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Biomedical subjects

R Ueda

Publications and source records attributed to R Ueda.

At least 307 records · Page 17Linked to original sources
PubMed1989

Elevated serum-soluble interleukin-2 receptor (Tac antigen) levels in chronic myelogenous leukemia patients with blastic crisis.

We examined the expression of cell-surface interleukin-2 (IL-2) receptor (Tac antigen) on peripheral blood leukemic cells and measured soluble IL-2 receptor p55(alpha) chain (sIL-2R) levels in sera from chronic myelogenous leukemia (CML) patients with blastic crisis. Flow cytofluorometric analysis performed by dual immunofluorescence in three cases demonstrated coexpression of Tac antigen with myeloid (CD13, CD14, or CD33) or lymphoid (CD10) antigen on significant proportions of peripheral blood leukemic cells. Radiolabeled IL-2-binding assay demonstrated the specific IL-2 binding sites in three cases examined. The exogenous IL-2, however, failed to induce proliferative response. A myeloid cell line, Yut-K3, established from peripheral blood leukemic cells from a CML patient with blastic crisis, also expressed cell-surface Tac antigen and CD13 concurrently. SIL-2R assay showed that Yut-K3 released a detectable amount of sIL-2R in its culture supernatant. The serum sIL-2R levels were significantly elevated (range: 2,580 to 172,000 U/mL) in 12 CML patients with blastic crisis and were slightly elevated in ten patients in chronic phase (range: 250 to 820 U/mL) and in three in accelerated phase (range: 790 to 1,305 U/mL) compared with those in 24 normal controls (range: 70 to 695 U/mL, P less than .01). These results indicated that the leukemic cells from CML patients with blastic crisis expressed and released IL-2 receptor (Tac antigen). Longitudinal studies performed in three cases of CML with blastic crisis showed that the change of serum sIL-2R level was closely associated with that of the number of peripheral blood leukocytes and blasts, the percentage of blasts and serum LDH levels, also suggesting that the serum sIL-2R level is a useful clinical indicator of the leukemic cell burden in vivo.

Adult↗
PubMed1989

Expression and amplification of myc gene family in small cell lung cancer and its relation to biological characteristics.

Eighteen small cell lung cancer (SCLC) lines (including nine lines established by this group) as well as 31 tumor samples from 23 SCLC patients were examined for the surface antigen phenotype and the expression and amplification of the myc gene family. The expression of NE-150 neuroendocrine, PE-35 panepithelial and OE-130 epithelial antigens corresponded well with the level of biomarkers of SCLC lines, i.e., the NE-150+/PE-35+/OE-130- phenotype corresponded to classic type, while the other phenotypes such as NE-150+/PE-35-/OE-130- to variant type. In tumor specimens, most classic SCLC (consisting of oat cell type and intermediate cell type, subtype a) showed NE-150+/PE-35+/OE-130- phenotype, while small cell-large cell carcinoma (intermediate cell type, subtype b) expressed various phenotypes. The amplification of the myc gene family was observed in nine out of 18 lines (50%) and five out of 23 patient tumors (22%). Higher levels of expression of either c-myc, N-myc, or L-myc were detected in 16 out of 18 lines (89%) and in five out of six patient tumors (83%), when compared with that of normal or fetal lung tissues. Thus, the higher expression without obvious myc gene amplification was observed. The cell lines and tumors with the amplified myc always expressed their corresponding myc genes. The results suggested that higher levels of expression of the myc gene family may play a significant role in the oncogenesis of SCLC. Amplification and/or high levels of expression of c-myc were observed not only in variant type SCLC lines, but also in classic type lines. Thus, they were not necessarily associated with distinct biomarkers of SCLC lines.

Antigens, Surface↗
PubMed1989

Interdigitating cell sarcoma (ICS). Evidence of interdigitating cell origin, immunocytochemical studies with monoclonal anti-ICS antibodies.

