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Biomedical subjects

T Ozeki

Publications and source records attributed to T Ozeki.

At least 37 records · Page 2Linked to original sources
PubMed1998

Formation of water-insoluble gel in dry-coated tablets for the controlled release of theophylline.

Sodium alginate (ALNa) of a natural polysaccharide is known to form a water-insoluble gel when combined with a bivalent metal. In this study, we prepared tablets containing ALNa and calcium gluconate (GLCa) as a bivalent metal, and studied the application of the water-insoluble gel involving the controlled release of a test drug by permeation of water. Dry-coated tablets containing theophylline (TP) as a model drug, ALNa and GLCa were prepared by the dry power compression method. The controlled release of TP was evaluated by the dissolution test according to JP XIII. The release rate was extremely high for the tablets which contained only TP and GLCa. A zero order or sigmoidal release profile was observed for the tablets that contained only TP and ALNa. On the other hand, the lowest dissolution rate and a sigmoidal release profile were observed for the tablet containing TP and GLCa in its core and ALNa in its outer phase. These results suggest that dry-coated tablets containing ALNa and GLCa and prepared by the direct powder compression method would be useful for the controlled release of drugs.

Alginates↗
PubMed1997

Sex-specific effects of growth hormone on hepatic 11beta-hydroxysteroid dehydrogenase activity and gene expression in hypothyroid rats.

To investigate the effects of growth hormone (GH) on 11beta-HSD1, we determined changes in hepatic 11beta-HSD1 activity in hypothyroid rats following treatment with subcutaneous (s.c) injection of GH for periods ranging from 24 h to 7 days. In male rats, hypothyroidism markedly reduced the hepatic 11beta-HSD1 activity and serum testosterone levels (p < 0.01). Subcutaneous injection of GH once daily to male hypothyroid rats for 48 h inhibited hepatic 11beta-HSD1 activity. However, the same daily dose of GH administered to male hypothyroid rats for 7 days, resulted in a marked increase in hepatic 11beta-HSD1 activity and gene expression (p < 0.01). Furthermore, daily s.c injections of GH to castrated male hypothyroid rats for 7 days reduced hepatic 11beta-HSD1 activity rather than inducing it, the same response seen in hypothyroid female rats. In addition, the treatment of castrated male hypothyroid rats with testosterone for 7 days significantly increased this enzyme activity (p < 0.01). The changes in hepatic 11beta-HSD1 were demonstrated to be associated with the testes in hypothyroid male rats following treatment with GH for 7 days. Moreover, the prolonged exposure to GH required to induce hepatic 11beta-HSD1 in intact hypothyroid male rats and the lack of a similar effect in castrated male hypothyroid rats suggests that this action is indirect and that it may be mediated by androgen production from Leydig cells of the testes and induced by the daily injections of GH. Treatment of hypothyroid male rats with GH at 6-h intervals, however, feminized the hepatic 11beta-HSD1 gene expression.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Two independent outbreaks of measles in partially vaccinated junior high schools in Tottori, Japan.

We analyzed retrospectively a relative risk of measles attacks in vaccinated vs. unvaccinated students using two independent outbreaks in Japan. The first involved 33/328 (10%) students where 64% students and 30% measles cases had been vaccinated. The second involved 27/241 (11%) students where 81% students and 48% measles cases had been vaccinated. The attack rates of vaccinated vs. unvaccinated students were significantly low (p < 0.001), but they accounted 25% in both episodes. The statistically significant clinical features among vaccinated and unvaccinated cases included the average duration of fever, 5.16 +/- 1.71 vs. 6.67 +/- 2.19 days (p = 0.01) and the incidence of complications, 0 vs. 25%, respectively. These results suggested that the measles in vaccinated cases were mostly due to secondary failures.

Adolescent↗
PubMed1995

[Fracture threshhold of rheumatoid arthritis patients].

The Bone mass measurement had been difficult while the fracture risk of the rheumatoid arthritic patient had been depended on osteoporosis. Recently, the accuracy of bone mass measurement became reliable that the adequate data could be obtained from the patients. This study shows the fracture threshold of rheumatoid patients by obtaining the bone mass density of those who had been suffering from fracture by DEXA. Twenty two limbs of 21 female patients were affected, average age of 65 and duration of 18 years, and the sites of fracture were femoral neck in 9 cases and humeral neck in 4 cases (62% of the fracture). The BMD of the spine in these patients shows. 828 g/cm2 which was below -3.4 sd of the normal japanese female and thought to be a fracture threshold in RA patients. The risk factors of the fractures in RA were ADL in the limbs, history of total joints arthroplasty and low body mass index.

Activities of Daily Living↗
PubMed1994

Decreased bradykinin binding sites in fibroblasts from progressive systemic scleroderma.

