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Biomedical subjects

K Hatake

Publications and source records attributed to K Hatake.

At least 181 records · Page 10Linked to original sources
PubMed1987

Diminution of contractile response of the aorta from endotoxin-injected rats.

The contractility of a helical strip of the thoracic aorta was studied in rats injected intraperitoneally with endotoxin. The contractile response to any of the agonistic agents, KCl, norepinephrine or 5-hydroxytryptamine was time dependently diminished in the endotoxin-injected rats compared to the controls. This diminution preceded the depression of blood pressure. When the external calcium concentration was increased from 2.5 to 7.5 mM after the KCl (80 mM)-induced contractile response reached a plateau, the diminished contractile response was reversed in the endotoxin-injected group. The strips from the endotoxin-injected rats showed a higher 45CaCl2 uptake into the vascular tissue with the KCl-stimulated contraction. These findings suggest that the blood pressure depression during endotoxic shock may be attributed partially to the diminished contractility of the blood vessels and that this diminution is induced by a disorder of calcium utilization within vascular smooth muscle during vascular contraction.

Animals↗
PubMed1987

Modulation of vascular tonus by the endothelium in experimental diabetes.

The role of the vascular endothelium in the contractile response of aortas from streptozotocin-induced diabetic rats was investigated using selected agents. Contractile response to KCl was not affected by removal of the endothelium in both diabetic and control groups, but was diminished in the diabetic rats compared to the control rats. Contractile response to clonidine markedly increased after removal of the endothelium in the control group, with the increment being less in the diabetic group. After removal of the endothelium, contractile response to clonidine was poorer in the diabetic group than the control group. Vascular relaxation induced by acetylcholine disappeared when the endothelium was removed in both diabetic and control groups. The degree of reaction to acetylcholine did not significantly differ between the two groups. These results suggest that in diabetic rats, abnormality of the endothelium-dependent vascular relaxation is specific for alpha 2 receptor while that of the vascular smooth muscle reactivity is not receptor-specific.

Acetylcholine↗
PubMed1987

Human colony-stimulating factor-producing lung cancer tissue releases a differentiation-inducing factor for human leukemic cells.

Human lung cancer that induced marked granulocytosis in both the patient and tumor-transplanted nude mice (G2 mice) and from which conditioned medium (G2-T-CM) exhibited human and mouse active colony-stimulating activity (CSA) has been reported (K. Ikeda et al. Cancer Res 1985; 45:4144-4249). Recently, we found differentiation-inducing activity (DIA) in G2-T-CM, which differentiated human promyelocytic leukemic cells (HL-60) to macrophage-like cells. Differentiated HL-60 cells were considered to be mature macrophages as judged by the positivity of butyrate esterase activity, the acquisition of Fc receptor, and the increment in capacity of phagocytosis and nitroblue tetrazolium reduction. The DIA in G2-T-CM was not attributed to interferons known to have DIA, because interferon activity was not found in G2-T-CM by bioassay (less than 4 U/ml) and by radioimmunoassay for gamma-IFN (less than 0.1 U/ml). Molecular weight of DIA was 36,000 Da and separated from CSA of which molecular weight was 22,000 Da by gel filtration on Sephadex G-150. DIA and CSA were also separated on chromatofocusing chromatography, because isoelectric point of DIA was mainly less than 4.0 and that of CSA was 4.3-5.7. This DIA was stable after heat treatment (56 degrees C for 30 min or 100 degrees C for 10 min) and in acidic condition (pH 2.0 for 24 hr). G2-T-CM is a good source of differentiation-inducing factor for further purification and molecular cloning.

Biological Products↗
PubMed1987

Differentiation-inducing factor for a human leukemic cell line produced by colony-stimulating factor producing human lung cancer tissue.

We have found that medium conditioned by a colony-stimulating factor producing tumor derived from a granulocytosis case with lung cancer contained a factor to differentiate a human promyelocytic leukemic cell line (HL-60) to macrophage-like cells that were butyrate esterase-positive and had phagocytosing activity and membrane Fc receptors. This differentiation-inducing factor was not active for a human myeloblastic cell line (KG-1), and was separated from a colony-stimulating factor by its molecular weight and isoelectric point. The conditioned medium did not contain a detectable amount of gamma interferon when tested by bioassay as well as by radioimmunoassay. This is the first report that a human lung cancer tissue produces not only a colony-stimulating factor, but also a differentiation-inducing factor. The conditioned medium is considered to be a good source of differentiation-inducing factor.

Animals↗
PubMed1986

Discrepancy between the production of interleukin 1, alpha-interferon and granulocytic colony-stimulating activity of human monocytes stimulated by a partially purified human urinary colony-stimulating factor.

