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Biomedical subjects

K Oshimi

Publications and source records attributed to K Oshimi.

At least 163 records · Page 9Linked to original sources

Cytotoxicity of interleukin 2-activated lymphocytes for leukemia and lymphoma cells.

Studies were undertaken to determine whether leukemia and lymphoma cells would be lysed by autologous and allogeneic lymphokine-activated killer (LAK) cells. Peripheral blood mononuclear cells (PBMC) from patients and normal donors were cultured for five days, 2 weeks, and 4 weeks with medium containing 2,500 units of recombinant interleukin 2 (IL-2) per mL, and their cytotoxicity was assayed by a five-hour 51Cr-release test. Of primary tumors isolated from patients with acute nonlymphoblastic leukemia, acute lymphoblastic leukemia, and non-Hodgkin's lymphoma, tumors of 37 out of 40 patients tested were shown to be susceptible to normal donors' LAK, and tumors of 18 of 20 patients tested were shown to be susceptible to autologous LAK. LAK cultured for longer periods showed a tendency to have lower cytotoxicity. LAK had also low, but significant, levels of cytotoxicity for nonmalignant target cells. Because PBMC expanded in IL-2-containing medium consisted mainly of OKT3-positive pan T cells, OKT8-positive suppressor/cytotoxic cells, and Leu-11-positive natural killer (NK) cells, and treatment with OKT3 and Leu-11 monoclonal antibodies (mAb) reduced LAK activity for autologous and allogeneic tumor cells, both T and NK cells appeared to be effector cells for LAK activity. Mechanisms of target-cell recognition in the LAK system seem to be different from those in alloreactive cytotoxic T lymphocytes (CTL) based on the results that, while cytotoxicity of alloreactive CTL was inhibited by the treatment of effector cells with mAb, OKT3, and OKT8, and by the treatment of target cells with a mAb that reacts with HLA class I antigen, LAK activity was not inhibited by the above treatment. When chromosomes of IL-2-expanded PBMC in nine patients and two normal individuals were analyzed, PBMC from one patient showed chromosomes of clonal abnormalities, and PBMC from five donors showed those of nonclonal abnormalities.

Antibodies, Monoclonal↗

A case of gastric carcinoma associated with excessive granulocytosis. Production of a colony-stimulating factor by the tumor.

A patient with gastric carcinoma exhibited an excessive granulocytosis (58,000/microliter) preoperatively, in the absence of overt infection. After resection of the primary tumor, the peripheral leukocyte count decreased promptly to the normal value. In a search for a colony-stimulating factor (CSF), the tumor was transplanted into nude mice. A marked neutrophilia was observed in the tumor-bearing mice, suggesting the production of CSF by the tumor. Media conditioned by the primary culture of the tumor cells revealed the presence of CSF activity as well. CSF-producing carcinomas have been detected in various organs; nevertheless, no cases of gastric carcinoma have hitherto been described. It is of particular interest that in this patient hypercalcemia was not observed, although it often accompanied CSF-producing tumors reported previously. Therefore, it is suggested that this tumor secreted pure CSF and that the CSF produced by the tumor did not necessarily induce hypercalcemia.

Aged↗

Natural killer-mediated lysis of normal and malignant target cells, and its regulation by monocytes.

After depletion of monocytes, natural killer (NK) cells were partially purified from peripheral blood by Percoll density gradient sedimentation. The NK cells were then cultured for 1 d and assayed for their cytotoxicity against various types of normal and malignant target cells. All types of target cells tested were found to be susceptible to NK cells. The susceptible targets were autologous T and B lymphocytes, mitogen-induced T and B blasts, monocytes, large granular lymphocytes, autologous or allogeneic lymphoma and leukemia cells isolated from patients, and cultured cell lines, including those resistant to interferon-activated lymphocytes. Such a broad spectrum of cytotoxicity was demonstrated in 1 d of culture, and freshly prepared NK cells were not cytotoxic, or, if anything, were less cytotoxic. Monocytes and their supernatants, added throughout the course of culture, markedly inhibited the development of their cytotoxicity. These results may suggest that, although NK cells having ability to lyse autologous normal and malignant target cells are present in vivo, their lytic activity is regulated by coexisting monocytes.

B-Lymphocytes↗

A case of T-cell chronic lymphocytic leukemia with an unusual phenotype and central nervous system involvement.

A case of T-cell chronic lymphocytic leukemia is reported. The leukemic cells had the morphologic features of medium-sized, mature-looking lymphocytes, and had an affinity for the central nervous system. Cytochemically, they were positive for alpha-naphthyl acetate esterase and acid phosphatase. They formed E-rosettes (E+) and reacted with OKT11 but not with OKT3/Leu-4, OKT4/Leu-3, OKT8/Leu-2, or OKM1, and did not possess IgG-Fc receptors (Fc gamma R). Functionally, they did not respond to phytohemagglutinin or concanavalin A, were not natural killer cells or antibody-dependent as well as alloantigen-reactive killer cells. Furthermore, they did not possess a helper or suppressor T-cell function for immunoglobulin synthesis. Results of immunologic studies suggest that the leukemic cells were derived from a normal counterpart of a lymphocyte subset present as a minor component of the peripheral blood, namely an E+, OKT3-, OKM1-, Fc gamma R- subset, the function of which is not yet identified.

