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Biomedical subjects

M Otsuka

Publications and source records attributed to M Otsuka.

At least 163 records · Page 9Linked to original sources
PubMed1997

Oestradiol release from self-setting apatitic bone cement responsive to plasma-calcium level in ovariectomized rats, and its physicochemical mechanism.

The effect of plasma calcium levels on the release of oestradiol from a self-setting apatite bone cement containing 0.5% oestradiol was investigated in ovariectomized rats. The profiles of in-vitro release from the cements in simulated body fluid containing 0, 5 or 10 mg calcium per 100 mL indicated that the rate of release of oestradiol decreased with increasing calcium concentration in the dissolution media. After subcutaneous implantation of oestradiol-loaded cement in healthy and vitamin D-deficient rats, oestradiol release in diseased rats with low plasma calcium levels was significantly higher than that in healthy rats. These results suggest that in-vitro release of oestradiol from apatite bone cement was dependent on the calcium concentration in the buffer and that the in-vivo release of oestradiol from apatite bone cement was dependent on plasma calcium levels.

Animals↗
PubMed1997

A case of rest angina due to microvascular spasm.

A 66-year-old woman underwent elective cardiac catheterization for investigation of periodic attacks of chest pain at rest. During the examination, a chest pain attack occurred unexpectedly, resulting in ST elevation in the precordial leads on electrocardiography. Immediate coronary arteriography demonstrated no organic stenosis but markedly delayed contrast medium perfusion in the mild to distal portion of the left anterior descending artery. These phenomena spontaneously disappeared about 3 min later, and the patient was diagnosed as having angina pectoris due to microvascular spasm. The demonstration of angina pectoris due to microvascular spasm by coronary arteriography during a spontaneous attack is very rare.

Aged↗
PubMed1997

A repeated-dose dermal toxicity study of hydrophobically modified hydroxypropyl methylcellulose in rats.

A six-month repeated-dose dermal toxicity study followed by a 30-day recovery test of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC), a new cellulose derivative used as a thickener for topical pharmaceuticals, was conducted using rats. Aqueous paste of HM-HPMC was applied to the skin of rats once daily at dose levels up to 60 mg/kg/day, which was the highest dose that could be administered. Items checked included general signs, urinalysis, hematology, ophthalmology, and histopathology. One rat died during the administration period owing to a malignant tumor in the hemopoietic system, which was not attributed to the test substance. Statistically significant differences were found in some test results, but those were not dose-dependent and were considered to be incidental or spontaneous. It was concluded that the test substance was not toxic upon chronic dermal administration at dose levels up to 60 mg/kg/day.

Administration, Cutaneous↗
PubMed1997

[Mutagenicity studies of (+/-)-4-diethylamino-1,1,-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a novel drug for urinary frequency and incontinence].

The mutagenicity of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was investigated by the reverse mutation test in bacteria, the chromosome aberration test in vitro, and the micronucleus test in mice. The reverse mutation test was performed at a dose from 31.3 to 4000 micrograms/plate, at which dose cell killing was observed, using Salmonella typhimurium TA100, TA1535, TA98, and TA1537, and Escherichia coli WP2uvrA. NS-21 did not increase revertant colonies significantly in any of the test strains with or without metabolic activation system (S9 mix). The chromosome aberration test was carried out at a dose from 3.75 to 140 micrograms/ml, at which dose more than 50% cell proliferation was inhibited, using cultured Chinese hamster lung cells (CHL/IU). No significant increases of the frequencies of cells with chromosome aberrations were observed with or without S9 mix. The micronucleus test was conducted in the bone marrow cells of Slc : ddY male mice. Mice were given NS-21 by a single oral administration at doses of 0, 43.8, 87.5, 175, and 350 mg/kg, the geometric mean dose between the maximum tolerated dose and the minimum lethal dose. There were no significant increases in the frequencies of micronucleated polychromatic erythrocytes at any dose levels. These results show that NS-21 has no mutagenic activity in vitro or in vivo.

Animals↗
PubMed1997

Torsades de pointes complicating pentamidine therapy of Pneumocystis carinii pneumonia in acute myelogenous leukemia.

