Search PubMed⌕ Search

Biomedical subjects

M Asano

Publications and source records attributed to M Asano.

At least 127 records · Page 7Linked to original sources
PubMed1998

Hypoxia and endothelin-1 induce VEGF production in human vascular smooth muscle cells.

Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is a secreted mitogen for vascular endothelial cells, and it promotes vascular permeability and neovascularization in vivo. We investigated the mechanisms by which low oxygen tension modulates the expression of VEGF in human aortic vascular smooth muscle cells (h-SMC) in vitro. Moreover, we measured VEGF levels in the cultured medium with or without endothelin-1 (ET-1) using a newly developed, highly sensitive, enzyme-linked immunosorbent assay. Hypoxia resulted in a substantial induction of VEGF transcripts at 3 and 24 hr. VEGF levels were significantly higher when h-SMC were cultured in medium containing ET-1 than when cultured in medium without ET-1. In conclusion, hypoxia and ET-1 constitute potent stimuli for VEGF production in h-SMC.

Cell Hypoxia↗
PubMed1998

Internal thoracic-carotid bypass surgery for Takayasu's arteritis.

BACKGROUND: Various carotid reconstructions have been used in Takayasu's arteritis (TA) to relieve brain ischemic insult. The indications and guidelines for surgical management, however, have remained poorly defined. The authors present a new reconstructive procedure using the sequential internal thoracic artery (ITA) as the donor for bypass surgery to supplement the cerebral blood flow. CASE DESCRIPTION: A 38-year-old woman presented with three episodes of syncope. The patient was admitted to our hospital and was diagnosed with TA. Before the operation, the patient was designated to undergo aortocarotid bypass using saphenous veins. However, a dilated ascending aorta with an extremely thin wall made it impossible. Finally, we decided to use the ITA as the donor for bypass surgery. This patient is now free of cerebral ischemic insult 8 months after the operation. CONCLUSION: Although the procedure is still at a preliminary stage, a successful case is briefly described.

Adult↗
PubMed1998

Caspase 1-independent IL-1beta release and inflammation induced by the apoptosis inducer Fas ligand.

Fas ligand is a well-characterized apoptosis inducer. Here we demonstrate that Fas ligand induces the processing and secretion of interleukin-1beta (IL-1beta) in peritoneal exudate cells. This IL-1beta secretion is independent of IL-1beta converting enzyme (caspase 1), yet it is inhibited by caspase inhibitors, indicating that a caspase(s) in addition to IL-1beta converting enzyme can process IL-1beta. Inoculation of tumor cells expressing Fas ligand into wild-type mice induces a massive neutrophil infiltration that is, in contrast, suppressed in IL-1alpha/beta knockout mice. These results demonstrate a newly discovered role for Fas ligand in inflammation, and challenge the dogma that apoptosis does not induce inflammation.

Animals↗
PubMed1998

Pharmacological characterization of a nonpeptide bradykinin B2 receptor antagonist, FR165649, and agonist, FR190997.

1. The nonpeptide bradykinin (BK) B2 receptor antagonist, FR165649 (8-[2,6-dichloro-3-[N-[(E)-4-(N-methylcarbamoyl)cinnamidoacetyl ]-N-methylamino]benzyloxy]-2-methylquinoline), and agonist, FR190997 (8-[2,6-dichloro-3-[N-[(E)-4-(N-methylcarbamoyl) cinnamidoacetyl]-N-methylamino]benzyloxy]-2-methyl-4-(2-pyridyl methoxy)quinoline) have been identified. These compounds have a common chemical structure, and the 2-pyridylmethoxy group is the only structural difference between them. 2. Both FR165649 and FR190997 displaced [3H]-BK binding to B2 receptors in guinea-pig ileum membranes, with an IC50 of 4.7 x 10(-10) M and 1.5 x 10(-9) M, respectively. They also displaced [3H]-BK binding to B2 receptors in human lung fibroblast IMR-90 cells, with an IC50 of 1.6 x 10(-9) M and 9.8 x 10(-10) M, respectively. 3. In guinea-pig isolated ileum-preparations, FR165649 had no agonistic effect on contraction and caused parallel rightward shifts of the concentration-response curves to BK on contraction. Analysis of the data produced a nominal pA2 value of 9.2+/-0.1 (n=5) and a slope of 1.4+/-0.1 (n=5). On the other hand, FR190997 induced concentration-dependent contraction of guinea-pig ilea with a pD2 of 7.9+/-0.2 and the contraction was inhibited by a specific peptide bradykinin B2 receptor antagonist, Hoe 140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]BK) in a non-competitive manner. 4. In IMR-90 cells, FR165649 had no agonistic effect on phosphatidyl inositol (PI) hydrolysis and caused parallel rightward shifts (approximately 200 fold shift at 10(-7) M) of the concentration-response curves to BK on PI hydrolysis. FR190997 induced concentration-dependent PI hydrolysis in IMR-90 cells with a pD2 of 8.4+/-0.1, and this effect was inhibited by Hoe 140. 5. These results indicate that FR165649 and FR190997 are, respectively, a potent bradykinin B2 receptor antagonist and agonist, and that the agonistic activity depends on the small part of the nonpeptide ligand. FR165649 and FR190997 may be useful tools for studying the relationship between ligands and receptors.

