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Biomedical subjects

T Fukui

Publications and source records attributed to T Fukui.

At least 487 records · Page 27Linked to original sources
PubMed1977

The pathogenesis of Bartter's syndrome. Functional and histologic studies.

We describe a patient with Bartter's snyndrome. In addition to the well-known characteristic findings by light microscopy, electron micrograms confirmed the presence of juxtaglomerular cell hyperplasia with polymorphous renin secretory granules and dense multivesicular bodies. Volume expansion by albumin infusion decreased plasma renin activity and aldosterone excretion, and improved the pressor response to exogenous angiotensin, suggesting that the renin-angiotensin-aldosterone system was not autonomous but that a decreased extracellular volume might be a major defect in this patient. During hypotonic saline diuresis, moreover, fractional free water clearance per fractional distal sodium delivery, CH2O/CH2O + CNa, was markedly depressed in the patient when compared with the value in the controls. Evidence presented suggests that chronic extracellular volume depletion exists as a consequence of an impaired sodium transport in the ascending limb of Henle's loop.

Adult↗
PubMed1977

Biologic activities of poly (2-azaadenylic acid) and poly (2-azainosinic acid).

Poly (2-azaadenylic acid) [(aza2A)n] and poly(2-azainosinic acid [(aza2I)n], two newly synthesized analogues of (A)n and (I)n, in which CH-2 of the purine ring is replaced by a nitrogen atom, have been evaluated in various biological assay systems. (Aza2A) n formed a complex with (U)n and (br5U)n, and (aza2I)n formed a complex with (C)n and (br5C)n, but these complexes were markedly destabilized relative to the corresponding (A)n or (I)n complexes. The (aza2A)n-and (aza2I)n-derived complexes failed to stimulate the production of interferon in primary rabbit kidney cells and human diploid fibroblasts, under conditions (A)n. (U)n, (I)n. (C)n and (I)n. (br5C)n induced high amounts of interferon. both (aza2A)n and (aza2I)n exerted a marked inhibitory effect on the endogenous RNA directed DNA polymerase (reverse transcriptase) activity associated with murine leukemia virus. They caused a relatively mild inhibition of complement activity in an hemolytic assay system.

Aza Compounds↗
PubMed1977

Polynucleotides. L. Synthesis and properties of poly (2'-chloro-2'-deoxyadenylic acid) and poly (2'-bromo-2'-deoxyadenylic acid).

Poly (2'-chloro-2'-deoxyadenylic acid) and poly (2'-bromo-2'-deoxyadenylic acid) were synthesized from the corresponding diphosphates with the aid of polynucleotide phosphorylase from E. coli. UV, CD, acid titration and mixing with poly (U) were investigated. Comparing these properties with those of poly (A) and poly (2'-azido-2'-deoxyadenylic acid), it was found that 2''substituents exert significant effects on the thermal stability of these polynucleotides, though the overall conformational structure was not greatly changed.

Circular Dichroism↗
PubMed1977

Polynucleotides. XLVI. 1 Synthesis and properties of poly (2'-amino-2'-deoxyadenylic acid).

Poly (2'-amino-2'-deoxyadenylic acid) [poly (Aa)] was prepared from chemically synthesized 2'-amino-2'-deoxy-ADP by the catalysis of polynucleotide phosphorylase. Poly (Aa) showed a similar UV absorption spectra to poly (A), but quite different CD spectra at pH 7.0 and 5.7. At the former pH it showed a single negative Cotton band and at the latter a curve with a large splitting of bands. Acid titration of poly (Aa) suggested protonated form below pH 7.0. Temperature absorption profiles and their dependency on sodium ion concentration suggested an ordered structure for poly (Aa) which is stabilized by stacking of bases and intrastrand interaction between 2'-amino and internucleotidic phosphate groups. Poly (Aa) forms a 1:2 complex with poly (U) at neutrality and its Tm was 45 degrees in the presence of 0.15M sodium ion.

