Search PubMed⌕ Search

Biomedical subjects

K Osawa

Publications and source records attributed to K Osawa.

At least 19 recordsLinked to original sources
PubMed1997

Metabolic inactivation of retinoic acid by a novel P450 differentially expressed in developing mouse embryos.

Retinoic acid (RA) is a physiological agent that has a wide range of biological activity and appears to regulate developmental programs of vertebrates. However, little is known about the molecular basis of its metabolism. Here we have identified a novel cytochrome P450 (P450RA) that specifically metabolizes RA. In vitro, P450RA converts all-trans RA into 5,8-epoxy all-trans RA. P450RA metabolizes other biologically active RAs such as 9-cis RA and 13-cis RA, but fails to metabolize their precursors, retinol and retinal. Overexpression of P450RA in cell culture renders the cells hyposensitive to all-trans RA. These functional tests in vitro and in vivo indicate that P450RA inactivates RA. The P450RA gene is not expressed uniformly but in a stage- and region-specific fashion during mouse development. The major expression domains in developing embryos include the posterior neural plate and neural crest cells for cranial ganglia. The expression of P450RA, however, is not necessarily inducible by excess RA. These results suggest that P450RA regulates the intracellular level of RA and may be involved in setting up the uneven distribution of active RA in mammalian embryos.

Amino Acid Sequence↗
PubMed1996

KS-505a, an isoform-selective inhibitor of calmodulin-dependent cyclic nucleotide phosphodiesterase.

The effects of KS-505a, a novel microbial metabolite, on the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaM-PDE) were investigated. (1) KS-505a potently inhibited the purified 61 kDa isoenzyme of CaM-PDE from bovine brain and required much higher doses to inhibit the purified 59 kDa isoenzyme of CaM-PDE from bovine heart. The inhibition of both isoenzymes was observed only in the presence of calcium-activated calmodulin (Ca2+/CaM). The IC50 values for the 61 and 59 kDa isoenzymes were 0.17 and 13 microM respectively with 20 microM cAMP as a substrate. (2) Kinetic analysis indicated that the inhibitory mode of KS-505a for the 61 kDa isoenzyme was competitive with respect to Ca2+/CaM; the K1 for KS-505a was 0.089 microM. The inhibition was not competitive with respect to the substrates cAMP or cGMP. (3) KS-505a did not interfere with the interaction between Ca2+/CaM and n-phenyll-naphthylamine, a hydrophobic fluorescent probe, nor was it adsorbed to CaM-conjugated gels in the presence of Ca2+, thereby indicating that KS-505a does not bind to Ca2+/CaM. (4) Trypsin-activated 61 kDa isoenzyme, which lacked the Ca2+/CaM-binding domain, was not inhibited by KS-505a at less than micromolar concentrations. Taken together, these results suggest that KS-505a apparently bound to a site in the Ca2+/CaM-binding domain of the 61 kDa isoenzyme and selectively inhibited Ca2+/CaM-activated 61 kDa isoenzyme activity. (5) In rat hippocampal slices, KS-505a at 10 micronM increased the intracellular cAMP concentration to approximately three times the basal level, whereas in rat striatal slices it had no effect on the cAMP concentration at concentrations of 1.0-10 microM, suggesting that each CaM-PDE isoenzyme functions differentially in these regions. These results demonstrate that KS-505a is a highly potent selective inhibitor both in vitro and in vivo and distinguishes between subfamily members within the CaM-PDE family.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Macrocarpals H, I, and J from the Leaves of Eucalyptus globulus.

A 50% EtOH extract of Eucalyptus globulus leaves yielded eight phloroglucinol--sesquiterpene-coupled constituents, including three novel compounds named macrocarpals, H, I, and J. Some of these compounds possessed antibacterial activity against oral pathogenic microorganisms with MIC values ranging from 0.20 micrograms/mL to 6.25 micrograms/mL. Inhibition of glucosyltransferase activity by these compounds was also noted.

Anti-Bacterial Agents↗
PubMed1995

Eucalyptone from Eucalyptus globulus.

A new cariostatic compound named eucalyptone was isolated from the leaves of Eucalyptus globulus. The structure of this compound was elucidated by spectroscopic methods.

Anti-Bacterial Agents↗
PubMed1994

Antibacterial trichorabdal diterpenes from Rabdosia trichocarpa.

Four antibacterial diterpenes, trichorabdals A, B, C and H were isolated from the leaves of Rabdosia trichocarpa and the relationship between their conformations analysed by spectroscopic and computational methods. Their antibacterial activity is discussed.