Animals↗
PubMed1998

Increase in serum vascular endothelial growth factor levels during altitude training.

The present study was performed to evaluate the effects of physical exercise at altitudes on serum vascular endothelial growth factor (VEGF) levels. Eight subjects underwent intensive swimming training for 21 days at 1886 m. After altitude training commenced, red blood cell (RBC) counts and erythropoietin levels increased, but both haemoglobin and haematocrit levels did not change significantly. The serum level of VEGF, measured by means of a highly sensitive chemiluminescence (ELISA), showed a transient decrease 10 days after start of the altitude training, thereafter increasing significantly to reach a peak level 19 days later, rising from 23.0 +/- 5.3 to 46.0 +/- 14.6 pg mL-1 (P < 0.05 vs. before). On return to low altitude in Japan, the level of VEGF decreased, and 1 month later had returned to initial levels. Endurance training at altitudes increases serum VEGF levels; this could be an adaptive reaction to hypoxic conditions. This result suggests that VEGF may provide a new physiological parameter for hypoxic stress imposed by high altitude training.

Adult↗
PubMed1998

An anti-human VEGF monoclonal antibody, MV833, that exhibits potent anti-tumor activity in vivo.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor for tumor angiogenesis and growth. We previously established the immunoneutralizing monoclonal antibodies (MAbs) to human VEGF, and showed that MV101 (IgG1) and MV303 (IgG2a) inhibited the growth of human solid tumor xenografts in nude mice. Then, we tried to develop another immunoneutralizing anti-VEGF MAb that exhibited more potent antitumor activity than MV101 or MV303. We obtained more than 140 clones of hybridomas that were producing anti-VEGF MAb from the mice immunized with recombinant human VEGF121. Among them, 26 clones showed the immunoneutralizing activity and MV833 possessed the most potent antitumor activity in vivo. A total of 9 i.p. administrations of 25 microg of MV833 inhibited the growth of human fibrosarcoma HT-1080 solid tumor xenografted in nude mice more potently than MV101 or MV303. Moreover, only 1 i.v. administration of 100 microg of MV833 on Day 1 after tumor inoculation also significantly inhibited the growth of HT-1080 in vivo, whereas MV101 and MV303 did not. All three MAbs inhibited the growth of human umbilical vein endothelial cells (HUVEC) induced by VEGF121 and the binding of 125I-labeled VEGF121 to HUVEC to a similar extent. The binding of MV101 and MV303 to VEGF121 was cross-competitive; however, MV833 weakly competed with the binding of MV101 to VEGF121. These findings indicated that MV833 recognized the region(s) of VEGF differently than MV101 or MV303, and this difference contributed to the superiority of antitumor activity of MV833.

Animals↗
PubMed1998

Abnormality of very long-chain fatty acids of erythrocyte membrane in alcoholic patients.

