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K Ozaki

Publications and source records attributed to K Ozaki.

At least 19 recordsLinked to original sources
PubMed1992

Biological activities and quantitative structure-activity relationships of spiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-triones as aldose reductase inhibitors.

A series of spiro[imidazolidine-4,4'(1'H)-quinazoline]- 2,2'5(3'H)-triones were prepared and tested for aldose reductase inhibitory activity. The 6'-halogenated derivatives were found to be highly potent in vitro inhibitors of male rabbit lens aldose reductase and in vivo inhibitors of polyol accumulation in the sciatic nerves of galactosemic rats. Of these, (4R)-6'-chloro-3'-methylspiro[imidazolidine-4,4'(1'H)-quinazoline] -2,2',5(3'H)-trione (67) showed the most potent in vitro and in vivo activities. An oral dose of 3 g/kg of compound 67 caused neither death nor behavioral abnormality in the preliminary acute toxicity study using mice and rats. Compound 67 was selected as a candidate for further evaluation. The quantitative structure-activity relationships in this series are also discussed.

Aldehyde Reductase↗
PubMed1992

Expression of a functional asialoglycoprotein receptor through transfection of a cloned cDNA that encodes a macrophage lectin.

The Gal/GalNAc-specific lectin on rat peritoneal macrophages (macrophage asialoglycoprotein binding protein, M-ASGP-BP) is structurally similar to rat hepatic asialoglycoprotein-binding protein (ASGP-BP) or rat hepatic lectin (RHL) and is highly homologous with the major component of RHL, RHL-1 (Ii, M, Kurata, H., Itoh, N., Yamashina, I., and Kawasaki, T. (1990) J. Biol. Chem. 265, 11295-11298). We found in this study that transfection with a cDNA clone that encodes a single polypeptide, M-ASGP-BP, was sufficient for the expression of an endocytic receptor for asialoorosomucoid (ASOR) on the COS-1 cell surface. The Kuptake value for ASOR for the transfected cells was 12.5 nM, which is similar to that for peritoneal macrophages (23 nM), and the number of ASOR bound on the cell surface was 1-8 x 10(5)/cell, this value being hundreds of times larger than that for peritoneal macrophages. 125I-ASOR bound on the surfaces of the transfected cells was rapidly internalized on incubation at 37 degrees C, and after 90 min of incubation, most of the radioactivity was recovered in acid-soluble degraded products from the medium. These results confirmed that the cDNA cloned in our previous study does in fact encode M-ASGP-BP and also that the single polypeptide chain can form a homooligomeric receptor (probably a hexamer or octamer) exhibiting high affinity for ASOR. The latter property was distinct from that of the hepatic ASGP-BP in that simultaneous transfection of two cloned cDNAs that encode RHL-1 and RHL-2/3 was required to produce an active ASOR receptor (McPhaul, M., and Berg, P. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 8863-8867). This M-ASGP-BP expression system may serve as a simple model with which to investigate the molecular mechanisms underlying carbohydrate-mediated endocytosis.

Animals↗
PubMed1992

Lack of effects of post-initiation cholesterol on 3,2'-dimethyl-4-aminobiphenyl-induced prostate carcinogenesis.

The effects of cholesterol on 3,2'-dimethyl-4-aminobiphenyl (DMAB)-induced rat prostate carcinogenesis were investigated in male F344 rats. Animals were given 10 subcutaneous (s.c.) injections of 50 mg/kg body weight of DMAB at 2-week intervals, each time 2 days after transfer from 1 week on 0.75 ppm of an ethinyl estradiol (EE)-supplemented diet to a basal diet. From week 20, the animals received treatment with cholesterol (2 or 1%, in the diet), saponin (1 or 0.2 mg/rat/week, s.c.), or clofibrate (0.3%, in the diet) for 40 weeks. Although serum cholesterol levels were significantly increased by administration of cholesterol itself, and were decreased by clofibrate, the incidences of atypical hyperplasias and carcinomas of the ventral prostate were very similar with all treatments. Thus, under the present conditions, high or low cholesteremia did not affect rat prostate lesion development.

