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N Tada

Publications and source records attributed to N Tada.

At least 127 records · Page 7Linked to original sources

Mouse alloantigen system Ly-m22 predominantly expressed on T lymphocytes and controlled by a gene linked to M1s region on chromosome 1.

Spleen cells from a DBA/2 mouse immunized with RL male 1 tumor cells, a radiation induced BALB/c T-cell leukemia, were hybridized with the nonsecretor myeloma line NS.1. Four established hybrid cell lines continuously secreted antibodies that recognized a new alloantigenic specificity, tentatively called Ly-m22. This antigen is detectable on nearly 60% of lymph node cells, and 30% of spleen cells by direct cytotoxicity assay, but did not lyse significant number of cells of thymus and bone marrow. By absorption test, these lymphoid organs, i.e., lymph node, spleen, thymus, and bone marrow, were shown to express Ly-m22 determinant. The newly found antigen is expressed predominantly on T-cells. Analysis of BXD and SWXL recombinant inbred strains revealed close linkage between Ly-m22 and Ltw-4 loci on chromosome 1. The estimated recombination frequency is 0.027 +/- 0.081.

Animals↗

Lipoprotein metabolism in diabetics treated with diet, oral hypoglycemic drug and insulin.

In view of the high incidence of hyperlipidemia and the low sialic acid content in the membranes of diabetics, we analyzed the percentage composition of apolipoprotein CII, known as an activator of lipoprotein lipase, and a subspecies of apolipoprotein CIII, an inhibitor of lipoprotein lipase, in triglyceride-rich lipoproteins. CIII can be sub-divided into three groups, CIII0, CIII1 and CIII2, according to sialic acid content by isoelectric focusing gel. In 82 diabetics, serum lipids and lipids in various lipoprotein fractions differed according to treatment, (diet, oral hypoglycemic drug or insulin). CIIIo/CII showed a positive correlation to plasma triglyceride and cholesterol. In the group receiving oral medication (N = 20), CIIIo/CII vs HDL-cholesterol showed a positive correlation, whereas CIII2/CII vs plasma triglyceride showed an inverse correlation. In the insulin group (N = 25), the percentage of CIIIo in VLDL apo C subspecies was inversely correlated with plasma cholesterol. In 38 diabetics whose HbA1 was also examined, CIIIo/CII increased with elevation of HbA1. CIIIo/CII in diabetics with HbA1 higher than 10% was significantly high compared with the index in other diabetics. The percentage of CIII1 in VLDL apo C subspecies was correlated to HbA1 level positively in the diet group but inversely in the insulin group. These results suggest that lipoprotein metabolism in diabetics may vary according to treatment and the sialylation of apolipoprotein may play an important role in determining the severity of this disease.

Aged↗

Characterization of T lymphocyte subsets with monoclonal antibodies: discovery of a distinct marker, Ly-m22, of T suppressor cells.

The study of cell surface antigens has accelerated in the few years since the advent of hybridoma technology to the point where many dozens of such markers have now been described. The functional heterogeneity of post-thymic T cells in the immune response, however, still exhibit complexities beyond the resolving power of our current repertoire of marker antigens. In this study, we investigated the surface phenotype of three types of effector T cells: helper cells, nonspecific suppressor cells, and cytotoxic T cells, using four recently discovered alloantigen systems of T cells: Ly-m10, Ly-m18, Ly-m19, and Ly-m22. SRBC-primed spleen cells were used as a source of specific helper T cells, and they were tested by their ability to promote antibody synthesis by B lymphocytes. Concanavalin A-activated suppressor cells were assayed by their ability to inhibit that response. Cytotoxic T cells were activated by alloantigen. We found Ly-m10 to be expressed on all three cell types tested, whereas Ly-m18 and Ly-m19 were absent from all three. Ly-m22, whose controlling locus is closely linked to the Mls region, had a unique distribution, being present solely on suppressor cells. Thus Ly-m22 emerged as a new marker that distinguishes nonspecific T suppressor cells (Ly-m22+) from T helper as well as cytotoxic T cells (Ly-m22-). Ly-m22 is the only antigen besides I-J so far known to be restricted to suppressor cells.

Animals↗

Cross-blocking studies with monoclonal antibodies against I-A molecules of haplotypes b, d and k.

For assessment of the distribution of allodeterminants on I-A molecules, binding inhibition studies were performed with monoclonal anti-I-A antibodies (mAb) in which pairs of labeled and unlabeled mAb were tested for cross-blocking on spleen cells of H-2 haplotypes b, d and k. The data suggest that allodeterminants are randomly distributed on the surface of the I-A molecule. Comparison of mAb with cross-reactivity for b, d or k haplotypes indicates that the allelic forms of determinants are located in analogous positions on different I-A antigens.

