Biomedical subjects

Y Morimoto

Publications and source records attributed to Y Morimoto.

At least 361 records · Page 20Linked to original sources

PubMed1992

Destabilization of whole skin lipid bio-liposomes induced by skin penetration enhancers and FT-IR/ATR (Fourier transform infrared/attenuated total reflection) analysis of stratum corneum lipids.

Whole skin lipid bio-liposomes (skin bio-liposomes), in size ranging from 2 to 8 microns, were prepared by a reverse phase evaporation technique using rat full thickness skin. Leakage of an encapsulated fluorescence probe, ANTS (delta-amino-1,3,6-naphthalene-trisulfonate), was measured by adding transdermal penetration enhancers (penetrants) into the medium where the skin bio-liposomes were present. Oleylamine induced a fast release of ANTS from the liposomes compared to lauryl-amine which showed a weak action. With these penetrants, the degree of ANTS release from the prepared bio-liposomes was found to correlate well with the results of frequency changes in the CH-asymmetric stretching band near 2920 cm-1 in the rat stratum corneum. The penetrant which caused relatively strong leakage of ANTS induced the significantly large shift of the peak toward the higher wave-numbers due to the perturbation in the structure of lipids of the stratum corneum. The skin bio-liposomes prepared from the rat full thickness skin could be useful in evaluating the penetrants.

Amines↗

PubMed1992

Anisoosmostic liver perfusion: redox shifts and modulation of alpha-ketoisocaproate and glycine metabolism.

1) In isolated perfused rat liver, 14CO2 production from [1-14C]alpha-ketoisocaproate or [1-14C]glycine as well as ketogenesis from alpha-ketoisocaproate were stimulated upon exposure to hypoosmotic perfusion media, whereas hyperosmotic exposure inhibited. The effects of anisotonicity were preserved when ketogenesis from alpha-ketoisocaproate and 14CO2 production from [1-14C]glycine were already stimulated by glucagon. On the other hand, ketogenesis from tyrosine (2 mM) or octanoate (0.1 mM) were almost unaffected by anisoosmotic exposure. 2) With all ketogenic substrates studied, hypoosmotic (hyperosmotic) cell swelling (shrinkage) decreased (increased) the beta-hydroxybutyrate/acetoacetate ratio in effluent perfusate. A shift of the mitochondrial and cytosolic NADH systems to a more oxidized (reduced) state following hypoosmotic (hyperosmotic) exposure was also found upon infusion of beta-hydroxybutyrate/acetoacetate and lactate/pyruvate as redox indicator metabolite couples. The effects of anisotonicity on the beta-hydroxybutyrate/acetoacetate ratio were reversible upon normoosmotic reexposure and persisted throughout anisoosmotic exposure despite completion of volume regulatory K+ fluxes within 10-15 min. Hepatic oxygen consumption decreased by about 10% during hyperosmotic cell shrinkage and was transiently stimulated during hypoosmotic exposure. 3) There was a close relationship between ketogenesis from alpha-ketoisocaproate (0.5 mM) and the mitochondrial redox state, as assessed by the beta-hydroxybutyrate/acetoacetate ratio in effluent, regardless of whether the pathway was modulated by anisotonicity or glucagon. 4) Isoosmotic cell swelling induced by addition of glutamine (3 mM) was without significant effect on ketogenesis from octanoate and stimulated ketogenesis and 14CO2production from [1-14C]alpha-ketoisocaproate only slightly (i.e. by less than 10%); however, in each case the hydroxybutyrate/acetoacetate ratio in effluent perfusate decreased by about 20% upon addition of glutamine. 5) Stimulation of 14CO2production from [1-14C]glycine by hypoosmotic exposure and glucagon was only slightly affected when the accompanying decrease of the beta-hydroxybutyrate/acetoacetate ratio was reversed by addition of beta-hydroxybutyrate. 6) The data are compatible with a hypotonicity (hypertonicity)-induced shift of the mitochondrial NADH system to a more oxidized (reduced) state, probably due to a alterations of respiration. Mitochondrial swelling probably also occurs under the influence of glutamine. Modulation of ketogenesis from alpha-ketoisocaproate, but not of glycine oxidation by anisoosmotic exposure and glucagon can be related to the accompanying redox shifts. The observations support the concept that cell volume may be an important parameter determining liver cell function.

