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Biomedical subjects

M Otsuka

Publications and source records attributed to M Otsuka.

At least 199 records · Page 11Linked to original sources
PubMed1996

Evaluation of urinary pyridinoline in healthy adults and patients with rheumatoid arthritis by an improved high-performance liquid chromatographic assay.

A modified method for the determination of pyridinoline using high-performance liquid chromatography (HPLC) has been applied to analyze the urine of healthy adults and patients with rheumatoid arthritis. The concentrations of pyridinoline in the urine of healthy Japanese men and women (average age: 50.6 and 51.8 yr, respectively) during morning fasting were 28.8 +/- 2.8 (SEM) and 34.8 +/- 3.5 nmol/mmol creatinine, respectively. In the case of patients with rheumatoid arthritis, the urinary concentration of pyridinoline was 49.1 +/- 8.3 nmol/mmol creatinine (women, average age, 61.1 yr), which was significantly higher than that of healthy women of the same age (p < 0.05). This study supports the application of HPLC for urinary pyridinoline analysis and as a screening test for patients with bone disease.

Adult↗
PubMed1996

Inhibitory effect of ascorbate on cell growth: relation to catalase activity.

The effect of ascorbate on cell growth was examined using primary cultured hepatocytes and chondrocytes elicited from guinea pigs and six kinds of cell lines derived from the tissue and blood of mammals. Cells were cultured in medium supplemented with or without ascorbate at various concentrations for 24 and 48 h. There were differences among the cells used here in the effect of ascorbate on growth, and also in the concentrations of ascorbate required to lower cell viabilities. This indicates that different cell species have varying sensitivities to ascorbate in medium. On the other hand, cells such as HL-60, which showed growth inhibition at higher concentrations of ascorbate in medium among observed cells, were damaged by the exposure to higher concentrations of hydrogen peroxide (H2O2). Furthermore, there was a positive correlation between the activity of catalase in cells that decomposed H2O2 and the concentration of ascorbate required to lower cell viability (p < 0.01). These results indicate that the concentration of ascorbate in medium required to inhibit cell growth depends on the activity of catalase in the cells.

Animals↗
PubMed1996

[The relief of postoperative pain by suppositories of buprenorphine or NSAID].

We evaluated the effects of suppositories of buprenorphine (BN) or NSAID (supp.) preoperatively administered for postoperative pain relief in patients who underwent elective gynecological surgeries. Fifty six patients were randomized into four groups: group B; 0.4 mg BN supp., group B+I; 0.4 mg BN supp. and 50 mg indomethacine (IND) supp., group B+D; 0.4 mg BN supp. and 50 mg diclofenac supp., group C; no supp. given as control. They were administered rectally after induction of general anesthesia. In all the supp. groups the patients had good pain relief during the first 24 hrs after the administration of supp. Group B+I seemed to have better pain relief, but, there was no statistical significance among the 3 groups. Nausea and vomiting were observed more frequently in group B and in control group C than in NSAIDs combined groups. The difference in the incidence rates was not significant. In conclusion, the simultaneous administration of BN and IND supp. was considered to be useful for postoperative pain relief without producing major side effects.

Adult↗
PubMed1996

[Hypoplastic mixed lineage leukemia successfully treated with low-dose cytosine arabinoside].

A 54-year-old male was admitted because of dyspnea on exercise. His peripheral blood revealed pancytopenia with severely hypoplastic bone marrow. Bone marrow aspiration showed a marked hypocellular marrow with 62.4% of blast cells. Cytochemical studies showed that peroxidase activity, alpha-nephtyl buthylate esterase activity and PAS reaction were negative, and that only ASD-chroloacetate esterase activity was positive. Surface marker analysis of blast cells showed positive result for CD5, 7, 33 and 34 antigens. The T-cell receptor beta gene was rearranged, but the immunoglobulin H chain gene showed a germ line configuration. Terminal Deoxynucleotydyl Transferase (TdT) was positive, but cellular surface and cytoplasmic immunoglobulin were not recognized. A diagnosis of hypoplastic mixed lineage leukemia was made and treated with low dose cytosine arabinoside, he resulted in complete remission. The relation between hypoplastic leukemia, AML-M0 and mixed lineage leukemia was also discussed.

Antimetabolites, Antineoplastic↗
PubMed1995

Cupric ion blocks NF kappa B activation through inhibiting the signal-induced phosphorylation of I kappa B alpha.

