Biomedical subjects

M Takei

Publications and source records attributed to M Takei.

At least 37 records · Page 2Linked to original sources

PubMed2000

In vitro antimicrobial activity of gatifloxacin against 873 clinical isolates from respiratory tract, urinary tract and surgical infections during 1997-1998 in Japan.

The in vitro activity of gatifloxacin was determined for 873 isolates from various infections during 1997-1998 in Japan. Gatifloxacin was active against streptococci, Escherichia coli, Klebsiella pneumoniae, Moraxella catarrhalis, Haemophilus influenzae and Neisseria gonorrhoeae, with MIC(90)s of </=0.39 mg/L. The activity was two- to 32-fold greater than that of ciprofloxacin and levofloxacin against Gram-positive bacteria, and comparable to that against Gram-negative bacteria. Gatifloxacin was more active than the other quinolones against quinolone-resistant staphylococci, Enterococcus faecalis, E. coli and Enterobacter cloacae. It also had good activity against penicillin- or macrolide-resistant Streptococcus pneumoniae and ampicillin-resistant H. influenzae.

Anti-Bacterial Agents↗

PubMed2000

A case of primary cardiac B cell lymphoma associated with ventricular tachycardia, successfully treated with systemic chemotherapy and radiotherapy: a long-term survival case.

We experienced a long-term survival case of primary cardiac lymphoma (PCL) demonstrating ventricular tachycardia (VT) as an initial sign, which was related to localized myocardial damage by lymphoma cells. A 70-year-old woman with sustained VT was admitted to the Kofu Municipal Hospital. VT ceased with the administration of disopyramide intravenously. The origin of the VT was the free wall of the right ventricular outflow tract (RVOT) as observed by electrocardiography on admission. A solitary mass in the free wall of the RVOT was found by echocardiography, chest computed tomographic scanning and magnetic resonance imaging. There was no evidence of extracardiac involvement. The patient was histologically diagnosed as PCL by endomyocardial biopsy. Chemotherapy started immediately after the diagnosis and the mass showed a marked reduction in size. After 8 cycles of chemotherapy, radiotherapy was performed. Pericardial thickness in the free wall of the RVOT developed without severe side effects. Complete remission has been maintained for 30 months after the initial diagnosis, and no recurrence and arrhythmias have been detected during the follow-up period. It was demonstrated that rapid diagnosis and chemotherapy followed by radiotherapy for PCL achieved better survival.

Aged↗

PubMed1999

Dual-acting agents with alpha1-adrenoceptor antagonistic and steroid 5alpha-reductase inhibitory activities. Synthesis and evaluation of arylpiperazine derivatives.

A series of arylpiperazine derivatives were prepared and evaluated for their alpha1-adrenoceptor antagonistic activities and 5alpha-reductase inhibitory activities. SAR study led to the identification of the potent dual-acting compound 2f, which had a pA2 value of 7.5 for alpha1-adrenoceptor antagonism and an IC50 value of 1.5 nM for 5alpha-reductase inhibition.

Adrenergic alpha-Antagonists↗

PubMed1999

S1319: a novel beta2-andrenoceptor agonist from a marine sponge Dysidea sp.

In the course of screening of potential leads for beta2-receptor agonists, we found a novel beta2-adrenoceptor selective agonist, S1319, from a marine sponge Dysidea sp. The active compound was isolated and structurally characterized as 4-hydroxy-7-[1-(1-hydroxy-2-methylamino)ethyl]-1,3-benzothiazole-2(3H)-o ne, a new member of the beta2-adrenoceptor agonist. This is the first example of a sponge-derived beta2-adrenoceptor agonist.

Adrenergic beta-2 Receptor Agonists↗

PubMed1999

Z-350, a new chimera compound possessing alpha1-adrenoceptor antagonistic and steroid 5alpha-reductase inhibitory actions.