Animals↗

PubMed1992

Semi-quantitative analysis of early microleakage around amalgam restorations by fluorescent spectrum method: a laboratory study.

Rhodamine B, a fluorescent substance, was used as a tracer to investigate in vitro early microleakage from around amalgam restorations in machinable mica glass-ceramic after thermal stress. Five types of amalgam, i.e., low-copper spherical, low-copper lathe-cut, high-copper admixture, high-copper lathe-cut, and high-copper spherical, were examined in the present study. The results indicated that early microleakage from alloys of lathe-cut particles was lower than that from alloys of spherical particles in both low-copper and high-copper amalgam restorations. A high-copper amalgam with a mixture of lathe-cut and spherical particles tended to exhibit the lowest early microleakage.

Ceramics↗

PubMed1992

[Study of postgastrectomy fatty liver].

Fatty liver was often found concomitantly by the ultrasound during the follow up study of the gastric cancer operation. By ultrasound, development of postgastrectomy fatty liver was seen in 29 out of 176 patients (16.5%) with several gastrectomies. The number of the patients with postgastrectomy fatty liver was 12 out of 104 patients (11.5%) with distal partial gastrectomy with B-I reconstruction, while that was 17 of 72 patients (23.6%) with total gastrectomy with several reconstructions. The incidence of postoperative fatty liver change was significantly higher in the patients under 59 years old compared to the elders. Seventy-five g oral glucose test induced oxyhyperglycemia and hyperinsulinemia in patients with gastrectomy, especially with total gastrectomy. Integrated plasma insulin and triglyceride responses during first one hour in postgastrectomy patients were significantly higher than preoperative values. Moreover, plasma insulin and blood sugar in response to oral glucose test were significantly higher in patients with postgastrectomy fatty liver, compared to those in patients without fatty liver. These results suggested that the postgastrectomy fatty liver was resulted from the abnormality of the glucose metabolism.

Age Factors↗

PubMed1992

[Pneumonia due to aspiration of povidone-iodine during anesthesia--a case report].

We report a case of pneumonia secondary to aspiration of povidone-iodine, which was used as an oral antiseptic. The patient was 17 y.o. female (body weight: 70 kg) who underwent a transsphenoidal resection of pituitary adenoma. Although she had a history of asthma during her childhood, no asthmatic attacks occurred for the past 10 yrs. After satisfactory anesthesia induction and tracheal intubation, 60 ml of 0.7% povidone-iodine solution was used to clean the oral cavity by a surgeon. Insufficient sealing by the cuff occurred after suturing the tube, which had made a needle hole in the cuff. Arterial oxygen saturation dropped to 90% and an increased resistance in the lungs was noted. The trachea was reintubated and she was transferred to the ICU. Her chest X-ray revealed signs of pneumonia and atelectasis in the right upper lobe. Mechanical ventilation with PEEP and periodical bronchial toilet were performed during her stay in the ICU for 42 hrs. A week was needed for the improvement of her X-ray findings. Although povidone-iodine is thought to be safe and affective antiseptics, severe complications from its aspiration may occur in patients whose airways are sensitive as observed in this case.

Adolescent↗

PubMed1991

Evaluation of x-ray diffraction data from protein crystals by use of an imaging plate.

A system has been developed which uses an imaging-plate diffraction apparatus to obtain structure factors for protein crystals. The latter is connected to a graphics workstation through an Ethernet. Pixel data from an imaging plate are transferred via the Ethernet to a workstation and processed to give the structure factors. The quality and precision of the diffraction data were examined from the point of view of spatial uniformity, linearity with exposure, decay with time, and reproducibility. X-rays from an 55Fe source and Debye-Scherrer rings from Si powder were used for calibration purposes. Finally, diffraction data were obtained and evaluated for lysozyme and cytochrome c-553 using this system. The results were satisfactory in terms of sensitivity and precision.

Protein Conformation↗

PubMed1991

Preparation of thermo-responsive polymer membranes. I.