Pentamidine isethionate induced torsades de pointes in a 33-year-old woman with acute myelogenous leukemia. This is the first report of Pentamidine-induced torsades de pointes in Japan for over ten years. On the 4th day of intravenous pentamidine for Pneumocystis carinii pneumonia, asymptomatic sinus bradycardia was noted with QT interval prolongation, and torsades de pointes were revealed on the 8th day. Although torsades de pointes was dissolved with discontinuation of the intravenous pentamidine and administration of magnesium sulfate, sinus bradycardia and prolonged QT interval persisted. Ventricular pacing resulted in no arrhythmia and normalization of the QT interval on the 10th day after discontinuation of pentamidine. Careful monitoring of the electrocardiogram should be carried out during intravenous pentamidine therapy.

Adult↗
PubMed1997

[Apolipoprotein E epsilon 4 allel frequencies, plasma alpha 2-macroglobulin and plasminogen activator inhibitor 1 levels in residents of a rural area in Gunma prefecture].

The apolipoprotein E4 (apoE4) epsilon 4 allele is a major riks factor for Alzheimer's disease. However, epsilon 4 is neither a necessary nor a sufficient condition for the development of this disease, and many cognitively healthy elderly people carry the epsilon 4 allele. To look for age-dependent changes in epsilon 4 allele frequencies in the general population, we measured the frequencies in 141 normal healthy residents of a mountainous rural area in north-west Gunma prefecture. Levels of cholesterols in plasma were measured and their relation to apoE genotypes was studied. We also measured the levels of alpha 2-macroglobulin (alpha 2M) and plasminogen activator inhibitor 1 (PAI-1) in blood, and studied their relation to apoE genotypes. Because low-density lipoprotein receptor-related protein (LRP) binds apoE, alpha 2M, and PAI-1, it is of interest to see whether the alpha 2M and PAI-1 concentrations in blood differ between epsilon 4 carriers and non-carriers. ApoE allele frequencies were 0.05, 0.84, and 0.11 for epsilon 2, epsilon 3, and epsilon 4, respectively. In both men and women, the frequency of epsilon 4 was lowest among those in the seventh decade of life. The frequency of epsilon 4 among octagenarians was high (0.17). Serum levels of total cholesterol and low-density lipoprotein cholesterol did not differ significantly between epsilon 4 carriers and non-carriers. The alpha 2M level in serum was higher in women than in men and was higher in older subjects than in younger subjects. Plasma PAI-1 levels were significantly higher in men than in women (Student's t-test, p = 0.0197). Neither alpha 2M levels nor PAI-1 levels differed between epsilon 4 carriers and non-carriers, which suggests that the levels of these two proteins in blood do not reflect the status of LRP in individuals with various apoE genotypes. Studies that include data on life style and diet are necessary before we can conclude that rural life contributes to longevity in epsilon 4 carriers.

Adult↗
PubMed1997

Effect of high concentration of ascorbate on catalase activity in cultured cells and tissues of guinea pigs.

This study showed that the inhibition of cell growth in 3T6, induced by the supplementation of ascorbate at 0.5 mM in cultured medium, was prevented by the addition of catalase in the range of 25-750 units/mL regardless of the degree of activity. However, cytotoxicity induced by concentrations of more than 2 mM ascorbate could not be prevented even when a high level of catalase (5,000 units/mL) was added to the medium. Catalase activity in medium supplemented with ascorbate decreased with incubation time; the higher the concentration of ascorbate, the greater the decrease in catalase activity. These results indicate that even though catalase is present at a high concentration in the medium, it cannot prevent cytotoxicity by a high concentration of ascorbate because the oxygen radical derived from ascorbate inhibits its activity. We therefore investigated whether the inhibition of catalase activity by ascorbate could be observed in animal tissues. The catalase activity in the tissues of guinea pigs 6h after the administration of ascorbate was lower than that in non-administered animals. When guinea pigs were fed diets containing 5 mg or 100 mg ascorbate/animal over a 90 weeks period, a clear affect on catalase activity in the high-dose ascorbate group as compared to that in the low-dose ascorbate group was not observed.

Animals↗
PubMed1997

[Molecular design of apoptosis inducing agents derived from bleomycin].