The effects of Z-350, (S)-4-[3-(4-{1-(4-methyl-phenyl)-3-[4-(2-methoxyphenyl)piperazine-1-yl]propoxy} benzoyl)indole-1-yl]butyric acid hydrochloride, a newly synthesized compound possessing alpha-adrenoceptor antagonistic and steroid 5alpha-reductase inhibitory actions, were studied in vitro. In functional experiments, Z-350 shifted the concentration/response curve for the phenylephrine-induced contraction of rabbit prostate, urethra and aorta to the right with pA2 values of 8.04, 7.57 and 7.13, respectively. The binding affinity of Z-350 for alpha1-adrenoceptors in rabbit prostate, urethra and aorta were estimated by the displacement of [3H]prazosin. The pKi values for this action of Z-350 were 7.53, 7.95 and 7.62 for the prostate, urethra and aorta, respectively. alpha1-Adrenoceptor subtype selectivities were studied in the submaxillary gland (r(1A) and liver (alpha1B) of rat. Z-350 inhibited the specific binding of [3H]prazosin to alpha1A and (alpha1B-adrenoceptors with pKi values of 7.82 and 7.29, respectively. Z-350 inhibited rat prostatic steroid 5alpha-reductase non-competitively with a pIC50 of 8.42. These results indicate that Z-350 is a alpha1-adrenoceptor antagonist and is a steroid 5alpha-reductase inhibitor. It is expected that Z-350 will be a candidate drug for the treatment of benign prostatic hyperplasia.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1999

Tracheal relaxing effects and beta2 adrenoceptor selectivity of S1319, a novel sponge-derived bronchodilator agent, in isolated guinea-pig tissues.

1. S1319 (4-hydroxy-7-[1-(1-hydroxy-2-methylamino)ethyl]-1, 3-benzothiazol-2(3H)-one acetate), a novel non-catecholamine beta-adrenoceptor agonist, has been compared with isoprenaline, salbutamol and formoterol for activity in vitro on a range of beta-adrenoceptor containing preparations from guinea-pig. 2. S1319, like isoprenaline, salbutamol and formoterol, relaxed preparations of guinea-pig trachea (contracted by histamine) in a concentration-dependent manner. The relaxing activity of S1319 appeared to be more potent than that of isoprenaline and salbutamol, and similar to that of formoterol (pD2 values of 10.58+/-0.03 vs 7. 60+/-0.01, 7.50+/-0.01 and 10.52+/-0.04, respectively), and was blocked by the beta2-adrenoceptor selective antagonist (ICI 118,551). The intrinsic activity of S1319 was close to 1.0. 3. In the beta1-adrenoceptor containing preparations, guinea-pig right and left atria, a monophasic inotropic response of S1319 was observed. The pD2 value of S1319 for left atrial and right atrial inotropism was 6.70+/-0.15 and 7.81+/-0.01, respectively. 4. The selectivity ratio (trachea/left atrial inotropism) of S1319, formoterol, salbutamol and isoprenaline was 8523, 284, 4.8 and 0.45, respectively. The relative selectivity ratio of S1319 was 18743, 1858 and 30 times greater than that of isoprenaline, salbutamol and formoterol, respectively. 5. Relaxant responses of guinea-pig trachea to S1319 declined rapidly when the agonist was washed from the tissues, with complete recovery within 30 min. The duration of action of S1319 was similar to that of isoprenaline and less than that of salbutamol and formoterol. 6. In summary, S1319, a sponge-derived beta-adrenoceptor agonist, is a potent and selective beta2-adrenoceptor agonist with a short-duration of action in isolated guinea-pig tracheas.

Adrenergic beta-Agonists↗

PubMed1999

The autonomic control of the transmural dispersion of ventricular repolarization in anesthetized dogs.

