Inhibition of aldose reductase activities by kampo medicines.
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Aldehyde Reductase↗
Biomedical subjects
H Shindo
Publications and source records attributed to H Shindo.
Tyrosine-specific dephosphorylation-phosphorylation with alkaline phosphatases and epidermal growth factor receptor kinase as evidenced by 31P NMR spectroscopy.
The dephosphorylation of phospho-amino acids with alkaline phosphatase (AlPase) from calf intestine or Escherichia coli and the phosphorylation of bovine serum albumin (BSA) with epidermal growth factor (EGF) receptor kinase from human A431 epidermoid carcinoma cells were investigated by 31P NMR spectroscopy. The initial rates of the dephosphorylation of phospho-tyrosine (P-Tyr) and phosphoserine (P-Ser) with AlPase were essentially the same in the one-substrate system. In the two-substrate system (P-Tyr plus P-Ser), however, the ratio of the initial rate for P-Tyr vs. P-Ser was 2.4 to 4.5 depending on the buffer and pH conditions employed. This substantiates for the first time the specificity of AlPases to P-Tyr over P-Ser at the free amino acid level. In the stationary phase of the overall process, the dephosphorylation of P-Ser became slow compared to that of P-Tyr in the one-substrate system. The decrease in the rate for P-Ser was further pronounced in the two-substrate system. For this remarkable effect, the rephosphorylation of serine was responsible, as demonstrated in the reaction mixture containing serine, Pi, and AlPase. BSA phosphorylated by EGF receptor kinase exhibited sharp 31P resonances around 0 ppm at neutral pH, far distant from the peak positions (4.9 ppm) of histone H1 phosphorylated by cAMP-dependent protein kinase. These NMR data are directed evidence that BSA was phosphorylated exclusively at the tyrosyl residues, whereas the phosphorylation of histone H1 was at the seryl residues.
Alkaline Phosphatase↗
In vivo phosphorylation of histones H1 and H5 in calf thymus and chicken erythrocyte as studied by 31P nuclear magnetic resonance spectroscopy.
The 31P NMR method was first applied to characterize in vivo phosphorylation of H1 and H5 in calf thymus and chicken erythrocytes as well as in vitro phosphorylation of H1 and H5 by cAMP-dependent protein kinase. The amino acid residues phosphorylated in vivo in the histones were exclusively serine residues, and the mole fraction of phosphoserine was estimated to be 0.34 and 0.27 per molecule of calf thymus H1 and chicken erythrocyte H5, respectively. Interestingly, chicken erythrocyte H1 was not phosphorylated in vivo. Three H1 subtypes from calf thymus H1 varied in the 31P NMR spectra, and the bisected fragments of calf thymus H1 and chicken erythrocyte H5 exhibited characteristic spectral patterns, indicating that there are considerable diversities of the degree of phosphorylation and phosphorylation sites in very-lysine-rich histones. Furthermore, it was found that the microenvironment of phosphoserine residues phosphorylated in vivo in calf thymus H1 and chicken erythrocyte H5 is quite distinct from that of phosphoserine residues phosphorylated in vitro by bovine heart cAMP-dependent protein kinase.
Animals↗
A velocity-gradient flow cell for Raman and emission spectroscopy of a deoxyribonucleic acid-drug solution.
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Aclarubicin↗
Mechanism of oligonucleotide loop formation in solution.
We have studied the tridecadeoxynucleotide CGCGAATTACGCG (I), which contains an additional A at position 9 compared to the dodecanucleotide of which the crystal structure has been determined. Sequence I exhibits no distinct melting curve and also has a concentration-dependent pattern of peaks on reverse-phase chromatography. This behavior is explained by a slow equilibration between loop and duplex forms in solution. We have characterized this equilibrium by proton NMR spectroscopy and shown that it is fully reversible by monitoring the two thymine methyl resonances, each of which occurs in two environments. Lower temperature and higher concentration favor the duplex; the midpoint of the transition is such that the loop predominates at room temperature. We have measured the van't Hoff enthalpy of formation of the duplex and the activation energy by temperature-jump and saturation-transfer experiments. The results are compared with those for the 17-mer sequence CGCGCGAATTACGCGCG (II), which contains two additional base pairs in the stem of the loop. The thermodynamic parameters and the effect of increasing salt concentration on the rate of conversion of the loop and duplex forms lead us to presume that the mechanism of interconversion involves complete strand separation and re-formation rather than cruciform formation and branch migration.
Base Sequence↗
The relation between structure and distribution of quaternary ammonium ions in mice and rats. Simple tetraalkylammonium and a series of m-substituted trimethylphenylammonium ions.
