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T Hanamura

Publications and source records attributed to T Hanamura.

At least 19 recordsLinked to original sources
PubMed2001

Effects of recombinant human macrophage colony-stimulating factor on atherosclerotic lesions established in the aorta of high cholesterol-fed rabbits.

Anti-atherosclerotic effects of human macrophage colony-stimulating factor were investigated using rabbits fed a high cholesterol diet. Rabbits fed a diet containing 2% cholesterol for 59 days developed hyperlipidemia and atheromatous aortic plaques. They were then administered 80 microg/kg/day of either macrophage colony-stimulating factor or human serum albumin, as a control, for the next 12 weeks. Compared with the control group, rabbits treated with macrophage colony-stimulating factor had significantly fewer plaques on the inner surface of the thoracic and abdominal aortae, and half the sectional area of thickened intima in the aortic arch, as well as in the thoracic and abdominal aortae. Macrophage colony-stimulating factor also decreased the cholesterol content of the atherosclerotic lesions. Serobiochemical analyses revealed that macrophage colony-stimulating factor increased the levels of high density lipoprotein-cholesterol significantly, without influencing other lipid parameters such as the level of low density lipoproteins. The effects of macrophage colony-stimulating factor were evident until the fourth week of drug injection, at which time anti-human macrophage colony-stimulating factor antibodies were clearly induced in the serum. These results indicate that exogenously administered macrophage colony-stimulating factor suppresses atherosclerotic lesions induced by a high cholesterol diet by activating lipid metabolism in vivo.

Animals↗
PubMed1997

Intravenously administered macrophage colony-stimulating factor (M-CSF) specifically acts on the spleen, resulting in the increasing and activating spleen macrophages for cytokine production in mice.

IL-6 was transiently expressed in sera of mice after a bolus intravenous injection with LPS and it peaked 2 h later. Intravenous administration of M-CSF at 250 micrograms/kg/day for 5 days prior to an injection of 25 micrograms/kg of LPS elevated the serum IL-6 level 10-fold higher than that of mice which were not given M-CSF. Although M-CSF had no effect on the number of macrophages in alveoli and peritoneal cavity, it tripled the number of spleen macrophages and increased macrophage-progenitor cells 7-fold when injected intravenously. Spleen macrophages from M-CSF-injected mice produced 5-fold more IL-6 in response to LPS-stimulation in-vitro. However, M-CSF-injection had lesser effects on LPS-induced IL-6 production from liver, alveolar and peritoneal macrophages. Exogenously administered M-CSF was detected at higher concentration and for longer duration in the spleen than in any other organs examined. Spleen macrophages incubated in-vitro with more than 1000 U/ml of M-CSF for 3 days also produced more LPS-induced IL-6 than untreated cells. These results indicate that intravenously administered M-CSF not only enhances macrophage development in the spleen, but also primes mature macrophages for cytokine production.

Animals↗
PubMed1997

Macrophage colony-stimulating factor (M-CSF) augments cytokine induction by lipopolysaccharide (LPS)-stimulation and by bacterial infections in mice.

We studied the effects of M-CSF on cytokine induction in vivo by LPS or by bacterial infection by comparing between the serum cytokine levels of mice administered with and without M-CSF. M-CSF at 250 micrograms/kg/day for 3 days significantly augmented serum IL-6 level induced by a subsequent injection of 25 micrograms/kg of LPS. The augmented IL-6-induction was dose-dependent from 50 to 1250 micrograms/kg/day of M-CSF, and required 2- to 3-doses of M-CSF at 250 micrograms/kg/day. Mice primed with M-CSF induced IL-6 in response to a 5-fold lower dose of LPS, and also produced higher levels of IL-1 alpha, IL-10, GM-CSF, TNF-alpha, and IFN-gamma than control mice. The priming effect of M-CSF was transient and reversible, and elicited independently of T-cells. An injection with intact bacteria, such as Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus also induced IL-6 in normal mice, and M-CSF administration augmented the induction of these cytokines. These results showed that M-CSF positively regulates LPS-dependent and -independent cytokine induction, suggesting a defensive effect against infectious agents through enhanced cytokine production.

Animals↗
PubMed1996

Effect of recombinant human macrophage-colony stimulating factor on marrow, splenic, and peripheral hematopoietic progenitor cells in mice.

