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Biomedical subjects

M Takei

Publications and source records attributed to M Takei.

At least 19 recordsLinked to original sources
PubMed2001

Sensitive measurement of positron emitters eluted from HPLC.

For sensitive analysis of the radioactive-metabolite in human PET, a radio-HPLC system coupled to a newly designed positron detector was constructed. The detector had the advantages of low noise level (1.7 +/- 1.0 cpm) and high sensitivity (32 +/- 1%) due to coincidence counting and large BGO crystals. Furthermore, the detector was easy to move, since a pair of the BGO housings coupled to photomultipliers was effectively arranged in parallel and a HPLC cell with different volume could be inserted between the BGO housing. This radio-HPLC system was useful for analyzing samples with low radioactivity. It was applied to the measurement of [11C]FLB457 in plasma, having high affinity and high selectivity with dopamine D2 receptors. Extremely low radioactivity of [11C]FLB457 (2500 dpm) could be analyzed by using the radio-HPLC system. The performance of this detector was compared with those of commercially available systems that had been used as sensitive detectors for HPLC.

Animals↗
PubMed2001

Decreased expression of signaling lymphocytic-activation molecule-associated protein (SAP) transcripts in T cells from patients with rheumatoid arthritis.

The function of Epstein-Barr virus (EBV)-specific cytotoxic T cells is disturbed in rheumatoid arthritis (RA) patients but the mechanism for this disturbance has remained unknown. In a recent study searching for the causative gene of X-linked lymphoproliferative syndrome, the gene possibly linked to EBV-specific cytotoxic T cells or NK cell-mediated cytotoxic activity to EBV-infected cells was discovered, and its product is now referred to as signaling lymphocytic-activation molecule-associated protein (SAP) or Src homology 2 domain-containing protein (SH2D1A). In the present study, we attempted to investigate the involvement of the SAP gene in RA using a quantitative real-time PCR; the expression level of SAP transcripts in peripheral leukocytes or T cells was examined for patients with RA. The expression level of SAP transcripts in peripheral leukocytes of 21 RA patients was significantly lower than that of 13 normal individuals (P = 0.0007), four patients with palindromic RA, 11 with inactive systemic lupus erythematosus (SLE) or 17 with chronic renal diseases. The decreased expression of SAP transcripts in RA patients was also observed in peripheral CD2(+) T cells compared with normal individuals. There was no mutation in the coding region of SAP cDNAs derived from peripheral leukocytes of five RA patients. The decreased expression of SAP transcripts in peripheral leukocytes or T cells of RA patients might lead to the failure of the immune system to eliminate the EBV-infected synovial lining cells in joints of RA patients. Our findings have suggested that decreased expression of the SAP gene might be involved in the onset or progress of RA.

Antigens, CD↗
PubMed2001

Contributions of the 8-methoxy group of gatifloxacin to resistance selectivity, target preference, and antibacterial activity against Streptococcus pneumoniae.

Gatifloxacin (8-methoxy, 7-piperazinyl-3'-methyl) at the MIC selected mutant strains that possessed gyrA mutations at a low frequency (3.7 x 10(-9)) from wild-type strain Streptococcus pneumoniae IID553. AM-1147 (8-methoxy, 7-piperazinyl-3'-H) at the MIC or higher concentrations selected no mutant strains. On the other hand, the respective 8-H counterparts of these two compounds, AM-1121 (8-H, 7-piperazinyl-3'-methyl) and ciprofloxacin (8-H, 7-piperazinyl-3'-H), at one and two times the MIC selected mutant strains that possessed parC mutations at a high frequency (>2.4 x 10(-6)). The MIC of AM-1147 increased for the gyrA mutant strains but not for the parC mutant strains compared with that for the wild-type strain. These results suggest that fluoroquinolones that harbor 8-methoxy groups select mutant strains less frequently and prefer DNA gyrase, as distinct from their 8-H counterparts. The in vitro activities of gatifloxacin and AM-1147 are twofold higher against the wild-type strain, eight- and twofold higher against the first-step parC and gyrA mutant strains, respectively, and two- to eightfold higher against the second-step gyrA and parC double mutant strains than those of their 8-H counterparts. These results indicate that the 8-methoxy group contributes to enhancement of antibacterial activity against target-altered mutant strains as well as the wild-type strain. It is hypothesized that the 8-methoxy group of gatifloxacin increases the level of target inhibition, especially against DNA gyrase, so that it is nearly the same as that for topoisomerase IV inhibition in the bacterial cell, leading to potent antibacterial activity and a low level of resistance selectivity.