Profiles of very long-chain fatty acids were studied in the erythrocyte membrane of five alcoholic patients. We identified three fatty acids as cis-16-pentacosenoic acid (C25:1), cis-17-hexacosenoic acid (C26:1), and hexacosenoic acid (C26:1), and hexacosanoic acid (C26:0) by gas chromatography-mass spectrometry. The ratios of C26:1/C22:0, C26:0/C22:0, C24:1/C22:0, and C24:0/C22:0 were increased. These findings suggest that active oxygen species or free radicals generated by chronic alcohol consumption in alcohol patients interrupt the peroxisomal beta-oxidation of fatty acids, because very long-chain fatty acids are mainly metabolized by the peroxisomal beta-oxidation system. This is the first study showing accumulation of very long-chain fatty acids in the erythrocyte membrane of alcoholic patients.

Alcoholism↗
PubMed1998

Antitumor effect of a neutralizing antibody to vascular endothelial growth factor on liver metastasis of endocrine neoplasm.

Distant metastasis of gastrointestinal endocrine neoplasm is resistant to currently available treatments. Because hematogenic metastasis is dominant, anti-angiogenic drugs are expected to be a novel therapy for this neoplasm. In the present study, the therapeutic effect of vascular endothelial growth factor neutralizing antibody (VEGFAb) on liver metastasis of an endocrine neoplasm was investigated experimentally. Cecal transplantation into nude mice of small pieces of EN-1, a xenotransplanted human intestinal endocrine neoplasm, resulted in liver metastasis. A treated group (n = 19) received 100 micrograms/mouse of VEGFAb intraperitoneally on alternate days from day 10 after tumor transplantation, and the control group (n = 19) received saline. Five of the 19 control mice died of tumor progression, of which 2 could not be evaluated. The cecal tumor weighed 6316 +/- 2333 mg (n = 17) in the control group and 1209 +/- 837 mg (n = 19) in the treated group (P < 0.01) 6 weeks after transplantation. Liver metastasis developed in 16 of 17 control mice and in 2 of 19 treated mice (P < 0.01). The VEGF level of the whole cecal tumor in the control group was significantly higher than that in the treated group (305.1 +/- 174.1 vs. 54.7 +/- 41.2 mg; P < 0.001). VEGFAb did not cause any body weight loss (28.52 +/- 1.63 in the control vs. 28.44 +/- 1.71 g in the treated group). These results indicate that VEGFAb may be a novel therapeutic agent for endocrine neoplasm with distant metastasis.

Aged↗
PubMed1998

Neuropeptides in the livers of mice during bacterial infections.

Neuropeptides such as substance P (SP) and vasoactive intestinal peptide (VIP) are known to act as immunomodulators. We investigated the induction of SP and VIP in the livers of mice infected with Listeria monocytogenes or injected with Tsukamurella paurometabolum. VIP was detected in the livers of mice after L. monocytogenes infection by an immunohistochemical technique and preproVIP mRNA, which was detected by reverse transcription-polymerase chain reaction (PCR), was induced post infection. However, no SP was detected. In contrast, SP, but not VIP was detected within granulomas in the livers of T. paurometabolum-injected mice, suggesting VIP and SP might be selectively induced in the liver by different bacterial infections.

Actinomycetales↗
PubMed1998

Development of melanocyte progenitors in murine Steel mutant neural crest explants cultured with stem cell factor, endothelin-3, or TPA.

Stem cell factor (SCF) has been suggested to be indispensable for the development of neural crest cells into melanocytes because Steel mutant mice (i.e., Sl/Sl(d)) have no pigmented hairs. On the other hand, it has been demonstrated that the addition of endothelin 3 (ET-3) or TPA to neural crest cell cultures can induce melanocyte differentiation without addition of extrinsic SCF. In this study, we excluded the influence of intrinsic SCF by using Sl/Sl mouse embryos to study more precisely the effects of natural cytokines, such as extrinsic soluble SCF or ET-3, or chemical reagents, such as TPA or cholera toxin. We found that SCF is supplied within the wild-type neural crest explants and that ET-3 cannot induce melanocyte differentiation or proliferation without SCF. These results indicate that SCF plays a critical role in survival or G1/S entry of melanocyte progenitors and that SCF initially stimulates their proliferation and then ET-3 accelerates their proliferation and differentiation. TPA has the ability to elicit neural crest cell differentiation into melanocytes without exogenously added SCF but it is not as effective as SCF because many more melanocytes developed in the wild-type neural crest explants cultured with TPA.