Alleles↗

Changes in very low density lipoproteins with cholesterol loading in man.

We have studied the effects of cholesterol loading in man, seeking changes in VLDL that may define a population of particles that resemble the atherogenic beta-VLDL in experimental animals. Comparisons were made in 6 men during two diets, containing either 200 mg or 1700 mg cholesterol daily. Although the total plasma cholesterol did not rise significantly over 4 wk of cholesterol loading (mean +/- SD 178 +/- 41 to 194 +/- 48 mg/dl), distinct changes in lipoprotein composition occurred; (1) HDL cholesterol rose significantly (34 +/- 4 to 41 +/- 5) and plasma apoprotein AI rose from 118 +/- 10 to 129 +/- 9 mg/dl. (2) Within VLDL, the proportion of apoproteins E:C rose from 0.18 to 0.32 (p less than 0.005), though the apoprotein E concentration did not change, (3) Within VLDL, the ratio of cholesteryl esters:triglycerides rose, (4) Within VLDL (Sf 20-400) a population of particles that bound to heparin on heparin-sepharose columns increased threefold; since these particles were richer in apoprotein E and in cholesteryl ester than were VLDL not bound to heparin, we conclude that cholesterol loading leads to an increase in smaller VLDL particles, possibly partly catabolized VLDL or independently secreted IDL, that resemble findings in cholesterol fed animals, and (5) Transport kinetics of apoprotein B in VLDL studied in four subjects did not show a rise in production but this does not rule out increased secretion of a cholesteryl ester, apoprotein E enriched subpopulation of VLDL.

Adolescent↗

Localization of allodeterminants on H-2Kb antigens determined with monoclonal antibodies and H-2 mutant mice.

The topographic arrangement of antigenic determinants on the H-2Kb molecule was investigated by antibody competition studies with a series of monoclonal anti-Kb antibodies. For identification of amino acid residues participating in formation of allodeterminants H-2Kb mutant mice with defined amino acid substitutions were analyzed. The determinants were found to be located in at least two spatially separate clusters on the H-2Kb molecule. Determinants of one cluster are affected by mutations at amino acid positions 155 and 156, whereas determinants of a second cluster are modified by amino acid substitutions at positions 77 and 89. For a third cluster of determinants no relevant amino acid positions could be identified, but competition data indicate that this cluster is adjacent to the second one. The data suggest that the first two domains of H-2 antigens carry most allodeterminants.

Amino Acid Sequence↗

Abnormal apolipoprotein composition in alcoholic hepatitis.

Alcoholic hepatitis leads to major derangements in lipoprotein metabolism. This study defines the characteristics of the abnormal high density lipoprotein and very low density lipoprotein in relation to the severity of the disease. In severely affected subjects very low density lipoprotein apolipoproteins were deficient in apolipoprotein E and apolipoprotein C. The concentration of high density lipoprotein was markedly reduced, although the proportion of high density lipoprotein 1 was substantially elevated when compared to normal subjects. High density lipoproteins were deficient in apolipoprotein AI and apolipoprotein AII but enriched in apolipoprotein E, apolipoprotein E complexes and apolipoprotein C, and contained a mixture of particles. The high density lipoprotein of subjects with alcoholic hepatitis contained a high proportion of material which bound to heparin affinity columns. This bound fraction contained a group of particles rich in apolipoprotein E, apolipoprotein E complexes and apolipoprotein C and was deficient in apolipoprotein AI and apolipoprotein AII. Examination by electron microscopy showed the presence of both discoidal and spherical particles, which varied in concentration according to the severity of the disease. Another fraction of high density lipoprotein, not bound to heparin, contained reduced amounts of apolipoprotein AI and apolipoprotein AII, consisted of disc-shaped particles and showed a higher esterified: free cholesterol ratio than the other high density lipoprotein fraction.

Apolipoprotein A-I↗

Application of monoclonal anti-HY antibody for human H-Y typing.

We have successfully produced monoclonal anti- H-Y antibody by fusing NS-1 myeloma cells with splenocytes from C57BL/6 females immunized with syngeneic male splenocytes. We have proved that the antibody is male specific and that it cross reacts with human H-Y. We have further tested 80 normal individuals for H-Y antigen and obtained significant differences between males and females. Therefore, the monoclonal anti- H-Y antibody is useful for clinical typing of human H-Y antigen.