A transcription factor NF kappa B, which regulates expression of various cellular genes involved in immune responses and viral genes including HIV, is sequestered in the cytoplasm as a complex with an inhibitory protein I kappa B. Various extracellular signals induce phosphorylation and rapid degradation of I kappa B alpha to release NF kappa B. Cu2+ was found to inhibit the activation of NF kappa B induced by TNF-alpha, TPA, or H2O2. Deoxycholate treatment of the cytoplasmic extract prepared from cells stimulated by TNF-alpha in the presence of Cu2+ resulted in the release of NF kappa B from I kappa B alpha, indicating that Cu2+ interferes with the dissociation of the NF kappa B-I kappa B complex. Neither phosphorylation nor degradation of I kappa B alpha was observed upon TNF-alpha stimulation in the presence of Cu2+. These results indicate that Cu2+ inhibits the release of NF kappa B by blockade of a signal leading to the phosphorylation of I kappa B alpha.

Animals↗
PubMed1995

Novel zinc chelators with dual activity in the inhibition of the kappa B site-binding proteins HIV-EP1 and NF-kappa B.

Both HIV-EP1 (also called PRDII-BF1 or MBP-1), a zinc finger protein, and NF-kappa B, a Rel family protein, bind to kappa B site present in the enhancer of multiple cellular and viral genes involved in immune function and inflammatory response including HIV-1 LTR and human interferon beta gene. When cells are exposed to extracellular stimuli such as virus or phorbol ester, the activity of both HIV-EP1 and NF-kappa B is induced. Thus, kappa B site-directed transcription could be regulated by two distinct proteins in a cooperative way. Novel heterocyclic compounds comprising (dimethylamino)pyridine and histidine units, i.e., 1-4, have been designed and synthesized, aiming at inhibition of these kappa B site-binding proteins to discriminate their functions. These compounds exhibited remarkable zinc-binding capability as revealed by NMR study. Compounds 1 and 2 showed a marked inhibitory effect on the DNA binding activity of HIV-EP1 by removing zinc without interfering with the DNA binding activity of NF-kappa B. Since it has been demonstrated that zinc somehow influences the DNA binding of NF-kappa B, the effect of these heterocyclic compounds and their zinc complexes on NF-kappa B was examined. Zinc complexes of 3 and 4 exhibited the inhibitory effect on the DNA binding of NF-kappa B and/or homodimeric complexes of p50 and p65 subunits of NF-kappa B without affecting HIV-EP1. Thus, it became possible to inhibit either one of the two kappa B site-binding proteins without inhibiting the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

Pharmacological characterization of GR82334, a tachykinin NK1 receptor antagonist, in the isolated spinal cord of the neonatal rat.

Pharmacological characteristics of [D-Pro9,[spiro-gamma-lactam]Leu10,Trp11]physalaemin-(1-11) (GR82334), a tachykinin NK1 receptor antagonist, and its effects on slow depolarizing responses of lumbar ventral roots evoked by primary afferent stimulation were examined in isolated spinal cord preparations of neonatal rats. GR82334 (1-3 microM) caused dose-dependent rightward shifts of the concentration-response curves for substance P, substance P methyl ester, delta-aminovaleryl [Pro9,N-Me-Leu10]substance P-(7-11) (GR73632) and neurokinin A in normal artificial cerebrospinal fluid and those for substance P methyl ester, GR73632 and neurokinin A in the presence of tetrodotoxin. GR82334 (10 microM) did not evoke gamma-aminobutyric acid (GABA) release from spinal cords of neonatal rats, whereas [D-Pro9,[spiro-gamma-lactam] Leu10,Trp11]substance P (GR71251), another tachykinin NK1 receptor antagonist, induced a significant increase in GABA release. GR82334 (1-3 microM) markedly depressed the slow depolarizing response of ventral roots, referred to as slow ventral root potential, evoked by the stimulation of the contralateral dorsal root or the ipsilateral saphenous nerve. In contrast, cyclo[Gln,Trp,Phe,Gly,Leu,Met] (L-659,877, 1 microM), a selective tachykinin NK2 receptor antagonist, did not depress the saphenous nerve-evoked slow ventral root potential and did not antagonize the action of neurokinin A to induce ventral root depolarization. The present results provide further evidence for the involvement of substance P, neurokinin A and tachykinin NK1 receptors in the primary afferent-evoked slow ventral root potentials.

Amino Acid Sequence↗
PubMed1995

Tachykininergic slow depolarization of motoneurones evoked by descending fibres in the neonatal rat spinal cord.

