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Biomedical subjects

M Takenaga

Publications and source records attributed to M Takenaga.

At least 19 recordsLinked to original sources
PubMed1997

Lecithinization of IL-6 enhances its thrombopoietic activity in mice.

This study was conducted to assess the merit of lecithinization of recombinant human interleukin-6 (IL-6) as a drug delivery system. IL-6 was lecithinized by covalently binding it with a phosphatidylcholine (lecithin, PC) derivative. The in-vivo thrombopoietic potency of lecithinized IL-6 (PC-IL-6) was greater than that of native IL-6 when administered subcutaneously, although the in-vitro bioactivity of PC-IL-6 was markedly reduced by lecithinization. When PC-IL-6 and native IL-6 were given in doses that produced the same level of thrombopoietic activity, the former stimulated less production of IgG1, a marker of the adverse effects of IL-6, than did the latter. Furthermore, PC-IL-6 persisted in the blood longer than native IL-6. Based on the above, PC-IL-6 appears to be useful as a drug delivery system and may also be useful in the treatment of drug-induced thrombocytopenia.

Animals↗
PubMed1997

Recurrent syncope induced by left ventricular outflow tract obstruction: demonstration in a patient with hypertrophic obstructive cardiomyopathy.

A 70-year-old man presented with repeated syncope induced by left ventricular outflow tract obstruction. He was referred to us because of repeated syncope with convulsion at rest. During syncope, electrocardiography showed marked ST segment depression with negative T waves in leads I, II, aVL, aVF and V2-V5 but no arrhythmias. Echocardiography revealed asymmetric septal hypertrophy and complete obstruction of the left ventricular outflow tract due to systolic anterior movement of anterior mitral leaflet and concomitant severe mitral regurgitation. During the catheterization study, syncope with convulsion developed repeatedly without antecedent cause, and was associated with a decrease in systemic blood pressure. Simultaneous pressure monitoring of the left ventricle and femoral artery showed a significant pressure gradient (maximum 110 mmHg). During each episode, systemic blood pressure rose spontaneously with the recovery of consciousness over several minutes. He received temporary atrioventricular sequential pacing and underwent successful mitral valve replacement. Four years later, he was doing well.

Aged↗
PubMed1996

Increased plasma adrenomedullin levels in chronic congestive heart failure.

Adrenomedullin is a potent vasodilator peptide and occurs in circulating blood of human beings and experimental animals. Because it is produced in intact aorta of rats and in cultured vascular endothelial cells, adrenomedullin seems to participate in regulation of local vascular tone. To determine the pathophysiological roles of adrenomedullin, we investigated its plasma concentrations in 49 patients with heart failure. Plasma adrenomedullin levels increased significantly with advancing severity of the disease (New York Heart Association functional class I, 4.1 +/- 1.0; II, 5.6 +/- 1.6; III, 6.4 +/- 0.8; IV, 13.2 +/- 6.8 (fmol/l). Plasma adrenomedullin was correlated with pulmonary artery pressure (r = 0.44, p = 0.0114) and pulmonary capillary wedge pressure (r = 0.53, p = 0.0002). These findings indicate that adrenomedullin may play some important role in the pathophysiologic makeup of heart failure by its vasodilating effects against the concomitant exaggeration of humor pressor agents such as catecholamine and the renin-angiotensin system. Hemodynamic changes in pulmonary circulation may have some influence on the increased synthesis and secretion of plasma adrenomedullin in chronic congestive heart failure.

Adrenomedullin↗
PubMed1996

Increased plasma adrenomedullin in acute myocardial infarction.

Adrenomedullin has a potent vasodilating effect comparable to that of calcitonin gene-related peptide. To investigate the pathophysiologic role of endogenous adrenomedullin, we determined sequentially the plasma adrenomedullin level in 15 consecutive patients with acute myocardial infarction (AMI). Plasma adrenomedullin was higher immediately after the onset of AMI and decreased gradually; plasma levels during the 3-week period after the AMI were higher than plasma levels in 15 healthy control subjects (p < 0.001), with higher levels in patients with congestive heart failure than in patients without congestive heart failure throughout the period of the study (p < 0.05). Plasma adrenomedullin was positively correlated with pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, and heart rate in the early stage of AMI. These findings suggest that the elevation of plasma adrenomedullin is related to the retention of body fluid volume, the enhancement of sympathetic activity, and/or the elevation of pressure in pulmonary vascular beds. Adrenomedullin may act against excessive vasoconstrictors increased in AMI.

