Biomedical subjects
Publications and source records attributed to T Shimamoto.
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In order to elucidate the effect of antibiotics (gentamicin) on placental amino acids transport, we investigated L-alanine transport using microvillous membrane vesicles prepared from full-term human placental by a rapid filtration technique. 1. The active transport of L-alanine into microvillous membrane vesicles was dependent on Na+ electrochemical gradient (extravesicular greater than intravesicular). And the double reciprocal plot of this Na+ dependent initial uptake rate versus L-alanine concentration exhibited an apparent Km of 0.79 + 0.23mM and a Vmax of 3.56 + 0.70n mol/mg protein/20 sec. 2. Gentamicin did not affect the Km value of this Na+ dependent L-alanine transport kinetics (0.77 + 0.19 mM [lmM gentamicin], 0.79 + 0.21mM [10mM gentamicin]). On the other hand, gentamicin apparently decreased, the Vmax value of this transport kinetics (1.99 + 0.48n mol/mg protein/20 sec [1mM gentamicin], 1.12 + 0.32n mol/mg protein/20 sec [10mM gentamicin]).
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A method affording direct estimation of the drug absorption rate from blood level data using arbitrary time intervals has been derived based on the staircase input principle. In the derivation, the drug was assumed to follow linear kinetics where the plasma concentration of the drug after an impulse input is expressed by a multiexponential function. Drug absorption was assumed to occur at a constant rate during each subsequent sampling interval. The absorption rate profiles obtained by the method using several numerical examples were expressed as a set of rectangular pulses. Divergence in the profiles reflected blood sampling measurement errors rather than errors due to the deconvolution. Smoothing of the rate profiles by calculating the mean of the absorption rates between adjacent time intervals gave realistic results. Absorption rate profiles for theophylline obtained by the method using published data gave information on the initiation and termination of the absorption as well as the extent of absorption from the dosage form.
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A new nonionic detergent, heptylthioglucoside, was synthesized and found to be more soluble than octylthioglucoside in water at low temperatures. Use of this detergent for solubilization and reconstitution of membrane proteins of Escherichia coli was examined. Heptylthioglucoside was as effective as octylthioglucoside and octylglucoside in solubilizing membrane proteins, and by the heptylthioglucoside-dilution procedure the H+-translocating ATPase (F1F0) and melibiose carrier could easily be reconstituted into liposomes. It is concluded that heptylthioglucoside is very useful in studies on membrane proteins.
The absorption mechanisms of gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate (DN-1417) and thyrotropin-releasing hormone (TRH) were studied in the rat. In situ absorption experiments were carried out by the radioimmunoassay, and experiments using everted sacs of small intestine were by radioactivity measurements with 14C-labeled DN-1417 or 3H-labeled TRH in the low concentration range of drug and by a high pressure liquid chromatography in the rather high concentration range of drug. The site specificity of absorption in the small intestine of rats could not be found with DN-1417, whereas TRH-T was absorbed from only the upper part of small intestine. Dose-proportional absorption of DN-1417 was observed in experiments of in situ as well as in vitro. Dose-proportional transfer of DN-1417 through the everted small intestine was also found within the concentration range from 120 ng/ml to 27 mg/ml, whereas the transfer ratio of TRH decreased with increase in the concentration of TRH. DN-1417 transfer from mucosal to serosal fluid was not inhibited by the replacement of medium Na ions by K ions, pretreatment of intestinal mucosa with HgCl2, the existence of an oligopeptide, or the existence of beta-lactam antibiotics which had been reported to be absorbed by active transport or carrier-mediated transport systems. While, TRH transfer was inhibited by the replacement of medium Na ions by K ions, pretreatment of intestinal mucosa with HgCl2, the existence of an oligopeptide, and the existence of beta-lactam antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS)
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The aim of the present study was to determine the source and transmission route of Streptococcus mutans. The frequency of this organism in saliva and plaque samples was compared among fifteen pairs of mothers and their children. The results showed that most of the mothers harboured almost equal or greater levels of S. mutans than their children. Similarities of the distribution of various serotypes and mutacin types were observed between these mothers and their offspring. Samples were also collected from plaque and/or carious lesions of the relatives of the subjects who carried one of the serotypes other than serotype c as the dominant S. mutans. The strains of the same serotypes of S. mutans which possessed similar mutacin patterns were predominantly detected in the siblings and mothers of each subject. However, a similar distribution of S. mutans strains was not clearly observed in other relatives including fathers, aunts, uncles and grandparents.
