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Biomedical subjects

A Okubo

Publications and source records attributed to A Okubo.

At least 73 records · Page 4Linked to original sources

Inhibition of the infectivity and cytopathic effect of human immunodeficiency virus by water-soluble lignin in an extract of the culture medium of Lentinus edodes mycelia (LEM).

Inhibition of the infectivity and cytopathic effect of human immunodeficiency virus type 1 (HIV-1) by the immunoactive fractions obtained from LEM, which is an extract of the culture medium of Lentinus edodes mycelia, is reported. A purified fraction, EPS4, obtained from LEM by ethanol precipitation followed by hydrophobic chromatography and gel filtration chromatography completely inhibited the HIV-1 induced cytopathic effect in vitro at concentrations of greater than or equal to 10 micrograms/ml. Chemical and spectral analysis revealed that EPS4 is composed of water-soluble lignins containing minor amounts of protein (3.2%) and sugars (12.2%). Taken together with the previously reported observation that EPS4 promotes the activation of macrophages and the proliferation of bone marrow cells, the fraction appears to possess both an immunostimulating activity and an anti-HIV effect in vitro.

Amino Acids↗

Membrane-associated interleukin 1 alpha as a mediator of tumor cell killing by human blood monocytes fixed with paraformaldehyde.

Human blood monocytes isolated by centrifugal elutriation from healthy donors were tested for ability to produce membrane-associated antitumor monokine(s) in response to activation stimuli such as various types of interferon (IFN) and/or synthetic desmethyl muramyl dipeptide (norMDP). IFNs (alpha, beta, and gamma) and norMDP rendered blood monocytes cytotoxic to allogeneic A375 melanoma cells, as assayed by measuring release of [125I]iododeoxyuridine in 72 h. When monocytes were treated with any type of IFN for 16 h, and then fixed with paraformaldehyde, they did not show cytotoxicity to A375 cells, but when they were fixed after treatment with norMDP or lipopolysaccharide they showed significant cytotoxicity to A375 melanoma cells. This membrane-associated antitumor monokine induced by the synergistic actions of suboptimal concentrations of IFN-gamma and norMDP, was cytotoxic to HT-29 colon cancer cells as well as A375 melanoma cells, but not to actinomycin D-treated L-929 cells. The fixed monocyte-mediated cytotoxicity against A375 melanoma cells was completely inhibited by a specific anti-interleukin 1 alpha antiserum, but not by a specific anti-interleukin 1 beta antiserum or monoclonal anti-TNF antibody. These results suggest that membrane-associated interleukin 1 alpha is involved through cell-to-cell contact in the host defense mechanism against cancer.

Acetylmuramyl-Alanyl-Isoglutamine↗

Tumor cytotoxicity of human monocyte membrane-bound interleukin-1 alpha induced by synergistic actions of interferon-gamma and synthetic acyltripeptide, FK-565.

Human blood monocytes were isolated by counter-flow centrifugal elutriation from healthy donors and these noncytotoxic monocytes were rendered tumoricidal to allogeneic melanoma (A375) cells by activation with a synthetic acyltripeptide (FK-565), as assessed by measuring release of [125I]iododeoxyuridine in 72 h. When monocytes were treated with FK-565 for 16 h, and then fixed with paraformaldehyde, they showed cytotoxicity to A375 melanoma cells. The fixed-monocyte-mediated cytotoxicity to A375 cells was induced by the synergistic actions of FK-565 and recombinant interferon-gamma (rIFN-gamma), but not other cytokines [rIFN-alpha A, rIFN-beta, tumor necrosis factor (TNF), interleukin (IL)-2, -3 and -6]. For synergistic activation of monocytes with induction of a membrane-associated antitumor monokine, the monocytes had to be incubated first with rIFN-gamma and then with FK-565. FK-565 also acted synergistically with rIFN-gamma to stimulate monocytes to produce membrane-associated IL-1 activity, which induced C3H/HeJ thymocyte blastogenesis in response to phytohemagglutinin P. The tumoricidal and thymocyte-stimulating activities of the fixed monocytes were almost completely inhibited by a specific anti-(IL-1 alpha) antiserum, but not by a specific anti-(IL-1 beta) antiserum or monoclonal anti-TNF antibody. These results suggest that membrane-associated IL-1 alpha of human blood monocytes can be induced by two activation signals (rIFN-gamma then FK-565) at their suboptimal concentrations.

Antineoplastic Agents↗

Killing of alveolar macrophages and of monocytes that have responded to granulocyte-macrophage colony-stimulating factor by human lymphokine-activated killer cells.