Adrenomedullin↗
PubMed1995

Calcitonin gene-related peptide mediates acetylcholine-induced endothelium-independent vasodilation in mesenteric resistance blood vessels of the rat.

The role of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves in acetylcholine chloride (ACh)-induced vasodilation was studied in the perfused mesenteric vascular bed isolated from the rat. Bolus infusions of ACh at smaller doses (0.1 and 1 nmol) produced rapid and short-lived vasodilation. However, larger doses (10 and 100 nmol) of ACh caused a rapid and subsequent long-lasting vasodilator response in which the duration of vasodilation was prolonged in a concentration-dependent manner. Pretreatment with capsaicin (1 mumol/L for 20 minutes) significantly shortened the duration of vasodilator response to ACh but did not affect the initial rapid phase of ACh-induced vasodilation. Chemical removal of the vascular endothelium by perfusion with sodium deoxycholate (1.75 to 1.80 mg/mL) for 30 seconds and subsequent treatment with N omega-nitro-L-arginine (100 mumol/L) to inhibit nitric oxide synthesis abolished the initial rapid vasodilator action of ACh at any given concentration. However, in the same preparation, increasing concentrations (from 1 to 1000 nmol) of ACh produced only the long-lasting vasodilator responses in a concentration-dependent manner. This long-lasting vasodilator response to ACh infusion was abolished by capsaicin pretreatment (1 mumol/L), human CGRP[8-37] (CGRP receptor antagonist, 1 mumol/L), and atropine (muscarinic ACh receptor antagonist, 1, 10, and 100 nmol/L) but not by hexamethonium (nicotinic ACh receptor antagonist, 1 and 10 mumol/L). In the preparations without endothelium, the bolus infusion of ACh (300 nmol for 30 seconds) evoked a long-lasting vasodilation and release of CGRP-like immunoreactivities into the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Diagnosis of t(2;5)(p23;q35)-associated Ki-1 lymphoma with immunohistochemistry.

Some Ki-1 lymphomas carry a specific chromosomal translocation, t(2;5)(p23;q35). We have recently found a novel hyperphosphorylated 80-kD protein tyrosine kinase, p80, in a human Ki-1 lymphoma with this translocation. Subsequent cDNA cloning showed that p80 is a fusion protein of two different genes on chromosome 2p23 and 5q35, the novel tyrosine kinase gene and nucleophosmin gene, respectively. In this study, we intended to detect p80 on lymphoma tissues with immunologic methods. Thus, we developed rabbit polyclonal antibody using a synthetic peptide corresponding to a part of its kinase domain. The antibody (anti-p80) immunoprecipitated and immunoblotted p80 specifically from AMS3. Then, to examine whether t(2;5)(p23;q35) was present on biopsied lymphomas, reverse transcriptase-polymerase chain reaction (RT-PCR) covering the fusion junction of p80 mRNA was performed. Among 10 Ki-1 lymphomas and 10 additional lymphomas other than the Ki-1 lymphomas, expression of p80 mRNA was detected in three cases exclusively. When these 20 cases and additional 30 lymphomas were immunostained with anti-p80, positive staining was noted exclusively in the three cases found by PCR to have harbored the p80 mRNA. Thus, the present immunostaining, as well as PCR, was shown to be efficient for detecting lymphomas producing this chimeric protein/mRNA.

Amino Acid Sequence↗
PubMed1993

Vasodilator effect of adrenomedullin and calcitonin gene-related peptide receptors in rat mesenteric vascular beds.

The effect of adrenomedullin, a novel peptide of 52 amino acids, on vascular tone was investigated in the perfused rat mesenteric vascular bed. In the vasculature contracted with methoxamine, perfusion of adrenomedullin (10(-11)-10(-7) M) caused a concentration-dependent decrease in perfusion pressure due to vasodilation. Additionally, a bolus infusion of adrenomedullin (300 and 500 pmol) produced a long-lasting vasodilator response, which was not affected in the presence of atropine (10(-7) M) and propranolol (10(-7) M). However, this response was inhibited in the presence of CGRP [8-37] (10(-6) M), an antagonist for CGRP receptor. These results suggest that adrenomedullin induces nonadrenergic and noncholinergic vasodilation in which CGRP receptors may be involved.