1. In the isolated spinal cord of the neonatal rat, repetitive electrical stimulation of the upper cervical region elicited a prolonged depolarization of lumbar motoneurones (L3-5) lasting 1-2 min, which was recorded extracellularly from ventral roots, or intracellularly. 2. This depolarizing response was markedly depressed by the excitatory amino acid receptor antagonists D-(-)-2-amino-5-phosphonovaleric acid (D-APV, 30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). The remaining response was further depressed by a 5-hydroxytryptamine (5-HT) receptor antagonist, ketanserin (3 microM). 3. In the presence of these antagonists, a small part of the depolarizing response of slow time course remained, and this response was partially blocked by the tachykinin NK1 receptor antagonists GR71251 (0.3-5 microM) and RP67580 (0.3-1 microM). In contrast, RP68651 (0.3-1 microM), the inactive enantiomer of RP67580, had no effect on the depolarizing response. 4. The slow depolarizing response in the presence of D-APV, CNQX and ketanserin was markedly potentiated by a peptidase inhibitor, thiorphan (1 microM). 5. This descending fibre-evoked slow depolarization became smaller after prolonged treatment (5-7 h) with 5,7-dihydroxytryptamine (10 microM), a neurotoxin for 5-HT neurones. Under such conditions, the effects of thiorphan and GR71251 on the slow depolarization were virtually absent. 6. Under the action of D-APV, CNQX and ketanserin, applications of tachykinins, substance P and neurokinin A produced depolarizing responses of lumbar motoneurones, and the responses were depressed by GR71251 and potentiated by thiorphan. 7. These results suggest that tachykinins contained in serotonergic fibres serve as neurotransmitters mediating the descending fibre-evoked slow excitatory postsynaptic potentials in motoneurones.

5,7-Dihydroxytryptamine↗
PubMed1995

Novel DNA photocleaving agents with high DNA sequence specificity related to the antibiotic bleomycin A2.

We have designed and synthesized a series of novel DNA photocleaving agents which break DNA with high sequence specificity. These compounds contain the non-diffusible photoactive p-nitrobenzoyl group covalently linked via a dimethylene (or tetramethylene) spacer to thiazole analogues of the DNA binding portion of the antibiotic bleomycin A2. By using a variety of 5' or 3' 32P-end labeled restriction fragments from plasmid pBR322 as substrate, we have shown that photoactive bithiazole compounds bind DNA at the consensus sequence 5'-AAAT-3' and induce DNA cleavage 3' of the site. Analysis of cleavage sites on the complementary DNA strand and inhibition of DNA breakage by distamycin A indicates these bithiazole derivatives bind and attack the minor groove of DNA. A photoactive unithiazole compound was less specific inducing DNA breakage at the degenerate site 5'-(A/T)(AA/TT)TPu(A/T)-3'. DNA sequence recognition of these derivatives appears to be determined by the thiazole moiety rather than the p-nitrobenzoyl group: use of a tetramethylene group in place of a dimethylene spacer shifted the position of DNA breakage by one base pair. Moreover, much less specific DNA photocleavage was observed for a compound in which p-nitrobenzoyl was linked to the intercalator acridine via a sequence-neutral hexamethylene spacer. The 5'-AAAT-3' specificity of photoactive bithiazole derivatives contrasts with that of bleomycin A2 which cleaves DNA most frequently at 5'-GPy-3' sequences. These results suggest that the cleavage specificity exhibited by bleomycin is not simply determined by its bithiazole/sulphonium terminus, and the contributions from other features, e.g. its metal-chelating domain, must be considered. The novel thiazole-based DNA cleavage agents described here should prove useful as reagents for probing DNA structure and for elucidating the molecular basis of DNA recognition by bleomycin and other ligands.

Base Sequence↗
PubMed1995

Expression of the intestinal T-lymphocyte-associated-molecule recognized by the HML-1 antibody on mononuclear cells from HTLV-I-infected subjects.

We investigated the expression of a monoclonal antibody (HML-1) defined antigen that appears on human intestinal T-lymphocytes in HTLV-I-related disease. We studied 25 ATL, and 24 healthy HTLV-I carriers. Patients with acute ATL showed a variety of the expression of the HML-1 antigen (range 0.4-74.8%). HML-1 expression on mononuclear cells (MNCs) in blood from patients with chronic ATL ranged from 1.7-43.6% (mean 13.5%). This level of expression was less than that of patients with acute ATL, but not significantly. In patients with smoldering ATL, the degree of patients with acute ATL, but not significantly. In patients with smoldering ATL, the degree of expression ranged from 1.6-13.3% (mean 8.0%). In contrast to patients with acute ATL, MNCs from patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and B-cell type chronic lymphocytic leukemia (B-CLL) did not express the HML-1 antigen, except for the 2 patients with ALL. Healthy HTLV-I carriers and healthy controls also were negative for HML-1 reactivity. In acute ATL, patients with gastrointestinal tract infiltration tended to have high expression of the HML-1 epitope. After stimulation with phytohemagglutinin (PHA), healthy HTLV-I carriers showed significantly increased expression of the HML-1 epitope (P < 0.05). Recently, the beta 7 integrin family has been found to play a specific role in mucosal localization or adhesion, and HML-1 protein was found to match the deduced beta 7 N-terminal sequence. We propose that the cellular gene responsible for HML-1 epitope expression may, like IL-2, IL-2R, etc., be transactivated by infection with HTLV-I, and HML-1 antigen gene expression by HTLV-I infection may lead to infiltration of ATL cells with highly expressed HML-1 epitope into the gut mucosa.

