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Biomedical subjects

T Noma

Publications and source records attributed to T Noma.

162 records · Page 9Linked to original sources
PubMed1984

Rearranged immunoglobulin heavy chain variable region (VH) pseudogene that deletes the second complementarity-determining region.

We have cloned two rearranged heavy chain variable region (VH) genes from the IgG-producing human cell line CESS. The VH gene, which is linked to the mu chain constant region (C mu) gene, has two deletions at residues 45-62 and 82A-90, the former of which corresponds closely to the second complementarity-determining region (CDR2). These results could indicate that translocation of CDR2 occurred and could give support to the argument that reassortment of the V mini-genes is involved in the generation of hypervariability during evolution. However, the rearranged pseudogene could have also arisen by fortuitous deletion. The other VH gene of CESS is an expressed form and is probably linked to the C gamma gene. The diversity region (D) segments used in these rearranged V genes are less than 38% homologous to known human germline D segments, indicating the presence of more unknown germline D segments.

Amino Acid Sequence↗
PubMed1984

Properties of human interleukin-2 receptors expressed on non-lymphoid cells by cDNA transfection.

We have established non-lymphoid cell lines HeLa, Ltk and NIH3T3 expressing the human interleukin-2 (IL-2) receptor by transfection of human IL-2 receptor complementary DNA. While IL-2 receptors on T cells are classified into the high and low affinity species, the receptors expressed on the cDNA-transfected non-lymphoid cells belong to the low affinity species. These IL-2 receptors could not transmit the growth signal although they were similar in size to those expressed on T cells. Phorbol ester-induced phosphorylation of the IL-2 receptors on HeLa cells did not affect the affinity of the receptor. We have also constructed a cDNA encoding a mutant IL-2 receptor that replaced the major phosphorylation site, the serine residue at position 247 with the glycine residue. This mutant IL-2 receptor expressed on non-lymphoid cells also had the low affinity for IL-2. The results indicate that the high and low affinity states of the IL-2 receptor are not solely determined by phosphorylation of the receptor. The IL-2 receptors expressed on these non-lymphoid cells were internalized four to eight times more slowly than those on T cells. Possible defects of the IL-2 receptors expressed on non-lymphoid cells are discussed.

Animals↗
PubMed1984

Low dose of deoxyguanosine increases IL-2 receptors of IL-2-dependent cultured T cells.

Deoxyguanosine ( dGuo ) is a purine nucleoside phosphorylase (PNP) substrate which has been shown to inhibit T lymphoblast growth, PHA-induced cell proliferation and suppressor T cell activity. Low dGuo concentrations (0.5-5 microM) increase interleukin-2 (IL-2) sensitivity of IL-2-dependent cultured T cells (CTC). dGuo alone has no direct mitogenic effect on CTC. The increased IL-2 sensitivity of CTC was more marked in the presence of low IL-2 concentrations than high ones. CTC incubated with dGuo at 37 degrees C for 24 hrs absorbed more exogenous IL-2 than control non-treated CTC. CTC incubated at 4 degrees in the presence of dGuo did not absorb any more IL-2 than control CTC. FACS analysis further showed increased Tac expression on CTC due to dGuo . These findings indicate that a 37 degrees incubation of CTC with dGuo increases the number of CTC IL-2 receptors. dGuo was not found to increase IL-2 production by PHA-stimulated PBM. Therefore, low dGuo concentrations selectively augment the sensitivity of cells responding to IL-2 by increasing IL-2 receptors.

Cells, Cultured↗
PubMed1983

Origin of adult T-cell leukemia virus. Implication for its zoonosis.

Adult T-cell leukemia virus (ATLV) is a retrovirus infecting man. The ATLV genome consists of long terminal repeat (LTR), gag, pol, env and pX sequences and does not carry a typical v-onc gene. The function of the pX sequence is unknown. To search for the origin of ATLV, segments of the ATLV genome were hybridized to DNAs of various species. The sequences homologous to the pX region of ATLV are represented in the genomes of mouse and rat but not in other species including primates and the human. Neither the pol nor U3 sequence of LTR is conserved in any cellular DNA examined. Sequences slightly homologous to the U3R sequence are found in rabbit, chicken and Xenopus. The results suggest that the pX sequence of ATLV might have derived from rodents. Since ATLV can infect primates, rabbit and rat, ATLV might have been prevalent among a wide variety of mammals and exchanged genetic segments (zoonotic) like influenza virus. If we assume that the original host of ATLV is a rodent rather than man, the pX sequence is homologous to host cellular sequences and reminiscent of the v-onc gene although the function of the pX sequence is not clear.

Animals↗
PubMed1982

[The relationship between the number of anti-thyroglobulin antibody forming cells from the cultured peripheral lymphocytes and the serum antibody titers in patients with chronic thyroiditis (author's transl)].