INTRODUCTION: The initiation of ventricular arrhythmias is in part associated with autonomic nervous tone. We investigated the effects of sympathetic and parasympathetic stimulation on the monophasic action potentials (MAPs) of the epicardium (EPi), mid-myocardial (M) region, and endocardium (Endo) in vivo. METHODS AND RESULTS: In 12 mongrel open chest anesthetized dogs, both sides of the cervical vagus nerves and stellate ganglia were crushed with a tight ligature. Right atrial pacing at 600 msec cycle length was begun after the sinus nodal area had been crushed. MAPs from the M region were measured by two needle electrodes that were supported by a W-shaped plastic frame. The epicardial, M region, and endocardial MAP durations at 90% repolarization (MAPD90) were 287+/-7, 315+/-7, and 290+/-8 msec, respectively. The MAPD90 from M cells was longer than that from Epi or Endo. Sympathetic stimulation shortened MAPD90 more in the M region (53+/-4 msec) than that in the Epi (27+/-3 msec) or Endo (26+/-4 msec). The transmural dispersion of repolarization during sympathetic stimulation was shorter than that of the control. Parasympathetic stimulation did not significantly affect any of the MAPD90 values. Simultaneous sympathetic and parasympathetic stimulation produced changes not significantly to those produced by sympathetic stimulation alone. CONCLUSION: Our results suggest that sympathetic activity can reduce transmural dispersion of repolarization under autonomic control in the canine heart under baseline conditions.

Action Potentials↗

PubMed1999

Effect of interleukin-3, interleukin 5 and hyaluronic acid on cultured eosinophils derived from human umbilical cord blood mononuclear cells.

BACKGROUND: Several studies have shown that cultured eosinophils can be generated from human umbilical cord blood mononuclear cells (UCMC) in the presence of interleukin (IL)-3 and IL-5 in vitro. Other reports have indicated that cellular adhesion to hyaluronic acid (HA) enhances the proliferation of cultured eosinophils derived from CD34+ cells purified from UCMC. The aim of this study was to obtain large numbers of mature eosinophils from UCMC using IL-3, IL-5 and HA, and to investigate their functions. METHODS: We examined several combinations of IL-3 and IL-5 and their effect on eosinophil development from UCMC in HA-coated on non-coated flasks. We also examined whether cultured eosinophils degranulated eosinophil-derived neurotoxin (EDN) induced by secretory immunoglobulin A conjugated to sepharose beads (sIgA-beads) and responded to eotaxin. RESULTS: Culture with HA-coated flasks for 35 days (in the presence of IL-3 and IL-5, with IL-3 omitted after day 14 of culture) caused a 11.2-fold augmentation in the proliferation of UCMC. On day 35 of the culture, 98% of cultured cells were eosinophils judging from May-Grünwald and Giemsa staining and transmission electron micrographs. The EDN content of the cultured eosinophils on day 35 was 156 ng/105 cells. Cultured eosinophils degranulated EDN induced by sIgA-beads and responded to eotaxin by chemotaxis and intracellular Ca2+ mobilization. CONCLUSION: We found a useful culture system to obtain large numbers of eosinophils derived from UCMC, which may facilitate the investigation of eosinophil function, since there was no significant difference in response to sIgA-beads and eotaxin between cultured and peripheral eosinophils.

Cell Degranulation↗

PubMed1999

Z-335, a thromboxane A2 receptor antagonist, suppresses the progression of arachidonic acid-induced hind limb gangrene in rats.

We have developed a new rat model of gangrenous peripheral vascular disease with vascular injury and occlusive thrombi. Rat hind limb gangrene was induced by injecting arachidonic acid (2 mg/leg) into the femoral artery. Using this model, we evaluated the effect of a thromboxane A2 receptor antagonist, Z-335, on the progression of hind limb gangrene. Z-335 (10 mg/kg/d, p.o.) ameliorated arachidonic acid-induced hind limb gangrene. In contrast, daltroban (10 mg/kg/d, p.o.) and cilostazol (100 mg/kg/d, p.o.) tended to improve the hind limb gangrene but their effects failed to reach statistical significance. Z-335 (10 mg/kg, p.o.) inhibited U-46619-induced, but not collagen-induced, platelet aggregation in rat whole blood. Daltroban (10 mg/kg, p.o.) showed a tendency to inhibit U-46619-induced platelet aggregation. Cilostazol (100 mg/kg, p.o.) did not inhibit U-46619- or collagen-induced platelet aggregation. Histopathological examination of the injured paws showed that Z-355 (10 mg/kg, p.o.) had partly inhibited the formation of occlusive thrombi. These results indicate that the thromboxane A2 receptor antagonist Z-335 is effective against arachidonic acid-induced hind limb gangrene in rats. Our experiments suggest that Z-335 may be beneficial in the prevention of gangrenous peripheral vascular disease.

