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Biomedical subjects

Y Takeda

Publications and source records attributed to Y Takeda.

At least 613 records · Page 34Linked to original sources
PubMed1994

A novel antitumor antibiotic, KW-2189 is activated by carboxyl esterase and induces DNA strand breaks in human small cell lung cancer cells.

KW-2189 has been selected as a lead compound for clinical trial among duocarmycin derivatives with structural similarity to CC-1065, a cyclopropylpyrroloindole. The purpose of this study was to examine the DNA-binding potency and the mechanisms of cytotoxicity of KW-2189. In order to analyze DNA-binding activity of KW-2189, plasmid pBR322 was treated with KW-2189 with or without pretreatment with carboxyl esterase, which we demonstrated to be an activating enzyme, and the products were examined by agarose gel electrophoresis and restriction enzyme analysis. Cytotoxic activity was examined by exposing a human small cell lung cancer cell line, NCI-H69 to KW-2189 with or without carboxyl esterase. Alkaline elution was performed to examine whether KW-2189 induces DNA strand breaks. DNA treated with KW-2189 and carboxyl esterase migrated faster than KW-2189-treated DNA, which migrated at the same rate as untreated DNA. In addition DNA treated with esterase-activated KW-2189 was protected from digestion by some restriction enzymes. KW-2189 showed concentration- and time-dependent growth inhibitory effect with IC50 values (drug concentration required for 50% growth inhibition) of 58 nM (96 h) to 1900 nM (1 h) in H69 cells. The IC50 values of 4-h exposure of H69 to KW-2189 with 0, 26, 130, 650 mU/ml carboxyl esterase were 460, 120, 30, and 7 nM, respectively. Time-dependent enhancement of cytotoxicity by carboxyl esterase was also observed. KW-2189 induced DNA strand breaks in H69 cells in a concentration-dependent manner around the IC50 value. We conclude that 1) KW-2189 is activated by carboxyl esterase to its active form(s), 2) activated KW-2189 has a stronger DNA-binding activity and cytotoxicity than KW-2189, 3) DNA cleavage is one of the major mechanisms of KW-2189-mediated cytotoxicity.

Antibiotics, Antineoplastic↗
PubMed1994

Production and cross-reactivity patterns of a panel of high affinity monoclonal antibodies to Vibrio cholerae O139 Bengal.

A series of monoclonal antibodies of different isotypes specific for Vibrio cholerae O139, the new pandemic strain of cholera, was produced. These mAbs reacted only with the reference strain (MO45) representing serovar O139 but did not react with any of the other reference strains representing serovars O1 to O140. Significantly, the mAbs did not agglutinate the R-cultures of V. cholerae (CA385, 20-93) which demonstrated the exceptional specificity of these mAbs and indicated that the mAbs recognized antigenic determinants unique for the O139 serovar. There was heterogeneity in the intensity of reactivity of the mAbs with strains of V. cholerae O139 isolated from diverse sources. Apart from 4H6, the other mAbs agglutinated all the O139 strains examined. 2D12 and 2F8 were the best mAbs based on the intensity of agglutination with all the O139 strains. Evaluation of 3A10 in comparison with a polyclonal anti-O139 antibody raised in rabbit using the slide agglutination format revealed that 3A10 fared as well as the polyclonal antibody for the laboratory identification of the O139 serovar. The acquisition of these mAbs provide reagents which would be very useful in the development of simple immunodiagnostic assays for the diagnosis of V. cholerae O139 infections.

Agglutination Tests↗
PubMed1994

So-called "immature dentinoma": a case presentation and histological comparison with ameloblastic fibrodentinoma.

The existence of the "dentinoma" as an independent entity has not been fully accepted, recently being regarded as an ameloblastic fibroma with formation of dentin and named an ameloblastic fibrodentinoma. However, there are histological differences between the several cases reported previously as "immature dentinoma" and the ameloblastic fibrodentinoma. This paper presents a case report of a dentin-forming intraosseous benign tumor without any histological features of ameloblastic fibroma. The patient was a 30-year-old woman with a rather well-circumscribed intraosseous lesion of the mandibular left premolar area. Histologically, the lesion consisted of dentin-like tissue with a tubular structure and globular calcifications, numerous epithelial strands and islands without enamel organ-like structure, and a cellular fibrous component without a primitive dental papilla-like appearance. The present case and a review of the literature suggest that epithelial elements in odontogenic fibroma-like lesions may occasionally have an inductive effect for dentin or dentin-like tissue formation.

