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Biomedical subjects

T Oguma

Publications and source records attributed to T Oguma.

At least 73 records · Page 4Linked to original sources
PubMed1993

Cloning and sequence analysis of the cyclomaltodextrinase gene from Bacillus sphaericus and expression in Escherichia coli cells.

The gene for cyclomaltodextrinase (CDase; EC 3.2.1.54) from Bacillus sphaericus E-244 was cloned in the recombinant plasmid pCD629. Sequencing a portion of pCD629 revealed a unique open reading frame of 1,773 nucleotides coding for a 591-amino-acid polypeptide. The deduced polypeptide sequence showed about 50% homology with that of a neopullulanase, and was slightly homologous to those of the cyclodextrin glucanotransferases and the alpha-amylases. The optimum pH, specific activity and Km value for beta-cyclodextrin of the CDase that has been produced in Escherichia coli cells were 8.0, 16.4 units/mg protein, and 0.41 mM, respectively. These values were almost identical to those from B. sphaericus E-244.

Amino Acid Sequence↗
PubMed1993

Studies on host specificity in Paragonimus westermani: ultrastructural study of inflammatory reactions to the parasite in rat muscles.

Inflammatory reactions to the lung fluke, Paragonimus westermani, in an abnormal host, the rat, were studied by electron microscopy. Inflammatory cells accumulated around the worms in rat muscles, but the reaction varied significantly in intensity as well as distribution of inflammatory cells from worm to worm in the same and different hosts. In an accumulation of inflammatory infiltrates around the worm, eosinophils were more commonly seen, and neutrophils and macrophages were fewer in number. Mast cells appeared rarely. Where inflammatory cells touched to the worms, the tegument of the worms was covered with moderately electron-dense flocculent material which included dense granules. This material, which probably consisted of immune complexes of host antibody and antigen secreted from tegumental granules, seemed to block the inflammatory cells from adhering to the worm surfaces. Inflammatory cells made direct contact with worm surfaces where flocculent material was absent. Dense secretory material was discharged from some eosinophils as a result of degranulation.

Animals↗
PubMed1993

Effects of pravastatin on lipid transfer protein and lecithin cholesterol acyltransferase in heterozygous familial hypercholesterolemia.

The effects of HMG CoA reductase inhibitor PRAVASTATIN on plasma lipoprotein levels, lipid transfer protein (LTP) activity and lecithin cholesterol acyltransferase (LCAT) activity were investigated in 20 patients with heterozygous familial hypercholesterolemia. Plasma total cholesterol decreased from 299.2 +/- 45.2 to 245.9 +/- 45.1 (mean +/- SD in mg/dl) (p < 0.0001), low density lipoprotein (LDL) cholesterol from 221.1 +/- 47.6 to 164.9 +/- 48.1 (p < 0.0001) and LDL-triglycerides from 38.0 +/- 10.2 to 30.2 +/- 8.8 (p < 0.0001). High density lipoprotein (HDL) cholesterol increased from 60.1 +/- 13.9 to 63.1 +/- 17.0 (p = 0.0264). The HDL-cholesterol: HDL-triglycerides ratio increased from 3.91 +/- 1.14 to 4.91 +/- 1.65 (p = 0.0029). Lipid transfer protein (LTP) activity (as % of transferred cholesteryl ester (CE)) decreased from 4.68 +/- 2.47 to 3.70 +/- 2.31 (p = 0.0024) and LCAT activity decreased from 113.1 +/- 29.9 (U/L) to 97.0 +/- 22.7. There was a negative correlation between LTP/LCAT ratio and HDL-C levels. These results suggested that the changes in plasma HDL-cholesterol concentrations during treatment with pravastatin may be related to the decreases in LTP and LCAT activity due to this drug.

Adult↗
PubMed1992

Study of the measurement of chondroitin sulphates in rabbit plasma and serum.

A highly sensitive high-performance liquid chromatography method, which was established by us for the determination of chondroitin sulphates in biological substances as their unsaturated disaccharides, was applied to elucidate the qualitative and quantitative differences in chondroitin sulphates in rabbit plasma and serum samples. In this work, it was found that rabbit plasma contains low-sulphated chondroitin 4-sulphate (approximately 40% sulphation at the 4-position of N-acetyl galactosamine), while serum contains the low-sulphated chondroitin 4-sulphate and fully sulphated chondroitin 4-sulphate (approximately 96% sulphation). The latter was released from platelets during coagulation of blood.