Reactive oxygen species (ROS) are often involved in the mechanism of apoptosis. Bleomycin consists of an oxygen activating domain and a DNA binding domain, and is an antitumour agent that induces double-strand scission in DNA by oxygen activation. However, bleomycin only weakly induces apoptosis in limited conditions. Previously we have reported efficient oxygen activation by iron complexes of synthetic models of bleomycin namely PYML designed by the direct analogy to the BLM metal core. Recently, novel ligands having symmetrized coordination environment consisting of two histidine units and a pyridine (HPH) were prepared. Oxygen activating efficiency of the iron complexes of the synthetic ligands increased by introducing electron donating substituent into the pyridine ring. HPH compounds have no DNA binding region which is present in bleomycin. HPH compounds but not bleomycin induced apoptosis in mouse leukemia L1210 cells.

Animals↗
PubMed1997

[Successful treatment of subdural hematoma with operation in a patient with acute promyelocytic leukemia].

A 51 year-old male admitted with petechiae and headache. Acute promyelocytic leukemia (APL) with disseminated intravascular coagulation (DIC) was diagnosed. He received all-trans retinoic acid (ATRA) with enocitabine and daunomycin for induction chemotherapy, and supportive therapy for DIC. On 2nd day after admission, subacute subdural hematoma was confirmed with CT scan. He had anisocoria and disturbance of consciousness, and was treated with neurosurgical operation for his life saving on the 3rd day. Although DIC was continued at this time, the operation was done without problem. The recurrence of hematoma has not occurred after the operation. Furthermore, the findings of DIC disappeared by the day 6 following induction therapy. He achieved a complete remission including cytogenetic findings on 35th day after administration of ATRA and received 3 times of combination chemotherapy as consolidation therapy. It may be difficult to do neurosurgical treatment in the setting of DIC. However, we should consider whether the indications for surgery operation according to the condition of each patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Estimation of myocardial viability and clinical significance of reverse redistribution in resting technetium-99m sestamibi myocardial single photon emission computed tomography in patients with acute myocardial infarction].

The clinical significance of reverse redistribution of technetium-99m sestamibi (MIBI) was investigated in 36 patients with acute myocardial infarction and angiographically confirmed single-vessel disease, but without previous infarction using resting MIBI myocardial single photon emission computed tomography (SPECT) and exercise-reinjection thallium-201 (Tl) myocardial SPECT. MIBI myocardial SPECT was performed 90 min and 300 min after injection of MIBI 370 MBq at rest. Four hours after exercise Tl imaging was completed, reinjection imaging was obtained. Wall motion abnormalities on left ventriculograms were analyzed at the onset of infarction and 1 month later. The severity scores on the MIBI early image, MIBI delayed image and Tl reinjection image were 98 +/- 18, 170 +/- 22 and 90 +/- 18, respectively. The reverse redistribution of MIBI was marked in acute infarction. A significant correlation of severity score was found between the MIBI early image and Tl reinjection image (r = 0.89). In 18 patients with significant stenosis of an infarct-related artery, there was a significant correlation between the degree of reverse redistribution and that of Tl redistribution (r = 0.826). A good correlation was found between the severity score on the MIBI early image and wall motion abnormality at 1 month after infarction (r = 0.816). There was a significant correlation between the degree of reverse redistribution and wall motion improvement (r = 0.782). Despite stenosis of the infarct-related artery, the wall motion abnormality was less in 22 patients with marked reverse redistribution (defect score on the MIBI delayed image was double that on the early image) than the other 14 patients. In conclusion, the MIBI early image may reflect myocardial viability and the reverse redistribution of MIBI was observed frequently in patients with acute myocardial infarction. Marked reverse redistribution was observed in patients with preserved left ventricular function. Because of the close correlation of reverse redistribution with Tl redistribution and wall motion improvement, reverse redistribution of MIBI is considered to occur in areas at risk for acute myocardial infarction.

Adult↗
PubMed1997

[A case of rheumatoid pachymeningitis].

