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Biomedical subjects

K Motoyoshi

Publications and source records attributed to K Motoyoshi.

At least 163 records · Page 9Linked to original sources
PubMed1991

Enhancing effects of human macrophage colony-stimulating factor on the secretion of human chorionic gonadotropin by human chorionic villous cells and tPA30-1 cells.

Human macrophage colony-stimulating factor (hM-CSF) concentration-dependently enhanced the secretion of human chorionic gonadotropin (hCG) by primary cultured human cytotrophoblastic cells and a human placental cell line, 3A-SubE (tPA30-1). Since this effect appeared 12 hours after the addition of hM-CSF and disappeared when protein synthesis was inhibited, it was surmised that hCG synthesis was enhanced by hM-CSF. When anti fms (hM-CSF receptor) antibody was added, hCG secretion by cultured human cytotrophoblasts in early pregnancy markedly decreased. These findings demonstrate that hM-CSF acts on the chorionic villous cells and promotes hCG synthesis by these cells.

Cell Line↗
PubMed1991

Induction of differentiation of human myeloid leukemia HL-60 cells by novel pyrimidine nucleoside analogs.

New pyrimidine nucleoside analogs (18 compounds) were synthesized and their growth-inhibiting and differentiation-inducing activities on human myeloid leukemia HL-60 cells were examined. Some of the analogs were found to induce nitroblue tetrazolium (NBT) reducing activity in the HL-60 cells. The inducing activities of these compounds were compared at their concentrations for 50% inhibition of cell growth. TI-79 (3-benzyl-5-methyl-3-(beta-D-ribofuranosyl)pyrido[2,3-d]pyrimidine- 2,4(1H,3H)-dione) was a very effective inducer of NBT-reduction and of differentiation of the cells into mature granulocytes. The induction of NBT-reducing activity by TI-79 was inhibited by high concentrations of the natural nucleoside, adenosine. Other differentiation inducers, such as retinoic acid, 1 alpha,25-dihydroxyvitamin D-3 and staurosporin markedly enhanced the induction of differentiation of HL-60 cells by TI-79. Nucleoside analogs such as TI-79 should be useful for differentiation therapy of some types of myelogenous leukemia.

Adenosine↗
PubMed1991

Induction of differentiation of human leukemia cells by inhibitors of myosin light chain kinase.

Inhibitors of myosin light chain kinase, 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9) and 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-7), induced Nitroblue tetrazolium reducing activity, lysozyme activity and morphological maturation of human monoblastic U937, THP-1 and promyelocytic HL-60 cells, but not of erythroblastic K562 cells. However, three analogs of ML-9, which are an inhibitor and an activator of protein kinase C, and a calmodulin antagonist, respectively, did not induce differentiation of the cells.

Azepines↗
PubMed1991

Characterization of macrophage colony-stimulating factor in body fluids by immunoblot analysis.

We characterized the molecular species of human macrophage colony-stimulating factor (hM-CSF) found in serum and urine, using immunoblot analysis after partial purification on an antibody-bound affinity column. Although antibodies were prepared using the recombinant product of the large form of hM-CSF with a molecular weight (MW) of 85 Kd as the antigen, this immunoblot system was also capable of detecting the small form of hM-CSF with a MW of 40 to 60 Kd. A single band with a MW of 43 Kd, which reacted with anti-recombinant hM-CSF IgG but not with control IgG, was found when serum and urine from normal adults underwent electrophoresis on reduced sodium dodecyl sulfate-polyacrylamide gel and subsequent immunoblotting. This band represented a subunit of the large form of hM-CSF, because the large form of hM-CSF is a homodimer of a subunit with a MW of 43 Kd and the small form of hM-CSF is a homodimer of a subunit with a MW of 20 to 30 Kd. Analysis of serum and urine from leukemic patients and pregnant women, who had higher serum levels of hM-CSF than normal adults, showed only a single band with a MW of 43 Kd as a hM-CSF-specific molecule. These results suggest that the large form of hM-CSF is the major species in human body fluids.

Body Fluids↗
PubMed1991

Effects of inhibitors of protein tyrosine kinase activity and/or phosphatidylinositol turnover on differentiation of some human myelomonocytic leukemia cells.

