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Biomedical subjects

A Saxon

Publications and source records attributed to A Saxon.

At least 109 records · Page 6Linked to original sources
PubMed1988

Imipenem cross-reactivity with penicillin in humans.

We examined the potential for IgE-mediated cross-reactivity between the carbepenems, a new class of beta-lactam antibiotics, represented by imipenem, and penicillins. In vivo skin testing with the relevant imipenem and penicillin determinants was undertaken. Having determined the concentrations of imipenem materials that did not induce false positive skin tests in nonpenicillin-allergic control subjects, we tested 40 subjects with a history of penicillin-allergic reactions. Twenty of these subjects were found to be nonallergic to penicillin on skin testing, and none of these subjects reacted to the imipendem determinants. In contrast, half the 20 subjects who were positive to one or more penicillin determinants also reacted to imipenem reagents. There was a good correlation between the penicillin and imipenem reagents to which the patients reacted. Imipenem should only be administered to penicillin-allergic subjects with similar precautions of penicillin administration to such patients.

Cross Reactions↗
PubMed1988

Enhanced ELISA: how to measure less than 10 picograms of a specific protein (immunoglobulin) in less than 8 hours.

In this paper we outline a flexible and rapid method to measure picogram quantities of isotype-specific immunoglobulin (Ig), including IgE. Only readily or commercially available reagents are required: isotype-specific, anti-human Ig murine monoclonal antibodies (Mab) to coat microtiter plates, polyclonal alkaline phosphatase-coupled isotype-specific F(ab)'2 or Fab' fragments as second antibodies, and an enhanced developing system that amplifies the signal-to-noise ratio of the quantitatively bound second antibody. The procedure is detailed in the appendix to enable easy application, even if one has no previous experience with ELISAs. This system can be used to detect less than 10 picograms of Ig in cultures supernatants of cells that contain mixtures of various Igs and it can be used to detect the product of a single cell producing Ig. This method also will be applicable to measurement of the minute quantities of lymphokines and other biologically active molecules produced in vitro and found in various fluids in vivo.

Antibodies, Monoclonal↗
PubMed1988

Functional and phenotypic characterization of human B lymphocyte subsets isolated by unit gravity sedimentation.

We report the use of unit gravity sedimentation with a CelSep apparatus to generate two volumetrically similar but functionally and phenotypically distinct subsets of human peripheral blood B cells. One subset, comprised of small B lymphocytes, underwent a significant size change in response to anti-mu, proliferated synergistically to low concentrations of anti-mu plus B cell growth factor (BCGF) or phorbol myristate acetate plus BCGF, and could be induced to produce immunoglobulin in response to pokeweed-mitogen-derived T-lymphocyte-replacing factors. These cells were primarily sIg+, B1+, B2+, and were virtually free of monocytes (less than 0.01%). Unlike these resting B lymphocytes, the large cells proliferated directly to BCGF, without displaying synergy with anti-mu. These cells displayed very little B2 (less than 7%), did not increase in volume in the presence of anti-mu, and made more immunoglobulin in response to TRF than the small resting B lymphocytes. However, neither population synthesized immunoglobulin spontaneously. This technique, which is highly reproducible, not equipment intensive, and produces high cell recovery (greater than 90%), allows for a precise analysis of the steps involved in the maturation of a resting B lymphocyte to an immunoglobulin-secreting cell.

B-Lymphocytes↗
PubMed1988

Bare lymphocyte syndrome. Consequences of absent class II major histocompatibility antigen expression for B lymphocyte differentiation and function.

The bare lymphocyte syndrome is a rare combined immunodeficiency disorder associated with the absence of class I and/or class II major histocompatibility (MHC) antigens. Although it has been inferred that the immune deficiency is a consequence of disordered MHC-restricted interactions among otherwise normal cells, the biological capabilities and differentiation of B lymphocytes deficient in class II MHC antigens have not been rigorously analyzed. We have examined the phenotypic and functional attributes of B cells with absent class II MHC antigens. Our data demonstrate that these B cells are intrinsically defective in their responses to membrane-mediated activation stimuli. In addition, virtually all the B cells had phenotypic evidence of arrested differentiation at an immature stage. Finally, these B cells also failed to express the C3d-EBV receptor normally present on all B lymphocytes. These data indicate that class II MHC molecules are vital participants in early events of the B cell activation cascade, and that other non-MHC membrane molecules may also be absent as a consequence of either arrested differentiation or as a result of the basic defect affecting the expression of MHC membrane antigens.

Antibody-Producing Cells↗
PubMed1988

Subset of natural killer cells is induced by immune complexes to display Fc receptors for IgE and IgA and demonstrates isotype regulatory function.