Adult↗

Cellular characteristics of neoplastic angioendotheliosis. An immunohistological marker study of 6 cases.

Neoplastic angioendotheliosis (NAE) is a rare, mostly fatal disease characterized by proliferation of large blastoid cells in small vessels of various organs. The origin of neoplastic cells remain undetermined. In this study, cell markers were studied immunohistologically on paraffin sections of six cases of NAE, by applying avidin-biotin-peroxidase (ABC) method and five antibodies which can demonstrate marker antigens on formalin fixed and paraffin embedded specimens. It was shown that the neoplastic cells were heavily stained with an anti-B lymphocyte monoclonal antibody LN-1 (6/6), moderately stained with another anti-B lymphocyte antibody LN-2 (5/6) and heavily stained with a monoclonal antibody which reacts with all levels of leukocytes (Dako-LC) (6/6). The cells did not show positive reaction with an anti-myelomonocytic antibody anti-Leu M1. The reaction against anti-Factor VIII, which can depict endothelial cells, was mostly negative, and if positive, was faint and indefinite, leading to an assumption that the reaction was against antigens in serum and not against neoplastic cells. These results suggest that the neoplastic cells of NAE are in the B lymphocyte lineage.

Antibodies, Heterophile↗

Lysis of lymphoma cells by autologous and allogeneic natural killer cells.

Studies were undertaken to determine whether natural killer (NK) cells would lyse autologous and allogeneic lymphoma cells. When large granular lymphocytes, which are known to mediate NK activity, were enriched from peripheral blood and used as effector cells, they lysed autologous lymphoma cells of all of eight patients tested, and those of healthy donors lysed lymphoma cells of all of ten patients tested. The addition of interferon to the culture medium enhanced their cytotoxicity in three of the eight patients in the autologous effector-tumor system and in four of the ten patients in the above allogeneic system. On the basis of the unlabeled target competition test and the decrease in cytotoxicity with anti-NK antibody treatment, NK cells appeared to be the main cytotoxic effector cells for autologous and allogeneic lymphoma cells.

Adolescent↗

Lysis of lymphoma cells by cultured large granular lymphocytes.

Studies were undertaken to determine whether in vitro-propagated large granular lymphocytes (LGL), which are known to mediate natural killer (NK) activity, would lyse autologous and allogeneic lymphoma cells. LGL from ten patients and two healthy donors were propagated in vitro for two to four weeks with interleukin 2-containing medium, and their cytotoxicity was tested in a 5-h 51Cr-release assay. Cultured LGL from all the patients and healthy donors demonstrated strong cytotoxicity against K562 target cells, a standard target in NK assay, while cultured LGL from the patients lysed autologous lymphoma cells from three of the ten patients tested and those of the two healthy donors lysed lymphoma cells from four of the ten patients. These findings indicate that, when LGL propagated in vitro in large numbers show lytic activity against autologous lymphoma cells, these LGL may have potential application in clinical trials.

Cells, Cultured↗

Neoplastic angioendotheliosis with B lymphocyte markers on neoplastic cells: a case report.

Neoplastic angioendotheliosis (NAE) is a rare disease characterized by the occlusion of small vessels by apparently neoplastic medium-sized cells. The origin of these cells remains undetermined, mainly because the diagnosis in most of these cases has been made on autopsy. This report describes a case of NAE from whom a biopsy specimen was obtained and studied immunohistologically. The cells occluding small vessels of this patient bear B cell markers such as monoclonal immunoglobulin (mu, lambda), Leu14, B1, OKB2, and Dako-PanB, whereas they do not react with antibodies against delta- and kappa-chain of immunoglobulin (Ig), or antibodies against markers of T cells, myelomonocytic cells and endothelial cells. These results show clearly that the cells occluding the small vessels of this patient are neoplastic and of B cell lineage. This is the first case of NAE in whom the neoplastic cells in the blood vessels have been proved to be of lymphocytic lineage.

Antibodies, Monoclonal↗

A case report of T-cell lymphoma with suppressor phenotype and helper function for immunoglobulin synthesis.

A patient with T-cell lymphoma is presented. The morphologic features of a biopsied lymph node were consistent with adult T-cell lymphoma with hypergammaglobulinemia, and most of the lymph node cells were reactive with monoclonal antibody OKT8, which detects suppressor/cytotoxic T lymphocytes. However, in a pokeweed mitogen-driven test system in which the capability of T lymphocytes to help or suppress the differentiation of B lymphocytes is measured, the lymphoma cells induced immunoglobulin synthesis of B lymphocytes, thus providing helper function. As far as we know, this is the first report on T-cell lymphoma having suppressor phenotype and helper function for immunoglobulin synthesis.

Antibodies, Monoclonal↗