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Biomedical subjects

N Asou

Publications and source records attributed to N Asou.

At least 91 records · Page 5Linked to original sources
PubMed1992

Human T-cell leukemia virus-1-positive cell line established from a patient with small cell lung cancer.

A stable cell line, KHM-3S, was established from a patient with small cell lung cancer (SCLC), who had a high serum level of soluble interleukin 2 receptors (sIL2-R) and was seropositive for human T cell leukemia virus (HTLV)-1. KHM-3S cells were positive for IL2-R (Tac) and NKH-1, but negative for other lymphocytic markers such as OKT 11, OKT 4, OKT 8, T cell receptor (WT 31), B 1, and B 4. Moreover, the KHM-3S cells were negative for leukocyte common antigen and strongly positive for neuron-specific enolase (NSE). Secretion of sIL2-R and NSE by the KHM-3S line was detected by an enzyme-linked immunosorbent assay. Rearrangement of the T cell receptor gene and monoclonal HTLV-1 integration were found by Southern blot analysis of KHM-3S DNA. However, Northern blot analysis showed no T cell receptor mRNA. KHM-3S may be useful for studies on the role of HTLV-1 in carcinogenesis and IL2-R expression in SCLC.

Antigens, Surface↗
PubMed1992

[Expression of multidrug resistance 1 and correlation with clinical drug resistance in acute leukemia].

Expression of multidrug resistance (mdr 1) gene, which encodes a transmembrane efflux pump referred to P-glycoprotein, leads to the decreased intracellular accumulation of various lipophilic drugs, such as vinca alkaloids, anthracyclines and epipodophyllotoxins. As these drugs are commonly used in chemotherapy for acute leukemia, it is of importance to determine whether mdr 1/P-glycoprotein expression is associated with clinical resistance. In several reports, some leukemia cells from untreated patients have expression of mdr 1/P-glycoprotein. We quantitatively detected low levels of mdr 1 expression in all cases of untreated acute leukemia and normal hematopoietic cells, using the reverse transcriptase-polymerase chain reaction. Carefully designed clinical trials including mdr 1 reversing agents may have significant consequences for the treatment of acute leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

[Reactive histiocytosis during initial remission induction therapy for acute myeloblastic leukemia].

Six of 14 patients with acute myeloblastic leukemia (AML) complicated reactive histiocytosis during initial remission induction therapy. All six patients had a high fever without signs of infection during initial chemotherapy, and periods of myelosuppression were prolonged. Histiocytes with a mature appearance, some of which phagocyted erythrocytes, thrombocytes or neutrophils, increased in the bone marrow. All of 3 patients tested showed high serum levels of ferritin. Two of 3 patients treated with 125 mg/day methylprednisolone achieved complete remission. In the remaining 3 patients, one patient achieved complete remission, but the others died of fungal pneumonia or sepsis. Thus, reactive histiocytosis is one of the severe complications in patients with AML undergoing chemotherapy.

Adult↗
PubMed1991

Discordant gene and surface expression of the T-cell receptor/CD3 complex in adult T-cell leukemia cells.

Cell surface expression of the T-cell receptor (TCR)/CD3 complex on the cells from 11 acute type adult T-cell leukemia (ATL) and 4 lymphoma type ATL patients was examined by flow cytometry. Cells from 10 of 11 acute ATL patients were TCR alpha beta+ and CD3+, and their mean fluorescence intensities were low (TCR alpha beta, 25.3-84.6; CD3, 22.8-87.8). Cells from two of four lymphoma type ATL did not express this complex, and the other two were CD3+, TCR alpha beta-. In contrast, the mean fluorescence intensity of the TCR/CD3 complex in cells from a patient with T4 chronic lymphocytic leukemia was not low (TCR alpha beta, 129.9; CD3, 117.1). mRNA expressions of the TCR alpha, beta, and CD3 gamma, delta, epsilon, and zeta chains were examined by Northern blots. ATL cells from two acute and two lymphoma types expressed amounts of this complex equal to or greater than those expressed by T4 chronic lymphocytic leukemia. CD3 delta and TCR beta mRNA in ATL and T4 chronic lymphocytic leukemia cells were equally stable to actinomycin D treatment. The synthesis of CD3 zeta protein by ATL cells was detected by Western blotting assay. On the basis of these findings, we discuss the possible involvement of the TCR/CD3 complex in activation of ATL cells.

