors, are currently attracting much attention. Even more important may be some lymphokines such as interleukin 4 and interferon gamma which have been shown to have opposite influences on IgE synthesis, both in vitro and in vivo. However, the role of anti-isotypic anti-IgE antibodies, which have been shown to occur frequently during an IgE response, also deserves to be further investigated. At the effector level, namely the development of immediate and late allergic reactions following renewed encounter with allergen, new concepts such as variable releasability and priming of effector cells by lymphokines have opened new investigative pathways. Indeed, pretreatment of neutrophils by granulocyte/monocyte colony-stimulating factor or basophils by interleukin 3 appears essential for production or optimal release of inflammatory mediators such as histamine, leukotrienes, or platelet-activating factor. Even the successive impact of purified lymphokines such as interleukins 3 and 8 on basophils may suffice to initiate mediator release. These phenomena may explain, at the molecular level, the induction of a state of hyperreactivity characteristic of the late-phase allergic reaction. They also suggest new immunopharmacological approaches for the treatment of allergy.

Colony-Stimulating Factors↗