Adult↗
PubMed1994

[Serotype and antibiotic susceptibility of isolates from children with group A streptococcal infection; observation for 10 years].

Six hundred and seventy isolates from children with group A streptococcal infections from 1981 through 1990 were typed serologically and their antibiotic susceptibilities were determined. Productivity of streptococcal pyrogenic exotoxins was also investigated in some isolates. Four hundred and seventy-nine strains were isolated from patients with pharyngitis, 133 from those with scarlet fever, 35 from those with suppurative infection and 23 from those with non-suppurative disease. With immediate treatment (antibiotics were started at the same day throat swabs were taken) for 10 days, 5.3% of the patients with pharyngitis including scarlet fever had relapses and 13.4% of those patients had recurrences. Of the episodes of recurrences 15.7% were due to the same M serotype strains. Six patients had two episodes of scarlet fever. M type of isolate was different in the first and the second episode of each patient. Pyrogenic exotoxin type was unprecedented in the second episode of 4 out of 6 patients. M-typable and T-typable rates of isolates were 90.7% and 97.3%, respectively. Coincidence between M and T types was 73.3% (83.0% if including strains with the same and mixed T-type). Prevalent M-serotypes were 12 and 4, but M1, 3, or 28 was the most prevalent type of isolates in certain years. None of the 670 strains was resistant to penicillin G and cephalexin. Resistant rate of isolates to erythromycin and linecomycin was 26.5% in 1981 and 18.4% in 1982. But a marked decrease has noted since 1983 and only one has been resistant since 1986.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1994

Regulation and physiological role of insulin-like-growth-factor-binding protein-1 in human granulosa cells.

The present study was undertaken to elucidate the physiological role and the regulation of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) in human luteinizing granulosa cells. IGFBP-1 abolished IGF-I-stimulated estradiol production by luteinizing granulosa cells in a dose-dependent manner with a 50% inhibitory concentration (IC50) of 0.27 nM. Similarly, IGFBP-1 inhibited 125I-IGF-I binding to granulosa cells. IGFBP-1 was identified by Western immunoblot and specific enzyme immunoassay in the granulosa-cell-conditioned medium after 24 h culture. Immunoreactive IGFBP-1 released into the medium was inhibited by both IGF-I and follicle-stimulating hormone dose-dependently with an IC50 of 0.14 and 0.13 nM, respectively, while human chorionic gonadotropin-stimulated IGFBP-1 release with a 50% effective dose (ED50) of 0.6 nM. These results suggest that IGFBP-1 is involved in follicular development and granulosa cell differentiation in the human ovary and that gonadotropins may influence IGF-I action by modifying IGFBP-1 levels within the ovary.

Binding, Competitive↗
PubMed1994

Gene expression of 11 beta-hydroxysteroid dehydrogenase in the mesenteric arteries of genetically hypertensive rats.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) modulates the access of corticosteroids to their receptors and plays an important role in controlling blood pressure. We determined 11 beta-HSD activity and mRNA levels in the mesenteric arteries of genetically hypertensive rats, the Dahl salt-sensitive hypertensive rat, and compared them with Dahl salt-resistant and Sprague-Dawley rats. 11 beta-HSD activity was expressed as the percent conversion of [3H]corticosterone to [3H]11-dehydrocorticosterone. 11 beta-HSD activity was significantly decreased in the mesenteric arteries of 8-week-old Dahl salt-sensitive hypertensive rats (11.4 +/- 1.4%) compared with Dahl salt-resistant rats (17.4 +/- 1.4%) or Sprague-Dawley rats (18.0 +/- 1.5%) of the same age (P < .05). There were no significant differences in 11 beta-HSD activity between 4-week-old Dahl salt-sensitive hypertensive and Dahl salt-resistant rats of the same age (15.3 +/- 1.3% and 15.1 +/- 1.9%, respectively). The concentration of 11 beta-HSD mRNA in the mesenteric arteries of 8-week-old Dahl salt-sensitive hypertensive rats was significantly lower than in Dahl salt-resistant or Sprague-Dawley rats of the same age (P < .05). There were no significant differences in the concentration of 11 beta-HSD mRNA in the mesenteric arteries of 4-week-old Dahl salt-sensitive hypertensive rats, Dahl salt-resistant rats, and Sprague-Dawley rats. These results indicate that 11 beta-HSD in the vascular wall may play a role in the pathogenesis of hypertension in this rat model.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Synthesis of corticosterone in the vascular wall.