Adult↗
PubMed1991

Leukaemia of novel gastrointestinal T-lymphocyte population infected with HTLV-I.

In a 72-year-old man with watery diarrhoea and leukocytosis the proliferation of abnormal cells was studied in specimens obtained by endoscopic biopsy of the gastrointestinal tract. Flow cytometry of leukaemia cells revealed a monoclonal expansion of "double-negative" (CD4-, CD8-) cells bearing T-cell receptor (TCR) alpha beta products. Southern blotting confirmed monoclonal integration of HTLV-I. A novel T-cell subset of double-negative TCR alpha beta cells in the gastrointestinal tract in adult man may be a target for HTLV-I infection.

Aged↗
PubMed1991

Regulatory mechanisms for the expression of a functional beta chain of interleukin 2 receptor on T4 chronic lymphocytic leukemia cells.

Monoclonal antibodies, each recognizing interleukin 2 receptor (IL-2R) alpha, or beta, were used to see the regulatory mechanisms of the expressions on leukemic cells from a patient with T4 chronic lymphocytic leukemia (T4-CLL). Cells from this patient expressed only IL-2R beta, and the expression was enhanced by medium cultivation. IL-1 enhanced the expression of not only IL-2R beta but also IL-2R alpha on the cells. Binding studies using 125I-IL-2 showed the presence of an intermediate receptor (734 sites/cell, Kd = 1.2 nM) and a few high-affinity receptor (172 sites/cell, Kd = 132 pM) on cells cultured with IL-1. IL-2 and IL-1 synergistically promoted the proliferation of the cells, suggesting that the induced IL-2R was functional. In addition, anti-IL-1 antibodies inhibited IL-2R beta expression by cultured cells, suggesting that it was dependent on IL-1 produced by the leukemic cells. These findings suggested that IL-1 might enhance the expression of IL-2R beta in a subset of human T cells, and implied a role of IL-1 in the proliferation of the leukemic T cells.

Aged↗
PubMed1991

Acute unclassified leukemia originating from undifferentiated cells with the aberrant rearrangement and expression of immunoglobulin and T-cell receptor genes.

To analyze the development pathways of early hematopoietic cells, we studied the rearrangement and expression of the immunoglobulin (Ig) and T-cell receptor (TCR) genes in 12 patients with acute unclassified leukemia (AUL). Leukemia cells from these patients were negative for myeloperoxidase staining and failed to express B-cell, T-cell, or megakaryocyte associated antigens. The expression of the CD7 antigen, myeloid associated antigens, or both was detected in three patients each. Ig and/or TCR gene rearrangements were detected in seven of the 12 patients, and five had rearrangement of both the Ig and TCR genes. Full length mature TCR gene transcripts were not demonstrated in most of the patients showing TCR gene rearrangements. In contrast, cells from two patients with germline configurations of the Ig and TCR genes tested expressed truncated forms of both Ig and TCR genes. These results suggest that AUL may generally originate from undifferentiated cells with an aberrant rearrangement and/or expression of the Ig and TCR genes.

Acute Disease↗
PubMed1991

[Analyses of T cell receptor and its clinical implications in T cell neoplasms].

We studied gene rearrangement and expression of immunoglobulin heavy (IgH) chain, T cell receptor (TCR) beta, gamma and delta chains in neoplastic T cells from patients with leukemia and lymphoma. Rearrangements of TCR beta and gamma chain genes were observed in most of T cell neoplasms. TCR delta chain gene rearrangements or deletions were detected in all 77 T cell neoplasms; 6 of 9 CD3- T cell neoplasms showed rearrangement, whereas biallelic deletion of TCR delta chain gene was the most common pattern in CD3+ T cell neoplasm (65 of 68 patients). One patient with CD3- T cell leukemia had TCR delta chain gene rearrangement with a germline configuration of TCR beta, gamma and IgH chain genes. TCR gamma and delta chain gene transcripts were detected in most of the CD3- T cell neoplasms, whereas mature TCR alpha and beta chain mRNA were demonstrated in the majority of the CD3+ T cell neoplasms. In 6 patients with CD7+ CD3- CD4- CD8- MPO- leukemia, only 2 patients had rearrangements and weak expressions of IgH, TCR gamma and delta chain genes. We also present two cases of double negative (CD3+ CD4- CD8-) leukemia; one is TCR gamma delta bearing LGL, the other is TCR alpha beta bearing ATL. These results suggest that most of T cell neoplasms preserve a pattern of genotypic and phenotypic expression reflecting their developmental pathways and differentiation levels of TCR bearing normal T cells.