Adrenomedullin↗
PubMed1993

Enhanced antitumor activity and reduced toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea administered in lipid microspheres to tumor-bearing mice.

Stable lipid microspheres (LM) and lipid nanospheres (LN) with average diameters of 200 nm and 50 nm, respectively, were used to encapsulate an lipophilic antitumor agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). LM and LN containing BCNU (lipo BCNU and s-lipo BCNU, respectively) were prepared by homogenizing a soybean oil solution of BCNU with egg yolk lecithin, and their antitumor activity via the intravenous route was tested against L1210 leukemia in mice and compared with that of BCNU dissolved in saline. Both lipo-BCNU and s-lipo BCNU showed significantly enhanced antitumor activity with reduced toxicity, when compared with the corresponding doses of BCNU alone. These results suggest that LM and LN may be suitable carriers for lipophilic antitumor agents and may enhance their efficacy.

Animals↗
PubMed1993

Application of lipid microspheres to prepare a thromboxane A2 receptor antagonist aerosol for inhalation.

The methyl ester of a new thromboxane A2 receptor antagonist, (+)S-145, i.e. (1R,2S,3S,4S)-(5Z)-7-(3-phenyl-sulfonyl-aminobicyclo[2,2,1]he pt-2-yl)heptenoic acid, was incorporated into lipid microspheres (lipo S-145-Me) and its pharmacological effect and tissue distribution were examined in guinea pigs following aerosol delivery. Bronchoconstrictive responses induced by intravenous injection of U46619 or the inhalation of ovalbumin were suppressed in a dose-dependent manner by aerosol inhalation of lipo S-145-Me, which was 3-10 times more potent that the unencapsulated calcium dihydrate of the original drug (S-1452). There was no significant difference in the airway tissue distribution of labelled lipo S-145-Me versus S-1452 after 2 or 5 min of inhalation, but the encapsulated drug showed marked accumulation in the lungs after 30 min of inhalation. The in vitro uptake of lipo [14C] S-145-Me by fresh human neutrophils and an eosinophil cell line was respectively 7 times and 3.5 times higher than that of [14C] S-1452. These results suggest that lipo S-145-Me has the potential to be used as an inhalational antiasthma agent, and that its effect may be partly attributable to a for inflammatory cells which are responsible for allergic airway inflammation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Lecithinization of superoxide dismutase potentiates its protective effect against Forssman antiserum-induced elevation in guinea pig airway resistance.

We synthesized lecithinized superoxide dismutase (PC-SOD), in which a lecithin derivative was covalently bound to recombinant human SOD. We selected PC4-SOD (4 molecules of the lecithin derivative bound to each SOD dimer) and PC10-SOD (10 molecules of the derivative to each SOD dimer) for our study. Both of these PC-SOD retained SOD activity in vitro and showed delayed plasma disappearance in vivo in rats. PC-SOD also had 4 to 20 times higher affinity in vitro for several kinds of cells than that of unmodified SOD. Because Forssman antiserum is known to induce bronchial obstruction in guinea pigs via actions of O2-, we studied the effect of PC-SOD on Forssman antiserum-induced respiratory resistance. Unmodified SOD was ineffective at the doses of 1,000 to 30,000 U/kg, whereas PC-SOD showed a dose-dependent inhibitory effect over the range of 10 to 1,000 U/kg. The ED50 of PC4-SOD and PC10-SOD were 140 and 240 U/kg, respectively, at 30 min after the challenge with Forssman antiserum. These findings suggest that the pharmacological potency of PC-SOD is over 200 times more than that of unmodified SOD, and that PC-SOD may have the potential for various clinical applications.

Airway Resistance↗
PubMed1991

Intrapericardial OK-432 instillation for the management of malignant pericardial effusion.