Animals↗

New mouse immunoglobulin A heavy chain allotype specificities detected using the hybridoma-derived IgA of I/St mice.

Immunizations of C57BL/6 and A mice with IgA derived from the I/St mouse strain yield alloantisera which detect two allotypic determinants of immunoglobulin A. The two determinants display discrete strain distributions. The first, identified by the alloantiserum C57BL/6 anti-IgA of I/St strain hybridoma ID150, follows the Ighc haplotype, and the second, identified by the alloantiserum A anti-IgA of I/St strain hybridoma ID150, correlates with Ighc and Ighb haplotypes. Absorption with monoclonal IgM, which has the same idiotype as the ID150 IgA clone, removed idiotype-specific antibodies from both alloantisera. The remaining antibodies are directed against determinants associated with the alpha chain constant region, as shown by absorption with monoclonal IgA. By use of recombinant inbred strains of mice and mice congenic at the Igh locus, the loci controlling both C alpha allotypic determinants have been mapped to the Igh region on chromosome 12.

Animals↗

Ly-m19: the Lyb-2 region of mouse chromosome 4 controls a new surface alloantigen.

Spleen cells from an SJL mouse immunized with 70Z/3 cells, an established pre-B cell line, were fused with cells of the nonsecretory myeloma line NS.1. One established hybridoma cell line (clone K10.6) continuously secreted antibody that recognized a new antigenic specificity tentatively named Ly-m19. This newly found antigen is detectable on both T and B cells. Cytotoxicity assays reveal that 75 percent of the spleen and lymph-node cells, 35 percent of bone-marrow cells, and 15 percent of thymus cells reacted with antibody of clone K10.6. Strains expressing the specificity Ly-m19.1 are characterized by negative reactions and include the strains AKR, CE/J, RF/J, GR/A, SJL, P/J, BDP/J, and LG/J. All other strains so far tested are Ly-m19.2. This strain distribution pattern distinguishes Ly-m19 from any known murine lymphocyte alloantigen, but it parallels the Lyb-2c haplotype. Linkage test of a set of AKXL recombinant inbred strains revealed close linkage of Ly-m19 and Lyb-2 loci on mouse chromosome 4.

Animals↗

A new mouse cell-surface antigen (Ly-m18) defined by a monoclonal antibody.

Spleen cells from C3H/An mice immunized with spleen cells of C57BL/6-H-2k mice were fused with myeloma cell line NS.1. One established hybrid cell line continuously secreted antibody that recognized a new surface antigen provisionally called Ly-m18. The new alloantigen is expressed on 90 percent of thymus cells, 55 percent of spleen cells, and 45 percent of either lymph-node or bone-marrow cells. It is also expressed on cells derived from brain, kidney, and liver. Fifty percent of either peripheral T or B cells express the Ly-m18 antigen, and some tumor cell lines with T, B, pre-B or stem cell characteristics are Ly-m18 (+). The strain distribution pattern distinguishes Ly-m18 antigen from all other murine lymphocyte alloantigens. The typing data of two sets of CXB and AKXL recombinant inbred strains indicate that the Ly-m18 gene is linked to the Ltw-2 locus which has not yet been assigned to a chromosome.

Animals↗

A new mouse cell-surface antigen (Ly-m20) controlled by a gene linked to Mls locus and defined by monoclonal antibodies.

Five monoclonal antibodies were established by the fusion of mouse myeloma cells (NS.1) with spleen cells from A and (A x C3H/An)F1 mice hyperimmunized with 70Z/3 tumor cells. These antibodies recognized a new antigenic specificity provisionally called Ly-m20.2. In direct cytotoxicity assays, 60 percent of cells in spleen, 40 percent in lymph node, 50 percent in bone marrow and less than 5 percent in thymus were found to react with three of the five antibodies, whereas the two others yielded somewhat lower cytotoxicity indices. The Ly-m20.2 antigen was also expressed on cells derived from liver and kidney but not on cells derived from brain. As judged from cytotoxicity assays with separated T and B cells, Ly-m20.2 antigen is carried preferentially on B lymphocytes. Direct plaque-forming cells (PFC) were completely eliminated by Ly-m20.2-specific antibody and complement. Linkage tests by analysis in 20 (CBA/J x C3H/An) x C3H/An backcross mice and by segregation analysis of BXH and SWXL recombinant inbred strains indicate close association of the loci controlling Ly-m20.2 and M1s antigens on chromosome 1.

Animals↗