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S Doi

Publications and source records attributed to S Doi.

At least 163 records · Page 9Linked to original sources

Expression and the functional role of a p70/75 interleukin 2-binding molecule in human B cell.

Expression of p70/75 IL-2-binding molecules and their functional roles in induction of Ig secretion by IL-2 were examined in human B cells. IL-2, at high concentrations induced higher levels of Ig secretion in Staphylococcus aureus strain Cowan I (SAC)-activated B cells than at low concentrations. About 50% of SAC-activated B cells, lacking Tac antigen, were also responsive to Ig secretion by IL-2, although the required dose of IL-2 was higher than that for Tac-positive B cells. H-31 antibody which recognizes Tac antigen did not inhibit the induction of Ig secretion by high concentrations of IL-2 in both Tac-negative and Tac-positive B cells, suggesting that IL-2 might induce Ig secretion through a receptor distinct from Tac antigens. In contrast, IL-2 was ineffective in the absence of SAC stimulation even at high concentrations. Upon analysis by SDS-PAGE, p70/75 IL-2-binding molecules were detected on Tac-negative SAC-activated B cells. Similar IL-2-binding molecules distinct from Tac antigen (p55) were detected in both Tac-positive B and T cells. However, neither p55 nor p70/75 IL-2-binding molecules could be detected in the absence of SAC stimulation. These observations suggest that p70/75 IL-2 binding molecules are induced in human B-cells in the presence or absence of Tac antigen by SAC stimulation and these determinants play an important function in the transduction of IL-2 associated signal for B cell differentiation.

Antibodies, Monoclonal↗

Novel receptor-mediated internalization of interleukin 2 in B cells.

Novel IL-2-binding molecules (p70 and p75) mediating internalization and degradation of IL-2 were examined by employing a human B lymphoblastoid line, SKW6-4 cells. High concentrations of IL-2 induced IgM secretion in these cells through a receptor distinct from Tac antigen. The acid-wash technique revealed that more than 60% of 125I-labeled IL-2 bound to the cells became acid-unremovable in the first 30 min of incubation at 37 degrees C and degradation products of 125I-IL-2 increased after 30 min of incubation. Treatment of the cells with NaN3 buffer inhibited the appearance of acid-unremovable 125I-IL-2, suggesting that acid-unremovable 125I-IL-2 was not due to fluid-phase pinocytosis but due to internalization. Loss of labeled bands by incubation of cells with 125I-IL-2 at 37 degrees C before affinity cross-linking demonstrated that 125I-IL-2 was internalized via novel IL-2-binding molecules. These results suggest that novel IL-2-binding molecules are responsible for internalization and may mediate signal transduction in B cells in the absence of Tac antigen.

Azides↗

Interleukin 2 functions through novel interleukin 2 binding molecules in T cells.

In this report, we examined whether novel interleukin 2 (IL-2) binding molecules (p70/75) are responsible for signal transduction and internalization of IL-2 in T cells by using a monoclonal antibody H-31 to Tac antigens. We found that H-31 inhibited the binding of IL-2 to Tac antigens but not novel IL-2 binding molecules. Scatchard plot analysis revealed that in the presence of H-31, intermediate affinity sites (Kd = 1 to 1.5 nM) were detectable and the number of them was similar to that of high affinity IL-2 receptor (IL-2R) (Kd = 10 to 15 pM) in the absence of H-31. Furthermore, the kinetics of endocytosis of IL-2 via p70/75 showed the same pattern as via high affinity IL-2R. Finally, high doses of IL-2 (100 to 10,000 U/ml) are required for the proliferation of T cells in the presence of H-31, whereas in the absence of H-31, physiologic doses of IL-2 (1 to 100 U/ml) induced the proliferation. These results taken together suggest that novel IL-2 binding molecules are related to signal transduction of IL-2 and that Tac antigens are essential for constructing of high affinity IL-2R, although Tac antigens may not be responsible for signal transduction.

Antibodies, Monoclonal↗

Regulation of differentiation in a population of cells interacting through a common pool.

We consider a model of a suspension of a cell population in a well-mixed medium. There are two chemical substances, say A and H, reacting in each cell of the population and the substance H can only diffuse from the inside of cell to the medium or vice versa across the cell membrane. The medium is well mixed that the concentration of H is kept uniform over the medium. Cells interact indirectly with each other through the medium. The differential equations governing the dynamics of the suspension are analyzed using standard techniques for differential equations. It is shown that the cell population divides into several groups in respect of the chemical concentrations as time elapses. It is also shown how the fraction of the number of cells belonging to each subgroup to the total number of cells is regulated. The results may be used to explain the mechanism for differentiation of multi-cellular organisms.