Extra-adrenal steroid 21-hydroxylation and 11 beta-hydroxylation occur in a variety of human tissues. This study was undertaken to determine whether the rat mesenteric artery produces corticosterone and to demonstrate the CYP11B1 mRNA in the vascular tissue. Isolated rat mesenteric arteries were perfused with Krebs-Ringer solution for 4 h. The perfusate was collected and chromatographed in a reverse-phase HPLC system. The fraction corresponding to synthetic corticosterone was collected and analyzed by mass spectrometry. The concentration of corticosterone in the perfusate from the adrenalectomized rats was measured using radioimmunoassay after separation with the HPLC system. The mass spectra of synthetic corticosterone was identical with corticosterone isolated from the perfusate of the rat mesenteric arteries. The radioactive peak of corticosterone was detected in the perfusate after perfusing the mesenteric artery with Krebs-Ringer solution containing [14C]-pregnenolone. The expression of CYP11B1, 11B2, and 11A mRNA was detected in the mesenteric artery using a RT-PCR. The production of corticosterone in the vascular wall was increased in the adrenalectomized rats compared with that of the controls. This study shows that the rat mesenteric artery produces corticosterone, and the corticosterone synthase is existed in the vasculature.

Animals↗
PubMed1994

The enantioselective metabolism of 4-isopropenyltoluene in rabbits.

4-Isopropenyltoluene (8) was administered orally to rabbits and the following four optically active metabolites, 2-(p-tolyl)propanoic acid (10), p-(1-carboxyethyl)benzoic acid (11), 2-hydroxy-2-(p-tolyl)propanoic acid (12), and 2-(p-tolyl)-1,2-propanediol (13) were isolated from urine in addition to an optically inactive metabolite, 4-isopropenylbenzoic acid (9). The enantiomeric ratios of the metabolites 10 and 11 were respectively R/S = 33:67 and 39:61 (S predominance), whereas those of the metabolites 12 and 13 possessing a tertiary hydroxyl group were R/S = 77:23 and 84:16 respectively (R predominance). The presumed metabolic pathways of 8 in rabbits leading to these metabolites are discussed.

Animals↗
PubMed1994

Fungal metabolites. XV. Primary structures of antibiotic peptides, hypelcins B-I, B-II, B-III, B-IV and B-V, from Hypocrea peltata. Application of electrospray mass spectrometry and electrospray mass spectrometry/mass spectrometry.

Hypelcin B is a mixture of antibiotic peptides produced by Hypocrea peltata. Hypelcins B-I, B-II, B-III, B-IV and B-V are components of this mixture purified by reversed-phase high-performance liquid chromatography. The amino acid sequences of these peptides were determined by electrospray mass spectrometry and electrospray mass spectrometry/mass spectrometry. The molecular weights of these peptides were all ca. 2000 and the structures were very similar.

Alamethicin↗
PubMed1994

Novel antitumor sesquiterpenoids in Achillea millefolium.

Three new antitumor sesquiterpenoids, achimillic acids A, B and C, were isolated as methyl esters from Achillea millefolium and their structures were determined spectroscopically. The compounds were found to be active against mouse P-388 leukemia cells in vivo.

Animals↗
PubMed1994

Lipase-catalyzed hydrolysis of some racemic 1-acetoxy-2-arylpropanes.

Racemic 1-acetoxy-2-phenylpropane (12) and 1-acetoxy-2-(2-naphthyl)propane (33) were hydrolyzed with lipase at 35-36 degrees C for 2 and 24 h to give predominantly (S)-2-phenyl-1-propanol (11) and (S)-2-(2-naphthyl)-1-propanol (32), respectively. However, racemic 1-acetoxy-2-(1-naphthyl)propane (25) was recovered intact even when the reaction was carried out for 240 h. On the other hand, the enantioselectivities towards racemic 2-phenyl (16), 2-(p-tolyl) (20), 2-(1-naphthyl) (28), and 2-(2-naphthyl) (36) derivatives of 1-acetoxy-2-propanol were very low.