Animals↗
PubMed1992

Phase I clinical studies of S-1108: safety and pharmacokinetics in a multiple-administration study with special emphasis on the influence on carnitine body stores.

S-1108, the prodrug of S-1006, was given to healthy volunteers three times a day (TID) for 8 days in a dose of 200 mg in a crossover placebo-controlled study. The safety of S-1108 and the pharmacokinetics of S-1006 and pivalic acid liberated from pivaloyloxymethyl ester of S-1108 were investigated. There were no abnormal symptoms or signs, as observed by physical and laboratory tests. The half-life and area under the concentration-time curve of S-1006 was reduced from 1.11 +/- 0.17 h at the first dose to 0.87 +/- 0.18 h at the last dose and from 7.30 +/- 1.10 to 5.20 +/- 0.85 micrograms.h/ml, respectively. However, there was no significant difference in the peak concentration between the two doses. Pivalic acid was found to be completely detoxified by conjugation with carnitine. The total urinary recovery of pivalic acid as pivaloylcarnitine was 98.7 +/- 3.6%, resulting in an increase of daily carnitine urinary excretion two- to threefold the predose value. During the multiple administration of S-1108, the plasma carnitine concentration was reduced to and maintained at 50 to 70% of the control value, suggesting that there might be enough carnitine store in the body to detoxify the pivalic acid in a dose of 200 mg TID. Moreover, the reduced plasma carnitine was rapidly returned to the control value within a few days after the cessation of the administration of 200 mg TID.

Adult↗
PubMed1992

Effect of antacid on absorption of the quinolone lomefloxacin.

The effect of antacid on the absorption of lomefloxacin (LFLX) in humans was studied. When LFLX was orally administered concomitantly with aluminum- and magnesium-containing antacids under fasting conditions, its level in plasma decreased by one-half and its area under the concentration-time curve was reduced by 40% compared with the levels observed after treatment with LFLX alone. The urinary recovery value also decreased by 40%. No such effects were noted after coadministration of LFLX and a nonmetallic antacid. This study confirmed the existence of chelate complexes of LFLX with Al3+ and Mg2+ and examined the chelating strength. The stability constants of LFLX with Al3+ and Mg2+ were measured and compared with those of ofloxacin and norfloxacin; little difference was observed among them. LFLX was found to bind more strongly with Al3+ than with Mg2+. Further, the existence of chelate formation was proven by 13C-nuclear magnetic resonance spectroscopy. The decrease in the LFLX level in plasma in humans could be explained by a reduced absorption of the Al(3+)- and Mg(2+)-LFLX chelate complexes.

Adult↗
PubMed1991

Hydrolysis of branched cyclodextrins by a cyclodextrin-hydrolyzing enzyme from Bacillus sphaericus E-244.

The action of a cyclodextrin-hydrolyzing enzyme from Bacillus sphaericus E-244 on branched alpha- and beta-cyclodextrins was investigated. Glucosyl-alpha-cyclodextrin (6-O-alpha-D-glucosylcyclomaltohexaose) and maltosyl-alpha-cyclodextrin (6-O-alpha-D-maltosylcyclomaltohexaose) were hydrolyzed to 6(3)-O-alpha-D-glucosylmaltohexaose and 6(3)-O-alpha-D-maltosylmaltohexaose, respectively. Glucosyl-beta-cyclodextrin (6-O-alpha-D-glucosylcyclomaltoheptose) and maltosyl-beta-cyclodextrin (6-O-alpha-D-maltosyclomaltohepatose) were also mainly transformed to 6(4)-O-alpha-D-glucosylmaltoheptaose and 6(4)-O-alpha-D-maltosylmaltoheptaose, respectively. These results suggest that the cyclodextrin-hydrolyzing enzyme cleaves branched alpha- and beta-cyclodextrins at an alpha-1,4 linkage which is located furthest from the branching point on the cyclodextrin ring.