Cell Differentiation↗
PubMed1991

[Biomolecular aspects of adult T-cell leukemia].

ATL (adult T-cell leukemia) is the first human cancer known to be caused by a retrovirus. ATL cells show usually positive for CD2, CD3, CD4, CD25 and HLA-DR, but negative for CD8. They produce a variety of cytokines, including IL-1, IL-2, TNF, ADF and PTHrP. PTHrP is considered to be responsible for hypercalcemia which is frequently observed in ATL. Recently, we reported two unusual cases of HTLV-I associated malignancy; 1) a case of CD4 and 8 double negative tumor affecting mainly gastrointestinal tract and 2) a case mimicking small cell lung cancer. IL-2-toxin, a conjugate of IL-2 and diphtheria toxin, has been prepared as a recombinant product and evaluated for the suppressive effect to ATL cells. Clinical trail of IL-2-toxin is now anticipated.

Antigens, CD↗
PubMed1990

Human T-cell leukemia virus type 1 associated with small cell lung cancer.

A patient with small cell lung cancer (SCLC) whose serum contained high levels of soluble interleukin-2 receptors is reported. Soluble interleukin-2 receptors in the supernatant of cultured SCLC cells obtained from the patient's pleural effusion while he had malignant pleuritis, increased almost linearly from the time of cell seeding. The expression of interleukin-2 receptors (Tac) on the SCLC cells were demonstrated by an immunofluorescence study. However, other lymphocytic markers, including OKT 11, OKT 4, OKT 8, B 1, and B 4, were not found on the cells with the exception of the natural killer cell marker, NKH-1. Southern blot analysis indicated the rearrangement of the T-cell receptor of the cancer cells. Moreover, monoclonal integration of human T-cell leukemia virus type 1 (HTLV-1) provirus in DNA from the cancer cells was also demonstrated. These observations suggest that some SCLC in HTLV 1 endemic areas are associated with HTLV-1.

Biomarkers, Tumor↗
PubMed1990

Establishment and characterization of acute B-cell lymphocytic leukemia cell line showing (8;14) and (14;18) chromosome translocation.

Cell line KHM-2B expressing two oncogene products, c-myc and bcl-2, was established from a patient with acute lymphocytic leukemia with an 8;14 and 14;18 chromosome translocation. Surface marker studies of the cell line showed that the cells were positive for HLA-DR, CALLA (CD10), B1 (CD20) and B4 (CD19), but negative for T11 (CD2). The fresh cells from peripheral blood of the patient had no surface immunoglobulins, whereas KHM-2B cells were positive for mu.lambda type surface immunoglobulin. A cytogenetic analysis of the cell line revealed two translocations, t (8;14) (q24;q32) and t(14;18)(q32;q21). Rearrangement of the c-myc and bcl-2 genes was detected by Southern blot analysis of the KHM-2B DNA. Northern blot analysis revealed production of c-myc and bcl-2 mRNAs. These results indicated that two oncogenes were activated by two translocations to immunoglobulin genes.

Antigens, Surface↗
PubMed1989

Synthesis of a novel cytokine and its gene (LD78) expressions in hematopoietic fresh tumor cells and cell lines.

The gene coding for the protein LD78 was isolated from stimulated human tonsillar lymphocytes by differential hybridization. The gene product consisted of 92 amino acids with characteristics of cytokines. LD78 gene transcripts were detected in eight of eight fresh samples of cells from patients with acute nonlymphocytic leukemia (ANLL) by Northern blot analysis. ANLL cells with monocytic features gave the strongest bands. RNA transcripts were found in two of three samples of cells from patients with adult T cell leukemia (ATL), eight of nine samples from patients with acute lymphocytic leukemia (ALL) of B cell lineage, and one of the three samples from patients with T cell ALL. KG-1, HL-60, HUT 102, MT-2, and MJ cell lines expressed the LD78 gene constitutively. The LD78 protein was detected in culture supernatants and cell lysates of HUT 102, MT-2, MJ, and fresh ATL cells by Western blot analysis. This protein was not found in culture supernatants or cell lysates of monocytic leukemia cells and HL-60 cells, although LD78 transcripts were found in those cells. The discrepancy between gene and protein expression might be explained by the stability of the mRNA. Thus, the protein may be involved in the neoplastic transformation of hematopoietic cells.

Biological Factors↗