Biomedical subjects
Publications and source records attributed to I Ueda.
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The absorbance maximum, lambda max, of a local anesthetic, benzyl alcohol, is shifted to longer wavelengths when solvent polarity is decreased. The shift was approximately a linear function of the dielectric constant of the solvent. This transition in electronic spectra according to the microenvironmental polarity is used to analyze benzyl alcohol binding to surfactant micelles. A facile method is devised to estimate the micelle/water partition coefficient from the dependence of lambda max of benzyl alcohol on surfactant concentrations. The effective dielectric constants of the sodium decyl sulfate, dodecyl sulfate and tetradecyl sulfate micelles were 29, 31 and 33, respectively. The partition coefficient of benzyl alcohol between the micelles and the aqueous phase was 417, 610 and 1089, respectively, in the mole fraction unit. The pressure dependence of the partition coefficient was estimated from the depression of the critical micelle concentration of sodium dodecyl sulfate by benzyl alcohol under high pressure up to 200 MPa. High pressure squeezed out benzyl alcohol molecules from the micelle until about 120 MPa, then started to squeeze in when the pressure was further increased. The volume change of benzyl alcohol by transfer from the aqueous to the micellar phase was calculated from the pressure dependence of the partition coefficient. The volume change, estimated from the thermodynamic argument, was 3.5 +/- 1.1 cm3.mol-1 at 298.15 K, which was in reasonable agreement with the partial molal volume change determined directly from the solution density measurements, 3.1 +/- 0.2 cm3.mol-1. Benzyl alcohol apparently solvates into the micelles close to surface without losing contact with the aqueous phase.
Penetration of 1-alkanols into monolayers of hydrophobic polypeptides, poly(epsilon-benzyloxycarbonyl-L-lysine) and poly(epsilon-benzyloxycarbonyl-DL-lysine), was compared with their adsorption on the air/water interface in the absence of monolayers. The polypeptide prepared from L-lysine is generally considered to be in the alpha-helical form whereas DL-copolymer polypeptide contains random-coiled portions due to the structural incompatibility between the two isomers. The free energy of adsorption of 1-alkanols on the air/water interface at dilute concentrations was -0.68 kcal X mol-1 per methylene group and 0.15 kcal X mol-1 for the hydroxyl group at 25 degrees C. In the close-packed state, the surface area occupied by each molecule of 1-alkanols of varying carbon chain-lengths showed nearly a constant value of about 27.2 A2, indicating perpendicular orientation of the alkanol molecules at the interface. About 75% of the water surface was covered by 1-butanol in this close-packed state. The mode of adsorption of 1-alkanols on the vacant air/water interface followed the Gibbs surface excess while the mode on the polypeptide membranes followed the Langmuir adsorption isotherm, indicating that the latter is characterized by the presence of a finite number of binding sites. The free energies of adsorption of 1-alkanols on the L-polymer monolayers were more negative than those on the vacant air/water interface and less negative than those on the DL-copolymer monolayers. Thus, the affinity of 1-alkanols to the interface was in the order of vacant air/water interface less than L-polymer less than DL-copolymer. The difference between the air/water interface and L-polymer was about 0.54 kcal X mol-1 and that between L-polymer and DL-copolymer was 0.17 kcal X mol-1 at 25 degrees C: the adsorption of 1-alkanols to the DL-copolymer was favored compared to the L-polymer. The polar moieties of the backbone of the DL-copolymer may be exposed to the aqueous phase at the disordered portion. Dipole interaction between this portion and 1-alkanol molecules may account for the enhanced adsorption of the alkanols to the DL-copolymer.
Water-in-oil emulsion was prepared from glycerol-alpha-monooleate, n-decane and water, and was used to analyze the behavior of bound water molecules in response to the addition of an inhalation anesthetic, enflurane. The motion of water molecules is monitored by proton nuclear magnetic resonance spectroscopy. To the first approximation, the half-height width of the proton signal of dispersed water is related to the spin-spin relaxation time and represents the motion of the water molecule. It appears that one of the two OH moieties of glycerol-alpha-monooleate forms a hydrogen bond with the water molecule in average. The half-height width of the dispersed water proton showed a maximal value when the glycerol alpha-monooleate/n-decane mole ratio was 4 X 10(-2). The cause of this maximum is not immediately clear, but it is suggested that the assembly mode of glycerol-alpha-monooleate may be different between the lower and higher concentration range. Enflurane decreased the half-height width of the dispersed water, indicating an increase in the motion of water molecules. This results demonstrates that the anesthetic weakened the hydrogen bond between water and glycerol-alpha-monooleate molecules, and released bound interfacial water. It is postulated that dehydration of the interface, as shown by the release of bound water, would interfere with the transport of current-carrying hydrated ions through membranes and may constitute a molecular mechanism of anesthesia.