The susceptibilities of human blood monocytes and alveolar macrophages (AM) to cytotoxicity mediated by lymphokine (IL-2)-activated killer (LAK) cells were examined. Monocytes and AM of healthy donors were obtained by counter-flow centrifugal elutriation (CCE) and bronchoalveolar lavage, respectively. The LAK activity induced by incubation of blood mononuclear cells (MNC) for 4 days with recombinant interleukin 2 (IL-2) was measured by a 4-h 51Cr release assay. The LAK cells were not cytotoxic to freshly isolated monocytes, but were cytotoxic to autologous fresh AM and monocytes that had been incubated for more than 4 days in medium alone. Blood monocytes that had been incubated for 4 days in medium with granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) or interleukin 3(IL-3) were much more susceptible than untreated monocytes to the cytotoxicity of LAK cells. When blood monocytes were separated by CCE into subpopulations of three sizes (small, medium and large), the medium- and large-sized monocytes showed greater responses to GM-CSF in terms of DNA synthesis and colony formation than the small-sized cells. After treatment with GM-CSF for 4 days, these medium and large monocytes were more susceptible than the small monocytes to the cytotoxic action of LAK cells. These results suggest that LAK cells may be important in situ in down-regulating the functions of mature macrophages and blood monocytes that have responded to GM-CSF.

Biological Factors↗

Normal human alveolar macrophages have more ability than blood monocytes to produce cell-associated interleukin-1-alpha.

Human alveolar macrophages (AM) were obtained by bronchoalveolar lavage from healthy donors, and their abilities to produce extracellular and cell-associated interleukin 1 (IL-1) in response to various activation stimuli were compared with those of autologous blood monocytes. The production of IL-1 alpha and IL-1 beta by monocytes and AM was examined by thymocyte co-stimulation assay and enzyme immunoassays (EIA). Results showed that when activated with lipopolysaccharide (LPS) or desmethyl muramyl dipeptide (norMDP), AM released much less extracellular IL-1 beta than did blood monocytes. In contrast, these activated AM produced more cell-associated IL-1 than did blood monocytes. When the IL-1 activity was examined by the thymocyte assay, the extracellular and cell-associated IL-1 produced by the two cell types were largely IL-1 beta and IL-1 alpha, respectively, as shown by antibody neutralization. The cell-associated IL-1 activity of AM induced by the synergistic actions of suboptimal concentrations of recombinant interferon-gamma (rIFN-gamma) and norMDP was also higher than that of autologous blood monocytes. Consistent with these findings on AM, macrophages generated in vitro by maturation of blood monocytes produced higher levels of cell-associated IL-1 activity than did freshly isolated monocytes. These observations suggest that AM may play a critical role in situ regulation of pulmonary inflammatory and immune reactions through production of cell-associated IL-1 alpha.

Adult↗

Induction of membrane-associated interleukin 1 alpha (IL-1 alpha) by synergistic activation of human blood monocytes with interferon gamma and muramyl dipeptide analog.

Human blood monocytes isolated by centrifugal elutriation from healthy donors were tested for ability to produce membrane-associated IL-1 in response to activation stimuli such as various types of interferons (alpha, beta and gamma) and/or synthetic des-methyl muramyl dipeptide (norMDP). When monocytes were treated with norMDP or lipopolysaccharide (LPS) for 16 hr, they released IL-1 into their culture supernatant. When these activated monocytes were fixed with paraformaldehyde (PFA), they stimulated blastogenic responses of C3H/HeJ mouse thymocytes to PHA, suggesting that membrane-associated IL-1 could be induced by norMDP or LPS. Membrane-associated IL-1 was also found to be induced by the synergistic actions of suboptimal concentrations of rIFN-gamma and nor MDP, but not of rIFN-alpha A or rIFN-beta with norMDP. A specific anti-IL-1 alpha antiserum completely inhibited membrane-associated IL-1 activity, but did not affect the thymocyte-stimulating activity of fixed monocytes. IL-1 alpha was detected by fluorescence staining using the anti-IL-1 alpha antiserum on monocytes fixed after gamma IFN-gamma and norMDP. These results suggest that IFN-gamma may be important in expression of membrane-bound IL-1 alpha by the human blood monocytes responsible for regulation of immune responses in vivo.

Acetylmuramyl-Alanyl-Isoglutamine↗

[Introduction of the information processing system of medical examinations of yusho patients and some results obtained by the 1986 survey].

Information processing system for newly established, unified medical examinations of yusho patients which started in September 1985 was presented. Some comparative analysis was also shown on the "important findings" in yusho patients residing in Fukuoka or Nagasaki prefecture. In the 1986 survey, Fukuoka male patients showed higher percentages of pigmentation in toe nail, gingiva and palpebral conjunctiva than Nagasaki (p less than 0.01), whereas Nagasaki male patients showed higher percentages of pigmentation in buccal and lip mucosa. Average concentration of PCB in blood was higher in Nagasaki male patients (6.79 ppb) than in Fukuoka patients (4.39 ppb), the difference being significant at 1% level.

Adolescent↗

[A family of pseudocholinesterase deficiency (silent type II)].