Three independent mouse monoclonal antibodies (mAbs) ID1 (IgG3), ID2 and ID3 (IgM) were raised against whole cells of a surgically resected human interdigitating cell sarcoma (ICS). In immunoperoxidase staining, these mAbs strongly stained the cytoplasm of ICS neoplastic cells as well as interdigitating cells in normal lymphoid tissues. These mAbs also detected monocyte/macrophages and dendritic cells, although their staining was highly variable depending on tissue distribution of the cells. Additional immuno-histological and enzyme histochemical study revealed that the neoplastic cells of ICS had cytoplasmic acid phosphatase and membranous alkaline phosphatase activity, and also possessed S100 beta protein, Ki-1 antigen. DAKO-macrophage antigen, and weak vimentin activity. Neither rearrangement of immunoglobulin heavy chain gene nor of T-cell receptor genes was detected in the DNA of ICS by Southern hybridization. These observations provide further confirmation of our previous finding (Nakamura et al. 1988, 1989) that the origin of ICS is interdigitating rather than lymphoid cell, and indicate that our mAbs could be useful as a cellular differentiation marker of interdigitating cells and for diagnosis of ICS.

Animals↗
PubMed1989

A human monoclonal antibody recognizing a surface antigen on stomach cancer cells.

Lymph-node lymphocytes of a patient with stomach cancer were fused with the mouse-human heterohybridoma, HM-5. A clone (2F9) was isolated that showed stable production of an IgM antibody reactive with NUGC-4 stomach cancer cell line. This antibody reacted predominantly with a cell surface antigen on cell lines originating from gastro-intestinal cancer and adenocarcinoma of lung, whereas it was not generally reactive with other types of cancers, or with normal kidney cells or fibroblasts. Biotin-labeled 2F9 antibody clearly stained cell smears and the nude mouse tumor of NUGC-4, but it did not show a positive reaction with stomach cancer tissues obtained from more than 10 patients, indicating that the antigen detected is very weakly expressed on tumor cells or on a limited number of stomach cancers. The antigen shed from NUGC-4 cell line was detected in the culture supernatant. 2F9 antibody precipitated a glycoprotein with a molecular weight of over 200 kilodaltons as well as a possible glycolipid, from NUGC-4 cells labeled with [3H]glucosamine or [35S]-H2SO4. Periodic acid treatment of the tissue section decreased reactivity with 2F9 antibody, but heat, neuraminidase or protease treatment did not. These results suggested that the epitope is present on a carbohydrate moiety not containing sialic acid, and that a part of the antigen molecule is sulfated.

Animals↗
PubMed1989

bcl-2 gene rearrangement analysis in Japanese B cell lymphoma; novel bcl-2 recombination with immunoglobulin kappa chain gene.

The rearrangement of bcl-2 gene was studied in 56 Japanese B cell lymphoma cases to investigate the contribution of bcl-2 gene to lymphomagenesis in Japan. Ten out of 56 cases showed bcl-2 gene rearrangement; it was detected in only 5 out of 16 follicular lymphoma cases (31%) and in 5 out of 40 diffuse B cell lymphoma cases (13%). The incidence of bcl-2 gene involvement in Japanese follicular lymphomas was lower than those reported in the United States. This might contribute to the lower incidence of follicular lymphoma cases in Japan. Novel recombination between bcl-2 and Ig kappa genes at the 5' region of bcl-2 and J kappa 4 segment was observed in one follicular lymphoma case, suggesting that bcl-2 gene is transcriptionally activated by Ig kappa enhancer. It was also suggested that this case had originated from a more differentiated B cell than most follicular lymphomas with bcl-2-Ig H recombination.

B-Lymphocytes↗
PubMed1989

Identification of myeloid origin in undifferentiated congenital leukemia by in vitro marrow culture study.

A case of congenital leukemia that originally did not express any lineage-specific antigenic markers is presented. The blast cell morphologic appearance was L1 according to French-American-British (FAB) classification and showed lymphoid characteristics by cytochemical staining and transmission electron microscopy. However, immunophenotyping using a variety of monoclonal antibodies did not confirm the lymphoid origin. Furthermore, the immunoglobulin heavy chain and T-cell receptor beta-chain genes were in germ-line configuration. The in vitro culture study defined the leukemia as of myeloid origin. The semisolid methylcellulose culture showed an acute non-lymphocytic leukemia-type growth pattern. Bone marrow blasts underwent myeloid differentiation with positive myeloperoxidase and butyrate esterase activity during a suspension culture. These findings indicate that this case represents an acute undifferentiated leukemia that has probably arisen from the malignant transformation of stem cells of myeloid progeny.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Blastogenic responses of human lymphocytes to a streptococcal preparation OK-432 and its fractions.