Bacillus↗
PubMed1991

Pharmacokinetic analysis of the effects of different foods on absorption of cefaclor.

Cefaclor is an oral cephalosporin antibiotic which has a broad antibacterial spectrum. The purpose of this study was to investigate the effect of food on the absorption of cefaclor and to analyze kinetically the absorption process of this drug. Cefaclor was given to eight volunteers at five test times: after overnight fasting, after two rice meals (350 and 700 cal [1 cal = 4.184 J]), and after two bread meals (500 and 1,000 cal). Urinary recoveries of cefaclor and concentrations of the drug in plasma were determined for each administration. Areas under the concentration-time curves and urinary recoveries were not affected by food intake, but the maximum concentration of drug in serum was reduced and the time to maximum concentration of drug in serum was prolonged depending on the type and the quantity of the meal. The larger the quantity of the meal, the more the maximum concentration of drug in serum and the time to maximum concentration of drug in serum were affected. The rice meals affected the absorption process of cefaclor more than the bread meals. The concentrations of cefaclor in plasma following administration after overnight fasting were well fitted to a conventional one-compartment model with a first-order absorption process, but those after the other administrations were not fitted to the model. For the pharmacokinetic analysis of those data, it was necessary to introduce a transfer process from administration site to absorption site to the conventional model. The concentrations in plasma after rice and bread meals were best fitted to the model with a zero-order transfer process than to that with a first-order process. The velocity of the transfer process depended on the type and volume of the meal.

Administration, Oral↗
PubMed1991

Analyses of rabbit platelet proteo-chondroitin sulfates localized on the surface and in the granules.

Platelet proteo-chondroitin sulfates localize on the surface and in the granules. Western blotting method is able to selectively detect core-proteins prepared from proteo-chondroitin sulfates by chondroitinase ABC digestion. A very highly sensitive high-performance liquid chromatographic method was established for the determination of chondroitin sulfates as their unsaturated disaccharides. These methods were applied to rabbit platelet proteo-chondroitin sulfates. It was found that both rabbit platelet surface proteo-chondroitin sulfate and granule proteo-chondroitin sulfate consist of a predominantly homogeneous chondroitin 4-sulfate and a single core-protein having a molecular weight of approximately 26 kDa.

Animals↗
PubMed1991

Relationship between plasma concentration of morphine and analgesic effectiveness.

Morphine is a key drug for cancer pain management. In this study, we analyzed plasma morphine concentration in cancer patients who received continuous morphine drip and/or oral administrations of morphine: (1) The plasma concentration of morphine varied widely in patients whose pain was satisfactorily controlled at a constant dosage of morphine. The absolute value of the plasma concentration of morphine necessary for effective pain control could not be estimated; (2) When MS Contin was given at the doses 20 mg, 30 mg, 40 mg, the plasma concentration of morphine increased with increasing dose. Thus, when the dose was increased according to the severity of pain, the plasma concentration of morphine increased and in turn an analgesic effect was obtained; (3) In those patients who had difficulty in taking oral preparations and/or blocked intestines, plasma concentration of morphine following oral administration was relatively low causing an unsatisfactory analgesic effect. However, by changing from oral administration to continuous drip infusion, the plasma concentration of morphine became higher and pain relief was obtained; (4) Continuous drip infusion of morphine progressively increased plasma concentration of morphine in parallel with the increase in the dose of morphine if the patients had no pleural effusion, ascites, and/or oedema. In contrast, plasma morphine concentration in patients with pleural effusion, ascites, and/or oedema was about half of that observed in patients who have normal distribution area. The rapid development of pleural effusion and ascites lowers the blood level of morphine; (5) To use the plasma concentration of morphine as an index for the analgesic effect, it is essential to develop a method to measure the plasma concentration of morphine rapidly.

Aged↗
PubMed1990

Purification and some properties of cyclodextrin-hydrolyzing enzyme from Bacillus sphaericus.

