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Biomedical subjects

H Bazin

Publications and source records attributed to H Bazin.

At least 145 records · Page 8Linked to original sources
PubMed1988

The interaction of IgG subclasses with solubilized Fc receptors of rat basophilic leukemia cells.

Rat basophilic leukemia (RBL) cells carry two surface glycoprotein molecules named R (or alpha) and H which, when detergent solubilized, bind to rat IgE-Sepharose. The same two molecules also bind to rat IgG-Sepharose but with a lower affinity. R is a component of the high affinity Fc receptor for IgE. In the present study the inhibition of the binding of R and H to rat IgG-Sepharose by various homologous and heterologous immunoglobulins was used to assess their relative affinities for the two receptor molecules. Ranking the rat immunoglobulins in order of their affinities for the R receptor yielded: IgE much greater than IgG2a greater than IgG1 greater than IgG2b; and for H: IgE greater than IgG2b greater than IgG1 greater than IgG2a. Rat IgG2c inhibited the binding of both R and H but a precise ranking could not be assigned. Conclusive evidence has been obtained for the Fc specificity of these interactions. The affinities of the mouse IgG subclass/R interactions can be ranked: IgG1 greater than IgG2a greater than IgG2b; and for the H receptor: IgG1 greater than IgG2b greater than IgG2a. All of the mouse proteins and other heterologous IgGs, such as those of sheep, goat, equine and rabbit origin, interacted considerably more strongly with H than with R. No interaction with mouse IgG3 could be detected under the conditions tested.

Animals↗
PubMed1988

Immunodetection of small cell lung cancer metastases in bone marrow using three monoclonal antibodies.

Detection of bone marrow metastases by indirect immunofluorescence methods was investigated using three monoclonal antibodies (MoAbs) raised against small cell lung cancer (SCLC). These antibodies, designated anti-LCA1, -LCA2 and -LCA3, recognize three different antigens on the surface of SCLC cells. Eighty-four bone marrow samples from 74 different patients were studied. Whereas tumor cells were found in 32 (38%) by MoAb staining, only 10 (12%) were positively identified using conventional morphological methods. Nine out of the morphologically positive specimens showed reactivity with at least two monoclonal antibodies. Among the 32 samples proven positive by immunofluorescence, an important antigenic variability was noted. Anti-LCA1 recognized tumor cells in 62%, anti-LCA2 and anti-LCA3 in 53%. Due to the recognition of bone marrow involvement by fluorescence methods in 26% of the 34 patients classified as limited disease, a new subgroup of limited disease patients was defined whose prognosis remains undetermined. Our results confirm the utility of immunodetection in the diagnosis of SCLC bone marrow metastases and emphasize the advantage of using a panel of MoAbs with different antigenic specificities. Further study is needed to determine the prognostic significance of bone marrow involvement established by immunodetection.

Antibodies, Monoclonal↗
PubMed1988

Delayed type hypersensitivity (DTH) in anti-IgM-treated B cell-depleted mice: analysis of induction and effector phase.

The induction and the effector phase of murine delayed type hypersensitivity (DTH) were evaluated in mice treated from birth with anti-IgM antibodies; these mice had no mature B cells and could not produce an antibody response. To study the effector phase, long-term cultured cloned helper T cells were injected subcutaneously together with the specific antigen into the hind footpad of normal and B cell-deficient mice. Antigen-specific DTH responses assessed by the local swelling reaction 24 h after transfer measured against a particulate antigen (sheep red blood cells, SRBC) as well as a soluble antigen (ovalbumin, OVA) were unaffected by the absence of B cells. To study the induction phase of DTH, 3-day immune in vivo primed lymphocytes from normal or B cell-depleted mice were adoptively transferred by subcutaneous injection into the hind footpad of naive syngeneic recipients. B cell depletion did not affect the induction of cells capable of responding to SRBC; in contrast, the response to soluble antigen (OVA) was significantly reduced, suggesting that B cells or their products participated in the induction of a DTH response to a soluble antigen.

Animals↗
PubMed1988

Unimpaired first-set and second-set skin graft rejection in agammaglobulinemic mice.

B cell and antibody-deprived B10.BR chronically suppressed by rabbit antimouse IgM serum rejected first-set allogeneic skin grafts as rapidly as control mice. We confirmed this finding using BALB/c mice born from B cell-deprived mothers and chronically treated with anti-IgM antibodies. Such mice had previously been shown to be agammaglobulinemic except for the suppressing monoclonal rat antimouse IgM antibody in their serum. These results indicate that in mice neither first nor accelerated second-set skin graft rejection reactions depend upon preexisting natural or specifically induced antibodies.