The numbers of bradykinin receptors (BK-R) in cultured dermal fibroblasts from patients with progressive systemic sclerosis (PSS) and from healthy controls were measured using a receptor binding assay. The numbers of BK-R were significantly fewer in PSS fibroblasts than in control fibroblasts (P < 0.02). However, no differences in affinity were observed in BK-R between PSS and control fibroblasts. The BK-R mRNA levels were determined in PSS and control fibroblasts by Northern blot hybridization using BK-R cDNA, but no significant differences were found. These findings suggest that the decrease in BK-R in PSS fibroblasts might occur during a posttranslational step.

Binding Sites↗
PubMed1993

Application of the solid dispersion method to the controlled release of medicine. III. Control of the release of slightly water soluble medicine from solid dispersion granules.

In order to control the release rate of slightly water soluble medicine by using the solid dispersion (SD) method, the SD was prepared with a water soluble polymer and the slightly soluble medicine, and the medicine release from the solid dispersion granules was studied. The SD granules were prepared by the evaporation of ethanol after dissolving into ethanol a slightly water soluble medicine (flurbiprofen (FP)) and soluble polymers (hydroxypropyl cellulose (HPC)). HPC has four grades of molecular weight. The release rate of FP from SD was measured by the rotating basket method (JP XII). The release rate of FP from the SD granules was markedly larger than that from FP powder, and it was larger with a lower HPC molecular weight. It is speculated that these results were mainly based on the molecular dispersion state of FP and HPC in SD.

Cellulose↗
PubMed1993

Application of the solid dispersion method to the controlled release of medicine. IV. Precise control of the release rate of a water soluble medicine by using the solid dispersion method applying the difference in the molecular weight of a polymer.

Solid dispersions were prepared by the evaporation of ethanol after dissolving into ethanol a water soluble medicine (oxprenolol hydrochloride (OXP)), four grades of water insoluble ethylcellulose (EC) and four grades of water soluble hydroxypropyl cellulose (HPC), both having different molecular weights. The precise control of the release rat of a water soluble medicine by applying the difference in the molecular weight of polymers was attempted. The pore size distribution in solid dispersion granules was measured before and after the dissolution test by mercury intrusion porosimetry to clarify the mechanism of medicine release from the granules when the molecular weights of polymers were different. The state of medicine in the solid dispersions was analyzed by thermal analysis and X-ray diffractometry. Although the difference was slight, the release rate of OXP from the granules of the OXP-HPC system decreased as the molecular weight of HPC increased. The release behavior of OXP in the OXP-EC system was scarcely affected by the molecular weight of EC. However, in the OXP-EC-HPC system, the release rate markedly decreased with a larger molecular weight of EC. It was thought from the results of the pore size distribution that there were two types of release routes for OXP; dissolving directly into the dissolution medium and diffusing in the swelled HPC phase, caused by the addition of HPC. The decrease in the release rate of OXP in the OXP-EC-HPC system was caused by the increase in the ratio of OXP dissolving via the latter route, occurring with a larger molecular weight of EC. These results suggest that it is feasible to precisely control the release of a water soluble medicine by varying the molecular weight of the polymers in the solid dispersion.

Cellulose↗
PubMed1992

Infection of Chang cells with hepatitis C virus using hepatic biopsy specimens from patients with chronic hepatitis (type C).

The presence of hepatitis C virus sequence was detected in liver tissue extracts by the polymerase chain reaction (PCR) method using primers of non-coding region in six out of eight cases with chronic hepatitis seropositive for Chiron's antibody. Subsequently, liver extracts from these cases were added to cell cultures of Chang cells for 3 days. The liver extracts of the six cases positive for PCR appeared to infect the Chang cells.

Adult↗
PubMed1992

Osteoclastic features of multinucleated giant cells responding to synthetic hydroxyapatite implanted in rat jaw bone.

Multinucleated giant cells (MGCs) that responded to synthetic hydroxyapatite (HAP) implanted in rat mandibles were studied with electron microscopy. HAP used in this study sintered at 200 degrees C (HAP200) and at 125 degrees C (HAP1250) after the synthesis by a wet method. One to three weeks after the intraosseous implantation of HAP, MGCs responding to HAP200 had not only well-developed ruffled border and the clear zone but well-developed perinuclear Golgi complex, many mitochondria and vesicles in their cytoplasms. MGCs responding to HAP1250 had the clear zone, but not the ruffled border although they showed similar cytoplasmic features to those of MGCs responding to HAP200. They merely extended short slender cytoplasmic processes to HAP1250. These results suggest that although osteoclast-like MGCs respond to HAP implanted in the bone, the development of the ruffled border-clear zone system depends on physicochemical properties of HAP.

Animals↗
PubMed1991

Autokinetic illusion as affected by suggestions of experimenter and observer.