An intracellular cyclodextrin-hydrolyzing enzyme from Bacillus sphaericus E-244 isolated from soil was purified to a homogeneous state by means of Triton X-100 extraction, DEAE-Sepharose column chromatography, hydrophobic and molecular-sieve HPLC. The enzyme was estimated to have an Mr of 72,000 by sodium dodecyl sulfate polyacrylamide gel electrophoresis and 144,000 by HPLC gel filtration on TSK gel G 3000 SW. It had a pH optimum of 8.0, and the enzyme, stable at 25 degrees C and pH 5.5-9.5 for 24 h, was inactivated at 50 degrees C for 10 min. The enzyme hydrolyzed beta-cyclodextrin more effectively than linear maltooligosaccharides such as maltopentaose, maltohexaose and maltoheptaose or polysaccharides such as starch, amylopectin, amylose and pullulan.

Bacillus↗
PubMed1990

Pharmacokinetics of flomoxef in mucosal tissue of the middle ear and mastoid following intravenous administration in humans.

The pharmacokinetics of flomoxef in serum and in the mucosal tissue of the middle ear and mastoid were studied in 9 patients undergoing tympanoplasties. All patients received 1 g of flomoxef intravenously. Flomoxef levels in serum and in mucosal tissue were determined by a bioassay method. The peak value of mean concentrations of flomoxef in the mucosal tissue was 30.3 +/- 11.7 micrograms/ml at 10 min after the administrations. Pharmacokinetic analyses showed that the concentration of flomoxef in the mucosal tissue was over 1.56 micrograms/ml (which is the MIC90 for the common pathogens of otitis media) for more than 2 h and decreased parallel with serum concentration with a half-life of about 40 min.

Adolescent↗
PubMed1990

[Pharmacokinetics of cis-diammine (glycolato) platinum (254-S), a new platinum antitumor agent, following an intravenous and intraperitoneal infusion bioactive platinum concentration profile].

The pharmacokinetics of cis-diammine (glycolato) platinum (254-S) was investigated in cancer patients following intravenous and intraperitoneal infusion. The serum concentrations of total and unbound 254-S were determined by bioassay and chemical assay as platinum. Platinum detected by bioassay was thought to be active and unchanged 254-S. Almost all of platinum in plasma were found to be active and unbound to protein because of no differences in the concentrations determined by bioassay and chemical assay and in plasma and plasma filtrate. In abdominal ascites, platinum concentrations determined by bioassay corresponded with those determined by chemical assay, suggesting that 254-S was stable in abdominal ascites. The Cmax and AUC of active 254-S in plasma determined by bioassay following an intraperitoneal infusion were about 60% and 60-80% of those following an intravenous infusion, respectively. These results showed that 254-S was well absorbed into systemic circulation from abdominal ascites as an active form. It is concluded that antitumor effect may be obtained following an intraperitoneal infusion of 254-S as well as for the reduction of abdominal ascites.

Aged↗
PubMed1989

Transport characteristics of ceftibuten, a new oral cephem, in rat intestinal brush-border membrane vesicles: relationship to oligopeptide and amino beta-lactam transport.

Ceftibuten undergoes H+-coupled uphill transport across rat small intestinal brush-border membrane vesicles. The effects of amino acids, peptides, folate, and beta-lactams on the uptake of ceftibuten were examined. Uptake of ceftibuten was competitively inhibited by dipeptides or tripeptides. A counter-transport effect on ceftibuten uptake was observed in the vesicle preloaded with these peptides, and the transport was temporarily against a concentration gradient (overshooting). On the other hand, ceftibuten uptake was not changed by amino acids and a tetrapeptide. Therefore, ceftibuten is predominantly transported via the oligopeptide transport system in the brush-border membranes. The relationship of ceftibuten transport to folate and other oral antibiotics was also investigated. Cyclacillin, cephradine, and cefadroxil exhibited both inhibitory and countertransport effects, but folate, cefaclor, and cephalexin showed only a slight inhibitory effect. As the transport of cefaclor showed no uphill uptake in the presence of a H+ gradient and its H+ stimulated uptake was small, a H+ gradient-independent carrier-mediated system seems to participate in its transport. These findings suggest that two different carrier-mediated transport systems, H+ gradient dependent and independent, may exist for oral cephems.

Amino Acids↗
PubMed1989

Transport characteristics of ceftibuten (7432-S), a new oral cephem, in rat intestinal brush-border membrane vesicles: proton-coupled and stereoselective transport of ceftibuten.