Anti-Infective Agents↗
PubMed2001

Hormonal effects of Z-350, possessing steroid 5alpha-reductase inhibitory and alpha1-adrenoceptor antagonistic actions, in the rat.

We examined the hormonal effects of Z-350, (S)-4-[3-(4-[1-(4-methylphenyl)-3-[4-(2-methoxyphenyl)piperazine-1-yl]propoxy]benzoyl)indole-1-yl]butyric acid hydrochloride, which has both alpha1-adrenoceptor blocking activity and steroid 5alpha-reductase inhibitory activity, in male and female rats. Z-350 administered orally for 14 days at a dose of 30 mg/kg to normal male rats significantly reduced the weight of the prostate and seminal vesicles without affecting the weight of the testis, epididymis, adrenals, kidney or liver. Prostatic levels of dihydrotestosterone decreased dose-dependently, with a slight increase in the level of testosterone at a Z-350 dose of 100 mg/kg. We observed no effects on the weight of the prostate in castrated rats or on the weight of the uterus in normal or 17beta-estradiol-treated female rats. These results suggest that Z-350 inhibits prostatic growth via inhibition of steroid 5-reductase without other hormonal effects.

5-alpha Reductase Inhibitors↗
PubMed2001

[Whole blood flow cytometry for detection of activated platelets. I. Platelet identification, blood collection and storage].

In order to assess platelet activation by flow cytometry and activation-dependent monoclonal antibodies, a minute volume(2.5 microliters) of citrated whole blood was mixed for 15 minutes with a cocktail of monoclonal antibodies(MoAb), including PAC1, (a MoAb specific for fibrinogen receptors), and a MoAb against CD62P, (an alpha-granule membrane protein which associates with platelet surface membranes when platelets are activated). After fixation with 1% formaldehyde, the percentage of platelets positive for PAC1 and/or MoAb-CD62P was measured by flow cytometry. Even in resting platelets without stimulation, about 15% of platelets were found to be PAC1-positive and 0.6% of platelets were CD62P-positive. If there was a one-minute delay after needle puncture and before blood collection, the number of PAC1-positive platelets was increased compared to that of blood obtained immediately after puncture. If blood was allowed to stand at room temperature, there was a gradual increase in the number of PAC1-positive platelets, and after 60 minutes, this increase became statistically significant. The addition of Iloprost, (a prostacyclin analogue), immediately after venipuncture did not completely prevent the increase in PAC1-positive platelets after 60 minutes. If the inhibitor was added after first incubating for 60 minutes, however, the percentage of PAC1-positive platelets was reduced to preincubation value. Although flow cytometry is a simple and powerful tool to assess platelet activation, there remain several methodological problems to be resolved before this method may be employed in routine clinical use.

Adult↗
PubMed2000

The effects of S1319, a novel marine sponge-derived beta2-adrenoceptor agonist, on IgE-mediated activation of human cultured mast cells.

