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Biomedical subjects

K Oshimi

Publications and source records attributed to K Oshimi.

At least 19 recordsLinked to original sources
PubMed1995

Telomeric DNA in normal and leukemic blood cells.

We studied telomeric DNA in leukemic cells as well as in normal T cells, B cells, monocytes, polymorphonuclear leukocytes, and bone marrow hematopoietic progenitor cells. No marked differences were observed in the sizes of the telomeric repeats in the various populations of normal blood cells obtained from donors in their twenties to sixties, and the telomere length ranged between 8.5 and 9.0 kb. The leukemic cells of 12 patients with acute leukemia (seven with myeloid and five with lymphoid leukemia) showed a variable reduction in the length of telomeric DNA, ranging from 2.7 to 6.4 kb. The average telomere length was 4.8 and 4.7 kb in myeloid and lymphoid leukemia, respectively, while the telomere length in peripheral blood mononuclear cells obtained from the same patients during complete remission was 8.5 and 7.9 kb, respectively. When the same Southern blots were hybridized with Alu or alphoid sequences, no marked changes in the sizes of the repetitive DNA sequences were observed, indicating that the DNA abnormality in the leukemic cells was specific to the telomere region. Investigation of telomeric DNA changes may be helpful in determining the biological properties of leukemic cells.

Adult↗
PubMed1995

[Clinical course of a HIV-seropositive patient with thrombocytopenia and hypergammaglobulinemia who was initially screened by annual complete physical examination].

A 57-year-old man was admitted because of hypergammaglobulinemia which was initially pointed out by annual complete physical examination. No significant abnormal findings were observed except polyclonal hypergammaglobulinemia at that time (IgG; 2,662 mg/dl, IgA; 422 mg/dl). Seven months later, he has progressed to show thrombocytopenia. The laboratory data showing the reduction of peripheral CD 4-positive T cells (CD 4; 0.2 x 10(9)/l, CD 4/8 ratio; 0.19) and positive serum HIV antibody revealed that his hypergammaglobulinemia and thrombocytopenia were resulted from HIV infection. The peripheral platelet count decreased to 28 x 10(9)/l at minimal point, however, it recovered to 160 x 10(9)/l within 7 months without treatment. His good performance status has been still maintained over 4 years. His whole clinical course suggests that there is no significant correlation between peripheral platelet counts, serum gammaglobulin levels or the amounts of PAIgG in this case. This case proposes that we should also consider a possibility of HIV infection for the patients showing hypergammaglobulinemia.

HIV Seropositivity↗
PubMed1995

[Characterization of peripheral blood natural killer (NK) cells in two patients with CD16+ CD56- NK cell-lineage granular lymphocyte-proliferative disorder].

In normal peripheral blood natural killer (NK) cells, the subset of CD16+ CD56+ cells is predominant, and that of CD16+ CD56- cells is rarely present. Because we have found the expansion of CD16+ CD56- NK cells in the peripheral blood of two patients with NK cell-lineage granular lymphocyte-proliferative disorders (NK-GLPD), the clinical findings and cellular characteristics of these patients were compared with those of CD16+ CD56+ NK-GLPD patients. Although CD16+ CD56- and CD16+ CD56+ NK-GLPD cells were morphologically different, clinical findings and courses, and NK activity did not differ significantly. Because strong NK activity was demonstrated in CD16+ CD56- NK-GLPD cells, the CD56 antigen, one of the adhesion molecules, did not seem to play a major role in NK cell-mediated cytotoxicity. The CD56 antigen is known to be more strongly expressed by immature NK cells than by mature NK cells. However, because interleukin 2-activated CD16+ CD56- NK-GLPD cells rapidly expressed the CD56 antigen, the degree of CD56 antigen expression did not always correlate with the maturity of NK cells.

Aged↗
PubMed1994

Expression of multidrug resistance P-glycoprotein on peripheral blood mononuclear cells of patients with granular lymphocyte-proliferative disorders.