Agammaglobulinemia↗
PubMed1988

Clearance of lymphocytic choriomeningitis virus in antibody- and B-cell-deprived mice.

The role of antibody in immune recovery from infection with lymphocytic choriomeningitis virus (LCMV) strain WE was evaluated in B-cell-depleted mice. Mice were treated from birth with either affinity-purified rabbit anti-mouse immunoglobulin M (IgM), normal rabbit immunoglobulin, or, alternatively, an affinity-purified monoclonal rat anti-mouse IgM antibody (LO-MM-9); untreated mice served as controls. B-cell depletion was considered complete in specifically treated mice according to the following criteria: absence of a significant response to the B-cell mitogen lipopolysaccharide, absence of B cells expressing immunoglobulin on their surfaces, absence of detectable IgM or IgG in serum, and presence in the serum of free anti-IgM antibodies. In organs of mu-suppressed BALB/c mice, LCMV-WE replicated, dependent upon organ, at the same rate or more rapidly and, in general, to higher titers than in normal rabbit immunoglobulin-treated mice; untreated mice eliminated the virus most rapidly and showed lower virus titers. In addition, LCMV-primed control mice cleared a second LCMV challenge very rapidly and contained no virus by day 3, whereas mu-suppressed mice had virus in their blood and organs (except the spleen) up to days 3 to 6. The observed effects of anti-mu treatment may reflect the action of neutralizing antibodies (which so far have been difficult to demonstrate in vivo) or other antibody-dependent antiviral mechanisms which, together with T cells, efficiently control LCMV clearance.

Animals↗
PubMed1988

6;7 chromosomal translocation in spontaneously arising rat immunocytomas: evidence for c-myc breakpoint clustering and correlation between isotypic expression and the c-myc target.

Our previous studies have shown that spontaneously arising immunocytomas in the LOU/Ws1 strain of rats contain a t(6;7) chromosomal translocation in all seven tumors studied (F. M. Babonits, J. Spira, G. Klein, and H. Bazin, Int. J. Cancer 29:431-437, 1982). We have also shown that the c-myc is located on chromosome 7 (J. Sümegi, J. Spira, H. Bazin, J. Szpirer, G. Levan, and G. Klein, Nature (London) 306:497-499, 1983) and the immunoglobulin H cluster on chromosome 6 (W.S. Pear, G. Wahlström, J. Szpirer, G. Levan, G. Klein, and J. Sümegi, Immunogenetics 23:393-395, 1986). We now report a detailed cytogenetic and molecular analysis of nine additional rat immunocytomas. The t(6;7) chromosomal translocation is found in all tumors. Mapping of the c-myc breakpoints showed that in 10 of 14 tumors, the c-myc breakpoints are clustered in a 1.5-kilobase region upstream of exon 1. In contrast with sporadic Burkitt's lymphoma and mouse plasmacytoma, only 1 of 14 tumors contains the c-myc breakpoints in either exon 1 or intron 1. Analysis of the sequences juxtaposed to the c-myc show that immunoglobulin H switch regions are the targets in at least five tumors and that there is a strong correlation between the secreted immunoglobulin and the c-myc target. Unlike sporadic Burkitt's lymphoma and mouse plasmacytoma, at least two rat immunocytomas show recombination of the c-myc with sequences distinct from immunoglobulin switch regions.

Animals↗
PubMed1988

Detection of small cell lung cancer bone marrow metastases by immunofluorescence.

It is well known that small cell lung cancer (SCLC) has a high propensity to metastasize to the bone marrow and that such involvement has a prognostic significance. A more accurate detection of these bone marrow metastases is thus mandatory. In this study, we analysed the results of the detection of these metastases using an indirect immunofluorescence test. For this purpose, 3 anti-SCLC rat monoclonal antibodies (MoAbs) specific for 3 different antigens (LCA1, LCA2, LCA3) have been utilized to examine 59 bone marrow samples from patients at time of diagnosis and 20 samples from chemotherapy treated patients. Eight patients had bone marrow clearly involved by morphological analysis. They all had fluorescent cells recognized at immunodetection with at least 2 MoAbs positive for 7 out of the 8 samples. Fifteen samples, negative by morphological analysis, were proven positive by immunofluorescence. In 12 cases, involvement was detected only by 1 MoAb (6 anti-LCA1, 2 anti-LCA2, 4 anti-LCA3). A correlation was found between the number of samples proven positive by morphological analysis and the number of positive MoAbs for these samples (p less than 0.005). Among the bone marrow samples provided by the 32 limited disease patients, LCA positive cells were detected in 9 (28%) compared to 14 out of the 27 (52%) samples from extensive disease patients (p less than 0.05). We concluded that the indirect immunofluorescence with a panel of MoAbs increases the rate of detection of bone marrow SCLC metastases.