This study was undertaken to examine the blastogenic responses of PBL to Streptococcal preparation OK-432 and its fractions. The results showed that OK-432 and its fractions, Su-PR and PM, have the mitogenic activity against human lymphocytes. The demonstration that PBL which had been cultured with OK-432 expressed IL-2 receptors and the blastogenic responses of PBL to OK-432 were inhibited by anti-IL-2 antibody suggested that IL-2 and IL-2 receptors might play a central role in OK-432-induced proliferation of human lymphocytes.

Adolescent↗
PubMed1989

Novel functions and cellular interaction of human lymphoid stromal cells with lymphoid cell lines in vitro.

Lymphoid stromal (SG) cells have been isolated from the lymph node of a patient with malignant lymphoma, and characterized by positive reaction with a monoclonal antibody against the T-zone stromal cells in human lymph nodes. B-acute lymphoblastic leukemia (BALL) cells showed prominent emperipolesis toward SG cells when they were cocultured, whereas T-acute lymphoblastic leukemia (TALL) cells attached firmly to the surface of SG cells. Autologous peripheral B and T cells behaved, respectively, in the same way as BALL and TALL cells. Both BALL and TALL cells while directly interacting with the SG cells were completely inhibited from incorporating [3H]thymidine, although radioactive grains were observed in 16.4%-12.4% of supernatant BALL and 13.8%-13.0% of supernatant TALL cells in each coculture. Furthermore the media conditioned by SG cells significantly increased the incorporation of [3H]thymidine into the TALL cells as much as 190% of the control. These results indicate that SG cells undergo tissue-specific cellular interactions with B- and T-lymphoid cell lines but not with a myeloid cell line, and they can modify their growth by two distinct mechanisms. SG cells proved to be very useful in studying the effect of the lymphoid microenvironment on the proliferation of lymphocytes in vivo.

Burkitt Lymphoma↗
PubMed1988

Three novel mouse monoclonal antibodies, OM-A, OM-B, and OM-C, reactive with mucinous type ovarian tumors.

Three mouse IgG1 monoclonal antibodies (MoAbs) reactive predominantly with cytoplasmic antigens of mucinous type ovarian tumors were produced. OM-A MoAb was reactive with 11 of 14 mucinous type and two of three endometrioid type ovarian tumors, although only a minor population of the tumor cells was positive in the latter type. This MoAb was not reactive with serous type, clear cell type, or other types of ovarian tumors, nor with various types of uterine carcinoma. Normal adult and fetal tissues of female genital organs were not positive with this MoAb. Among nongynecological carcinomas, three of six metastatic tumors to the ovary from the gastrointestinal tract, one of five gastric carcinomas, and one of eight lung adenocarcinomas were positive. As for normal adult and fetal tissues of nongynecological origin, epithelium of the normal stomach, small bowel, and bronchus as well as epithelium of fetal small and large bowel and secretory products were weakly positive. Thus, this MoAb showed a selected specificity against mucinous and endometrioid types of ovarian tumors. OM-B MoAb showed a broader specificity than OM-A, reacting with all mucinous type, two of three endometrioid type, and three of 16 serous type ovarian tumors, but not with clear cell type tumors. Adenoma type, but not squamous type, cervical carcinomas and one-half of endometrial carcinomas were positive. This antigen is present in cervical mucosa, but not in ovary or endometrium. OM-C MoAb showed a specificity similar to, but broader than that of, OM-B; i.e., 11 of 14 mucinous type, two of three endometrioid type, nine of 16 serous type, and one of nine clear cell type ovarian tumors were positive. It is reactive with adenoma type uterine carcinoma and normal mucosa of the uterine cervix and with normal surface epithelium of the oviduct. Among nongynecological tumors, OM-B antigen was present in metastatic tumors to the ovary as well as in gastric and pancreatic carcinomas, while OM-C was in metastatic tumors to the ovary and gastric and colonic carcinomas. Thus, the serological analysis showed that these three MoAbs showed selective specificities to mucinous and endometrioid types of ovarian tumors. Preliminary characterization of these three OM antigens suggested that these are distinct from carcinoembryonic antigen or ABH blood group-related antigens.

ABO Blood-Group System↗
PubMed1988

Antigenic phenotype and biological characteristics of two distinct sublines derived from a small cell lung carcinoma cell line.