The activities of protein tyrosine kinase and phosphatidylinositol turnover have been found to be associated with cell growth and differentiation. We examined the effects of some inhibitors for these biochemical activities in human myelogenous leukemia cells. Genistein, which is known to inhibit the activities of protein tyrosine kinase, phosphatidylinositol turnover and topoisomerase II, induced nitroblue tetrazolium (NBT) reduction and lysozyme activity in ML-1, HL-60 and U937 cells. Morphological studies showed that genistein-induced differentiation of myeloblastic ML-1 cells into promyelocytes and of promyelocytic HL-60 cells into mature granulocytes. The differentiation-inducing effect of genistein was augmented by addition of 1 alpha,25-dihydroxyvitamin D3 (VD3) or retinoic acid, VD3 being more effective than retinoic acid. Methyl 2,5-dihydroxycinamate, a protein tyrosine kinase inhibitor, had only a weak effect in inducing differentiation of ML-1 cells. On the other hand, psi-tectorigenin was more effective than genistein in inducing the differentiations of ML-1 and HL-60 cells. Psi-tectorigenin is reported to inhibit phosphatidylinositol turnover without inhibiting protein tyrosine kinase. Thus modulation of phosphatidylinositol turnover might be more important than that of protein tyrosine kinase activity for differentiation of some myelogenous leukemia cells.

Cell Differentiation↗
PubMed1991

Second relapse of acute promyelocytic leukemia (ANLL-M3) with t(15;17) and t(1;3)(p36;q21).

We describe herein a patient with acute promyelocytic leukemia (APL)-(ANLL-M3) whose bone marrow cells in the second relapse showed t(1;3)(p36;q21) together with t(15;17) (q22;q11-q12). Although a total of 21 patients with t(1;3) have been reported so far, among which three cases with de novo acute nonlymphocytic leukemia were included, our patient is the first case with APL. The hematologic findings in our case confirmed the previous observations that this anomaly is associated with relatively high platelet count and the multi-myeloid lineage involvement of leukemic cells. Our patient responded well to chemotherapy and achieved first and second remission with 42 months of total survival, contrary to our expectation that patients with this anomaly have a poor prognosis.

Chromosomes, Human, Pair 1↗
PubMed1991

Stereographic and stereometric study of sebaceous gland hyperplasia in rabbit pinnas induced by topically applied substances.

Tetradecane (TD), testosterone (TS), and dimethyl sulfoxide (DMSO) were separately inuncted on rabbit pinnas once a day; the pinnas were biopsied on days 1, 3, 7, and 28. Untreated pinnas and squalane-treated pinnas were used as controls. Three-dimensional images of sebaceous glands were reconstructed from their serial histologic sections using a computer-image analysis system. By stereometry, the sebaceous gland volumes gradually increased during the course of treatments with TS and DMSO, whereas the volumes of TD-treated sebaceous glands increased, reached the maximum on day 7, and then decreased. The acinus number was increased by all the substances, the DMSO-treated sebaceous glands on day 28 showing the largest number of acini. The volumes of individual acini increased until day 28 with TS treatment, whereas with TD and DMSO treatments they increased, reached the maximum on day 7, and then decreased. Stereographically, each untreated control sebaceous gland was composed of 20-30 pear-shaped acini. On day 28, acini of TS-treated sebaceous glands were swollen and ovoid in shape, DMSO-treated sebaceous glands resembled a bunch of grapes, and acini of TD-treated sebaceous glands were widely scattered and showed globular swelling arising from an elongated tube. Hyperplastic responses of sebaceous glands are quite different according to substances applied topically.

Administration, Topical↗
PubMed1991

Enhanced neutrophil functions in a patient with colony-stimulating activity-producing lung cancer.

We studied neutrophil functions in a patient with colony-stimulating activity (CSA)-producing lung cancer. A 59-year-old man had an abnormal chest X-ray and leucocytosis, predominantly with neutrophils. Pneumonectomy was performed, and the histological diagnosis of the tumour was large-cell carcinoma of the lung. The tumour induced marked granulocytosis in tumour-transplanted nude mice, and the conditioned media of the tumour contained very strong human-active CSA. Superoxide release and membrane depolarization in neutrophils stimulated by the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine, were markedly enhanced in the patient. These findings suggest that CSA produced by the tumour primed neutrophil functions in vivo in the patient.

Animals↗
PubMed1991

Effects of macrophage colony-stimulating factor on reduction of viable bacteria and survival of mice during Listeria monocytogenes infection: characteristics of monocyte subpopulations.

Mice could well tolerate infection with a lethal dose of Listeria monocytogenes after intraperitoneal preinjections with 250 micrograms of macrophage colony-stimulating factor (M-CSF) per kg of body weight for 5 days. The characteristic changes in the surface markers (Mac-1, LFA-1, and F4/80) of peripheral monocytes were also investigated in order to analyze the mechanism of protection by M-CSF. This investigation shows the excellent effect of intraperitoneal preinjections of M-CSF on the reduction of viable Listeria organisms and the improvement of survival after an intravenous Listeria infection.