Two experiments were done to examine whether an experimenter's suggestion and self-suggestion could affect the autokinetic illusion and to specify that effect. Exp. I compared the effect of a facilitative suggestion with a suppressive one, by measuring the moving latency, duration, frequency, and by analyzing the movement trace. Time and frequency did not detect any effects of marked individual differences. Trace analysis, on the other hand, showed that suggestions were effective in the expected direction for some subjects. Exp. II gave the suggestion for and against subjects' dominant direction of the movement and was designed to specify the effect. While effects indicated by time and frequency measures were not consistent, the movement trace showed the effect in suggested directions, which was more distinct for subjects whose nonsuggested illusion was not so markedly directed. These findings indicate that suggestion could affect the spatiotemporal aspect of the illusion, so the trace analysis may be useful for studies in this field.

Adult↗
PubMed1990

Receptor-linked early events induced by vasoactive intestinal contractor (VIC) on neuroblastoma and vascular smooth-muscle cells.

Vasoactive intestinal contractor (VIC) caused a series of biochemical events, including the temporal biphasic accumulation of 1,2-diacylglycerol (DAG), transient formation of Ins(1,4,5)P3, and increase in intracellular free Ca2+ [( Ca2+]i) in neuroblastoma NG108-15 cells. In these cellular responses, VIC was found to be much more potent in NG108-15 cells than in cultured rat vascular smooth-muscle cells. The single cell [Ca2+]i assay revealed that in the presence of nifedipine (1 microM) or EGTA (1 mM), the peak [Ca2+]i declined more rapidly to the resting level in VIC-stimulated NG108-15 cells, indicating that the receptor-mediated intracellular Ca2+ mobilization is followed by Ca2+ influx through the nifedipine-sensitive Ca2+ channel. Pretreatment with pertussis toxin only partially decreased Ins(1,4,5)P3 generation as well as the [Ca2+]i transient induced by VIC, whereas these events induced by endothelin-1 were not affected by the toxin, suggesting involvement of distinct GTP-binding proteins. The VIC-induced transient Ins(1,4,5)P3 formation coincident with the first early peak of DAG formation suggested that PtdIns(4,5)P2 is a principal source of the first DAG increase. Labelling studies with [3H]myristate, [14C]palmitate and [3H]choline indicated that in neuroblastoma cells phosphatidylcholine (PtdCho) was hydrolysed by a phospholipase C to cause the second sustained DAG increase. Down-regulation of protein kinase C (PKC) by prolonged pretreatment with phorbol ester markedly prevented the VIC-induced delayed DAG accumulation. Furthermore, chelation of intracellular CA2+ completely abolished the second sustained phase of DAG production. These findings suggest that PtdCho hydrolysis is responsible for the sustained production of DAG and is dependent on both Ca2+ and PKC.

Animals↗
PubMed1990

Dual effects of staurosporine on arachidonic acid metabolism in rat peritoneal macrophages.

Staurosporine is a microbial anti-fungal alkaloid having a most potent inhibitory activity on protein kinase C and is recently found as a non-12-O-tetradecanoylphorbol-13-acetate (non-TPA)-type tumor promoter of mouse skin, although tumor promotion induced by a TPA-type tumor promoter teleocidin is suppressed by staurosporine. When rat peritoneal macrophages were incubated in the medium containing various concentrations of staurosporine, prostaglandin E2 production and release of radioactivity from [3H]arachidonic acid-labeled macrophages were stimulated at concentrations of 1 and 10 ng/ml. But higher concentrations of staurosporine such as 100 and 1000 ng/ml showed no stimulative effect on prostaglandin E2 production although cytoplasmic free calcium levels were increased in a dose-dependent manner. Staurosporine-induced stimulation of prostaglandin E2 production was inhibited by treatment with cycloheximide, suggesting that a certain protein synthesis is prerequisite for the stimulation of arahcidonic acid metabolism. At higher concentrations (100 and 1000 ng/ml), staurosporine inhibited TPA-type tumor promoter (TPA, teleocidin and aplysiatoxin)-induced stimulation of arachidonic acid metabolism probably due to the inhibition of protein kinases. Tumor promotion activity and anti-tumor promotion activity of staurosporine might be explained by the fact that the lower concentrations of staurosporine stimulate arachidonic acid metabolism and the higher concentrations of staurosporine inhibit the tumor promoter-induced arachidonic acid metabolism, respectively.

Alkaloids↗
PubMed1990

Purification and characterization of cytosolic diacylglycerol kinases of human platelets.