A partially purified human urinary colony-stimulating factor (pp-CSF), with a specific activity of 1.0 X 10(6) U/mg protein, was purified by using a stepwise DEAE-cellulose anion exchange chromatography and a molecular sieve high performance liquid chromatography (TSK gel G3000SW) sequentially. Production of three kinds of monokines by human peripheral blood monocytes was tested in vitro, which contained granulocytic colony-stimulating activity (G-CSA), interleukin 1 (IL-1) and interferon alpha (IFN-alpha). Human peripheral blood mononuclear cells were separated by Ficoll-Hypaque density gradient centrifugation, and monocytes were obtained by adherence to dishes. Although pp-CSF stimulated monocytes to produce G-CSA in vitro, it failed to stimulate the IL-1 or IFN-alpha production. The discrepancy between production or release of these three kinds of monokines by human monocytes stimulated with pp-CSF suggests that pp-CSF preferentially stimulates human monocytes to produce G-CSA. To test the effects of pp-CSF on human monocytes in vivo, we performed i.v. infusions of pp-CSF to four volunteers, and we then took peripheral blood monocytes. Compared to before the infusion of pp-CSF, G-CSA production by monocytes was enhanced, while production of IL-1 and IFN-alpha was not enhanced after the infusion of pp-CSF. These results suggest that pp-CSF stimulates monocytes to produce G-CSA but not to produce IL-1 nor IFN-alpha.

Cells, Cultured↗
PubMed1986

Mode of action of human urinary colony-stimulating factor.

Human urinary colony-stimulating factor (CSF-HU) has been highly purified using procedures containing DEAE cellulose, phenyl Sepharose CL-4B, Sephadex G-200, hydroxylapatite, and high performance liquid chromatography. The final preparation had a specific activity of 3.3 X 10(7) U/mg protein. Although the purified CSF-HU was not active on human monocyte-depleted bone marrow cells, it stimulated human peripheral blood monocytes obtained from five healthy volunteers to produce human active granulocytic colony-stimulating factor (G-CSF), which stimulated human monocyte-depleted bone marrow cells to form granulocytic colonies. The human G-CSF-producing activity of CSF-HU was not neutralized by polymyxin B, which is known to inhibit the effect of endotoxin. Newly produced G-CSF had an approximate molecular weight of 24,000 daltons as judged by chromatography on Sephadex G-150. These results indicate that CSF-HU stimulates human monocytes to produce human G-CSF in vitro.

Colony-Stimulating Factors↗
PubMed1985

A murine cell line (2E10.4.13) produces five hemopoietic stimulators, and interleukin-2 and interleukin-3.

An interleukin-2 (IL-2)-independent murine lymphocyte clone (2E10.4.13) with the Thy1+Lyt1+2-T200+ phenotype was separated from the original IL-2-dependent natural killer (NK) cell line (PEC-1). Erythroid burst-promoting activity (BPA), erythropoietin (Ep), granulocyte/macrophage, megakaryocyte and eosinophil colony-stimulating factors (GM-, MK- and Eo-CSF), IL-2 and Interleukin-3 (IL-3) were produced when these cells were stimulated with phorbol myristate acetate (PMA). When the conditioned medium was run through ion-exchange high-performance liquid chromatography, BPA, Ep, GM-CSF, MK-CSF and Eo-CSF were eluted in the same region as IL-3. In contrast, MK-CSF, much of the GM-CSF and half of the Eo-CSF were eluted in a distinct region where no IL-3 was detected. Chemical analyses of the hemopoietic factors derived from a single T inducer clone indicated that all the hemopoietic activities were associated with IL-3 activity. Some CSF activities (GM-, MK- and Eo-CSF) also could be mediated by the distinct molecules from IL-3, evidence that heterogeneous molecules are responsible for CSF activity.

Animals↗
PubMed1985

Interleukin 1 (IL 1)-dependent lymphokine production by human leukemic T cell line HSB.2 subclones.

Cloning of a human T cell leukemic cell line, HSB.2, was performed by a limiting dilution method to obtain clones with high levels of IL 2 production. None of the subclones that were obtained produced IL 2 constitutively, and only a low level of IL 2 was produced by the stimulation of these subclones with phytohemagglutinin (PHA) alone. High levels of IL 2 production (greater than 300 U/ml) were observed in several clones when stimulated with a cocktail of PHA and IL 1. Among them, HSB.2-A7-D2, A7-D9, or C5-B2 subclones, which were selected after cloning twice, were most effective in IL 1-dependent IL 2 production. HSB.2 subclones exhibited IL 1-dependent production of a variety of lymphokines other than IL 2, e.g., interferon-gamma (IFN-gamma), B cell growth factor (BCGF), and colony-stimulating factor (CSF). We observed that subclones with high IL 2-producing capacity tended to produce high levels of IFN-gamma or BCGF as well, while the capacity of CSF production was not parallel to these properties. Although several subclones were found to produce IFN-gamma and BCGF simultaneously with minimal IL 2 activity, no subclones with an exclusive BCGF production were obtained. Furthermore, when supernatants from the stimulated A7-D9 subclone were applied to an Ultro-gel AcA54 gel chromatography, it was revealed that IL 2 activity (m.w. 17K to 18K) and IFN-gamma (40K to 45K) were clearly separated, whereas two peaks of BCGF activity coincided with each peak of IL 2 and IFN-gamma, respectively. On the other hand, CSF activity was eluted at a different peak (30K to 35K). These data indicate that IL 2, IFN-gamma, and CSF activities are based on distinct molecules, whereas BCGF activities are indistinguishable from IL 2 and IFN-gamma. The HSB.2 subclones thus selected will provide a useful model for delineating the mechanism of IL 1-dependent lymphokine(s) production, and are a promising candidate for better lymphokine(s) producers.