Cell Differentiation↗

Cellular and genetic analyses of IL-2 production and IL-2 receptor expression in a patient with familial T-cell-dominant immunodeficiency.

Cellular and genetic analyses of interleukin-2 (IL-2) production and IL-2 receptor (IL-2R) expression were examined in a immunodeficient patient and his family members. Mononuclear cells (MNC) of the patient showed no proliferative response (stimulation index, less than 2) to T-cell mitogens (PHA and Con A) and were defective in IL-2 production and IL-2R expression (less than 1%), whereas productions of other lymphokines (B-cell differentiation factor and IFN-gamma) were not impaired significantly. His brother died of the same disease and his father also lacked in proliferative response and IL-2 production by PHA stimulation. In Southern blot analyses using DNA probes of IL-2 and IL-2R, patterns of the patient were the same as those of healthy volunteers, whereas the transcription of DNA coding for IL-2R to mRNA was lacking in the patient. These results suggest that inheritant defects of IL-2 production and IL-2R expression reside in this family and the defects are not linked to DNAs coding for IL-2 and IL-2R but to a transcriptional deficiency.

Concanavalin A↗

Western blot detection of scrapie-associated fibril protein in tissues outside the central nervous system from preclinical scrapie-infected mice.

We describe a method of sample preparation to detect scrapie-associated fibril (SAF) proteins in small amounts of scrapie-infected mouse tissues by Western blot analysis using an antiserum to a synthetic peptide that corresponds to the N-terminal region of hamster prion protein. SAF proteins were efficiently detected in brain tissue by this procedure. The proteins were also detected in preparations from spleen and lymph node. SAF proteins were detected in brain samples at 24 weeks after intraperitoneal infection. Using spleen samples, the proteins were detected from mice in the preclinical stage (from 4 weeks after infection), clinical symptoms of scrapie were observed in some mice from 22 weeks after infection.

Animals↗

Effects of the antiserum against a fraction enriched in scrapie-associated fibrils on the scrapie incubation period in mice.

An antiserum against a fraction enriched for scrapie-associated fibrils (SAF), was examined for its effects on scrapie incubation period by inoculating mice either intraperitoneally or intracerebrally with various dilutions of the serum mixed with scrapie-infected mouse brain homogenate. After intraperitoneal inoculation the mean time of the incubation period increased with increasing concentrations of the antiserum in a statistically significant fashion, when the serum dilutions were made with phosphate-buffered saline. After intracerebral inoculation, however, there were no statistically significant differences between the control group and any of the antiserum-groups. When the antiserum dilutions were made with pre-immune serum, the mice inoculated intraperitoneally also showed no significant differences between the two groups. These results indicate that the specific antibodies to SAF have no effect on the scrapie infectivity.

Animals↗

A novel B cell line established from Ki-1-positive diffuse large cell lymphoma.

A novel cell line, designated KIS-1, was established from a patient with Ki-1-positive diffuse large cell lymphoma. Multiple phenotypic analysis of the KIS-1 cells was carried out with a total of 22 monoclonal antibodies defining hematopoietic cell subsets and lineages. The KIS-1 cells were positive for Ki-1, B4, HLA-DR, and 2D1 (common leucocyte) antigens, but were negative for the antigens reportedly specific for T cells, natural killer cells, granulocytes, monocytes, interdigitating reticulum cells and dendritic reticulum cells. The genomic analysis of the KIS-1 cells showed not only the rearrangement of JH and J kappa genes but also the probable rearrangement of C lambda genes. Moreover, the cells produced immunoglobulin lambda chains. Thus, KIS-1 was considered to be of B-cell lineage. The lymphoma-cell derivation of KIS-1 was based on the following facts. The cytochemical, immunologic, cytogenetic properties and the results of the molecular genomic analysis in the KIS-1 cells were essentially the same as those of the original tumor cells, and the KIS-1 cells were negative for Epstein-Barr virus-associated nuclear antigen. KIS-1 is the only known B-cell line derived from Ki-1-positive diffuse large cell lymphoma, and should be useful for defining the biological implications of Ki-1 antigen.

Antigens, Differentiation↗

Immunogenotypes of lymphoid malignancies; the rearrangement of T cell receptor beta chain gene can occur before the gamma chain gene rearrangement.

Immunoglobulin (Ig) and T cell receptor (TcR) gene rearrangements were analyzed in 101 cases of lymphoid malignancies in association with a surface phenotype study. In leukemias/lymphomas with mature phenotype, there is a good correlation between phenotypes and genotypes. However, in leukemias/lymphomas with immature phenotype, we found many discordances between phenotypes and genotypes, suggesting the stochastic nature of hematopoietic cell differentiation at the early stage. As for TcR beta and gamma chains, the rearrangement of gamma chain gene is considered to occur slightly prior to that of beta chain gene. However, we observed a mature T cell malignancy, adult T-cell leukemia, with rearranged beta chain gene and germ line gamma chain gene, showing the possible existence of another pathway of T cell differentiation.