Antibodies, Monoclonal↗
PubMed1988

HgC12 induces T and B cells to proliferate and differentiate in BN rats.

Mercuric chloride induces in Brown-Norway (BN) rats an autoimmune disease characterized by the production of various autoantibodies and by a marked increase in the IgE serum concentration. This agent is responsible for a T dependent polyclonal activation of B cells, which is probably due to the emergence of autoreactive T cells. The aim of this study was to evaluate the effect of HgCl2 injections on lymphoid organs and on the serum concentration of the various Ig isotypes. HgCl2 induced (1) a lymphoproliferation in spleen and lymph nodes involving B and T helper cells while the number of T suppressor/cytotoxic cells was not modified, (2) an increase in the number of Ig containing cells resulting in a rise in all serum Ig isotypes, and (3) an early thymic atrophy probably immunologically mediated, which was not involved in the induction phase of the disease since adult thymectomy had no effect. These findings demonstrate that the polyclonal effect of HgCl2 is not isotype-restricted although the IgE response is predominantly affected and they support evidence for a major role for an excess of T help in the HgCl2-induced polyclonal activation of B cells. It was also observed that B cell areas are present in normal BN rat thymuses, the potential role of which in the induction of autoimmunity remains to be investigated.

Animals↗
PubMed1988

Aberrant class switching juxtaposes c-myc with a middle repetitive element (LINE) and an IgH intron in two spontaneously arising rat immunocytomas.

Our previous studies of spontaneously arising rat immunocytomas of the Lou/Wsl strain have shown that Ig switch regions are frequently the targets for c-myc recombination. In several tumors, however, we were unable to show recombination of the c-myc with Ig switch regions. We have cloned the rearranged c-myc fragments from 2 of these tumors, IR209 and IR223, and found that the c-myc recombines with a LINE region in the IR209 and with intron 1 of the epsilon locus in the IR223. Although switch regions are not found at the breakpoints, the sequences at the breakpoints share limited homology with Ig switch recognition sequences. This suggests that the switch recombinase enzymes are able to recognize sequences in addition to the defined switch recombination sites. At the same time, both the LINE and epsilon intron 1 sequences are located within the Ig cluster, providing further evidence for the selection of c-myc activation by Ig sequences in the pathogenesis of rat immunocytoma, mouse plasmacytoma, and Burkitt's lymphoma.

Animals↗
PubMed1988

K-cell-mediated cytotoxicity induced with rat monoclonal antibodies. I. Antibodies of various isotypes differ in their ability to induce cytotoxicity mediated by rat and human effectors.

Among the rat antibodies tested in this study, monoclonals of IgG2a isotype were the best, IgG1 and IgG2b being also effective, for induction of K-cell-mediated cytotoxicity of relevant nucleated target cells by rat effectors (Nude spleen cells). The single rat monoclonal IgE tested was also active. Rat antibodies of IgM and IgA classes of immunoglobulins were not active in that system. IgG2c and IgD monoclonals were not tested. Using the same panel of reagents, cytotoxicity mediated by human K cells (peripheral blood mononuclear cells) was only induced by the IgG2b class of rat monoclonals.

2,4-Dinitrophenol↗
PubMed1987

Suppression of IgE responses by passive antigen inhalation: dissociation of local (mucosal) and systemic immunity.

Animals from high- and low-IgE-responder rat strains were preexposed to antigen-containing aerosols of different droplet sizes, prior to parenteral antigenic challenge. Depending upon the type of aerosol employed, systemic immunological tolerance developed in high-IgE-responder animals in the IgE antibody class either with or without concomitant production of salivary IgA, indicating that the two antibody isotypes were under independent control, and further that IgA-mediated immune exclusion was not central to the development of tolerance in the IgE class. Low-IgE-responder rats exhibited biphasic salivary IgA responses during exposure, which could not be recalled by subsequent parenteral challenge, suggesting that secretory immunity in the respiratory tract may also be down regulated by repeated exposure to airborne antigens.

Aerosols↗
PubMed1987

Studies of the IgE binding sites to rat mast cell receptor with proteolytic fragments and with a monoclonal antibody directed against epsilon heavy chain: evidence that the combining sites are located in the C epsilon 3 domain.