Cell Line↗
PubMed1985

Human colony-stimulating activity-producing tumor: production of very low mouse-active colony-stimulating activity and induction of marked granulocytosis in mice.

We reported previously a human lung cancer which induced marked granulocytosis both in the patient and in the tumor-transplanted nude mice (G-1 mice), and whose conditioned media (G-1-T-CM) contained both human-active colony-stimulating activity (h-CSA) (810 colonies/ml) and mouse-active colony-stimulating activity (m-CSA) (530 colonies/ml), suggesting that the CSA produced by the tumor caused granulocytosis both in the patient and in G-1-mice. We reported here another human lung cancer which induced marked granulocytosis both in the patient and in the tumor-transplanted nude mice (G-2-mice). However, in contrast to the tumor reported by us previously, the conditioned media of this tumor (G-2-T-CM) contained only very weak m-CSA (86 colonies/ml), although h-CSA was very strong (7332 colonies/ml). The ratio of m-CSA to h-CSA in G-1-T-CM (0.654) was 55-fold higher than that in G-2-T-CM (0.012). Gel filtration of G-2-T-CM on a Sephadex G-150 column denied the presence of colony-inhibiting activity which inhibited m-CSA in G-2-T-CM. Since the addition of serum obtained from G-2 mice did not enhance m-CSA in G-2-T-CM, it seems unlikely that the G-2 tumor produced an inactive form of m-CSA which was activated in G-2 mouse serum. G-2-T-CM tended to maintain the number of colony-forming units in spleen in mouse bone marrow during liquid cultures, while G-1-T-CM did not. These results may indicate that the G-2 tumor produced a humoral factor which has very weak CSA and acts on stem cells rather than on committed progenitors.

Animals↗
PubMed1985

Two antigenically different types of colony-stimulating activities in sera of patients with aplastic anemia.

Sera obtained from seven normal volunteers and 11 patients with aplastic anemia were assayed for two types of colony-stimulating activity (CSA) using monolayer agar cultures containing human unfractionated and monocyte-depleted bone marrow cells. Sera obtained from normal volunteers had low CSA for unfractionated bone marrow cells and no CSA for monocyte-depleted bone marrow cells. On the other hand, sera obtained from patients with aplastic anemia (patients' sera) had moderate CSA for both unfractionated and monocyte-depleted bone marrow cells. The patients' serum CSA titer for unfractionated bone marrow cells rose markedly with the addition of a small amount of diluted control rabbit serum (control serum) into the CSA assay system, while it did not rise with addition of the same amount of diluted rabbit antiserum against partially purified human urinary colony-stimulating factor (CSF) (antiserum). The patients' serum CSA titer for monocyte-depleted human bone marrow cells rose with the addition of control serum as well as antiserum. These findings indicate that the addition of rabbit serum enhances colony formation by human bone marrow cells in the presence of aplastic anemia sera as a source of CSA, and that sera of patients with aplastic anemia contain two antigenically different types of CSA: one that is active on human unfractionated bone marrow cells and partially neutralized by the addition of antiserum, and another that is active on human monocyte-depleted bone marrow cells and is not neutralized by the addition of antiserum.

Adult↗
PubMed1984

Inhibitory activity on murine granulocytic colony formation of bone marrow cell-conditioned medium obtained from colony-stimulating factor-producing tumor-bearing nude mice.

The effects of bone marrow-conditioned medium obtained from colony-stimulating factor-producing tumor-bearing nude mice (G-BM-CM) on mouse and human granulocyte-macrophage colony formation and mouse erythroid colony and burst formation were studied. Addition of G-BM-CM into the mouse granulocyte-macrophage colony-forming system containing colony-stimulating activity more strongly inhibited granulocyte colony formation than did mixed granulocyte-macrophage and macrophage colony formation, while it did not change the number of granulocyte colonies formed by human bone marrow cells stimulated by human granulocyte colony-stimulating activity. Addition of G-BM-CM slightly increased mouse erythroid colony and burst numbers when it was added into an erythroid colony-forming system stimulated by erythropoietin (1 unit/ml), and into the erythroid burst-forming system stimulated by erythropoietin (1 unit/ml) and 7% spleen cell-conditioned medium. These results might indicate that G-BM-CM mainly blocked commitment of mouse granulocyte-macrophage colony-forming cells to granulocytic progeny.

Animals↗
PubMed1983

Acute myelomonocytic leukemia following remission of sarcoidosis.

A 55-year-old woman was described who developed an acute myelomonocytic leukemia 4 years after remission of sarcoidosis. This association is of particular interest since pronounced T cell dysfunction appears in sarcoidosis. We traced serum angiotensin-converting enzyme and serum or urinary lysozyme levels of this patient.

Clinical Enzyme Tests↗