Two types of liquid crystal (LC)-entrapped membranes, (a) polymer alloyed membranes and (b) LC-adsorbed membranes, were investigated for the purpose of developing the drug delivery systems (DDS) with thermal stimuli responsing. Polymer alloyed membranes were obtained by polymerizing acrylic monomers in presence of LC and LC-adsorbed membrane were obtained by adsorbing LC into porous hydrophobic polymer membrane. It was made clear from the indomethacin permeation experiments below and above the gel-liquid crystal phase transition temperature of the LC that the extent of thermo-sensitivity for LC-adsorbed membranes was greater than that for the alloyed membrane. The permeability ratio (38 degrees C vs. 32 degrees C) was found to be about 120 with the LC-adsorbed membrane. It was suggested from the results that the LC-adsorbed membrane was one of the useful candidates as a thermo-responsive system for DDS.

Biocompatible Materials↗

PubMed1991

Preparation of thermo-responsive membranes. II.

Two types of liquid crystal (LC)-immobilized membranes were prepared by a soaking method and sandwich method to control the permeation of indomethacin, as a model drug, in response to local and systemic fever. Monooxyethylene trimethylolpropane tristearate (MTTS) was used as a model LC because it has a gel-liquid crystal phase transition temperature near the body temperature, 39-40 degrees C in phosphate buffered saline (pH 7.4). Two porous polypropylene (PP) membranes were soaked into 20% MTTS chloroform solution in the soaking method, and two PP membranes were poured with the melted MTTS and pressed in the sandwich method. Thermo-response efficacy of the soaked membrane was dependent upon the content of MTTS in MTTS membrane, and the MTTS content above the void volume of PP membrane (38%) was needed for high efficacy. On the other hand, the sandwich membrane exhibited higher thermo-response efficacy than the soaked membrane, because more LC was embedded in the pores of sandwich membrane than that of the soaked membrane. The sandwich membrane permeation of indomethacin was sharply controlled by temperature changes between 32 and 38 degrees C.

Administration, Cutaneous↗

PubMed1991

Species differences in percutaneous absorption of nicorandil.

The species difference in skin permeability, Kp, of nicorandil was determined by using excised skin samples from hairless mouse, hairless rat, guinea-pig, dog, pig, and human. The Kp value of nicorandil in hairless mice was the greatest among the six species, and those in pigs and humans were in good agreement. To clarify the reasons for the species difference, various skin characteristics in each species were measured. It was suggested that the difference of skin surface lipids in each species affected the partitioning of nicorandil from vehicle to stratum corneum, and that such a difference would be a main factor for the species difference in nicorandil permeability. Since pig and human skins had similar surface lipids, barrier thickness, and morphological aspects, percutaneous absorption studies using excised pig skin samples would be useful for the estimation of in vitro human skin permeation behavior.

Adult↗

PubMed1991

1H NMR studies on ferricytochrome c3 from Desulfovibrio vulgaris Miyazaki F and its interaction with ferredoxin I.

The 1H NMR signals of the heme methyl, propionate and related chemical groups of cytochrome c3 from Desulfovibrio vulgaris Miyazaki F (D.v. MF) were site-specifically assigned by means of 1D NOE, 2D DQFCOSY and 2D TOCSY spectra. They were consistent with the site-specific assignments of the hemes with the highest and second-lowest redox potentials reported by Fan et al. (Biochemistry, 29 (1990) 2257-2263). The site-specific heme assignments were also supported by NOE between the methyl groups of these hemes and the side chain of Val18. All the results contradicted the heme assignments for D.v. MF cytochrome c3 made on the basis of electron spin resonance (Gayda et al. (1987) FEBS Lett., 217 57-61). Based on these assignments, the interaction of cytochrome c3 with D.v. MF ferredoxin I was investigated by NMR. The major interaction site of cytochrome c3 was identified as the heme with the highest redox potential, which is surrounded by the highest density of positive charges. The stoichiometry and association constant were two cytochrome c3 molecules per monomer of ferredoxin I and 10(8) M-2 (at 53 mM ionic strength and 25 degrees C), respectively.

Binding Sites↗

PubMed1991

Changes in natural killer cell activity in normal pregnant and postpartum women: increases in the first trimester and postpartum period and decrease in late pregnancy.