Here we present a 53-year-old woman with rheumatoid pachymeningitis. The subject had rheumatoid arthritis (RA) for 15 years. In April, 1996 she began to experience intermittent headaches. In September, her headaches became severe and continuous. In October, she suddenly developed ptosis of the left eye and diplopia. She also started to have dysphagia and she found it increasingly difficult to eat. She was admitted to our hospital on November 1, 1996. Neurological examinations revealed palsies of the left IIIrd, IVth, and VIth, and bilateral IXth, and Xth cranial nerves. Laboratory findings showed leukocytosis, elevated blood sedimentation rate, and positive CRP. Serum RA titer was positive (30x). The cerebrospinal fluid was normal and bacteriological examination was negative. T1-weighted MRI demonstrated hypertrophic cranial dura extending from the falx cerebri to tentorium cerebelli, which was enhanced markedly by Gd-DTPA. The dura adjacent to the cavernous sinus and the clivus were also thickened, which probably caused her cranial polyneuropathies. The dural biopsy showed massive infiltration of the inflammatory cells throughout the dura, proliferation of collagen fibers, and necrotic granuloma with neutrophilic infiltrations. Neither rheumatoid nodules, nor vasculitis were found. Despite the absence of rheumatoid nodules in the dural biopsy, the clinical features, pathologic specimens, and MRI findings of the thickened dura were most consistent with rheumatoid pachymeningitis. Administration of dexamethason ameliorated her headache on the 4th hospital day, and the cranial polyneuropathies completely disappeared on the 35th hospital day. The dural enhancement previously seen on the contrast T1-weighted MRI was diminished. Serum RA titer was also normalized (10x). Rheumatoid pachymeningitis is an extremely rare disease, and only 16 cases were reported in the literatures. Hypertrophic pachymeningitis should be considered as a diagnostic possibility in RA patients who have prolonged headache, and Gd-DTPA MRI is recommended to demonstrate the dural involvement.

Arthritis, Rheumatoid↗
PubMed1997

The in vitro and in vivo indomethacin release from self-setting bioactive glass bone cement.

The in vivo and in vitro drug release profiles from a self-setting bioactive CaO-SiO2-P2O5 glass bone cement containing indomethacin as a model drug were investigated. The cement containing 2% and 5% indomethacin (IMC) powder hardened within 5 min after mixing with ammonium phosphate buffer. After setting, in vitro drug release from drug-loaded cement pellets in a simulated body fluid (SBF) at pH 7.25 and 37 degrees C continued for two weeks. The hardened cement gradually formed low-crystallinity hydroxyapatite during the drug release test in SBF. An IMC-loaded cement device (2% and 5% drug) was implanted in the subcutaneous tissue on the back of rats. The in vivo IMC release from the cement increased and attained maximum levels (Cmax of 2% and 5% drug-loaded cements was 0.27 and 3.37 micrograms/ml, respectively) at Tmax, 3 and 0.5 d, respectively, upon subcutaneous (s.c.) administration in rats. This suggested that the s.c. administration of the cement provided IMC release for a much longer period than s.c. administration of the solution, and the plasma IMC concentration was dependent on the drug concentration in the cement. The plasma IMC concentration and the area under the curve from 2% and 5% IMC-loaded cements in rats were dependent on the concentration of IMC in the cements. The in vivo IMC concentration in plasma obtained by the deconvolution method was much lower than that delivered in SBF in vitro. Scanning electron microscopy and photomicrographs of cross sections showed that the bioactive bone cement had excellent biocompatibility with the surrounding soft tissues.

Animals↗
PubMed1996

Construction and characterization of a recombinant adenovirus vector carrying the human preproinsulin gene under the control of the metallothionein gene promoter.

A new adenovirus vector carrying human-preproinsulin (h-PPI) genomic DNA, which was placed under the control of the mouse metallothionein gene promoter, was constructed. In the recombinant virus-infected cells, h-PPI gene expression increased as a function of ZnSO4 concentration. Reversed-phase high-performance liquid chromatography analysis revealed that the recombinant adenovirus-infected cells secreted immature insulin containing proinsulin and incorrectly processed insulin. Tyrosyl phosphorylation of human insulin receptor substrate 1 occurred when HepG2 cells were treated with the cultured medium, indicating that the h-PPI gene product was functionally active in vitro. We also examined the biological activity of the product using diabetic severe combined immunodeficient mice and confirmed that the h-PPI gene product reduced the blood glucose concentration in vivo. This study suggests that the adenovirus vector can be used to express a foreign gene under the control of an external promoter in various human cells.