Animals↗
PubMed1998

In vivo characteristics of injectable poly(DL-lactic acid) microspheres for long-acting drug delivery.

Poly(DL-lactic acid) (PLA) microspheres containing testosterone (T) were prepared by the solvent evaporation process to evaluate their physical properties such as size distribution, shape, drug content, in vivo controlled drug release, pharmacological influences on the prostate gland in castrated rats, and histopathological findings of tissues surrounding the implants. The in vivo release of T from PLA microspheres containing 30 mg of drug obtained with chloroform was continued over a 6-week period. This effect is attributed to high dispersibility of T in the device when obtained with chloroform. Both serum drug levels and prostate gland weight recovery suggested the effects of a long-acting drug delivery system. The histopathological findings showed that the devices used were completely degraded 10 weeks after injection.

Animals↗
PubMed1998

Preparation and characterization of oil-in-water type poly (D,L-lactic acid) microspheres containing testosterone enanthate.

Poly (D,L-lactic acid) (PLA) microspheres containing testosterone enanthate (ET) were prepared by using an oil-in-water (O/W) emulsion technique. The size distribution of the microspheres obtained could be explained by a log-normal distribution, and as a result, it was found that ET fully incorporates into microspheres even when the drug is loaded at up to 50%. On the other hand, the dissolution behavior of ET from microspheres was strongly dependent on particle size, suggesting that dissolution of the drug from microspheres can be easily controlled by controlling the preparative conditions.

Calorimetry, Differential Scanning↗
PubMed1998

Effect of divalent polyethylene glycol units, conjugated on human granulocyte colony-stimulating factor, on biological activities in vitro and in vivo.

New divalent (two-chain type) polyethylene glycol (PEG) conjugates of a derivative of human recombinant granulocyte colony-stimulating factor (rhG-CSF), ND28, were synthesized by a novel conjugation method using triazine ring and amino butyric acid, and separated into mono-, di- and tri-PEG2(two chains)-ND28 with high purity of more than 90%, to examine the effect of the number of PEG units on their biological properties. Three species of PEG2-ND28 conjugates showed reduced but clear in vitro bioactivity and receptor binding inhibitory activity, and an inverse correlation between the number of PEG units and the activity was seen. On the other hand, the in vivo granulopoietic effect of tri-PEG2-ND28 in mice was observed to be most potent and long-lasting for 6 days after only one administration, and was followed by di-PEG2-ND28 and mono-PEG2-ND28. The plasma concentration of tri-PEG2-ND28 was maintained at a high level for 3 days after administration, while that of PEG-unbound ND28 disappeared within 30 h. There was a positive correlation between the number of PEG units and both the granulopoietic effect and the plasma half-life. These results suggest that the number of PEG units attached to the rhG-CSF can increase their stability during circulation in the plasma of mice, in turn resulting in a long-lasting granulopoietic effect in vivo.

Animals↗
PubMed1998

Significance of circulating hepatocyte growth factor level as a prognostic indicator in primary breast cancer.

The circulating hepatocyte growth factor (HGF)/scatter factor level is frequently increased in advanced cancer patients. In this study, we have assessed the prognostic value of the circulating HGF level determined by enzymatic immunoassay in primary breast cancer patients. Of 200 primary breast cancer patients, 54 (27.0%) showed the increase of serum HGF level according to the age-matched cutoff values. The prognosis of the patients with the increased HGF level was statistically worse than that of the patients with normal HGF level (P = 0.0001, log-rank test). Multivariate analysis confirmed that the increase in HGF level was an independent prognostic indicator in primary breast cancer patients. In the background analysis, the increase in serum HGF level was significantly associated with tumor size, nodal status, and histological evidence of venous invasion. The data indicate that up-regulation of the circulating HGF level may predict systemic tumor spread and early relapse in primary breast cancer patients.

Adult↗
PubMed1998

Pharmacological profile of nicardipine hydrochloride in anesthetized dogs with acute heart failure. Part 1: Hemodynamic effects in normal dogs and dogs with acute heart failure.