Changes in the activity and number of natural killer (NK) cells in peripheral blood in normal pregnant and postpartum women were examined. NK activity was measured in a 4-h 51Cr-release assay and evaluated by conventional relative lytic units and absolute lytic units which represent the total NK activity within a fixed volume of circulating blood. The number of NK cells was analyzed with FITC-conjugated monoclonal antibodies and by use of an automated flow cytometer. Unexpectedly, the relative NK activity increased in the first trimester and also for 1 month postpartum compared to the activity in normal non-pregnant controls. On the other hand, absolute NK activity decreased in the third trimester compared to the activity in normal non-pregnant controls. The percentage of CD57+ cells decreased in the second trimester, but the percentage of CD16+ cells did not change during pregnancy or the postpartum period. The absolute counts of CD57+ cells and CD16+ cells decreased in the second and third trimesters and increased transiently in the postpartum period. These findings indicate that the increased NK activity in the first trimester and at 1 month postpartum is induced by increased cytotoxic activity of individual NK cells, and that the decreased NK activity in late pregnancy is induced by a decrease in the numbers of NK cells. These physiological changes may play an important role in implantation in early pregnancy, protection of the fetal allograft in late pregnancy and in the natural defense against infection during the puerperal period.

Adult↗

PubMed1991

High-level secretion of human apolipoprotein E produced in Escherichia coli: use of a secretion plasmid containing tandemly polymerized ompF-hybrid gene.

A gene encoding the mature form of human apolipoprotein E (h-apoE) was fused to the secretion signal coding sequence of the Escherichia coli major outer membrane protein F (ompF) which was preceded by a consensus Shine-Dalgarno sequence. Two copies of this hybrid gene were inserted tandemly into an expression vector and expressed in E. coli under the transcriptional control of two tac promoters regulated by lac repressors. By the addition of isopropyl-beta-D-thiogalactopyranoside (IPTG) to the growth media, cells synthesized h-apoE at the level of 27.2 micrograms per A600 and up to 22% of the total cellular protein. The h-apoE produced by E. coli was processed precisely, secreted into the periplasmic space and formed protein aggregates there. However, despite aggregation, they were easily dissolved in water and actively formed protein-lipid complexes with dimyristoyl phosphatidyl choline (DMPC). These results demonstrated that E. coli cells are able to synthesize and secrete a large amount of active h-apoE using a prokaryotic signal sequence.

Amino Acid Sequence↗

PubMed1991

In vitro release profile of mitomycin C from albumin microspheres: extrapolation from macrospheres to microspheres.

To analyze the in vitro release profiles of mitomycin C from albumin microspheres prepared by chemical denaturation in a multiparticulate system, a method to calculate the total cumulative amount of mitomycin C released from a batch of microspheres was developed. Mitomycin C-loaded albumin macrospheres (diameter in mm range) were prepared, and the in vitro release kinetics of mitomycin C from individual macrospheres were determined. Then the relationship between the kinetic parameters and the physical parameters (e.g., diameter, weight) was investigated under the assumption that macrospheres and microspheres behave identically. Further, the size distribution of microspheres was measured, and the total cumulative amount of mitomycin C released from albumin microspheres was calculated. The release profiles of mitomycin C from individual macrospheres fitted first-order release kinetics better than spherical matrix kinetics. The calculated initial mitomycin C contents and first-order release rate constants for individual macrospheres were correlated with the weight and reciprocal of surface area of the macrospheres, respectively. The observed in vitro release profile for the microspheres agreed with the calculated values. These results suggest that this method is valid for calculating drug release from albumin microspheres.

Albumins↗

PubMed1991

Effects of amino acid substitution on three-dimensional structure: an X-ray analysis of cytochrome c3 from Desulfovibrio vulgaris Hildenborough at 2 A resolution.

The three-dimensional structure of cytochrome c3 from Desulfovibrio vulgaris Hildenborough has been determined by use of the molecular replacement method and refined at 2.0 A resolution. A suitable crystal of the cytochrome c3 was obtained from buffer solution (25 mM Tris-HCl, pH 7.4), with 75% ethanol as the precipitating reagent. Crystallographic data are as follows: a = 43.17 A, b = 62.91 A, c = 41.17 A, orthorhombic, P2(1)2(1)2(1) and Z = 4. Constrained least-squares refinement and a molecular dynamics procedure with a simulated structure annealing method yielded a crystallographic R-factor of 0.212. The similarity in the folding pattern of both cytochromes c3 is established, the mean deviation of the polypeptide backbone between the two structures being 0.367 A. Most of the amino acids substitutions from DvMF were located on the surface of the molecule, and in particular, S27 and V86 were placed near the propionic acid of the heme group so as to hang over the heme and the cleft of the molecule.