Aminobiphenyl Compounds↗
PubMed1992

A single optical fiber fluorometric device for measurement of intracellular Ca2+ concentration: its application to hippocampal neurons in vitro and in vivo.

We developed a new system to measure the intracellular Ca2+ concentration in the deep region of the central nervous system with a single optical fiber (300 microns in diameter), used for both excitation and detection of the fluorescence of previously loaded fura-2. With this system, a brain region loaded with fura-2 was illuminated by a rotating disc bearing three different interference filters of 340, 360 and 380 nm at a rate of 600 rpm. The emitted fluorescence was collected by the same fiber connected to a photomultiplier whose output was fed into a computer which regulates the timing of illumination and detection. The time course of the change in the fluorescence due to 340, 360 or 380 nm excitation was measured simultaneously at the maximum sampling rate of 10 points/s. Ratios of fluorescence intensities were obtained after the experiment. After confirming that this system was sensitive enough to detect the change of intracellular Ca2+ concentration in cultured hippocampal neurons and hippocampal slices during depolarization by high potassium medium (50 mM), we applied this system to anesthetized rats. In the hippocampus preloaded with fura-2, characteristic changes in fluorescence intensities ascribed to an increase in intracellular Ca2+ concentration were detected after asphyxia. The system is potentially useful for investigating the physiological and pathological roles of Ca2+ in the brain.

Anesthesia↗
PubMed1992

Enhancement of therapeutic efficacy of aclarubicin against lymph node metastases using a new dosage form: aclarubicin adsorbed on activated carbon particles.

Seven days after a subcutaneous inoculation of 5 x 10(5) P388 leukemia cells into the foot pad of the left hind paw of donor mouse, aclarubicin (0.2 mg/kg body weight) was injected subcutaneously into the hind paw of the opposite foot pad in the form of ACR-CH or aclarubicin aqueous solution. On day 10, the left popliteal and the lower para-aortic lymph nodes taken from each donor were transferred intraperitoneally to a normal recipient mouse. The combined survival time of recipients and the viable P388 leukemia cell number in popliteal and para-aortic lymph nodes were estimated with a calibration formula. Our results showed that the survival curve of recipients given ACR-CH was statistically improved compared with that of other treatment groups.

Aclarubicin↗
PubMed1992

Modifying effects of various chemicals on tumor development in a rat wide-spectrum organ carcinogenesis model.

The efficacy of a wide-spectrum organ carcinogenesis model for detection of modification potential of exogenous agents was investigated in F344 male rats. Groups of animals were sequentially injected with N-bis(2-hydroxypropyl)nitrosamine (1000 mg/kg body weight, i.p., in saline, twice in week 1), N-ethyl-N-hydroxyethylnitrosamine (1500 mg/kg body weight, i.g., in distilled water, twice in week 2) and 3,2'-dimethyl-4-aminobiphenyl (75 mg/kg body weight, s.c., in corn oil, twice in week 3) for wide-spectrum initiation of target organs and then given one of 10 test chemicals, comprising 6 hepatocarcinogens and 4 non-hepatocarcinogens, for 12 weeks. All 10 chemicals exerted modifying effects in their respective target organs. Enhancing influence could be detected in the liver and urinary bladder with 2-acetylaminofluorene, ethionine, and 3'-methyl-4-dimethylaminoazobenzene; in the liver and thyroid with 4,4'-diaminodiphenylmethane and phenobarbital; in the esophagus and urinary bladder with N-butyl-N-(4-hydroxybutyl)nitrosamine; in the forestomach and urinary bladder with butylated hydroxyanisole; in the liver with 7,12-dimethylbenz[a]anthracene and in the liver and lung with 3-methylcholanthrene. Inhibitory effects on development of glutathione S-transferase placental form-positive liver cell foci were observed with clofibrate. The results indicate that the present model can be reliably utilized as a whole body medium-term bioassay system for assessment of environmental cancer modifiers.