Expression of Fc receptors for IgE (FcER) or IgA (FcAR) on purified natural killer (NK) cells was investigated. No FcER+ and a few FcAR+ NK cells were detectable on freshly separated NK (NKH-1+) cells from normal donors. Incubation of NK cells with IgE-anti-IgE immune complexes or IgA-anti-IgA immune complexes induced up to 10 and 20% FcER+ or FcAR+ cells, respectively. These FcR were induced on CD3- but not on CD3+ NKH-1+ cells. In contrast, NK cells from patients with various dysgammaglobulinemias could not be induced to express FcER or FcAR corresponding to their abnormal circulating IgE and/or IgA levels. Enriched FcER+ or FcAR+ induced NK cell supernatants from normals enhanced IgE or IgA synthesis from Ig secreting B cell lines in an isotype-specific fashion without increasing proliferation. Thus NK cells, after interaction with specific Ig isotypes in complexes, express FcR and produce differentiation factors for that isotype.

Antibody Specificity↗
PubMed1987

IgE-enhancing activity directly and selectively affects activated B cells: evidence for a human IgE differentiation factor.

T cells from highly atopic individuals spontaneously secrete in vitro a factor that specifically induces IgE synthesis from normal human B cells. We investigated the effects of such T cell supernatants derived from atopic individuals (TCSN-A) on functionally distinct B cell subsets to determine at what developmental stage B cells become responsive to this IgE-enhancing activity. B cells from normal and allergic donors were separated into subsets of small resting and large activated cells by density centrifugation or unit gravity sedimentation. When stimulated by TCSN-A, large activated B cells made more IgE than small resting B cells. The difference was as much as 3300% in comparing these subsets from allergic donors. Similarly, resting B cells stimulated by Staphylococcus aureus Cowan I (SAC) made 52 to 125% more IgE in response to TCSN-A than unstimulated small resting B cells. However, IgE production from large B cells, already activated in vivo, was not enhanced by the addition of SAC. Notably, the IgE level synthesized by in vivo large activated B cells from allergic persons was markedly greater than that seen with similar cells from normal donors, whereas resting B cells purified from allergic and normal donors produced comparable levels of IgE in response to TCSN-A. These results suggest that this enhancing activity functions as an IgE differentiation factor for activated B cells. This was further confirmed by the effects of TCSN-A on the IgM- and IgE-secreting EBV-transformed human B cell line K1D5. TCSN-A specifically enhanced IgE synthesis from these cells; TCSN from normal donors, IL 2, IFN-gamma, and BCGF did not. These results confirm that this activity functions as an IgE-specific differentiation factor, directly influencing activated B cells to synthesize IgE.

B-Lymphocytes↗
PubMed1987

Constitutive production of B cell differentiation factor-like activity by human T and B cell lines.

A lymphokine demonstrating human B cell differentiation factor (BCDF)-like activity was isolated from immature (MOLT-4f, CCRF-CEM and CCRF-HSDB-2) and mature (HUT-78) malignant human T lymphoid cell lines and from human B lymphoblastoid cell lines (BJAB and ALL-7031-B). All the cell lines were grown long term in serum-free medium. This BCDF-like activity has a molecular mass in the range of 40-60 kDa and stimulates immunoglobulin synthesis of cell lines capable of producing IgA (GM-1056), IgG (GM-1500 and CESS) and IgM (CBL#3). It was not produced by a myeloid cell line. We were only able to identify the differentiation activity produced by the T and B cell lines by using appropriate molecular mass fractions from the serum-free medium as controls. This BCDF-like activity is different from that of the human BCDF so far described as it has a higher molecular mass and is constitutively produced by malignant T lymphoid cell lines which are human T cell leukemia virus-I negative and by B lymphoblastoid cell lines.

Antibody Formation↗
PubMed1987

Jacalin, an IgA-binding lectin, inhibits differentiation of human B cells by both a direct effect and by activating T-suppressor cells.

Jacalin, a lectin extracted from the seeds of Artocarpus intergifolia (jackfruit), has been reported to bind specifically to IgA while inducing B-cell polyclonal immunoglobulin secretion. We confirmed that jacalin only binds to IgA and not to IgG or IgM and extended these findings by showing that it does not bind to IgE. Addition of jacalin to either unfractioned peripheral blood lymphocytes or purified B cells failed to induce immunoglobulin synthesis; indeed immunoglobulin production was diminished in the presence of jacalin. We found that jacalin directly inhibited the induction of immunoglobulin synthesis from B cells in the presence of T-cell replacing factor. Cell lines making IgG, IgM, and IgA were inhibited by jacalin. Furthermore, T cells incubated with jacalin also inhibited immunoglobulin production by stimulated B cells. Under these conditions jacalin was found to be a potent mitogen for T cells but to induce little or no activation of B cells. Jacalin appears to be a potent T-cell mitogen which can induce suppressor T cells for Ig production. It also has a direct inhibitory effect on B-cell Ig production.

Adult↗
PubMed1987

Modulation of ongoing human immunoglobulin synthesis by natural killer cells.

