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Biomedical subjects

N Tada

Publications and source records attributed to N Tada.

At least 145 records · Page 8Linked to original sources

Secretion of either of a pair of immunoglobulins, IgM or IgX, in somatic hybrid cells derived by fusion of a B-cell lymphoma cell line carrying both immunoglobulin isotypes.

The 1.29 cell line is a nonsecreting B-cell leukemia which bears two different immunoglobulin isotypes on its surface, IgM and IgX. The 1.29 cells were hybridized with nonsecreting myeloma cells giving rise to dozens of immunoglobulin secreting hybridomas. These fall into three groups differing in the class of immunoglobulin they secrete. Cells of the first group secrete pentameric IgM (mu, kappa), those of the second group secrete an unknown immunoglobulin, IgX, which may constitute an allotype of IgA, and those of the third group produce light chains only. The two complete immunoglobulins, IgM and IgX, have the same idiotype, as revealed by serological cross-reactivity of an exhaustively absorbed rabbit anti-idiotype serum. The molecular sizes of the heavy chains of the secreted IgM and IgX are slightly smaller than the mu and delta chains, respectively, which are derived from the surface of normal B cells as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Animals↗

A new surface antigen (PC.2) expressed exclusively on plasma cells.

Somatic cell hybridization of NS.1 nonsecretor myeloma cells with spleen cells of (DBA/2 X C57BL/6)F1 mice immunized against the myeloma MOPC 70A of BALB/c mice led to the establishment of five hybridoma clones which continuously secrete anti-MOPC 70A cytotoxic antibodies. The respective antigen detected by each of the five monoclonal antibodies is expressed both on plasmacytomas and on antibody-secreting cells as the only normal cell type. The tissue distribution of this new antigen is different from that reported for the alloantigen PC.1, and we have therefore designated it as PC.2. On the basis of immune elimination of direct and indirect plaque-forming cells, all mouse strains tested express PC.2 determinants, identifying PC.2 essentially as an autoantigen. Conventional anti-PC.1 alloantiserum contains antibodies to the PC.2 determinant, and these antibodies are distinguishable from the anti-PC.1 antibodies proper by the fact that only the latter are absorbed by liver cells. Monoclonal anti-PC.2 antibodies are not directed against MuLV-(murine leukemia virus)--associated antigens as over 20 ecotropic, several MCF (mink colony forming recombinant, and xenotropic viruses failed to react in immunofluorescence assays.

Animals↗

Studies of the mouse Ly-6 alloantigen system. I. Serological characterization of mouse Ly-6 alloantigen by monoclonal antibodies.

Three monoclonal antibodies were produced by fusing mouse myeloma cell line NS-1 with spleen cells from C3H/An mice hyperimmunized with B6-H-2k spleen cells. These antibodies recognized an alloantigen displaying a similar strain distribution pattern to the Ly-6.2 and Ala-1.2 alloantigens. Analysis of CxB and BxH recombinant inbred mice revealed close linkage of genes controlling Ly-m6 and Ly-6. The monoclonal antibodies lysed 70 percent of cells in lymph nodes and 60 percent in spleen in direct cytotoxicity assays, but did not lyse significant numbers of cells of thymus and bone marrow. Separated T and B cells were reactive with the antibodies, but T cells were more sensitive to the antibody and complement than B cells. Virtually all cells in cultures of cells activated in the mixed lymphocyte reaction or by Concanavalin A were reactive with the monoclonal antibodies. Direct plaque-forming cells were completely eliminated by the monoclonal antibody and complement. By absorption tests, cells from all organs tested so far (thymus, lymph node, spleen, bone marrow, brain, kidney and liver) were shown to express the Ly-m6 determinant. Tumor cell lines with T, B or stem cell characteristics were reactive with the monoclonal antibody by direct cytotoxicity and absorption assays.

Absorption↗

Ly-m11: the H-3 region of mouse chromosome 2 controls a new surface alloantigen.

Spleen cells from an SJL mouse immunized with B10.S spleen cells were fused with the nonsecretor myeloma line NS.1. One established hybrid cell line continuously secreted antibody that recognized a new antigenic specificity, tentatively called "Ly-m11." This newly found antigen is detectable on nearly 100 percent of spleen and lymph-node cells, 70 percent of bone-marrow cells, and 20 percent of thymus cells by direct cytotoxicity assays, and on the cells derived from kidney and liver. Strains that are Ly-m11 (+) include C57BL/6, C57BL/10J, B10.S, C57BR/cdJ, C57L/J, and C57BL/KsJ. Other mouse strains so far tested are Ly-m11 (-). The strain distribution pattern distinguished Ly-m11 from any known murine lymphocyte alloantigens, but it follows the H-3 alpha haplotype which is defined by skin transplantation. Linkage tests of nine congenic strains of H-3 and/or H-13/alpha loci and five recombinant inbred lines including CXB, BXH, AKXL, SWXL, and BXD revealed no recombinations between H-3 and Ly-m11 loci on chromosome 2. This newly discovered Ly-m11 alloantigen could itself constitute a minor histocompatibility antigen detectable by serological means.