The binding sites of rat IgE to mast cell receptor were investigated by the use of proteolytic fragments and a monoclonal antibody to epsilon chain (MARE-1). Three main fragments were characterized by short-time papain digestion of IgE: F(ab')2-E, a fragment related to the C, 4 domain, and an asymmetric fragment corresponding probably to an IgE molecule with one proteolyzed C, 3 domain. Neither F(ab')2-E nor C, 4 could interfere with the binding of IgE to rat mast cells. These two fragments did not show significant polymerization upon heating at 56 degrees C, while large amounts of polymers were produced from whole IgE, MARE-1 monoclonal antibody was found to react neither with F(ab')2 nor with C, 4, thereby suggesting its interaction with the C, 3 domain. MARE-1 was found to inhibit partially (about 55%) the binding of IgE to its receptor. Taken together the results indicate that the binding sites of IgE to rat mast cell receptor are located within the C, 3 domain. In addition, isolation of the C, 4 domain will be useful to evaluate its participation in the affinity of IgE to receptors of other cells such as lymphocytes or macrophages.

Animals↗
PubMed1987

Inhibition of the reverse transcriptase from HIV by 3'-azido-3'-deoxythymidine triphosphate and its threo analogue.

3'-Azido-3'-deoxythymidine triphosphate (erythro) and its threo isomer were synthesized and investigated for their inhibition of HIV reverse transcriptase from virus isolate U 937/HTLV-III. The erythro isomer was a competitive inhibitor of the reaction directed by (rA)n(dT)12-18 and the Ki value was 0.0022 microM. The threo isomer was at least 100-fold less active. The inhibition was specific for dTMP incorporation, and dGMP incorporation using (rC)n(dG)12-18 as template/primer was not affected. The Km value for dTTP varied between 0.7 microM and 1.7 microM. Reverse transcriptase from nine HIV isolates were tested for inhibition by the erythro isomer and only slight differences in sensitivity were observed.

Antiviral Agents↗
PubMed1987

Rat C3 conversion by rat anti-2,4,dinitrophenyl (DNP) hapten IgA immune precipitates.

Monomeric (m-) and polymeric (p-) anti-DNP monoclonal (MC) rat IgA antibodies (Ab) were tested for precipitation with DNP-bovine serum albumin (DNP-BSA) and C3 conversion in rat serum, with rat MC anti-DNP IgG2b used as reference. At equivalence, p-IgA rapidly precipitated DNP-BSA, with little antigen (Ag) left in the supernatant. In contrast, m-IgA at five-fold higher concentration precipitated Ag very slowly, with less than 50% of Ag precipitated at equivalence. The Ag/Ab weight ratio at equivalence was 0.13 for both m- and p-IgA, but the molar ratio was 0.3 for m-IgA and close to 1.0 for p-IgA, suggesting a higher avidity of p-IgA. Rat C3 conversion by rat IgA immune precipitates (IP) was about 20% with m-IgA and 40% with p-IgA. EGTA did not significantly affect these figures. Therefore, rat MC IgA IP activated the rat alternative C pathway. Neither rat nor mouse IgA anti-DNP IP activated C3 in normal human serum.

Animals↗
PubMed1987

Different patterns of inhibition of avian myeloblastosis virus reverse transcriptase activity by 3'-azido-3'-deoxythymidine 5'-triphosphate and its threo isomer.

The two isomers 3'-azido-3'-deoxythymidine 5'-triphosphate (erythro-AZT-TP) and 1-(3'-azido-2',3'-dideoxy-beta-D-xylofuranosyl)thymine 5'-triphosphate (threo-AZT-TP) were studied as inhibitors of the reverse transcriptase activity of avian myelobastosis virus. Kinetic analysis of the (rA)n X (dT)12-18 (a standard template primer complex of polyriboadenylate and oligodeoxythymidylate of indicated length)-directed reaction revealed that erythro-AZT-TP was a competitive inhibitor with respect to dTTP, whereas threo-AZT-TP was a noncompetitive inhibitor. The apparent Ki values, as calculated from Dixon plots, were 0.48 and 5.5 microM, respectively, compared with a Km value for dTTP of about 70 microM. These results indicate that erythro-AZT-TP had an approximately 150-times-higher affinity to the enzyme than dTTP had and that the avian myeloblastosis virus reverse transcriptase had different binding sites for the two isomers.

Avian Leukosis Virus↗
PubMed1987

Neonatal IgE injections do not modify Nippostrongylus brasiliensis-induced and mercuric chloride-induced IgE increase in the rat.

The effect of neonatal IgE injections on total IgE responses was studied in two rat models. After Nippostrongylus brasiliensis infection, no differences in serum IgE level and surface or cytoplasmic IgE expression were observed between IgE-treated and control LOU/C rats. Likewise, after HgCl2 injection, IgE-treated Brown-Norway rats and controls showed no difference in serum IgE level or in the development of autoimmune glomerulonephritis and proteinuria. It has been concluded that IgE-class-restricted tolerance, induced by neonatal injections of IgE, cannot be observed in rats after strong IgE stimulation.

Animals↗