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Biomedical subjects

M Shibata

Publications and source records attributed to M Shibata.

At least 613 records · Page 34Linked to original sources
PubMed1988

Clinical effects of selective thromboxane A2 synthetase inhibitor in patients with nephrotic syndrome.

To determine if a selective thromboxane (TX)A2 synthetase inhibitor is clinically effective for the treatment of nephrotic syndrome, 11 patients with nephrotic syndrome were treated only with OKY-046, (E)-3-4-(1-imidazolylmethyl)phenyl-2-propenoic acid hydrochloride monohydrate, for at least 8 weeks. Urinary excretion of protein, TXB2, 2,3-dinor-TXB2, and beta-N-acetyl-D-glucosaminidase decreased with OKY-046. Creatinine clearance value, and urinary excretion of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), however, did not show any significant change, while serum albumin level increased. Two patients with minimal change nephrotic syndrome showed complete remission only with OKY-046. These results demonstrate that the selective TXA2 synthetase inhibitor is an effective drug for the treatment of chronic glomerulonephritis accompanied by nephrotic syndrome.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Hyperthermia induced by pre-pontine knife-cut: evidence for a tonic inhibition of non-shivering thermogenesis in anaesthetized rat.

Temperature of colon, interscapular brown adipose tissue (IBAT) and paw skin (index of vasomotor activity) were monitored before and after microwire knife lesions at the pre-pontine or/and the post-mammillary levels in the urethane-anaesthetized rats at room temperature of 23-24 degrees C. Following the pre-pontine, but not the post-mammillary cut, colonic and IBAT temperatures increased by 3-4 degrees C within 90-240 min. IBAT temperature rose faster with a shorter latency and attained a higher steady-state value than colonic temperature; skin temperature, however rose by only 0.8 degrees C. A procaine microinjection into the pre-pontine area transiently increased by more than 1 degree C both colonic and IBAT temperatures, with similar kinetics as for the knife cut. Cardiac output distribution was measured using radiolabelled microspheres. Brown adipose tissue (BAT) was found to be the only organ to which the fractional blood flow increased dramatically (12 times over baseline value) during the development of hyperthermia. Propanolol, injected after the hyperthermia had fully developed, decreased IBAT and then colonic temperatures. Hexamethonium decreased both colonic and IBAT temperatures with a concomitant rise in skin temperature while tubocurarine was without effect. It is concluded that the hyperthermia observed after the pre-pontine lesion results from an increased sympathetic stimulation of BAT thermogenesis triggered by the release of a tonic inhibitory control on its heat production. Such an inhibitory system would be located somewhere between the lower midbrain and the upper pons.

Adipose Tissue, Brown↗
PubMed1987

Promotion by L-ascorbic acid of urinary bladder carcinogenesis in rats under conditions of increased urinary K ion concentration and pH.

Dietary administration of 5% L-ascorbic acid plus 3% K2CO3 to male F344 rats clearly enhanced the development of preneoplastic and neoplastic lesions of the urinary bladder initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine. Promotion of carcinogenesis by L-ascorbic acid and K2CO3 was associated with changes in urinary parameters: elevation of pH, increased K+ concentration, and increase in total ascorbic acid.

Animals↗
PubMed1987

Multistep modeling of protein structure: application towards refinement of tyr-tRNA synthetase.

The scope of multistep modeling (MSM) is expanding by adding a least-squares minimization step in the procedure to fit backbone reconstruction consistent with a set of C-alpha coordinates. The analytical solution of Phi and Psi angles, that fits a C-alpha x-ray coordinate is used for tyr-tRNA synthetase. Phi and Psi angles for the region where the above mentioned method fails, are obtained by minimizing the difference in C-alpha distances between the computed model and the crystal structure in a least-squares sense. We present a stepwise application of this part of MSM to the determination of the complete backbone geometry of the 321 N terminal residues of tyrosine tRNA synthetase to a root mean square deviation of 0.47 angstroms from the crystallographic C-alpha coordinates.

Computer Graphics↗
PubMed1987

Structural elements and organization of the ancestral translational machinery.

The molecular mechanisms underlying the primitive translational apparatus have been studied in light of present day protein biosynthesis. Using the structural information available from the contemporary system as a key to its function, both the structural necessities for an early adaptor and the multipoint recognition properties of such adaptors have been investigated. This was done by first critically examining the potential feasibility of right- and left-handed hairpin adaptor models. Second, a molecular model of the contemporary transpeptidation complex has been constructed in order to ascertain the structural requirements of the adaptor molecule needed for peptidyl transfer. Third, a model of the tRNATyr-tyrosyl tRNA synthetase complex including the positioning of the disordered region is proposed. This model is used to illustrate those required recognition properties of aminoacyl synthetase which lead to a perspective on the structure of the ancestor synthetase.

Amino Acyl-tRNA Synthetases↗
PubMed1987

Single radial complement fixation test using NP-containing plates: a simple and sensitive method for the detection of influenza infection.