Chemical Phenomena↗
PubMed1977

Polynucleotides. XLV Synthesis and properties of poly(2'-azido-2'-deoxyinosinic acid).

Poly (2'-azido-2'-deoxyinosinic acid), [poly (Iz)], was synthesized from 2'-azido-2'-deoxyinosine diphosphate by the action of polynucleotide phosphorylase. Poly (Iz) has UV absorption properties similar to poly (I) and hypochromicity of 11% at 0.15M Na+ and neutrality. In solutions of high Na+ ion concentration, poly (Iz) forms a multi-stranded complex and its Tm at 1.0M Na+ ion concentration was 43 degrees. Upon mixing with poly (C), poly (Iz) forms a 1:1 complex having a Tm lower than that of poly (I)-poly (C) complex in the same conditions. The effect of substitution at the 2'-position of the poly (I) strand was discussed in relation to the interferon-inducing activity.

Azides↗
PubMed1977

Affinity of glucose analogs for alpha-glucan phosphorylases from rabbit muscle and potato tubers.

The action of phosphorylase b from rabbit muscle and potato phosphorylase was inhibited to various extents by several glucose analogs. Like glucose itself, all of the glucosidic oxygen-substituted analogs tested in kinetic experiments showed a nonlinear competitive inhibition for muscle phosphorylase b and a linear competitive one for potato phosphorylase. 5-Thio-D-glucose, one of the ring oxygen-substituted analogs, also inhibited the action of muscle phosphorylase b in the same manner, while the inhibition pattern of 5-amino-D-glucose (nojirimycin) was of a linear noncompetitive type. Since the conformation of 5-amino-D-glucose in aqueous solution is half-chair (Reese et al. (1971) Carbohyd. Res. 18, 381-388), the unusual kinetic behavior of the compound toward muscle phosphorylase b was supposed to be due to its half-chair conformation. In the glucosidic oxygen-substituted analogs, the affinity for both muscle phosphorylase b and potato phosphorylase decreased with decreasing order of magnitude of electronegativity of the glucosidic atom. The strong positive correlation between the affinity and the electronegativity suggests that D-glucose-1-P, the substrate, may bind to phosphorylase with the formation of a hydrogen bond between its glucosidic oxygen and a hydrogen donor of the enzyme.

1-Deoxynojirimycin↗
PubMed1977

The mode of binding of pyridoxal 5'-phosphate in rabbit muscle glycogen phosphorylase b: circular dichroism and absorption studies.

Large bands absorbing at 251 and 335 nm were observed in the difference circular dichroism and difference absorption spectra of the holo- versus the apo-enzyme of rabbit muscle phosphorylase b. In addition to the previously known band at 335 nm, the band at 251 nm is here assigned to the bound pyridoxal 5'-phosphate (PLP). These observed difference spectra are simulated by the optical properties of the enol-imine form of the Schiff base rather than those of the substituted aldimine. Pyridoxal and salicylaldehyde also bound to apophosphorylase in the same manner as PLP. Since analogs having no hydroxyl group at the ortho position to the aldehyde group did not bind to the apoenzyme, the hydroxyl group is thought to be important in stabilizing the interaction between apophosphorylase and PLP. The PLP bound at Site I of bovine serum albumin, which is known to be one of the PLP-binding proteins absorbing at 330-340 nm, showed two prominent bands at 253 and 335 nm. The circular dichroism and absorption spectra induced by the binding of PLP fit those of the enol-imine of the Schiff base, as in the case of phosphorylase.

Animals↗
PubMed1976

Enzymatic synthesis of poly-beta-hydroxybutyrate in Zoogloea ramigera.