Animals↗

Increased catabolism of high density lipoprotein in alcoholic hepatitis.

The kinetics of high density lipoprotein apoprotein A-I were determined in three subjects with severe alcoholic hepatitis. Lipoprotein was obtained from three healthy subjects, radioiodinated, and injected into the patients and the donors. The catabolic rate of A-I was two to four times higher in the patients compared to a group of 18 control subjects studied previously. In the patients only, about 20% of the radiolabeled apoproteins rapidly appeared in the lipoprotein-poor fraction of plasma, which also contained substantial amounts of unlabeled A-I. The findings show that the reduced concentration of A-I in alcoholic hepatitis (less than half-normal), is due not to diminished synthesis (synthesis was normal) but to rapid degradation. This may reflect disruption of abnormal high density lipoproteins due to lack of cofactors.

Adult↗

Human cell membrane components bound to beta2-microglobulin in T cell-type cell lines.

Cell membrane components bound to beta2-microglobulin were isolated from Renex 30 (a nonionic detergent)-solubilized membrane materials of two human T cell-type cell lines, MOLT-4 and CCRF-CEM, by gel filtration and lectin affinity chromatography. The isolation was carried out by following the beta2-microglobulin activity by radioimmune inhibition assay. The T cell membrane components bound to beta2-microblogulin had a uniform molecular size of about 200,000 daltons and most of them showed an affinity to lentil lectin. The isolated membrane components were radioiodinated and examined for identity to HLA antigens by sequential precipitation with rabbit anti-HLA antiserum (specific to HLA large components) and with rabbit anti-beta2-microblogulin antiserum. In addition to HLA antigens, the beta2-microglobulin-bound components obtained from the MOLT-4 cells were found to contain certain membrane components that are the same in molecular size as the HLA large components but that are different antigenically from the HLA large components. On the other hand, the beta2-microglobulin-bound membrane components obtained from the CCRF-CEM cells were all HLA antigens. No other membrane components were involved in the binding.

Cell Line↗

3H-Thymidine labeled mast cells in mice treated with 20-methylcholanthrene: proliferation of precursor cells, their transformation into mast cells and migration of the latter.

In an attempt to clarify the kinetics of increase of mast cells, autoradiographic studies were performed on the mice which received a painting of 20-methylcholanthrene on the skin. In the first experiment, mice received 20-methylcholanthrene painting on their back for two, four and eight weeks. A fourty-eight hours' cumulative labeling with 3H-thymidine was performed directly before sacrifice. No labeled mast cells were found in the painted skin, despite a marked increase of mast cells in number. In the second experiment, mice received 20-methylcholanthrene painting for thirty-one days. A twenty-four hours' cumulative labeling was performed three, five, seven, fourteen, twenty-one and thirty-one days before sacrifice. A high labeling index of mast cells, up to 61.29%, was obtained in each group. When the time lapse between the time of cumulative labeling and the sacrifice is long, the labeling index is higher in the subcutaneous tissue, and when the time lapse is short, the labeling index is higher in the subepidermal tissue. From these results it was concluded that; 1) An increase of mast cells is due predominantly to the proliferation of precursor cells and their transformation into mast cells. 2) The proliferation of precursor cells occurs mainly in the subepidermal layer of the skin. 3) After the transformation, mast cells may migrate into the deeper layer of the skin.

Administration, Topical↗

Immune response gene (Ir-SRBC) exerts its effect via macrophages in inbred rats.

In the previous report, strain differences of inbred rats were investigated in the antibody response to sheep erythrocytes (SRBC). A low-responder strain (Fischer rats) produced only IgM antibody, but other high-responder strains switched over from IgM to IgG antibody to SRBC. Pretreatment with incomplete Freund's adjuvant made Fischer rats a high-responder. These results seemed to indicate that there are malfunctions of macrophages, together with T cells, in Fischer rat strain. In this report, strain differences in the phagocytic activity of macrophages were examined using radiolabelled SRBC. High uptake of SRBC by the spleen in the low responder rats, and vice versa, was confirmed in various experimental conditions. Genetic analyses were made of the specific spleen uptake of the radiolabelled SRBC in backcrossed rats. The result clearly showed that the degree of spleen uptake of the radiolabelled SRBC is genetically determined by a single gene and this property itself has a close negative correlation with the ability of each rat to produce haemolysin against SRBC. These results strongly suggest that the Ir-SRBC gene exerts its effect, at least in part, via macrophages. The relationship between the function of the macrophage and the antibody response is discussed.

Animals↗