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Biomedical subjects

A Basten

Publications and source records attributed to A Basten.

At least 109 records · Page 6Linked to original sources

Analysis of allergen-specific IgE responses in 341 allergic patients. Associations between allergens and between allergen groups and clinical diagnoses.

An allergic population of 341 patients was studied using 14 different allergen extracts in skin prick tests and radioallergosorbent tests (RAST) in an attempt to identify important allergen sources in the Sydney area and to examine relationships between these diagnostic methods and a number of clinical parameters. A computer based statistical analysis of the data revealed that: (a) male patients showed a significantly higher frequency of skin test reactivity to extracts of house dust and the house dust mite Dermatophagoides farinae; (b) the incidence of positive prick test reactions declined with age; (c) cross-reactive allergenic determinants were found in taxonomically-related extracts (e.g. between different house dust mites, pollens, and fungi); (d) a clear correlation emerged between relative potency using a histamine standard and RAST score which supports the continued use of histamine as a standard in skin prick testing; and (e) important associations between certain allergens and clinical diagnosis emerged (e.g. positive skin test reactions to house dust mites and epithelia but not pollens were associated with asthma).

Adolescent↗

Central nervous system echovirus infection in Bruton's X-linked hypogammaglobulinemia.

A patient with Bruton's X-linked hypogammaglobulinemia, who developed the typical syndrome associated with systemic echovirus 3 infection whilst on routine intramuscular gammaglobulin replacement therapy, is described. Following regular infusions of specific antibody-containing plasma from his spouse, he has shown sustained clinical improvement over a period of two years, and is, therefore, one of the very rare cases with this syndrome to survive for more than a few months.

Adolescent↗

Mycobacterium leprae antigens involved in human immune responses. I. Identification of four antigens by monoclonal antibodies.

Four distinct antigens were identified in soluble sonicates of Mycobacterium leprae by using a panel of 11 monoclonal antibodies. Cross-reactivity studies with other mycobacterial species were conducted by using ELISA and immunoblot assays, and demonstrated that determinants on two of the antigens were present in many mycobacteria, whereas the other two were limited in distribution. Competitive inhibition experiments with radiolabeled monoclonal antibodies showed cross-inhibition between antibodies identifying two of the four antigenic bands. These two bands, of Mr 4.5 to 6 KD and 30 to 40 KD, were resistant to protease treatment after immunoblotting. In contrast, the two other bands of 16 and 70 KD were protease-sensitive. Although all four bands reacted with some human lepromatous leprosy sera in immunoblots, the 4.5 to 6 KD and 30 to 40 KD bands were most prominent. Lepromatous leprosy sera also inhibited the binding of radiolabeled monoclonal antibodies to each of the four antigens, with the mean titer causing 50% inhibition being higher for antibodies reacting with the 4.5 to 6 KD and 30 to 40 KD bands. These findings indicated that all four antigens were involved in the human B cell response to M. leprae.

Animals↗

Co-expression of an epitope on human free kappa-light chains and on a cytoplasmic component in activated T cells.

K-1-21 is a murine monoclonal antibody that reacts with human kappa-light chains in free form but not when they are associated with immunoglobulin heavy chains. K-1-21 was unexpectedly shown to bind to a determinant, STA (Sezary T cell antigen), detected by immunofluorescence in the cytoplasm but not on the surface of Sezary T cells isolated from peripheral blood (4/4 cases) and in Sezary T cells from lymph node and bone marrow (one patient). STA was detected in F2/F7, CCRF-CEM, Molt-4, and CCRF-HSB (four human T ALL cell lines), in JURKAT (a human T cell leukemia line), and in MLA144 (a Gibbon T cell lymphoma line). It also occurred in Leu-3a+ antigen-specific T cell clones (6/6 tested). Moreover, although STA was absent from freshly isolated normal T cells, its expression could be evoked in E+ cells from peripheral blood by in vitro culture with phytohemagglutinin. Thus, STA appears to be a cytoplasmic marker for activated T cells. Cytoplasmic inhibition immunofluorescence studies indicated that K-1-21 binding to STA in Sezary cells or T cell lines was inhibited by preincubation of the K-1-21 antibody with purified kappa-Bence Jones protein. STA from radiolabeled MLA144 cell lysates was immunoprecipitated by K-1-21 and was identified on polyacrylamide gel electrophoresis under reducing conditions as a protein of m.w. 57,000. Additional experiments are underway to define the molecular basis of the interesting cross-reactivity between a determinant in T cells and the K-1-21 reactive epitope on free kappa-light chains.

Antigen-Antibody Reactions↗

The distribution of the Qa-2 alloantigen on functional T lymphocytes.