OBJECTIVE: This study aimed to evaluate the ability of S1319 (4-hydroxy-7-[1-(1-hydroxy-2-methylamino) ethyl]-1,3-benzothiazol-2(3H)-one acetate), a novel beta2-adrenoceptor selective agonist derived from marine sponge, to inhibit IgE-mediated activation of human cultured mast cells (HCMC) in vitro. MATERIALS AND METHODS: We examined the effect of S1319 (racemate) on tryptase release and tumor necrosis factor-alpha (TNF-alpha) production in HCMC generated from human cord blood cells, after cross-linking of high affinity immunoglobulin E receptors (FcepsilonRI), compared with those of the nonselective beta-adrenoceptor agonist, isoproterenol (R-isomer), the selective beta2-adrenoceptor agonist, salbutamol (racemate), and the selective and long-acting beta2-adrenoceptor agonist, formoterol (racemate). We also evaluated the effect of S1319 on the intracellular cAMP level, inositol phosphate production and protein tyrosine phosphorylation in HCMC. RESULTS: S1319 and beta-adrenoceptor agonists inhibited the IgE-mediated release of tryptase. Approximate IC50 values of S1319, formoterol, isoproterenol and albuterol for the inhibition of tryptase release were 0.51+/-0.12, 0.15+/-0.1, 0.80+/-0.09, and 28+/-32.4 nM, respectively. S1319 and beta-adrenoceptor agonists also inhibited TNF-alpha production by HCMC in a concentration-dependent manner. Approximate IC50 values of S1319, formoterol and isoproterenol for the inhibition of TNF-alpha production were 0.19+/-0.03, 0.28+/-0.02 and 0.32+/-0.03 nM, respectively. S1319 caused a concentration-dependent increase in total cell cyclic AMP levels in HCMC. On the other hand, S1319 inhibited the accumulation of inositol 1,4,5-triphosphate and IgE-mediated protein tyrosine phosphorylation of 42-kDa protein, p42 mitogen activated protein (MAP) kinase (ERK-2). CONCLUSION: These results indicate that S 1319 and beta-adrenoceptor agonists are potent inhibitors of the IgE-mediated release of mediators from HCMC.

Adrenergic beta-Agonists↗
PubMed2000

Familial amyloidotic polyneuropathy (ATTR Ser50Ile): the first autopsy case report.

We report an autopsy case of a pedigree of familial amyloidotic polyneuropathy (FAP) with a mutation of isoleucine-50 transthyretin (ATTR Ser50Ile). A 47-year-old man started developing severe diarrhea and weight loss at age 41 years, followed by urinary incontinence, autonomic-nervous-system abnormalities and serious heart failure; the diagnosis of FAP (ATTR Ser50Ile) was made on the basis of genetic, histochemical and immunohistochemical analysis. Six years after the initial symptoms, he died of septic shock. Autopsy revealed suppurative peritonitis, perforation of the sigmoid colon and marked systemic amyloid deposition. The total amount of amyloid deposited in the heart was greatly increased and was much lower in the thyroid gland and kidneys compared with amyloid deposits in ordinary FAP (ATTR Val30Met). Amyloid deposition in peripheral vessel walls was prominent, particularly in lymphatics and veins. His elder sister, 54 years old, started to develop orthostatic hypotension at age 49 years, followed by dysesthesia, diarrhea and severe congestive heart failure. Endomyocardial biopsy revealed severe TTR-amyloid deposition; ultrastructural examination demonstrated that amyloid fibrils were deposited disproportionately and extended radially around microvessels.

Aged↗
PubMed2000

Genetic linkage of Kozak sequence polymorphism of the platelet glycoprotein Ib alpha with human platelet antigen-2 and variable number of tandem repeats polymorphism, and its relationship with coronary artery disease.

The -5 C/T polymorphism of platelet glycoprotein (GP) Ib alpha is a major determinant of the level of GP Ib/V/IX complex surface expression. We investigated the frequency of this polymorphism among Asian populations. The gene frequencies of cytosine (C) in this polymorphism were 0.283 and 0.219 in Japanese and Korean populations respectively. The C allele is linked with human platelet antigen (HPA)-2a and smaller types of variable number of tandem repeats (VNTR). A novel allele, C-HPA-2a-D of VNTR, was found. No association was observed between these alleles and coronary artery disease in this case-control study. The clinical relevance of this polymorphism in the thrombotic status remains undetermined.

Adult↗
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↗