Animals↗

PubMed1999

Arachidonic acid-induced hind limb gangrene: a new experimental rat model of peripheral vascular disease.

The purpose of this study was to investigate the characteristics of arachidonic acid-induced peripheral vascular disease in rats. Injecting arachidonic acid (2 mg/leg) into the femoral artery caused hind limb gangrene. Histopathological examination revealed occlusive thrombi and marked vascular injury, including denudation of the endothelium and degeneration of the media in the paw arteries. Arachidonic acid injection markedly enhanced the platelet response to both U-46619 and collagen. Although the number of circulating platelets did not differ between sham-operation rats and arachidonic acid-injected rats, the numbers of circulating white blood cells and red blood cells were raised 10 d after arachidonic acid injection. Thrombocytopenia, induced before arachidonic acid injection, markedly suppressed arachidonic acid-induced hind limb gangrene in rats. In addition, the combined administration of aspirin (100 mg/kg/d, p.o.) and ticlopidine (300 mg/kg/d, p.o.) prevented the progression of arachidonic acid-induced hind limb gangrene. These results suggest that platelets are involved in the progression of arachidonic acid-induced hind limb gangrene. This experimental rat model may be suitable for developing novel drugs for the treatment of peripheral vascular disease.

Animals↗

PubMed1999

[Effect of liver hydrolysate on hepatic proliferation in regenerating rat liver].

The effect of liver hydrolysate (LH) derived from bovine liver on rat liver regeneration after partial hepatectomy (PH) were investigated. Oral administration of LH increased rat liver weight dose-dependently at 24 h after PH. Hepatic ornithine decarboxylase (ODC) activity and proliferating cell nuclear antigen (PCNA) labeling index were measured in regenerating rat liver as markers of cell proliferation. ODC activities at 4 and 24 h after PH were significantly increased by LH administration. PCNA labeling index at 24 h after PH were also increased by LH administration. These results suggest that LH stimulates liver regeneration in partially hepatectomized rats.

Animals↗

PubMed1999

Evaluation of expression of CD15 and sCD15 in non-small cell lung cancer.

Changes in cell membrane carbohydrate antigens play an important role in metastatic potential associated with carcinogenesis and in prognostic factors. We investigated immunohistochemically the expression of CD15 and sialyl CD15 (sCD15) in lung cancer tissue by using Leu-M1 antibody and MXKM-93 antibody, respectively, and then assessed the relationship between their expression and the patient outcome. Lung cancer tissue expression of CD15 was significantly higher in adenocarcinoma (55.9%) and squamous cell carcinoma (44.7%) than in small cell carcinoma (10%) (p=0.01, p=0.006). Expression of sCD15 was significantly higher in adenocarcinoma (52.9%) than in squamous cell carcinoma (10.5%) or small cell carcinoma (10%) (p<0. 0001, p=0.016). No association was found between CD15 expression and clinical stage, but sCD15 expression increased with clinical stage (stage I+II vs. III+IV: 16.7% vs. 39.6%; p=0.049). Expression of CD15 (1.5%) was significantly lower than expression of sCD15 (12.3%) in normal surrounding tissue. Examination of associations with outcome in NSCLC revealed that expression of sCD15 in resected cases, and expression of CD15 in non-resected cases were significantly correlated with shortening of median survival time (p<0.05). When associations with prognostic factors were assessed by univariate analysis, expression of sCD15 was found to be correlated with distant metastasis, and expression of CD15 with decrease in performance status (PS). In the multivariate analysis by the Cox proportional hazard model, sCD15 and CD15 negativity contributed to longer survival time after PS and clinical stage. The results of a combination assay of CD15 and sCD15 showed that expression of both carbohydrate antigens significantly shortened survival time in both the resected and non-resected group (log-rank test, p<0.05). This combination assay also appeared to be extremely useful in predicting the outcome in all clinical stages of NSCLC.

Adenocarcinoma↗

PubMed1999

Z-350, a novel compound with alpha 1-adrenoceptor antagonistic and steroid 5 alpha-reductase inhibitory actions: pharmacological properties in vivo.