The effects of human macrophage colony-stimulating factor (M-CSF) on marrow, splenic, and peripheral progenitor cells (CFU-M, CFU-GM, and CFU-G) were investigated in mice administered recombinant human M-CSF (8-4,000 micrograms/kg). Single injection of 4,000 micrograms/kg of M-CSF resulted in a decrease in the number of marrow progenitor cells (CFU-M, CFU-GM, and CFU-G) on day 2 followed by a gradual increase, returning to the original level on day 4 or 5. In contrast, each type of splenic progenitors tested for started to increase markedly on day 2, reaching a level 4- to 15-fold higher than that of the basal value on day 3 or 4. Peripheral CFU-M, CFU-GM, and CFU-G also increased on day 2. In addition, administration of 800 micrograms/kg of M-CSF in mice caused a decrease in marrow CFU-G, as well as an increase in splenic CFU-G. The present results indicate that treatments of mice with pharmacological concentrations of human M-CSF affect the number of progenitor cells not only of monocyte/macrophage lineage but also of granulocyte lineage. Also, the coincidence between decrease of marrow progenitor cells and increase of splenic and peripheral progenitor cells suggests that the progenitor cells are released from bone marrow to peripheral blood and reseeded to the spleen by the action of M-CSF.

Animals↗
PubMed1996

Effects of macrophage colony-stimulating factor (M-CSF) on lipopolysaccharide (LPS)-induced mediator production from monocytes in vitro.

M-CSF is a macrophage-lineage-specific growth factor that causes proliferation and differentiation of progenitor cells in the bone marrow. To investigate the effects of M-CSF on more matured cells, human monocytes were cultured in the presence or absence of M-CSF for 6 days. Addition of M-CSF at more than 10(2) U/ml resulted in higher viability and caused morphological differentiation to large macrophage-like cells. LPS-induced mediator production was also compared between M-CSF-treated and control cell. Monocytes were incubated with or without M-CSF for 3 days, and were stimulated with 1 microgram/ml of LPS for 2 days. IL-1 beta was not detected in the both culture supernatants, and PGE2 production was not influenced by M-CSF. However, amounts of G-CSF, GM-CSF, IL-6, and TNF-alpha produced in response to 1 microgram/ml of LPS were 1.5 to 2 times greater from monocytes treated with 10(4) U/ml of M-CSF than from control cells. The priming effect of M-CSF on LPS-induced cytokine production was found to require 3-day preincubation, and reached a maximum at the concentration of 10(4) U/ml. M-CSF-treated cells responded to a 10 times lower concentration of LPS than control cells in terms of cytokine production. M-CSF was also shown by flowcytometric analysis to influence the expression of CD14, a receptor for LPS, which might render monocytes more sensitive to LPS.

Cells, Cultured↗
PubMed1994

Progesterone-dependent secretion of macrophage colony-stimulating factor by human endometrial stromal cells of nonpregnant uterus in culture.

Recent studies have suggested that macrophages colony-stimulating factor (M-CSF), a hematopoietic glycoprotein essential to the proliferation and differentiation of mononuclear phagocytes and their progenitor cells, is also involved in the reproductive process in mice and humans. In this study, we examined, by enzyme-linked immunosorbent assay, the supernatants of stromal cell-enriched fraction (SF) of human nonpregnant endometrium for the presence of M-CSF during culture with progesterone (P) or estrogen. The bioactivity of M-CSF was assessed in a colony-forming assay of murine bone marrow cells. In addition, the M-CSF level in the culture supernatant of SF further purified by subculture, of epithelial cell-enriched fraction purified from human endometrium, and of peripheral blood lymphocytes, including about 10% monocytes, was examined with or without P, because SF is contaminated by epithelial cells and macrophages, both of which are suggested to secrete M-CSF. During 2-week culture, the level of M-CSF in the supernatants of SF cultured with P was markedly higher than that of control culture and estrogen-treated culture on any day tested, except for the first 2 days. P had a dose-dependent effect on M-CSF production by SF. Estrogen also enhanced M-CSF production by SF, but did not show dose dependency. The SF culture supernatants showed a colony-forming activity that was completely blocked by neutralizing anti-M-CSF antibody. SF subcultured three times, which was confirmed to be of more than 99% purity, secreted M-CSF in a P-dependent manner. M-CSF was also detected in the culture supernatants of epithelial cell-enriched fraction and peripheral blood lymphocytes, but P-dependent M-CSF production was not shown in these cultures. These results suggest that human endometrial stromal cells themselves can secrete bioactive M-CSF in a P-dependent manner in vitro, indicating that the M-CSF reported to be present in human endometrium is secreted in part by stromal cells and may play a role in the regulation of endometrial function under P control.