The enzyme activity synthesizing poly-beta-hydroxybutyrate (PHB) was mainly localized in the PHB-containing particulate fraction of Zoogloea ramigera I-16-M, when it grew flocculatedly in a medium supplemented with glucose. On the other hand, the enzyme activity remained in the soluble fraction when the bacterium grew dispersedly in a glucose-starved medium. The soluble PHB synthase activity became associated with the particulate fraction as PHB synthesis was initiated on the addition of glucose to the dispersed culture. Conversely, the enzyme activity was released from the PHB-containing granules to the soluble fraction when the flocculated culture was kept incubated without supplementing the medium with glucose. PHB synthase was also incorporated into the newly formed PHB fraction when partially purified soluble PHB synthase was incubated with D(-)-beta-hydroxybutyryl CoA in vitro. Although attempts to solubilize the particulate enzyme were unsuccessful, and the soluble enzyme became extremely unstable in advanced stages of purification, both PHB synthases had the same strict substrate specificity for D(-)-beta-hydroxybutyryl CoA, and showed the same pH optimum at 7.0.

Coenzyme A Ligases↗
PubMed1976

Circular dichroism studies on glycogen phosphorylase from rabbit muscle. Interaction with the allosteric activator adenosine 5'-monophosphate.

Circular dichroism (CD) spectra of glycogen phosphorylase from rabbit muscle have been measured in the presence of various ligands, particularly in the near-ultraviolet wavelength region. Phosphorylases a and b gave similar positive CD spectra as each other, in the 250-310-nm region. The differences in CD between the a and b forms, as well as the CD changes induced by binding of substrate and other ligands except nucleotides to the enzyme, are all relatively small. Binding of AMP and other nucleotides to phosphorylases a and b, and NaBH4-reduced phosphorylase b, however, induces much larger CD spectral changes than the above. The difference CD curve obtained by subtracting the phosphorylase b curve from that of the enzyme- AMP complex is smooth, with a positive maximum at 266 nm and a negative at 289 nm. The results with various other nucleotides show that the induced Cotton effects are dependent on the base chromophore of the nucleotides. The rotational strength of the induced Cotton effect in phosphorylase b by AMP increases under various conditions, under which the affinity of the enzyme for AMP is enhanced, e.g., the addition of glucose 1-phosphate, inorganic phosphate, fluoride ion, divalent metal cations, and spermine, low temperatures, and conversion of the enzyme to the a form. On the contrary, these factors little affect the induced Cotton effects by IMP, GMP, and dAMP. Amylodextrin gave no effect on the extrinsic Cotton effect by binding of AMP plus Mn2+ to phosphorylase b, while it did retard the AMP-induced tetramerization of the enzyme. It is suggested that the interaction of nucleotides with phosphorylase involves stacking between the base ring of the bound nucleotides and an aromatic amino acid residue at the allosteric site of the enzyme, and that, in the high affinity form of the enzyme for AMP, particular bondings are newly formed between the enzyme and the nucleotide allowing the heterotropic cooperativity.

Adenosine Monophosphate↗
PubMed1976

Synthesis and biological activity of pyrazolo[3,4,-d]pyrimidine nucleosides and nucleotides related to tubercidin, toyocamycin, and sangivamycin.

The 6-aza analogues of toyocamycin and sangivamycin were prepared as potential cytotoxic agents. The toyocamycin analogue (4-amino-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine-3-carbonitrile) could not be obtained directly from its O-acetylated precursor but was accessible via 4-amino-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine-3-thiocarboxamide. The identity of the nitrile was verified by its ultraviolet, infrared, and mass spectra, and by its conversion to the corresponding 3-carboxamide and thiocarboxamide when treated with water or hydrogen sulfide, respectively. Bioassay of the synthetic compounds in comparison with 4-amino-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (6-azatubercidin) and 4-amino-2-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine revealed that the 3-thiocarboxamido derivative was more cytotoxic to the growth of mouse fibroblasts than 6-azatubercidin, effecting killing of 3T6 cells at less than or equal to 1 mug/ml. 4-Amino-1-(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (but not its 2-ribofuranosyl isomer) was shown to act as a substrate for adenosine deaminase from calf intestinal mucosa with an apparent Km of 125 (vs. 20 for adenosine) and the corresponding 5'-diphosphate of 6-azatubercidin was polymerized by polynucleotide phosphorylase (Micrococcus luteus) in the presence of Mn2+ to afford a homopolymer and copolymers with adenosine. The copolymers directed the binding of [3H]lysyl-tRNA to the A-site of ribosomes from Escherichia coli, but could not be used for the synthesis of polylsine in a cellfree system. The copolymer consiting of adenosine and 6-azatubercidin in a 2:1 ratio was found to form a 1:1 complex with poly(uridylic acid) at 4degreesC.