The alpha(1)-adrenoceptor-antagonistic and steroid 5alpha-reductase-inhibitory actions of Z-350 [(S)-4-{3-{4-{1-(4-methylphenyl)-3-[4-(2-methoxyphenyl)piperazine-1-y l]propoxy}benzoyl}indole-1-yl}butyric acid hydrochloride] were investigated in rabbits and rats in vivo. Z-350 (1-30 mg/kg), administered intraduodenally, dose-dependently inhibited phenylephrine-induced increases in prostatic urethral pressure with an ED(50) value of 3.8 mg/kg in anesthetized male rabbits, whereas the effects on mean blood pressure and orthostatic hypotensive response were weaker when compared with other alpha(1)-adrenoceptor antagonists, tamsulosin and prazosin. Z-350 (1-10 mg/kg p.o.) dose-dependently inhibited the prostatic steroid 5alpha-reductase activity in rats with an ED(50) value of 2.8 mg/kg. The daily oral administration of Z-350, at >==10 mg/kg for 7 days, significantly reduced the prostatic growth induced by testosterone in castrated rats, with no effect on dihydrotestosterone-induced prostatic growth. These results indicate that Z-350 exhibited alpha(1)-adrenoceptor-antagonistic and 5alpha-reductase inhibitory actions at almost equal doses in vivo, and was expected to improve the bladder outlet obstruction associated with benign prostatic hyperplasia with smaller cardiovascular adverse effect.

5-alpha Reductase Inhibitors↗

PubMed1998

Antiplatelet effect of Z-335, a new orally active and long-lasting thromboxane receptor antagonist.

We investigated the pharmacological characteristics of Z-335 ((+/-)-sodium[2-[4-(chlorophenylsulfonylaminomethyl)indan-5-yl]ace tate monohydrate), a new indan derivative. Z-335 inhibited the specific binding of [3H]SQ-29548 to human platelets and guinea pig platelet membranes. The IC50 values of Z-335 for human platelets and guinea pig platelet membranes were 29.9 +/- 3.1 nM with a slope of 1.09 +/- 0.05 and 32.5 +/- 1.7 nM with a slope of 1.07 +/- 0.02, respectively. Z-335 inhibited thromboxane A2 receptor-mediated human and guinea pig platelet aggregation in vitro and oral administration of this drug to guinea pigs inhibited U-46619- and collagen-induced platelet aggregation for 24 h. Z-335 dose-dependently prevented the occurrence of U-46619-induced pulmonary thromboembolism in mice and the protective effect of this drug (0.3 and 3 mg/kg, p.o.) lasted for 24 h. These results strongly suggest that Z-335 is a potent, orally active and long-lasting thromboxane A2 receptor antagonist, which may be useful as an antiplatelet drug.

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

PubMed1998

A new thromboxane receptor antagonist, Z-335, ameliorates experimental thrombosis without prolonging the rat tail bleeding time.

We investigated the antithrombotic activity of Z-335, a new thromboxane A2 receptor antagonist, using experimental thrombosis models, and also tested its effect on the rat tail bleeding time. Z-335 (0.1, 0.3, and 1 mg/kg, p.o.) dose-dependently prevented the occurrence of arachidonic acid-induced pulmonary thromboembolism in mice. During photochemically induced thrombosis in the femoral artery of guinea pigs, Z-335 (0.3, 1, and 3 mg/kg, i.v.) dose-dependently prolonged the time required to form thrombi. Moreover, Z-335 (10 mg/kg/day, p.o.) strongly suppressed lauric acid-induced hind limb injury in rats. Z-335 (0.3, 3, 30, and 300 mg/kg, p.o.) did not prolong the tail bleeding time in rats. These results strongly suggest that Z-335 ameliorates experimental thrombosis without prolonging the rat tail bleeding time, and may therefore be a useful antithrombotic drug.

Animals↗

PubMed1998

Inhibitory effect of adenosine on degranulation of human cultured mast cells upon cross-linking of Fc epsilon RI.