Adult↗
PubMed1993

Enhancing effects of IL-2 on M-CSF production by human peripheral blood monocytes.

Monocytes have the capacity to produce granulopoietic factors such as M-CSF and G-CSF. Our findings here showed that interleukin-2 (IL-2), at a concentration of more than 0.05 ng/ml, led to a 12-fold increase in the production of M-CSF in the human peripheral blood mononuclear cells after 72 h incubation compared to the control culture. Even in purified monocyte cultures with added IL-2, a 3-fold increase in M-CSF production was observed at an IL-2 concentration of 50 ng/ml. The enhancing effect of IL-2 on M-CSF secretion was also observed when IL-2-stimulated non-phagocytic cell-conditioned medium was added to monocyte cultures. These results indicated that IL-2, both directly and indirectly, activated monocytes to enhance the production of M-CSF. In addition, the expression of IL-2 receptor (CD25) on monocytes was more enhanced in cultures containing IL-2 than in cultures without IL-2. On the other hand, IL-2 did not induce G-CSF production in purified monocytes. These in vitro results suggest that when IL-2 is used clinically, the various biological activities of M-CSF should also be taken into consideration.

Cells, Cultured↗
PubMed1993

Macrophage colony-stimulating factor as a tumor marker for epithelial ovarian cancer.

OBJECTIVE: To determine the serum level of macrophage colony-stimulating factor in ovarian cancer patients in order to evaluate its role as a marker for ovarian cancer. METHODS: Serum macrophage colony-stimulating factor levels were assayed in 69 patients with epithelial ovarian cancer, 55 with benign ovarian tumors, and 634 healthy individuals, including 398 women, using an enzyme-linked immunosorbent assay. RESULTS: The average serum macrophage colony-stimulating factor level was 754.4 +/- 153.9 U/mL in healthy females; 1056 U/mL (mean plus 1.96 standard deviations) was considered to be the upper limit of normal. Serum macrophage colony-stimulating factor levels were significantly elevated in patients with ovarian cancer (average 1460.5 +/- 1006.2 U/mL; P < .001) and exceeded 1056 U/mL in 42 of the 69 patients with ovarian cancer (61%). No differences in levels were observed among the histologic types. No definite relationship was found between serum levels of macrophage colony-stimulating factor and those of CA 125. We found that 96% of the patients with ovarian cancer had high serum levels of macrophage colony-stimulating factor and/or CA 125 values. There was no significant difference in the levels of macrophage colony-stimulating factor between patients with benign ovarian tumors and healthy controls. Only 7.3% of the group with benign tumors had levels exceeding 1056 U/mL. CONCLUSION: Macrophage colony-stimulating factor is a marker for ovarian cancer. Determination of serum levels can be useful in detecting ovarian cancer, particularly in combination with CA 125.

Adult↗
PubMed1993

[Within-day and day-to-day variations of serum M-CSF levels in healthy volunteers].

We have investigated on within-day and day-to-day variations of serum M-CSF levels in healthy volunteers (ranges of age: 20-21 years old). M-CSF levels in serum were measured using enzyme-linked immunosorbent assay (ELISA). Serum M-CSF levels in early morning were 1.31 +/- 0.30 ng/ml (mean +/- SD, n = 10) in male volunteers, 1.50 +/- 0.13 ng/ml (n = 10) in female volunteers. No significant difference was observed between male and female volunteers in serum M-CSF levels. No significant within-day variations in serum M-CSF levels were also observed. Serum M-CSF levels in period of thirteen days in each individual person were almost constant (n = 5). The inverse correlation was observed between M-CSF levels and number of neutrophils. The correlation, however, was not observed between M-CSF levels and number of monocytes. The present results suggest that there are mechanisms in vivo which maintain serum M-CSF in a constant level in each individual person.

Adult↗
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

Effect of intracisternal injection of endothelin-1 on regional cerebral blood flow in cats.