Longer than unit length plus and minus strand RNAs were detected in hop stunt viroid (HSV) infected cucumber leaf tissues by Northern blot hybridization analysis using strand-specific probes. To elucidate the role of these longer than unit length RNAs in the viroid replication cycle, we synthesized tandemly repeated plus and minus strand HSV RNAs in vitro from cloned HSV cDNA and assayed their infectivities. Two and four unit tandemly repeated plus strand RNAs were infectious, but one unit plus, and one, two and four unit minus strands were noninfectious. Taking these data into consideration, we propose a revised rolling circle model for viroid replication.
Restriction fragments composed of only hop stunt viroid (HSV) cDNA were prepared from recombinant clone pHS-P4P, which carries four tandemly repeated HSV cDNAs, and inoculated into cucumber cotyledons. The results showed that double-stranded cDNAs consisting of 1 to 3 units of HSV sequences were infectious. In cucumber plants inoculated with these double-stranded cDNAs, infectious RNA molecules indistinguishable from authentic HSV were propagated.
An arginine auxotrophic mutant was obtained from Streptomyces griseoflavus (bicozamycin-producing strain). The mutant grew on synthetic agar supplemented with either arginine, ornithine, citrulline or argininosuccinate, but produced massive aerial mycelium and bicozamycin only with citrulline. In liquid culture, citrulline also completely restored the ability of the mutant to produce bicozamycin. Culture with arginine or ornithine markedly changed intracellular pools of these ornithine-cycle amino acids, but did not affect the other amino acid pools. The ability to produce antibiotic (but not that to form aerial mycelium) was partially restored by certain mutations to ethionine resistance (Eth-1 and Eth-2). These mutations caused decreased or increased S-adenosylmethionine synthetase activity, but both resulted in a 4.5-8-fold increase in the intracellular S-adenosylmethionine pool. Exogenous addition of S-adenosylmethionine (0.5-3 mM) also partially restored the antibiotic-producing ability of the arginine auxotroph. No difference in the S-adenosylmethionine pool was observed in organisms grown with arginine and citrulline. It was suggested that citrulline and S-adenosylmethionine are somehow involved in the initiation of differentiation and secondary metabolism of S. griseoflavus.
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High-precision solution densimetry was used to determine volume parameters for the interaction of inhalation anesthetics with water, nonpolar solvent, and phospholipid vesicles. The precision of the densimeter is mainly limited by the constancy of the temperature during measurement. Therefore, temperature stability was maintained within +/- 0.0005 degrees and monitored by a microprocessor-controlled Thermistor thermometer with 0.0001 degrees resolution. All values were obtained at 25 degrees. Because volatile anesthetics in liquid form usually contain water, they were purified by passage through activated aluminum oxide columns. The molal volumes of dried preparations at the pure liquid states were: halothane, 106.3(3); isoflurane, 123.6(6); and enflurane, 121.9(9) cm3 X mole-1 at 298.150 degrees K. The mean molal excess volumes of anesthetic-water mixtures were negative at dilute anesthetic concentrations in water and positive at dilute water concentrations in liquid anesthetics. These values were dependent on the mole fractions of each component and showed a minimum in the water-rich region and a maximum in the anesthetic-rich region. In water, the partial molal volumes were halothane 93.7, isoflurane 103.4, and enflurane 98.6 cm3 X mole-1 at infinite dilution, and increased as the anesthetic concentration was increased. The partial molal volumes of water in liquid anesthetics were in halothane 21.7, isoflurane 21.0, and enflurane 20.5 cm3 X mole-1 at infinite dilution, and decreased as the anesthetic concentration was decreased. The mean excess volumes of the anesthetic-decane mixture were positive in the entire mixing range. The partial molal volumes of anesthetics in n-decane at infinite dilution were halothane 114.9, isoflurane 135.3, and enflurane 135.2 cm3 X mole-1. The mean specific excess volumes of the mixture of anesthetics and dimyristoylphosphatidylcholine vesicle suspension showed positive values. The partial molal volume was not evaluated because of the theoretical difficulty in estimating it in a dispersed two-phase system. Because the mean excess volume of anesthetics dissolved in water is always negative and that incorporated into phospholipid suspension is positive, anesthetics expand the total volume of the model membrane system when translocated from water to the membrane. Anesthesia occurs when the mean excess volume of the total system exceeds a limiting value, and the bulk membrane size is irrelevant. Although the present result in no way disclaims alternative hypotheses, it demonstrates that the pressure reversal of anesthesia can be explained without assuming any specific receptors for these anesthetics.