Animals↗
PubMed1992

Effects of modifying agents on conformity of enzyme phenotype and proliferative potential in focal preneoplastic and neoplastic liver cell lesions in rats.

Development of preneoplastic lesions in the rat liver under the influence of various modifiers was investigated with particular attention to changes in simultaneous expression of altered enzyme phenotype within the lesions (conformity) and proliferation potential. Degree of conformity of marker enzymes such as glutathione S-transferase placental form (GST-P), glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase, adenosine triphosphatase and gamma-glutamyltranspeptidase was compared with levels of 5-bromo-2-deoxyuridine labeling. After initiation with diethylnitrosamine, rats were administered the hepatopromoter sodium phenobarbital (PB, 0.05%), the antioxidant ethoxyquin (EQ, 0.5%), or a peroxisome proliferator, clofibrate (CF, 1.0%) or di(2-ethylhexyl)-phthalate (0.3%) and killed at week 16 or 32. The PB promoting regimen was clearly associated with increase in the numbers of high conformity class lesions simultaneously expressing three to five enzymes, and elevated proliferation potential. The inhibitor, EQ, in contrast, brought about a time-dependent decrease in conformity so that only 1 or 2 alterations were most commonly observed at week 32. Lesion populations in the peroxisome proliferator- and especially CF-treated cases were characterized by obvious dissociation between degree of conformity and proliferative status. Such treatment-dependent differences were not always correlated with the size of the lesion. The results thus suggested that the conformity and proliferation potential of preneoplastic lesions are dependent on modification treatment. Overall, GST-P was found to be the most reliable marker, although G6PD was less influenced in the peroxisome proliferator cases.

Adenosine Triphosphatases↗
PubMed1992

[A clinical study of bacteremia in the last fifteen years].

Between 1976 and 1990, 208 cases of bacteremia in our department were studied. Community acquired bacteremias were only 18 (8.7%) cases. Bacteremias, particularly caused by Gram positive organisms, increased significantly after 1981, compared with the first five years. It was related to the marked increase in cases of venous access devices and less sensitivity of the Gram positive organisms to the new cephem antibiotics. In the study, 144 (69.2%) cases were eradicated. Severe underlying diseases or complication of pneumonia influenced the eradication rate of bacteremia. Bacteremia caused by methicillin resistant Staphylococcus aureus or Pseudomonas aeruginosa showed poor prognosis. The average duration from onset to death, was 5.1 days. Forty cases (62.5%) died within 3 days. Among the 201 cases, leukocytosis (WBC greater than 10,000/mm3) was present in 38.3%, while leukopenia (WBC less than 1000/mm3) in 25.3%. Eradication rate between the two groups was not significant. CRP was elevated (greater than 8.5 mg/dl) in 63.5%. The prognosis of this group was significantly poor. Elevation of serum bilirubin was also related with increase of mortality. According to these results, empiric therapy before the isolation of organisms is the most important strategy for treatment of bacteremia.

Adolescent↗
PubMed1992

[Influences of hypercholesterolemia on the vessel function of isolated rat thoracic aorta].