Two sublines, SCLC-MOA1 (MOA1) and SCLC-MOA2 (MOA2), were established from the SCLC-MO cell line, which was originally derived from an oat cell type of small cell lung carcinoma (SCLC). SCLC-MO showed typical culture morphology of SCLC, growing as tightly packed floating aggregates, while both MOA1 and MOA2 grew as a monolayer. MOA2 showed markedly shorter culture doubling time and higher colony forming efficiency than SCLC-MO and MOA1. When transplanted into nude mice, both SCLC-MO and MOA1 showed intermediate cell type histology, while MOA2 showed a picture of large cell carcinoma as non-SCLC. As for biomarkers, SCLC-MO showed a transitional state between the classic and the variant types, while MOA1 was the variant type. In contrast, MOA2 lost the biomarker characteristic of SCLC, showing rather non-SCLC type. SCLC-MO expressed NE-150 neuroendocrine antigen, but lacked PE-35 panepithelial antigen which is generally present on SCLC. It lacked also OE-130 epithelial antigen which is generally absent from SCLC. Thus, the phenotype was NE-150+/PE-35-/OE-130-, which was different from the major phenotype of SCLC, NE-150+/PE-35+/OE-130-. MOA1 was weakly positive for PE-35, showing NE-150+/PE-35 +/- /OE-130-, while MOA2 was positive for OE-130, but lost NE-150, i.e., NE-150-/PE-35+/OE-130+, showing a non-SCLC phenotype. Thus, a good concordance was observed between the antigenic phenotype and the biological characteristics of these SCLC lines. The results altogether suggested that a part of large cell carcinoma in the tumor of the patient may be derived from SCLC. Karyotype analysis showed that there were several marker chromosomes including deletion of chromosome 3p shared by these three cell lines, supporting the belief that MOA1 and MOA2 originated from SCLC-MO. Southern blot analysis showed the amplification of the L-myc related gene, probably rearranged L-myc, in the primary SCLC tumor as well as in SCLC-MO and MOA1. Northern blot analysis showed the 2.2-kilobase transcripts hybridized with a L-myc probe were observed in SCLC-MO and MOA1, but not in MOA2. In contrast, the c-myc transcript was detected only in MOA2. The activity of the myc gene family may contribute to certain biological characteristics of SCLC.

Animals↗
PubMed1988

Immunohistological analysis of thymic tumors with PE-35 monoclonal antibody reactive with medullary thymic epithelium.

PE-35 mouse monoclonal antibody (MoAb) (IgG1) detecting an epithelial antigen with a molecular weight of 35,000 was characterized serologically. Immunoperoxidase staining and double immunoenzymatic staining showed that PE-35 antigen is predominantly on nonlymphoid cells in the medulla of thymus. By immunoelectron microscopy, thymic epithelial cells in the medulla were positive with PE-35 MoAb, but macrophages, interdigitating reticulum cells, and thymocytes were negative with this MoAb, which demonstrated that PE-35 is a valuable marker for medullary epithelium. Using PE-35 and other MoAbs detecting thymic epithelial antigens (TE-3A, RFD-4, TE-4, and HLA-DR), 25 thymomas were studied, together with 6 other tumors of thymic origin. Among 25 thymomas, all 6 cases of epithelial type and 8 of 14 mixed lymphoepithelial type were positive with PE-35 MoAb, but only one of 5 lymphocytic type was positive. PE-35 antigen has a tendency to be expressed in the cases retaining medullary type thymocytes, with the phenotype of cluster of differentiation (CD) 1-/CD3+/CD6+, and also in the area of medullary differentiation. TE-3A, RFD-4, and TE-4 MoAbs reacted with most thymoma cases regardless of the types. HLA-DR was, however, expressed on a part of thymomas and the phenotype combined with that of PE-35 was as follows: PE-35+/HLA-DR+, 8 cases; PE-35+/HLA-DR-, 8 cases; PE-35-/HLA-DR+, 8 cases; PE-35-/HLA-DR-, one case. The results suggested that thymoma may originate from different subsets and/or different stages of thymic epithelium.

Antibodies, Monoclonal↗
PubMed1988

Mouse monoclonal antibodies detecting disialogangliosides on mouse and human T lymphomas.