The effect of endothelin-1 on regional cerebral blood flow (rCBF) was investigated in adult mongrel cats. Endothelin-1 was injected into the cisterna magna and rCBF was measured by the hydrogen clearance method before and every 30 minutes for 180 minutes after the injection. Endothelin-1 (10(-11) mol and 10(-9) mol) induced a significant decrease in rCBF and an increase in arterial pressure. The effects of endothelin-1 on rCBF and arterial pressure were mediated, at least in part, by Ca2+, because pretreatment with intracisternally injected nicardipine prevented the changes. Cerebral angiograms obtained before and after endothelin-1 injection demonstrated severe constriction of the basilar artery, but constriction of the internal carotid and middle cerebral arteries was mild. Since the rCBF measured was in the territory of the middle cerebral artery, the decrease in blood flow was probably not solely due to the artery constriction. Other mechanisms such as arteriole constriction and/or regulation of rCBF by the central nervous system may also occur.

Animals↗
PubMed1990

Effects of ebselen (PZ51) on ischaemic brain oedema after focal ischaemia in cats.

Using a transorbital middle cerebral artery (MCA) occlusion model in cats, we evaluated the anti-oedema effects of a new anti-inflammatory agent, ebselen (PZ51), on ischaemic cortical oedema caused by prolonged ischaemia and recirculation. Local cerebral blood flow was measured by the hydrogen clearance method in the MCA territory and the corresponding cortical specific gravity was assessed by a microgravimetric technique. Ebselen had no significant effect on normal and ischaemic lCBF, while it significantly ameliorated post-ischaemic hypoperfusion following recirculation. In the severely ischaemic regions, microgravimetry showed the beneficial effects on the ischaemic oedema caused by prolonged ischaemia and recirculation as well. Although the exact site of action is undetermined in this study, the observed effects of ebselen may be ascribed to this agent's broad-spectrum of anti-inflammatory activities.

Animals↗
PubMed1989

The role of free radicals and eicosanoids in the pathogenetic mechanism underlying ischemic brain edema.

Results of our consecutive study on the pathogenic mechanism underlying ischemic brain edema are summarized in this paper. Pertinent findings are as follows: (1) there is a close correlation between the influxes of water and sodium following ischemia; (2) the edema fluid can be regarded as the ultrafiltrate of serum; (3) there is a significant increase in the brain content of HETEs following ischemia; (4) the lipoxygenase activity of brain microvessels is increased following ischemia; (5) the lipoxygenase activity as well as the Na+, K+-ATPase activity of brain microvessels are enhanced by a hydroperoxide, 15-HPETE; (6) inhibition of Na+, K+-ATPase of brain microvessels by intraarterial infusion of ouabain resulted in a significant decrease in edema formation; and (7) not the cyclooxygenase, but the lipoxygenase pathway seems to be involved in the enhancement of microvessel Na+, K+-ATPase. Lipoxygenase(s) and Na+-K+-ATPase of brain microvessels, the activities of which are enhanced by an increased level of free radicals and/or hydroperoxides, may play a significant role in the occurrence of ischemic brain edema.

Animals↗
PubMed1989

Effect of indomethacin and a free radical scavenger on cerebral blood flow and edema after cerebral artery occlusion in cats.

Using the middle cerebral artery occlusion model in cats, we evaluated the possible role of the cyclooxygenase pathway in alterations of local cerebral blood flow and the development of cortical edema following prolonged ischemia or recirculation. We divided 57 cats into three groups, and each cat received saline (control), indomethacin, or the free radical scavenger ONO-3144. Each group was subdivided into prolonged ischemia (4 hours of occlusion: PI) and recirculation (2 hours of occlusion followed by 2 hours of recirculation: RC) subgroups. We compared local cerebral blood flow and cortical specific gravity between the PI and RC subgroups of the control and drug-treated groups. In the PI subgroup, indomethacin did not influence the time course of local cerebral blood flow but significantly worsened the decrease in cortical specific gravity. On the other hand, indomethacin significantly improved postischemic hypoperfusion and ameliorated the decrease in cortical specific gravity in the RC subgroup. The effects of ONO-3144 were similar to those of indomethacin, except that ONO-3144 did not affect cortical specific gravity in the PI subgroup. Indomethacin inhibits cyclooxygenase activity, whereas ONO-3144 scavenges the oxygen-centered radical released in the conversion of prostaglandin G2 to prostaglandin H2. Thus, prostaglandins do not seem to play a major role in the occurrence of brain edema due to prolonged regional ischemia. By contrast, oxygen-centered radicals released from the cyclooxygenase pathway appear to be at least partially responsible for the occurrence of recirculation-induced edema and postischemic hypoperfusion.