Mature male rats (SD strain, 8-week-old) were fed with a normal diet or a high cholesterol diet (HC: 1.5% cholesterol and 0.5% Na cholate in the normal diet) up to 8 weeks, and we examined how the vascular function level of the isolated thoracic aorta and the histological figures of some tissues including the aorta would change. 1) The contracting reactivity to phenylephrine (Phe, 10 microM) and the relaxing reactivity to acetylcholine (1 microM) measured thereafter remained unchanged during the period of aging and were not influenced by HC-feeding. The addition of L-arginine (Arg, 100 microM) did not affect the results. 2) The ability of the aorta to release NO and to relax, which was evaluated as the extent of the endothelium-dependent potentiation by NG-monomethyl-L-arginine (NMA) of the Phe contraction, did not change by HC-feeding up to 4 weeks, but appears to be attenuated after 8-week feeding. 3) The EC50 of NMA for the potentiation estimated without the addition of Arg remained unchanged, while the one in the presence of Arg gradually increased with aging but not with HC-feeding. 4) The histopathological study of the aorta and other tissues failed to detect any notable atherogenic changes in any of the HC-fed groups. The results indicate that under the experimental conditions employed, HC-feeding would not develop any significant atherogenic histopathological changes in the endothelium-smooth muscle preparation, but may induce some dysfunction in the NO-release mediated and auto-regulatory function of the vascular tone.

Acetylcholine↗
PubMed1992

Nucleotide sequence of the gene for an alkaline endoglucanase from an alkalophilic Bacillus and its expression in Escherichia coli and Bacillus subtilis.

The gene for an alkaline endoglucanase from the alkalophilic Bacillus sp. KSM-64 was cloned into the HindIII site of pBR322 and expressed in Escherichia coli HB101. The nucleotide sequence of a 4.1-kb region of the HindIII insert had two open reading frames, ORF-1 and ORF-2. The protein deduced from ORF-1 was composed of 244 amino acids with an M(r) of 27,865. Subcloning analysis proved that the alkaline endoglucanase was encoded by ORF-2 (822 amino acids with an M(r) of 91,040). Upstream from ORF-2, there were three consensus like sequences of the sigma A-type promoter of Bacillus subtilis, a putative Shine-Dalgarno sequence (AGGAGGT), and a catabolite repression operator-like sequence (TGTAAGCGGTTAACC). The HindIII insert was subcloned into a shuttle vector, pHY300PLK, and the encoded alkaline endoglucanase gene was highly expressed both in E. coli and B. subtilis. One of the three promoter-like sequences in ORF-2 could be suitable for high levels of enzyme expression in both host organisms.

Amino Acid Sequence↗
PubMed1992

Morphological characterization of hypersensitive human radicular dentin and the effect of a light-curing resin liner on tubular occlusion.

A dentin biopsy technique was employed to compare the morphological features of hypersensitive and non-sensitive human radicular dentin. Specimens sampled from different areas in the same root surface displaying hypersensitivity or non-sensitivity were prepared for examination in the scanning electron microscope (SEM). Before analysis some specimens were exposed to surface demineralization and digestion of collagen to allow observation of subsurface portions of the dentinal tubules. In another set of observations the potential of a light-curing resin liner to penetrate root dentin in vitro and to maintain tubular occlusion over time following treatment of hypersensitive radicular dentin were examined. Orifices of many dentinal tubules were open in hypersensitive regions while non-sensitive areas generally displayed tubules occluded with mineralized material. SEM-images of HCl-collagenase treated specimens demonstrated the frequent presence of membrane-like structures in tubules of hypersensitive dentin. In non-sensitive dentin these structures were sparse. Topical application of a light-curing resin liner to wedge shaped defects prepared in radicular dentin of extracted human teeth resulted in a surface coating with a resin thickness of 20-50 microns. Resin penetrated dentinal tubules to a depth of more than 5 microns. Dentin biopsies examined 6 months after treatment with the liner showed presence of resin-like material in a majority of the tubules in dentin where hypersensitivity was no longer perceived. In none of the specimens did the liner remain as a surface coating. In areas of recurrent hypersensitivity more than half of the tubules presented with open orifices.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Etching, Dental↗
PubMed1992

[Enhancement of therapeutic efficacy of aclarubicin against lymph node metastases using a new dosage form: aclarubicin adsorbed on activated carbon particles].