Six monoclonal antibodies (MAbs) (4 IgG3 and 2 IgM) were produced by hybridomas obtained from A/J mice immunized with EL4(C57BL/6 derived-T lymphoma). They were found to react with antigens expressed on both mouse and human T-lymphomas but not on B lymphomas or normal cells. All of these antibodies reacted with the disialoganglioside GD2, GalNAc beta I----4(NeuAc alpha 2----8NeuAc alpha 2----3)Gal beta I----4Glc-Cer, by 3 different assay systems including the immune adherence inhibition test, enzyme-linked immunosorbent assay, and enzyme immunostaining on thin-layer chromatography. The binding specificities of these MAbs to disialogangliosides differed. Four MAbs (AI-201, AI-287, AI-410, and AI-425) showed restricted specificities, detecting only GD2, whereas the other 2 (AI-245 and AI-267) had a broader specificity, recognizing GD2, GD3, and GDlb. No evidence was obtained for the presence of the antigenic epitope in glycoproteins of mouse and human tumor cells. The ganglioside content of EL4 was low in comparison with that of M14 (a human melanoma cell line).

Animals↗
PubMed1988

Gene encoding human p250 T-cell activation antigen maps to human chromosome 11.

Human p250 T-cell activation antigen detected by a monoclonal antibody, B1.19.2, is a single peptide antigen with a molecular weight of 250 kilodaltons and is classified serologically into cluster of differentiation, CDw26. Concordance between the presence of human chromosome 11 and the reactivity with B1.19.2 was demonstrated by chromosomal analysis of 23 clones derived from three hybrid series obtained from the fusion of human activated lymphocytes or T-cell chronic lymphocytic leukemia cells and BW5147 mouse T-cell leukemic cells. The results indicated that the presence of chromosome 11 was essential for the expression of p250 T-cell activation antigen. Moreover, the gene for this antigen was assigned to chromosome 11pter----p11.2 by analysis of the hybrid clones retaining the translocated chromosome of 11.

Animals↗
PubMed1988

Serum soluble interleukin-2 receptor levels in patients with adult T-cell leukemia and human T-cell leukemia/lymphoma virus type-I seropositive healthy carriers.

Using an enzyme-linked immunosorbent assay (ELISA) technique, we measured the soluble interleukin 2 receptor (s-IL-2R) levels in the sera of patients with adult T-cell leukemia (ATL) in Japan. The s-IL-2R levels in the sera of the ATL patients were markedly higher (range 540-310, 400 U/ml, mean +/- SD = 62,800 +/- 81,000 U/ml, n = 42) than those in normal individuals (range 42-950 U/ml, mean +/- SD = 322 +/- 198 U/ml, n = 35, P less than 0.01). The patients with acute-type or lymphoma-type ATL had high s-IL-2R levels (range 11,900-310,400 U/ml, mean +/- SD = 110,340 +/- 370 U/ml, n = 15; range 26,400-214,400 U/ml, mean +/- SD = 90,170 +/- 59,040 U/ml, n = 7, respectively). All of the patients with hypercalcemia (Ca greater than 10 mg/dl) or elevated serum LDH levels (LDH greater than 500 IU/liter) also had s-IL-2R levels above 10,000 U/ml. The high s-IL-2R levels in the sera of ATL patients indicate abnormal IL-2 receptor production and its release from the leukemic cells in vivo. Thus, the serum s-IL-2R level may be a sensitive and useful marker to monitor the total amount of tumor cells in ATL, especially in the lymphoma type. We next examined the serum s-IL-2R levels in human T-cell leukemia/lymphoma virus type-I (HTLV-I) seropositive healthy carriers to investigate whether there might be abnormal IL-2 receptor expression in such individuals. However, there was no statistically significant difference between the s-IL-2R level of 71 HTLV-I seropositive healthy carriers (range 65-880 U/ml, mean +/- SD = 394 +/- 212 U/ml) and that of 71 age- and sex-matched normal individuals (range 33-950 U/ml, mean +/- SD = 357 +/- 224 U/ml) who lived in Okinawa Prefecture.

Adult↗
PubMed1988

Assignment of a gene coding for a human T-cell antigen with a molecular weight of 40,000 daltons to chromosome 17.

Hybrid human-mouse T-cell clones reactive with Tp40 antibody, which detects cluster of differentiation (CD)7 antigen on human T lymphocytes, were established. Karyotype analysis showed that human chromosome 17 was essential for the expression of CD7 antigen. The presence of this chromosome was confirmed by enzyme analysis of galactokinase, which is coded by a gene on human chromosome 17.

Animals↗