Anti-Bacterial Agents↗
PubMed1994

An investigation of diterpenes from the leaves of Rabdosia trichocarpa and their antibacterial activity against oral microorganisms.

The ethanolic extract of Rabdosia trichocarpa leaves showed antibacterial activity against cariogenic mutans streptococci and periodontopathic Porphyromonas gingivalis. Chromatographic separation and purification of the extract afforded ten diterpenes, including one novel ent-kauren type compound named trichoranin. Some of these compounds possess potent antibacterial activity against these oral micro-organisms, indicating that these diterpenes may be useful natural substances for the maintenance of oral health.

Anti-Bacterial Agents↗
PubMed1994

International Federation of Clinical Chemistry (IFCC): systematic top-down approach to clinical chemistry.

This paper introduces a systematic approach to organizing the discipline of clinical chemistry. The approach is called a top-down, systems approach because it starts at the top with the most general concepts and works down through less general concepts to the most specific details and techniques. The hypothesis is that the discipline can be organized into hierarchical levels of functional processes and operational approaches to those processes. The functional processes represent what clinical scientists do; the operational approaches represent how they do it. Because functional processes change little, if at all, with time, they are use to develop a stable infrastructure or framework for the discipline. That infrastructure is then used to organize and understand operational approaches that tend to change rapidly with time in response to technological advances. This paper begins with the most general functional processes and then uses selected examples of the more general functions to illustrate lower hierarchical levels of functional processes and operational approaches.

Animals↗
PubMed1992

Relationship between cholesterol sulfate and intercellular cohesion of the stratum corneum: demonstration using a push-pull meter and an improved high-performance thin-layer chromatographic separation system of all major stratum corneum lipids.

To investigate the role of cholesterol sulfate (CS) as an intercellular glue or cement in the stratum corneum, we compared the relationship between CS levels and magnitude of the intercellular cohesion of the stratum corneum between the palm and the upper arm. Using a push-pull meter, the palm displayed approximately seven times the magnitude of cohesion of the stratum corneum as the upper arm (n = 11). CS and other stratum corneum lipids were extracted from the palm and the upper arm (n = 22) by a cup method and determined by our improved high-performance thin-layer chromatography (HPTLC). Despite a great difference in the magnitude of cohesion (p less than 0.01), CS levels and ratios of CS to ceramides and CS to cholesterol in the stratum corneum showed no significant differences between the palm and the upper arm. Our results suggest that differences in CS cannot account for the differences in cohesion between palm and upper arm.

Adult↗
PubMed1992

Isoflavanones from the heartwood of Swartzia polyphylla and their antibacterial activity against cariogenic bacteria.

The methanolic extract of Swartzia polyphylla DC. heartwood had antibacterial activity against cariogenic bacteria, the mutans Streptococci. The chromatographic purification of the extract afforded seven flavonoids. Among them, three known isoflavanones, dihydrobiochanin A, ferreirin and darbergioidin, and one new isoflavanone, 5,2',4'-trihydroxy-7-methoxyisoflavanone (dihydrocajanin) had potent antibacterial activity against cariogenic bacteria. This effect was not detected on isoflavone derivatives. A comparative antibacterial study of various flavonoids was further performed, and their structure-activity relationship was discussed.

Anti-Bacterial Agents↗
PubMed1992

[Determination of sennoside A in oriental pharmaceutical decoctions containing Rhei Rhizoma by ion-pair high-performance liquid chromatography].

A simple method using ion-pair high-performance liquid chromatography was established for the rapid and precise determination of sennoside A in oriental pharmaceutical decoctions containing Rhei Rhizoma. This method was compared with other two methods, i.e. ion-suppression and phosphate buffer methods. Sennoside A was eluted without interference in this ion-pair method, while the determination of sennoside A was interfered by co-existing components in the other two methods.

Anthraquinones↗
PubMed1992

KS-505a, a novel inhibitor of bovine brain Ca2+ and calmodulin-dependent cyclic-nucleotide phosphodiesterase from Streptomyces argenteolus.

A novel compound, KS-505a was isolated from the culture broth of a strain identified as Streptomyces argenteolus A-2. The compound inhibited bovine brain Ca2+ and calmodulin-dependent cyclic-nucleotide phosphodiesterase with an IC50 value (the concentration causing 50% inhibition) of 0.065 microM. The compound around that concentration had little or no effect on heart calmodulin-dependent and -independent cyclic-nucleotide phosphodiesterases, and protein kinase C.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

The inhibitory effect of plant extracts on the collagenolytic activity and cytotoxicity of human gingival fibroblasts by Porphyromonas gingivalis crude enzyme.