In order to determine the relationship between structure and distribution in mono-quaternary ammonium ions, the distribution of a series of 14C-labeled tetraalkylammonium and substituted trimethylanilinium ions in mice were comparatively studied by means of whole-body autoradiography and radioassay. The partition coefficient in n-octanol/water were also determined. With tetraalkylammonium, the concentration in blood and tissues decreased in the order of tetramethyl, tetraethyl and tetrapropylammonium, which was opposite to expectation based on their partition coefficient values, but was in the order of increasing steric hindrance at the cationic head. With substituted trimethylanilinium, the concentrations in the blood, skeletal and cardiac muscles, diaphragm and salivary gland after i.v. injection to mice increased in the order: m-NO2 less than Cl less than OCH3 less than H less than CH3. This did not coincide with the order of increasing the partition coefficients, but coincided with the decrease of the Hammett sigma-constants of the substituent. These results were interpreted on the basis of the assumption that the ion-pair formation of the cationic head with an anionic site of the tissue macromolecules played an important role in determining distribution. It was pointed out that although the lipophilic character of the molecule has been often cited as the most important factor determining the distribution of the drugs, the ionic character of the molecule or of the functional group can participate as a more important factor in determining tissue distribution.
Animals↗
Total assignments of the 1H NMR of decanucleotide duplexes containing the recognition sites of restriction enzymes.
Complementary DNAs, decanucleotides, were synthesized by solid phase synthesis. They contain six base pairs with different sequences in the center, flanked by GC pairs to stabilize the ends of the helix. All the imino and non-exchangeable protons of these decamers in aqueous solution were assigned by NOESY experiment. Sequence dependent exchange rates of imino protons and the chemical shifts of non-exchangeable protons were examined.
Base Composition↗
Distinction and similarity in the structure of histones H1 and H5 as indicated by 13C nuclear-magnetic-resonance spectroscopy.
The 13C nuclear magnetic resonance studies have been carried out on histones H1 and H5, by focusing our interest on possible formation of specific salt bridges between acidic and basic amino acid residues in the proteins and also on the structural difference between the two proteins. The 13C chemical shift and pKa values of the carboxyl group of glutamic acid residues in the histones coincided with those of free glutamic acid. Based on this result and another experiment using completely modified lysine residues in the histones, no evidence for a specific interaction between acidic and basic residues has been found. It has also been shown that the pH-effects of aliphatic and aromatic resonances are quite different between H1 and H5, suggesting that the globular domain of H5 is more stable than that of H1. The correlation time (1.5 ns) for the alpha-carbons of H5 estimated from 13C nuclear Overhauser enhancement was twice as long as that of H1 (0.9 ns), indicating that the backbone in the N-terminal and C-terminal domains of H5 is less mobile than that of H1.
Arginine↗
Phosphorus-31 nuclear magnetic resonance of highly oriented DNA fibers. 1. Static geometry of DNA double helices.
The static geometry of the phosphodiesters in oriented fibers of DNA and a variety of polynucleotides was investigated by solid-state 31P nuclear magnetic resonance (NMR) spectroscopy. The structural parameters of the phosphodiester backbone expressed by two Euler angles beta and gamma were estimated on the basis of the NMR spectra of natural DNA, poly(dA).poly(dT), poly(rA).poly(dT), and poly-(rA).poly(rU). The Euler angles were calculated by using the known single crystal structures of a decamer, r(GCG)d(TATACGC), and a dodecamer, d(CGCGAATTCGCG). The distribution pattern of the Euler angles was quite different between these two oligonucleotides due to the different types of conformation, and it was fully consistent with the 31P NMR results, showing that the conformation of the B form DNA is very heterogeneous while that of the A or A' form is much more invariable with regard to the base composition. The structural parameters were also calculated by using various structures determined by the X-ray fiber diffraction studies, and they were evaluated on the basis of the 31P NMR data. Notably, poly(dA).poly(dT) fibers exhibited abnormal 31P NMR spectra which were very broad in line width and were not appreciably perturbed by hydration; a coiled double-helical structure is proposed as the most plausible model for this polymer.
Animals↗
Phosphorus-31 nuclear magnetic resonance of highly oriented DNA fibers. 2. Molecular motions in hydrated DNA.
31P nuclear magnetic resonances (NMR) of salmon sperm DNA, poly(rA).poly(rU), and poly(rA).poly(dT) fibers were measured as a function of relative humidity. The results indicated that the spectra were strongly perturbed by the molecular motions occurring in the hydrated fibers. The humidity dependence of the spectra at a number of orientations of the fibers relative to the magnetic field was reasonably explained by taking into account at least three motional modes, namely, conformational fluctuations, restricted rotation about a tilted axis, and rotational diffusion about the helical axis. The rotational diffusion about the helical axis was found to perturb the spectral line shapes most strongly, and its constants were 1.5 X 10(4) and 5.0 X 10(4) S-1 for DNA fibers at 92% and 98% relative humidities, respectively. A DNA-RNA hybrid, poly(rA).poly(dT), has been shown to adopt different conformations on two strands at high relative humidity [Zimmerman, S. B., & Pheiffer, B. H. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 78-82], which was unquestionably confirmed in the present study: that is, the 31P NMR spectra from the hydrated form of this polymer were clearly explained by assuming that one strand had an A-like conformation and the other a B-like conformation.
Animals↗
Induction of activated macrophages by intraperitoneal injection of mitomycin C in mice.