Animals↗
PubMed1989

Prostaglandin profiles in relation to local circulatory changes following focal cerebral ischemia in cats.

We explored the temporal and topographic relations between local cerebral blood flow and regional brain prostaglandin profile following prolonged or transient occlusion of the middle cerebral artery in cats. Each experimental group was subjected to a sham operation, prolonged ischemia, or recirculation. Local cerebral blood flow was measured by the hydrogen clearance method. Following in situ freezing, cortical samples were obtained from each gyrus for determination of prostaglandin (PG) F2 alpha, PGE2, 6-keto-PGF1 alpha, and thromboxane (TX) B2 concentrations by radioimmunoassay. During prolonged ischemia, the concentrations of PGF2 alpha and PGE2 within the middle cerebral artery territory were significantly increased. Immediately after recirculation, there was a prominent but transient increase in PGF2 alpha and PGE2 in gyri that had been exposed to moderate ischemia (perifocal area). By contrast, the increases in these prostaglandins were slow and less prominent in gyri that had been exposed to severe ischemia (the focal area). The concentration of 6-keto-PGF1 alpha did not change during prolonged ischemia but transiently increased following recirculation in both the focal and perifocal areas. The TXB2 concentration did not change in any experimental group. Our study revealed a homogeneous increase in the regional brain content of PGE2 or PGF2 alpha in spite of the heterogeneous reduction of local cerebral blood flow during prolonged ischemia. Following recirculation, the focal and perifocal areas exhibited different patterns of prostanoid content. No correlation was found between local cerebral blood flow and the regional concentration of any prostaglandin examined.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

[Clinical use of castable ceramics (OCC) crown].

The new ceramics material (OCC) was developed for the purpose of aesthetic restration which can be fabricated by an usual lost wax process and it produces accurate marginal fit. OCC possesses mechanical, chemical, and physical properties. This article is discussed utility and security of OCC complete crown on the clinical application from Dec, 1986 to Jun, 1989. The results may be summarized as follows: 1) 2 of 69 cases were broken down in the period from Dec, 1986 to Jun, 1989. These reasons are caused by the lack of occlusal thickness and unsuitable fit of crown. 2) Although 4 of 69 cases are stained by tobacco tar and 5 of 69 cases are suffered from plaque accumulation, these staining and plaque accumulation are improved by plaque control. 3) An allergic reaction or an abnormality of oral tissues haven't been recognized during test period of clinical use. Consequently OCC crown showed itself about safety and usefulness.

Crowns↗
PubMed1988

Quantitation and identification of human monocytic colony-stimulating factor in human serum by enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) system for the quantitation of human monocytic colony-stimulating factor (hM-CSF) was established, which was based on the "dual antibody immunometric sandwich" principle using horse and rabbit polyvalent antibodies against human urinary colony-stimulating factor (CSF-HU). The minimal detectable level of hM-CSF was 10 U/mL, and the assays showed good reproducibility. As measured by this method, the average serum hM-CSF level of 20 normal adults was 540 +/- 110 U/mL (range, 300 to 800 U/mL). The peak of hM-CSF measured by ELISA was identical to that measured by bioassay when semipurified CSF-HU was fractionated by reversed-phase high performance liquid chromatography (HPLC). This method detected two types of hM-CSF, which had approximate molecular weights of 85 Kd (CSF-HU) and 45 Kd in human serum and urine; the ratio of 85:45 Kd was very high in serum and the amounts of the two types were nearly equal in urine. After anticancer chemotherapy, the serum hM-CSF level of one half of the patients with hematological malignancy was elevated according to the reduction in neutrophil number, while it was almost in the normal range in the other half of the patients, indicating the possibility that anticancer chemotherapy damaged the hM-CSF-producing cells. This ELISA method may be useful for monitoring the serum hM-CSF level after anticancer chemotherapy.

Adult↗