Antigens, Neoplasm↗
PubMed1995

Effect of particle size of metastable calcium phosphates on mechanical strength of a novel self-setting bioactive calcium phosphate cement.

Resistance to compressive strength after setting of the calcium phosphate cement consisting of tetracalcium phosphate (TECP), dicalcium phosphate dihydrate (DCPD), and 40 wt/wt% of a synthetic hydroxyapatite (HAP) was tested. An equimolar mixture of the calcium phosphate powder containing DCPD (particle diameter [D] 0.52-3.33 microns) and TECP (D, 1.1-13.1 microns) transformed into HAP at 37 degrees C, 100% RH after being mixed with 25 mM phosphoric acid. X-ray diffraction suggested that the cement containing fine particles of DCPD and TECP completely transformed to HAP, but that mixtures containing larger particles did not. Because particle size of both DCPD and TECP affected the compressive strength of the cement, the crystal growth of HAP during cement formation depended on the specific surface area (Sw) of the raw materials. The crystallite size of transformed HAP was estimated based on X-ray diffraction peaks at 25.8 and 32.8 degrees attributable to the 002 and 300 planes. The crystalline size attributable to the 300 plane decreased with increasing Sw, but that attributable to the 002 plane showed no significant relationship. The compressive strength of the cement after hardening increased with an increase of its Sw. This suggested that the harder calcium phosphate cement was (derived) from the smaller particle size of the raw materials.

Bone Cements↗
PubMed1995

Drug release from a novel self-setting bioactive glass bone cement containing cephalexin and its physicochemical properties.

A novel device containing cephalexin as a model drug using a self-setting bioactive cement based on CaO-SiO2-P2O5 glass was investigated. The device consisted of 95 wt/wt% glass powders and 5 wt/wt% cephalexin powder hardened within 5 min after mixing with a phosphate buffer. After setting, in vitro drug release from homogeneous or heterogeneous drug-loaded cement pellets in a simulated body fluid (SBF) at pH 7.25 and 37 degrees C continued for over 4 weeks. The hardened cement gradually formed low-crystallinity hydroxyapatite with high bioactivity in hard bone tissue and reduced in volume by about 5% during dissolution testing in SBF. Consequently, 30% of the loaded drug was squeezed from the cement system at the initial stage of the drug release, and the remainder released more slowly. Because the heterogeneous system consisting of the cement and drug-loaded pellet avoided the drug-squeezing effect, it showed a longer drug release term than the homogeneous drug-loaded cement. The heterogeneous system using the hardened cement after soaking in SBF at 37 degrees C for 10 days showed very slow drug release at the initial stage because it completely avoided the drug-squeezing effect, and the release was a zero-order pattern.

Cephalexin↗
PubMed1995

Programmable drug release of highly water-soluble pentoxifylline from dry-coated wax matrix tablets.

The programmable release of pentoxifylline from a dry-coated wax matrix tablet containing behenic acid as wax matrix was investigated at 37 degrees C in Japanese Pharmacopeia XII 1st (pH 1.2) and 2nd (pH 6.8) fluids. The dry-coated tablet consisted of a low drug concentration (33% w/w) in the outer layer tablet and a high concentration (50-67% w/w) in the core. The drug release from the wax matrix significantly increased after penetrating the core; therefore, the drug release profiles showed specific biphasic curves. Because the contact angle of the wax matrix tablet increased with a decrease in the drug concentration, the fluid penetration in wax matrix tablet increased with an increase of the drug concentration. The time required for 75% drug release (T75) decreased with an increasing drug concentration in the core, and the T75 at pH 6.8 was slightly longer than that in pH 1.2. The larger core tablet had a shorter T75, indicating that the drug release rate was controlled by regulating the drug concentration and/or the weight of the core tablet.

Chemical Phenomena↗
PubMed1995

Effect of compression temperature on the consolidation mechanism of chlorpropamide polymorphs.

The effect of environmental temperature on the compression mechanism of chlorpropamide (CPM) polymorph, forms A and C, was investigated with an eccentric type tabletting machine with two load cells and a noncontact displacement transducer. The temperature of the die was controlled at 0 and 45 degrees C by a thermocontroller. Sample powders (200 mg), which were also controlled at 0 and 45 degrees C by a thermocontroller, were compressed at almost 230 MPa. The tabletting dynamic processes of CPM forms A and C at 0 and 45 degrees C were evaluated by Cooper and modified Heckel analyses. The results suggest that particle brittleness or plasticity was affected by compression at different temperatures. The higher tablet hardness of form A at 45 degrees C was thought to be caused by the increased plasticity of primary particles, whereas that of form C at 45 degrees C was ascribed to the decreased size of the secondary particles.

Chemistry, Pharmaceutical↗