Amino Acid Sequence↗

PubMed1991

In-vitro DNA synthesis of keratinocytes in normal human skin, psoriasis, seborrhoeic keratosis, Bowen's disease and basal cell carcinoma.

The DNA-synthesizing cells in benign and malignant keratotic diseases including psoriasis, seborrhoeic keratosis, Bowen's disease and basal cell carcinoma were studied. Cells in S-phase were labelled after small pieces of the lesions were incubated in tissue culture medium that contained 5-bromo-2'-deoxyuridine (BrdU). The labelling of DNA was analysed using the labelling index and pattern. Although the malignant diseases tended to show a higher DNA labelling index, neither this nor the loss of polarity alone was associated with malignancy. However, a higher DNA labelling index together with a loss of polarity was characteristic for malignancy.

Bowen's Disease↗

PubMed1991

Influence of isosorbide dinitrate concentration on its skin permeability from adhesive matrix devices.

Adhesive matrix devices containing a model drug, isosorbide dinitrate (ISDN), were prepared with three different types of pressure sensitive adhesives (PSAs). ISDN permeation through excised hairless rat skin from the different devices was measured in vitro. For each PSA type, the steady state permeation rate of ISDN increased proportionally with an increase of ISDN concentration in the PSA and reached a maximum level at a certain concentration. Although the concentrations reaching the maximum skin permeation level varied among PSA types, the maximum rate for each PSA type was largely similar to that for ISDN aqueous suspension. The release rate of ISDN from devices was too fast to influence the skin permeation rate for all devices. In the PSA of devices showing maximum skin permeability, ISDN crystalline was observed by polarizing microscopy and differential scanning calorimetry. These results suggest that the skin permeation of ISDN from adhesive matrix devices was controlled by the thermodynamic activity of the drug in the PSAs.

Adhesiveness↗

PubMed1991

Studies on the synthesis of condensed pyridazine derivatives. IV. Synthesis and anxiolytic activity of 2-aryl-5,6-dihydro-(1)benzothiepino[5,4- c]pyridazin-3(2H)-ones and related compound.

A series of 2-aryl-5,6-dihydro-(1)benzothiepino[5,4-c]pyridazin-3(2H)- ones and related compounds were synthesized and evaluated for their ability to displace 3H-diazepam from rat brain membranes in vitro, and to prevent bicuculline induced convulsions in mice in vivo. Compounds with a 4'-methoxyphenyl (36) or 4'-chlorophenyl group (37, 39--42) as 2-aryl substituents showed prominent activities in both the in vitro and in vivo tests. Among them, 2-(4'-chlorophenyl)-5,6-dihydro- (37) and 2-(4'-chlorophenyl)-5,6-dihydro-10-fluoro-(1)benzothiepino[5,4-c]+ ++pyridazin- 3(2H)-one 7-oxides (41) showed activity twice as potent as diazepam in an anticonflict test (Vogel type, rats) while exhibiting less muscle relaxation (rotarod test, mice) and augmentation of gamma-aminobutyric acid-induced chloride current (Icl) in isolated frog sensory neurones than diazepam. Compound 37 (Y-23684) was selected from this series as a candidate for further development. The structure-activity relationships are discussed.

Animals↗

PubMed1991

[Inhibition by Y-25130 of the von Bezold-Jarisch effect evoked by 5-HT or 2-methyl-5-HT in anesthetized rats].

Effect of Y-25130 on 5-hydroxytryptamine3 (5-HT3) receptors was investigated using the von Bezold-Jarisch effect (BJE) in anesthetized rats. Intravenous or intraduodenal administration of Y-25130 antagonized the BJE evoked by 5-HT and its effect was over 100 times more potent than that of metoclopramide. Y-25130 also completely blocked the BJE induced by 2-methyl-5-HT, a selective 5-HT3 receptor agonist. The BJE induced by 5-HT was not antagonized by spiperone, ketanserin, phenoxybenzamine, yohimbine and haloperidol, but antagonized by atropine. Atropine inhibited the bradycardia caused by electrical stimulation of the vagus nerve, but Y-25130 had no inhibitory effect. These results indicate that Y-25130 possesses a potent and selective 5-HT3 receptor antagonistic property.

Anesthesia↗