Hydrolysis↗
PubMed1994

Bending of DNA in solution caused by a protein from Arabidopsis that binds to a TATA element.

The TFIID complex, which is a general transcription factor, helps to activate and regulate the transcription associated with eukaryotic promoters. A TATA element-binding protein (TBP), a central subunit of the TFIID complex, binds to TATA elements. Circular permutation analysis showed that purified recombinant TBP-1 from Arabidopsis (aTBP-1) introduced a bend in DNA around a TATA element in DNA fragments in solution. The bending was a slow process. A bend in DNA caused by a TBP-1 was seen under an electron microscope, as was an aTBP-DNA complex after immunochemical staining.

Arabidopsis↗
PubMed1994

Quantitative measurement of portal blood flow by magnetic resonance phase contrast: comparative study of flow phantom and Doppler ultrasound in vivo.

A non-invasive method for measuring portal blood flow by magnetic resonance (MR) phase contrast was evaluated in a flow phantom and 20 healthy volunteers. In a flow phantom study, the flow volumes and mean flow velocities measured by MR phase contrast showed close correlations with those measured by electromagnetic flowmetry. In 20 healthy volunteers, the cross-sectional areas, flow volumes and mean flow velocities measured by MR phase contrast correlated well with those measured by the Doppler ultrasound method. Portal blood flow averaged during the imaging time could be measured under natural breathing conditions by using a large number of acquisitions without the limitations imposed on the Doppler ultrasound method. MR phase contrast is considered to be useful for the non-invasive measurement of portal blood flow.

Adult↗
PubMed1994

Immunosuppressive acidic protein in intraocular fluids.

The levels of immunosuppressive acidic protein (IAP) in the vitreous fluid or the aqueous humor were measured in patients with ocular diseases. Undiluted samples of vitreous humor were obtained during pars plana vitrectomy in patients with uveitis, proliferative diabetic retinopathy, and premacular fibrosis. In patients with intraocular tumors, vitreous samples were aspirated after enucleation. Aqueous humor was aspirated during cataract surgery, and levels of IAP were measured in patients with secondary cataract due to uveitis and senile cataract. Single radial immunodiffusion assay was used to quantify IAP levels. To determine the intraocular synthesis of IAP, we calculated the percentage of IAP in patients with uveitis. Patients with uveitis, tumors, and diabetic retinopathy had significantly higher levels of vitreous IAP than patients with premacular fibrosis. The percentage of vitreous IAP was higher in patients with uveitis than in those with tumors and diabetic retinopathy. Patients with uveitis also had markedly higher aqueous IAP levels than patients with senile cataract. In one patient with Behçet's disease, the IAP level was higher in the active stage than in the inactive stage. Our results suggest that immunosuppressive acidic protein could be produced in the eye and that it might modulate intraocular inflammatory processes.

Aqueous Humor↗
PubMed1994

[Distribution of the 70kD stress protein in corneas with alkali burns].

The immunolocalization of 70kD stress-protein (SP 70) was investigated in white rabbit corneas with alkali burns. Corneal alkali burn injuries were induced with 6 mm circular filter paper discs soaked in 1N NaOH. Corneas of 1, 3, 5, and 7 days after alkali injury were immunostained with mouse monoclonal anti-SP 70 antibody. In the control rabbit cornea, immunostaining for SP 70 was observed in the nuclei of the basal cells and of the wing cells. On day 1 after alkali injury, total epithelial defect was observed. Immunostaining for SP 70 was not seen in corneas with total epithelial defect. Three days after injury, epithelial resurfacing with corneal edema was observed. Basal cells showed immunostaining for SP 70 in their nuclei and cytoplasm. Five days after injury, irregular basal cells and a few wing cells with cytoplasmic processes were recognized. Both cells showed diffuse cytoplasmic and nuclear immunostaining for SP 70. Seven days after injury, the corneal wound was healed, and SP 70 was observed in the nuclei of the epithelial cells again. It appears that SP 70 has a role in corneal epithelial healing after alkali burn injury.

Alkalies↗