The expression of Qa-2 on functional lymphocytes was investigated in vitro and in vivo by using a monoclonal anti-Qa-2 antibody. In vitro treatment of T cells with antibody and complement demonstrated that T cells mediating help or delayed-type hypersensitivity for anti-SRBC responses were Qa-2+. In addition, cytotoxic T cells and either their precursors or cells involved in their generation were Qa-2+, as were anti-HGG suppressor T cells. Panning techniques were also used to show that secondary suppressor T cells were Qa-2+ and that there may be heterogeneity in suppressor T cells defined by Qa-2 expression. In vivo treatment of mice with anti-Qa-2 resulted in decrease in immune responsiveness seen by i) prolongation of skin grafts with either H-2D or I-A differences, ii) suppression of delayed-type hypersensitivity, and iii) inhibition of T cell-mediated suppression. Finally, IgG, but not IgM, anti-body-forming cells were Qa-2+.

Animals↗

The surface expression of a tumor-associated antigen on human kappa myeloma cells.

The monoclonal antibody K-1-21 defines an antigen, KMA (kappa myeloma antigen) on the surface of human kappa myeloma cells. K-1-21 also recognizes human kappa light chains in free form but not when covalently bonded to heavy chains. To examine the relationship between KMA and this determinant on free kappa chains, the surface expression of KMA was examined on the IgG, kappa myeloma line LICR LON/HMy2 (HMy2). No patching or capping was observed in the presence of K-1-21 alone, but KMA could be capped if the cells were incubated with K-1-21 followed by fluorescein isothiocyanate-conjugated sheep F(ab')2 anti-mouse immunoglobulin. Capping was not affected by the inhibitors calcium ionophore or dibucaine. When IgG molecules were removed from the cell surface by capping with anti-IgG antiserum both KMA and free kappa light chains could still be detected with K-1-21 and a polyvalent anti-kappa antiserum, respectively. By contrast, after removal of all surface kappa chains with the polyvalent anti-kappa serum, no staining was observed with K-1-21 indicating that KMA may be an epitope on free kappa chains inserted in the membrane of kappa myeloma cells but absent from normal cells. KMA cell surface expression varied with the stage of the cell cycle. Flow cytometric analysis of K-1-21-stained HMy2 cells from either continuous cultures or from elutriated fractions enriched for various cell cycle phases showed that, within the cycling population, cells in G2 + M expressed KMA at a higher frequency and density than did cells in G1.

Antibodies, Monoclonal↗

Induction of memory and effector suppressor T cells by perinatal exposure to antigen.

The development of tolerance and suppression after perinatal exposure to antigen was studied to clarify the role of suppressor cells in self tolerance. Deaggregated human gamma globulin (dHGG) was administered transplacentally to fetal mice by injecting their mothers at various stages of pregnancy. Other mice were exposed to dHGG present in the colostrum of foster mothers previously injected with dHGG. Nonspecific suppression was seen on adoptive transfer of spleen cells from all donors less than six weeks of age. After that time, HGG-specific primary suppression by Ly-1-2,3+Ia+ T cells was detected in all animals exposed to dHGG either pre- or postnatally and persisted for up to three months. In addition, recall of specific memory suppression by antigen challenge was demonstrable for up to six months. Tolerance, on the other hand, was generated only by higher doses of dHGG in utero and was relatively short-lived when compared to suppression. The short duration of tolerance could not be attributed to the generation of T helper cells, since no significant HGG-specific helper activity was detected after perinatal exposure to HGG; rather it was thought to be due to the failure of small doses of dHGG to generate sufficient effector T suppressor (Ts) cells to inactivate the continually increasing number of HGG-specific B cells being generated during ontogeny. Since perinatal tolerance to HGG is known to be prolonged by repeated exposure to antigen, this model implies that the maintenance of natural self tolerance is Ts cell dependent and requires the continued presence of antigen.

Aging↗

Antigens and allergens from the common house dust mite Dermatophagoides pteronyssinus. Part I. Demonstration of multiple allergens by immunochemical and biologic analyses.

The complexity of a highly allergenic water-soluble extract of the common house dust mite Dermatophagoides pteronyssinus has been investigated by use of the preparative fractionation techniques of ultrafiltration, gel permeation chromatography, and isoelectric focusing, and the allergenic properties of the resultant fractions are assessed by skin prick tests, RAST, and a histamine-release assay. In addition, two analytical approaches were used to identify allergens-radioimmunoelectrophoresis and a new technique for detecting IgE-binding proteins separated by isoelectric focusing and transferred onto a nitrocellulose membrane by transverse electrophoresis. These various techniques for allergen detection revealed differences in the number and distribution of allergens in the crude mite extract. The data obtained are consistent with the conclusion that allergenic activity of D. pteronyssinus extracts is due to the existence of a number of antigenically distinct allergens and not due to a single, major allergen.