Cell Differentiation↗

Phenotypic conversion of T lymphoblastic lymphoma to acute biphenotypic leukemia composed of lymphoblasts and myeloblasts. Molecular genetic evidence of the same clonal origin.

Acute biphenotypic leukemia composed of lymphoblasts and myeloblasts developed in a patient with T lymphoblastic lymphoma (T-LBL) who had an anterior mediastinal mass. A novel myeloid cell line, termed TK-1, has been established from his peripheral blood after the leukemic conversion. The identical rearranged pattern of T cell receptor gamma-chain gene was observed among the DNAs derived from lymph node cells in the lymphoma phase, the myeloid cell line TK-1, and the subclones with different karyotypes (TK-1B and TK-1D), which showed that myeloid cells had been derived from the T-LBL of the same patient. This finding demonstrates that phenotypic conversion occurs in the clonally propagating tumor cells and suggests that some hematopoietic cells retain the capacity to adopt either lineage.

Acute Disease↗

Expression of novel interleukin 2 binding molecules and their functional roles in human B cell differentiation.

Expressions and functional roles of novel IL-2 binding molecules (p70, 75) in the differentiation of B cells into Ig secreting cells were explored by using human several B cell lines and tonsillar B cells. Affinity-crosslinking studies revealed that five of nine B cell lines expressed p70 and p75 without detectable Tac antigen (p55) expression and the expression was associated with B cell maturation. In tonsillar B cells, small high-density B cells did not express p70 and p75, whereas large low-density B cells, which were thought to be activated in vivo, expressed them. Binding assays of radiolabeled IL-2 showed that the affinity of these molecules was intermediate (kD = 1-3 nM, 700-3,000 sites/cell). Furthermore, high concentrations of IL-2 (greater than 100 U/ml) induced Ig productions in large B cells and two of five cell lines. These results taken together suggest that B cells may express novel IL-2 binding molecules, associated with B cell differentiation and differentiate into Ig secreting cells by IL-2 through novel IL-2 binding molecules.

Antigens, Surface↗

[Marginal periodontitis and the immune system. III. Differences in peripheral blood lymphocyte subsets before and after treatment in adult periodontitis patients].

The lymphocyte subsets in the peripheral blood of 8 individuals, aged 25 to 57 yr, with moderate to advanced adult periodontitis were analyzed before and after treatment by means of flow cytometry, and then compared with the findings in 20 normal adults (aged 30 to 45 yr). The results were as follows: the percentage of OKT-8+ (CD 8) in the patients (20.25 +/- 7.15%) was lower than that in normal individuals (31.50 +/- 6.03%, P less than 0.01) while the OKT-4/OKT-8 ratio (2.34 +/- 1.18) was higher than the corresponding ratio in the controls (1.23 +/- 0.37); however, there was no significant difference in the percentages of OKT-3+ (CD 3), OKT-4+ (CD 4) and Leu-12+ (CD 19) between patients and normal subjects. The percentages of OKT-3+, OKT-4+, OKT-8+, Leu-12+ and OKT-4/OKT-8 after the periodontal therapy did not show a significant difference compared with the data obtained before treatment. These results indicate that the decrease in suppressor/cytotoxic T-cell population may be a kind of pathological disposition of the initiation and/or course of adult periodontitis.

Adult↗

Significance of extra 18q- chromosome in Japanese t(14;18)-positive lymphoma.

Karyotype evolution of t(14;18)-positive lymphoma was studied in 13 Japanese patients. The extra 18q- chromosome, found in six of ten patients with complex karyotypes, was the most common change subsequent to a t(14;18)(q32;q21) chromosome translocation. The additional change was interpreted as being a duplication of an 18q- derived from a t(14;18). The six patients had transformed histology of follicular small cleaved cell lymphoma or diffuse large cell lymphoma, and five of them had extranodal expansion associated with a poor prognosis. These findings indicate that the extra 18q-, together with other chromosome abnormalities, is closely associated with the advanced grade disease of t(14;18)-positive lymphoma, and the extra chromosome is evolutionally comparable with the second Philadelphia (Ph1) chromosome often found in the blastic phase of chronic myelocytic leukemia carrying a t(9;22)(q34;q11). In addition, since the extra 18q- is rarely found in American patients with t(14;18)-positive lymphoma, there appears to be a difference in the karyotype evolution between Japanese and American patients.

Chromosome Aberrations↗