The transport characteristics of ceftibuten in rat intestinal brush-border membrane vesicles were investigated by a rapid filtration technique. Ceftibuten uptake was markedly stimulated by an inwardly directed H+ gradient (pH 7.5 inside, pH 5.5 outside) in comparison with that in the absence of a H+ gradient. The uptake at 30 sec was four times greater than that observed at equilibrium (overshoot phenomenon), while the H+ gradient-stimulated uptake of ceftibuten was markedly reduced in the presence of FCCP, a protonophore. These results suggested H+-coupled uphill transport of ceftibuten. In contrast, an inwardly directed Na+ gradient had no effect on ceftibuten uptake. The valinomycin-induced K+ diffusion potential (inside positive) significantly stimulated the ceftibuten uptake, suggesting net transfer of the negative charge. In contrast to the cis-isomer ceftibuten, the trans isomer of ceftibuten is not readily absorbed from the intestine, and its uptake was found not to be affected by a H+ gradient. Since the lipophilicity of the trans isomer is similar to that of ceftibuten, the uptake process appears to be stereoselective. The initial uptake of ceftibuten and its analogue cefaclor was concentration dependent under a H+ gradient. The apparent Km value was 0.2 mM for ceftibuten and 3.0 mM for cefaclor.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

Phase I clinical studies of 7432-S, a new oral cephalosporin: safety and pharmacokinetics.

Phase I clinical studies of 7432-S, a new oral cephalosporin, including a randomized placebo-controlled trial were conducted with 40 healthy volunteers. In single-dose studies, 7432-S was orally administered at doses of 25, 50, 100, and 200 mg. The mean plasma levels peaked at 2.1 to 3.0 hours and reached 1.9, 3.6, 5.6, and 11.6 micrograms/ml, respectively. Linear correlation was observed between plasma AUC values and doses given. The half-lives of the plasma levels were 0.88 to 2.26 hours with a mean of 1.53 +/- 0.33 hours. The mean urinary recoveries were 67.5 to 75.2% of the dose within 24 hours. 7432-S was partially metabolized to 7432-S-trans which was excreted in urine at 7.2 to 9.2% of the doses. Study of the meal effect showed that AUC values and peak levels were not altered although the time to the peak levels was slightly prolonged. In multiple-dose studies, 100 mg of 7432-S twice daily for 2 weeks and 200 mg twice daily for 1 week were administered and there was no abnormal accumulation of 7432-S in plasma throughout the study. No significant differences were observed in plasma levels and urinary recoveries between single- and multiple-dose regimens. Clinical symptoms, physical tests, laboratory parameters, and fecal levels of vitamins K1 and K2 were in normal ranges. 7432-S was concluded to be safe and well tolerated.

Administration, Oral↗
PubMed1987

Effects of alcohol-metabolizing enzyme inhibitors and beta-lactam antibiotics on ethanol elimination in rats.

The in vivo effects of alcohol-metabolizing enzyme inhibitors and beta-lactam antibiotics upon the ethanol elimination rate were examined in rats. Intravenous administration of ethanol caused a dose-dependent increase in blood ethanol level, and the ethanol elimination could be well described by a two compartment model. Pretreatment of rats with enzyme inhibitors caused a marked decrease in the ethanol elimination rate associated with the depression of the enzyme activities. Fasting of the animals caused a decrease in the ethanol elimination rate per animal associated with a decrease in the liver weight. However, no alteration was evident when the rate was expressed as the rate per g of liver. When animals were pretreated with a high dose of N-methyltetrazolethiol (NMTT)- containing beta-lactam antibiotics or NMTT itself, which causes a disulfiram-like reaction, the ethanol elimination rate per animal was depressed concomitant with an increase in the blood acetaldehyde level. The ethanol elimination rate in these animals showed lower values even when expressed as the rate per g liver. On the other hand, administration of cephems without NMTT, which cause no disulfiram-like reaction, led to a slight decline in the elimination rate per animal, although no alteration was detected when the rate was expressed as the rate per g liver. The findings indicated that the ethanol elimination in vivo per animal is regulated by the total capacity of the alcohol-metabolizing enzyme activities in the whole liver.

Acetaldehyde↗