Adenosine is a potent bronchoconstricting agent that is released by activated mast cells and hypoxic lung tissue. However, both inhibition and stimulation of mediator release from human lung mast cells by adenosine have been described, and this discrepancy seems to be due to contaminating cells or the effects of enzymatic treatment. We, therefore, investigated the effects of adenosine and its receptor-specific analogues on human cultured mast cells (HCMC). Adenosine inhibited Fc epsilon RI-mediated tryptase release from HCMC in a dose-dependent manner, and this inhibitory effect was completely blocked by the A2a receptor antagonist ZM241385. The specific agonist of A2a adenosine receptors CGS21680 inhibited the release of tryptase more potently than A1 and A3 agonists, and A2a receptor mRNA was detected by RT-PCR, suggesting the involvement of A2a receptors in the inhibitory effects of adenosine. In addition, adenosine increased intracellular cAMP level in a dose-dependent manner and inhibited protein tyrosine phosphorylation including that of ERK-2. These results suggest that adenosine acts via A2 receptors to inhibit Fc epsilon RI-mediated mediator release from human mast cells.

Adenosine↗

PubMed1998

Piglets produced by transfer of vitrified porcine embryos after stepwise dilution of cryoprotectants.

A total of 498 porcine embryos at various stages of development collected from superovulated gilts was used to investigate cryopreservation. First, blastocysts (BL), expanded blastocysts (ExB), and hatched blastocysts (HB) were used to determine the effect of exposure to concentrated solutions of ethylene glycol as cryoprotective additives (CPAs) on embryo survival. Then, survival of other embryos after vitrification by rapid cooling was determined. Based on their development after 48 h in culture, embryos were not injured by being exposed to 2.0 M ethylene glycol (EG) for 15 min or to 2.0 M EG for 5 min and then to a solution of 8.0 M EG in 7% polyvinylpyrrolidone (PVP) for 1 min. The CPAs were removed from the embryos by diluting them with 1.7 M galactose. To vitrify the embryos, they were exposed to 2.0 M EG for 5 min and then were pipetted directly into short columns of 8.0 M EG-PVP contained within (1.25-ml plastic straws and separated from long columns of 1.7 M galactose by an air bubble. The straws were plunged directly into LN2. After the straws were warmed rapidly in a 25 degrees C water bath, the embryos were immediately mixed with galactose within the straws by shaking them vigorously to mix the contents. In sequential experiments, three methods were used to dilute the CPA solutions. Method 1: Embryos in the EG-PVP-galactose mixture were expelled from the straws and rinsed and cultured in modified CZB medium (mCZB). Method II: Embryos in the mixture were placed briefly into 1.5 M EG and then rinsed and cultured in mCZB. Method III: Embryos in the mixture were rinsed in 1.0 M EG and then in 0.5 M EG and finally rinsed with mCZB and cultured. After 48 h in culture, the respective percentages of survival of embryos vitrified as BL, ExB, or HB were: Method I, 21, 32, and 13%; Method II, 9, 40, and 24%; Method III, 35, 85, and 71%. Of 20 additional ExB vitrified embryos diluted by Method III and transferred into a recipient, four developed into live piglets; two other recipients failed to litter although one had been pregnant for 65 days. These results demonstrate that porcine embryos can be successfully cryopreserved by rapid cooling in EG-PVP and by careful dilution of the CPA after warming.

Animals↗

PubMed1998

Successful methotrexate therapy for adult Still's disease with marked thrombocytopenia.

A 34-year-old Japanese woman developed spiking fever, splenomegaly, arthritis, neutrophilia, hyperferritinaemia (22517 ng/ml), elevated C-reactive protein (9.1 mg/ml) and severe thrombocytopenia (1.7 x 10(4)/microl). The patient had depressed antithrombin III activity and abnormally high concentrations of both fibrin degradation products and thrombin-antithrombin complexes. This condition was resistant to high-dose prednisolone therapy (120 mg/day) and non-steroidal anti-inflammatory drugs. We initiated oral methotrexate therapy (7.5 mg/week, orally) with a favourable outcome. The patient's spiking fever subsided on the first day of methotrexate administration. Elevated levels of ferritin and C-reactive protein in the sera rapidly normalised. Methotrexate rapidly improved the disease state which suggested that methotrexate act via modulation of cytokine production or secretion.

Administration, Oral↗