Allergens↗

Antigens and allergens from the common house dust mite Dermatophagoides pteronyssinus. Part II. Identification of the major IgE-binding antigens by crossed radioimmunoelectrophoresis.

Crossed immunoelectrophoresis demonstrated 51 antigens in a water-soluble extract of the house dust mite Dermatophagoides pteronyssinus. Autoradiography demonstrated that 11 of the antigens bound IgE antibodies in the sera of house dust mite-allergic patients. IgE antibodies in 23 different sera reacted with from one to eight antigens. On the basis of Lowenstein's (1978) definition of a "major allergen," two of the antigens, numbers one and 36 would be described as "major allergens." Apart from antigen number 36 that has already been demonstrated to be an important allergen in patients allergic to D. pteronyssinus, the clinical importance of the other 10 IgE-binding antigens has yet to be assessed. Reasons against use of the term "major allergen" and its replacement with the title "clinically important allergen" are advanced.

Allergens↗

Suppressor T cell memory. Induction and recall of HGG-specific memory suppressor T cells and their role in regulation of antibody production.

Regulation of the antibody response to the hapten, dinitrophenyl (DNP), was studied using human gammaglobulin (HGG) as the carrier in an adoptive transfer system. CBA mice immunized at least 4 weeks previously to HGG or DNP served as the source of T helper cells and hapten-primed B cells, respectively. The addition of spleen cells from donors recently primed to HGG in immunogenic form (aHGG) suppressed the collaborative anti-DNP PFC response as effectively as cells from tolerant donors. The suppressive effect was antigen-specific and was mediated by a T cell with the same phenotype (Ly-1-, Ly-23+, Ia+) and induction kinetics as those previously identified in HGG-tolerant animals. During the primary response to HGG an early burst of helper activity was detected initially, followed by a wave of suppression which peaked at day 7 and subsequently waned, allowing adoptive helper function to reappear during the third week. When previously immunized animals were boosted with soluble HGG after primary suppression had waned, the sequential appearance of helper and suppressor activity was accelerated, and the secondary suppressive effect was more profound and of longer duration than that observed during a primary response. Although helper activity was not apparent during the peak of secondary suppression, helper T cells (Th) had not been functionally deleted since treatment of the donor spleen cells with anti-Ia and complement to deplete suppressor T cells (Ts) before adoptive transfer resulted in significant augmentation of the anti-DNP response. The secondary suppressive effect was formally shown to be mediated by activated Ts effector cells bearing the same surface markers as the cells responsible for primary suppression. The results suggest that the Ts population, like other lymphocyte subsets, contain memory cells capable of rapid reexpression of effector function upon secondary exposure to antigen. These cells are considered to be of a major importance in maintenance of immune homeostasis.

Animals↗

Human antigen-specific IgA responses in blood and secondary lymphoid tissue: an analysis of help and suppression.

Antigen-specific IgA responses to influenza virus were obtained from lymphocytes derived from human secondary lymphoid tissue but not from the circulating pool (blood). T helper cells for IgA were present in both the circulating pool and secondary lymphoid tissue, were of the Leu-3A+ subset, and were relatively radioresistant. In addition, T alpha cells were shown to be important, but not crucial, for IgA helper responses. T cell-dependent suppression of IgA responses was demonstrated with T cells from both mucosal and systemic lymphoid tissue and was mediated by a radiosensitive Leu-2a+ cell. In contrast to T cells, functional B cell precursors for antigen-specific IgA responses were found only in secondary lymphoid tissue and not in the circulating pool.

Antibodies, Viral↗

A tumor-associated antigen specific for human kappa myeloma cells.

A monoclonal antibody (K-1-21) raised against a kappa Bence Jones protein exhibits unique binding properties to malignant plasma cells. K-1-21 is an IgG1 kappa antibody that reacts with human kappa light chains in free form, but shows no reactivity with heavy chain-associated kappa light chains. By immunofluorescence, K-1-21 binds to the surface of LICR LON/HMy2 (HMy2) kappa myeloma cells and to plasma cells from a majority (8/11) of patients with various types of kappa myeloma; it did not bind to the surface of normal cells, nor to malignant cells of non-kappa myeloma origin. Flow cytometry analysis of K-1-21 binding to HMy2 cells indicated that the surface reactivity of K-1-21 could be completely inhibited by preincubation of the antibody with purified kappa light chains, whereas no inhibition occurred after preincubation with lambda chains or intact human IgG. Thus, the epitope recognized by K-1-21 on the cell surface may be similar, if not identical, to the determinant recognized on soluble free kappa light chains, and constitutes a tumor-associated antigen with selectivity for kappa myeloma cells. K-1-21 may therefore have clinical potential in patients with kappa myeloma.

Animals↗