The single radial complement fixation (SRCF) test using nucleoprotein (NP) was compared with the haemagglutination inhibition (HAI) test in the course of the evaluation of the protective efficacy of influenza vaccine. In the case of persons who were not vaccinated, the percent incidence of infection was almost the same (which confirmed by HAI test or by SRCF test), whereas in the case of vaccinees, there was a significant difference between the incidence confirmed by HAI (7.9%) and SRCF (19.4%) tests. The SRCF test was shown to be a simple and sensitive method for detection of a significant rise in antibody titre against influenza virus.

Antibodies, Viral↗
PubMed1987

13-week subchronic toxicity study with morpholine oleic acid salt administered to B6C3F1 mice.

The effect of subchronic administration of morpholine oleic acid salt (MOAS) was studied in B6C3F1 mice. The dose levels of MOAS used were 0%, 0.15%, 0.3%, 0.6%, 1.25%, and 2.5% in drinking water. Reduced weight gains were noted in both sexes in the 2.5% group as compared to controls, but reductions were not significant. Water consumption values showed a dose-related tendency for a decrease in both females and males. Urine analysis showed significant elevation of specific gravity in the males in the 0.6%, 1.25%, and 2.5% groups and the females in the 1.25% and 2.5% groups. Significant elevation of plasma urea nitrogen was observed in males of the 1.25% and 2.5% groups and in females of the 0.6%, 1.25%, and 2.5% groups. The relative weight of the kidneys showed a dose-dependent increase that was statistically significant for the 1.25% and 2.5% MOAS groups in both sexes. Except for cloudy swelling of the proximal tubules of the kidneys in mice on the 2.5% regimen, no treatment-related histopathological alterations were observed in organs of either sex.

Animals↗
PubMed1987

A genetically engineered P450 monooxygenase: construction of the functional fused enzyme between rat cytochrome P450c and NADPH-cytochrome P450 reductase.

A hybrid cDNA encoding a fused enzyme consisting of rat cytochrome P450c and rat NADPH-cytochrome P450 reductase was constructed by combining the cytochrome P450c cDNA with the cDNA fragment encoding the protease-solubilized moiety of the NADPH-cytochrome P450 reductase. The hybrid cDNA was inserted between the yeast alcohol dehydrogenase I promoter and terminator of the expression vector pAAH5 to yield expression plasmid pAMP19. Saccharomyces cerevisiae AH22 cells transformed with the expression plasmid pAMP19 produced a 130-kD protein reactive with both anti-cytochrome P450c Ig and antireductase Ig. The yeast cells containing the fused enzyme exhibited about four times higher monooxygenase activity toward 7-ethoxycoumarin than those containing rat cytochrome P450c alone. The fused enzyme was purified from the yeast microsomal fraction by sequential chromatography with DEAE-cellulose and 2',5'-ADP Sepharose 4B columns. The preparation had an apparent molecular weight of 130 kD and the same sequence of the 10 amino-terminal amino acids as that of rat cytochrome P450c. Spectral properties of the fused enzyme indicated the presence of a protoheme, flavin adenine dinucleotide, and flavin mononucleotide in the molecule. The reaction mechanism of the fused enzyme followed first-order kinetics. These results clearly indicate that the fused enzyme is a new self-catalytic P450 monooxygenase. Trypsin treatment of yeast microsomes containing the fused enzyme suggested that the P450 moiety is embedded in the microsomal membrane with the reductase moiety lying on the cytoplasmic side.

Animals↗
PubMed1987

Expression in Saccharomyces cerevisiae of chimeric cytochrome P450 cDNAs constructed from cDNAs for rat cytochrome P450c and P450d.

Three chimeric cytochrome P450 cDNAs were constructed by replacing the central region, carboxy-terminal region, or both central and carboxy-terminal regions of cytochrome P450c cDNA with the corresponding regions of cytochrome P450d cDNA. These were inserted between the alcohol dehydrogenase I promoter and terminator of yeast expression vector pAAH5 to form expression plasmids pACDC2, pACCD1, and pACDD2. On introduction of each of these plasmids into Saccharomyces cerevisiae AH22 cells, chimeric cytochrome P450 proteins were expressed in AH22/pACDC2, AH22/pACCD1, and AH22/pACDD2 cells at the level of at least 10(5), 4 X 10(5) molecules per cell, respectively. The reduced CO-difference spectra showed that AH22/pACCD1 and AH22/pACDD2 cells contained 4 X 10(5) and 10(5) molecules per cell of the corresponding chimeric cytochrome P450 hemoproteins, designated as cytochrome P450ccd and cytochrome P450cdd, respectively. Cytochrome P450ccd exhibited higher monooxygenase activities toward 7-ethoxycoumarin, acetanilide, and benzo[alpha]pyrene than cytochrome P450c, although the substrate specificity of cytochrome P450ccd seemed to be the same as that of cytochrome P450c. Cytochrome P450cdd exhibited lower activities toward 7-ethoxycoumarin and benzo[alpha]pyrene, and a higher activity toward acetanilide as compared with those of cytochrome P450c and cytochrome P450ccd. Therefore, the substrate specificity of cytochrome P450cdd seemed to be the same as that of cytochrome P450d. These results suggest that the central one-third region of cytochrome P450c and cytochrome P450d is responsible for substrate-binding, and that the carboxy-terminal third of both cytochromes P450 plays an important role in electron transport.