Animals↗
PubMed1990

Human monocyte colony-stimulating factor enhances the clearance of lipoproteins containing apolipoprotein B-100 via both low density lipoprotein receptor-dependent and -independent pathways in rabbits.

To investigate the effects of recombinant human monocyte colony-stimulating factor (M-CSF) on plasma cholesterol metabolism, we injected M-CSF intravenously into New Zealand White rabbits (n = 13) at a dose of 100 micrograms/day for 7 days. After the treatment, the plasma cholesterol levels fell by 33.2% from 61.4 +/- 25.9 to 41.0 +/- 10.2 mg/dl (mean +/- S.D.). We also injected a large dose of M-CSF (500 micrograms/day) for 6 days into Watanabe Heritable Hyperlipidemic rabbits, which are deficient in low density lipoprotein (LDL) receptors. Again, there was a significant reduction in plasma cholesterol levels by 36.2% from 730.5 +/- 176.4 to 466.0 +/- 104.9 mg/dl (n = 4). In the kinetic studies in New Zealand White rabbits with very low density lipoprotein, LDL, and methylated LDL, the removal rates of those lipoproteins were increased 1.9-, 1.7-, and 2.0-fold, respectively, after the treatment. Immunoblot analysis of LDL receptors in the treated rabbits showed no significant changes in LDL receptor proteins in livers but a great increase in spleens and bone marrows compared with the controls. Messenger RNA was also estimated by Northern blotting in both groups, and the results were compatible with those from the immunoblot. The data suggest that M-CSF stimulates the clearance of lipoproteins containing apolipoprotein B-100 via both LDL receptor-dependent and -independent pathways in target cells of M-CSF and reduces plasma cholesterol.

Animals↗
PubMed1990

Enhancement of the antibody-dependent tumoricidal activity of human monocytes by human monocytic colony-stimulating factor.

Human monocytic colony-stimulating factor (hM-CSF) stimulates mature cells as well as progenitor cells of human monocyte lineage. In the present study, we investigated the effect of completely purified native hM-CSF on the tumoricidal activity of human monocytes against Raji (Burkitt lymphoma-derived cell line) using a chromium release assay. Preincubation of human peripheral blood monocytes with hM-CSF for 48 h markedly enhanced their antibody-dependent cellular cytotoxicity (ADCC). This enhancing effect was dependent on the concentration of hM-CSF, and maximal enhancement was achieved at the concentration of 66 ng/ml. The number of receptor sites on monocytes against the Fc portion of immunoglobulin G increased 2- to 4-fold during 48 h incubation with hM-CSF. These results suggest that hM-CSF stimulates monocyte-ADCC by increasing the number of Fc receptor sites on human monocytes.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

Effect of human macrophage colony-stimulating factor on granulopoiesis and survival in bone-marrow-transplanted mice.

Human macrophage colony-stimulating factor (hM-CSF) has been isolated from normal human urine and purified to a homogeneous protein. The effect of hM-CSF on granulopoiesis was investigated in BALB/c mice transplanted with a suboptimal number of bone marrow cells. Lethally irradiated (7.8 Gy) mice were transplanted with 1 x 10(6) syngeneic mouse bone marrow cells and treated with a daily intraperitoneal dose of 64 micrograms/kg of hM-CSF for 5 days following the transplant. The hM-CSF injection resulted in stimulation of the recovery of blood neutrophils as well as an increase in the number of granulocyte-macrophage progenitor cells (CFU-GM) in the femur and spleen. The survival of lethally irradiated mice was dependent on the cell number transplanted; most mice transplanted with 2 x 10(4) cells died within 2 weeks. The recovery of hematopoiesis in mice transplanted with 2 x 10(4) cells was modestly but significantly stimulated by hM-CSF administration initiated from 5 days before or 1 day after transplantation for a 5-day period. Furthermore, the hM-CSF administrations markedly reduced the mortality in these mice during the early period after the transplantation. Since anaerobic bacteria were frequently detected in arterial blood immediately before the deaths but were not found in the surviving mice, it is speculated that early deaths occurring within 2 weeks after the transplant may be caused by opportunistic infections, and hM-CSF injection may prevent these mortal infections through its stimulating effect on monocyte-macrophage functions that are responsible for the production of hematopoietic regulators.

Animals↗
PubMed1990

Double-blind test of human urinary macrophage colony-stimulating factor for allogeneic and syngeneic bone marrow transplantation: effectiveness of treatment and 2-year follow-up for relapse of leukaemia.