The immunological findings and clinical course of 33 patients with granular lymphocyte-proliferative disorders (GLPD) are presented. Based on the surface phenotypes of peripheral blood granular lymphocytes (GL), the GLPD were divided into two groups, namely CD3+ T cell-lineage GLPD (T-GLPD) and CD3- CD16+ NK cell-lineage GLPD (NK-GLPD). Twenty-one patients had T-GLPD, and 12 had NK-GLPD. One patient with T-GLPD and two patients with NK-GLPD had progressive clinical courses and died of the disease despite receiving combination chemotherapy. Among eleven patients analysed for the expression of multidrug resistance P-glycoprotein, six of eight patients with T-GLPD and all three patients with NK-GLPD clearly expressed P-glycoprotein. Since patients with immature NK-GLPD appear to undergo a progressive clinical course, we suggest that therapeutic trials using P-glycoprotein blockers in addition to chemotherapy might be beneficial for such patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Cytotoxicity of cytokine-induced killer cells coated with bispecific antibody against acute myeloid leukemia cells.

Various types of cytokines have been used in in vitro experiments to generate cytokine-induced killer (CIK) cells that are reactive to patient acute myeloid leukemia (AML) cells. Of these CIK cells, interleukin-2 (IL-2)-activated peripheral blood mononuclear cells, i.e., lymphokine-activated killer (LAK) cells, with the initial addition of the anti-CD3 monoclonal antibody (T3 LAK cells), are the most potent cytotoxic lymphocytes, and have marked proliferative capacity. The cytotoxicity of such T3 LAK cells against CD13+ AML cells is further enhanced by the addition of anti-CD3 x anti-CD13 bispecific antibody (BsAb) during the cytotoxicity assay. The combined use of T3 LAK cells and the BsAb can be used for ex vivo purging of CD13+ AML cells in autologous bone marrow transplantation. Other cytokines, such as IL-7 or IL-7 in combination with IL-2, or newly identified cytokines, will also be tested in attempts to obtain more specific and more potent effector cells. Studies of methods to increase the susceptibility of AML cells to CIK are also required.

Acute Disease↗
PubMed1994

Interleukin-11.

Interleukin-11 (IL-11), a stromal cell-derived cytokine, has been known to act widely in hematopoietic and non-hematopoietic systems. IL-11 supports the growth of certain types of plasmacytoma and hybridoma cells, acts with interleukin-3 (IL-3) in shortening the Go period of early progenitors. IL-11 supports megakaryocyte colony formation and maturation, and acts as an autocrine growth factor in megakaryoblastic cell lines. In addition, IL-11 stimulates erythrocytopoiesis, enhances antigen-specific antibody responses, induces the synthesis of acute phase proteins, inhibits lipoprotein lipase activity and adipocyte differentiation, and promotes neuronal development. Administration of rhIL-11 to mice resulted in an increase of neutrophils and platelets. The human IL-11 gene is localized at 19q13.3-13.4, and codes 199 amino acids and 23 kDa with no N glycosylation. Its receptor and signal transduction share partially those of interleukin-6 (IL-6). Further analysis of its role in normal and pathological state is necessary to determine the exact function and its application for clinical uses.

Acute-Phase Proteins↗
PubMed1994

Combination of interleukin-2-stimulated lymphocytes and bispecific antibodies that efficiently lyse leukemic cells does not affect bone marrow CD34-positive stem cell function in vitro.

We have recently reported that a combination of lymphokine-activated killer (LAK) cells and bispecific antibodies (BsAb) efficiently lysed autologous and allogeneic leukemic blasts that had surface antigens reactive with the BsAb. The effector cells used in that experiment were peripheral blood mononuclear cells stimulated with interleukin-2 (IL-2) for 2 weeks, with the initial addition of anti-CD3 moAb; these were termed T3-LAK effector cells. In this study, we examined the effects of T3-LAK cells and BsAb on autologous normal CD34+ BM cells in both cytotoxicity and colony formation assays. When T3-LAK cells were incubated with CD34+ BM cells, low levels of cytotoxicity were induced against the CD34+ BM cells and the cytotoxicity was enhanced by the addition of anti-CD3 Fab' x anti-CD 13 Fab' BsAb but not by the addition of anti-CD3 Fab' x anti-CD10 Fab' BsAb. This enhancement appeared to be due to the lysis of CD34+CD13+ BM cells. When T3-LAK cells were preincubated with CD34+ BM cells in the presence or absence of the BsAb and plated for colony assay, neither the T3-LAK cells nor the BsAb affected granulocyte-macrophage or mixed-cell colony formation by CD34+ BM cells. Taken together with our previous finding that T3-LAK cells used in combination with the BsAb markedly inhibited colony formation by leukemic progenitor cells, these results indicate that this combination provides a potential new strategy for CD34+ BM cell purging in autologous BMT.