Cardiovascular effects of nicardipine hydrochloride (NIC, CAS 54527-84-3, Perdipine), a calcium channel blocker, were investigated in anesthetized normal dogs and dogs with acute heart failure (AHF), and compared with those of nitroglycerin (NTG). In open-chest anesthetized dogs, NIC (0.1-10 micrograms/kg/min i.v.) dose-dependently increased cardiac output (CO) and coronary blood flow as well as decreased mean blood pressure (MBP). NIC had no effect on heart rate (HR) or maximum rate of rise of left ventricular pressure (max. dp/dt). In contrast (0.1-10 micrograms/kg/min i.v.) decreased MBP, but did not change the other cardiovascular parameters. NIC and NTG did not prolong PQ, QRS or QTc intervals. In addition, NIC was effective in the presence of dobutamine. In the anesthetized dog model of ischemic AHF induced by coronary ligation, and ischemia/angiotensin II-induced AHF, NIC (1 and 3 micrograms/kg/min i.v.) increased CO and stroke volume, and reduced total peripheral resistance without decreasing HR or cardiac contractility. Furthermore, in the ischemia/angiotension II-induced AHF model, NIC decreased left ventricular end-diastolic pressure (LVEDP). In contrast, NTG (1-10 micrograms/kg/min i.v.) decreased LVEDP in both AHF models; but did not increase CO. These results suggest that NIC improves hemodynamics in dogs with AHF mainly by reducing afterload without adversely affecting the cardiac contractility or conduction system, while NTG exerts its effect on AHF by reducing preload. NIC injection would thus appear to be beneficial in the treatment of AHF.

Acute Disease↗
PubMed1998

Pharmacological profile of nicardipine hydrochloride in anesthetized dogs with acute heart failure. Part 2: Effect on myocardial metabolism.

The effect of nicardipine hydrochloride (NIC, CAS 54527-84-3, Perdipine) on myocardial metabolism was investigated in an experimental model of ischemic acute heart failure (AHF) induced by coronary ligation in anesthetized dogs. The left anterior descending and/or circumflex coronary ligation decreased coronary sinus blood flow (CBF), maximum rate of rise of left ventricular pressure (max. dp/dt), cardiac output (CO) and stroke volume (SV), and increased left ventricular end-diastolic pressure, indicating the development of AHF. In this ischemic AHF model, NIC (3 micrograms/kg/min i.v. infusion for 15 min) increased CBF, CO and SV, and reduced systemic and coronary artery resistances, resulting in the improvement of AHF. During the effective period, NIC decreased myocardial oxygen consumption and the coronary arterio-venous difference of oxygen content, carbon dioxide pressure and pH. At the same time, NIC did not decrease the lactate extraction. These results suggest that NIC improves hemodynamics and the balance of myocardium oxygen supply and demand in dogs with AHF by means of reducing afterload and dilating coronary artery.

Acute Disease↗
PubMed1998

Serum copper and ceruloplasmin activity at the early growing stage in foals.

Serum concentrations of copper (Cu), zinc (Zn), manganese (Mn), calcium (Ca) and inorganic phosphorus (P), as well as antigenic ceruloplasmin (Cp) and oxidase activity as a functional index for copper metabolism, were measured in 10 foals (5 males and 5 females) and their dams. Samples were harvested from the foals within 1 wk after birth and monthly from 1 to 17 mo of age. Samples were collected from their dams in the perinatal period (monthly from 2 mo before delivery to 5 mo postpartum). Serum oxidase activity, antigenic Cp and Cu in foals were extremely low at 1 wk. Serum Cp had the lowest value of 17.0 +/- 8.0 (mean +/- SD) mg/dL within the 1st wk, then increased rapidly up to 43.7 +/- 5.8 mg/dL at 1 mo, and maintained this level until the 17th mo. Serum Zn in foals had the highest value of 73.2 +/- 13.1 micrograms/dL within 1 wk, then decreased to 38.3 +/- 5.9 micrograms/dL by 17 mo. Serum Mn, Ca and P in mares were almost stable and within established reference ranges for our laboratory in the perinatal period, and these values in foals were also in the normal range. Even on appropriate feeding, serum Cu, Cp and oxidase activity were quite low a few weeks after birth, while a higher proportion of Cp-binding copper was found in the foals. This might be caused by the limited synthesis of ceruloplasmin in this period. These data suggest that newborn foals are in a critical situation of marginal copper status in the early stage of growth.

Aging↗