Freshly separated human NK cells (NKH-1+) inhibited IgE synthesis from IgE myeloma U266/AF-10 as much as 70% whereas they enhanced IgG and IgA synthesis 200 and 500% from the lymphoblastoid cell lines GM-1500 and GM-1056, respectively. The inhibition of IgE synthesis by NK cells was due to a direct cytolytic effect on AF-10. This could be reversed using K562 cells in a cold target competition assay. NK cells also inhibited spontaneous IgE as well as IgG and IgA synthesis from B cells of highly atopic donors. On the other hand the enhancement of Ig secretion by NKH-1+ cells was shown to be mediated by soluble factors released from NK cells. Furthermore when NK cells were preincubated with immune complexes (IgE-IC) constructed of human IgE and mouse IgG1 monoclonal anti-human IgE, inhibition of IgE synthesis was reversed, and in some cases actual enhancement of IgE synthesis was observed, while enhancement of IgG and IgA synthesis was not affected. In contrast to NK cells, T cells depleted of NK cells (T-NK), when activated by IgE-IC, suppressed IgE synthesis in an isotype specific fashion. Thus, NK and T-cell modulation of ongoing Ig synthesis involve distinct mechanisms.

Antibody Formation↗
PubMed1987

A mechanism for the suppression of ongoing IgE synthesis.

IgE synthesis from the human plasmacytoma U266/AF-10 was suppressed by addition of IgE immune complexes (IgE-IC). This suppression was isotype-specific as synthesis from other B cell lines was unaffected. Using IgE-IC constructed with a monoclonal antibody that recognizes PS protein-IgE and not ND IgE (the IgE protein made by U266/AF-10), we have shown that this suppression was mediated through the cross-linking of the Fc epsilon receptor.

Antibodies, Anti-Idiotypic↗
PubMed1987

Natural killer cell interaction with IgE in the control of ongoing human IgE synthesis.

Fresh natural killer (NK) cells from normal donors inhibited IgE synthesis from U266/AF-10 cells via a direct cytolytic effect. This inhibition was 'reversed' by incubation of NK cells with human IgE-anti-IgE immune complexes (IgE-IC) for 16 h without a decrease in NK-mediated cytotoxicity. Upon incubation with IgE-IC, Fc epsilon receptors (FcER) were induced on 3-9% of NK cells. These IgE-IC induced FcER+ NK cells from normal donors secreted (an) IgE-specific factor(s) which enhanced U266/AF-10 IgE production without increasing DNA synthesis. Production of this IgE differentiation factor(s) explains the apparent reversal of NK cell inhibition of IgE production.

Antibodies, Anti-Idiotypic↗
PubMed1987

Immediate hypersensitivity reactions to beta-lactam antibiotics.

Allergic reactions to the beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, and monobactams) are a major factor limiting their use. Immediate hypersensitivity reactions to penicillins depend on the presence of preformed allergic (IgE) antibodies to several penicillin determinants. These materials can be used in in-vivo skin testing to exclude those patients at risk for immediate or accelerated allergic reactions. The cephalosporins have not had their relevant determinants defined as related to allergic reactions. The results of in-vivo challenges of patients with IgE to penicillin suggest the incidence of reactivity of cephalosporins in patients allergic to penicillin is less than generally appreciated. The monocyclic beta-lactam antibiotic, aztreonam (a monobactam), failed to show cross-reactivity with penicillin antibodies, because immune reactivity toward the monobactam was directed against side chain rather than nuclear determinants. On the other hand, the new bicyclic carbapenem beta-lactam drugs, represented by imipenem, showed extensive in-vivo cross-reactivity with penicillins.

Anti-Bacterial Agents↗
PubMed1986

Home intravenous immunoglobulin therapy by self-administration.

Immunoglobulin replacement therapy is required by patients with certain antibody deficiency syndromes and is finding increasing application in other immune disorders such as immune thrombocytopenia. We describe the long-term home administration of intravenous gamma-globulin by seven patients themselves using a portable infusion pump. Over a period of as long as 2 years, this has proven to be effective, safe, and cost efficient and a good alternative to hospital or physicians' office-based infusions.

Agammaglobulinemia↗
PubMed1986

Species-specific allergens from the salivary glands of Triatominae (Heteroptera:Reduviidae).

We investigated allergenic cross-reactivity among species of the blood-feeding insects of the subfamily Triatominae. By skin testing, patients allergic to either Triatoma protracta or T. rubida gave positive responses only to the respective salivary antigen. RAST-inhibition experiments demonstrated that binding of IgE antibodies to T. protracta antigen was not inhibited by salivary extracts from T. rubida, T. cavernicola, T. rubrofasciata, or Rhodnius prolixus. The same level of species specificity was found for IgE antibodies to T. rubida. By direct RAST, no T. rubida positive serum bound T. protracta antigen, and 29 of 30 T. protracta positive sera failed to bind T. rubida. One serum from a T. protracta-allergic patient contained IgE antibodies to both T. protracta and T. rubida. RAST-inhibition experiments demonstrated that these antibodies did not cross-react and that this person had separate species-specific antibodies to T. protracta and T. rubida antigens. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of salivary extracts demonstrated that the lower molecular weight bands that contain the antigens responsible for human allergic reactions differed in number and size in all species tested. These studies demonstrate species specificity for the allergic response to Triatoma and stress the importance of accurate insect identification and the need for species-specific antigens for diagnosis and immunotherapy.

Allergens↗