Antibodies, Bispecific↗
PubMed1994

[Nasal NK-cell lymphoma].

A 75-year-old man was admitted to our hospital on June 1st, 1993, because of nasal obstruction, epistaxis, fever, night sweats and weight loss. Examination disclosed a 2-cm white necrotic mass in the nasal septum, and a biopsy disclosed non-Hodgkin's lymphoma, diffuse, mixed-type. Imprint smears showed cytoplasmic azurophilic granules in the tumor cells. Dense granules were demonstrated by electron microscopy. The tumor cells were CD1-2+3-4-7+8-16+56+57-, and T cell receptor genes were in germline configuration. NK activity against K562 was strongly positive. Based on morphologic, phenotypic, immunogenotypic, and cytotoxic findings, the tumor cells seemed to be derived from activated NK cells. Because the tumor cells were positive for the EB virus and CD21 antigen, EB virus seemed to have infected CD21-positive NK cells and transformed them. MDR P-glycoprotein was also positive. This finding may explain why nasal lymphomas are resistant to chemotherapy and have a poor prognosis.

Cell Transformation, Viral↗
PubMed1993

Ca2+ response in single human T cells induced by stimulation of CD4 or CD8 and interference with CD3 stimulation.

A Ca2+ imaging method has been used to demonstrate simultaneously the magnitude and time course of the increase in the intracellular Ca2+ concentration ([Ca2+]i) in 10-30 individual human peripheral T cells following stimulation by anti-CD4 or anti-CD8 monoclonal antibody (MAb) as well as anti-CD3 MAb. The rise in [Ca2+]i began within 10 s of the introduction of the MAb and reached a peak of 240 nM (mean of 73 cells) in 20-40 s. The peak was followed by a slow decrease persisting for 6-8 min. Comparing Ca2+ responses in the presence and absence of external Ca2+, the rise in [Ca2+]i was found to be caused by both transient intracellular Ca2+ release and a long-lasting Ca2+ influx from outside the cell. Cross-linking of CD4 or CD8 using anti-IgG antibody augmented the response in individual cells, as seen in the higher peak (365-390 nM) and the longer duration (over 10 min). Simultaneous stimulation of CD3 and CD4 did not cause a summation of Ca2+ responses but caused a suppression in the CD3-mediated Ca2+ response. The results support the view that CD4 and CD8 play a role in signal transduction for T cell activation and that the CD4-derived signal interferes with the CD3-derived signal at some stage in the signalling pathway causing the Ca2+ response.

Antibodies, Monoclonal↗
PubMed1993

Expression of multidrug resistance P-glycoprotein on peripheral blood mononuclear cells of patients with granular lymphocyte-proliferative disorders.

Some patients with granular lymphocyte-proliferative disorders (GLPD) have been reported to have an aggressive clinical course with a poor prognosis and to be refractory to chemotherapy. In this study, expression of multidrug resistance P-glycoprotein on peripheral blood mononuclear cells (PBMC) of 11 patients with GLPD was examined by staining with MRK 16, a monoclonal antibody that binds to an external epitope of P-glycoprotein, and with the dye rhodamine, a known substance to be excreted from the cells through P-glycoprotein. Among those tested, the PBMC of six of eight patients with T-cell-type GLPD as well as those of three of three patients with natural killer cell-type GLPD expressed P-glycoprotein significantly. Furthermore, PBMC of two of two patients were also poorly stained with the dye rhodamine, and the treatment of PBMC with either verapamil or quinidine, multidrug resistance-reversing agents, led to their increased staining, suggesting that these PBMC actively release chemotherapeutic agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

A bispecific antibody enhances cytokine-induced killer-mediated cytolysis of autologous acute myeloid leukemia cells.