Animals↗
PubMed1987

Therapeutic application of phenylalanine immunoadsorbent with on-line regeneration.

To improve the adsorption capacity of the artificial reticuloendothelial system containing phenylalanine as a ligand, a regeneration method for the adsorbent during plasma perfusion was developed. The adsorbed rheumatoid factor, immunoglobulins, and complements were demonstrated to be elutable from the adsorbent with a 5% glucose solution in vitro. The regeneration method was applied to the treatment of a patient with rheumatoid arthritis. During each plasma perfusion, the adsorbent was regenerated, usually twice, with a 5% glucose solution at a flow rate of 50 ml/min. After each regeneration, the adsorption capacity of the adsorbent was found to be improved by determining the pre- and post-column plasma titers of a rheumatoid arthritis hemagglutination test.

Aged↗
PubMed1987

Multimodal responses of preoptic and anterior hypothalamic neurons to thermal and nonthermal homeostatic parameters.

The hypothesis that thermosensitive neurons in the preoptic anterior hypothalamic nuclei (POAH) have a principal role in central thermoregulation is based on numerous findings, suggesting correlations between the activity of thermosensitive neurons and thermoregulatory responses. Such relationships have been observed during thermal (local and peripheral) and pharmacological stimulation, during modulation of neural inputs from extra-POAH brain regions, and during actual thermoregulatory responses. Recent studies using in vitro slice preparations and conscious animals have revealed that 40-70% of POAH thermosensitive neurons respond to nonthermal homeostatic parameters such as local osmolality, blood pressure, and nonthermal emotional stimuli. About two-thirds of the POAH thermosensitive neurons, which responded in monkeys during bar press thermoregulatory tasks, changed their activity during bar press feeding behavior. A high degree of convergence of thermal and nonthermal homeostatic signals on the POAH neurons, together with abundant neural connections between the POAH and divergent areas of the brain, suggests that POAH thermosensitive neurons may be involved in the coordination of thermoregulation and nonthermal autonomic and behavioral responses controlled from the hypothalamus.

Angiotensin II↗
PubMed1987

Urinary prostaglandins and thromboxane in patients with chronic glomerulonephritis.

To evaluate the potential contribution of prostaglandins (PGs) and thromboxane (TX) to the development of chronic glomerulonephritis, we measured the urinary excretion of PGE, PGF2 alpha, 6-keto-PGF1 alpha and TXB2 by radioimmunoassay in 36 patients with chronic glomerulonephritis. In patients with nephrotic syndrome, urinary excretion of PGE and TXB2 was highly increased, whereas that of PGF2 alpha and 6-keto-PGF1 alpha remained normal. In patients with non-nephrotic chronic glomerulonephritis, urinary excretion of TXB2 was significantly increased, whereas that of PGE and 6-keto-PGF1 alpha remained normal and that of PGF2 alpha was significantly decreased. In patients with chronic renal failure, the urinary excretion of all PGS and TX was markedly decreased presumably due to a decrease in the number of cells which can metabolize arachidonic acid. These results suggest that TXA2 plays an important role as an exaggerating factor in the development of chronic glomerulonephritis, particularly that accompanying nephrotic syndrome, and that renal synthesis of PGE is compensatorily increased to maintain renal function in nephrotic syndrome.

Adolescent↗
PubMed1987

Effect of neurotropin on hyperalgesia induced by prostaglandin E2, naloxone, melatonin and dark condition in mice.

Subcutaneous injection of formaldehyde into mouse hind paw elicited pain responses consisting of licking or biting of the paw, which were observed biphasically. The first and second phases were enhanced by melatonin and melatonin, naloxone, prostaglandin E2, respectively. Mice kept in the dark also exhibited hyperalgesic response. When neurotropin was injected intraperitoneally 30 min prior to those treatments, hyperalgesia was suppressed to the control level. Aspirin inhibited only the second hyperalgesic phase.

Analgesics↗
PubMed1987

Inhibition of Streptococcus mutans glucosyltransferase by M-GTFI, a new inhibitor.

Two hundred strains of soil microorganisms were screened for the production of inhibitors of the glucosyltransferase activity of Streptococcus mutans strain, K1-R. The strain producing the greatest amount of inhibitor was one recently isolated in our laboratory. It has now been identified as a strain of Micromonospora narashinoensis on the basis of morphological and physiological studies. The inhibitor, M-GTFI, affects the glucosyltransferase that produces the water-insoluble glucan rather than that which produces the water-soluble glucan. Fuchsin-sulphite staining of the inhibitor after its purification by polyacrylamide gel electrophoresis indicates that it is probably an acidic substance. It had Mr 5700 as was determined by gel filtration. From an examination of the effects of this inhibitor on representative strains of S. mutans other than K1-R, there is a suggestion of a similar selectivity for the water-insoluble glucan-forming activity in other strains.

Dental Caries↗