Anti-thyroglobulin antibody forming cells (AFC) were generated from the cultured peripheral lymphocytes of patients with chronic thyroiditis. In order to clarify whether this reflects the antibody formation in vivo, the number of antibody forming cells generated in the culture was related to the serum antibody titer in 121 cases. There was no case which produced more than 10 AFC from 2 x 10(5) B-cells in the group with the low serum antibody titer (less than 10(2)), while 29.4% produced more than 10 AFC in the patients with antibody titer of 20(2) and 20(4) and 65.2% in the group with titer of 80(2) approximately 640(2). The average number of AFC of the last group was 31.4 +/- 17.7 (SD). AFC and serum antibody titers were estimated on various occasions with the same patients. A good relationship was observed between these two parameters. There was no significant correlation between the numbers of AFC and serum antimicrosome antibody titers.

Adolescent↗
PubMed1982

In vitro detection of anti-thyroglobulin antibody forming cells from the lymphocytes of chronic thyroiditis patients and analysis of their regulation.

Anti-thyroglobulin (anti-Tg) antibody forming cells were detected by plaque forming cell (PFC) assay, using B cells depleted of sheep erythrocyte (SRBC) binding cells and T cells separated without SRBC interaction. When 2 x 10(5) non-T cells were combined with the same number of T cells from chronic thyroiditis patients, more than 20 PFC were detected; few, if any, PFC developed from normal lymphocytes. T cells were generally needed to produce quantifiable PFC, suggesting that helper T cells are required for this autoantibody formation. A positive relationship existed between the number of PFC and the serum anti-Tg antibody titres of the same patients. The generation of Tg-specific PFC from patient lymphocytes was markedly suppressed by normal T cells or T cells from patients whose lymphocytes did not produce PFC. The same level of suppression was also seen on the addition of culture supernatant from Tg antigen stimulated T cells. Autologous T cells, from patients whose lymphocytes produced PFC, did not show such suppressor effects, suggesting that in chronic thyroiditis patients, the regulatory T cell function preventing anti-Tg autoantibody formation is impaired.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

Construction of chimaeric processed immunoglobulin genes containing mouse variable and human constant region sequences.

The specificity of monoclonal antibodies provides a powerful diagnostic and therapeutic tool in investigating human neoplasia. Radiological scanning and immunotherapy with mouse tumour-specific monoclonal antibodies have been applied to patients with some success, but a major problem is the neutralization of the mouse antibody induced by repeated administration of heterologous antibodies. To avoid or reduce such immune reactions, chimaeric immunoglobulins consisting of mouse variable (V) and human constant (C) regions can be synthesized. We have constructed a recombinant retrovirus DNA carrying genomic heavy-chain (H) variable-diversity joining (VH-D-JH) and C gamma 1 genes from different species and show here that the chimaeric intervening sequences are spliced out precisely. This procedure provides a useful method to construct the chimaeric mouse-human immunoglobulin gene to be expressed in Escherichia coli, yeast and animal cells. Unexpectedly, a hidden splice donor site in the 5'-flanking region of a human VH gene is used in place of the donor site of the leader sequence exon, resulting in the formation of the V region without the leader sequence.

Animals↗
PubMedDate not supplied

Inhibition by eicosapentaenoic acid of oxidized-LDL- and lysophosphatidylcholine-induced human coronary artery smooth muscle cell production of endothelin.

The objectives of the present study were (1) to determine whether oxidized low-density lipoprotein (LDL) and lysophosphatidylcholine (lyso-PC), a major phospholipid component of oxidized LDL, stimulate the production of endothelin-1 (ET)-1 in cultured human coronary artery smooth muscle cells (SMCs), and (2) to examine the possible effect of an antiatherogenic agent, eicosapentaenoic acid (EPA), on oxidized-LDL- and lyso-PC-stimulated ET-1 production in these cells. Oxidized LDL (10-50 microg/ml) and lyso-PC (10(-7) to 10(-5) mol/l) stimulated ET-1 production in a concentration-dependent manner. By contrast, the effects of native LDL and phosphatidylcholine were modest or absent. Lyso-PC (10(-7) to 10(-5) mol/l) and oxidized LDL (10-50 microg/ml) significantly induced particulate protein kinase C (PKC) activation. Lyso-PC- and oxidized-LDL-stimulated ET-1 production was significantly inhibited by PKC inhibitor, PKC (19-36). EPA (80-160 micromol/l) clearly suppressed ET-1 production stimulated by oxidized LDL and lyso-PC in a concentration-dependent manner. Furthermore, EPA (160 micromol/l) significantly inhibited lyso-PC (10(-5) mol/l)- and oxidized LDL (50 microg/ml)-induced particulate PKC activation. Results suggest that oxidized LDL and lyso-PC stimulate ET-1 production by a mechanism involving activation of PKC, and that EPA suppresses ET-1 production stimulated by lyso-PC as well as oxidized LDL probably through the modulation of PKC in human coronary artery SMCs. EPA may exert an antiatherosclerotic effect, in part, through these mechanisms.

Angiotensin II↗