Seven days after a subcutaneous inoculation of 5 x 10(5) P388 leukemia cells into the foot pad of the left hind paw of donor mouse, aclarubicin (0.2mg/kg body weight) was injected subcutaneously into the hind paw of the opposite foot pad in the form of ACR-CH or aclarubicin aqueous solution. On day 10, the left popliteal and the lower para-aortic lymph nodes taken from each donor were transferred intraperitoneally to a normal recipient mouse. The combined survival time of recipients and the viable P388 leukemia cell number in popliteal and para-aortic lymph nodes were estimated with a calibration formula. Our results showed that the survival curve of recipients given ACR-CH was statistically improved compared with that of other treatment groups.

Aclarubicin↗
PubMed1992

[Cancer chemotherapy for lymph nodal metastases using activated carbon particles adsorbing methotrexate].

A new dosage format (MTX-CH) of methotrexate (MTX) comprises MTX adsorbed onto fine activated carbon particles which has strong affinity to lymphatics. MTX-CH was tested for its therapeutic effects on lymph node metastases in mice experimental model. It is known that metastases have been established in the regional lymph nodes of all mice 7 days after subcutaneous inoculation with P388 leukemia cells at 5 x 10(5) cells/mouse in left hind foot pad, and that assay mice survival time becomes short in proportion to log [P388 cell number inoculated intraperitoneally]. Therefore, drug treatment was carried out on day 7, and the regional nodes were extirpated and transferred intraperitoneally to assay mice on day 10. The survival time of mice to whom transferred were the nodes of mice treated with MTX-CH was significantly longer compared with those treated with MTX aqueous solution.

Animals↗
PubMed1992

[Effects of induced hypotensive anesthesia on the blood coagulation-fibrinolysis system measured by thrombelastography--comparison between prostaglandin E1 and trimethaphan].

The coagulation-fibrinolysis system has been studied in two groups of 16 patients classified ASA 1 undergoing radical mastectomy during controlled hypotensive anesthesia induced by prostaglandin E1 (PGE1) or by trimethaphan (TMP) under enflurane anesthesia. Thrombelastography (TEG) was used to evaluate both coagulation and fibrinolysis systems, while simultaneously measuring platelet aggregation in response to ADP and collagen, prothrombin time (PT), activated partial thromboplastin time (APTT), serum concentrations of fibrinogen, and platelet counts. In the PGE1 group, APTT was significantly shortened (P less than 0.05) while the drug was being infused, but there was no statistically significant difference between the two groups, which was considered due to the effect of enflurane. Also, no statistically significant changes were noted in the other measured parameters. These results suggest that controlled hypotensive anesthesia using either PGE1 or TMP under enflurane anesthesia produces no significant changes in the blood coagulation-fibrinolysis system and that both are useful for the management of bleeding during surgery. Further, TEG was found to reflect other parameters properly. It is therefore useful for monitoring the blood coagulation-fibrinolysis system during anesthesia.

Adult↗
PubMed1992

[Effect of nafamostat mesilate on the renin-aldosterone system].

It has been reported that continuous intravenous infusion of nafamostat mesilate (FUT) produces hyperkalemia due to reduced urinary excretion of potassium. The present study was performed to see whether renin-aldosterone effect is involved in this inhibition of potassium excretion. Ten patients were studied who had been given this drug (4 mg.hr-1) to prevent postsurgical pancreatitis or DIC. Urine potassium output decreased significantly from 44 +/- 5 microEq.min-1 prior to administration of FUT to 18 +/- 4 microEq.min-1 in 3 hours, sodium/potassium ratio increased significantly from 1.7 +/- 0.7 prior to administration of FUT to 5.4 +/- 3.3 in 5 hours; and plasma aldosterone decreased significantly from 92 +/- 24 pg.ml-1 prior to administration of FUT to 63 +/- 22 pg.ml-1 in 6 hours. The results suggest that hyposecretion of aldosterone may be one of the main causes of hypokalemia. Reduced secretion of aldosterone may be due to other factors than the suppression of renin-angiotensin system.

Benzamidines↗