Antibiotics, Antineoplastic↗
PubMed1976

Polynucleotides. XLII1. Limited addition of 2'O-onitrobenzyl nucleotides to the 3'-end of ribooligonucleotide with polynucleotide phosphorylase.

2'-O-o-Nitrobenzyluridine, -cytidine and -adenosine were phosphorylated with phosphoryl chloride to the corresponding 5'-phosphates and led to 5'-diphosphates by the method of Moffatt and Khorana. These 2'-O-oNB-nucleoside 5'-diphosphates were incubated with a primer CpApA and polynucleotide phosphorylase in the presence of Mn2+. Tetranucleotides CpApApU, CpApApC and CpApApA were obtained after photosensitive removal of oNB groups in yields of 54-70%.

Benzyl Compounds↗
PubMed1976

Role of purine N-3 in the biologic activities of poly(A) and poly(I).

Poly(c3A) (poly 3-deazaadenylic acid) and poly(c3I) (poly 3-deazainosinic acid) differ in biological reactivity from their parent compounds poly(A) and poly(I) and from their 7-deaza counterparts poly(c7A) and poly(c7I). Three parameters of biological reactivity were evaluated : (1 degree) interferon induction, (2 degrees) anti-complement activity, (3 degrees) reverse transcriptase inhibition. Unlike poly(A)-poly(U), poly(I)-poly(C) and poly(I)-poly(br5C), the mixtures of poly(c3A) + POLY(U), poly(c3I) + poly(C), and poly(c3I) + poly(br5C) failed to elicit an interferon response in "super-induced" primary rabbit kidney cells; Poly(I) and its analogs poly(c3I) and poly(c7I) inhibited hemolytic complement activity, whereas poly(A) and its analogs poly(c3A) and poly(c7A) failed to do so. Both poly(I) and poly(c7I), but not poly(c3I), lost their anti-complement potency when annealed to either poly(C) or poly(A)-poly(U). Similarly, poly(I) and poly(c7I), but not poly(c3I), suppressed the interferon inducing ability of poly(A)-poly(U), suggesting that both poly(I) and poly(c7I), but not poly(c3I), added to poly(A)-poly(U) to form a triple-helical structure. Poly(I), poly(C7I) and poly(c7A)exerted a distinct inhibitory effect on turine leukemia virus, while under the same conditions poly(c3I) and poly(c3A) showed little, if any, inhibitory effect.

Animals↗
PubMed1976

Polynucleotides. XL. Synthesis and properties of poly 2'-azido-2'-deoxyadenylic acid.

Poly 2'-azido-2'-deoxyadenylic acid (Poly Az) was synthesized from 2'-azido-2'-deoxyadenosine diphosphate by polynucleotide phosphorylase. Poly (Az) has U.V. absorption properties similar to poly (A) and hypochromicity of 40% at 0.1 M Na+ and neutrality. CD curve also resembled to that of poly (A), but has smaller ellipticity. Titration of poly (Az) with HCl gave a transition at pH 5.5, but exact structure of the acid-form complex was not elucidated. Upon mixing with poly (U), poly (Az) forms a 1:1 and 1:2 complexes having Tm's somewhat higher than that of poly (A)- poly (U) complex in the same condition.

Azides↗