Adenoviridae↗
PubMed1996

Fluorescence detection of specific sequence of nucleic acids by oxazole yellow-linked oligonucleotides. Homogeneous quantitative monitoring of in vitro transcription.

We have developed a fluorescent DNA probe, oxazole yellow (YO)-linked oligonucleotide complementary to a target DNA/RNA, which can enhance the fluorescence on hybridizing with a target nucleotide. We demonstrated the applicability of the YO-linked oligonucleotide probe to real-time monitoring of the in vitro transcription process of a plasmid DNA constructed containing the 5'-terminus non-coded region of hepatitis C virus RNA. In the process of in vitro transcription in the presence of YO-linked complementary oligonucleotide, the fluorescence of the reaction mixture showed a time-dependent linear increase corresponding to the generated target RNA product.

Benzoxazoles↗
PubMed1996

Inhibition of adenylyl cyclases by 12(S)-hydroxyeicosatetraenoic acid.

The inhibition of adenylyl cyclase (AC) by a 12-lipoxygenase metabolite of arachidonic acid, 12(S)-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE), was investigated using three different kinds of cells: NRK-49F (normal rat kidney fibroblasts), AtT-20 (mouse pituitary tumor cell line) and HL-60 (human leukemia cells) cells. The inhibition was very obvious in NRK-49F and AtT-20 cells, but it was almost negligible in HL-60 cells. There was no difference in terms of the binding of 12-HETE to NRK-49F and HL-60 cells. Pretreatment of NRK-49F cells with pertussis toxin almost completely ADP-ribosylated Gi proteins, but it did not affect the inhibition of 12-HETE on AC in this cell. This result excludes the involvement of Gi proteins in 12-HETE-mediated inhibition of AC. It was revealed that the characteristics of ACs in these cells were quite different in response to agonists and forskolin, suggesting that these cells do have different isoform of AC. We conclude that 12-HETE inhibits the activity of AC depending upon the isoform.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1996

Specific interaction with guanine residues of Z-form DNA by bleomycin-nickel(III) complex.

The Ni(III) complex of bleomycin (BLM) reacts with guanine residues of the oligomer duplex only under high salt condition (4.5 M NaCl) where the (dC-dG)6 sequence exists as the isolated Z-form segment. In addition, the (dC-dG)n inserts were subcloned into a plasmid so that reactivity of the BLM-Ni(III) complex with restriction fragments could be examined. Results are reported for two fragments: an EcoRI-DdeI fragment in which the (dC-dG)n insert is flanked at the 5' end by a segment of B-DNA and a HindIII-DdeI fragment in which the (dC-dG)n fragment is embedded at both ends by stable B-DNA forming segments. The BLM-Ni(III) complex does not bind to (dC-dG)5 sequence of pBRZ10 DNA fragment under any conditions, but to several guanine residues of (dC-dG)8 and (dC-dG)12 sequences of pBRZ16 and pBRZ24 DNA fragments in 4.5 M NaCl solution. In the fragments of pBRZ16 and pBRZ24 DNAs, the BLM-Ni(III) complex reacts with most of guanine bases of (dC-dG)8 and (dC-dG)12.

Base Sequence↗
PubMed1996

Metal-chelating inhibitors of a zinc finger protein HIV-EP1. Remarkable potentiation of inhibitory activity by introduction of SH groups.

HIV-EP1 is a C2H2 type zinc finger protein which binds to DNA kappa B site present in the long terminal repeat of HIV provirus. Previously we have reported zinc chelators having histidine--pyridine--histidine skeleton and were successful in inhibiting the DNA binding of HIV-EP1 by removing zinc from the zinc finger domain. Aiming at the potentiation of the inhibitory activity of our previous zinc chelators, herein synthesized were novel chelators comprising pyridine and aminoalkanethiol. These showed marked inhibitory activity on the DNA binding of HIV-EP1. In particular, one of them having a bis(2-mercaptoethyl) amino side chain showed inhibitory activity (IC50, approximately 4 microM) 10 times stronger than that of the strongest inhibitor that we reported previously. It appeared that these inhibited the DNA binding of HIV-EP1 by a mechanism distinct from that of the previous histidine-based inhibitors.

Animals↗