Three isozymes of diacylglycerol kinase (DGK), DGK-I, DGK-II, and DGK-III, were purified from the cytosol of human platelets by successive chromatography on DEAE-cellulose, Ultrogel AcA34, heparin-Sepharose, ATP-agarose, Mono Q, phenyl-Superose, HCA-hydroxyapatite, Wakopak G40, and TSK-3000SW columns. Two DGK species (DGK-I and DGK-III) were purified to apparent homogeneity, and upon SDS-polyacrylamide gel electrophoresis, they showed a single band of apparent molecular mass of 152 kDa (DGK-I) or 58 kDa (DGK-III). The peptide mapping analysis showed that DGK-I and DGK-III are structurally different. DGK-II was only partially purified, and its apparent Mr was estimated to be 75,000 by gel filtration. The specific enzyme activities of the three isozymes were increased 1,480-fold (DGK-I), 690-fold (DGK-II) and 2,100-fold (DGK-III) over original platelet cytosol. The activities of DGK-II and DGK-III were markedly enhanced by the presence of deoxycholate or phosphatidylserine, whereas DGK-I activity was not much affected by the anionic compounds. All of the three activities were strongly suppressed by phosphatidylcholine. Triton X-100 and octyl glucoside were strongly inhibitory to all of the enzymes, although to different extents. The DGK inhibitor, R59022, inhibited DGK-II and to a lesser extent DGK-III, but little affected DGK-I activity. DGK-I was much more heat-stable than DGK-II and DGK-III. The Km values for ATP were 150 microM for DGK-I, 245 microM for DGK-II, and 450 microM for DGK-III. The apparent Km values for suspended diolein were not much different among the DGKs and were in the range of 50-80 microM. These observations indicate that human platelet cytosol contains DGK isozymes with different enzymological properties. Furthermore, the three DGKs isolated from human platelets were found not to cross-react with the antibody raised against porcine brain 80-kDa DGK, thus indicating that human platelets contain novel species of DGK.

Blood Platelets↗
PubMed1990

Glycopeptides in pus of acute pleurisy patients.

Glycopeptides were isolated from tryptic digests of pus from acute pleurisy patients. The hexose, hexosamine, and sialic acid contents rose over the first 2-4 days after admission to the hospital, continued at high levels for 5-8 hospital days, and fell to low levels after 9 hospital days. The course of duration after admission to the hospital was divided into three stages: 1-4 days after admission to the hospital, 5-8 hospital days, and 9-21 hospital days. Materials corresponding to these three stages were then collected for fractionation by DEAE-cellulose column chromatography. Fractionation of glycopeptides by DEAE-cellulose column chromatography yielded three glycopeptide fractions at 0.05 to 0.2 M NaCl. Column chromatography of crude material on DEAE-cellulose showed an increase in the 0.2 M NaCl fraction from the concentrate over a period of 4-8 hospital days due to a large increase in sialic acid-rich glycopeptide fraction.

Adult↗
PubMed1990

Interleukin-1 and -2 in sera of patients with chronic hepatitis (type B).

IL-1 beta and IL-2 values in serum from 28 patients with chronic hepatitis B diagnosed by liver biopsy and 23 healthy controls were measured by the radioimmunoassay (RIA) method. Though both values in patients seropositive for anti-HBe were slightly higher than those in patients seropositive for HBeAg, the differences between the two groups were not statistically significant. In contrast, the relationship between IL-1 beta and IL-2 in patients with chronic hepatitis was statistically significant (P less than 0.001). In general, high values of serum IL-1 beta and IL-2 were seen in patients with chronic persistent hepatitis and low values of serum IL-1 beta and IL-2 were seen in patients with chronic active hepatitis (severe) and in some of these with chronic persistent hepatitis. Serum IL-1 beta and IL-2 values of all patients with chronic hepatitis were higher than in healthy controls (P less than 0.001). Serum IL-1 beta and IL-2 in chronic hepatitis (B) are important indicators of the grade of the inflammatory state of the liver.

Adult↗
PubMed1989

Signal transduction in the onset of terminal keratinocyte differentiation induced by 1 alpha,25-dihydroxyvitamin D3: role of protein kinase C translocation.

We have investigated the possible involvement of phosphoinositide turnover in the keratinocyte differentiation induced by 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3]. The mass contents of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol and intracellular calcium level were measured in murine keratinocytes stimulated with 1 alpha,25(OH)2D3 or its derivatives. Although production of these second messengers was enhanced, there were no significant differences in time- and dose-dependences between 1 alpha,25(OH)2D3 and its derivatives. These vitamin D3 compounds promoted the translocation from the cytosol to membrane of protein kinase C (PKC). Despite such common profiles in the early signal transduction parameters, only 1 alpha,25(OH)2D3 induced formation of a cornified envelope characteristic of keratinocyte differentiation. Down-regulation of PKC by prolonged pretreatment with PDBu or inhibition of the enzyme with H-7 caused marked suppression of 1 alpha,25(OH)2D3-induced formation of cornified envelopes. These findings imply that PKC is necessary but not sufficient for the onset of terminal differentiation by 1 alpha,25(OH)2D3, and also that another as yet unspecified signal generated specifically by the active vitamin D3 is required for keratinocyte differentiation.

Animals↗