It is well known that plant extracts inhibit some enzymatic activities. The present study examined the inhibitory effects of natural plant extracts against the collagenolytic activity of Porphyromonas gingivalis. The enzyme was isolated from a culture supernatant of P. gingivalis 381. The aqueous and 50% ethanolic extracts of Ginkgo biloba, Mosla chinensis, Salvia officinalis, Cinnamomum cassia, and a catechin extract of Camellia sinensis exhibited strong inhibitory effects on collagenolytic activity. The activities of these plant extracts were higher than that of tetracycline-HCl. They also inhibited the cytotoxicity of P. gingivalis crude enzyme against human gingival fibroblasts. C. sinensis catechin was the most effective agent in neutralizing the cytotoxicity of P. gingivalis. The aqueous and 50% ethanolic extracts of C. cassia had relatively strong anti-cytotoxic activity. Although the other samples strongly inhibited the collagenolytic activity of P. gingivalis, they were not effectively anti-cytotoxic. The present findings suggest that C. sinensis and C. cassia extracts are effective in reducing the pathogenicity of periodontopathic bacteria.

Catechin↗
PubMed1990

Reduction in microalbuminuria in diabetics by eicosapentaenoic acid ethyl ester.

Eicosapentaenoic acid (EPA) ethyl ester (1.8 g/d) was administered to 16 diabetic patients (5 insulin-dependent and 11 noninsulin-dependent diabetics) for 6 mon. EPA in total plasma fatty acids increased from 4.0 +/- 2.4 mol% (mean +/- SD) to 7.5 +/- 3.1 mol% (p less than 0.001). Albumin excretion, measured with spot urine, was significantly reduced from 65 to 36 mg/g creatinine (geometric means, p less than 0.001). Fasting blood sugar levels, glycohemogloblin, body weight and blood pressure did not change significantly during the study. There were also no significant changes in serum levels of creatinine, urea nitrogen, total cholesterol and triglycerides. Although no overt hemorrhage was observed in the patients, hematocrit was reduced from 42.6 +/- 2.8% to 41.0 +/- 3.9% (p less than 0.02). Ten other similar diabetic patients (4 insulin-dependent and 6 noninsulin-dependent diabetics) were followed as a reference group, not concomitantly, for 6 mon with neither EPA ethyl ester nor placebo. The parameters mentioned above were not changed significantly in this group during 6 mon. EPA administration might retard the appearance of overt diabetic nephropathy.

Aged↗
PubMed1990

Calmodulin antagonistic action of KS-504a, a novel metabolite of the fungus Mollisia ventosa.

KS-504a inhibited bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase (CaM-PDE) with an IC50 value of 122 microM. The inhibition was reversed by a high concentration of calmodulin. Calmodulin-independent activities of the enzyme were not affected by the compound at the same concentration ranges. Ca2(+)-dependent interaction of the compounds with calmodulin was shown using hydrophobic fluorescence probes. These data indicated that the compound exerted its effects on CaM-PDE by interacting with calmodulin. KS-504a also inhibited other calmodulin-dependent enzymes at different concentration ranges; myosin light chain kinase was inhibited at the lowest concentrations with an IC50 value of 6.3 microM. The inhibition mechanism was competitive with respect to calmodulin and non-competitive to ATP.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1990

Inhibitory effects of aqueous extract of cacao bean husk on collagenase of Bacteroides gingivalis.

Natural materials containing tannin were examined to determine whether they possessed any inhibitory activity against collagenase obtained from the culture supernatant of Bacteroides gingivalis. The collagenolytic activity was determined with Collagenokit CLN-100 (Collagen Technological Co., Tokyo) using FITC-conjugated collagen type 1. Among the test samples, only an aqueous extract of cacao (Theobroma cacao) bean husk strongly inhibited the bacterial collagenase. This inhibitory potency was at the same level as that of tetracycline-HCl.

Cacao↗
PubMed1990

Studies of the antibacterial activity of plant extracts and their constituents against periodontopathic bacteria.

Plant extracts and their constituents were tested for antibacterial activity against periodontopathic bacteria, including Actinobacillus, Capnocytophaga, Fusobacterium, Eikenella and Bacteroides species. The essential oils of two labiatae plants, Mosla chinensis Maxim. and Pogostemon cablin Benth., and five terpenoids, hinokitiol, thymol, carvacrol, patchoulialcohol and pogostone, showed antibacterial activity. The terpenoids were especially effective against Bacteroides species.

Bacteria↗