Ten patients with malignant pericardial effusion were treated with intrapericardial injection of OK-432 (penicillin-treated and heat-treated lyophilized powder of the substrain of Streptococcus pyogenes A3). After intrapericardial insertion of a catheter, a maximal volume of pericardial fluid was withdrawn with cytologic confirmation of malignancy. Five or 10 Klinische Einheit (KE) (KE is a unit used to express the strength of a preparation) of OK-432 diluted in 20 ml of saline was injected into the pericardial space in seven and three patients, respectively. It was repeated in case of reaccumulation. Seven patients were treated only once and the remaining three required a second treatment. Complete control of pericardial effusion was achieved in all patients for an average of 329 days (range, 54 to 790 days). Fever and chest pain were experienced in six and five patients, respectively, but were controlled with antipyretics. Two of three patients who received 10 KE of OK-432 experienced hypotension that was successfully controlled with vasopressor drugs with or without reaspiration of pericardial fluid. Rapid reactive reaccumulation of the pericardial fluid was thought to be a cause of hypotension. A follow-up computed tomography (CT) scan was performed in seven patients and a thickened pericardium was noticed in five; no patients had constrictive pericarditis. These results suggest that intrapericardial administration of 5 KE of OK-432 is an effective and safe treatment for malignant pericardial effusion.

Adult↗
PubMed1990

[Atrial septal defect with idiopathic thrombocytopenic purpura: a case of open-heart surgery].

A 40-year-old woman of atrial septal defect associated with idiopathic thrombocytopenic purpura (ITP) was successfully operated upon under cardio-pulmonary bypass. Steroids had been given preoperatively, resulting in an increase of the platelet count from 0.7 X 10(4)/mm3 to 20.6 X 10(4)/mm3. Steroids could be withdrawn before the operation. No bleeding tendency was encountered during and after surgery. This is the 6th case of open-heart surgery associated with ITP in the literature.

Adult↗
PubMed1988

In vitro effect of trichosanic acid, a major component of Trichosanthes japonica on platelet aggregation and arachidonic acid metabolism in human platelets.

The in vitro effect of trichosanic acid (TCA; C18:3, omega-5), a major component of Trichosanthes japonica, on platelet aggregation and arachidonic acid (AA) metabolism in human platelets was studied. TCA dose-dependently suppressed platelet aggregation of platelet rich plasma and washed platelets. TCA decreased collagen (50 micrograms/ml)-stimulated production of thromboxane B2 (TXB2) and 12-hydroxyhepta-decatrienoic acid (HHT) in a dose-dependent manner, while that of 12-hydroxyeicosatetraenoic acid (12-HETE) was rather enhanced. The conversion of exogenously added [14C]AA to [14C]TXB2 and [14C]HHT in washed platelets was dose-dependently reduced by the addition of TCA, while that to [14C]12-HETE was increased. Similar observations were obtained when linolenic acid (LNA; C18:3, omega-3) was used. These results suggest that TCA may decrease TXA2 formation in platelets, probably due to the inhibition of cyclooxygenase pathway, and thereby reduce platelet aggregation.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1987

In vitro effect of cinnamic aldehyde, a main component of Cinnamomi Cortex, on human platelet aggregation and arachidonic acid metabolism.

The in vitro effect of cinnamic aldehyde, a main component of Cinnamomi Cortex, on platelet aggregation and arachidonic acid (AA) metabolism in human platelets was studied. Cinnamic aldehyde reduced platelet aggregation of both platelet rich plasma and washed platelets, dose-dependently. This compound also decreased the formation of the metabolites of AA such as thromboxane B2 (TXB2), 12-hydroxy heptadecatrienoic acid and 12-hydroxyeicosatetraenoic acid in collagen-stimulated washed platelets. The conversion of exogenous [14C]AA to cyclooxygenase metabolites or 12-lipoxygenase metabolite was not altered significantly by the addition of cinnamic aldehyde. On the other hand, collagen-induced release of [14C]AA and its metabolites from washed platelets prelabeled with [14C]AA was markedly reduced by the addition of cinnamic aldehyde. These results suggested that cinnamic aldehyde suppressed the release of AA from platelet membrane phospholipids and then reduced the formation of thromboxane A2. This inhibitory effect of cinnamic aldehyde on AA release and TXB2 formation may contribute to reduced platelet aggregation.

Acrolein↗