We report here a case of pseudocholinesterase (E.C. 3.1.1.8) deficiency, silent type II. The proband was a 29-year-old healthy man. His parents were cousins. A family study revealed that 9 out of 17 members of family investigated (paternal side 6, maternal side 3) concentrations. Serum cholinesterase activity were correlated well with serum albumin concentrations in both healthy people and patients with chronic liver diseases. The ratio of cholinesterase activity to albumin concentrations in serum was found more useful to detect heterozygous pseudocholinesterase deficiency than the serum cholinesterase activity alone. Both the dibucaine number and the fluoride number were within normal range in all family who showed low cholinesterase activity in serum. The amount of immunoreactive substance in serum against anticholinesterase antibody was normal in the proband as well as his family, while it was about twice of the value expected from their activity in those who had low ratio of serum cholinesterase activity to albumin concentrations. These results altogether suggested that the proband was a case of homozygous pseudocholinesterase deficiency, silent type II.

Adult↗

Aqueous flare and cell measurement using laser in endogenous uveitis patients.

We verified the applicability of the newly developed laser aqueous flare-cell meter in 124 consecutive patients with endogenous uveitis. The flare intensity was expressed in equivalent bovine serum albumin concentration and the number of cells per 0.075 mm3 of the aqueous humor. A comparison between the laser flare-cell readings and conventional slit-lamp gradings indicated a linear correlation between the two findings for aqueous flare. There was a correlation between the two findings for the aqueous cells, but the relationship seemed nonlinear, and the aqueous cell readings remained low except for severe aqueous cells graded as 3+ in slit-lamp grading. The measurement of the aqueous flare with the present apparatus was found to be highly useful in assessing the degree of anterior uveitis, but the cell counts need a careful interpretation.

Adolescent↗

Synergism of synthetic acyltripeptide and its analogs with recombinant interferon gamma for activation of antitumor properties of human blood monocytes.

Human blood monocytes freshly isolated by centrifugal elutriation from healthy volunteers were not cytotoxic to allogeneic A375 melanoma cells, but they were activated to the tumoricidal state by incubation in vitro with FK-565, (heptanoyl-gamma-D-Glu-(L)-meso-alpha,epsilon-A2pm(L)-D-A laOH), which is a synthetic acyltripeptide closely resembling cell wall peptidoglycan peptides of Streptomyces in structure. Among 11 different derivatives of FK-565, 7 analogs were more potent activators of monocytes for tumor cell killing than FK-565. The maximal expression of tumoricidal monocytes was dependent on the concentration of FK-565 or its analogs added and the ratio of monocytes to target tumor cells. In a parallel experiment, a combination of a subthreshold concentration of FK-565 or its analogs (FR-42148 and FR-42149) and recombinant interferon gamma (rIFN-gamma) induced significant monocyte-mediated tumorcell killing, indicating that the effects of rIFN-gamma and acyltripeptide or its analogs in monocyte activation are synergistic. In contrast to rIFN-gamma, recombinant rIFN-alpha A and rIFN-beta had additive effects with acyltripeptide or its analogs in human monocyte activation. These results suggested that synthetic acyltripeptide and its analogs combined with rIFN-gamma could be of clinical value for in situ activation of the tumoricidal activity of human blood monocytes responsible for eradication of cancer metastases.

Adjuvants, Immunologic↗

A new method for obtaining biomicroscopic photographs of the vitreous.

We describe a new method for obtaining photographs of the vitreous in vivo using an automatic-exposure photo-slitlamp microscope in combination with a high-speed color-reversal film and a Goldmann-type contact lens. Using our method, we investigated the microscopic characteristics of various vitreoretinal disorders. The patients studied comprised four cases with rhegmatogenous retinal detachments and one case with the sudden onset of vitreous floaters with posterior vitreous detachment (PVD). Our technique enabled us to obtain detailed images of vitreoretinal relationships, and to obtain a clearer understanding of vitreoretinal disorders than has been provided by previous methods. We conclude that our method is useful for clinical investigations of various vitreoretinal disorders.

Adult↗

[Lymphokine-activated killer (LAK) adoptive immunotherapy: optimal method for large-scale LAK induction].

Adoptive immunotherapy with lymphokine-activated killer (LAK) cells shows promise as a treatment for malignant disease, but one of the difficult problems associated with the LAK therapy is the method to induce 10(11) to 10(12) of LAK cells. In a study for optimal LAK induction, monocytes separated with counterflow centrifugal elutriation markedly augmented LAK cell induction from lymphocytes in spite of having no cytotoxicity when cultured alone; LAK activity was sufficiently induced from mononuclear cells (MNC) containing approximately 20% of monocytes; LAK activity was induced depending on the serum concentration, and at least 5% of human AB serum in RPMI 1640 was referred to induce optimal LAK activity; and roller bottle was preferable to tube or flask especially at higher MNC density. We concluded that roller bottle with 4 X 10(6) cells/ml of MNC suspended in 1 liter of RPMI 1640 containing 5% AB serum would be the optimal condition for large-scale LAK induction, and administration of LAK cells on the 3rd and 4th day of culture is favorable for weekly performance of LAK adoptive therapy.

Cell Separation↗