In order to evaluate effects of interferon (IFN) and its inducers on neutrophil functions, neutrophil chemiluminescence (ChL) was assayed in 12 patients treated with IFN (human lymphoblastoid interferon, 3.0 X 10(6) units/day i.m. daily) or Ge-132 (2,250 mg/day p.o. daily). The peak levels of neutrophil ChL, assayed one week after the initiation of treatment, were increased in comparison to those before treatment, but one month after treatment they were decreased to pretreatment levels in spite of the daily administration of the agent. On the basis of these results, it was concluded that IFN and Ge-132 enhanced the host defence mechanism including the activation of neutrophils, which appeared at the early phase of the host reaction.
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The fraction of hen egg albumin glycopeptides mixture, which passes through a Dowex 50-H+ column, contains two sulfate-containing glycopeptides. Based on the structural studies of oligosaccharides released from the glycopeptides by hydrazinolysis, their structures were elucidated as follows. (formula; see text)
A marked increase of serum transaminase activities, histological changes of livers similar to those seen in viral hepatitis in man, and inhibition of hepatic protein synthesis were observed in rats following a single injection of D-galactosamine-HCl. These galactosamine-induced phenomena were prevented by the pretreatment of polyriboinosinic acid-polyribocytidylic acid 24 h before the galactosamine administration.
The oral bioavailability of new formulations of ceftizoxime sodium was investigated in animals and humans. In rats, one of the formulations tested showed significant improvement, with a urinary excretion of 47.7% (0--24 hr). Good results were obtained also in dogs. In humans, the mean peak serum level was 3.6 micrograms/ml at 3.3 hr postadministration for formulation 10. The average ceftizoxime AUC at 0--8 hr was 17.3 micrograms hr/ml and urinary excretion of ceftizoxime was 9.6% (0--24 hr). The concentrations in the serum exceeded the minimum inhibitory concentrations for most of the commonly encountered bacterial pathogens.
Recent disputes about the relevance of membrane expansion to the mechanism of anesthesia indicate that there is confusion about the concept of membrane expansion and stabilization. One theory suggests that the membrane is expanded when its size is increased by the size of the incorporated anesthetic molecules, whereas another theory contends that extra space must be created over the size of the incorporated anesthetic molecules in order for the membrane to be considered as expanded. This article is intended to clarify the discrepancies between these concepts. The volume theories of anesthesia are reviewed critically. The volume change of the membrane, induced by the interaction of anesthetics, is not a simple summation of membrane volume and anesthetic volume. There are a number of factors that affect the volume when anesthetic molecules interact with the membrane in water. The theories that envision membrane expansion as the increase of volume by the size of anesthetic molecules assume that there is no interaction between membrane and anesthetic molecules (if there is interaction, there is excess volume change) and are incompatible with the pressure reversal of anesthesia. The physical meaning of the pressure reversal of anesthesia is described, and the absolute necessity of the presence of excess volume for pressure to antagonize anesthesia is discussed. Excess volume expansion per se may not be the cause of anesthesia, but the mechanism by which the excess volume is created must be the key event that induces anesthesia. The mean excess volume hypothesis postulates that the size of the membrane is irrelevant to anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Sixteen patients with hematologic neoplasms were treated with Human Lymphoblastoid Interferon (HL-BI) derived from Namalwa cell line. They were 6 multiple myeloma, 8 acute leukemia and 2 malignant lymphoma patients. All patients were previously treated with anticancer agents except one case with multiple myeloma. HLBI, 3.0 X 10(6) IU/day, was daily administered by intramuscular injection at least for 4 weeks. Three of 6 multiple myeloma responded to HLBI with a decrease of more than 25% in serum myeloma protein level. A case with pleural effusion due to massive infiltration of myeloma cells treated with intrathoratic administration of HLBI, in whom complete disappearance of pleural effusion was recognized. On the other hand, no patients with acute leukemia and malignant lymphoma responded except one case with acute lymphocytic leukemia, in which bone marrow lymphoblasts decreased transiently. Fever episodes, 13 of 16 cases, were more frequently seen but were manageable. Transient leukocytopenia and thrombocytopenia were also observed in 4 and 7 of 8 cases, respectively. No anaphylactoid reaction was seen. Thus, HLBI was expected useful in the clinical management of multiple myeloma.