A randomized, double-blind placebo-controlled phase III clinical trial was performed to study the effects of human urinary macrophage colony-stimulating factor (hM-CSF) after allogeneic and syngeneic bone marrow transplantation (BMT) in 60 hM-CSF treated and 59 placebo control patients. HM-CSF was administered at a daily dose of 2 x 10(5) units/kg from day 1 to day 14 after BMT. Significant differences between hM-CSF and control patient were found in the recovery time to greater than 0.5 x 10(9) granulocytes/l and the survival rate during the initial 120 d without retransplantation. There was no difference in the incidence or grade of graft-versus-host disease (GVHD). There was no difference in the rate of leukaemic relapse at 24-36 months after BMT in patients with acute lymphocytic, acute nonlymphocytic, or monocytic leukaemia. The results of this trial show that human M-CSF improves the outcome of BMT without any influence on the occurrence of leukaemic relapse or GVHD.

Adolescent↗
PubMed1990

Plasma cholesterol-lowering activity of monocyte colony-stimulating factor (M-CSF).

We investigated the action of monocyte colony-stimulating factor (M-CSF) on plasma cholesterol metabolism. Recombinant human monocyte colony-stimulating factor (rhM-CSF) was intravenously injected into Watanabe heritable hyperlipidemic (WHHL) rabbits that were deficient in LDL receptor. The treated rabbits showed decreases in plasma total cholesterol levels from 493 +/- 39 to 416 +/- 45 mg/dl (about 15%) during the treatment. The decrease in total plasma cholesterol level was due to decreased levels of lipoproteins containing apo B 100 such as VLDL, IDL, and LDL. The effect of M-CSF on the LDL-receptor-deficient animal in vivo and evidence from Northern blot analysis of liver suggested that M-CSF lowers plasma cholesterol level through activated uptake of lipoproteins containing apo B 100 via pathways other than the hepatic LDL receptor. We have started a clinical study to evaluate the plasma cholesterol-lowering effect of M-CSF in patients with familial hypercholesterolemia, and have observed a decreased in total plasma cholesterol level in one of three patients treated with M-CSF. M-CSF may provide new insight into plasma cholesterol metabolism and a possible new tool to treat patients with hypercholesterolemia and atherosclerosis.

Animals↗
PubMed1990

[Myelofibrosis associated with immunological abnormalities].

A 74-year-old man was admitted to the National Defense Medical College Hospital because of purpura on the extremities. The blood hemoglobin level was 11.5 g/dl, the white blood cell count 7. 3 x 10(9)/l with 3% blastic cells, and the platelet count 4.0 x 10(9)/l. There was leukoerythroblastosis with only mild teardrop appearance of erythrocytes. The blastic cells consisted of two types, megakaryoblast-like cells and myeloblast-like cells. There was a very mild hepatosplenomegaly, but no lymphadenopathies. The bone marrow aspirations yielded dry taps. The marrow biopsy specimen revealed myelofibrosis associated with trilineage hyperplasia, but no apparent infiltration of leukemic cells. Platelet-associated IgG (PAIgG) had a high titer and the response to platelet transfusions was poor. On prednisolone and colchicine, the blastic cells in the peripheral blood disappeared and the platelet count increased. He died of pneumonia. The autopsy showed myelofibrosis with hyperplasia of myeloid and erythroid lineage in the bone marrow. Megakaryocytes were relatively few and there was no infiltration of leukemic cells.

Aged↗
PubMed1989

Enhancing effect of human monocytic colony-stimulating factor on monocyte tumoricidal activity.

Human monocytic colony-stimulating factor (hM-CSF) enhances several effector functions of human peripheral blood monocytes. In this study, we investigated the effect of the Mr 85,000 form of hM-CSF on the tumoricidal activity of human monocytes against several leukemic cell lines using a 12-h chromium release assay. Human peripheral blood monocytes preincubated with hM-CSF for 48 h showed more effective killing activity towards K562, U937, Daudi, and HL60 cells as compared with the cells preincubated with medium alone. Maximal enhancement of the tumoricidal activity was achieved by hM-CSF at concentrations of 50-100 ng/ml. A trace amount of lipopolysaccharide contained in the hM-CSF did not seem to contribute to the enhancing effect, as the addition of a lipopolysaccharide-neutralizing agent, polymyxin B, to the preincubation mixture did not reduce this effect. Anti-tumor necrosis factor antiserum partially blocked the tumoricidal activity mediated by hM-CSF, indicating that tumor necrosis factor may participate in the hM-CSF-mediated increase of monocyte tumor cell-killing activity. These results suggest that in addition to other monocyte-activating factors, hM-CSF augments monocyte tumoricidal activity against a wide spectrum of tumor targets.

Cell Line↗