An anti-CD3 Fab' x anti-CD13 Fab' bispecific antibody (BsAb) was generated. This BsAb reacted with both CD3+ T cells and CD13+ acute myeloid leukemia (AML) cells. We investigated whether cytokine-stimulated peripheral blood mononuclear cells (PBMC) could lyse patient AML cells after addition of the BsAb. When interleukin-2 (IL-2)-stimulated PBMC were assayed for their cytotoxicity against 51Cr-labeled allogeneic and autologous CD13+ AML cells, their activity was markedly enhanced by the addition of the BsAb. PBMC stimulated with IL-2 plus anti-CD3 monoclonal antibody (MoAb) showed higher proliferative ability and higher cytotoxicity if this was expressed as lytic units per culture. IL-7-stimulated PBMC also exhibited enhanced cytotoxicity against CD13+ AML cells after addition of the BsAb. Ultrastructurally, CD13+ AML cells incubated with IL-2 plus anti-CD3 MoAb-stimulated PBMC and the BsAb showed apoptotic morphologic changes. A colony assay for AML blast progenitors showed that the colony formation of CD13+ AML cells was inhibited by the addition of autologous IL-2 plus anti-CD3 MoAb-stimulated PBMC, and that this inhibition was further enhanced by the addition of the BsAb. A colony assay for normal bone marrow progenitor cells showed that the addition of autologous IL-2 plus anti-CD3 MoAb-stimulated PBMC and the BsAb inhibited the formation of granulocyte-macrophage colonies and mixed-cell colonies. However, the degree of inhibition was smaller than that for the AML blast colonies. Taken together, these findings suggest that this BsAb may be useful for ex vivo purging of CD13+ AML cells in autologous bone marrow transplantation.

Antibodies, Monoclonal↗
PubMed1993

Autophagolysosomes exhibiting lysosomophagy in the granular lymphocytes of patients with granular lymphocyte-proliferative disorders.

The ultrastructure of granular lymphocytes (GLs) in the peripheral blood of 12 patients with granular lymphocyte-proliferative disorders (GLPDs) was studied. Autophagolysosomes exhibiting so-called "lysosomophagy" were seen in the GLs of four of these patients but not in normal individuals. Because rod-shaped lysosomes beginning to enclose other lysosomes were seen, the autophagolysosomes exhibiting lysosomophagy in GLs were thought to be formed by the same wrapping mechanism. As far as we know, this is the first report of lysosomophagy in lymphocytes.

Adult↗
PubMed1993

The effects of leukemia inhibitory factor and interleukin 6 on the growth of acute myeloid leukemia cells.

The effects of leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) on blast progenitors from acute myeloblastic leukemia (AML) were examined using a blast colony assay in a serum-free culture system. LIF and IL-6 stimulated colony growth in 2 and 5, respectively, of 11 cases studied. The simultaneous addition of LIF with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3) or IL-6 produced a statistically significant increase of colony numbers in 3, 6 and 7 of 11 cases, respectively. Numbers of colonies increased significantly when IL-6 was added simultaneously with GM-CSF or IL-3 in 5 and 4 of 11 cases, respectively. LIF or IL-6 used in the primary culture did not significantly change the numbers of secondary colonies compared to GM-CSF. Previous exposure to LIF and IL-6 did not alter cellular phenotype or morphology, indicating that LIF and IL-6 did not induce the differentiation of fresh AML blasts.

Adult↗
PubMed1993

Circulating megakaryocyte progenitors in myeloproliferative disorders are hypersensitive to interleukin-3.

Previous studies have reported that megakaryocyte progenitors in myeloproliferative disorders (MPD) formed spontaneous megakaryocyte colonies without the addition of megakaryocyte colony-stimulating factor (Meg-CSF). To determine whether this spontaneous colony formation is due to autocrine proliferation of MPD megakaryocyte progenitors or to hypersensitivity to Meg-CSF that might exist in the culture system, we investigated colony-forming unit-megakaryocytes (CFU-Meg) in the peripheral blood of 11 MPD patients, using serum-free cultures. Spontaneous megakaryocyte colonies were observed in serum-free cultures of nonadherent mononuclear cells (NAdMNC) obtained from MPD patients with thrombocytosis, whereas the NAdMNC of MPD patients without thrombocytosis, that of patients with reactive thrombocytosis and normal subjects never formed spontaneous colonies. However, the spontaneous colonies from MPD patients with thrombocytosis disappeared in cultures using highly purified CD34-positive cells as target cells. To study the hypersensitivity of megakaryocyte progenitors to Meg-CSF, dose-response experiments were performed with interleukin-3 (IL-3). CFU-Meg from MPD patients with thrombocytosis showed maximal growth at the concentrations of IL-3 lower than those for normal subjects. CFU-Meg of MPD patients without thrombocytosis and that of patients with reactive thrombocytosis showed the same colony growth response to IL-3 as that of normal subjects. This result indicates that the CFU-Meg of MPD patients with thrombocytosis are hypersensitive to IL-3. It also suggests that spontaneous colony formation by NAdMNC is not due to the autocrine growth of megakaryocyte progenitors but is due to the hypersensitivity of megakaryocyte progenitors to Meg-CSF, such as IL-3, released by accessory cells. Furthermore, it is possible that such hypersensitivity of CFU-Meg to IL-3 might be a pathogenic factor in MPD with accompanying thrombocytosis.