The host cellular response to IP injection of mitomycin C was studied in C3H/HeN mice. As assessed by in vitro cytolysis assay using 125I-iododeoxyuridine-labelled tumour target cells, mitomycin C-induced peritoneal macrophages showed the maximum tumouricidal activity 4 days after the IP injection. The tumouricidal activity was dependent on the dose of mitomycin C injected and it was detectable against syngeneic, allogeneic and xenogeneic tumour target cells. In addition, these tumouricidal macrophages were found to be augmented in functions of both incorporation of 2-deoxy-D-glucose and phagocytosis of sheep red blood cells. Among the other anti-cancer drugs, which were used at a dose of three-fifths of LD50, only adriamycin (7.5 mg/kg) was capable of inducing activated macrophages as much as mitomycin C (3 mg/kg). Cyclophosphamide (225 mg/kg), methotrexate (60 mg/kg) and vincristine (1.5 mg/kg) were able to augment incorporation of 2-deoxy-D-glucose and phagocytosis of sheep red blood cells, but not tumouricidal activity. Differential cytolysis assay was performed for two cell lines of P 388 tumour target cells, the mitomycin C-sensitive original cell line and the mitomycin C-resistant subline, demonstrating no significant difference in macrophage-mediated tumour cell lysis between these cell lines. Based on these results, it was concluded that mitomycin C, when injected IP induced activated macrophages in the peritoneal cavity. A better understanding of the effect of anti-cancer drugs on macrophage tumouricidal activity may be useful in designing more effective local chemotherapy for malignant peritoneal effusions.
Animals↗
Involvement of the histidine residues in the pH-induced conformational change of histone H5.
Comparative studies on the conformational stability of histones H1 and H5 have been carried out by monitoring the pH-induced conformational transitions of the proteins by CD and 1H NMR spectroscopies. The transition point of H1 agrees with the pKa of the carboxyl groups of the acidic residues. In contrast, the transition of H5 is associated with the ionization of the histidine residues which exist exclusively in H5, as well as the deionization of the acidic residues. These observations, combined with the result of the deuterium exchange rates of the histidine C-2 protons, led us to conclude that His-25 and His-62, which are buried in the globular domain, play an important role in the conformational stability of histone H5.
Animals↗
Backbone geometry of oriented DNA fibers as revealed by 31P chemical shielding anisotropy.
Since the 31P solid state NMR is concerned only with information on the phosphodiester orientations of DNA, the data from DNA fibers do not provide information about helical parameters such as the pitch and axial rise/residue. However, the method is extremely useful to elucidate the backbone conformations of DNA, especially under hydrated conditions where the X-ray fiber diffraction method cannot reveal much about structural details like multiplicity of the backbone conformations. It was shown that the conformation of the A family of DNA is rather restricted within a limited range, whereas multiple conformations generally exist in the B family of DNA fibers. The appearance of the structural multiplicity in DNA fibers under hydrated conditions suggests the important roles of the structure of DNA in gene regulation.
Animals↗
[Diagnosis and treatment of acute pancreatitis].
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Acute Disease↗
Direct evidence for a bimorphic structure of a DNA-RNA hybrid, poly(rA).poly(dT), at high relative humidity.
31P solid state nuclear magnetic resonances of highly oriented poly(rA).poly(dT) fibers demonstrated that this hybrid undergoes a conformational transition induced by hydration at about 90% relative humidity, namely, the hybrid has a single backbone conformation of the A family below 87% and two distinct conformations above 92% relative humidity. The structural model (of the B-like form) proposed on the basis of the x-ray diffraction data of this hybrid by Zimmerman and Pheiffer (Zimmerman, S.B., and Pheiffer, B.H. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 78-82) was proved to be fully consistent with our NMR data.
DNA↗
Multiple conformations coexist and interchange in natural B DNA fibers.
31P nuclear magnetic resonance (n.m.r.) of highly oriented NaDNA and LiDNA fibers was measured as a function of relative humidity over the range from 66% to 98%. The humidity dependence of the spectral patterns of NaDNA fibers shows that the A form has a single conformation while the B form has multiple conformations, and that interconversion between the A and B conformers in the transition region is slow compared to the n.m.r. time-scale (approximately 10(-5) s). Two major conformations of the B form of LiDNA are found to be stable at low relative humidity and they rapidly interchange at high relative humidities. The spectral patterns of immobilized LiDNA are compatible with the single-crystal structure of double-stranded oligo nucleic acids.
DNA↗
Pituitary abnormalities detected by high resolution computed tomography with thin slices in primary hypothyroidism and Turner syndrome.
Pituitary hyperplasia, microadenoma or an empty sella was detected in three children with primary hypothyroidism and three with Turner syndrome with the use of high resolution contrast-enhanced computed tomography (CT) with thin slices. Hyperplasia or microadenoma of the pituitary gland frequently occurs secondary to primary hypothyroidism and gonadal dysgenesis, and recognition of these results may eliminate unnecessary surgery in favor of hormone replacement therapy. High resolution contrast-enhanced CT, especially coronal CT, with thin slices is very helpful in demonstrating these pituitary abnormalities.
Adenoma↗