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The nucleotide sequence of the promoter region of the melibiose operon of E. coli was determined. Consensus sequences for the -35 region, the Pribnow box and the binding site for cyclic AMP receptor protein were found in this region. The possible secondary structure of this DNA region was very similar to that of the promoter region of the lactose operon. A possible initiation ATG preceded by a Shine-Dalgarno sequence with proper spacing was present just downstream of the promoter region. The possible sequence of 52 amino acid residues in the NH2 terminus of the alpha-galactosidase were determined.
The nucleotide sequence of the melB gene coding for the melibiose carrier in Escherichia coli has been determined. The melibiose carrier is predicted to consist of 469 amino acid residues, resulting in a protein with a molecular weight of 52,029. The predicted carrier protein is highly hydrophobic (70% nonpolar amino acid residues). The hydropathic profile suggests that there are 10 long hydrophobic segments in the primary structure of the carrier protein. Most of them seem to traverse the membrane. Although the hydropathic profile of the melibiose carrier is similar to that of the lactose carrier as a whole, homology in the primary structure between the two carriers is very low. Furthermore, no homology in the nucleotide sequence is found in the structural genes for the two carriers. However, the nucleotide sequences of the intergenic regions are very similar between the melibiose operon and the lactose operon. There is a typical intercistronic regulatory sequence in the 3'-flanking region of the melB as well as in that of the lacY, which suggests the presence of another gene downstream of the melB.
The vaginal absorption of leuprolide (a potent luteinizing hormone-releasing hormone analogue), which has the potential for producing regression of hormone-dependent tumors as well as high gonadotropin-releasing and ovulation-inducing activities, was evaluated in rats by radioimmunoassay. Gonadotropin (luteinizing hormone and follicle-stimulating hormone) release was concomitantly determined. Although leuprolide disappeared rapidly from the serum after intravenous administration (the biological half-lives were 8.4 min in the alpha-phase and 33.2 min in the beta-phase), long-lasting serum levels were observed when the analogue was administered vaginally. The vaginal absorption was enhanced by adding citric acid to the test solution. The absolute bioavailability, estimated by the AUC of serum leuprolide levels, was 25.8% over 6 h and 38.0% over 12 h in the 5% citric acid solution (pH 3.5). The sustained release of gonadotropin was also obtained after vaginal administration of the analogue. A linear dose absorption correlation of leuprolide was obtained in the range of 10-1000 micrograms/kg in an aqueous solution or methylcellulose jelly. The release of gonadotropin showed a plateau level at greater than 10 micrograms/kg, which corresponds to an effective dose for antitumor activity. The vaginal absorption of leuprolide varied with the estrous cycle, but this effect was eliminated by prior subcutaneous pretreatment with the analogue.
A significant positive relationship was found between alcohol intake and blood pressure for men 40-69 years old living in urban Osaka (492 men) and in rural Akita (395 men), Japan, surveyed from 1975 to 1977. Both mean blood pressure and the prevalence of hypertension were related to alcohol intake in a graded fashion. Stepwise multiple regression also showed that both systolic and diastolic pressure were associated with alcohol intake independent of ponderosity index, serum cholesterol, triglycerides, hemoglobin, uric acid, smoking, and age. This cross-sectional study indicates a continuous--and not a threshold--relationship between alcohol and blood pressure, with the effect of even moderate consumption, e.g. 28-55 g per day (equivalent to about 2-4 U.S. drinks per day).
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A mycotoxin, (E)-ascladiol, was established as a direct precursor of patulin in cell-free preparations of Penicillium urticae patulin-minus mutants J1 and S11, but not S15. Isomerization to a side product, (Z)-ascladiol, was nonenzymatically catalyzed by sulfhydryl compounds.
The vaginal absorption of a potent luteinizing hormone-releasing hormone analog (leuprolide), and the gonadotropins (luteinizing hormone and follicule-stimulating hormone)-releasing response after continuous vaginal and subcutaneous administration of the analog to rats were determined by the radioimmunoassay. A marked suppressive effect on the gonadotropin-releasing response along with long-lasting serum levels of leuprolide were paradoxically observed after consecutive 3-d vaginal administration of the analog at doses of 1 microgram/kg or greater. Pituitary function recovered progressively with cessation of the treatment but was not complete 4 d after cessation. Continuous vaginal and subcutaneous infusion resulted in an almost complete inhibition of both gonadotropins response. It is suggested that effective desensitization of the pituitary gonadotropin response is elicited by continuous administration of leuprolide and, therefore, the vaginal administration resulting in prolonged serum levels of the analog could be preferable as a self-administration method for medical treatments such as anti-tumor therapy and birth control.