Adult↗
PubMed1993

[Mechanism of immunosuppressive therapy for aplastic anemia].

The mechanism of therapeutic effect of anti-lymphocyte globulin (ALG) and cyclosporin A (CyA) on patients with aplastic anemia was studied. When peripheral CD8 positive cells obtained before therapy were cocultured with bone marrow CD34 positive cells obtained after hematological recovery, the number of colony forming unit granulocyte-macrophage (CFU-GM) and burst forming unit erythroid (BFU-E) were decreased. This result indicates that ALG and CyA inhibits CD8 positive cells which suppress the growth of progenitor cells, resulting in the recovery of hematopoiesis. Next we investigated the plasma concentrations of cytokines including G-CSF, GM-CSF, IL-6, IL-1 alpha and IL-1 beta after ALG treatment. Although the elevation of plasma concentrations of G-CSF and GM-CSF after ALG treatment were found in 11 of 13 patients and in 2 of 13 patients respectively, cytokine production by ALG appeared to be unrelated to the therapeutic effect of ALG for aplastic anemia.

Adult↗
PubMed1993

Heterogeneity of CD7+ 4- 8- 1- leukemia: usefulness of cytoplasmic antigen detection for subclassification.

We identified CD3 and myeloperoxidase (MPO) antigens in the cytoplasm of leukemic cells from 15 patients with CD7+ 4- 8- 1- leukemia. Seven patients, five of whom had a mediastinal mass, had only cytoplasmic CD3 (cCD3) antigen; these seven were regarded as possibly being of T-lineage type. Six patients, one of whom had a mediastinal mass, showed both cCD3 and MPO; they were considered to have mixed lineage type. Two patients had neither cCD3 nor cytoplasmic myeloid antigens; they were therefore considered to have stem cell type. These two latter types were considered as the subgroups: mixed lineage or stem cell type. Patients with T-lineage type were good responders to L-17M therapy; four out of five who received L-17M therapy achieved complete remission. There were significant differences between the two subgroups in relapse-free survival, patients with T-lineage type exhibiting better prognosis than other types (p < 0.05).

Adult↗
PubMed1993

Laboratory findings and clinical courses of 33 patients with granular lymphocyte-proliferative disorders.

The hematological and immunological findings and clinical courses of 33 patients (13 male, 20 female; median age at presentation, 60 years) with granular lymphocyte-proliferative disorders (GLPD) are presented. Based on the surface phenotypes of peripheral blood granular lymphocytes (GL), the GLPD were divided into CD3+ T cell-lineage GLPD (T-GLPD) and CD3- CD16+ natural killer (NK) cell-lineage GLPD (NK-GLPD). Twenty-one patients had T-GLPD, and 12 had NK-GLPD. One patient with T-GLPD and two patients with NK-GLPD had progressive clinical courses and died of the disease despite receiving combination chemotherapy. Twelve patients with T-GLPD were found to have severe anemia at presentation or during the course of the disease; four of them fulfilled the diagnostic criteria of pure red cell aplasia, and the others had closely related conditions. Six of these 12 patients were treated with cyclophosphamide, and all responded to the treatment. In 16 patients, the clinical course was stable, and spontaneous regression was observed in two patients. Since some of the patients with NK-GLPD had stable clinical courses while some had progressive clinical courses, clinical findings in these two groups were compared. We found, taking into consideration our cases and those reviewed in the literature, that age less than 40 years, fever, lymph node swelling, hepatosplenomegaly, and GL with CD16(Leu-11)-CD56+CD57- phenotype and low or absent antibody-dependent cellular cytotoxicity seemed to be predictors of a progressive clinical course.

Adult↗